Abstract in English:

One of the most serious clinical manifestations of tuberculosis (TB) is the central nervous system (CNS) presentation, which results in neurological disorders and cognitive impairments that may lead to reduced social skills. Few studies have assessed TB neuropsychological symptoms after infection. This review article investigated the incidence and spectrum of cognitive impairment related to complications in patients with CNS-TB and compiled data on the pathophysiology, diagnosis, and treatment of the disease. An extensive literature review was performed, and a total of 286 published studies were selected for manual screening. For analysis purposes, 43 studies were included in this review. CNS-TB mainly affects young children and is fatal in over 50% of cases, with survivors showing high morbidity. The characteristics of this disease include meningitis and brain tissue granulomas. This leads to extensive neurological involvement, resulting in a complex mechanism that alters the structure and composition of cells in the brain including the cerebellum and spinal cord. It also impairs language development, reading, and learning complex tasks, and therefore affects the patient's social adjustment. The results of our review provide information connecting the basis of neuroscience and clinical medicine, especially childcare. Furthermore, early diagnosis is imperative to prevent serious cognitive consequences of TB in the developing CNS.

Abstract in English:

Volemic control is essential for maintaining tissue perfusion and fluid homeostasis, with cardiorenal and endothelial mediators regulating intravascular composition, often impaired in pathological states. Notably, intestinal epithelial cells are highly sensitive to volume fluctuations, resulting in changes in intestinal permeability that may not be detected by current diagnostic methods. This review offers a comprehensive description of the main mediators involved in volemic regulation, their impact on intestinal morphofunctionality, and specific details regarding epithelial cells. Additionally, key biomarkers - especially lactulose/mannitol - for assessing intestinal barrier disruption are highlighted, and a novel approach is proposed using liquid chromatography-mass spectrometry to investigate gut alterations in heart failure and exercise-induced stress, which are silent and neglected conditions with significant repercussions on intestinal barrier function.

Abstract in English:

Ferroptosis is an iron-dependent programmed cell death characterized by lipid peroxidation. Ferroptosis plays a key role in the dysfunction of vascular endothelial cells (VECs), which may promote pathological vascular damage through oxidative stress, inflammatory response, and barrier integrity destruction. The pathogenesis of vertebral artery (VA) type cervical spondylosis (CSA) is complex. Cervical degeneration and other factors can induce ferroptosis of VA VECs. This review systematically reviews the cutting-edge research results on the biological characteristics of ferroptosis, analyzes its molecular mechanism in the regulation of VECs function, and systematically discusses its internal relationship with CSA pathogenesis. This study provides a new perspective on the pathogenesis of CSA, as well as a new theoretical basis and potential intervention targets for developing targeted treatment strategies and disease prevention.

Abstract in English:

Bladder cancer (BCa) is a histologically and molecularly heterogeneous disease and is one of the leading causes of cancer death globally. The main risk factors are sex (with incidence 3 to 4 times higher in men), tobacco usage, occupational exposure to carcinogens, and persistent infections, such as those caused by Schistosoma haematobium. Urine and the bladder were recently confirmed to be non-sterile, prompting investigations into the urinary and intratumoral microbiomes and their roles in tumor stage, prognosis, and therapy response. In this context, the role of the urinary and intratumoral microbiome in bladder carcinoma is among the most promising areas in translational uro-oncology. Recent evidence demonstrates the presence and diversity of microbial communities in both urine and bladder cancer tissue, with patterns associated with tumor stage and prognosis. Chronic inflammation, genotoxin production, altered carcinogen metabolism, and modulation of the immune microenvironment are biological processes that provide a rationale for the functional role of these microorganisms in the bladder. Furthermore, microbial profiles have been correlated with responses to intravesical therapies (such as BCG - Bacillus Calmette-Guérin) and, potentially, with systemic immunotherapies. The microbiome can help identify predictors of treatment response and potential adjuvant interventions, and offers a non-invasive, translational pathway for diagnosis and surveillance. This review summarizes current evidence on the microbiome in bladder cancer patients and its prognostic and therapeutic potential.

Abstract in English:

Meningiomas are the most common primary intracranial tumors, and xenotransplantation models help to study their behavior and test therapies. This research developed a model implanting WHO grade I meningothelial meningioma into the peritoneum of immunosuppressed rats, comparing it to subcutaneous implantation. The primary objective was to analyze tumor growth and progression, focusing on the role of the microenvironment. Peritoneal implants (1.87±0.25 cm) grew significantly larger than subcutaneous implants (0.86±0.14 cm) (P<0.0001). An inverse correlation was found between weight variation and the difference in implant sizes, indicating that weight loss in animals was associated with larger implant growth. Animals that lost weight had significantly larger implants compared to those that gained weight. Implantation site and the animal's weight variation can significantly impact the growth of meningothelial meningioma fragments, with peritoneal implants showing greater growth and weight loss correlating with larger tumors.

Abstract in English:

With the emergence and rise of the COVID-19 pandemic in 2020, many health services were interrupted and reallocated due to system overload. Tuberculosis (TB) care was one of the affected services during this period, especially in regions with greater social vulnerabilities. Thus, this study aimed to describe the distribution of TB cases before and during the COVID-19 pandemic on an island in the Brazilian Amazon. This quantitative descriptive retrospective study evaluated the distribution of 797 new confirmed and notified cases of TB in residents of the sixteen municipalities in the region of Marajó Island (Pará, Brazil), from 2017 to 2022. The data were obtained from the Development and Administration Company of the Metropolitan Area of Belém and Google Earth, using the ArcGIS and TerraView software for georeferencing notification points in each municipality of the archipelago. The Kernel density estimator and scan statistics were used to analyze the point patterns. Almost all municipalities in the archipelago showed variations during the study years. The scan statistics showed a greater number of cases in the pre-pandemic years of 2017-2019. These data indicated that the factors related to the increase and decrease in the number of cases must be analyzed, as the decrease may be related to the underreporting of patients due to the lack of access to health resources in more isolated areas.

Abstract in English:

Accumulating evidence has pointed out that the altered expression of long non-coding RNAs (lncRNAs) is involved in the physiopathology of breast cancer (BC). However, the role of lncRNAs in BC progression remains poorly understood. Here, we evaluated cDNA microarray data from a previous study from our group to investigate the effects of SPARC expression on the transcriptome of MCF7 cells before and after treatment with docetaxel. We analyzed our gene expression data to identify differentially expressed long non-coding RNAs (DELncRNAs). In combination with in silico analysis, we selected a group of DELncRNAs with potential prognostic and predictive value for BC patients with tumors of different intrinsic subtypes. Overall, we identified 260 DELncRNAs comparing MCF7 cells with different expressions of SPARC after docetaxel treatment. Nine DELncRNAs (LOC646762, FLJ13224, CASC2, LOC100130691, MGC12916, LOC100190986, LOC283856, KIAA0125, and MIR155HG) showed significant associations with BC survival on the KM Plotter platform. Of these 9 DELncRNAs, MIR155HG, LOC283856, LOC100190986, and KIAA0125 were significantly correlated with recurrence-free survival and overall survival rates of BC patients, suggesting they could help predict the outcome of BC patients as prognostic factors. Moreover, in silico analysis showed that these DELncRNAs were able to predict BC patients' responses to different treatment protocols.

Abstract in English:

According to the most recent Global Status Record of Road Traffic, the number of road traffic deaths continues to rise. The risk of a road traffic death is more than 3 times higher in low-income countries than in high-income countries. However, the effect of time of day on road accidents is barely considered in public policies to reduce the chance of an accident. This study aimed to estimate the chance of an accident for every hour of the day in Brazil. From the raw data on accidents, their hourly distribution was derived, with a one-hour resolution. The data on the flow of vehicles on the highways was similarly organized. In the specific case of the flow, the total average flow for all sensors on Brazilian highways from 2015 to 2017 was used. It was clearly observed that the chance of an accident, in general, is on average 3-3.5 times higher between 02:00 and 04:00 h than during 07:00-19:00 h. Two other peaks were also noticed, the first one at around 07:00 h and a second one around 18:00 h, which were linked to an excess of vehicle traffic (rush hours) but were lower when compared to the chance during the night. The chance of a road accident in the middle of the night was higher compared to the rest of the 24 hours, similar to high-income countries.

Abstract in English:

Microbiology education is traditionally lecture-based, with few studies exploring active methodologies such as serious games. In this context, this study aimed to develop a serious card game, ‘Bakterion', as a teaching tool for antimicrobial education. The game was designed based on Game Design Thinking, following the stages of Empathy, Ideation, and Implementation. Inspired by the game Munchkin®, Bakterion includes a rulebook, markers, and 200 cards featuring illustrations based on electron microscopy and laboratory materials. The cards were designed to be easy to use, allowing players to correlate elements even without prior specialized knowledge. The game presents an innovative approach to microbiology education, fostering student engagement and active participation. Bakterion may serve as a promising tool for teaching microbiology and antimicrobial resistance, complementing traditional methods. Future studies should assess the impact of Bakterion on student learning.

Abstract in English:

This in vitro and in vivo study assessed dealcoholized red wine (DRW) effects on cytokine profile in macrophage (MQ)-periodontal ligament fibroblast (PDLFs) co-cultures and its impact on blood parameters, inflammatory/bone markers, cytokine expression, and periapical bone loss in rat apical periodontitis (AP). A MQ-PDLFs co-culture and Wistar rats with induced AP were exposed to DRW or red wine (W), with DMEM or water as controls (C). Cell cultures were analyzed for cytokine profile using a multiplex immunoassay. Rats underwent blood profiling, radiography, qRT-PCR, and histometric analysis of AP. Statistical significance was set at 5%. Multiplex analysis of the co-culture revealed that DRW induced lower interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels compared to C and W, higher IL-10 level than C, and lower IL-1β level only compared to W (P<0.05). Radiographic images confirmed AP development in rats. DRW showed a reduced monocyte count compared to C (P<0.05), but the inflammatory/bone markers in plasma were similar (P>0.05). Additionally, DRW showed lower IL-1β expression than C, and higher IL-10 expression only compared to W in AP (P<0.05). Periapical bone loss was similar among groups (P>0.05). In conclusion, DRW promoted an anti-inflammatory profile in co-cultures and in vivo. However, these effects did not translate into differences in lesion size or bone loss within the experimental model evaluated.

Abstract in English:

Astrocytes play critical roles in the physiological responses of the central nervous system (CNS). Located near pre- and postsynaptic sites, they detect released neurotransmitters and gliotransmitters that modulate neuronal function. Astrocytic responses to neurotransmitter excitation often involve increases in cytoplasmic calcium, triggering the release of gliotransmitters that further influence neuronal activity. The nucleus of the solitary tract (NTS), a brainstem region integrating diverse physiological functions such as cardiovascular, respiratory, digestive, and metabolic reflexes, is modulated by astrocytic activity. To better understand the dynamics and diversity of calcium responses in NTS astrocytes to the primary excitatory neurotransmitter glutamate, we investigated individual subpostremal NTS astrocytes in brainstem slices from mice using the calcium fluorescent dye Fluo-4. We observed that only a subset of astrocytes exhibited an increase in cytoplasmic calcium in response to glutamate, while a smaller fraction showed a decrease in cytoplasmic calcium. Interestingly, in the presence of tetrodotoxin, which inhibits action potentials, the proportion of astrocytes with increased calcium levels was halved, and most astrocytes instead exhibited decreased calcium levels. Further analysis revealed that response peaks were correlated with total calcium levels after glutamate application, whereas response latencies and widths of positive calcium signals were not correlated with peak values. Negative peaks have distinct kinetics from positive peaks, corroborating that they represent different processes. These findings demonstrate that NTS astrocytes constitute a heterogeneous population with diverse responses to extracellular glutamate, highlighting their complexity in modulating brainstem functions.

Abstract in English:

Schistosomiasis can lead to vascular damage resulting in pulmonary arterial hypertension (PAH). Although its pathophysiology remains unclear, cytokine imbalance is known to play a key role. This study aimed to evaluate serum mediators in association with hemodynamic, echocardiographic, and histological parameters in a murine model of Schistosoma mansoni-induced pulmonary hypertension (Sch-PH). Twenty male C57BL/6 mice were randomized into infected group and non-infected control group. Sch-PH was induced by intraperitoneal inoculation of S. mansoni eggs (240 eggs/g body weight), followed by intravenous administration (175 eggs/g). After 21 days, systolic pulmonary artery pressure was measured by right ventricular catheterization (RHC), and cardiac function was assessed by transthoracic echocardiography. Animals were then euthanized for collection of lungs and heart for histopathology, and blood samples were obtained for quantification of interleukin (IL)-6, IL-10, and tumor necrosis factor (TGF)-β1 by ELISA. The Sch-PH group had significantly lower tricuspid annular plane systolic excursion and pulmonary artery acceleration time/pulmonary ejection time ratio (P<0.05), and increased pulmonary artery peak flow, tricuspid and pulmonary regurgitation, IL-6, and TGF-β1 levels (P<0.05). IL-10 was undetectable. Lung tissue showed inflammatory infiltrates, alveolar and perivascular granulomas, and S. mansoni eggs. Pulmonary arteries exhibited intimal thickening, medial hypertrophy, and fibrosis. Cardiac tissue presented inflammatory foci, fibroblast proliferation, and thickening of connective septa. IL-6 and TGF-β1 were elevated in Sch-PH and correlated with echocardiographic and hemodynamic alterations. These findings suggest a role for these mediators in Sch-PH pathogenesis and highlight the potential for targeting inflammatory pathways in this condition.

Abstract in English:

This study evaluated prevalence, incidence, and progression of carotid intima-media thickness (cIMT) and carotid artery plaques (CAP) in rheumatoid arthritis (RA) patients compared with controls during 8 years of follow-up. A case-cohort analysis of data from the ELSA-Brasil cohort was conducted, with cIMT and CAP measured by carotid ultrasound at baseline and follow-up. Linear regression was used to estimate cIMT mean and progression (ΔcIMT). Logistic regression was used to estimate odds ratios (OR) for elevated cIMT (≥75th percentile), CAP prevalence, incidence, and progression. Models were adjusted for sociodemographic and cardiovascular risk factors, excluding participants with prior cardiovascular disease. A total of 1,289 participants (188 RA, 1,101 controls) were included in the cIMT analysis and 585 (93 RA, 492 controls) in the CAP analysis. RA was not associated with baseline cIMT (β=0.00; 95%CI: -0.02-0.02; P=0.930), high cIMT (OR=1.04; 95%CI: 0.69-1.57; P=0.864), or ΔcIMT (β=0.00; 95%CI: -0.01-0.02; P=0.688). Incidence of elevated cIMT showed a non-significant trend toward higher risk in RA (OR=2.01; 95%CI: 0.88-4.59; P=0.098). No associations were found for CAP prevalence at baseline (OR=1.64; 95%CI: 0.92-2.91; P=0.090), prevalence at follow-up (OR=0.75; 95%CI: 0.41-1.36; P=0.342), incidence (OR=0.78; 95%CI: 0.37-1.63; P=0.508), or progression (β=-0.33; 95%CI: -0.72-0.07; P=0.102). This study found no independent association between RA and cIMT or CAP.

Abstract in English:

Athletes mobilize both aerobic and anaerobic systems to produce energy during soccer matches, and it drastically modifies the concentration of metabolites related to muscle damage and energy metabolism. The fatigue-associated mechanism seems to encompass tricarboxylic acid cycle (TCA) disturbances, with a greater contribution of lipid-pathway metabolites in women during soccer matches. However, to the best of our knowledge, the effects of matches played during two championships on the metabolites and pathways associated with energy production in female players have not yet been described. Metabolomic analysis in sports context can better characterize the main metabolites related to energy production and the metabolic pathways. The aim of this study was to describe the variation in metabolites over the course of two championships in female players' urine, highlighting the occurrence of energy production-associated metabolites and the metabolic pathways they may arise from. Urine samples were collected before and after six matches of two championships. Nuclear magnetic resonance metabolomic approach was used for this purpose. Citrate, succinate, 1-methylnicotinamide, alpha-hydroxyisobutyrate, malonic and glycolic acids, phosphocreatine, and lactate were the compounds originated from energy generation processes with high scores in variable importance prediction (VIP), impacting on partial least squares discriminant analysis (PLS-DA) groupings of players. Phenylalanine biosynthesis, tyrosine and tryptophan biosynthesis, and the TCA cycle were mobilized before the matches, and the metabolism of taurine and hypotaurine were modulated across both moments.

Abstract in English:

Fatigability is critical for understanding older adults' physical and mental health. The Pittsburgh Fatigability Scale (PFS) is widely employed to measure perceived fatigability, reflecting how fatigue impacts performance and its association with adverse health outcomes. This study aimed to evaluate the psychometric properties of the PFS adapted for Brazilian older adults (PFS-Brasil), focusing on perceived physical and mental fatigability. Confirmatory factor analysis (CFA) validated the bifactorial model. Internal consistency was assessed using Cronbach's alpha, while test-retest reliability was evaluated through the intraclass correlation coefficient (ICC) and Bland-Altman Plot. Convergent validity was determined by correlating PFS-Brasil score with physical and cognitive performance measures, and ceiling and floor effects were analyzed. CFA confirmed the two-factor structure of the PFS-Brasil. The Physical and Mental subscales showed high internal consistency (α=0.89 and 0.86, respectively). Test-retest reliability demonstrated good agreement (ICC for Physical=0.84; Mental=0.83). Higher fatigability score correlated with poorer physical performance on the Short Physical Performance Battery (SPPB) and the 6-Minute Walk Test (6MWT), with physical score showing weak to moderate correlations (P=-0.22 to -0.37) and mental score showing weak correlations (P=-0.20 to -0.25). Mental fatigability was weakly correlated with inhibitory control. The PFS-Brasil demonstrated robust psychometric properties, supporting its reliability and validity for assessing perceived physical and mental fatigue in older adults. Its use is recommended in clinical and research settings to identify individuals at risk of physical and psychological decline, promoting better health outcomes and quality of life in aging.

Abstract in English:

Acute lung injury (ALI) is a common complication of sepsis in connection with excessive inflammation and accumulation of oxidative stress. Sorting nexin 10 (SNX10) is a sorting nexin family member involved in inflammatory processes. This study aimed to explore the function of SNX10 in ALI. The cecal ligation and puncture (CLP) model was established to induce ALI in C57BL/6J mice. CLP mice exhibited elevated levels of SNX10 expression in the lung tissues. Mice were intratracheally injected with 50 μL adenovirus (108 PFU) containing short hairpin RNA plasmid targeting SNX10. SNX10 knockdown mice showed remission of CLP-induced pulmonary edema, hemorrhage, inflammatory infiltration, and thickened alveolar septum. SNX10 downregulation reduced reactive oxygen species (ROS) levels, increased superoxide dismutase activity and glutathione content, and decreased malondialdehyde content in the lung tissues. SNX10 knockdown decreased the phosphorylation of NF-κB p65 and its nuclear translocation, thus inhibiting the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6. Furthermore, SNX10 downregulation inhibited the NLRP3, p20 caspase 1, and ASC protein levels and the levels of IL-18 and IL-1β. A549 cells were treated with lipopolysaccharide (LPS) (10 μg/mL) for 24 h to simulate the inflammatory condition and SNX10 was knocked down using small interfering RNA. SNX10 knockdown cells showed increased viability and less ROS accumulation. Consistent with the in vivo results, the NF-κB/NLRP3 pathway and the secretion of inflammatory cytokines were inhibited after SNX10 knockdown in A549 cells. In summary, SNX10 downregulation mitigated sepsis-induced oxidative stress and pulmonary inflammation by inhibiting the NF-κB/NLRP3 pathway.

Abstract in English:

Patients with acquired immune deficiency syndrome (AIDS) are more vulnerable to opportunistic infections (OIs) such as Talaromycosis marneffei (TSM), which is associated with a high mortality rate. Nevertheless, the effect of TSM on the cardiovascular system of affected patients remains elusive. To that end, this research aimed to investigate the impact of TSM on the cardiovascular system in the individuals with HIV/AIDS. Participants were assigned to the HIV/AIDS patients group or the HIV/AIDS patients with TSM (HIV/AIDS+TSM) group. A total of 120 individuals were included in the present study, with 59 in the HIV/AIDS group and 61 in the HIV/AIDS+TSM group. Myocardial serum markers, color Doppler cardiovascular ultrasound (CCU), and 24-h ambulatory electrocardiograph (AECG) data were collected and analyzed for both groups. Compared with the HIV/AIDS group, the HIV/AIDS+TSM group exhibited a significant increase in left and right diameters of the right atrium (LR-RA) and right ventricle (LR-RV), while the anteroposterior diameter of the right ventricle outflow tract (AT-RVOT), the interventricular septal thickness (IVS), and the left ventricular posterior wall thickness (LVPW) were significantly reduced. The HIV/AIDS+TSM group showed higher AECG abnormality rates, particularly for non-sinus rhythms and ST-T changes. Our findings demonstrated significant cardiac functional alterations in HIV/AIDS patients with TSM co-infection compared to HIV/AIDS alone, underscoring the necessity for enhanced cardiovascular monitoring in this vulnerable population.

Abstract in English:

This case-control study compared perinatal and laboratory factors between preterm infants who received unfortified human milk (HM) and those who received HM fortified with FM85®. The sample included 38 low birth weight (LBW) preterm infants admitted to a neonatal intensive care unit between June 2022 and May 2023, excluding those with comorbidities or formula use. Perinatal variables including gestational age, birth weight, head circumference (HC), and mode of delivery were analyzed for associations with fortifier use using chi-squared and Student's t-tests. Laboratory values were compared across nutritional stages using the Kruskal-Wallis and Mann-Whitney tests. Very preterm infants (confidence interval [CI]: 4.02-21.10; P<0.001) and those with LBW (CI: 1.30-5.75; P=0.009) were more likely to receive the fortifier, particularly those with poor weight progression during trophic feeding (CI: 1.12-16.30; P=0.039). Altered HC (CI: 1.49-8.24; P=0.004) and cesarean delivery (CI: 2.24-11.30; P<0.001) were also associated with FM85® use. Both groups showed laboratory abnormalities with neutrophils, initially elevated, decreasing (P<0.0001), while lymphocytes increased (P<0.0001). Red blood cell (P=0.00026) and hemoglobin levels (P=0.00007) worsened. Sodium and calcium levels rose significantly (P<0.0001 for both). HM fortification did not significantly alter most laboratory values, except for red blood cell count. LBW, altered HC, and cesarean delivery were associated with a greater likelihood of fortifier use. Immunological changes occurred even with fortification. Homologous fortifiers may represent a more physiological alternative.

Abstract in English:

Perinatal stress can have lasting effects on hormone regulation and behavior. An association between maternal separation and depressive illness is well established. The present study was undertaken to investigate the effects of maternal separation on both motivational and consummatory measures and on the temporal patterning of sexual behavior in male rats. Litters were separated from their mothers for 180 min per day from P1 to P21 (birth=P0) and placed in an isolated box. Control litters remained with their mothers and were not disturbed. At 90 days of age, the sexual behavior of the male rats was assessed using both standard behavioral parameters and mount bout analysis. The forced swim test, open field test, and elevated plus maze test were used to assess anxious and depressive behavior. Each rat was subjected to a single type of behavioral protocol. The inhibitory effect of maternal separation on the sexual behavior of male rats was shown by an increase in mount, intromission, and ejaculation latencies, mount and intromission frequency, and interintromission interval, and a decrease in intromission ratio. Maternally separated rats showed a delayed temporal patterning of sexual behavior. In addition, there was an increase in depressive and anxiety-like behavior in maternally separated rats. The present results suggest that perinatal stress induced by maternal separation leads to changes in sexual behavior and depressive and anxiety-like behavior in male rats. In this sense, early postnatal stress may cause behavioral changes that persist into adulthood.

Abstract in English:

Proteinuria is a prevalent and significant adverse response (ADR) associated with numerous pharmaceuticals, and we employed the online public FDA Adverse Event Reporting System (FAERS) database to investigate a cohort of medications that may induce this ADR. This analysis aimed to identify and assess the most prevalent and significant medicines linked to the risk of proteinuria. We examined the publicly accessible FAERS database from 2004 to 2024. Utilizing the search term “proteinuria” and classifying by generic drug name, we aggregated reports of drug-related responses or trends in proteinuria, subsequently analyzing the data through a combination of ratio-of-reported-ratio (ROR) and proportional-reported-ratio (PRR) to identify and examine twelve medications that may induce proteinuria. A total of 16,355 adverse event reports related to proteinuria were identified in the FAERS database between 2004 and 2024. Among these, 21 drugs demonstrated statistically significant associations with proteinuria based on multivariate logistic regression, with the highest signals observed for voclosporin (ROR: 63.57) and lenvatinib (ROR: 41.01). Drug classes most strongly associated included anticancer agents, immunosuppressants, and antiviral drugs. Notably, the onset of proteinuria varied significantly across drug types, with anti-inflammatory agents showing the earliest median onset (5.4 days), while digestive system drugs and antivirals exhibited delayed onset exceeding 1,000 days on average. These findings underscore the need for early and long-term renal monitoring depending on drug category. Prompt assessment of nephrotoxicity risk is essential during the initial phase of medication, hence offering a more precise foundation for drug screening and optimization.

Abstract in English:

Human stem cells can divide and differentiate into various cell types. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are multipotent cells with high regenerative, anti-inflammatory, and immunomodulatory properties. Ethanol, the main component of alcoholic beverages, induces cytotoxicity and oxidative stress in cells. In recent years, natural compounds have gained attention for their potential protective effects against ethanol-induced cellular damage. p-Cymene is one such compound that acts as an antioxidant. This study aimed to evaluate the potential of p-cymene to reduce the harmful effects of alcohol on ethanol-induced cytotoxicity and oxidative stress in UC-MSCs through in silico and in vitro approaches. In silico pharmacokinetic and toxicity analyses of p-cymene were used, followed by in vitro evaluation using ethanol-injured UC-MSCs. Cell viability, antioxidant [glutathione (GSH), super-oxide dismutase (SOD)], inflammatory, proliferative, apoptotic, and wound healing assays were performed across different concentrations to assess protective effects. The pharmacokinetic analysis showed that p-cymene exhibited considerable pharmacokinetic properties by following Lipinski's Rule of Five. Toxicity analysis revealed no toxic effects of p-cymene, suggesting its potential as a natural compound. Further in vitro experimentation showed that p-cymene independently restored cell viability, reduced inflammation, stabilized Nanog, improved vascular endothelial growth factor (VEGF), enhanced antioxidants (GSH, SOD), promoted wound healing, and reduced cell death in ethanol-injured cells, with the 50 µM concentration being the most effective. These findings support our hypothesis that p-cymene protects UC-MSCs from ethanol-induced damage.

Abstract in English:

We aimed to expound the precise application of target-controlled infusion (TCI) of esketamine combined with sufentanil in anesthesia for video-assisted thoracoscopic surgery (VATS) and its effect on hemodynamics, postoperative pain, and safety. Eighty patients scheduled for thoracoscopic procedures were randomly assigned to either a control group [n=40, conventional empiric anesthesia (sufentanil plus propofol)] or an observation group [n=40, TCI of esketamine and sufentanil]. Hemodynamic indices [mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), stroke volume (SV), cardiac output (CO), systemic vascular resistance (SVR), and oxygen saturation (SpO2)] were recorded before anesthesia (T0), after induction of anesthesia (T1), 30 min of anesthesia (T2), and at the end of surgery (T3). Recovery profiles [length of stay in the post-anesthesia care unit (PACU), awakening time], Ramsay sedation scores (T0-T3), visual analog scale (VAS) pain scores at 2, 24, and 48 h post-op, and adverse event rates were compared. The observation group showed smaller hemodynamic fluctuations from T1 to T3. At T3, this group had higher MAP, SV, and CO (P<0.05), steadier CVP and SVR, faster recovery (PACU stay and awakening times shorter, P<0.01), lower VAS scores at 24 and 48 h, higher Ramsay scores at T2 and T3, and lower overall adverse event rates (P=0.018) than the control group. TCI of esketamine plus sufentanil improved intraoperative hemodynamic stability, shortened recovery, enhanced early analgesia, and reduced adverse reactions in VATS, supporting its precision and safety.

Abstract in English:

Disulfidptosis is a new form of programmed cell death. However, there is limited information available regarding the impact of disulfidptosis on septic acute respiratory distress syndrome (ARDS). The 16 disulfidptosis-related genes (DRGs) were collected from a previous study. Gene expression data of sepsis and septic ARDS samples were downloaded from the Gene Expression Omnibus database. The risk score model in septic ARDS was constructed based on the DRGs, followed by the investigation of immune microenvironment in septic ARDS patients. Furthermore, septic ARDS patients were divided into different subtypes based on disulfidptosis modification patterns, and their immune characteristics were investigated. Finally, the differentially expressed genes among different subtypes were identified, and a diagnostic model was constructed. The risk score model based on 6 DRGs was constructed to distinguish sepsis patients from septic ARDS patients, with good performance. The immune microenvironment in septic ARDS patients was slightly different from sepsis patients. Additionally, septic ARDS patients were divided into two subtypes based on DRGs. Finally, three diagnostic models based on 3 hub genes were constructed to classify the two subtypes in septic ARDS patients. Our findings indicated that disulfidptosis might play a role in the immune microenvironment of septic ARDS.

Abstract in English:

This study aimed to compare the effectiveness of combining trunk stretching with lumbar segmental stabilization versus exclusively performing lumbar segmental stabilization exercises for treating chronic nonspecific low back pain (CNLBP). Thirty-four CNLBP subjects were randomized into two groups: active trunk stretching + lumbar segmental stabilization (AS+LSS, n=17) and placebo stretching + lumbar segmental stabilization (PS+LSS, n=17). One-hour sessions were performed twice a week for six weeks. Pain intensity, pain quality, functional disability, global impression of recovery, emotional state, symptoms, and adverse effects were assessed at baseline, after 6 weeks, and at 12 and 24 weeks follow-up. Both groups experienced significant reductions in pain intensity and functional disability after the intervention. Depression and anxiety showed significant improvements during the intervention but did not persist at follow-up. No statistically significant differences were observed between the groups for the studied variables. The study concluded that both protocols are beneficial for CNLBP patients, suggesting that lumbar segmental stabilization exercises alone are sufficient for reducing pain and functional disability.

Abstract in English:

Mitochondrial dysfunction contributes critically to epileptogenesis. Therefore, identifying key mitochondrial function-associated genes in epilepsy may provide novel insights into its pathogenesis. We employed expression quantitative trait loci (eQTLs) and Mendelian randomization analyses to assess mitochondrial-epilepsy causality, with leave-one-out validation confirming the reliability and directionality of the results. The results revealed that hydroxyacylglutathione hydrolase (HAGH), oxysterol-binding protein-related protein 1A (OSBPL1A) and pantothenate kinase 2 (PANK2) were pivotal epileptogenic genes. HAGH modulates the mechanistic target of rapamycin complex 1 (mTORC1) signaling and fatty acid metabolism pathways. OSBPL1A mediates apoptotic and reactive oxygen species (ROS) pathways. PANK2 regulates phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling and Notch signaling cascades. Additionally, these genes participate in inflammatory pathways, including T cell receptor (TCR), mitogen-activated protein kinase (MAPK), and tumor necrosis factor (TNF) signaling. We demonstrated that HAGH, OSBPL1A, and PANK2 constitute core pathogenic mechanisms in epilepsy. These genes potentially govern epileptogenesis through mitochondrial regulation via neuroinflammatory, immunomodulatory, and apoptotic pathways. Our findings provide a foundation for investigating epileptogenesis, discovering therapeutic targets, and identifying prognostic biomarkers.

Abstract in English:

Preeclampsia (PE) is a life-threatening obstetric complication, and DNA methylation and immune system disorders play a key role in its development. This study aimed to explore the potential mechanisms and values of abnormally methylated immune-related differentially expressed genes (DEGs) in PE. Gene expression profiles and methylation data of PE were downloaded from the Gene Expression Omnibus (GEO) database. Immune-related genes were downloaded from the ImmPort database. Subsequently, differential expression analysis, functional annotation, immune cell infiltration analysis, Pearson correlation analysis, construction of classification models and miRNA-mRNA interaction network, and real-time PCR validation were carried out. Ten key abnormally methylated immune-related DEGs (ESRRG, FGF10, AHNAK, STC2, PPARG, LTF, MX1, ESR1, RELB, and JAG2) were identified and may be potential diagnostic biomarkers for PE. The decision tree (DT), random forests (RF), and support vector machine (SVM) classification models constructed based on these 10 genes exhibited a certain level of diagnostic accuracy. Compared with a single DEG, these classification models may have relatively higher diagnostic reference value. Functional annotation results showed that rap1, PI3K-Akt, and calcium signaling pathways may play a regulatory role in PE. The infiltration levels of monocytes, M2 macrophages, neutrophils, Tregs, and eosinophils in the PE group were abnormal. Key abnormally methylated immune-related DEGs were significantly correlated with the infiltration levels of immune cells. Moreover, 6 miRNA-mRNA pairs (hsa-miR-181b-5p-ESR1, hsa-miR-152-3p-ESR1, hsa-miR-26b-3p-ESR1, hsa-miR-4672-ESRRG, hsa-miR-502-3p-AHNAK, and hsa-miR-3059-5p-STC2) were identified. Key abnormally methylated immune-related DEGs may be associated with the immune mechanism of PE, given their correlation with related signaling pathways and immune cell infiltration.

Abstract in English:

Pulmonary fibrosis is a chronic, progressive, fatal lung disease characterized by abnormal lung tissue repair and intense collagen accumulation in the lungs. Despite intensive efforts, no specific treatment has been found. The aim of this study was to investigate the effects of a high-fructose diet on lung tissue, whether the use of metformin corrects the damage caused by high fructose, and the possible relationship with transient receptor potential (TRP) channels. Lung damage was induced by adding 200 g/L fructose to the drinking water of Sprague-Dawley rats (n=32) for 10 weeks. In the groups in which the effect of metformin was examined, metformin (dissolved in saline) was administered intraperitoneally at a dose of 100 mg/kg in the last two weeks of the study. Inflammation and TRP channel levels were measured by ELISA. Histopathological evaluation was also assessed by Masson's Trichrome staining. A high-fructose diet caused collagen deposition, inflammation, and intra-alveolar hemorrhage in lung tissue. Interleukin-6 and TRPC6 channel protein levels in lung tissue were higher in the high-fructose group than in the control group. These effects were prevented by metformin treatment. Metformin administration and manipulation of TRPC6 channels may be a therapeutic target for the treatment of pulmonary fibrosis.

Abstract in English:

The creation of bone lesions using a well-established surgical technique is essential for obtaining histological images in experimental models that aim to study the pathophysiology of bone repair. In this study, we report the steps of a surgical method to induce bone defects in Wistar rats, providing a basis for experimental studies requiring precision in these lesions, especially for future experimental tests and subsequent histological analysis. The animal model remains an important alternative for investigating the inflammatory process and bone regeneration. The model consists of creating experimental, non-critical surgical bone defects in the femurs of Wistar rats (Rattus norvegicus, 90 days old, weighing between 250-300 g) using a 2-mm spherical drill and a low-speed motor. The present report includes reproducible information on the selection of the animals and the materials needed to perform anesthesia and surgery to induce bone defects. It also provides details on post-surgical care, sample collection, and preparation of samples for histological processing. The steps presented here can significantly increase the accuracy of lesion creation and allow for more precise results in the analysis of bone architecture and repair.

Abstract in English:

Thrombotic occlusion of the radial artery is the most frequent complication of transradial angiography. This study sought to investigate biomarker-based predictors of radial artery occlusion (RAO) after coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). Consecutive patients who underwent cardiac catheterization through radial artery route for diagnostic or therapeutic purposes were included in the study retrospectively. The clinical, laboratory, and angiographic data were obtained from hospital records. All patients were invited for a follow-up visit one week after discharge and radial artery pulse examination was performed. The patients with reduced or absent radial artery pulse or complaints related with the radial artery intervention site at follow-up visit were examined by a radiologist with superficial Doppler ultrasonography. The patients were categorized according to the patency of the radial artery and there were 46 patients with an occluded radial artery and 204 patients with a patent radial artery after CAG and/or PCI. Platelet count was higher in the occluded artery group than in the patent radial artery group. Creatinine level was lower and estimated glomerular filtration rate (e-GFR) was higher in the occluded radial artery group compared to the patent radial artery group. Multivariate logistic regression analysis showed that platelet count (OR: 1.010, 95%CI: 1.001-1.018, P=0.031) and creatinine (OR:0.030, 95%CI: 0.001-0.821, P=0.038), but not e-GFR (OR: 1.031, 95%CI: 0.991-1.073, P=0.128) were independently associated with RAO. Platelet count and creatinine were found to be independent predictors of RAO after transradial cardiac catheterization.

Abstract in English:

Sleep deprivation induces profound metabolic disturbances in the brain, while regular physical exercise is recognized for promoting neuroprotection and energy balance. This study investigated the effects of chronic treadmill exercise on the cortical and hippocampal metabolic profiles of sleep-deprived Swiss mice using the entire 1H-NMR spectrum. Male mice (n=48) were assigned to four groups: Control, Exercise (EX), Sleep Deprivation (SD), and Exercise before Sleep Deprivation (EX+SD). The EX group underwent 8 weeks of aerobic training, and SD was induced by 72-h total sleep deprivation. Brain metabolomic analysis revealed that the cortex and hippocampus shared a qualitatively similar metabolic composition, with taurine, creatine, and lactic acid as the most abundant metabolites. Exercise increased cortical levels of lactic acid, creatine, taurine, and other metabolites involved in glycolysis, the TCA cycle, and osmoregulation, while SD disrupted energy-related metabolites and increased glial markers such as myo-inositol. The EX+SD group exhibited a cortical metabolic profile similar to controls, indicating that prior exercise preserved neuroenergetic balance in this region. In contrast, hippocampal metabolism remained partially affected by SD, despite exercise preconditioning. These findings suggest that exercise confers region-specific metabolic resilience, especially in the cortex, by modulating pathways related to pyruvate metabolism, glutamate turnover, and astrocytic-neuronal coupling. Regular physical activity may thus act as a non-pharmacological strategy to mitigate SD-induced neurochemical imbalances.

Abstract in English:

Matrix metalloproteinases (MMP) act as effectors and regulators in normal growth and development as well as in pathological processes. The gelatinases MMP2 and MMP9 exhibit similar structures and biological reactions. The purpose of this study was to clarify the relationship between MMP9 and MMP2 in lipopolysaccharide (LPS)-induced osteoblasts. MC3T3-E1 cells were pretreated with or without TGF-β1 inhibitor (20 nM) and SMAD2/3 inhibitor (20 nM) for 1 h, and then with pcDNA3.1-mMMP9 (0.8 μg/mL) for 48 h. Quantitative real-time PCR, western blot, and immunocytochemistry were performed to detect MMP2, TGF-β1, and/or SMAD2/3 expression. Luciferase reporter assay and electrophoretic mobility shift assay (EMSA) were performed to examine the regulatory effect of SMAD2/3 on MMP2 gene transcription. RUNX2, OSX, ALP, type I collagen, and OCN expression was detected in LPS (20 μg/mL)-stimulated MC3T3-E1 cells after MMP9 treatment. MMP9 activated the expression of TGF-β1 and phosphorylation of SMAD2/3. Phosphorylated SMAD2/3 translocalized into nuclei to bind to SMAD-binding elements in the promoter of the MMP2 gene, inhibiting MMP2 gene transcription. Additionally, MMP9 increased RUNX2, OSX, ALP, COL I, and OCN expression in LPS-induced MC3T3 cells. MMP9 may regulate osteogenesis through TGF-β1-SMAD2/3/-MMP2 signaling during the inflammation process.

Abstract in English:

Th17 cytokines play a central role in the pathophysiology of chronic allergic pulmonary inflammation, influencing multiple signaling pathways that promote inflammation, oxidative stress, and airway remodeling. We evaluated the modulation of the NF-κB, VAChT, and Rho-kinase signaling pathways, and the effects of anti-interleukin (IL)-17 treatment on airway alterations in a murine model of chronic allergic inflammation were exacerbated by lipopolysaccharide (LPS). We studied airway hyperresponsiveness, inflammation, oxidative stress pathways, tissue remodeling, and the expression of various markers in male BALB/c mice with ovalbumin (OVA)-induced chronic allergic inflammation, with or without anti-IL-17 treatment. Twenty-four hours before the end of the experiment, the OVA-sensitized animals were treated with LPS (OVA-LPS-anti-IL-17). Mice treated with OVA-LPS-anti-IL-17 exhibited decreased elastance of the respiratory system after methacholine challenge, along with reduced infiltration of eosinophils, neutrophils, lymphocytes, and macrophages. Anti-IL-17 treatment also reduced the expression of TNF-α, TARC/eotaxin, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, MMP-9, MMP-12, TIMP-1, TGF-β, iNOS, NF-κB, ROCK1, ROCK2, types I and III collagen, decorin, lumican, biglycan, fibronectin, and 8-iso-PGF2α in airway cells, as well as the mRNA expression of IL-17, VAChT, and arginase 1 in lung tissue, compared to the OVA and OVA-LPS groups (P<0.05), except for TNF-α and actin, which were not reduced compared to the OVA group, and Rrs, actin, and VAChT, which were not reduced compared to the OVA-LPS group. Thus, IL-17 blockade helped control bronchial hyperresponsiveness, modulate the IL-17/NF-κB/VAChT/Rho-kinase pathway, suppress chemokine expression, mitigate airway remodeling, and reduce NO-arginase expression in this asthma mouse model with LPS-induced exacerbation.

Abstract in English:

The introduction of combination antiretroviral therapy (cART) has significantly reduced AIDS-related morbidity and mortality. However, the prevalence of age-associated comorbidities, particularly cardiovascular diseases (CVD), has increased, becoming a leading cause of mortality in people living with HIV. This study investigated the interaction between cART regimens and dietary composition on electrocardiographic (ECG) parameters and myocardial histopathology. A total of 120 weanling Sprague Dawley rats were allocated to one of three diets for 15 weeks: normal chow, a calorie-dense low protein (CDLP) diet, or a calorie-dense normal protein (CDNP) diet. Each dietary group was then subdivided into four treatment groups for a further 9 weeks: a standard group (normal saline), Test group 1 (dolutegravir (DTG) plus tesamorelin), Test group 2 (DTG only), and a positive control (classical cART regimen). ECG recordings and histological assessments were performed at week 24. Significant intergroup variations in ECG indices were observed, including Q, R, S, and T wave amplitudes, PR interval, QRS duration, ST height, and QTc (all P<0.0001). Myocardial fibrosis (P<0.0001) was evident in animals from the TG2 (DTG only) and PC (classical regimen) groups maintained on CDLP and CDNP diets. These findings demonstrated that CDLP and CDNP diets, combined with DTG-based or classical cART regimens, exerted deleterious cardiac effects, promoting myocardial fibrosis that disrupts normal electrical conduction and may predispose to arrhythmogenesis. Tesamorelin prevented these effects, implicating growth hormone pathway dysfunction in the underlying pathology.

Abstract in English:

Cytomegalovirus (CMV) infection increases morbidity in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Despite advancements in prevention and treatment, CMV reactivation remains a considerable concern following allo-HSCT. In this study, we aimed to evaluate the impact of CMV reactivation in allo-HSCT recipients on clinical outcomes and patient survival, as well as to identify the risk factors associated with CMV reactivation. This retrospective observational cohort study included data from 67 transplantations performed between 2019 and 2022 at a private hospital in Belo Horizonte, Brazil. Clinical, laboratory, and procedural data were collected. The median age of the patients was 47.0 years, and 52.2% of them were women. The most frequent indication for allo-HSCT was acute myeloid leukemia (28.4%), followed by myelodysplastic syndrome (16.4%). CMV reactivation occurred in 62.7% of the recipients, and the median time to CMV reactivation was 32.5 days. Six patients (9.0%) presented with CMV end-organ disease (83.3% were free of systemic disease); however, when present, gastrointestinal involvement was the most common disease (4.5%). In the multivariate analysis, the risk factors for CMV reactivation included acute lymphoblastic leukemia (P=0.006), mismatched human leukocyte antigen (HLA)-unrelated donors (P=0.002), and graft-versus-host disease (P=0.024). One-year overall survival was 57.7%. However, CMV reactivation was not significantly associated with mortality after controlling for confounding factors. CMV reactivation remains a common complication following allo-HSCT, with leukemia type, donor type, and graft-versus-host disease affecting the risk of disease recurrence. No direct correlation was observed between CMV recurrence and increased mortality or patient survival.

Abstract in English:

Despite the clinical importance of combining acetaminophen and opioids in multimodal analgesia, their compatibility has not been determined. This study aimed to investigate the stability and feasibility of mixing acetaminophen injection with six commonly used opioid drugs. Acetaminophen injection was mixed with each of the six opioid drugs at room temperature (25°C). Changes in appearance, pH, and acetaminophen concentrations were monitored at different time intervals to evaluate compatibility. Compatibility was defined as no visible changes, pH variation <1.0, and acetaminophen concentration ≥90% of baseline. The results indicated that acetaminophen injection, when mixed with six commonly used opioid drugs, remained stable for up to 48 h at room temperature. No significant changes were observed in the appearance of the mixtures, which remained clear and free of precipitation. The pH of the mixtures fluctuated by less than 1.0 unit, and the acetaminophen concentration remained above 90% of the baseline value, with a variation of less than 10%. Acetaminophen injection was compatible with morphine, sufentanil, hydromorphone, pentazocine, butorphanol, and nalbuphine for at least 48 h at 25°C, supporting their co-use in patient-controlled intravenous analgesia. Further studies should define pharmacokinetics and adverse effects of these combinations.

Abstract in English:

We aimed to analyze the effect of mind map-guided nursing on pain control after transurethral resection of the prostate (TURP). Eighty patients with benign prostatic hyperplasia undergoing TURP were randomly separated into either a control group (routine perioperative nursing) or an intervention group (mind map-guided nursing). Visual Analog Scale (VAS) scores were employed to compare pain levels at 24 and 48 h postoperatively. Additional outcomes included the number of patient-controlled analgesia activations, time to first flatus, and length of hospital stay. Quality of life (Short Form-36 (SF-36)), sleep quality (Pittsburgh Sleep Quality Index (PSQI)), anxiety and depression (Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS)), and prostate function (International Prostate Symptom Score (IPSS)) were evaluated before and after nursing interventions. Patient satisfaction with nursing care was also compared. After nursing interventions, the intervention group exhibited lower VAS scores at 24 and 48 h postoperatively, fewer analgesia pump activations, shorter time to first flatus, and reduced length of hospital stay, higher SF-36 scores across all dimensions, lower PSQI, SAS, SDS, and IPSS scores, as well as higher nursing satisfaction versus the control group (all P<0.05). Mind map-guided nursing alleviated postoperative pain following TURP, enhanced quality of life, sleep quality, and mental state, promoted prostate function recovery, and enhanced patient satisfaction with nursing.

Abstract in English:

Citation analysis has emerged as a key area in scientometrics. However, the global movement toward open science, alongside the pervasive “publish or perish” culture, underscores the need to reevaluate the paradigm of citations as a measure of impact and quality. Brazil, a top 15 producer of scientific articles, has established the Lattes Platform, a comprehensive resource data on virtually active researchers in the country. Herein, the Brazilian scientific landscape was analyzed by integrating a widely used global ranking based on large-scale citation metrics with individual-level data from the Lattes Platform. The analysis assessed the impact, distribution, and disparities of Brazilian science across disciplines, geographic regions, and institutional affiliations from 2019-2023. Results showed that Brazilian researchers account for approximately 0.43% of the world's most cited scientists, a significant underrepresentation relative to Brazil's population share and scientific potential. Most highly cited scientists are concentrated in three states within the Southeast region, reflecting longstanding economic and infrastructural advantages. The majority of top Brazilian scientists work in Life Sciences, with particular representation in the subfields Zoology, Tropical Medicine, and Mycology & Parasitology. While Brazil's scientific output compares favorably with other South American and African countries, it remains behind nations with higher gross domestic products per capita and Human Development Index. Nonetheless, 73% of the most cited researchers receive national Research Productivity Grants, indicating a positive correlation between citation and qualified scientific excellence. These findings offer a deeper understanding of Brazilian scientific production from a citation perspective and advocate for strategic policy shifts.

Abstract in English:

Women with ovarian cancer may be at increased risk of severe COVID-19 outcomes. This study aimed to compare mortality and clinical outcomes between women with severe COVID-19, with and without a history of ovarian cancer. We conducted a matched case-control study using national surveillance data. Cases included women with severe COVID-19 and a history of ovarian cancer; controls were women with severe COVID-19 without such history. Matching was done at a 1:4 ratio using age, comorbidities, vaccination status, diagnosis date, and region. The primary outcome was COVID-19-related mortality. A total of 474 ovarian cancer cases and 1,896 controls were included. Mortality was significantly higher in women with ovarian cancer (54.9 vs 32.7%, P<0.001). Multivariate analysis showed that ovarian cancer increased the risk of death (OR: 2.76, 95%CI: 2.22-3.43). Age also influenced mortality: OR 2.57 (95%CI: 2.11-3.13) for women aged 65-84, and OR 3.86 (95%CI: 2.52-5.97) for those 85 and older. Vaccination provided protection: complete vaccination (OR: 0.67, 95%CI: 0.51-0.88) and complete vaccination plus booster (OR: 0.35, 95%CI: 0.27-0.47). Women with ovarian cancer had a significantly higher risk of death from severe COVID-19. Vaccination, particularly with a booster, was associated with 65% reduced mortality.

Abstract in English:

To investigate the effects of Mucin 1 (MUC1) in human triple-negative breast cancer MDA-MB-231cells, the MDA-MB-231 cell line with MUC1 knockout (231-MUC1-KO) was constructed by CRISPR/Cas9 gene editing. Cell proliferation was evaluated using EDU and colony formation assays, and cell migration and invasion were detected by transwell assay. Autophagy flow was assessed by western blot and Ad-mCherry-GFP-LC3B dual-fluorescence system and validated by lysosome inhibitor barfimycin A1 and autophagy inducer rapamycin. Key proteins of autophagosomes and lysosomal fusion (STXl7, SNAP29) and lysosomal tagged protein (LAMP1) were detected by western blot, and lysosomal pH was evaluated by Lysotracker Red fluorescence. MUC1 expression was low in human normal breast epithelial cells MCF-10A, but was highly expressed in human MDA-MB-231 cells and tissues. Successful MUC1 knockout was confirmed by gene sequencing, RT-qPCR, and western blot. Loss of MUC1 gene expression in 231-MUC1-KO significantly reduced proliferation, migration, and invasion. Compared with the control group, MUC1 knockout led to a significant increase of autophagy-related proteins LC3-II and p62, which is consistent with the effect of lysosome inhibitor bleomycin A1. After adding the autophagy inducer rapamycin, compared with the control group, the accumulation of LC3-II and p62 proteins also further increased. The expression level of LAMP1 was downregulated and the lysosome pH increased, but the expression levels of STXl7 and SNAP29 were not affected. These findings suggest that MUC1 promotes malignant behaviors in MDA-MB-231 cells by regulating autophagic flow, likely through lysosomal dysfunction-mediated autophagy blockade.

Abstract in English:

Traumatic brain injury (TBI) is a major global health concern. The lateral fluid percussion injury (LFPI) model, widely used in rodents to simulate nonpenetrating TBI, has limited translational applicability due to anatomical differences between rodent and human brains. The common marmoset (Callithrix jacchus), a New World primate with a quasi-gyrencephalic brain, offers a promising alternative. This study aimed to standardize the LFPI model in marmosets by comparing trauma responses across parietal and temporal lobes. Ten adult marmosets underwent LFPI in these regions. Lesion volume was measured using Nissl staining; astrocytic and microglial responses were assessed via GFAP and Iba-1 immunofluorescence, and degenerating neurons were identified with Fluoro-Jade B. Righting reflex time and hemorrhage presence were evaluated as injury markers. Percussion aiming at the temporal lobe injury resulted in the most prominent lesions, epidural and subdural hematomas, and significant neuronal degeneration. Astrocytes showed longer processes after temporal trauma in the cortex and fewer branches in the hippocampal region CA1 than in the naive group. In contrast, hippocampal microglia showed fewer elongated branches in CA1 and dentate gyrus (DG), indicative of a reactive phenotype. Our results highlighted region-specific vulnerability, with temporal injury triggering the most pronounced inflammatory and degenerative responses. The marmoset LFPI model effectively mirrored key aspects of human TBI, supporting its translational relevance.

Abstract in English:

Endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of diabetic nephropathy. In this study, we aimed to investigate the protective effects of zingerone on the kidney and elucidate the underlying mechanisms in streptozotocin (STZ)-induced diabetic mice. Diabetic mice were randomly assigned to three groups: untreated control, diabetic control, and STZ+zingerone-treated group. Over a 3-month period, we monitored body weight, blood glucose (BG), blood urea nitrogen (BUN), serum creatinine (SCR), 24-h urinary protein (UP) excretion levels, and 24-h urinary volume (UV). Renal injury, apoptosis, inflammation, and ER stress were evaluated using histopathology, TUNEL staining, reverse transcription polymerase chain reaction (RT-PCR), western blotting, and immunofluorescence. In vitro, mouse glomerular mesangial cells were exposed to high glucose, with or without zingerone or the ER stress inhibitor phenylbutyric acid (PBA). Thereafter, the expression levels of ER stress markers (CHOP and GRP78), inflammatory factors (NF-κB and TGF-β1), and apoptotic indices were assessed. Diabetic mice exhibited significantly elevated BG, BUN, SCR, 24-h UP, and ER stress marker levels, along with increased 24-h UV, renal apoptosis, and inflammation. Zingerone treatment significantly mitigated these parameters and improved renal pathological manifestations. In vitro, both zingerone and PBA effectively suppressed high glucose-induced ER stress, inflammation, and apoptosis in mesangial cells. These findings demonstrated that zingerone attenuated diabetic renal injury through inhibition of ER stress-related pathways and downstream inflammation, thereby underscoring its potential as a therapeutic candidate for diabetic nephropathy.

Abstract in English:

Helicobacter pylori (H. pylori) is a major gastric cancer pathogen. Recent studies have linked H. pylori infection to microRNA (miRNA) dysregulation. H. pylori outer membrane vesicles (OMVs) support bacterial survival and pathogenesis, but the OMV-miRNA interactions remain unclear. To address this lack of understanding, we co-cultured the H. pylori strain NCTC11637 and its OMVs with the gastric epithelial cell line GES-1 and gastric cancer cell lines SGC-7901 and HGC-27. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) showed hsa-miR-302a-3p upregulation in the GES-1 line and hsa-miR-184 upregulation in the SGC-7901 and HGC-27 lines. To explore the OMV-miRNA mechanisms, we built transfected models: GES-1 with hsa-miR-302a-3p overexpression and SGC-7901 and HGC-27 with hsa-miR-184 overexpression or inhibition. The experimental study on the malignant behavior of tumors (i.e., proliferation, migration, invasion, and clonogenic assay) showed enhanced malignant phenotypes in the overexpressed cells. Hsa-miR-184 inhibition reversed these effects in the cancer cells. Intriguingly, hsa-miR-302a-3p overexpression in the GES-1 cells enhanced tumorigenesis via anchorage-independent growth, which is a key carcinogenic trait. Next, we identified differential proteins in the overexpressed cells via proteomic mass spectrometry. Finally, we validated the target proteins and analyzed the signaling pathways to elucidate the mechanisms. We found that H. pylori OMV-induced hsa-miR-302a-3p upregulation may promote gastric cancer initiation, while hsa-miR-184 overexpression may drive progression. This study provides a basis for the diagnosis and treatment of gastric cancer.

Abstract in English:

Respecting the patient's preferred place of death is a key indicator of the quality of palliative care. However, clinical factors may influence this outcome. This study aimed to compare the clinical profiles, symptom burden, and medical interventions of patients who died at home versus those who died in an inpatient setting (hospital) within the context of a Brazilian public healthcare institution. A retrospective study was conducted involving 227 patients who were followed by the Palliative Care Team at the Instituto de Assistência Médica ao Servidor Público Estadual (IAMSPE). Sociodemographic and clinical variables, symptom control, and pharmacological interventions were analyzed using generalized linear mixed models (GLMMs). Of these patients, 59.47% (n=135) died in the hospital ward and 40.53% (n=92) died at home. No statistically significant differences were observed between age or sex and place of death. Hospitalized patients presented with a greater number of symptoms, although no significant differences were found for pain and dyspnea. Most of the patients also had multiple metastases. The use of oxygen was significantly higher in the inpatient setting, while oral and enteral feeding was more feasible at home. Although the total number of medications administered was higher in the hospital, there were no significant differences in the use of morphine and midazolam between the groups. In conclusion, clinical severity was a key factor influencing hospitalization until death. Despite equivalent symptom control between settings, expanding access to structured home-based palliative care could enable patients to experience end-of-life care aligned with their preferences.

Abstract in English:

A wide range of non-tuberculous mycobacteria (NTM) species have been identified worldwide, with increasing recognition of their clinical importance in pulmonary disease. To evaluate the diversity, frequency, antimicrobial resistance profile, and clinical characteristics of pulmonary NTM cases in Pernambuco, Brazil, we conducted a descriptive clinical-epidemiological and comparative cross-sectional study of pulmonary NTM (PNTM) along with pulmonary tuberculosis (PTB). Pulmonary biological samples were obtained and analyzed by bacilloscopy, culture, and biochemical tests for PNTM and PTB diagnosis. Molecular analysis for hsp65 and rpoB genes was also performed to confirm NTM species and classified as slowly growing mycobacteria (SGM) or rapidly growing mycobacteria (RGM). Antimicrobial susceptibility tests were also performed with 13 different drugs. Twenty-one PNTM cases were identified. They were significantly associated with a previous history of TB (66.7%) and occurred more frequently in males (67.7%). The age of the PNTM group (52.0±14.7 years) was significantly higher than PTB group (44.0±14.8 years; P=0.006). Six different NTM species were detected (three SGM and three RGM): M. kansasii (57.1%), M. intracellulare (9.5%), M. abscessus subsp. abscessus (9.5%), M. abscessus subsp. bolletii (9.5%), M. fortuitum (9.5%), and M. asiaticum (4.8%). Among the cases, 15 specimens demonstrated antimicrobial resistance to at least one drug. This is the first study to describe the frequency, diversity, and antimicrobial resistance of NTM species associated with pulmonary disease in Pernambuco, providing relevant epidemiological data to support diagnosis and management in this endemic region for tuberculosis.

Abstract in English:

Syphilis in pregnant women remains an important public health problem in Brazil, especially in urban contexts marked by social inequalities and weaknesses in the organization of health services. In the Amazon region, territorial, socioeconomic, and healthcare-related characteristics influence access to prenatal care, timely diagnosis, and the control of vertical transmission. Thus, this study aimed to analyze the spatiotemporal patterns of syphilis among pregnant women in a health region of the Brazilian Amazon. This is an ecological, descriptive, and quantitative study that evaluated 5,607 positive cases of syphilis in pregnant women residing in the 1st Health Region (Metropolitan I) of Pará, composed of Belém, Ananindeua, Marituba, Benevides, and Santa Bárbara, reported between 2019 and 2024. Data were obtained from the Pará State Health Department, and the “geocodebr” package from the National Institute for Space Research and the R software were used for georeferencing the geographic coordinates of each case. Kernel Density Estimation analysis identified the presence of high-density clusters in the 2019-2020 and 2023-2024 biennia. Spatial scan analysis identified Marituba as a significant cluster, indicating higher risk and a constant concentration of cases throughout the analyzed period. Syphilis in pregnant women presents a heterogeneous and persistent spatiotemporal pattern in the region, requiring integrated, territorialized, and intersectoral strategies.

Abstract in English:

Pancreatic adenocarcinoma (PAAD) is a highly aggressive and lethal malignancy originating from the epithelial cells lining the pancreatic ducts. To date, no robust biomarkers have been established to reliably predict PAAD prognosis. To identify potential transcriptional biomarkers, we analyzed transcription factor expression in PAAD patients from The Cancer Genome Atlas (TCGA) and identified ZNF821 as a novel prognostic marker. Higher ZNF821 expression was significantly associated with improved patient survival and was positively correlated with increased immune infiltration and cytotoxic activity within the tumor microenvironment. Additionally, elevated ZNF821 levels predicted a favorable response to immunotherapy. We further discovered that tumors downregulate ZNF821 through DNA methylation, facilitating immune evasion during tumor progression. To investigate its functional mechanisms, we analyzed proteins regulated by or interacting with ZNF821. Moreover, we identified existing drugs that may target ZNF821, suggesting potential therapeutic applications for PAAD. Experimental validation using RT-PCR confirmed ZNF821 downregulation in pancreatic cancer cell lines. Furthermore, tumor growth comparisons between ZNF821-overexpressing and ZNF821-null models demonstrated that ZNF821 enhances anti-tumor immunity, contributing to tumor suppression. In summary, our study identified ZNF821 as a novel prognostic biomarker in PAAD, offering new insights into tumor immune evasion and potential therapeutic strategies.

Abstract in English:

Among the morbidities triggered by obesity, metabolic dysfunction-associated steatotic liver disease (MASLD) stands out, with its progression resulting from the deposition of lipid molecules in the liver. There is a growing interest in natural/functional foods as an alternative for improving health, as well as for the treatment and prevention of diseases. Capsinoids (Cap) - bioactive compounds present in peppers of the genus Capsicum annuum - have been studied for promoting loss of adiposity and increased caloric expenditure. Therefore, this study aimed to investigate the effects of Cap on liver parameters in obese (Ob) rats induced by a high-fat diet (HFD). Male Wistar rats were initially randomized into two groups: standard diet (SD) and HFD. The protocol lasted 27 weeks, including 19 weeks of induction and maintenance of obesity and 8 weeks of Cap treatment. At week 19, the HFD rats were redistributed into the Obese (Ob) and Obese capsinoids (ObCap) groups, and the ObCap group was supplemented daily with chronic Cap treatment by orogastric gavage (10 mg Cap/kg daily). Cap treatment was not effective in improving adiposity and inflammatory parameters of obesity, although it reduced ghrelin, cholesterol, and hepatic fat accumulation, and attenuated MASLD progression, which may be promising for combating chronic diseases related to lipid metabolism.

Abstract in English:

This study aimed to investigate the role of microglia and NOD-like receptor protein 3 (NLRP3) inflammasome-mediated neuroimmune pathways in the analgesic effects of electroacupuncture (EA) in a mouse model of Parkinson's disease (PD). Male C57BL/6 mice (8 weeks old) were randomly assigned to the control, PD model, and PD + EA groups. PD was induced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), while control mice received saline. EA was administered to the motor cortex once daily for five consecutive days in the PD + EA group, whereas PD model mice were restrained without receiving EA stimulation. Behavioral assessments were performed to evaluate motor function and nociceptive sensitivity. Immunohistochemistry, immunofluorescence, and western blot analyses were used to quantify tyrosine hydroxylase (TH), ionized calcium-binding adapter molecule 1 (Iba-1), NLRP3 inflammasome components, and inflammatory cytokines in key brain regions. Compared with control mice, PD model mice showed reduced motor performance and heightened nociceptive sensitivity, accompanied by a decrease in TH-positive neurons and an increase in Iba-1-positive microglia in both the substantia nigra and amygdala. EA significantly improved motor performance and increased pain thresholds. Moreover, EA preserved TH-positive neurons, suppressed microglial activation, and downregulated the expression of NLRP3, ASC, caspase-1, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the amygdala. These findings suggest that EA alleviates PD-related pain, possibly by modulating microglial activation and NLRP3 inflammasome signaling in the amygdala, thereby reducing neuroinflammation.

Abstract in English:

The combination of drugs for malaria treatment holds promise, although the potential for drug-drug interactions remains insufficiently explored in novel therapeutic combinations. This study aims to assess these interactions using physiologically based pharmacokinetic modeling, supported by data-driven parameter optimization, as a step towards the preclinical development of a formulation containing chloroquine and colchicine. Given that both compounds share metabolic pathways involving CYP3A4 and CYP2D6, we developed individual and population models using a middle-out strategy in PK-Sim®, an open-source software, and validated these models by comparing predicted and observed pharmacokinetic parameters. Simulations evaluated competitive inhibition between the compounds. The results indicated no significant changes in systemic exposure, with the area under the curve and maximum concentration values remaining consistent between single and combined administration. Our findings suggest that the proposed modeling is a powerful tool for predicting pharmacokinetic interactions during the preformulation stage, offering mechanistic insight and supporting rational decision-making prior to in vivo studies. The absence of significant drug-drug interactions between chloroquine and colchicine reinforces the feasibility of advancing this combination in future therapeutic development.

Abstract in English:

Curcumin inhibits osteoclastogenesis and mitigates osteoporosis. Our data demonstrated that curcumin decreases membrane-bound RANKL (mRANKL) levels on osteoblasts. Notably, mRANKL exerts a more prominent role in osteoclastogenesis than its soluble counterpart (sRANKL). This study aimed to explore the role of RANKL membrane localization in curcumin-regulated osteoclastogenesis. We primarily investigated the effect of curcumin on mRANKL expression in osteoblasts in vitro and in vivo. Using fluorescence-activated cell sorting (FACS) for RANKL and co-culture experiments of osteoclast precursors (OCPs) with osteoblasts, we further analyzed the association between curcumin's indirect inhibition of osteoclast differentiation and mRANKL production. Finally, we explored the involvement of matrix metalloproteinase 14 (MMP14) in curcumin-mediated regulation of mRANKL levels. The results showed that curcumin significantly reduced mRANKL expression in osteoblasts. Curcumin also abrogated the upregulated RANKL levels in osteoblasts of Tg-hRANKL transgenic mice. Co-culture assays revealed that curcumin exerted the weakest inhibitory effect on osteoclast differentiation when OCPs were co-cultured with mRANKL-negative osteoblasts. Additionally, curcumin increased MMP14 expression in osteoblasts and enhanced the MMP14-RANKL interaction. Importantly, silencing MMP14 in osteoblasts reversed curcumin-inhibited mRANKL levels and osteoclast differentiation. Collectively, our findings indicated that curcumin inhibited mRANKL production in osteoblasts, which contributes to its therapeutic effect on osteoclastic osteoporosis.