Abstract in English:

Bone fractures must undergo a complex healing process involving intricate cellular and molecular mechanisms. They require a suitable biological environment to restore skeletal stability and resolve inflammation. Scaffolds play a vital role in bone regeneration, thus reducing disease burden. Autologous bone graft represents the gold standard of therapy. However, its application is limited due to various reasons. Nanotechnology, in the form of nanomaterials and nano-drug delivery systems, has been proven to increase the potency of active substances in mimicking extracellular matrix (ECM), thereby providing physical support benefits and enhancing therapeutic effectiveness. Various materials, including protein, metal oxide, hydroxyapatite, and silica are modified with nanoparticle technology for the purposes of tissue regeneration therapy. Moreover, the properties of nanomaterials such as size, seta potential, and surface properties will affect their effectiveness in bone regeneration therapy. This review provides insights that deepen the knowledge of the manufacturing and application of nanomaterials as a therapeutic agent for bone regeneration.

Abstract in English:

Biomaterials stimulate diverse biological responses, including inflammation, wound healing, foreign body reactions, and fibrous encapsulation, all critical for evaluating biocompatibility and effectiveness. These responses are influenced by the material's physicochemical and biological properties, such as composition, texture, and surface characteristics. Adverse reactions, such as severe inflammation or fibrous encapsulation, can hinder tissue integration, jeopardizing patient health and increasing healthcare costs. This review aimed to summarize the current scientific evidence on biological responses to biomaterials. A systematic search was conducted through multiple databases (VHL, PubMed, SCOPUS, EMBASE, and Web of Science) including in vitro and in vivo studies that compared biomaterial interactions with the natural immune response (innate and adaptive). From the 791 articles identified, 25 met strict inclusion criteria. These studies revealed variations in immune responses and material surface characteristics, highlighting advancements made to enhance tissue integration. Bioactive materials demonstrated greater potential for tissue regeneration, while inert materials triggered moderate inflammatory reactions. This variability emphasizes the need for a personalized biomaterial selection, considering both short-term biocompatibility and long-term tissue functionality. This review underscores the importance of comprehensive evaluation to optimize biomaterial performance in clinical applications.

Abstract in English:

The biological permeability and water solubility of drugs can pose substantial obstacles to oral drug delivery, the most common mode of drug administration for improving human health. Solubility determines the amount of drug that can be dissolved in solution, whereas permeability is the ability to permeate across biological membranes, determining therapeutic efficacy and safety. Some biological barriers, such as gastrointestinal pH, enzymes, and mucus, may affect the dissolution or absorption of therapeutic drugs. Physical or chemical approaches can be used to modify the water solubility or enhance the permeability. Moreover, nanocarriers, which can increase drug stability through encapsulation, enhance absorption due to their extensive surface area, and facilitate the targeted administration of medications to certain areas, could be useful for drug delivery systems. Nanoparticles can increase drug solubility by particle size reduction, complexation, and drug encapsulation and increase permeation by retention in tumors, opening of tight junctions, membrane fluidization, or intestinal mucoadhesion. Despite the many advantages of nanoparticle drug formulations, they also have several limitations, such as complicated manufacturing processes, nanotoxicity, and stability issues. In this article, we provide a comprehensive description of nanoparticle tools for maximizing oral drug delivery.

Abstract in English:

Oxidative stress plays a key role in the mechanisms underlying pathophysiological processes, such as inflammation, age-related degenerative phenomena, atherosclerosis, hypertension, cancer, diabetes mellitus, neurodegenerative diseases, xenobiotic toxicity, among others. It is generated by the production of free radicals, resulting from the oxidative metabolism of cells. Oxidative stress is an important defense against infections. It acts specifically as a vasodilator and helps modulate antioxidant mechanisms. However, the effects become harmful when its production increases or antioxidant mechanisms are excessively reduced. Toxic metals from environmental and occupational exposure are silent agents that induce oxidative stress. Metals such as mercury (Hg), aluminum (Al), cadmium (Cd), and lead (Pb) are known to be toxic to various organs and tissues in our body. The present mini-review focuses on the cardiovascular system, considering that the interplay between oxidative stress and toxic metals acting silently is involved in their harmful effects, especially on the etiopathogenesis of cardiovascular disorders. A brief review is also given regarding the mechanisms of modulation of redox homeostasis by organic mechanisms, pharmacological approaches that can act directly or indirectly as antioxidants, and food-derived compounds that appear to be effective inhibitors of oxidative stress, thus preventing the harmful effects of free radicals.

Abstract in English:

The therapeutic benefits obtained from the presence of larvae of certain flies in infected wounds have been mentioned since ancient times. Currently, the so-called maggot therapy or biosurgery is considered a simple, safe, relatively low-cost, and highly effective alternative for treating a wide variety of infected, necrotic, and difficult-to-heal wounds, including those caused by multidrug-resistant bacteria. In addition to the debridement of necrotic wound tissue promoted by larvae, especially from the green bottle fly (Lucilia sericata; Diptera: Calliphoridae), there is much evidence that their native excretions and secretions (NES) contain components with varied antimicrobial activity against Gram-positive and Gram-negative bacteria and activity against fungi. Furthermore, studies have shown the antibiofilm effect of NES. Biofilms represent an additional problem for wound healing because they prevent the action of antibiotics on the pathogens infecting the wound. The antimicrobial effects of crude NES or its molecular components described in studies sometimes present contrasting results when compared. This is probably due to the laboratory methodological aspects used, which range from the preparation of larvae and extraction of NES to the tests used to evaluate their antimicrobial activity. This review aimed to bring together a diversity of laboratory procedures and results that have been described for the antimicrobial potency of NES. Moreover, it aimed to contribute to a greater standardization of the methodologies adopted in new studies to generate more consensual and comparable results.

Abstract in English:

Myocardial ischemia-reperfusion injury (MIRI), a common secondary complication of cardiovascular diseases (CVDs), leads to significant psychological and physiological distress in patients. Pathophysiological reactions including inflammatory response, oxidative stress injury, platelet aggregation, vascular endothelial dysfunction, and programmed cell death are involved in the pathogenesis of MIRI. Prolonged use of conventional therapies (e.g., NSAIDs, calcium channel blockers, beta-blockers, and antiplatelet agents) may exacerbate cardiovascular damage due to adverse effects. Thus, identifying complementary and alternative therapies with better efficacy and safety profile is imperative. Unlike single-target pharmacological approaches, Salvia miltiorrhiza Bunge exhibits pleiotropic effects by modulating multiple pathways, including inflammation, oxidative stress, and vascular function. This review summarizes the protective mechanisms of Salvia miltiorrhiza against MIRI, highlighting its potential as a translational therapy for MIRI and guiding future preclinical studies.

Abstract in English:

This systematic review of inception prospective cohort studies aimed to investigate whether autoantibodies are potential prognostic factors for short- and long-term clinical outcomes of COVID-19. Searches were conducted in MEDLINE, EMBASE, AMED, GLOBAL HEALTH, and COCHRANE databases from 2019 to 2022. When possible, meta-analysis was conducted, otherwise findings from individual studies were reported using odds ratios (OR) with 95% confidence intervals (CI). Quality of evidence was summarized using the GRADE criteria. We identified 2292 references, 18 inception prospective cohort studies (3178 patients) were included in the systematic review, and 12 studies reached criteria for meta-analysis. Studies achieved, in general, low to moderate risk of bias. Moderate quality of evidence showed that anti-interferon (IFN) was associated with increased risk of severity (OR=7.75; CI=1.79-33.61) and mechanical ventilation (OR=4.19; CI=2.06-8.53), but not with COVID-19 mortality (OR=1.68; CI=0.63-4.44). Antiphospholipids were not associated with COVID-19 mortality (OR=1.42; CI=0.85-2.37; P=0.18; I2=3.21) nor with thrombosis risk (OR=1.41; CI: 0.71-2.8; P=0.33). Antinuclear antibody level was not associated with risk of mortality or severity (risk for mortality: OR=3.8; CI=0.78-18.6; P=0.1; I2: 32.3; severity: OR=1.74; CI=0.96-3.16; P=0.07). Evidence currently available is insufficient for a quantitative analysis of autoantibodies association with long COVID-19. Anti-IFN measurement should be considered in COVID-19 follow-up. In a population-based rational, optimized vaccination strategies should be considered for individuals with anti-IFN antibodies since it could represent a risk for a worse prognosis. High-quality prospective studies for short- and long-term disease effects and autoantibody evaluation are still needed.

Abstract in English:

During the climacteric period, the decline in ovarian hormones leads to changes in the lipid profile. Physical exercise is the main non-pharmacological recommendation for controlling lipid levels. However, the effects on the lipid profile in perimenopausal and postmenopausal women are incipient and inconclusive. In this context, we searched the Embase, PubMed, Scopus, and Web of Science databases for randomized clinical trials on the effects of exercise on the lipid profile of these women. We excluded studies that did not specify criteria for classifying the climacteric phase, that involved women undergoing hormone replacement therapy, or that examined combined treatments or acute effects of physical exercise. The meta-analysis indicated that general physical exercise increased high-density lipoprotein cholesterol (HDL-C) levels (mean difference [MD]=4.89; 95% confidence interval [95%CI]=0.97 to 8.81) in perimenopausal women. For obese postmenopausal women, 16 weeks of aerobic training increased HDL-C levels (MD=3.88; 95%CI=0.56 to 7.20) and reduced total cholesterol (MD=-22.36; 95%CI=-29.67 to -15.05) and low-density lipoprotein cholesterol (LDL-C) levels (MD=-17.86; 95%CI=-25.97 to -9.75), whereas 12 weeks of resistance training increased HDL-C levels (MD=4.20; 95%CI=1.16 to 7.23) and decreased triglycerides (MD=-14.86; 95%CI=-26.62 to -3.09) and LDL-C levels (MD=-16.36; 95%CI=-28.05 to -4.67). Overall, the results showed that physical exercise regulated lipid profiles in perimenopausal and postmenopausal women. Specifically, 12 weeks of resistance exercise and 16 weeks of aerobic exercise improved the lipid profile of obese postmenopausal women.

Abstract in English:

Low back pain (LBP) is a common type of pain that causes disability and impairs cognitive function. With over 80% of adults estimated to experience LBP during their lifetime, this type of pain not only has a significant impact on the individual, but also on public health systems and national economies. Unfortunately, there is no single standard of care for patients with LBP. N-acetylcysteine (NAC), which is used clinically to treat acetaminophen overdose, has recently been tested as a potential treatment for LBP. NAC is inexpensive and commercially available, and it has an established tolerance and safety profile. However, NAC's efficacy in LBP has not been established. This scoping review presents a summary of studies investigating the effects of NAC and the potential benefits in LBP treatment, and highlights its potential molecular mechanisms and side effects. A systematic literature search in Pubmed/MEDLINE, Embase, Scopus, Science Direct, Web of Science, Cinahl, and Lilacs databases was conducted. The PRISMA-ScR checklist was used to ensure integrity of the review. The scoping review protocol was registered in the Open Science Framework. No limit was set on study language and publication date. In total, 2357 articles were located, of which 16 were included. The studies show that NAC has potential for LBP treatment, but data are derived only from a few clinical trials and preclinical studies. Thus, there is much to learn and more clinical studies should be performed before NAC can be clinically recommended for the treatment of LBP.

Abstract in English:

Preeclampsia (PE) is a disease of pregnancy characterized by the new onset of hypertension accompanied by proteinuria and/or other signs of maternal organ dysfunction that manifests after 20 weeks of gestation. MicroRNAs (miRNAs) are small non-coding RNAs (19-25 nucleotides) that function in the post-transcriptional regulation of gene expression. Many studies have suggested that different microRNA expression profiles may be associated with the development of PE. Hence, this study aims to report differentially expressed microRNAs that may be associated with the pathogenesis of PE and investigate whether different miRNA expression profiles are associated with different PE classifications and different phases of pregnancy. The bibliographic search was conducted from September 2021 to August 2024 and was performed on MEDLINE/PubMed, EMBASE, and Web of Science. This systematic review followed the methodological guidelines of the Cochrane Collaboration Manual for Systematic Intervention Reviews and was written according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Of the 1362 studies identified, 263 articles were selected as the sample of this study. The most frequently cited upregulated microRNAs were: miR-210, miR-155, miR-518b, miR-181a, miR-125b, miR-183, and miR-16. The most frequently cited downregulated microRNAs were: miR-363, miR-18a, miR-144, miR-149, miR-16, miR-18b, and miR-195. This study will serve as a reference to guide future experimental research. In addition, knowledge of the expression profiles of microRNAs associated with PE can help in the development of new protocols for early prediction of the disease.

Abstract in English:

This systematic review investigates the effects of the ayahuasca beverage (Aya) in various animal models. Using the PRISMA protocol and adhering to the Cochrane Handbook for Systematic Reviews, a comprehensive selection of 2,359 documents was identified from the Web of Science, Medline, and Scopus databases between 2012 and 2022. Following the inclusion and exclusion criteria, 14 articles were included in the final analysis. The analysis revealed a diversity in the selection of animal models that included different developmental stages and various forms of Aya intoxication, including acute and chronic doses, and varying concentrations of the active principles. The studies revealed that Aya causes significant alterations in the motor and cognitive behavior of animals, especially associated with the serotonergic system, which seems to contribute to the negative symptoms also observed in schizophrenia and depression. Despite the evidence found, this review highlights the scarcity of more robust pre-clinical studies with methodological standardization to make more conclusive comparisons, especially given the need to identify potential toxic and neurochemical effects of Aya on organisms for a safer assessment of its therapeutic use.

Abstract in English:

Cutaneous melanoma, a lethal neoplasm originating from epidermal melanocytes, stands out for its resistance to conventional therapies and high metastatic rate. Given the urgent need for new therapeutic approaches, this study focuses on the antitumor potential of natural compounds derived from plants, recognized as primary sources of antineoplastic chemotherapeutics. In this systematic review, we selected studies that evaluated the efficacy of such compounds in vivo, using the murine melanoma B16 model. The research was registered at the International Platform of Registered Systematic Review and Meta-Analysis Protocols under the number INPLASY202490019 and conducted using the PubMed, Science Direct, Scopus, and Embase databases, following predefined eligibility criteria and standardized terms from the MeSH and DeCS databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and data were extracted using a Microsoft Excel® spreadsheet. Of the 361 identified studies, 33 were deemed eligible for analysis. Parameters such as routes of treatment administration and induction of melanoma, duration of treatment, and others were collected. The SYRCLE tool was used to identify methodological gaps, such as the absence or insufficient description of randomization and blinding. The results indicated that natural products, especially terpenes, flavonoids, phenolic compounds, quinones, fatty acids, and plant sterols, have considerable antimelanoma activity, with tumor inhibition above 70% and antimetastatic properties. These findings underscore the importance of investigating the potential of these plant compounds as antineoplastic agents and establishing standardized experimental protocols to increase the reliability of the results.

Abstract in English:

Antiretroviral therapy (ART) is essential to reduce viral load and restore CD4+ T cell levels in people living with HIV/AIDS (PLWHA). However, different treatment protocols influence the levels of cytokines, important mediators of the immune response. This study aimed to evaluate cytokine levels in PLWHA on therapy with tenofovir (TDF), lamivudine (3TC), and dolutegravir (DTG). The results showed that PLWHA on treatment had a significant increase in CD4+ T lymphocyte levels and a reduction in CD8+ T lymphocyte levels compared to naive (untreated) individuals. Furthermore, PLWHA treated with TDF/3TC/DTG had a significant reduction in interleukin (IL)-4 and IL-10 levels (P<0.02; P=0.047) compared to other ART regimens. Naive individuals had higher levels of IL-2 and interferon (IFN)-γ, while their levels of tumor necrosis factor (TNF), IL-4, and IL-10 were lower. These findings suggested that TDF/3TC/DTG treatment modulated cytokines, reducing chronic inflammation and improving the immune response in PLWHA. The decrease in anti-inflammatory cytokines, such as IL-4 and IL-10, may be associated with better regulation of the immune system, resulting in greater control of infection and a balanced inflammatory response.

Abstract in English:

Cancer is the second leading cause of death worldwide. Cancer cachexia is a multifactorial catabolic syndrome responsible for almost one third of cancer-related deaths. Drug repurposing has been used in oncological research and drugs like clenbuterol and metformin seem to be reasonable candidates in the context of cancer cachexia, because the former is a β2-agonist that stimulates muscle gain and the latter has anti-inflammatory properties. The aim of this study was to assess the effects of a short-term treatment with metformin and clenbuterol, isolated or combined, on tumor growth and cancer cachexia parameters in Walker 256 tumor-bearing rats, a model of cancer cachexia. To this end, Wistar rats were separated into 8 groups and 4 of them were injected with Walker 256 tumor cells (W groups). Control (C) and W groups received the following treatments: metformin (M), clenbuterol (Cb), or metformin combined with clenbuterol (MCb). Body and tumor weight, metabolic parameters, and oxidative damage in the tumor were assessed. Compared to the C group, the W group showed body weight loss, hypoglycemia, hyperlactatemia, and hypertriacylglycerolemia. None of the treatments could reverse body weight loss, although they reversed the alterations of the assessed plasma metabolic parameters. Surprisingly, only clenbuterol alone reduced tumor weight. Hydrogen peroxide production and lipid peroxidation in tumor tissue was increased in this group. In conclusion, metformin and clenbuterol ameliorated metabolic cachexia parameters in Walker tumor-bearing rats, but only clenbuterol reduced the tumor weight, probably, through a lipid peroxidation-dependent cell death.

Abstract in English:

Osteosarcoma (OS) remains the most common bone tumor and the prognosis for many patients remains stagnant due to the unsatisfactory therapeutic effect of conventional treatment regimens. This research explored the effect and mechanism of a novel natural product, Eriocalyxin B (EB), in pathogenesis and immunotherapy in OS. Cell Count Kit 8 assay, colony formation assay, and wound healing assay were employed to detect the proliferative, colony-forming, and migratory abilities of human OS cells following EB treatment. Moreover, xenograft growth assay was performed to assess the effect of EB on OS in vivo. Subcutaneous OS models constructed in immunocompetent mice were employed to evaluate the effect of EB treatment in combination with immune checkpoint blockades (ICBs) PD1ab and CTLA4ab. Immunohistochemistry (IHC) staining was utilized to detect the level of CD8+ T cells infiltration and Ki67 expression. TARGET database, RNA interference technology, and qPCR assay were employed to explore the mechanism of EB on OS. EB inhibited the proliferative, colony-forming, and migratory abilities of the human OS cells MG63 and U2OS both in vitro and in vivo. TARGET data analysis demonstrated that up-regulation of TCEA3 was significantly negatively correlated with overall survival in OS patients. EB exerted anti-tumor activity via downregulation of TCEA3. EB, in conjunction with ICBs, synergistically optimized anti-tumorigenic activity against OS in immunocompetent mice. EB may promote infiltration of CD8+ T cells and down-regulate Ki67 expression. These results signaled that EB may have a role as a candidate therapeutic or preventive agent for the treatment of OS.

Abstract in English:

Necrotizing enterocolitis (NEC) is a severe intestinal disease of multifactorial origin that primarily affects premature infants. Approximately 27% of NEC babies develop short gut (SG) secondary to extensive intestinal resection, and 10% will have chronic dependence on total parenteral nutrition. We evaluated the Botox treatment in SG model rats. Twenty-day-old weanling male rats (weight range 38-70 g, n=72) were divided into four groups (n=18 each): 1) Control (fed a regular liquid diet); 2) Botox (Control submitted to laparotomy and intestinal injection of Botox®); 3) SG (short gut); and 4) SG and Botox (SG+Botox®). After seven post-operative days, samples were collected for biometrics [body weight (BW), intestine weight (IW) and IW/BW ratio (IBR), and intestine length (IL) and height (IH)], histometric analysis [villous height (VH), crypt depth (CD), muscular thickness (MT), and PCNA index)], and intestinal transit time (ITT). BW, IW, and IL decreased in SG (P<0.05). IH, VH, and PCNA index increased in Botox groups [Control = SG < Botox and SG+Botox (P<0.05)], CD increased in Botox, SG, and SG+Botox (P<0.005), and MT was higher in SG and SG+Botox. Botox groups had lower ITT (P<0.05). Botox provided dilatation and histological changes in SG. These findings suggested that Botox improved adaptation and might be applied in SG with promising results.

Abstract in English:

Frailty is a significant risk factor for adverse outcomes in elderly surgical patients. Gait speed assessment is a new tool recently used to stratify risk for these pre-operative adverse outcomes. In this prospective study of 392 frail elderly patients undergoing abdominal surgery, we investigated the predictive value of preoperative gait speed for postoperative outcomes. Patients were divided into two groups based on their 6-meter gait speed: normal (≥0.8 m/s, n=184) and slow (<0.8 m/s, n=208). The slow group was older, had more comorbidities, and higher American Society of Anesthesiologists (ASA) grades (P<0.05). They also had significantly higher rates of 30-day overall complications (38.9 vs 18.5%, P<0.01), severe complications (12.0 vs 4.3%, P<0.01), and 1-year mortality (15.4 vs 6.5%, P=0.008) compared to the normal group. Pulmonary infection, wound infection, and delirium were the most common complications. Multivariate logistic regression confirmed slow gait speed as an independent risk factor for 30-day complications (OR=2.38, 95%CI: 1.41-4.01) and 1-year mortality (OR=2.19, 95%CI: 1.07-4.48). Our findings demonstrated that preoperative 6-meter gait speed effectively predicted short-term complications and mid-term mortality in frail elderly patients undergoing abdominal surgery. This suggests the need for individualized perioperative management strategies for high-risk patients with slow gait speed to potentially improve their prognosis.

Abstract in English:

Sirtuins (SIRTs) are key regulators of cellular metabolism, involved in a wide range of physiological and pathological processes. However, there is scarce knowledge about the effect of sugar consumption and physical activity on SIRTs in kidney disorders. Here, we evaluated the impact of prolonged consumption of an isocaloric high-sugar diet (HSD) and physical training on the modulation of renal Sirts and the link between these alterations and possible obesity-associated kidney damage. Newly weaned male Wistar rats were fed a standard chow diet (STD) or HSD ad libitum and then subjected or not to regular workload swimming training for 18 weeks. Morphometric and biochemical parameters were analyzed, and the kidneys were removed for lipid quantification, histological analysis, and for Sirts1-7 expression. HSD led to the development of obesity, increased serum triglyceride levels, and glucose intolerance, regardless of higher caloric consumption. However, training was able to partially inhibit the HSD-induced obesogenic effect. No changes were identified in kidney mass, lipid content, histology, and creatinine clearance among the groups; these results were associated with a decrease in the renal expression of Sirt2-3 and Sirt7; however, training was able to reverse this modulation. The interaction between HSD and training led to an increase in Sirt4-7. However, Sirt1 remained constant among experimental groups. In conclusion, our results indicated that the transcriptional modulation of Sirts precedes HSD-induced damage and loss of kidney function, as well as a possible protective adaptive response of physical exercise on long-term Sirts expression.

Abstract in English:

It has been confirmed that the expression of miR-501-3p is closely related to the behavior of several cancers. This study aimed to elucidate the effects of miR-501-3p/SPC24 axis on the behavior of renal cancer cells and to identify its prognostic value in renal cancer. First, the expression of miR-501-3p in the renal cell carcinoma (RCC) cell line was detected using real-time quantitative polymerase chain reaction (RT-qPCR). Second, cell function identification experiments were performed, including CCK-8, scratch, transwell invasion, and flow cytometry assays. Several databases were applied to explore the possible mechanism of miR-501-3p tumor suppressor effect in RCC. To explore the value of miR-501-3p/SPC24 axis in predicting renal cancer patient overall survival (OS), GEPIA (http://gepia.cancer-pku.cn/index.html) was used. Finally, western blot was performed to detect the expression level of SPC24 in renal cancer cells predicted by bioinformatics analysis. Dual-Luciferase Reporter Assay was used to verify if SPC24 is a target of mir-501-3p. MiR-501-3p was found to be down-regulated in cancer cells and tissues and to play a role in suppressing tumor cell proliferation, cell viability, cell migration, and cell invasion, while promoting apoptosis. We also found that high expression levels of SPC24 were associated with shorter OS time in patients diagnosed with renal cell carcinoma. In addition, the results of TCGA data analysis and western blot showed that the tumor suppressor effect of miR-501-3p may be achieved by targeting SPC24. The MiR-501-3p/SPC24 axis affects cell proliferation, migration, invasion, apoptosis, and prognosis in renal cell carcinoma.

Abstract in English:

Malaria is a parasitic disease of great relevance in global public health. The development of new sensitive and specific diagnostic high-throughput methods remains a challenge in the eradication of this disease. In this study, we developed a flow cytometry test using latex microbeads and polyclonal antibodies obtained from rabbits and mice for the detection of the P. vivax lactate dehydrogenase (PvLDH) antigen. We processed 50 samples from Brazilian patients diagnosed with malaria caused by P. vivax and 40 samples from healthy individuals. The assay presented sensitivity of 64%, specificity of 97%, a positive predictive value of 97%, and a negative predictive value of 57% when analyzed using the fluorescent labeling method. Using the mean fluorescence intensity (MFI) analysis method, the sensitivity was 53%, specificity was 89%, the positive predictive value was 95%, and the negative predictive value was 33%. In both methods of analysis, we observed significant statistical differences between the analyzed groups (P-value <0.0001). A high correlation (0.60) between the two methods and a low correlation between PvLDH concentration and parasite density was found. The test was able to detect the PvLDH protein with high specificity, but its sensitivity should be improved. More promising results were observed when the samples were analyzed according to the percentage of fluorescent labeling. Improvement of this assay would enable its application as a serological test for the detection of asymptomatic patients and for the validation of rapid diagnostic tests.

Abstract in English:

The aim of the present study was to describe the use of tapering, carbohydrate (CHO) supercompensation, and supplementation strategies self-reported by athletes in the Olympic triathlon category. A total of 72 triathletes (61 males and 11 females) answered an online questionnaire about their training and performance, supercompensation strategies, carbohydrate supplementation, and use of supplements and other ergogenic substances. The information was summarized and subjected to descriptive analysis. Shapiro-Wilk test was applied to check data normality. The t-test was used to investigate differences in the analyzed variables between sexes. Almost all triathletes reported to have performed tapering (93.05%) and approximately half of them adopted a CHO supercompensation strategy (48.61%); updated CHO supercompensation was the most used strategy (27.77%). Most participants (86.11%) used CHO supplementation during competitions, but in amounts below the 60 g/h recommended for most athletes (96.77%). Thus, since few triathletes performed supercompensation, in addition to the insufficient amount of supplemented carbohydrate taken by them, it could be concluded that triathletes were not sufficiently aware of nutritional recommendations or did not adopt them.

Abstract in English:

The stiffening of the conductance arteries is a hallmark of ageing and increases drastically after menopause. Therefore, the augmentation index (AIx), a surrogate for arterial stiffness, could be related to the decline in baroreflex sensitivity. We sought to investigate the relationship between resting AIx and spontaneous cardiac baroreflex sensitivity (cBRS) during handgrip exercise in ageing women. Thirteen young women (YW: 24±5 years; 24±2 kg/m2) and nine postmenopausal women (PMW: 60±5 years; 26±3 kg/m2) underwent the protocol, which consisted of 10 min of supine resting followed by 3 min of static handgrip exercise at 40% of the maximal voluntary force. The AIx was provided by the aortic pressure waveform and cBRS was calculated using the sequence technique, and vagal activity was accessed via heart rate variability using the root mean square of successive differences (RMSSD) index. Resting AIx was higher in PMW compared to YW (YW: 8±10%; PMW: 23±8%; P<0.01), while the cBRS (YW: 16±12 ms/mmHg; PMW: 10±5 ms/mmHg; P=0.08) and RMSSD (YW: 46±35 ms; PMW: 34±12 ms; P=0.26) were similar in YW and PMW. At rest, there was no significant (P>0.05) relationship between the AIx and cBRS in YW and PMW. However, in PMW, a negative (slope=-0.22) and strong (r=-0.70; P=0.03) relationship was observed between AIx and cBRS for the increment of blood pressure during the handgrip exercise. The stiffening of the arterial tree is one possible mechanism to explain the decrease of spontaneous cardiac baroreflex sensitivity during exercise in postmenopausal women.

Abstract in English:

Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumor that poses a major hazard to people's health. ZC3H12D, which belongs to the family of CCCH-type zinc finger-containing proteins, is a negative regulator with a key function in immune modulation. However, it is still unclear how ZC3H12D affects the immune infiltration and prognosis of HNSCC. In this study, the data obtained from various databases were used to assess ZC3H12D expression in HNSCC and in various tumors under the HNSCC classification. The association between clinical features and ZC3H12D expression in HNSCC was evaluated using the UALCAN database. Additionally, a ROC curve was employed to analyze the diagnostic value of ZC3H12D. The effect of ZC3H12D on prognosis was assessed using Kaplan-Meier curves, Cox analysis, and the nomogram model. Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were employed to investigate the underlying role of ZC3H12D in HNSCC. The association between ZC3H12D expression and the tumor microenvironment and immune checkpoints were investigated by TIMER2 and Tumor Immune Single Cell Hub 2 databases and various packages in R. The findings demonstrated a significant up-regulation of ZC3H12D expression in HNSCC, while ZC3H12D expression was found to be associated with clinical parameters. Our study also demonstrated that ZC3H12D could act as a potential prognostic biomarker for HNSCC, especially oral squamous cell carcinoma. Additional analyses have shown that ZC3H12D was associated with common immune checkpoint genes and may be related to immune infiltration in HNSCC.

Abstract in English:

Alpinia zerumbet, a plant native to East Asia, is widely found on the Brazilian coast, where it is used in folk medicine as an antihypertensive, diuretic, and anxiolytic. This study investigated the effects of the hydroalcoholic extract obtained from Alpinia zerumbet leaves (AZE) on cardiovascular changes and oxidative status in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto male rats, 90 days old, treated or not with AZE (50 mg/kg/day in drinking water) for six weeks, were used in this study. Blood pressure (BP) was assessed weekly by tail plethysmography. At the end of treatment, the animals were anesthetized with thiopental (70 mg/kg, ip), blood was collected through abdominal aorta puncture, the thoracic aorta and left ventricle were isolated for morphometric analysis and immunostaining of NOX-4, SOD-2, 8-isoprostane, and angiotensin II AT1 receptors (AT1R), and the mesenteric arterial bed (MAB) was isolated for the assessment of vascular function. Oxidative damage in lipids and proteins and the enzymatic antioxidant activity were evaluated in plasma samples by spectrophotometry. AZE normalized BP in SHR. Although the treatment did not improve the MAB vascular dysfunction, it reversed the cardiovascular remodeling in the aorta and left ventricle. In addition, AZE improved antioxidant activity in plasma and SOD-2 immunostaining in the thoracic aorta and left ventricle, decreased protein carbonylation in plasma, and reduced 8-isoprostane, NOX-4, and AT1R immunostaining in the cardiovascular system. The results suggested that AZE reversed hypertension and cardiovascular remodeling in SHR, which was associated with lower oxidative stress and AT1R.

Abstract in English:

Nasopharyngeal carcinoma (NPC) is a malignant tumor predominantly influenced by Epstein-Barr virus infection and genetic factors. The transforming growth factor-beta (TGF-β) superfamily is implicated in various cellular processes, including tumorigenesis. This study aimed to detect the role of one TGF-β superfamily member activin receptor type IIB (ACTRIIB) in NPC. This study analyzed NPC datasets, including GSE12452, GSE102349, and GSE53819. ACTRIIB expression and N-glycosylation levels were assessed by western blot, real-time PCR, immunofluorescence, and immunohistochemistry in NPC cells and tissues. As indicated by the datasets, ACTRIIB was significantly upregulated in NPC tissues, and the up-regulation was associated with poor prognosis. This study confirmed the N-glycosylation of ACTRIIB primarily at the forty-second amino acid, an asparagine. The N-glycosylation of ACTRIIB promoted the localization of ACTRIIB to the cell membrane and prevented the degradation of the protein by lysosomes, through which ACTRIIB activated the downstream Smard1/2 to promote tumor cell proliferation and invasion. Inhibition of N-glycosylation or knockdown of ACTRIIB resulted in reduced cell proliferation and invasion and increased the cell sensitivity to docetaxel. In conclusion, N-glycosylation of ACTRIIB was a critical post-translational modification that enhanced protein stability and induced membrane localization, which facilitates the functions of ACTRIIB in cell proliferation and invasion in NPC. Inhibition of ACTRIIB N-glycosylation could potentially serve as a therapeutic strategy to improve the efficacy of chemotherapy in NPC.

Abstract in English:

Hepatic ischemia reperfusion injury (HIRI) is a pathophysiological and complex systemic process involving multiple tissues and organs. Gastrodin (GSTD), a natural compound from Gastrodia elata, displays a variety of interesting pharmacological activities. Heme oxygenase-1 (HO-1), a stress-responsive protein, has a cytoprotective defense response against oxidative and inflammatory injuries. The aim of this investigation was to elucidate whether GSTD plays a protective role against HIRI by regulating HO-1 expression. GSTD (100 mg/kg) or zinc protoporphyrin (15 mg/kg; an HO-1 inhibitor) was administered to HIRI C57 male mice. GSTD decreased glutamic pyruvic transaminase and glutamic oxaloacetic transaminase levels in HIRI mice. Inflammatory (TNF-α and IL-6) and oxidative-stress (malondialdehyde, MDA) markers of HIRI mice were decreased by GSTD. GSTD up-regulated HO-1 protein and mRNA expression in HIRI mice but decreased caspase-3 and -9 protein expression. GSTD lowered mRNA expression of apoptosis-related genes (caspase-3, -9, -12, and Bax) in the liver of HIRI mice but enhanced mRNA level of the anti-apoptotic Bcl-2 gene. Consistent with in vivo results, GSTD displayed a similar regulatory effect on the expression of mRNA (HO-1, caspase-3, -9, -12, Bax, and Bcl-2) and protein (HO-1, caspase-3 and -9) as well as inflammatory (TNF-α and IL-6) and on oxidative stress factors (superoxide dismutase and MDA) in BRL-3A cells transfected with small interfering HO-1 RNA in a hypoxia-reperfusion model. In conclusion, GSTD up-regulated HO-1 expression to play a protective role in HIRI by anti-apoptotic, anti-inflammatory, and antioxidant effects. GSTD is a promising natural compound that alleviated HIRI in liver surgery.

Abstract in English:

Although correlated to peak oxygen uptake (VO2), the six-minute walk test (6MWT) alone cannot provide precise physiological insight regarding the specific cause(s) of exercise limitations. We aimed to analyze whether 6MWT is able to properly detect differences in the cardiorespiratory responses between patients with stable coronary artery disease (SCAD) and those with ischemic cardiomyopathy (IC) and determine whether the degree of abnormality in ejection fraction is related with impaired submaximal exercise capacity. Twenty-two subjects with SCAD and 19 subjects with IC underwent a 6MWT while simultaneously using a mobile telemetric cardiopulmonary monitor to assess cardiorespiratory responses. VO2 response at exercise onset was used to obtain VO2 on-kinetics, and the slope of ventilation vs carbon dioxide output (VE/VCO2) was calculated. IC subjects exhibited significantly delayed VO2 on-kinetics compared with the SCAD group (P<0.01) and higher VE/VCO2 slope (IC=40.45 [95%CI: 39.76 to 41.1] vs SCAD=34.36 [95%CI: 34.03 to 34.69], P=0.001). The left ventricular ejection fraction (LVEF) was moderately correlated with VO2 on-kinetics in the SCAD group, but no relationship was found in the IC group. Pulmonary function was correlated with the VE/VCO2 slope only in the IC group. Subjects with IC presented slower VO2 on-kinetics during the 6MWT than those with SCAD. Once reduction in left ventricular function is achieved, LVEF had no association with exercise capacity. Pulmonary function could help identify IC patients at risk of ventilatory inefficiency and may add diagnostic power to the 6MWT.

Abstract in English:

Sleep duration is associated to various health impairments, while its comprehensive association with tinnitus is rarely investigated. The current study aimed to explore the relationship between sleep duration and tinnitus incidence, and to determine the optimal sleep duration relating to the lowest tinnitus risk. Data of participants from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2012 and 2015 to 2018 were retrieved. A total of 13,871 participants were eligible and included in the analysis. Generally, sleep duration was lower in participants with tinnitus compared to those without (7.15±1.76 vs 7.30±1.51 h, P<0.001). After adjustment by demographics, lifestyle, and chronic diseases, a U-shaped relationship between sleep duration and tinnitus incidence was observed, with the inflection point at 8.5 h. Interestingly, in participants with sleep duration <8.5 h, sleep duration exhibited an independent negative correlation with tinnitus risk [OR=0.88 (95%CI: 0.84-0.93), P<0.001], while in participants with sleep duration ≥8.5 h, sleep duration had an independent positive association with tinnitus risk [OR=1.16 (95%CI: 1.04-1.28), P=0.006]. In conclusion, a U-shaped relationship was found between sleep duration and tinnitus incidence, with a sleep duration of about 8.5 h being associated with the lowest tinnitus risk.

Abstract in English:

Neutrophil extracellular traps (NETs) are a novel regulatory mechanism of neutrophils, which can promote endothelial cell inflammation through direct or indirect pathways and play a crucial role in the occurrence and development of atherosclerosis (AS). This study aimed to explore the mechanism of NETs in AS progression using bioinformatics methods. We acquired datasets from Gene Expression Omnibus (GEO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and used Weighted Gene Co-expression Network Analysis (WGCNA) to identify communal genes shared by NET-related genes. Gene Ontology (GO) and KEGG enrichment analyses were conducted. Machine learning algorithms were used to identify hub genes, then protein-protein interaction (PPI), CO-expression network construction, nomogram model building and validation, and immune infiltration analysis were performed. Data were verified by qPCR. Four datasets related to AS progression were included. Module genes shared 27 genes with NRGs. Pathways related to immune regulation, leukocyte migration, and others were identified. Machine learning revealed SLC25A4 and C5AR1 as hub genes. SLC25A4 and C5AR1 were confirmed to have predictive value for intraplaque hemorrhage (IPH), advanced AS plaques, ruptured plaques, and unstable plaques. These pathologic changes are closely related to AS progression and are the main contents of AS progression. Immune infiltration analysis revealed 4 immune cells associated with IPH, among them resting dendritic cells, which were closely related to SLC25A4. In qPCR validation, SLC25A4 and C5AR1 were shown to be consistent with the bioinformatic analysis results. These findings provided novel insights into the molecular characteristics of NRGs and potential therapies for AS progression.

Abstract in English:

1α,25-Dihydroxyvitamin D3 (VD3), the active form of vitamin D, plays a crucial role in wound healing. In this study, we aimed to investigate the effect of VD3 on the proliferation and differentiation of epidermal stem cells (EpSCs) and monitor its impact on re-epithelialization. We established a murine full-thickness skin defect model and applied four doses of VD3 (0, 5, 50, and 250 ng/mouse/day) to the wounds topically for three days. Immunostaining and flow cytometry confirmed the effect of VD3 on the proliferation and differentiation of EpSCs in wounds. This effect of VD3 (0, 1, 10, and 50 nM) on EpSCs and its possible mechanism were further confirmed in vitro by CCK8, westen blot, immunostaining, and flow cytometry. We found that on day five post-wounding, the means±SD length of the neo-epidermis was 195.88±11.57, 231.84±16.45, 385.80±17.50, and 268.00±8.22 μm in the control, 5, 50, and 250 ng groups, respectively, with a significant difference from the control (all P<0.05). Immunostaining and flow cytometry showed that VD3 improved the proliferation and differentiation of K15+ EpSC (vs control, all P<0.05), K14+ epidermal progenitor cells (vs control, all P<0.05), and K10+ epidermal terminal cells (vs control, all P<0.05) in vivo and in vitro. The PI3K signaling pathway appeared to underlie this response because significant inhibition of the response was found when inhibitors were used to inhibit PI3K. Our study demonstrated that VD3 is a potent promoter of cutaneous wound healing by stimulating EpSC proliferation and differentiation through PI3K activation.

Abstract in English:

During the COVID-19 pandemic in Shanghai, medical workers were more vulnerable to psychological problems. This two-phase cross-sectional survey was conducted by online questionnaires to investigate the symptoms of depression, anxiety, stress, post-traumatic stress disorder (PTSD), and fatigue in healthcare workers during the outbreak of COVID-19 and after the resumption of work and production in Shanghai. The questionnaire included the Depression Anxiety Stress Scale-21 (DASS-21), the Impact of Event Scale-Revised (IES-R), and the Fatigue Assessment Instrument (FAI). In Phase I (n=2192), the prevalence of depression, anxiety, stress, and PTSD symptoms among medical staff was 45.48, 41.93, 20.35, and 75.55%. In Phase II (n=1031), after work resumed in Shanghai, the prevalence was 19.79, 21.44, 28.23, and 12.22%, respectively. Fatigue had a mean score of 121.23±45.776 in Phase I and 144.73±44.141 in Phase II. Binary logistic regression identified risk factors associated with this psychological status: personal and familial chronic disease history; occupation, including doctor, nurse, or administrative staff; working in the fever clinic, infectious disease department, emergency or intensive care unit, hemodialysis room, or clinical laboratory; work experience of 3-6 years or 7-10 years; and involvement in nucleic acid sampling team. Medical staff self-reported comparatively high rates of depression, anxiety, stress, and, especially, PTSD symptoms during the COVID-19 pandemic in Shanghai. Our study indicated that after work resumption in Shanghai, it appeared that the overall mental health of medical staff improved somewhat. Nevertheless, the high level of fatigue exhibited still cannot be ignored.

Abstract in English:

Maximum oxygen uptake (V̇O2max) equations from developed countries are inaccurate for developing countries. Accordingly, we aimed to develop equations to predict treadmill V̇O2max over time based on variables other than exercise test in adults from the USA and Brazil undergoing cardiopulmonary exercise testing (CPET). We analyzed data from 2,170 adults who underwent two CPETs (1,307 men; 20-85 years) from the USA (n=1,880) and Brazil (n=290) with a second test after 2.0±1.7 years on average. We fit linear mixed-effects models to develop equations using 90% of the sample, randomly selected. In the remaining 10% of the cohort, we used the coefficient of variation, intraclass correlation coefficient, and the Bland and Altman plots to cross-validate the optimal equation. Our best linear mixed model equation was as follows: V̇O2max (mLO2·kg-1·min-1) = 62.01 - (0.23×Ageyears) - (0.001×Age×Age) - (0.65×Body mass indexkg/m 2) + (5.47×Sexfemales=0; males=1) + (2.78×CountryBrazil=0; USA=1) - (0.68×Arterial hypertensionno=0; yes=1) - (0.45×Hyperlipidemiano=0; yes=1) - (2.02×Smokingno=0; yes=1) - (4.36×Insufficiently activeno=0; yes=1) - (1.67×Beta-blockersno=0; yes=1); R2=0.566. Our main equation was reliable at baseline according to Bland and Altman plot results (mean difference, 0.01 mLO2·kg-1·min-1: 95%CI, -13.94 to 13.98; P=0.966) and over time (0.44 mLO2·kg-1·min-1: 95%CI, -13.5 to 12.4; P=0.439). Demographic and anthropometric attributes, cardiovascular risk, and beta-blockers are valuable for predicting V̇O2max at baseline and over time. The developed equations may apply to countries with socioeconomic and demographic characteristics such as Brazil and the USA.

Abstract in English:

As limb muscle function is age- and sex-related, both elbow and knee isokinetic muscle functions and their main predictors, such as physical activity level and cardiovascular risk factors, should be determined. We aimed to describe the percentiles of normality of the isokinetic muscle function of the knee and elbow joints. Secondarily, we developed equations to predict muscle function in apparently healthy adults aged 20-80 years, including cardiovascular risk factors. We conducted a cross-sectional study with 1,334 adults. We collected sociodemographic data, self-reported cardiovascular risk, anthropometry, body composition (bioelectrical impedance), moderate-to-vigorous physical activity (MVPA) (triaxial accelerometry), and isokinetic muscle function. Multiple regression analysis was used to develop equations to predict isokinetic muscle function. Percentiles of normality for muscle function were described by sex and age (20-39, 40-59, and >60 years). The models accounted for 49.6-70.9% of the total variability of muscle function, but MVPA and cardiovascular risk slightly influenced the coefficient of determination (additional ΔR2=0.003-0.006). Demographic and anthropometric variables were more relevant predictors of isokinetic muscle function (R2=0.50-0.70) than MVPA and cardiovascular risk. Even though they correlated with muscle function, cardiovascular risk and MVPA failed to explain the variability of muscle function largely determined by anthropometric and sociodemographic data. The percentile values and equations developed will help in interpreting the isokinetic muscle function and improve its clinical use.

Abstract in English:

Age-related macular degeneration (AMD), particularly the wet form characterized by choroidal neovascularization, is a leading cause of vision loss. Dysregulation of regulatory T cells (Tregs), key modulators of inflammatory responses, may contribute to wet AMD pathogenesis. This study explored the involvement of Tregs and the Rac1 signaling pathway in modulating Treg-derived cytokine expression and their role in choroidal neovascularization during wet AMD progression. Peripheral blood samples from healthy controls, dry AMD patients, and wet AMD patients were collected. An in vitro transmembrane co-culture system of Tregs and human choroidal endothelial cells (HCECs) was employed to investigate the impact of Tregs (with or without Rac1 silencing) on the angiogenic phenotype of HCECs. A mouse model of AMD was established to evaluate the effects of a Rac1 inhibitor and IL-10/TGF-β neutralization on Tregs and choroidal neovascularization. An increased Treg percentage in the CD4+ T lymphocyte population was found in the peripheral blood samples of wet AMD patients. Tregs from wet AMD patients showed an increased expression of Rac1 and an elevated production of IL-10 and TGF-β1. Rac1 silencing suppressed Treg stability and differentiation, and impaired the pro-angiogenic effect of Tregs on HCECs. In the animal model of AMD, the administration of a Rac1 inhibitor or neutralizing antibodies against IL-10/TGF-β1 reduced Treg abundance and attenuated choroidal neovascularization. Rac1 upregulation in Tregs promoted IL-10 and TGF-β1 production to mediate choroidal neovascularization in wet AMD. Targeting Rac1 and Treg-derived IL-10/TGF-β1 production in Tregs may serve as a strategy to ameliorate AMD progression.

Abstract in English:

Osteonecrosis of the femoral head (ONFH) is a debilitating condition characterized by the death of bone cells in the hip joint, resulting in profound disability. This condition has a significant global prevalence. Glucocorticoid (GC)-induced apoptosis of bone cells serves as a crucial cellular mechanism underlying ONFH. The protein kinase C zeta (PKCζ) and c-Jun N-terminal kinase (JNK)/c-Jun cascades have been implicated in the progression of ONFH, yet their interrelationship and contributions to disease development remain unclear. The objective of this study was to investigate the combined impact of PKCζ and JNK/c-Jun signaling on dexamethasone (Dex)-induced apoptosis in osteoblasts in vitro and in GC-induced ONFH rat models in vivo. In vitro experiments were conducted using hFOB1.19 osteoblastic cells to scrutinize the effects of Dex-induced apoptosis. The role of the PKCζ/JNK/c-Jun signaling pathway in this process was examined using naringenin-7-O-β-D-Glucuronide (N7G), a PKC inhibitor, and anisomycin, a JNK activator. The findings were further validated using a rat model of ONFH in vivo. Our results revealed that PKCζ activation augmented JNK/c-Jun signaling and facilitated Dex-induced osteoblast apoptosis. Inhibition of PKCζ with N7G mitigated these effects, while JNK activation with anisomycin intensified them. Similar regulatory effects on osteoblast apoptosis and ONFH progression were observed in the in vivo rat models. Glucocorticoids can induce osteoblast apoptosis and contribute to the development of ONFH by activating the PKCζ/JNK/c-Jun signaling pathway. This study provides compelling evidence supporting the potential therapeutic value of comprehending the pathogenesis of ONFH and developing targeted treatments for this debilitating condition.

Abstract in English:

Prenatal care is of fundamental importance and must be carried out by a multidisciplinary healthcare team, including dental care, as several changes and complications affecting the oral cavity may occur during pregnancy. This was a cross-sectional study that aimed to analyze the hematological profile of pregnant women with and without periodontal disease (PD). Data were obtained by consulting medical and dental records, which were stratified into two subgroups: pregnant women with PD (n=107) and pregnant women without PD (n=42). Study variables were related to PD, sociodemographic, clinical, and laboratory characteristics. Data were collected from the complete blood count and the following indices were calculated: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), derived NLR (dNLR), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI), and systemic immune-inflammation index (SII). The mean age in both subgroups was 27 years. Pregnant women with less education had more PD. Mean corpuscular volume was significantly higher in pregnant women with PD, probably a reflection of folate deficiency. White blood cell and lymphocyte counts were significantly higher in pregnant women with periodontitis, possibly reflecting an inflammatory process caused by bacterial invasion of the periodontium with systemic repercussions. This study reinforces the need for a multidisciplinary team, including a dentist, in prenatal care, to lower the risk of complications for the mother and child.

Abstract in English:

Dysfunction of the intestinal epithelium barrier (DIEB) is frequent and can lead to serious complications in early childhood when diagnosis and clinical intervention are limited, especially in children with environmental enteric disease and malnutrition. The use of refined analytical techniques is increasingly necessary in this context. This study aimed to validate the high-performance liquid chromatography method coupled with tandem mass spectrometry (LC-MS/MS) to measure DIEB by lactulose:mannitol ratio detection (LM test) in samples of children with different social profiles from Fortaleza, Ceará. The first experimental set was conducted to validate the method through laboratory parameters, such as limit of detection (LD), limit of quantification (LQ), specificity/selectivity, linearity, accuracy, and precision. All validation parameters achieved detection and recovery standards within an acceptable coefficient of variation. Community samples (human development index (HDI) from 0.000 to ≤0.499) were obtained from children from the cohort study Malnutrition-Enteric Diseases, Fortaleza-CE (environmental enteric disease; EED group). The control group samples came from a school located in a region with a high HDI (>0.8). Mannitol excretion was lower in the EED group than in the control group (P<0.0001). On the other hand, LM was higher in this group compared to the control group (P<0.0001). For the first time, a robust analytical approach was used to detect biomarkers of environmental enteropathy (LM) in community samples, confirming with high-sensitivity the damage to the intestinal epithelial barrier function in populations living in low socio-economic conditions.

Abstract in English:

Coptisine (COP), a naturally occurring alkaloid, is recognized for its varied pharmacological impacts and its supportive function in intestinal well-being. However, the role of COP to protect the colonic epithelium in colitis has not been extensively investigated. The objective of this study was to assess the efficacy of COP in ameliorating colitis by investigating intestinal histopathology, mucosal barrier function, and transient receptor potential (TRP) signaling pathways in mice with colon disease compared to a control group, thereby elucidating the underlying mechanisms of its action. The results demonstrated a marked improvement in diarrhea and bleeding, an improvement in general behavioral competencies of the mice, and a decrease in disease activity index (DAI) scores. Histopathological analysis indicated a reduction in intestinal inflammation and an enhancement of intestinal mucosal barrier function. Our research identified that the protein expressions of the TRP family including transient receptor potential cation subfamily M member 8 (TRPM8), transient receptor potential vanilloid 1 (TRPV1), and transient receptor potential ankyrin 1 (TRPA1) were significantly upregulated with COP treatment. Compared with the model, COP markedly downregulated cytosolic phospholipase A2 (cPLA2) levels, while upregulating calcitonin gene-related peptide-1 (CGRP-1) protein expressions. Our study revealed that COP enhanced intestinal barrier function by modulating the cPLA2/TRPM8/CGRP-1 signaling pathway, thus shedding light on the mechanism by which COP mitigates inflammation in the intestinal mucosa. These findings provided new insights on COP as a therapeutic agent in ulcerative colitis (UC).

Abstract in English:

Rapid dissemination of Klebsiella pneumoniae carbapenemase (KPC) is a leading cause of treatment failure, significantly increasing morbidity and mortality rates among inpatients, particularly in the intensive care unit (ICU). This study aimed to detect the occurrence of carbapenemase- and carbapenem-resistant-encoding genes in K. pneumoniae isolates from COVID-19 positive and negative patients, and to assess their impact on patient outcomes. A prospective analysis was conducted at a tertiary care hospital in Saudi Arabia, collecting 97 carbapenem-resistant K. pneumoniae (CRKP) isolates from patients with COVID-19 during 2020-2021. Isolates were obtained from various clinical specimens. Antimicrobial susceptibility assays were performed using the Automated Vitek-2 system, and data were analyzed using IBM SPSS Statistics. The predominant carbapenemases identified were Oxacillinase-48 (OXA-48), followed by KPC and New Delhi metallo-β-lactamase (NDM), with Imipenemase (IMP) and Verona integron-encoded metallo-β-lactamase (VIM) being the least prevalent. COVID-19 did not significantly affect the distribution of these genes (P>0.05); however, COVID-19 status and age over 60 years significantly impacted the outcomes of CRKP patients. Other factors such as gender, total ICU or ward stay, and comorbidities did not significantly affect CRKP infection outcomes. The most common carbapenem-resistant genes identified were blaKPC, blaNDM, and blaOXA-48; however, they were not significantly associated with increased mortality.

Abstract in English:

Axons of dopaminergic neurons projecting from substantia nigra to striatum are severely affected in the early stage of Parkinson's disease (PD), with axonal degeneration preceding the loss of cell bodies. Our previous study indicated that the dysfunctional retrograde axonal transport could lead to the death of dopaminergic neurons resulting in PD (10.1111/j.1471-4159.2008.05526.x). However, dynein, as the main molecule involved in retrograde axonal transport, was not affected. This study aimed to verify the hypothesis that dynactin rather than dynein may be one of the key factors in the retrograde degeneration of dopaminergic neurons in the early stage of PD. Dynactin morpholino was used to inhibit the expression of dynactin in transgenic (Vmat2:GFP) zebrafish, resulting in a significant decrease of diencephalon dopamine neurons and synuclein aggregation in the basal plate region. In the dopaminergic SH-SY5Y cell line, dynactin-siRNA knockdown resulted in the expression of dynein shifting from dispersed distribution to concentration in synapses and cytoplasm near axons, and the fusion rate of dynein to dynactin was decreased, especially in axons, which blocked the retrograde axonal transport of α-synuclein and autophagy flow. Our results linked the knockdown of dynactin gene to the dysfunction of axonal microtubule transport system, suggesting that dynactin may be one of the key factors contributing to the retrograde degeneration of dopaminergic neurons in the early stage of PD.

Abstract in English:

Sprint interval training (SIT), which consists of vigorous-intensity exercise interspersed with periods of rest or low-intensity exercise, can improve human anaerobic performance. Probiotic strains, including yeasts (e.g. Saccharomyces boulardii; Sb), have beneficial effects on human health; however, evidence regarding the effects of probiotics on anaerobic performance is unavailable. The current study investigated whether Sb supplementation influences the SIT-induced changes to the following performance variables: peak (PPO) and mean (MPO) power output. Fifteen healthy individuals (twelve men and three women) were randomly divided into two groups: placebo (PLA; n=8) and Sb (n=7). The individuals performed six SIT sessions on a cycle ergometer (four to seven 30-s all-out sprints thrice weekly). During the training period, participants ingested a capsule containing PLA or at least 1×109 Sb cells daily for 14 days. Performance-related variables were compared between the first and last training sessions. Sb supplementation did not influence the changes in PPO and MPO across the two weeks of training (P>0.05); therefore, the data from both groups were analyzed collectively to assess performance changes induced by SIT. Training increased PPO, an index of anaerobic power, in the sixth session compared to the first session (by 8±11% in the first sprint; +1.0±1.2 W/kg; P=0.008) but did not change MPO. In conclusion, short-term SIT improved the participants' anaerobic performance (power), as evidenced by increased PPO. Sb supplementation did not affect the improved anaerobic power caused by SIT.

Abstract in English:

The COVID-19 pandemic has caused a global crisis, overwhelming hospitals and intensive care units (ICU) and leading to an increase in nosocomial infections due to prolonged hospitalization and other risk factors. The present study evaluated the prevalence of secondary fungal infections in critically ill patients with COVID-19. This is a retrospective, single-center study conducted in a hospital in northeastern Brazil, which evaluated 1,364 medical records of patients admitted to a COVID-19 ICU during 2020 and 2021. A total of 327 pathogenic yeasts were isolated from 132 (40.4%) respiratory, 70 (21.4%) blood, 124 (37.9%) urine, and one (0.3%) surgical wound samples. Fungal infections were diagnosed in the intermediate (5 to 12 days) or late (≥12 days) stage of hospitalization. The most frequent yeast isolated from critically ill COVID-19 patients was Candida albicans [126 (67.7%) and 60 (42.6%)], followed by Candida tropicalis [25 (13.4%) and 39 (27.7%)]. Candida parapsilosis isolates increased 5.7-fold in 2021 [40 (28.4%)] compared to 2020 [7 (3.8%)]. The least frequently isolated in 2020 and 2021 were Nakaseomyces glabratus [4 (2.2%) and 1 (0.7%)], and Pichia kudriavzevii, which was isolated only in 2021 (1 (0.7%)). During the study period, a decrease in susceptibility to antifungals was observed: susceptibility to voriconazole reduced from 100 to 77.2%, to flucytosine from 99.4 to 78.8%, and to micafungin from 99.4 to 83.6%. The changes in the frequency of species causing secondary infections in critically ill COVID-19 patients and susceptibility to the antifungals indicate the need for early and adequate diagnosis to minimize negative outcomes.

Abstract in English:

Cellular senescence is an important cause of age-related degenerative diseases, including osteoarthritis (OA). Chondrocyte senescence is crucial in OA onset and progression. As a non-invasive, safe, and widely used physical rehabilitation factor, the effect and mechanism of low intensity pulsed ultrasound (LIPUS) on chondrocyte senescence remain unclear. This study evaluated the inhibitory effect of LIPUS on OA chondrocyte senescence in vitro and in vivo. The effect of LIPUS on chondrocyte senescence was examined by RT-qPCR, enzyme-linked immunosorbent assay (ELISA), and western blotting. Changes in levels of reactive oxygen species (ROS) and γ-h2ax foci in senescent chondrocytes were detected using fluorescent staining. Chondrocyte senescence was evaluated by senescence-associated β-galactosidase (SA-β-gal) staining. The PI3K inhibitor LY294002 and the PI3K agonist 740Y-P were used to investigate whether PI3K/AKT/mTOR signalling was involved in the effect of LIPUS in senescent chondrocytes. Chondrocyte senescence and cartilage degeneration were analyzed in a destabilization of the medial meniscal (DMM) mouse model by immunohistochemistry, hematoxylin and eosin staining, and safranin-O/fast green staining. LIPUS inhibited the expression of the senescence-associated secretory phenotype (SASP) factors CCL4 and CCL2 and the senescence phenotype in doxorubicin-treated chondrocytes by inhibiting the PI3K/AKT/mTOR pathway. LIPUS alleviated chondrocyte senescence and attenuated OA progression in the DMM mice. These results demonstrated a novel role for LIPUS in inhibiting chondrocyte senescence and the SASP by modulating PI3K/AKT/mTOR signalling. Our findings expanded the clinical application of LIPUS and provide a new, non-invasive, and safe treatment approach to prevent and treat age-related degenerative joint disorders.

Abstract in English:

Oral tolerance is an immunological phenomenon that results from protein intake and that has systemic effects on inflammation. Previous research has shown that parenteral injection of tolerated proteins reduces inflammatory infiltrate and improves skin wound healing. Herein, we tested whether the injection of tolerated proteins improves the healing of several wounds on different parts of the body, such as on the skin of the back and on the external ear (the auricle). To induce oral tolerance to ovalbumin (OVA), eight-week old C57BL/6 mice drank egg white diluted 1:5 in water for 3 consecutive days. The control mice drank water. Seven days after oral treatment, mice were submitted to excisional injuries on the skin of the back (6 mm) and ears (4 mm). Minutes before the injuries, the mice received an intraperitoneal injection of OVA + Al(OH)3. Seven and 40 days after the injuries, tissue samples were collected and processed for histological analysis of the wounds. The results showed that the injection of OVA in animals that drank OVA reduced the inflammatory infiltrate in all lesions. In addition, injection of OVA in animals that drank OVA promoted better organization of the extracellular matrix, with thicker and intertwined collagen fibers in the neodermis, resulting in smaller scars on the skin. Furthermore, the healing area of the ears of OVA-tolerant animals showed chondrocyte aggregates and less obvious fibrous scar tissue compared with control animals. In conclusion, systemic effects of oral tolerance positively influenced the healing of several lesions on different parts of the body.

Abstract in English:

The objective of the present study was to compare and test the applicability of different protocols for accessing aerobic capacity in Sprague Dawley rats using treadmill running. Fifteen 70-day-old adult Sprague Dawley rats (270-290 g) were used. After 5 days of adaptation to the treadmill, the animals underwent 7 days of evaluations with a 48-h interval between each protocol. On the first two days, they underwent, in random order, a graded exercise test, with (GXT2) or without (GXT1) blood sample collections to determine blood lactate concentrations and the anaerobic threshold. In the subsequent 4 days, they underwent continuous 30-min efforts to determine the maximal lactate steady state (MLSS) with the intensity prescribed in percentages of the maximum speed (MaxS) obtained in GXT1, and on the last day they underwent the minimum lactate (ML) protocol. The MaxS obtained in GXT2 was higher than in GXT1, and there was a moderate correlation (r=0.614, P=0.011) between them. In many cases, lactate and glucose blood concentrations did not show the expected kinetics, making aerobic capacity determination impossible using these protocols. MLSS showed a higher success rate compared to other protocols (MLSS=80%; GXT2=47%; ML=60%). In conclusion, with the MLSS protocol, it is only possible to measure time to exhaustion at each intensity, which does not exactly reflect aerobic capacity, and the use of blood lactate and glucose concentrations to evaluate the aerobic capacity of rats in incremental and ML treadmill running protocols is still discouraged.

Abstract in English:

Immune checkpoint blockade with anti-programmed cell death protein 1 (PD-1) antibody has become a hot topic for the treatment of human malignancies. Here, we aimed to investigate whether the percentage of PD-1 in CD8+ tumor-infiltrating lymphocytes correlates with the progression of colonic-derived peritoneal adenocarcinoma (PA). Peripheral blood and tissue samples from 40 patients with colonic-derived PA were collected and subjected to multicolor flow cytometry analysis of the percentage of peripheral PD-1+CD8+ T cells. The multiple immunofluorescence method was used to detect the positive percentages of PD-1 and CD8 in the tissues. The enrolled patients were divided into groups by recurrence interval (less than 6 months, greater than two years) and differentiation grade (low, well/moderate). In the colonic-derived PA tissues, the percentages of cells positive for PD-1, CD8, and PD-1+CD8+ were higher in the paracancer tissues compared with cancerous tissues. PD-1+CD8+ T cells had an increased presence in peripheral blood than in tissues. Our data also indicated that colonic-derived PA patients with less than a six-month recurrence interval presented higher levels of PD-1 in CD8+ tumor-infiltrating lymphocytes in than the two-year recurrence group. The level of PD-1+CD8+T cells in the tissue correlated with the clinical outcome of colonic-derived PA. Higher percentages of PD-1+CD8+T cells correlated with a shorter progression-free survival (PFS). PD-1 in CD8+ tumor-infiltrating lymphocytes may have a good predictive value for immunotherapy of colonic-derived PA and act as the prognostic factor for PFS.

Abstract in English:

Liraglutide (LIRA) is an agonist of the GLP-1 receptor used in the treatment of type 2 diabetes with a cardioprotective effect, although little is known about the effects of LIRA in post-menopause. We aimed to evaluate the effects of LIRA in the cardiovascular system of ovariectomized spontaneously hypertensive rats (SHR). SHR rats were separated into two groups: ovariectomized (saline) and ovariectomized + liraglutide (0.6 and 1.2 mg/kg for 4+4 weeks, respectively). Systolic blood pressure (SBP) was indirectly evaluated at the beginning and end of treatment. Diastolic, systolic, and mean blood pressure were evaluated in the carotid artery of anesthetized animals, while left ventricle systolic blood pressure (LVSBP) and left ventricle derivatives (-dP/dt; +dP/dt) were evaluated in the left ventricle. An oral glucose tolerance test (GTT) was conducted. Antioxidant enzymes and calcium-handling proteins were analyzed in heart tissue by western blot. Treatment with LIRA increased the expression of antioxidant enzymes (superoxide dismutase (SOD2) and catalase). No changes were observed in the GTT, cardiac hemodynamics, blood pressure, and calcium-handling protein expression. A decrease in visceral fat depot was observed without changes in final body weight. LIRA induced an antioxidant subclinical effect in ovariectomized SHR female rats without changing glucose metabolism and cardiac blood pressure.

Abstract in English:

Oleanolic acid (OA) is recognized for its anticancer properties, which are similar to those of conventional chemotherapeutic agents used in clinical practice. However, its role in modulating the sensitivity of cancer cells to fluorouracil (5FU) has not yet been documented. This study aimed to examine the effects of OA and 5FU co-administration on hepatocellular carcinoma (HCC) and uncover the mechanisms involved. In this study, the efficacy of combination therapy with OA and 5FU in treating HCC was evaluated using the MTT cell proliferation assay, plate clone formation assay, Hoechst 33342 staining, western blot assay, and Ca2+ fluorescence probe. The results demonstrated that compared with the use of OA or 5FU alone, OA and 5FU combination therapy significantly inhibited the proliferation of HEPG2 cells and enhanced cell apoptosis and Ca2+ levels in HCC. Additionally, the inhibitory effect of OA and 5FU combination therapy on cell proliferation and apoptosis was partially reversed by the calcium channel blocker 2-aminoethyldiphenyl borate (2-APB). In summary, these findings indicated that synergistic treatment with OA and 5FU can enhance cell apoptosis, inhibit cell proliferation, and regulate Ca2+ signaling in HCC, providing new guidance for the clinical treatment of HCC.

Abstract in English:

Endometrial cancer (EC) is the most common pelvic gynecologic malignancy in developed countries, and its incidence is also increasing in developing countries. Endometrioid endometrial carcinoma (EEC) is the most frequent subtype. EEC is often associated with favorable clinicopathological features and a good prognosis, especially when diagnosed in stage I. Although some patients have no signs to predict locally advanced or metastatic disease, they may present tumor relapse in the future. There is no biomarker capable of predicting the relapse of stage I EEC. The present study applied a transcriptome analysis to identify differentially expressed genes in stage I EEC, comparing relapsed with non-relapsed tumors. The estrogen receptor 1 gene (ESR1) was overexpressed in EEC stage I samples from patients who developed relapse by 4.3-fold compared to non-relapsed tumors. Subsequently, an independent set of 64 stage I EEC samples was used to validate ESR1 gene overexpression in relapsed tumors and assess estrogen receptor alpha (ERα) protein levels. ESR1 was confirmed to be overexpressed in samples from relapsed tumors, and its expression level was an independent prognostic variable for disease-free (hazard ratio=7.25) and overall survival (hazard ratio=5.15). In contrast, Erα did not show different values between relapsed and non-relapsed tumors. We concluded that ESR1 overexpression is a biomarker for poor prognosis in stage I EEC.

Abstract in English:

There are significant gaps in understanding the extent of the damage caused by COVID-19, with few publications examining its link to contrast sensitivity function (CSF). The aim of the present study was to evaluate CSF at low, medium, and high spatial frequencies in individuals with and without a history of COVID-19. Thirty adults, both male and female, aged between 18 and 49 years, participated in the study, 15 with a history of COVID-19 and 15 without. CSF was measured using Metropsis software (version 11) and vertical sine-wave gratings with spatial frequencies ranging from 0.2 to 19.8 cycles per degree (cpd). The results indicated COVID-19-related changes in CSF at spatial frequencies of 6.1 (U=36.00; P=0.003; r=-0.55), 13.2 (U=29.00; P=0.001; r=-0.61), 15.9 (U=17.00; P=0.001; r=-0.70), and 19.8 cpd (U=13.00; P=0.001; r=-0.73). The observed decrease in CSF within specific spatial frequency bands suggested that the visual system of individuals exposed to COVID-19 required higher contrast levels to detect high spatial frequencies. This psychophysical finding indicated that COVID-19 altered the functioning of the visual system and likely affected the neural mechanisms responsible for processing high spatial frequencies.

Abstract in English:

The primary objective of the present study was to identify differentially expressed genes (DEGs) associated with castration-resistant prostate cancer (CRPC) to verify the potential mechanism of CRPC progression. DEGs from CRPC datasets were filtered with a P<0.05 and Spearman correlation coefficient ≥0.3. Serpin peptidase inhibitor, clade A member 3 (SERPINA3), was uniquely present in three CRPC datasets, and its low expression in CRPC was confirmed in cell lines and tissues. Colony formation, transwell assays, and subcutaneous tumor formation experiments in mice demonstrated that overexpression of SERPINA3 may significantly inhibit the proliferation and invasion of PC3 cells. Mechanistic studies revealed that, in prostate cancer (PCa), SERPINA3 can activate the interleukin (IL)-17 and tumor necrosis factor (TNF)α signaling pathways by promoting the expression of CXC chemokine ligand 2 (CXCL2), thereby increasing the recruitment of M1 macrophages into the tumor microenvironment and inhibiting the progression of PCa. The current results indicated that the expression of SERPINA3 may be negatively correlated with CRPC, and it could promote the M1 polarization of macrophages and inhibit the progression of CRPC by increasing the expression of CXCL2.

Abstract in English:

Bladder cancer is the most prevalent malignancy of the urinary tract, with significant advancements in treatment achieved over recent decades. Nonetheless, the immunological mechanisms underlying bladder cancer progression remain elusive, and only a limited number of patients derive benefit from current immune checkpoint inhibitors. Here, we conducted a single-cell RNA sequencing analysis of 44,022 cells from peripheral blood mononuclear cell samples of bladder cancer patients and a healthy donor. Our findings indicated that the proportions of T cells and neutrophils are higher in bladder cancer patients than in the healthy donor. LAG3, HAVCR2, and CTLA4 had elevated expression levels in CD8-T2-GZMK cell clusters from patients. CD8-T7-STMN1 cells highly expressed ITGAE, CD38, and STMN1. Furthermore, NK3-CMC1, more prevalent in patients, showed a high expression of TIGIT. Additionally, Bcell2-TCL1A and Bcell3-MS4A1 were characterized by the high expression of inhibitory receptor marker genes. Gene set variation analysis suggested that Mono4-THBS1 may play a role in promoting tumor hypoxia and angiogenesis. Neu-FCGR3B exhibited high levels of IL4R and CD274 expression. Our study indicated that LAG-3 and TIM-3 may serve as novel potential immune checkpoint inhibitors in bladder cancer treatment. The phenotypes of NK3-CMC1, Bcell2-TCL1A, and Bcell3-MS4A1 might be altered by tumor progression. Mono4-THBS1 could potentially be a source of tumor-enriched monocyte-like cells. Neu-FCGR3B may play a detrimental role in the anti-tumor response and could emerge as a predictive marker for bladder cancer. Overall, these high-resolution transcriptomic data offer invaluable insights for identifying new therapeutic targets and biomarkers in bladder cancer immunotherapy.

Abstract in English:

The aim of this study was to explore sex differences in neuromuscular fatigue during a severe-intensity cycling exercise. Twenty-four healthy participants (12 women and 12 men) cycled at 80% of the difference between gas exchange threshold and maximal power output to the limit of tolerance. Neuromuscular fatigue was assessed by the decrease in maximal voluntary contraction of the knee extensors before and after exercise, and central and peripheral fatigue was measured by the decrease in voluntary activation and quadriceps potentiated twitch force before and after exercise. Women presented shorter time to task failure (P=0.025) and lower levels of neuromuscular fatigue (P=0.006) and peripheral fatigue (P<0.001) than men. Women and men showed different patterns of muscle activation during exercise, with women presenting greater muscle activation at the beginning of exercise and sustaining this elevated muscle activation throughout exercise, while men increased muscle activation from the beginning to the end of exercise. In conclusion, women had lower levels of neuromuscular fatigue, mainly caused by lower levels of peripheral fatigue, and a different muscle activation pattern in an exhaustive severe-intensity cycling exercise.

Abstract in English:

The objective of this study was to estimate the prevalence and factors associated with oral changes, including infections and other oral conditions in pregnant women who underwent prenatal care in public health units in the city of Divinópolis, Minas Gerais. This was a cross-sectional study carried out with baseline data from a cohort of 588 pregnant women (aged 14 to 43 years) from 2019 to 2023. Data were collected through interviews and oral clinical examination, using a structured questionnaire. The event of interest was the presence of oral infection. The absolute and relative frequencies of the variables were calculated. Logistic regression was used to evaluate the association between the explanatory variables and the presence of oral infection, with estimation of odds ratios and 95% confidence intervals. Among the participants, 47.8% had oral infections. In the multivariate analysis, the variables that showed a significant association with oral infection were: lower education, last visit to the dentist more than 6 months ago, lower frequency of flossing, regular intake of alcoholic beverages, and self-report of poor oral health. This study highlighted sociodemographic and behavioral disparities and the importance of prenatal dental care. Insights for adapting interventions were provided, although further studies are needed.

Abstract in English:

The 6-minute walk test is frequently used to assess the functional capacity of the cardiac disease population. Nevertheless, anthropometric differences can confound or misestimate performance, which highlights the need for new parameters. This study aimed to investigate the potential of the body weight-walking distance product (D·W) compared to the 6-minute walk test distance to predict exercise capacity measured by oxygen uptake (VO2) on-kinetics in coronary artery disease (CAD) patients. A cross-sectional study was conducted in a tertiary-care reference institution. Forty-six participants with multivessel CAD with and without left ventricular dysfunction underwent a 6-minute walk test with simultaneous use of mobile telemetric cardiopulmonary monitoring to evaluate VO2 kinetics and other cardiorespiratory responses. The Borg rating of perceived exertion for lower limb discomfort was only correlated with the D·W (P=0.007). The percent predicted and actual distance were only modestly to moderately correlated with VO2 on-kinetics (R2=0.12 and R2=0.29, P<0.05). All the associations of VO2 on-kinetics parameters were improved, showing a stronger correlation to the D·W (R2=0.49, P<0.0001), which also had a larger effect size to identify differences between coronary disease patients compared to distance walked (d=1.32 vs d=0.84). The D·W demonstrated potential to be better than the distance walked in determining VO2 on-kinetics in participants with CAD with and without left ventricular dysfunction.

Abstract in English:

The incidence of chronic pain in the general population is highly correlated to anxiety disorders, which promote negative effects on the quality of life. Stretch injury is the primary cause of nerve dysfunction and injury in the civilian population. Here, we characterized changes in nociception, anxiogenic-like behaviors, and astrocyte expression in the low-intensity sciatic nerve-stretch injury (NSI) model. Male Wistar rats were submitted to NSI, chronic constriction injury of the sciatic nerve (CCI), or sham surgery (SHAM). Animals were submitted to nociceptive tests (von Frey, acetone, and hot plate) before surgery and 6, 12, 18, and 24 days post-surgery. Anxiety-like behaviors were assessed in the open field test (OFT) 23 days after surgery. Immunofluorescence for astrocyte activity (glial fibrillary acidic protein (GFAP)) was performed in cortical, thalamic, and brainstem areas involved with pain and emotional processing. Animals submitted to NSI showed increased mechanical allodynia and thermal hyperalgesia, similar to those submitted to CCI. In the OFT, both NSI and CCI animals showed an increase in anxiety-like behaviors. Also, NSI animals presented an increased expression of GFAP in all analyzed areas, similar to CCI animals. In conclusion, the NSI model produced behavioral alterations comparable to those observed in the CCI model, including hypersensitivity to mechanical and thermal (heat) stimuli that lasted for more than three weeks. Additionally, both models induced a similar increase in GFAP expression in cortical, thalamic, and brainstem regions.

Abstract in English:

Peripheral neuropathy (PN) is a common side effect of docetaxel (DTX). In this study, we aimed to evaluate the effects of montelukast (MNT), a leukotriene receptor antagonist drug, against DTX-induced PN in rats. Thirty-two male rats were divided into four groups and treated for four weeks: control (sham), DTX (5 mg/kg per week, ip), MNT (10 mg/kg per day, po), and DTX+MNT (5 mg/kg per week, ip + 10 mg/kg per day, po). Behavioral tests (hot plate, tail flick, and rotarod) were conducted. Histopathological, molecular (RT-PCR), and biochemical (ELISA) analyses were performed on sciatic nerve, liver, and serum samples. MNT reduced the malondialdehyde (MDA) levels and increased the superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) parameters in sciatic nerve tissues. Unlike DTX, MNT resulted in increased Bcl-2 gene expression and decreased caspase-3 (Cas-3) and Bax expressions. DTX caused sensory and motor neuropathy, as revealed by the hot plate, tail flick, and rotarod tests. The co-administration of MNT significantly mitigated the sensory and motor neuropathy induced by DTX. MNT improved the levels of NCAM, p38α MAPK, and nuclear factor kappa B (NF-κB), which were impaired in the sciatic nerve tissues due to DTX administration. Additionally, it reduced the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which had increased due to DTX. Histopathological examination revealed that DTX-related sciatic nerve damage was mitigated by MNT administration. The results indicated that MNT may have a protective effect against DTX-induced PN in rats.

Abstract in English:

Oils and fats have a wide range of health benefits, especially those that have a high concentration of polyunsaturated fatty acids, like fish oils. Unfortunately, oils are highly susceptible to heat, light, and oxygen degradation, causing them to lose the qualities that would make them interesting for the public. With this in mind, this study compared two methods of spray-drying, a technique that helps preserve the stability of oils in storage for longer periods of time. Emulsions made with skimmed milk powder and with maltodextrin and whey protein hydrolysate were spray-dried, resulting in 2 different microencapsulated fish oils. They were compared regarding encapsulation efficiency, water activity, moisture content, and peroxide index. The skimmed milk showed better results, with a 28.17% lower peroxide index than the non-encapsulated oil and lower water activity and moisture content compared to the emulsion using maltodextrin (2.690±0.19% vs 6.747±0.29% moisture content and 0.376±0.013 vs 0.554±0.006 water activity). Since skimmed milk powder is rather cheap, it is ideal for spray-drying, a simple and fast technique. In this way, fish oil can be safely microencapsulated in powder form, lasting longer than the oil capsules currently available, since the oil is protected from light, temperature, moisture, and oxidation. In addition, the oily odor is masked, making it more appealing to the consumer, and it may be combined with other powders, like vitamins and minerals, which opens up new possibilities for the production of supplements.

Abstract in English:

The present study aimed to evaluate the protective effects of Aloe vera on doxorubicin (DOX)-induced degeneration in ovarian follicles and stromal cells in mice. Mice (n=48) were randomly divided into six groups. The positive control group mice received pretreatment of N-acetylcysteine orally (po), followed by a single intraperitoneal (ip) dose of DOX after 1 h (NAC+DOX). The negative control group mice were pre-treated with saline (po) and administered a single DOX dose (ip) after 1 h (SAL+DOX). The other groups of mice were pre-treated with different concentrations (0.1, 1.0, or 10.0 mg/kg; po) of Aloe vera and then received a single dose of DOX (ip) after 1 h (AV0.1+DOX, AV1.0+DOX, and AV10.0+DOX). The control group received saline po and ip (SAL+SAL). Aloe vera was administered once daily for 3 consecutive days. On the fourth day, the ovaries were processed for histological analysis, immunohistochemistry, and real-time PCR (mRNA for superoxide dismutase (SOD), catalase (CAT), nuclear factor erythroid 2-related factor 2 (NRF2), and tumor necrosis factor-α (TNF-α). Results showed that 0.1 and 1.0 mg/kg Aloe vera protected ovarian follicles and stromal density against DOX-induced degeneration. Furthermore, 0.1 and 1.0 mg/kg Aloe vera reduced TNF-α protein expression and increased NRF2, SOD, and CAT mRNA levels. In conclusion, 0.1 and 1.0 mg/kg Aloe vera had protective effects against DOX-induced degeneration in ovarian follicles and stromal cells in mice.

Abstract in English:

External factors accelerate cellular senescence in the skin and compromise its repair process. Psychological stress impairs skin wound healing, but no study examined its role in cellular senescence during skin tissue repair. Thus, this study evaluated the effect of stress on cellular senescence during skin wound healing. Human dermal fibroblasts (HDFs) and human skin from aged and young donors were treated with a non-lethal dose of epinephrine or hydrogen peroxide following a stress-induced premature senescence protocol. In vitro, epinephrine or hydrogen peroxide promoted the expression of senescence-associated β-galactosidase, p53, and notch target gene hairy and enhancer of split 1 (HES1) in HDFs, confirming the induction of premature senescence. A higher expression of matrix metalloproteinase-9 and interleukin-8 was observed in HDFs incubated with epinephrine or hydrogen peroxide, confirming a pro-inflammatory senescence-associated secretory phenotype. The protein levels of silent information regulator sirtuin 1, which is associated with a longer lifespan, were not changed in HDFs submitted to stressful conditions. In ex vivo experiments, epinephrine administration impaired wound closure and increased HES1 expression in aged human skin. In conclusion, stress-induced high epinephrine level induced premature senescence in HDFs, which contributes to impaired wound healing in young and aged skin.

Abstract in English:

The aim of this study was to evaluate the effect of high-intensity childhood games on cardiac autonomic regulation, obesity biomarkers, and body composition in overweight or obese children compared to moderate-intensity games. A single-blind, randomized controlled study was conducted including children aged 6 to 9 years with overweight or obesity. Participants were randomly assigned to two groups: 33 in the moderate-intensity interval game group (MIIG) and 29 in the high-intensity interval game group (HIIG). The intervention lasted 16 weeks, with measurements conducted under double blinding. The study followed institutional ethical standards and was registered on ClinicalTrials.gov (CT NCT05294601). A total of 74 children were recruited, with 7 excluded after sports medicine assessment, leaving 67 children randomized. Five participants dropped out during the study. HRV analysis revealed significant differences in frequency dominance in the HIIG group. High-frequency power, linked to parasympathetic dominance, increased from 59.3 to 65.8 nu (P=0.03), while low-frequency power, related to sympathetic activity, decreased from 40.6 to 34.13 nu (P=0.04). Salivary leptin concentrations decreased significantly from 0.33 to 0.32 ng/mL (P=0.008) in the MIIG group and from 0.35 to 0.32 ng/mL (P=0.004) in the HIIG group. Childhood games positively impacted anthropometry, HRV, and leptin concentrations in both intensity groups, indicating metabolic improvement. However, only the high-intensity strategy enhanced parasympathetic dominance and sympathetic-parasympathetic balance, potentially reducing long-term cardiovascular risk.

Abstract in English:

Many ways of classifying steatotic liver disease (SLD) with metabolic conditions have been proposed. Thus, SLD-related variables were verified using a decision tree. We tested if the suggested components of the actual classification (metabolic dysfunction-associated steatotic liver disease, MASLD) are also present in young and middle-aged adults. In a cross-sectional study involving 6,839 adults (median age: 46 years, 69.5% men) in a primary care setting, a decision tree was created to determine potential clinical and laboratory variables related to SLD. The odds ratio (OR) with a respective 95% confidence interval (95%CI) was calculated for both sexes. SLD frequency was 26.6% (23% in men). More variables and with higher ORs for the association with SLD were identified in women: category 1 (body mass index (BMI) ≥29 kg/m2, age <51 years, high-sensitivity C-reactive protein (hs-CRP) ≥0.195 mg/dL): OR=10.9, 95%CI: 4.40-26.6; category 2 (BMI <9 kg/m2, metabolic syndrome (MS), age ≥50 years, neck circumference (NC) ≥36 cm): OR=8.1, 95%CI: 2.2-29.9; and category 3 (BMI ≥29 kg/m2, age <51 y-old, dyslipidemia, high-density lipoprotein cholesterol (HDL-c) <42 mg/dL): OR=4.7, 95%CI: 2.20-10.7. For men: category 1 (waist circumference (WC) ≥101 cm, alanine aminotransferase (ALT) <28 mg/dL, glycated hemoglobin (HbA1c) ≥5.7%): OR=4.7, 95%CI: 2.8-7.9; and category 2 (WC ≥101 cm, ALT ≥28 mg/dL): OR=3.2, 95%CI: 2.5-4.0). The decision tree identified more variables related to SLD, particularly in women, such as age of more than 50 years, elevated hs-CRP, and NC≥36 cm than variables related to MASLD.

Abstract in English:

Obesity is a serious health problem worldwide and the search for new control methods and therapies is imperative. Studies indicate that a variety of obesogenic diets may increase the risk of developing type 2 diabetes mellitus (T2D) by causing insulin resistance in peripheral tissues. The chronic increase in free fatty acids associated with obesity may increase insulin demand by pancreatic beta cells and induce intrinsic beta cell dysfunction through endoplasmic reticulum (ER) stress, which is associated with beta cell loss during the development of T2D. Physical exercise approaches have been emerging as powerful tools and adjuncts in a variety of conditions, improving glucose homeostasis, oxygen uptake, and metabolism. Here, we showed that a 16-week endurance training program mitigated the deleterious effects of an obesogenic diet on glycemic homeostasis, insulin secretion, and ER stress markers as well as islet health markers in C57/BL6 obese mice. The results corroborated the assumption that physical exercise is an effective therapy to avoid beta cell death in glucose metabolism dysfunction and T2D in obese individuals.

Abstract in English:

Immune regulation plays an important role in the pathogenesis of intervertebral disc degeneration (IDD). However, the mechanism of immune regulation in IDD is still unclear. All IDD data were downloaded from a public database. The differentially expressed (DE) immune-related genes in IDD were identified by the limma package in R. Functional enrichment analyses were performed to explore potential immune-related biological pathways in IDD. We also identified differentially expressed microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) and constructed an mRNA-miRNA-lncRNA network. ROC analysis was performed to reveal potential diagnostic biomarkers for IDD. To understand the potential role of immune cells in IDD, xCell and Pearson correlation analyses were performed. Finally, expression validation was performed using real-time PCR. C5AR2, NFATC2, FCGR3A, hsa-miR-302d-3p, and MIR17HG were identified in IDD. ROC analysis results suggested that C5AR2 had good diagnostic accuracy, and FCGR3A and NFATC2 had sufficient diagnostic accuracy, which implied that they may be potential diagnostic markers of IDD. We also found that a large number of immune-related signaling pathways, such as cytokine-cytokine receptor interaction, chemokine signaling pathway, toll-like receptor signaling pathway, and Nod-like receptor signaling pathway, were significantly enriched. C5AR2, hsa-miR-302d-3p, and MIR17HG were significantly correlated with multiple immune cell types, such as cDC, CD8+ Tem, macrophage M1, neutrophils, and plasma cells. The C5AR2-hsa-miR-302d-3p-MIR17HG axis may play a role in immune regulation by regulating the infiltration level of related immune cells in the IDD microenvironment. The identification of key immune-related molecules, cells, and signaling pathways in IDD is of great significance to reveal the pathogenesis of IDD.

Abstract in English:

Total hysterectomy is a commonly performed gynecological procedure used to treat uterine pathologies. This study aimed to establish a total hysterectomy mouse model and investigate the effect of estradiol valerate on humoral immune function in BALB/c mice. Our results showed that the ratios of CD4+ and CD8+ subpopulation and hepatitis B virus antibody IgG content were reduced in the total hysterectomy (TH) group compared with the control group (P<0.05). The measured indices showed varying degrees of improvement after estradiol valerate administration. The numbers of CD19+ B lymphocytes significantly increased in the TH group (P<0.05) compared with the control group. There was a significant reduction of the size of germinal centers within lymph nodes in the TH group. This effect was reversed by estrogen supplementation. In summary, reduced estrogen levels following total hysterectomy may impair B lymphocyte activation, IgG secretion, and plasma cell production, leading to compromised immune function. Early treatment with estradiol valerate reverses impaired immune function and enhances antigen-induced antibody production in mice.

Abstract in English:

Obstructive sleep apnea (OSA) is linked to cardiovascular complications, including myocardial dysfunction, yet early detection remains difficult. This retrospective study aimed to develop a combined logistic regression and QUEST decision tree model to predict early myocardial dysfunction in OSA patients. Echocardiography left ventricular global longitudinal strain (LVGLS) and right ventricular free wall longitudinal strain (RVFWLS) were used to assess myocardial function in OSA patients. Predictive models were constructed using clinical parameters. External validation involved 100 OSA patients from a respiratory sleep clinic. LVGLS and RVFWLS were significantly impaired in OSA patients, particularly in moderate-to-severe cases. BMI, percentage of sleep time with oxygen saturation <90% (CT90%), and arterial bicarbonate were identified as key predictors. The combined model achieved superior predictive accuracy, with an area under the curve of 0.91 for LVGLS and RVFWLS reductions, outperforming individual models. External validation confirmed the stability and generalizability of the model. The combined logistic regression and QUEST decision tree model accurately predicted early myocardial dysfunction in OSA patients, providing a valuable tool for personalized risk assessment and early intervention.

Abstract in English:

The aim of this study was to evaluate the dynamic variations in the quantitative parameters of diffusion-weighted imaging (DWI) at different b-value combinations in a prostate cancer (PCa) mouse model for noninvasive monitoring of histopathological changes. Twenty-five male C57BL/6J mice were randomly allocated into a control group (n=5) or an experimental group (n=20). The experimental groups were used to establish the PCa model. On days 9, 12, 15, and 18 post-modeling, 5 mice were randomly selected for MRI, including T1WI, T2WI, T2WI SPIR, and DWI. The b-values were set at 0, 500, 1000, 1500, and 2000 s/mm2. Apparent diffusion coefficient (ADC) and exponential apparent diffusion coefficient (EADC) values from different b-value combinations were measured. Post-MRI, tumors were excised for histopathological analysis. DWI quantitative parameters, tumor nuclear fraction, and Ki-67 area fraction were compared on different days, along with correlation analysis. ADC values gradually decreased as tumor progressed, whereas EADC values gradually increased. Tumor nuclear fraction increased over time. Ki-67 increased first and then decreased. Tumor nuclear fraction was negatively correlated with the ADC value and positively correlated with the EADC value. The Ki-67 was positively correlated with the ADC value and negatively correlated with the EADC value. ADC values at b=1000, 1500 s/mm2 and the EADC values at b=0, 500 s/mm2 demonstrated the strongest correlations with the tumor nuclear fraction; the ADC and EADC values at b=500, 1000 s/mm2 were more strongly correlated with Ki-67, being potential noninvasive imaging biomarkers for monitoring changes in tumor histopathology.

Abstract in English:

Cervical cancer remains a leading cause of cancer-related mortality among women worldwide, despite treatment advances. The most common form is squamous cell cervical carcinoma, primarily associated with human papillomavirus (HPV) type 16. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid with promising anticancer properties both in vitro and in vivo. The aim of this study was to evaluate the antiproliferative, anti-migratory, and anti-invasive effects of chrysin on the SiHa human cervical cancer cell line (HPV-16-positive) using a 3D cell culture model with spheroids. Cell viability was assessed using the resazurin assay, while cytostatic effects were monitored by measuring spheroid size through imaging. Migration was evaluated with the spheroid migration assay. The expression of matrix metalloproteinase (MMP)-2, MMP-9, and vascular endothelial growth factor (VEGF) was quantified by immunoenzymatic assays. Chrysin treatment exhibited concentration-dependent cytotoxic and cytostatic effects, reducing cell proliferation and decreasing SiHa spheroid size. Additionally, chrysin inhibited cell migration and invasion, potentially reducing metastatic potential, primarily by decreasing the production of MMP-2 and VEGF. These findings suggest that chrysin has therapeutic potential for squamous cell cervical carcinoma and warrants further in vivo preclinical studies.

Abstract in English:

This study aimed to evaluate the effects of the ketamine-xylazine (KX) anesthetic mixture on autonomic and cardiovascular functions in normotensive rats (Wistar) and spontaneously hypertensive rats (SHR), using both spectral and symbolic analyses. Male Wistar (n=22) and SHR (n=28) rats were intramuscularly anesthetized with KX, and their femoral artery and vein were cannulated for pulsatile arterial pressure recording and drug administration. Autonomic function was assessed 24 and 48 h post-surgery through spectral and symbolic analyses of heart rate (HR) and systolic arterial pressure (SAP) variability. KX anesthesia significantly decreased mean arterial pressure (MAP) 24 h post-surgery in both Wistar and SHR rats. Spectral analysis revealed increased sympathetic modulation in the vascular bed of SHR 48 h post-surgery. In Wistar rats, there was a significant reduction in parasympathetic modulation at 48 h, as indicated by root mean square of successive RR interval differences (RMSSD) and high frequency (HF) (nu) indices. Symbolic analysis, however, detected no significant changes in autonomic modulation. These data are consistent with the notion that KX anesthesia significantly impacts autonomic and cardiovascular functions, with differential effects observed between Wistar and SHR rats. Spectral analysis proved more effective than symbolic analysis in detecting these changes. These findings highlight the need for careful consideration of anesthetic effects in experimental research and suggest that optimizing anesthetic protocols could improve clinical outcomes by minimizing adverse autonomic impact.

Abstract in English:

Serum biomarkers are crucial for identifying complications of obesity. This study evaluated serum levels of leptin, vascular endothelial growth factor (VEGF), myeloperoxidase (MPO), C-reactive protein (CRP), oxidized low-density lipoprotein (OXLDL), low-density lipoprotein (LDL), and other biochemical parameters in a rat model of high-fat diet (HFD)-induced obesity to investigate potential relationships between these biomarkers and microvascular function. Rats in the HFD group were fed a high-fat diet for 23 weeks, whereas control rats received a standard diet. Microvascular function was assessed using the post-occlusive reactive hyperemia (PORH) test; PORH responses were measured in the right forelimbs using laser Doppler flowmetry. Serum samples were then collected to measure the aforementioned biomarkers. Results showed decreased PORH responses in the HFD group, indicating impaired microvascular function. Serum levels of leptin, MPO, CRP, LDL, and OXLDL were significantly higher in the HFD group. Strong correlations were observed between microvascular dysfunction and LDL, OXLDL, MPO, and CRP. No significant changes were found in VEGF or HDL levels. These findings suggest that increased LDL oxidation to OXLDL in obesity contributes to vascular impairment, likely due to increased oxidative stress and inflammation mediated by elevated MPO and CRP. Further research focusing on the roles of LDL, OXLDL, MPO, and CRP may provide deeper insights into the mechanisms underlying microvascular dysfunction in obesity.

Abstract in English:

Obesity is an independent risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD). Non-pharmacological strategies, such as strength training (ST), have been investigated for their effectiveness in attenuating MASLD. This study evaluated the effects of ST on hepatic fat accumulation in an experimental model of obesity. Thirty-day-old male Wistar rats (∼150 g) were assigned to either a standard diet (SD) or a high-fat diet (HFD). The experimental protocol lasted 26 weeks and was divided into two phases: 1) obesity induction and maintenance (16 weeks) and 2) ST intervention (10 weeks). After the 16th week, HFD-fed rats were further divided into sedentary obese (Ob) and obese trained (ObST) groups. The ST protocol consisted of 4-5 vertical ladder climbs with 60-s intervals, three times per week, using 50-100% of maximal load. Body weight (BW), fat pads, total body fat (BF), adiposity index (AI), and muscle strength were assessed, as were glycemic, lipid, inflammatory, and histological parameters. ST reduced BW, epididymal and visceral fat depots, triglycerides, total cholesterol, glucose, leptin, and tumor necrosis factor (TNF)-α levels while improving insulin resistance. In conclusion, ST significantly attenuated hepatic steatosis in obesity, promoting metabolic and anti-inflammatory benefits. These findings suggest that ST may be an effective therapeutic strategy for MASLD, and further studies are needed to elucidate its molecular mechanisms and clinical applications.

Abstract in English:

This study aimed to systematically evaluate the risk of drug-induced pulmonary edema (DIPE) using the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. This retrospective pharmacovigilance study utilized FAERS data from the first quarter of 2004 to the second quarter of 2024. We identified drugs with at least 10 reported DIPE cases as primary suspects (PS). The DIPE signals were assessed using four methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM). Multivariate logistic regression was employed to control for confounding factors, and the timing of DIPE onset was statistically analyzed. Out of 173 target drugs, 37 were identified with DIPE risk. The top five drugs were naloxone, dasatinib, nifedipine, anti-thymocyte globulin, and pioglitazone. Multivariate logistic regression indicated that all except pioglitazone were independent risk factors for DIPE. The onset time of DIPE varied by age and gender for some drugs. This study is the first to identify the DIPE risk systematically associated with multiple drugs. It highlights the need for clinicians and pharmacists to be aware of these high-risk drugs and to monitor high-risk populations closely to ensure medication safety.

Abstract in English:

Statins have been shown to have antifibrotic effects on various tissues and organs, but their ability to improve chronic colitis-associated intestinal fibrosis and their mechanisms of action remain unclear. The objective of this study was to investigate the role of pitavastatin in chronic colitis-associated intestinal fibrosis and its possible mechanisms. We established a mouse model of chronic colitis-associated intestinal fibrosis through repeated administration of dextran sodium sulfate (DSS) and treated the mice with pitavastatin. The severity of intestinal fibrosis, serum inflammatory factor levels, and expression levels of intestinal fibrosis-related genes in mice were assessed using pathological histological staining, immunohistochemical staining, reverse-transcription PCR, RNA sequencing, and enzyme-linked immunosorbent assay. In vitro, we treated a human colon fibroblast cell line (CCD-18Co) with or without transforming growth factor-β1 stimulation using pitavastatin. Western blot, Cell Counting Kit-8 assay, and Transwell assay were used to analyze the activation of colonic fibroblasts, protein expression levels of genes related to intestinal fibrosis, and cell proliferation and migration abilities. Pitavastatin significantly attenuated DSS-induced chronic colitis and intestinal fibrosis. In vitro, pitavastatin concentration-dependently inhibited the activation of CCD-18Co cells, significantly reduced the expression levels of the intestinal fibrosis-related proteins Col1A1, IGF-1, IGF-1R, MMP-3, and TIMP-1, and significantly inhibited cell proliferation and migration while markedly increasing MMP-9 protein expression. Additionally, after silencing the IGF-1 and IGF-1R genes in CCD-18Co cells, the promotion of MMP-9 expression by pitavastatin was significantly inhibited. These findings suggest that pitavastatin may be a promising antifibrotic drug for future treatment of intestinal fibrosis.

Abstract in English:

Keratinocyte hyperproliferation and excessive inflammatory responses are associated with psoriasis pathogenesis. Trifolirhizin has anti-inflammatory and anti-proliferation effects. The purpose of the study was to investigate the role of trifolirhizin in psoriasis-like skin lesions and its molecular mechanism. Imiquimod-induced psoriasis-like mouse models were treated with trifolirhizin. Skin lesions and inflammatory factors were assessed. In vitro, human HaCaT keratinocytes were stimulated by a mixture of interleukin (IL)-1α, IL-17, IL-22, tumor necrosis factor (TNF)-α, and oncostatin M (M5) to establish a psoriatic keratinocyte model. Cell viability and cycle were assessed via CCK-8 assay and flow cytometry. Inflammatory factors, autophagy levels, and AMPK-mTOR pathway activation were detected by western blot. Trifolirhizin dose-dependently inhibited epidermal layer erythema, scaling, and thickening and reduced epidermal thickness and IL-12 level in an imiquimod-induced psoriasis-like mouse model. Trifolirhizin also inhibited cell viability, PCNA expression, and excessive synthesis and secretion of IL-8 and IL-12 in HaCaT keratinocytes induced by M5. Furthermore, the inhibition of autophagy and AMPK-mTOR pathway could be reversed by trifolirhizin in M5-induced HaCaT keratinocytes and skin lesions from imiquimod-mediated psoriasis-like mouse model. The improvement effects of trifolirhizin could be inhibited by the autophagy inhibitor chloroquine. Trifolirhizin up-regulated autophagy through the AMPK-mTOR pathway, improved the hyperproliferation and excessive inflammatory responses of keratinocytes, thus alleviating psoriatic skin lesions. Trifolirhizin may have therapeutic potential in improving the progression of psoriasis.

Abstract in English:

It is unclear who benefits the most from atherosclerotic cardiovascular disease (ASCVD) screening imaging. This study aimed to identify features associated with positive coronary artery calcium scores (CACS) in individuals with diabetes using machine learning (ML) techniques. ELSA-Brasil is a cohort study with 15,105 participants aged 35 to 74 years in six Brazilian cities. We analyzed 25 sociodemographic, medical history, symptom-related, and laboratory variables from 585 participants from the São Paulo investigation center with CACS data and no overt cardiovascular disease at baseline. We used six ML algorithms to build models to identify individuals with positive CACS. Feature importance was determined by SHapley Additive exPlanations (SHAP) values. The best performer ML algorithm was the XGBoost Classifier (accuracy: 94.8%). Age (SHAP: 0.220), systolic blood pressure (SHAP: 0.102), and body mass index (SHAP: 0.075) were the most important variables to identify ASCVD in individuals with diabetes in XGBoost models. Considering all ML models in our analysis, age, systolic blood pressure, and sex were frequently influential variables. We obtained high accuracy with our best model, using information generally present in current clinical practice. ML models may help clinicians select patients with characteristics most probably associated with a positive CAC. Age, systolic blood pressure, body mass index, and sex may be useful markers to identify those at higher risk for subclinical ASCVD.

Abstract in English:

Glioblastoma (GBM) is the most prevalent tumor in the central nervous system in adults. Lactotransferrin (LTF) is a molecule involved in the growth of various tumors. However, the underlying mechanism of LTF in GBM progression and chemotherapy resistance remains unclear. In this study, the clinical and diagnostic value of LTF were evaluated. In vitro and in vivo experiments were performed to explore the functional role of LTF in GBM. Immunoprecipitation and immunofluorescence assays were performed to clarify the effect of LTF on nuclear factor-κB (NF-κB) activation. LTF was overexpressed in GBM and correlated with poor prognosis. LTF promoted GBM cell proliferation, invasion, and temozolomide (TMZ) resistance. Mechanism assay results indicated that LTF competitively binds to p65, rescuing the inhibited effect of PP2A on p65 phosphorylation, thereby activating the NF-κB signaling pathway. Our results confirmed that highly expressed LTF promoted GBM progression and TMZ resistance through the NF-κB signaling pathway.

Abstract in English:

Breast cancer is the most frequent neoplasm and has the highest mortality rate among women. In the Afro-descendant population, these tumors may appear earlier and assume a more aggressive behavior. This study aimed to assess the epidemiological and clinical behavior of breast cancer in a predominantly Afro-descendant population, identify risk and prognostic factors, and compare them with already available data. Clinical and sociodemographic data were obtained from medical records and interviews with the patients involved. The variables ethnicity, age, number of children, monthly income, and education were used to describe the epidemiological profile and the results of clinical evaluation and pathological anatomy study. The immunohistochemical analysis was used to correlate the clinical characteristics of the tumors and prognosis. Afro-descendant women represented 77% of the population and the mean age at diagnosis was 54.4 years. Approximately 75% had up to 2 children, 20.5% had low income, and 37.3% had a low level of education. Infiltrating ductal carcinoma was diagnosed in 91% of patients, 70.2% had a moderate degree of differentiation, luminal subtype A was the most prevalent (39%), and a higher than global average percentage had a triple negative profile (22.9%). Early stages were identified in 53.4% of patients and only 4.8% were diagnosed with metastatic disease. The recurrence rate was 11.6%, and the mortality rate was 6.8%. The present study showed that unfavorable sociodemographic and clinical aspects, such as the high prevalence of triple-negative tumors, were not associated with a worse prognosis.

Abstract in English:

The aim of this study was to investigate the correlation between pre-stroke frailty status and post-stroke cognitive impairment (PSCI) in patients with acute large artery atherosclerotic cerebral infarction. One hundred and eight patients with acute large artery atherosclerotic cerebral infarction admitted in our hospital from July 2020 to July 2023 were prospectively enrolled. Patients were stratified into frailty (46 cases) and non-frailty groups (62 cases) based on FRAIL scale scores. During the 6-month follow-up after the onset of cerebral infarction, patients were evaluated using the Chinese modified version of Montreal Cognitive Assessment (MoCA) scale for cognitive function and were divided into PSCI (52 cases) and non-PSCI (56 cases) groups. The frailty group showed significantly higher age, prevalence of hypertension and diabetes comorbidities, smoking and alcohol consumption rates, National Institutes of Health Stroke Scale (NHISS) score, and Modified Rankin Scale (mRS) score than those in the non-frailty group (P<0.05, P<0.01). The incidence of PSCI in the frailty group was also significantly higher than that in the non-frailty group (78.3 vs 25.8%, P<0.01). Compared to the non-PSCI group, the PSCI group had higher age, shorter education duration, fewer cases of reperfusion therapy, and greater frailty (P<0.05, P<0.01). Logistic regression analysis showed that pre-stroke frailty was an independent risk factor for PSCI (P<0.01). Timely assessment of the frailty status in patients with acute large artery atherosclerotic cerebral infarction is beneficial for preventing, delaying onset, and reducing the incidence of PSCI.

Abstract in English:

Satellite glial cells (SGCs) within the dorsal root ganglion (DRG) possess the potential for transdifferentiation. Our previous study (doi: 10.1007/s12257-019-0317-x) has identified lncRNA ENSRNOT00000087717 (lnc87717) and its target AKT1 as potential regulators in the differentiation process of DRG-SGCs. In this study, the cell morphology of SGCs was assessed using immunofluorescence cytochemistry during the differentiation following knockdown of lnc87717, as well as downregulation or upregulation AKT1. The subcellular localization of lnc87717 was visualized by fluorescence in situ hybridization (FISH). The mRNA expression levels of lnc87717, AKT1, BDNF, TrkB, proBDNF, and p75NTR were assessed using qRT-PCR. For the in vivo study, 27 male Sprague-Dawley rats aged 6-9 weeks were used to establish the sciatic nerve injury model. The number of apoptotic cells in DRGs was subsequently detected in the AKT1 inhibitor, activator, and control group after the administration of proBDNF antiserum. In vitro, following knockdown of lnc87717, there was a significant decrease in the expression levels of proBDNF, BDNF, TrkB, and p75NTR (P<0.05). Furthermore, the number of nestin-positive SGCs and the expression of lnc87717 and AKT1 were increased in the AKT1-activated group (P<0.05). In vivo, compared to the control group, the number of apoptotic cells in the DRG was increased in the AKT1-inhibited group. Additionally, the expressions of lnc87717 and AKT1 were significantly upregulated (P<0.05), whereas the expression levels of PI3K, NF-κB, and Bad were significantly downregulated (P<0.05) in DRGs following AKT1 up-regulation compared to those in the control group. The differentiation of DRG-SGCs is suggested to be mediated through the activation of AKT1, while lnc87717 downregulates AKT1.

Abstract in English:

The global prevalence of overweight status and obesity has increased considerably. Obesity is the common pathological basis of numerous diseases and a crucial triggering factor for diabetes. This study aimed to investigate the role of activating transcription factor 3 (ATF3) in the adipogenic process of adipocytes and the related compounds of Chinese medicine potentially targeting ATF3. The differentially expressed genes (DEGs) in high-fat diet (HFD) or overweight patients were identified by analyzing Gene Expression Omnibus (GEO) data profiles GSE112999, GSE112740, and GSE48964. qRT-PCR and western blot were conducted to detect the expression levels of related genes. Oil-red O staining was conducted to detect lipid droplet formation within 3T3-L1 adipocytes. Compounds that interacted with ATF3 were screened through the pharmacological database and analysis platform of the traditional Chinese medicine system. Furthermore, the eugenol effect on ATF3 expression was evaluated. ATF3 expression was increased in the adipose tissues of HFD mice and in clinically obese patients. Knock down of ATF3 promoted adipocyte lipid droplet formation, upregulated the protein levels of adipocyte markers (Fabp4 and PPARγ), elevated intracellular triglyceride (TG) levels, and activated the AKT signaling pathway. Eugenol effectively promoted ATF3 expression and inhibited adipocyte differentiation and adipogenesis. ATF3 expression was found to be elevated within the adipose tissues of overweight patients, whereas ATF3 knockdown promoted adipocyte differentiation and lipid accumulation by activating the PI3K/AKT signaling pathway. Therefore, ATF3 overexpression or supplementation with eugenol may be a potential method for overcoming obesity.

Abstract in English:

This research aimed to evaluate the impact of stress at the end of the pregnancy on bone health and body composition of Wistar rats after the breastfeeding period. The 90-day pregnant Wistar rats were divided into 2 groups (n=7/group): the stress group (SG) and the control group (CG). The stress protocol was carried out over 8 days, with 4 different types of stressor stimuli during the third week of pregnancy. Serum corticosterone, osteoprotegerin (OPG), nuclear factor kappa beta ligand (RANKL), calcium, and phosphorus were measured by an ELISA kit and body composition by the carcass technique. Bone mineral density, content, and area were measured in the femur by dual-energy X-ray absorptiometry, and the maximum force, breaking force, and elastic modulus were measured using a flexural test with a load cell (50 kgf). Results with P<0.05 were considered significant and data are reported as means±SD. Corticosterone was higher in SG (P=0.04), showing the effectiveness of the protocol, but no differences were observed in OPG, RANKL, calcium, phosphorus, and body composition. SG had lower bone mineral density (P=0.01) and lower maximum strength (P=0.04). Stress during the gestational period promoted deleterious effects on maternal bone health after the lactation period, shown by the reduction of bone mineral density and maximum strength, affecting bone quality; no difference was found in body composition.

Abstract in English:

Pregnancy feto-maternal complications (PFMCs) contribute significantly to morbidity and mortality, with placental hypoxia as a key factor. Current methods for detecting fetal hypoxia are limited. This study aimed to evaluate the roles and biomarker potential of hypoxia-inducible factor (HIF)-1α, erythropoietin (EPO), and cell-free fetal hemoglobin (cf-HbF) in PFMCs. In a cross-sectional study, we quantitatively immunoassayed plasma levels of these biomarkers in 136 healthy pregnant women (age 29.618±5.19 years) and 118 women with complications (age 30.53±5.46 years) who had voluntarily consented and were enrolled sequentially and anonymously. Results indicated significantly higher biomarker levels in complicated pregnancies (P<0.001), with worsening trends for preeclampsia, ectopic pregnancy, abortion, gestational diabetes, and preterm labor with premature rupture of membranes. Only EPO levels showed pregnancy duration-dependent changes in healthy controls (encompassing 6 to 41 weeks; r=0.230, P=0.015). Strong correlations among the three biomarkers were found in both groups (r=0.402/P<0.001; r=0.724/P<0.001), with HIF-1α correlating with body mass index (BMI) in healthy controls (r=0.204/P=0.032). ROC analysis demonstrated high sensitivity and specificity in differentiating between groups (P<0.001), with cf-HbF showing the highest performance (AUC=0.923), followed by HIF-1α (AUC=0.882) and EPO (AUC=0.826). In conclusion, HIF-1α, EPO, and cf-HbF were associated with PFMCs and showed promising potential as biomarkers for distinguishing healthy from complicated pregnancies, with cf-HbF being the most significant. Their high levels also pointed to hypoxic adaptation dysfunction and/or resistance, as a pathogenic culprit.

Abstract in English:

This study aimed to analyze the compromised cortical and subcortical brain structures and quantify the volume of ischemic lesions in patients with hemispatial neglect after stroke treated with transcranial direct current stimulation (tDCS). This cross-sectional study was conducted using data from the ELETRON Trial. Computed tomography (CT) images of 23 patients who underwent anodal tDCS (A-tDCS), cathodal tDCS (C-tDCS), or placebo (sham-tDCS) were included. Lesion mapping based on high-resolution volumetric CT images was performed using an automated anatomical labeling atlas. The proportion of damage in each region and brain damage between groups were compared using chi-squared and Fisher's exact tests. The behavioral inattention test (BIT-C) score was significantly higher in the C-tDCS group than in sham-tDCS group (P=0.03). Gray matter analysis revealed that lesion extension in the A-tDCS group was 325.580 mm3, in C-tDCS was 231.700 mm3, and in the sham-tDCS was 241.574 mm3. The lesion extension in the white matter was 37.076 mm3 in the A-tDCS group, 22.258 mm3 in the C-tDCS group, and 40.556 mm3 in the sham-tDCS, all centered on the superior longitudinal fasciculus. Overall, the A-tDCS group presented with a larger lesion area in the gray matter than the C-tDCS group (P=0.046). The C-tDCS group showed a smaller proportion of areas with white matter damage than the A-tDCS (P=0.011) and S-tDCS (P=0.002) groups. Hemispatial neglect was significantly improved after C-tDCS; however, the extent of gray and white matter damage was smaller for this group.

Abstract in English:

Postinduction hypotension (PIH), a common complication of general anesthesia, occurs more frequently in hypertensive patients. This hypotensive state may induce hypoxia in vital organs, potentially progressing to organ dysfunction or even death. In this prospective cohort study, the primary outcome was incidence of PIH. The preanesthesia baseline parameters included demographic characteristics (age, sex, and body mass index [BMI]) and laboratory biomarkers (serum uric acid, hemoglobin, and lipoprotein levels). Noninvasive blood pressure was systematically monitored at five time points: preinduction (T0), postinduction (T1), immediately postintubation (T2), 5 min postintubation (T3), and 10 min postintubation (T4). This study involved 271 hypertensive patients with a median age (interquartile range) of 56.0 (17.0) years. The cohort comprised 134 males (49.4%) with a mean BMI of 23.8±2.94 kg/m2. PIH occurred in 165 patients (60.8%) following general anesthesia. Univariate logistic regression revealed potential associations between PIH and serum uric acid levels, advanced age, elevated baseline systolic blood pressure, grade 3 hypertension, fasting duration, and ASA class III status. Multivariate logistic regression suggested that serum uric acid may exert a protective effect, whereas grade 3 hypertension, age, and baseline systolic blood pressure emerged as risk modulators. Notably, a composite model incorporating age, baseline systolic blood pressure, hypertension severity, and serum uric acid level demonstrated enhanced predictive capacity (AUC=0.863 vs 0.712 for serum uric acid level alone, both P<0.01). Serum uric acid level demonstrated a moderate inverse correlation with PIH, whereas grade 3 hypertension, age, and baseline systolic blood pressure emerged as potential risk factors for PIH occurrence.

Abstract in English:

We have previously demonstrated that different modalities of endurance exercise combined with lower muscle glycogen content elicit several physiological and molecular benefits in men. In this study, we hypothesized that these exercise strategies modulate monocarboxylate transporters (MCTs) and plasma lactate. We investigated MCT1 and MCT4 gene expression after two forms of exercise (i.e., once daily and twice-a-day) under low carbohydrate (CHO) availability (Acute - Study 1) and whether three weeks under once daily or twice-a-day training differentially affected plasma lactate during exercise (Chronic - Study 2). In Study 1, five participants performed a high-intensity interval exercise (HIIE) 2 h (twice-a-day) or 15 h (once daily) after exercise and diet manipulations to reduce endogenous CHO stores or without previous CHO manipulation (Control). Muscle biopsies were collected before, right after, and 3 h after HIIE. In Study 2, plasma lactate was measured during a graded exercise test before and after three weeks of once-daily (n=7) or twice-a-day training (n=7). MCT1 gene expression increased from before to after and 3-h post-HIIE only in the twice-a-day exercise (P<0.05). MCT4 gene expression was unaltered in all conditions (P>0.05). The plasma lactate curve shifted to the right in both training approaches, without differences in lactate slope reduction between once-daily (-0.49±0.58 mmol·L-1·min-1) and twice-a-day (-0.46±0.73 mmol·L-1·min-1) exercise. In conclusion, twice-a-day training increased acute MCT1 gene expression but did not result in chronic changes in plasma lactate response during exercise.

Abstract in English:

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation, which may be associated with hepatic and biliary manifestations such as non-alcoholic fatty liver disease (NAFLD). Despite the high risk of hepatic manifestations among patients with IBD, few studies in Brazil have assessed the frequency of these diseases. Therefore, this study aimed to analyze the prevalence of liver disease by ultrasound in patients with IBD. This was a single-center, cross-sectional study that included patients with IBD who were followed up at an outpatient clinic. The clinical and sociodemographic data, disease activity, biochemical test results, and Doppler liver ultrasonography results were assessed. Descriptive and association tests were used for statistical analyses. A total of 138 patients were included: 64.49% females, mean age 45.55±14.17 years, and body mass index of 26.92±5.07 kg/m2. In total, 63 (45.65%) patients had CD and 75 (54.35%) had UC. Most patients were in either clinical (58.39%) or endoscopic remission (52.55%). Liver ultrasound revealed NAFLD in 58 patients (42.03%), which was classified as mild (36.21%), moderate (46.55%), or severe (17.24%). Seven patients had choledocholithiasis and three had chronic liver disease. Liver disease was associated with changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), hematocrit, hemoglobin, and fasting glucose levels. Liver disease is frequent in IBD patients, with NAFLD being the most prevalent. Screening for liver disease in patients with IBD is recommended for early detection and immediate treatment of the alterations, in order to prevent complications and progression to cirrhosis.

Abstract in English:

Sacha inchi oil (SIO) is characterized by its high content of polyunsaturated fatty acids (PUFAs), metabolites with beneficial properties on health. The objective was to evaluate the fatty acid (FA) profile of wild SIO and its effect on biochemical parameters of lipid metabolism under a high-fat diet. Twenty-four albino rats were grouped into groups I, II, III, and IV, which ingested ad libitum the following diets: conventional diet without supplementation (CDOS), conventional diet supplemented with SIO (CDWS), hyperlipidic diet without supplementation (HDOS), and hyperlipidic diet supplemented with SIO (HDWS) for 6 weeks. The FA content of SIO was assessed by gas chromatography-mass spectrometry. The lipid profile was analyzed by the enzymatic-spectrophotometric method, and cytokines and lipid mediator levels were measured via enzyme-linked immunosorbent assay (ELISA). Α-linolenic acid (ALA) and linoleic acid (LA) constitute 82% of this oil. Two-way ANOVA showed interaction effects between diet and supplement on interleukin (IL)-10 levels, and SIO-supplemented diet significantly decreased triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-C), and the TG/HDL-C ratio levels. Wild SIO is high in ALA and LA. SIO supplementation reduced TG, VLDL-C, and the TG/HDL-C ratio, modulated IL-10, and slightly improved leptin, resolvin-D1 (RvD1), and IL-6 levels.

Abstract in English:

Candida biofilm is difficult to control due to the poor penetration and unspecificity of antifungal drugs against the microorganisms associated with this structure. Nanoparticles have been investigated for their antimicrobial potential. In this context, the present study evaluated the antibiofilm activity of silver nanoparticle colloids (AgNPs) against candida isolated from the oral cavity. AgNPs were prepared in two different ethanolic syntheses - without and with ammonium hydroxide: AgNP-1 and AgNP-2, respectively. AgNPs were characterized by atomic absorption spectroscopy (AAS), UV-visible (UV-vis) absorption electron spectroscopy, zeta potential, dynamic light scattering (DLS), and transmission electron microscopy (TEM). Subsequently, they were evaluated against biofilm formation by clinical isolates of Candida albicans and Candida krusei by determining the minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and minimum biofilm formation inhibitory concentration (MBIC50). AgNPs inhibited biofilm formation of tested C. albicans and C. krusei and showed antibiofilm activity at subinhibitory concentrations against all yeasts. AgNP-1 inhibited biofilm formation at concentrations between 7.55 and 60.46 µg/mL and AgNP-2 between 7.71 and 30.80 µg/mL. The characterization of AgNP showed that AgNP-1 and AgNP-2 differ mainly in size and dispersion, with AgNP-2 being monodisperse, indicating that these characteristics could be related to the activity against the formation of C. albicans and C. krusei biofilm, and the silver nanoparticles may represent innovative and complementary alternatives to the available antifungal arsenal.

Abstract in English:

Minimally invasive autopsy (MIA) is used to understand the pathophysiological mechanisms and clinical outcome of diseases. One of its many advantages is the lower risk of contamination in case of infectious diseases and the quick tissue collection procedure compared to conventional autopsies, which reduces cold ischemia time. Here we investigated the potential role of MIA for molecular pathology studies by comparing RNA yield and quality after RNA extraction from frozen lung tissue samples collected from different methods: MIA, lobectomy, and transbronchial biopsy (TBB). Our results revealed that RNA yield was significantly higher (P<0.05) in the TBB group compared to the lobectomy and MIA groups. However, 93% of MIA samples were non-degraded, showing similar results to TBB, where all had a DV200≥70%. Therefore, MIA proves to be a novel tool for molecular pulmonary pathology in diagnostic and/or research settings.

Abstract in English:

Chronic use of glucocorticoids is one of the most common causes of osteoporosis. Triterpenes have a positive effect on bone metabolism, which encourages research into the anti-resorptive properties of these natural compounds. In this study, the anti-resorptive effect of the semisynthetic compound 3β,6β,16β-tripropionyloxylup-20(29)-ene (CL-P2), obtained from the natural lupane-type triterpene 3β,6β,16β-trihydroxylup-20(29)-ene (CL-1) isolated from Combretum leprosum Mart., was investigated in a glucocorticoid-induced osteoporosis (GIO) model in rats. GIO was induced by dexamethasone (7 mg/kg, im; 1×/week, 65 days). On the 36th day, treatment was started (gavage) with CL-P2 (0.01 or 0.1 mg/kg; 30 days). After this time interval, the rats were euthanized and the femurs and lumbar vertebrae were collected for analysis by microcomputed tomography (micro-CT), quantity and type of collagen (Picrosirius Red), micro-Raman spectrometry, and histomorphometric analysis using hematoxylin and eosin (H&E) staining. The organs were collected for toxicity analysis (HE). CL-P2 increased trabecular volume, number of trabeculae and bone mineral density as evidenced by micro-CT analysis in the third lumbar vertebra (L3), as well as the amount of total collagen and type I collagen in L2. In the analysis of the femurs, CL-P2 promoted an increase in the number of osteoblasts and osteocytes and a reduction in the number of osteoclasts, as well as change in the mineral composition of these bones, suggested by the increase in the carbonate-to-phosphate ratio (CTPR) identified by micro-Raman spectrometry. Histopathological analysis of the organs revealed the pre-clinical safety of CL-P2. CL-P2 had bone-protective benefits and may be a biotechnologically viable product as a supplemental therapy for GIO.

Abstract in English:

Plastination is a technique for preserving biological tissues, in which body fluids are replaced by a curable polymer. Epoxy resin is used for 2-5 mm sections of anatomical segments, with the German-made Biodur® E12 being the best known and most widely used resin. A few alternative epoxies can be used in the technique, but research should be developed to identify options that are cheaper and less bureaucratic to acquire. This study aimed to find, adapt, and apply an alternative epoxy resin formulation and its curing system for the plastination process as a potential substitute for Biodur® E12. The methodology was divided into the search of a resin for national commercialization in Brazil, the development of the final formulation, the testing of its use in plastination, and the evaluation of the resin and final specimens. From market research, E48 epoxy (brand not disclosed) was selected, and its formulation was changed with the addition of a plasticizer for use in impregnation. A total of 150 Wistar rat cross-sections were plastinated with the control polymer (E12) and with the developed test resin (E48). Based on the positive results of the shrinkage analysis (no statistical difference) and confocal and stereoscopic microscopy, it was concluded that the modified E48 is a great alternative to E12.

Abstract in English:

Escherichia coli is a common intestinal microorganism that can cause a variety of diseases in humans and animals. The aim of this study was to evaluate the therapeutic effects of fish oil rich in omega-3 against intestinal infection caused by enteroaggregative E. coli (EAEC). Minimum inhibitory and bactericidal concentrations were determined, along with toxicity assays using HT-29 intestinal cells and Tenebrio molitor larvae. Swiss mice infected with EAEC 042 were used to assess the in vivo therapeutic potential of fish oil. Histological analyses of the liver, kidney, and colon were conducted to identify tissue alterations such as inflammation and necrosis. Fish oil exhibited a bacteriostatic effect on E. coli and was non-toxic to HT-29 cells at concentrations up to 50 mg/mL. It also enhanced survival in treated larvae. In infected mice, bacterial colony counts were significantly lower in the fish oil-treated group. Histological evaluation showed reduced inflammatory infiltrates in the liver and colon, and no progression of hepatic hydropic degeneration was observed in treated animals, unlike in the untreated infected group. These findings indicated that fish oil rich in omega-3 possesses antimicrobial activity against E. coli, is non-toxic to both cells and animal models, and effectively reduces intestinal infection and associated tissue damage in mice. This suggests its potential as a supportive therapeutic agent for infections caused by pathogenic E. coli.

Abstract in English:

Helicobacter pylori is an infectious agent linked to significant gastric pathologies, which makes it a public health concern. The enzyme-linked immunosorbent assay (ELISA) is widely used for epidemiological studies and for investigating virulence factors like the cagA gene. Due to the varying antigenic profiles of bacterial strains across different populations, the local validation of serological tests is essential. This study aimed to evaluate the performance of two commercial serological tests - the MyBiosource HP-CagA-IgG ELISA kit and the Sunlong Human IgG (CagA-IgG) ELISA kit - in detecting the cagA virulence factor and to assess its prevalence in bacterial isolates from a population in the southwest region of Bahia. A total of 88 individuals were enrolled, and 34 tested positive for the cagA factor via real-time PCR. After establishing customized cutoff points, the MyBiosource kit demonstrated a sensitivity of 55.88%, specificity of 50%, and accuracy of 52.22%, while the Sunlong kit showed a sensitivity of 70.59%, specificity of 60%, and accuracy of 64.29%. Despite these results, neither test met satisfactory performance standards, with sensitivity below 75% and specificity ranging from 50 to 60%. The overall prevalence of H. pylori infection was 56.8%, with a cagA prevalence of 68% among positive cases. Further investigations using additional commercial tests are recommended to enhance diagnostic outcomes for this population.

Abstract in English:

Sepsis is a life-threatening organ dysfunction with a high incidence rate and mortality. The aim of this study was to investigate monocyte-related signaling pathways and hub genes in sepsis survivors and non-survivors. Sepsis-related data were downloaded from Gene Expression Omnibus (GEO) database. Cell annotation and cell communication analysis were performed to identify signaling pathways and ligand-receptor pairs related to monocytes. Immune cell infiltration, functional annotation, differential expression, and correlation analysis were performed to screen for hub genes associated with monocytes. In addition, survival analysis, transcription factors, and drug prediction were also performed on the hub genes. Compared with sepsis survivors, monocytes decreased in sepsis non-survivors. Cell communication results showed that monocytes were also the main signal transmitters and receivers in both the sepsis survivor and the sepsis non-survivor groups. A total of 25 signaling pathways related to monocytes were identified, such as MIF, ANNEXIN, GALECTIN, THBS, ITGB2, CCL, MHC-I, MHC-II, CD23, ICAM, and SEMA4. Subsequently, 6 hub genes (CCR1, CD4, CD47, ITGAX, LILRB1, and PLXNB2) associated with monocytes were identified. Univariate Cox analysis showed that CD4, ITGAX, LILRB1, PLXNB2, and age were associated with the prognosis of sepsis. Multivariate Cox analysis showed that ITGAX and age might be independent prognostic factors for sepsis. ITGAX and CD4 are associated with transcription factors SPI1 and MYB, respectively. Moreover, drug prediction results showed that tregalizumab was an agonist of CD4. This study revealed the monocyte-associated signaling pathways and hub genes, which may contribute to the understanding of the molecular mechanisms of sepsis survivors and non-survivors.

Abstract in English:

Fractal analysis (FA) of neutrophils has demonstrated potential in identifying changes in chromatin associated with clinical parameters in individuals with chronic diseases. Therefore, this study aimed to investigate FA of neutrophils' nuclei from patients with Trypanosoma cruzi and/or HIV. Fifty-three individuals were recruited and divided into four groups: T. cruzi-infected patients with chronic chagasic cardiomyopathy (CCC) (n=18), seropositive HIV individuals (SPHIV) (n=14), T. cruzi-HIV coinfected patients (n=9), and healthy individuals (n=12). Micrographs of neutrophils underwent FA using a box-counting method in the ImageJ software. Clinical parameters obtained from patients' medical records, such as left ventricle mass index (LVMI), left ventricle ejection fraction (LVEF), risk of ischemic stroke (IS), and sudden death were analyzed. FA was lower in patients compared to the control group (P<0.0001). Chagas disease (CD) patients showed higher FA when the LVEF was higher (r=0.53), which increased the risk of sudden death (r=-0.62). In SPHIV, when FA was higher, T CD4+ lymphocyte count was also higher (r=0.66) and the T CD8+ lymphocyte count was lower (r=-0.54). Coinfected individuals showed higher FA, when LVEF (r=0.60), neutrophil to lymphocyte ratio (r=0.80), total lymphocytes (r=0.70), and T CD4+ lymphocyte count (r=0.70) were increased, and T CD8+ lymphocyte count was decreased (r=-0.70). FA was an independent marker of changes in neutrophil chromatin and has proven to be a prognostic tool and a method for risk stratification for adverse events, survival, and mortality in individuals infected with T. cruzi and/or HIV.

Abstract in English:

The aim of this study was to establish reference intervals for lymphocyte subpopulations in the peripheral blood of Brazilian adults, and to assess potential variations by gender and age groups. The study assessed 351 healthy participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Lymphocyte subpopulations were analyzed by dual platform using automated hematological analyzer Sysmex XN-3000 and the four-color flow cytometer on the FACSCalibur. Reference intervals were established using the 2.5th and 97.5th percentiles. Z-score was employed to ascertain the need for distinct reference intervals across gender and age groups. The Mann-Whitney test, with a significance level set at P<0.05, was conducted to identify differences among population groups. The absolute and relative reference intervals were: total lymphocytes: 1.0-2.9 (×103/µL); CD3+: 721.0-2311.5 cells/μL, 59.1-84.5%; CD4+: 421.4-1523.8 cells/μL, 32.5-61.6%; CD8+: 175.3-879.8 cells/μL, 12.3-39.1%; CD4+CD8+: 0.8-4.1 cells/μL; CD19+: 85.2-501.6 cells/μL, 5.6-21.0%; NK: 83.9-444.4 cells/μL, 4.3-23.5%. Significant gender and age differences were observed in both the relative and absolute values of most lymphocyte subpopulations. There are variations in lymphocyte subsets across the global population, underscoring the need to establish tailored reference intervals for distinct populations, particularly for Helper T lymphocytes, B lymphocytes, and NK cells.

Abstract in English:

SARS-CoV-2, the causative agent of the COVID-19 pandemic, remains a significant threat to global public health. Therefore, rapid and accurate detection of the virus continues to be of critical importance. Among the specific gene regions of SARS-CoV-2, the Nucleocapsid (N) protein gene is one of the most frequently targeted for viral identification, with NIID_2019-nCOV_N being a notable example. While reverse transcriptase polymerase chain reaction (RT-PCR) remains the gold standard for diagnosis, alternative molecular detection methods are still limited. In this study, a lateral flow assay (LFA) was developed for the detection of a conserved gene region within NIID_2019-nCOV_N. Gold nanoparticles (AuNPs) were employed to enable visual detection, and the assay was designed based on nucleic acid hybridization principles. Two different membrane types (M17 and M12), three oligonucleotide probe concentrations (2, 4, and 8 µM) conjugated to AuNPs, and the assay's limit of detection (LOD) were evaluated. The target sequence from NIID_2019-nCOV_N was successfully detected by the naked eye within 5-6 min. No significant differences in performance were observed between the two membrane types across all probe concentrations, and the LOD was determined to be 1 pM. Consequently, the nucleic acid-based lateral flow assay (NABLFA) designed in this study, which targets a specific conserved base sequence, demonstrated high potential for rapid and sensitive molecular detection of SARS-CoV-2. Furthermore, this approach may be adapted for the identification of emerging viral variants or future outbreaks.

Abstract in English:

The 2017 US guidelines for the prevention, detection, evaluation, and management of high blood pressure in adults proposed the diagnosis of hypertension at 130/80 mmHg, while the European Society of Cardiology and 2020 Brazilian Guidelines of Hypertension maintain the 140/90 mmHg cut-off. We aimed to evaluate how the cut-off established by the American Heart Association guidelines would impact the prevalence of hypertension in the ELSA-Brasil cohort and compare the clinical characteristics among these subgroups. The participants were part of the ongoing ELSA-Brasil multicenter cohort, with baseline data collected between 2008 and 2010, consisting of 15,105 public servants of both sexes aged 35 to 74 years. Hypertension (≥140 or ≥90 mmHg or use of antihypertensive drugs in the last two weeks if below these values) prevalence was 36.2% (95%CI: 35.4-36.9, n=5,456) with the Brazilian cut-off and 51.4% (95%CI: 50.6-52.1, n=7,756) when considering the US cut-off (SBP≥130 or DBP≥80 mmHg). In general, those with high blood pressure (HBP) presented an intermediate-risk profile compared to the hypertension group. Lowering the hypertension cut-off caused an absolute increase of 15.2% in the prevalence of hypertension in the sample of public servants studied. HBP individuals showed intermediate-risk profile between normal blood pressure and hypertension and represented a large fraction of the population who may benefit from treatment.

Abstract in English:

Delirium is a common complication in intensive care units (ICU). The PRE-DELIRIC model has shown promise in early delirium prediction, but its performance in Chinese ICU settings remains unclear. The objective of this study was to validate the PRE-DELIRIC model in a Chinese mixed medical-surgical ICU and evaluate its utility in guiding nursing interventions for delirium prevention. In this single-center retrospective cohort study, adult patients admitted to the ICU between January 2023 and October 2024 were included. The PRE-DELIRIC score was calculated within 24 h of admission. Delirium was assessed using Confusion Assessment Method for the ICU (CAM-ICU) every 8 h. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUROC). Among 580 patients, 176 (30.4%) developed delirium. The model showed good discrimination (AUROC 0.84; 95%CI: 0.81-0.87) and calibration (Hosmer-Lemeshow χ2=8.96, P=0.34). At the optimal cut-off point of 30%, sensitivity was 81.8% and specificity 78.2%, with 90.8% negative predictive value. Performance remained consistent across surgical (AUROC 0.84), medical (AUROC 0.86), and trauma patients (AUROC 0.85). Delirious patients had longer ICU stays (median 11.2 vs 7.1 days, P<0.001) and higher mortality (15.9 vs 10.4%, P=0.028). The PRE-DELIRIC model demonstrated reliable predictive performance in Chinese ICU settings. Integration into routine nursing assessment could guide individualized preventive interventions and optimize resource utilization.

Abstract in English:

This study aimed to investigate the impact of targeted nursing care combined with nutritional support on the clinical outcomes of diabetic nephropathy (DN) patients undergoing maintenance hemodialysis (HD). Clinical indicators such as serum creatinine (SCr), blood urea nitrogen (BUN), fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and K (urea clearance) × t (dialysis time) / V (volume of urea distribution) (Kt/V), as well as inflammatory indicators such as high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, and tumor necrosis factor-α (TNF-α), and nutritional indicators such as transferrin (TRF), albumin (ALB), and prealbumin (PA) were measured. SF-36 quality of life scale scores were assessed, and adverse events and patient satisfaction with care were recorded. Post-intervention, the experimental group exhibited lower SCr, BUN, FBG, HbA1c, hs-CRP, IL-6, and TNF-α, and higher body mass index, Kt/V, TRF, ALB, and PA than the control group (all P<0.05). Additionally, the experimental group demonstrated higher nursing satisfaction scores, and lower total incidence of adverse events compared to the control group (all P<0.05). Targeted nursing care combined with nutritional support applied to DN patients during HD helped improve residual renal function, reduce the body's inflammatory response, improve nutritional status and the quality of life, reduce adverse events, and at the same time, improve nursing satisfaction.

Abstract in English:

Biochanin A (BCA), a phytoestrogen with broad therapeutic potential, is a promising molecule for alleviating post-menopausal symptoms and treating disorders related to reproductive metabolism. Nevertheless, the effect of BCA on inflammatory changes caused by postmenopausal obesity is unclear. Thus, this study focused on investigating the impact of BCA on the adipose tissue and liver of ovariectomized (OVX) mice subjected to a high-fat diet (HFD). We found that BCA treatment reduced the crown-like structures (CLS), adipocyte area, and hypertrophic adipocyte distribution. This was accompanied by an increase in the anti-inflammatory cytokines interleukin (IL)-5 and IL-10 and the expression of Mrc1 (CD206), a marker for M2 macrophages. Furthermore, there was a reduction in the extent of hepatic steatosis, triglyceride content, and the expression of Nos2, the M1 marker. We concluded that BCA exerted an anti-inflammatory response in the tissues, promoting a resolving profile, although the metabolic profile of the animals was not altered. This study was the first to demonstrate the anti-inflammatory effect of BCA in ovariectomized animals with established obesity.

Abstract in English:

Diabetic osteoporosis (DOP) is a complication of prolonged hyperglycemia. Hydrogen sulfide (H2S) has been identified as a protective factor in bone development. However, the mechanism by which H2S antagonizes the effects of high glucose (HG) on osteoblasts remains unclear. The effects of HG and H2S on osteoblasts were assessed through transcriptomic and metabolomic sequencing to identify key changes in gene expression and metabolism. Reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), alkaline phosphatase (ALP) activity, mineralization, iron ion levels, malondialdehyde (MDA) levels, cell proliferation, and protein expression were evaluated. Transcriptomic analysis revealed significant upregulation of the ferroptosis pathway in HG-treated osteoblasts. Fer-1 and H2S antagonized the HG-induced decrease in osteoblast cell proliferation, increase in ROS production, decrease in MMP, decrease in ALP, decrease in mineralized nodules, and increase in iron ions and MDA. Transcriptome analysis showed Fer-1 was involved in upregulating the synthesis, secretion, and action of parathyroid hormone and estrogen synthesis, while downregulating the mitogen-activated protein kinases (MAPK) pathway. Metabolomic analysis showed H2S restored glutathione metabolism, reducing pyroglutamic acid and L-5-oxoproline levels. Transcriptome sequencing identified downregulated genes (hmox1, ncoa4) and an upregulated gene (slc40a1) related to ferroptosis in the H2S + HG group compared with the HG group. Western blot analysis indicated H2S increased GPX4 and SLC7A11 levels while reducing ACSL4 expression compared with the HG group. Ferroptosis may be involved in the pathogenesis of DOP and H2S can effectively alleviate osteoblast injury by inhibiting ferroptosis in DOP.

Abstract in English:

Colorectal cancer (CRC) is the fourth-leading cause of cancer-related mortality worldwide. Semaphorin 6A (SEMA6A) is a member of the semaphorin family, and its specific biological function in CRC progression remains unclear. Bioinformatics analysis revealed that SEMA6A expression was downregulated in CRC tissues and that low expression of SEMA6A was associated with a poor prognosis. Compared with those in normal colorectal epithelial cells, SEMA6A expression levels were lower in CRC cell lines. CACO2 and SW48 cells were chosen to construct stable SEMA6A-knockdown and SEMA6A-overexpressing cell lines. SEMA6A knockdown promoted CACO2 proliferation. Conversely, SEMA6A overexpression inhibited the proliferation and promoted the apoptosis of SW48 cells. Transwell and wound healing assays demonstrated that SEMA6A overexpression inhibited the invasion and migration ability of SW48 cells. SEMA6A overexpression might impede CRC cell migration and invasion by inhibiting the epithelial-to-mesenchymal transition, as evidenced by the downregulation of N-cadherin expression and the upregulation of E-cadherin expression in SW48 cells. To further validate the role of SEMA6A in CRC progression in vivo, transplanted tumor and liver metastasis mouse models were constructed in nude mice by injecting stable SEMA6A-overexpressing SW48 cell lines. SEMA6A overexpression inhibited tumor growth in SW48 tumor-bearing mice and the expression of Ki-67 in tumor tissues. In addition, SEMA6A overexpression resulted in a marked decrease in liver metastasis of CRC cells, with decreased numbers of hepatic metastatic nodules and infiltration of cancer cells. In summary, SEMA6A overexpression alleviated CRC progression by inhibiting tumor growth and metastasis both in vivo and in vitro.

Abstract in English:

After SARS-CoV-2 infection, severe COVID-19 may develop with persistent sequelae, even after hospital discharge. This condition may result from tissue damage or immune alterations caused by the virus, including immune dysregulation, hyperinflammation, loss of immune tolerance, excessive neutrophil extracellular trap (NET) production, and antibody cross-reactivity (molecular mimicry), which can promote autoantibody development. This study evaluated autoantibody expression in patients with long COVID-19 and its potential relationship with symptoms. Conducted in Baixada Santista, São Paulo, Brazil, the study involved 55 participants aged 21-85 years who had tested positive for SARS-CoV-2. Blood samples were collected two years post-discharge, and serum was analyzed for inflammatory and autoimmune markers, including antinuclear antibody (ANA), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), procalcitonin (PCT), Venereal Disease Research Laboratory test (VDRL), and C-reactive protein (CRP). Results were compared to a control group of 21 individuals who never tested positive for COVID-19. Among severe COVID-19 patients, 26 reacted to ANA, 16 to VDRL, 2 had elevated RF, 12 had increased PCT, and 11 had high CRP, whereas the control group showed no reactive results. Anti-CCP values were not significant. Findings suggest that hyperinflammation may contribute to autoimmunity, particularly in cases of reactive ANA levels, linking COVID-19 symptoms to autoimmune responses.

Abstract in English:

A hallmark of COVID-19 patients is the reduction of the lymphocyte population accompanied by activation, senescence, and exhaustion markers. We investigated patients admitted to hospital wards who either recovered after a short hospitalization or progressed to critical illness. Patients (n=48) were recruited between May and September 2020; 19 healthy volunteers were enrolled as controls. Blood samples were collected on days 0, 3, and 7 of hospitalization and around 30 days after discharge (convalescence sample, CS30). Lymphocyte counts and extended immunophenotyping were performed by flow cytometry and analyzed using conventional and stochastic methods. At D0 and D7, total lymphocytes, natural killer cells, T cells, TCD4 cells, and TCD8 cells were lower in patients than in volunteers but were restored at CS30. The stochastic analysis identified 11 distinct clusters of lymphocytes, nine of them with significant differences between patients and healthy controls. Clusters of TCD8+ memory cells showing activation, senescence, and exhaustion were increased in patients during hospitalization and in the convalescence samples. In contrast, clusters 5 (TCD4+ Central Memory exhausted activated) and 7 (TCD4+ Central Memory exhausted) were decreased in patients during the disease compared to healthy controls. Overall, the conventional flow cytometry analyses corroborated the findings from the stochastic analysis, showing that effector memory (EM) and TEMRA subsets exhibited sustained markers of exhaustion and senescence, particularly in TCD8+ cells. Our findings reinforce lymphopenia, T cell activation, senescence, and exhaustion as essential immunological features of COVID-19; while cell counts fully recovered, lymphocytes remained dysfunctional in convalescent samples.

Abstract in English:

We aimed to explore the effect of omnibearing operating room nursing in total hip arthroplasty (THA) and its influence on postoperative pain. One hundred and twenty patients who underwent THA were enrolled and assigned into either a control group or an observation group, with 60 cases in each group. The control group received routine nursing, and the observation group received omnibearing operating room nursing in addition to routine nursing. Perioperative indicators, postoperative pain, physical signs, hip function, quality of life, complications, as well as nursing satisfaction were compared between the two groups. Compared to the control group, the observation group showed shorter operation time and hospital stay, less intraoperative blood loss, lower visual analogue scale (VAS) scores post-operation, a lower rate of additional analgesic use, and decreased respiratory rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP) at 7 days after operation, as well as elevated Harris Hip Score (HHS) dimension scores, total scores, and SF-36 scores, lower total incidence rate of complications, and higher total satisfaction rate of nursing care (all P<0.05). Omnibearing operating room nursing can relieve postoperative pain, promote the recovery of hip joint function, improve the quality of life, decrease the occurrence of complications, and enhance patients' nursing satisfaction.

Abstract in English:

This study aimed to explore the construction and application of a nomogram model for early-stage cervical central lymph node metastasis (CLNM) in papillary thyroid cancer (PTC) combined with Hashimoto's thyroiditis (HT). The study included 360 patients with pathologically diagnosed PTC. Of these, 100 patients had PTC with concurrent HT. Univariate and multivariate analyses were conducted to identify risk factors for CLNM in patients with PTC and HT. A nomogram was designed to guide clinical decision-making. Age, gender, thyroid peroxidase antibody status, tumor diameter, tumor location, multifocal lesions, capsular invasion, calcification, aspect ratio ≥1, irregular morphology, and tumor diameter ≥1 cm strongly correlated with CLNM in patients with PTC combined with HT. Notably, capsular invasion, aspect ratio ≥1, calcification, and irregular morphology were risk factors for CLNM in patients with PTC combined with HT. A nomogram was constructed to visualize and graphically calculate the probability of CLNM development in these patients. Our findings indicated that the independent risk factors for CLNM development in patients with PTC combined with HT are capsular invasion, aspect ratio ≥1, calcification, and irregular morphology. The nomogram model developed in this study has great potential for clinical applications.

Abstract in English:

Quercetin has therapeutic potential in the treatment of musculoskeletal lesions, but presents poor oral absorption because of its low water solubility and structural instability. Its penetration through the skin can be enhanced by quercetin-loaded nanostructured lipid carriers (NLC-Q), which is increased when applied with massage, but this has not yet been tested. This study aimed to evaluate the effect of massage with NLC-Q gel on biochemical parameters after a traumatic lesion of the gastrocnemius muscle. Forty-five male Wistar rats were divided into five groups (control, lesion, lesion treated with NLC-Q gel, lesion treated by massage with placebo gel, and lesion treated by massage with NLC-Q gel). The gastrocnemius muscle was lesioned by mechanical crushing, and treatments began 24 h after injury. Massage was performed at 12 h intervals for a total of five 5-min sessions. Serum and muscle creatine kinase (CK) concentrations and muscle oxidative stress (concentration of reactive oxygen species [ROS], lipid peroxidation, protein carbonyls, and activities of superoxide dismutase and catalase enzymes) were evaluated 96 h after lesion formation. Blood CK levels increased in all injured groups (P<0.001); however, the interventions reduced plasma CK compared to the lesion group (P<0.05). Interventions reduced lipid peroxidation (P<0.05), but only the NLC-Q gel and massage with NLC-Q gel reduced the concentration of ROS and protein oxidation in the lesion group (P<0.05). These findings indicated that NLC-Q gel and massage with NLC-Q gel can help repair muscle damage and reduce oxidative stress parameters.

Abstract in English:

Schistosomiasis remains a major global health concern, affecting approximately 260 million people, with 440 million experiencing morbidity and over 800 million at risk of infection. According to the World Health Organization (WHO), it ranks as the second most socioeconomically impactful infectious disease and the third most significant parasitic disease in terms of public health. This study aimed to improve immunodiagnostic tools for Schistosoma mansoni in resource-limited settings by developing monoclonal antibodies (MoAbs) using locally available materials. MoAbs were produced using hybridoma technology and assessed for specificity to soluble worm antigen preparation (SWAP) through ELISA. Immuno-phosphatase and immuno-peroxidase staining were employed to localize target antigens across various life cycle stages and assess cross-reactivity with related species. Four distinct MoAbs demonstrated strong phosphatase and peroxidase activity in the gut and tegumental tubercles of S. mansoni adult worms, with extreme (4+) phosphatase staining. The dorsal tubercles and oral/ventral suckers showed strong (3+) peroxidase staining. S. mansoni schistosomula showed positive staining in the oral sucker and penetration glands, while cercariae showed no reactivity. Cross-reactivity with S. haematobium was minimal, showing only weak (1+) peroxidase staining in gut and tegumental structures, as well as the intact worm's tegumental tubercles and suckers. In conclusion, the MoAbs developed exhibited high specificity for S. mansoni with limited cross-reactivity to S. haematobium, supporting their potential utility in locally produced, sensitive immunodiagnostic tools to strengthen schistosomiasis control and elimination efforts in endemic regions.

Abstract in English:

The current therapy for myocardial infarction focuses on reestablishing blood flow in the coronary arteries to reduce the ischemic area, but the subsequent damage caused by reperfusion cannot be ignored. Liquiritin, a primary flavonoid compound found in the medicinal plant licorice, exhibits distinct pharmacological properties including neuroprotection, anti-inflammatory, antioxidant, and anti-apoptotic effects. However, further research on its role and mechanism in myocardial ischemia-reperfusion (I/R) injury is needed. The aim of this work was to elucidate the protection of liquiritin against myocardial I/R insult and whether liquiritin-mediated autophagy restoration was associated with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in vivo and in vitro. Liquiritin administration by oral gavage inhibited pathological injury of myocardial I/R injured rats, evidenced by improved cardiac function and reduced infarct size. Moreover, liquiritin restored excessive autophagy by promoting the phosphorylation of protein kinase B (AKT) and mammalian target of rapamycin (mTOR), which was accompanied by PIK3CA upregulation. Mechanistically, silencing PIK3CA in rat H9c2 cardiomyoblasts diminished the beneficial effects against oxygen-glucose deprivation/reoxygenation (OGD/R) injury reflected by exacerbated apoptosis and dysregulated autophagy mediated by the classical PI3K/Akt/mTOR pathway. Liquiritin inhibited excessive autophagic flux via decreasing autophagosome-lysosome fusion, which was similar to the effect of the autophagy inhibitor chloroquine. Moreover, this phenomenon was enhanced when liquiritin and chloroquine were used in combination. Collectively, our work revealed that the protective effect of liquiritin against myocardial I/R injury may be attributed to its autophagy restoration mediated by PIK3CA.

Abstract in English:

This study was designed to identify new biomarkers for early diagnosis of acute myocardial infarction (AMI). GSE66360 and GSE48060 datasets were downloaded from the Gene Expression Omnibus (GEO) database. The “limma” tool was used to screen differentially expressed genes (DEGs). A total of 557 anoikis-related genes (ARGs) were obtained from the GeneCard database. Differentially expressed ARGs (DEARGs) were obtained by intersecting DEGs with ARGs. The least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), and Random Forest (RF) were used to screen the hub DEARGs. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of hub DEARGs. A total of 21 DEARGs were obtained, all of which were up-regulated in AMI samples. Functional enrichment analysis showed that the DEARGs were mainly enriched in peptidase activity and extracellular matrix. Immune cell infiltration analysis revealed a significant difference in 14 immune cells between the AMI and normal groups. Nine feature risk genes, including ITPRIP, MMP9, NAMPT, CDKN1A, PLAUR, PLAU, SERPINA1, THBS1, and FN1 were screened by LASSO, SVM, and RF. The RT-qPCR analyses verified that the feature genes were up-regulated in AMI patients, which were basically consistent with the main bioinformatics analysis results. We also validated 9 hub DEARGs in the GSE48060 dataset and constructed a nomogram by integrating these DEARGs. This study analyzed the differential expression of ARGs and immune profiles in AMI and normal samples, screened 9 risk feature genes for predicting AMI, and provided a theoretical basis for the immunotherapy regimen of AMI.

Abstract in English:

Antiretroviral therapy (ART) has transformed HIV from a life-limiting infection into a manageable chronic condition, shifting attention toward the emerging challenges faced by the growing population of adults aged 50 years or older living with HIV. This observational cohort study tracked 1,018 individuals treated in the medical system in Brazil, a middle-income country, to better understand the effectiveness of traditional and simplified ART regimens in older adults living with HIV (OALH), a frequently underrepresented group in clinical studies. Older adults, those aged 50 and above, living with HIV achieved significantly higher rates of undetectable viral load (89.4 vs 83.2%, P<0.006) and fewer cases of virological failure, defined as HIV-RNA >500 copies/mL (2.5 vs 10.1%; P<0.0001) than younger adults aged 18-49, and demonstrated superior immune recovery through significantly greater CD4+ T-cell counts (P=0.0012). The multivariate analysis found that improved clinical outcomes (undetectable viral load) were most highly correlated with the simplified treatment regime and more years of treatment duration. These findings highlight the value of simplified ART regimens and sustained treatment duration, which were observed to be more frequent in OALH.