Abstract in English:The high burden of kidney disease, global disparities in kidney care, and the poor outcomes of kidney failure place a growing burden on affected individuals and their families, caregivers, and the community at large. Health literacy is the degree to which individuals and organizations have, or equitably enable individuals to have, the ability to find, understand, and use information and services to make informed health-related decisions and actions for themselves and others. Rather than viewing health literacy as a patient deficit, improving health literacy lies primarily with health care providers communicating and educating effectively in codesigned partnership with those with kidney disease. For kidney policy makers, health literacy is a prerequisite for organizations to transition to a culture that places the person at the center of health care. The growing capability of and access to technology provides new opportunities to enhance education and awareness of kidney disease for all stakeholders. Advances in telecommunication, including social media platforms, can be leveraged to enhance persons’ and providers’ education. The World Kidney Day declares 2022 as the year of “Kidney Health for All” to promote global teamwork in advancing strategies in bridging the gap in kidney health education and literacy. Kidney organizations should work toward shifting the patient-deficit health literacy narrative to that of being the responsibility of health care providers and health policy makers. By engaging in and supporting kidney health-centered policy making, community health planning, and health literacy approaches for all, the kidney communities strive to prevent kidney diseases and enable living well with kidney disease.
Abstract in English:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused several problems in healthcare systems around the world, as to date, there is no effective and specific treatment against all forms of COVID-19. Currently, drugs with therapeutic potential are being tested, including antiviral, anti-inflammatory, anti-malarial, immunotherapy, and antibiotics. Although antibiotics have no direct effect on viral infections, they are often used against secondary bacterial infections, or even as empiric treatment to reduce viral load, infection, and replication of coronaviruses. However, there are many concerns about this therapeutic approach as it may accelerate and/or increase the long-term rates of antimicrobial resistance (AMR). We focused this overview on exploring candidate drugs for COVID-19 therapy, including antibiotics, considering the lack of specific treatment and that it is unclear whether the widespread use of antibiotics in the treatment of COVID-19 has implications for the emergence and transmission of multidrug-resistant bacteria.
Abstract in English:The use of bladder antimuscarinics is very common in the elderly. However, recent population-based studies that assessed the use of anticholinergics or bladder antimuscarinics showed an increased risk of dementia when these drugs were used for a prolonged period. Several of these population-based studies included patients who used solifenacin, which is a bladder antimuscarinic released in 2005 with the prospect of being a more selective antimuscarinic for M3 receptors (M3R), which could make it a safer drug when trying to avoid unwanted effects of older bladder antimuscarinics such as oxybutynin, especially with regard to changes in cognition. Since the various bladder antimuscarinics have distinct pharmacological characteristics, such as in the ability to penetrate the blood-brain barrier, in selectivity for muscarinic receptors, and in brain efflux mechanisms, their effects on the central nervous system (CNS) may vary. Solifenacin was the drug selected in this review, which aims to describe the results of several articles published in recent years reporting the effects of solifenacin on cognition or the risk of dementia development. Although preclinical studies show that solifenacin can also act on brain M1 receptors (M1R), short-term clinical studies have shown it to be safe for cognition. However, there are no long-term randomized studies that prove the safety of this drug for the CNS. Thus, until the safety of solifenacin has been established by long-term studies, it seems advisable to avoid prolonged use of this drug in elderly patients.
Abstract in English:Recent findings have confirmed relationships between coronavirus disease (COVID-19) and multiple organ dysfunction. The prevalence of cardiac and renal involvement in COVID-19 has been increasingly reported and is a marker of severe disease that not only directly or indirectly affects the organs, but may also exacerbate the underlying comorbid illness. In addition, patients affected by the new coronavirus present a systemic inflammatory condition that results in damage to several tissues, especially the heart, kidneys, and vessels. It is well known that the heart and kidneys are closely related, so that any change in one of the organs can lead to damage to the other, establishing the so-called cardiorenal syndrome. Herein, we explore some case reports of patients with COVID-19 who had heart and kidney abnormalities, consequently resulting in worse prognosis of the disease. These results highlight the importance of understanding the cause and effect between the cardiac and renal systems and the course of early SARS-CoV-2 infection.
Abstract in English:There is a high incidence of non-obese type 2 diabetes mellitus (non-obese-T2DM) cases, particularly in Asian countries, for which the pathogenesis remains mainly unclear. Interestingly, Goto-Kakizaki (GK) rats spontaneously develop insulin resistance (IR) and non-obese-T2DM, making them a lean diabetes model. Physical exercise is a non-pharmacological therapeutic approach to reduce adipose tissue mass, improving peripheral IR, glycemic control, and quality of life in obese animals or humans with T2DM. In this narrative review, we selected and analyzed the published literature on the effects of physical exercise on the metabolic features associated with non-obese-T2DM. Only randomized controlled trials with regular physical exercise training, freely executed physical activity, or skeletal muscle stimulation protocols in GK rats published after 2008 were included. The results indicated that exercise reduces plasma insulin levels, increases skeletal muscle glycogen content, improves exercise tolerance, protects renal and myocardial function, and enhances blood oxygen flow in GK rats.
Abstract in English:The aim of this study was to review the symptomatic manifestations of COVID-19 in children in the scientific literature. An integrative review of studies published between December 2019 and September 5, 2021, from the Medical Literature Analysis and Retrieval System Online, Web of Science, Scopus, Literatura Latino-Americana em Ciência de Saúde, and Base de Dados de Enfermagem databases, was carried out to answer the following research question: What symptomatic manifestations does COVID-19 cause in children?”. Twenty articles were included. The main symptoms described were fever, cough, diarrhea, vomiting, sore throat, dyspnea, headache, abdominal pain, malaise, and weakness or tiredness. The findings of this review can contribute to the diagnosis and clinical decision-making of the health team by providing information that facilitates the identification of COVID-19 in the target population, favoring early identification, better care, and consequently a better prognosis.
Abstract in English:Patients with mild cognitive impairment eventually progress to Alzheimer's disease (AD) causing a strong impact on public health. Rosmarinus officinalis has long been known as the herb of remembrance and can be a potential cognition enhancer for AD. The aim of this review was to summarize the qualitative and quantitative aspects of R. officinalis and its active constituents in enhancing cognition. A structured search was conducted on Google Scholar and PubMed to find relevant studies that assessed the effect of R. officinalis extract or any of its active constituents on cognitive performance in animals. The following information was extracted from each study: 1) article information; 2) characteristics of study animals; 3) type of intervention: type, dose, duration, and frequency of administration of R. officinalis; and 4) type of outcome measure. Data were analyzed using Review Manager and meta-analysis was performed by computing the standardized mean difference. Twenty-three studies were selected for qualitative analysis and fifteen for meta-analysis. From the fifteen included papers, 22 with 35 comparisons were meta-analyzed. Effect sizes for intact and cognitively impaired animals were 1.19 (0.74, 1.64) and 0.57 (0.19, 0.96), indicating a positive effect on both groups. The subgroup analyses showed substantial unexplained heterogeneity among studies. Overall, R. officinalis improved cognitive outcomes in normal and impaired animals, and results were robust across species, type of extract, treatment duration, and type of memory. However, studies had a considerable amount of heterogeneity, and subgroup analyses failed to find any heterogeneity moderator.
Abstract in English:We aimed to study the mechanism behind worse coronavirus disease-19 (COVID-19) outcomes in men and whether the differences between sexes regarding mortality as well as disease severity are influenced by sex hormones. To do so, we used age as a covariate in the meta-regression and subgroup analyses. This was a systematic search and meta-analysis of observational cohorts reporting COVID-19 outcomes. The PubMed (Medline) and Cochrane Library databases were searched. The primary outcome was COVID-19-associated mortality and the secondary outcome was COVID-19 severity. The study was registered at PROSPERO: 42020182924. For mortality, men had a relative risk of 1.36 (95%CI: 1.17 to 1.59; I2 63%, P for heterogeneity <0.01) compared to women. Age was not a significant covariate in meta-analysis heterogeneity (P=0.393) or subgroup analysis. For disease severity, being male was associated with a relative risk of 1.29 (95%CI: 1.19 to 1.40; I2 48%, P for heterogeneity <0.01) compared to the relative risk of women. Again, age did not influence the outcomes of the meta-regression (P=0.914) or subgroup analysis. Men had a higher risk of COVID-19 mortality and severity regardless of age, decreasing the odds of hormonal influences in the described outcomes.
Abstract in English:Vocal fold leukoplakia (VFL) has a risk of malignant transformation. Therefore, patients can have symptoms such as dysphonia, vocal strain, difficulty breathing, and dysphagia. Additionally, there is a genetic predisposition that can be associated with genetic polymorphisms. We aimed to evaluate the influence of genetic polymorphisms and protein levels in the etiology of VFL. Our study followed the PRISMA checklist and was registered on PROSPERO database. The questions were: “Are genetic polymorphisms involved in the etiology of VFL? Are protein levels altered in patients with VFL?”. Eligibility criteria were case control studies that compared the presence of polymorphisms or/and protein levels of subjects diagnosed with VFL and healthy controls. Of the 905 articles retrieved, five articles with a total of 1038 participants were included in this study. The C allele of the single nucleotide polymorphisms (SNP)-819 T/C IL-10, A allele of the SNP -592 A/C IL-10, CT genotype of the SNP rs11886868 C/T BCL11A, GG genotype of the SNP rs4671393 A/G BCL11A, LL genotype, and L allele of (GT)n repeat polymorphisms of the HO-1 were risk factors for VFL development. Nevertheless, there was a lack of association between VFL and the -1082 A/G IL-10, rs14024 CK-1, and -309 T/G Mdm2 SNPs. The concentrations of the MDM2, BCL11A, and HO-1 proteins were modified, while IL-10 levels were normally expressed in these subjects. In conclusion, most markers evaluated in this review could be potential indicators to develop effective therapies, avoiding a malignant transformation of the lesion.
Abstract in English:Hypovolemia induced by hemorrhage is a common clinical complication, which stimulates vasopressin (AVP) secretion by the neurohypophysis in order to retain body water and maintain blood pressure. To evaluate the role of brain L-glutamate and angiotensin II on AVP secretion induced by hypovolemia we induced hemorrhage (∼25% of blood volume) after intracerebroventricular (icv) administration of AP5, NBQX, or losartan, which are NMDA, AMPA, and AT1 receptor antagonists, respectively. Hemorrhage significantly increased plasma AVP levels in all groups. The icv injection of AP5 did not change AVP secretion in response to hemorrhage. Conversely, icv administration of both NBQX and losartan significantly decreased plasma AVP levels after hemorrhage. Therefore, the blockade of AMPA and AT1 receptors impaired AVP secretion in response to hemorrhage, suggesting that L-glutamate and angiotensin II acted in these receptors to increase AVP secretion in response to hemorrhage-induced hypovolemia.
Abstract in English:Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases in the elderly. The aim of this study was to explore the effects of AD on cardiac function and autonomic nervous function, and the feasibility of electrocardiogram (ECG) in monitoring the development of AD. APP/PS1 double transgenic mice were used in the Morris water maze (MWM) experiment to evaluate the changes of cognitive ability of AD mice, then the non-invasive ECG acquisition system was used and the changes of ECG intervals and heart rate variability (HRV) were analyzed. AD mice already had cognitive dysfunction at the age of 5 months, reaching the level of mild dementia, and the degree of dementia increased with the course of disease. There were no significant changes in ECG intervals in the AD group at each month. The mean square of successive RR interval differences, percentage of intervals >6 ms different from preceding interval, and normalized high frequency power component in the AD group were decreased and low-to-high frequency power ratio and normalized low frequency power component were increased. Combined with the results of the MWM, it was shown that the regulation mechanism of sympathetic and parasympathetic nerves in mice was already imbalanced in early stage AD, which was manifested as the increase of excessive activity of sympathetic nerves and the inhibition of parasympathetic activities. Therefore, ECG-based analysis of HRV may become a means of daily monitoring of AD and provide an auxiliary basis for clinical diagnosis.
Abstract in English:The effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation associated with exercise training at different intensities and frequencies on skeletal muscle regeneration of muscle-injured rats was investigated. Male Wistar rats were divided into sedentary and trained groups. The sedentary groups were subdivided into non-injured (SED-Ct), non-injured supplemented with HMB (SED-Ct-HMB), injured (SED), and injured with HMB (SED-HMB), and the trained groups were injured, supplemented with HMB, and then divided into training three times a week without load (HT3) or with load (HT3L) and training five times a week without load (HT5) and with load (HT5L). The rats received a daily dose of HMB associated with 60 min of swimming with or without 5% body mass load for 14 days. On the 15th day, cryoinjury was performed in the right tibialis anterior muscle (TA), and 48 h later, supplementation and training continued for 15 days. After the last session, the TA was dissected and a cross-sectional area (CSA) of muscle fibers was used to determine the percentage of CSA fibers and connective tissue (%CT), as well as the total and phosphorylated protein contents. SED-HMB showed increased CSA and decreased %CT and TGF-β when compared to SED. HT3 showed increased CSA and reduced %CT accompanied by increased IGF-1/Akt, myogenin, and MuRF1, and decreased TGF-β. The CSA of HT5L also increased, but at the cost of a higher %CT compared to the other groups. Our results demonstrated that HMB associated with training without load and with lower frequency per week may be a valuable strategy for skeletal muscle regeneration.
Abstract in English:More information is needed on asthma control and health-related quality of life (HRQoL) in smokers with severe asthma. The main study objective was to characterize the association of HRQoL and disease control with cigarette smoking in individuals with severe asthma. A secondary objective was to analyze subject characteristics according to asthma onset: asthma that developed before smoking initiation versus asthma that developed after smoking initiation. This cross-sectional study included subjects with severe asthma aged 18-65 years. HRQoL was assessed using the Asthma Quality of Life Questionnaire (AQLQ) and asthma control was assessed using the Asthma Control Test (ACT) and Global Initiative for Asthma (GINA) criteria. Of the 87 patients studied, 58 (66.7%) were classified as asthmatics who had never smoked and 29 (33.3%) as asthmatics with smoking exposure. The proportion of subjects with uncontrolled asthma was higher in the asthma and smoking group (GINA criteria: P=0.032 and ACT criteria: P=0.003. There were no between-group differences in overall AQLQ score (P=0.475) or AQLQ domain scores (P>0.05). Fifty-eight subjects (66.7%) were nonsmokers, 20 (23%) had asthma onset before smoking, and 9 (10.3%) had asthma onset after smoking. Asthma onset before smoking was associated with uncontrolled asthma (P=0.013). In subjects with severe asthma, smoking was associated with a higher rate of uncontrolled disease but not with HRQoL scores.
Abstract in English:The aim of this study was to analyze the spatio-temporal distribution of tuberculosis (TB) in the elderly population in the city of Belém, PA from 2011 to 2015 according to the Living Conditions Index (LCI). This was an epidemiological, descriptive, ecological, and retrospective study involving 1,134 cases. Data were collected through the Information System of Notifiable Diseases (SINAN). For data analysis, we used the incidence coefficient, global and local empirical Bayesian model, Kernel density, and Kernel ratio. The construction of the LCI was based on the United Nations Development Program (UNDP) method. The incidence of TB remained the same over the five years studied. No neighborhood was found to have a high incidence of TB and a high LCI, but most of the cases occurred in the south of the city where the neighborhoods with the most precarious conditions are located. Moreover, the lowest incidence was in neighborhoods that historically had better infrastructure. Spatial analysis tools facilitate studies on the dynamics of disease transmission such as TB. In this study, it was shown that TB is heterogeneously distributed throughout the municipality. Living conditions, especially in slums, influenced TB incidence.
Abstract in English:We evaluated whether hyaluronan (HA) levels in the sputum could be used as a noninvasive tool to predict progressive disease and treatment response, as detected in a computed tomography scan in non-small cell lung cancer (NSCLC) patients. Sputum samples were collected from 84 patients with histological confirmation of NSCLC, 33 of which were in early-stage and 51 in advanced-stage disease. Patients received systemic chemotherapy (CT) after surgery (n=36), combined CT and immunotherapy (IO) (n=15), or targeted therapy for driver mutation and disease relapse (N=4). The primary end-point was to compare sputum HA levels in two different concentrations of hypertonic saline solution with overall survival (OS) and the secondary and exploratory end-points were radiologic responses to treatment and patient outcome. Higher concentrations of HA in the sputum were significantly associated to factors related to tumor stage, phenotype, response to treatment, and outcome. In the early stage, patients with lower sputum HA levels before treatment achieved a complete tumor response after systemic CT with better progression-free survival (PFS) than those with high HA levels. We also examined the importance of the sputum HA concentration and tumor response in the 51 patients who developed metastatic disease and received CT+IO. Patients with low levels of sputum HA showed a complete tumor response in the computed tomography scan and stable disease after CT+IO treatment, as well as a better PFS than those receiving CT alone. HA levels in sputum of NSCLC patients may serve as a candidate biomarker to detect progressive disease and monitor treatment response in computed tomography scans.
Abstract in English:Sepsis causes long-term disability, such as immune dysfunction, neuropsychological disorders, persistent inflammation, catabolism, and immunosuppression, leading to a high risk of death in survivors, although the contributing factors of mortality are unknown. The purpose of this experimental study in rats was to examine renal (rSNA) and splanchnic (sSNA) sympathetic nerve activity, as well as baroreflex sensitivity, in acute and chronic post-sepsis periods. The rats were divided into two groups: control group with naïve Wistar rats and sepsis group with 2-mL intravenous inoculation of Escherichia coli at 108 CFU/mL. Basal mean arterial pressure, heart rate, rSNA, sSNA, and baroreflex sensitivity were evaluated in all groups at the acute (6 h) and chronic periods (1 and 3 months). Basal rSNA and sSNA were significantly reduced in the surviving rats, as was their baroreflex sensitivity, for both pressor and hypotensive responses, and this effect lasted for up to 3 months. A single episode of sepsis in rats was enough to induce long-term alterations in renal and splanchnic sympathetic vasomotor nerve activity, representing a possible systemic event that needs to be elucidated. These findings showed that post-sepsis impairment of sympathetic vasomotor response may be one of the critical components in the inability of sepsis survivors to respond effectively to new etiological illness factors, thereby increasing their risk of post-sepsis morbidity.
Abstract in English:Oral tolerance blocks the development of specific immune responses to proteins ingested by the oral route. One of the first registries of oral tolerance showed that guinea pigs fed corn became refractory to hypersensitivity to corn proteins. Mice fed with chow containing corn are tolerant to zein, and parenteral injection of zein plus adjuvant blocks immunization to unrelated proteins injected concomitantly and reduces unspecific inflammation. Extensive and prolonged inflammatory infiltrate in the wound bed is one of the causes of pathological wound healing. Previous research shows that intraperitoneal injection of zein concomitant with skin injuries reduces the inflammatory infiltrate in the wound bed and improves wound healing. Herein, we tested if one subcutaneous injection of zein before skin injury improves wound healing. We also investigated how long the effects triggered by zein could improve skin wound healing. Mice fed zein received two excisional wounds on the interscapular skin under anesthesia. Zein plus Al(OH)3 was injected at the tail base at 10 min, or 3, 5, or 7 days before skin injuries. Wound healing was analyzed at days 7 and 40 after injury. Our results showed that a zein injection up to 5 days before skin injury reduced the inflammatory infiltrate, increased the number of T-cells in the wound bed, and improved the pattern of collagen deposition in the neodermis. These findings could promote the development of new strategies for the treatment and prevention of pathological healing using proteins normally found in the common diet.
Abstract in English:The aim of the present investigation was to study the toxic influences of taxol (TXL) on the testes of rats and the protective impact of melatonin (MLT) against such effects. Rats were classified into control, sham, TXL, MLT, and MLT+TXL-treated groups. Histological and ultrastructural changes were observed in testicular tissues of TXL-intoxicated rats including thickening of tunica albuginea and degenerative alterations in spermatogenic, Sertoli, and Leydig cells. A significant increase (P≤0.05) was found in the thickness of tunica albuginea and numbers of tubules without sperm, apoptotic germinal epithelia, and apoptotic Leydig cells, whereas the diameter of tubules and height of germinal epithelia displayed a significant decrease (P≤0.05) compared with the control, sham, and MLT-treated groups. Immunohistochemically, a marked decrease (P≤0.05) in Bcl-2 immunoreactivity and significant elevation (P≤0.05) in P53 and caspase-3 immunoreactivities were recorded. Co-treatment of MLT and TXL modulated such histological, histomorphometrical, and ultrastructural changes induced by TXL. Also, MLT had a protective effect against testicular apoptosis induced by TXL, as shown by the elevated expression of Bcl-2 and decreased expression of P53 and caspase-3. In conclusion, the current investigation proved that MLT had a protective role against TXL-induced testicular cytotoxicity, which may be a result of inhibition of testicular apoptosis.
Abstract in English:Heart rate variability (HRV) is a relevant physiological variable for the estimation of cardiac autonomic function. Although the gold standard for HRV registration is the electrocardiogram (ECG), several applications (APPs) have been increasingly developed. The evaluation carried out by these devices must be compatible with ECG standards. The aim of this study was to compare the data obtained simultaneously with ECG and APP with chest heart rate transmitters. Fifty-six healthy individuals (28 men and 28 women) were evaluated at rest through a short simultaneous HRV measurement with both devices. Data from both acquisition systems were analyzed separately using their own analysis software and exported and analyzed using a validated software. Signal recordings were compatible between the two acquisition systems (Pearson r=0.99; P<0.0001). Although a high correlation was found for the HRV variables obtained in the time domain (Spearman r=0.99; P<0.0001), the correlation decreased in the frequency domain (Pearson r=0.85; P<0.0001) when two software programs were used. Comparison of the averages of spectral analysis parameters also showed differences when HRV data were analyzed separately in each device for low-frequency (LF) and high-frequency (HF) bands. Although the portability of these mobile devices allows for optimal HRV evaluation, the direct analysis obtained from these devices must be carefully evaluated with respect to frequency domain parameters.
Abstract in English:Clinical indicators do not adequately predict the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) following percutaneous coronary intervention (PCI). The low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio is expected to be a reliable predictor of the long-term prognosis of these patients. This study aimed to explore the correlation between the LDL/HDL ratio and long-term prognosis in STEMI patients undergoing PCI. Patients with confirmed STEMI who underwent PCI in 7 hospitals in China from January 2009 to December 2011 were enrolled. Information about clinical endpoints, including all-cause death and major adverse cardiovascular events, was collected. Overall, 915 patients were included for analysis, the average follow-up time was 112.2 months. According to the LDL/HDL ratio, the patients were divided into 3 groups using the three-quantile method: low (LDL/HDL≤1.963), medium (1.963<LDL/HDL<2.595), and high (LDL/HDL≥2.595) LDL/HDL groups. The rate of coronary revascularization was higher in the high LDL/HDL group (28.52%) than in the low (17.38%, P=0.001) and medium (19.34%, P=0.010) LDL/HDL groups. The hazard ratio of coronary revascularization was significantly higher in the high LDL/HDL group than in the low (P=0.007) and medium (P=0.004) LDL/HDL groups. Increased LDL/HDL ratio was an independent risk factor for long-term coronary revascularization in STEMI patients undergoing PCI (HR=1.231, 95%CI: 1.023-1.482, P=0.028). These findings suggest that an increased LDL/HDL ratio was an independent risk factor for long-term coronary revascularization in STEMI patients undergoing PCI. The risk of coronary revascularization was significantly increased in patients with LDL/HDL≥2.595.
Abstract in English:Anoikis is a type of apoptosis that occurs in response to the loss of adhesion to the extracellular matrix (ECM). Anoikis resistance is a critical mechanism in cancer and contributes to tumor metastasis. Nitric oxide (NO) is frequently upregulated in the tumor area and is considered an important player in cancer metastasis. The aim of this study was to evaluate the effect of NO on adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells. Here, we report that anoikis-resistant endothelial cells overexpress endothelial nitric oxide synthase. The inhibition of NO release in anoikis-resistant endothelial cells was able to decrease adhesiveness to fibronectin, laminin, and collagen IV. This was accompanied by an increase in cell invasiveness and migration. Furthermore, anoikis-resistant cell lines displayed a decrease in fibronectin and collagen IV protein expression after L-NAME treatment. These alterations in adhesiveness and invasiveness were the consequence of MMP-2 up-regulation observed after NO release inhibition. The decrease in NO levels was able to down-regulate the activating transcription factor 3 (ATF3) protein expression. ATF3 represses MMP-2 gene expression by antagonizing p53-dependent trans-activation of the MMP-2 promoter. We speculate that the increased release of NO by anoikis-resistant endothelial cells acted as a response to restrict the MMP-2 action, interfering in MMP-2 gene expression via ATF3 regulation. The up-regulation of nitric oxide by anoikis-resistant endothelial cells is an important response to restrict tumorigenic behavior. Without this mechanism, invasiveness and migration potential would be even higher, as shown after L-NAME treatment.
Abstract in English:Species of the genus Leishmania parasitize mammals and have life cycles that alternate between vertebrate and invertebrate hosts. Most species develop in a hematophagous arthropod and infect a specific vertebrate host that may belong to diverse orders and families. Visceral leishmaniasis is a chronic zoonosis with a wide geographic distribution, affecting 350 million people globally, mostly in areas with a high risk of infection. In Brazil, this disease not only has a high incidence but is also expanding to new areas, both in urban centers and rural areas, including territories with tribal communities, due to increasing human intervention. The objective of this study was to perform cathepsin L-like gene-based molecular diagnosis of Leishmania infantum in the indigenous Tapirapé ethnic group in the state of Mato Grosso. From the 372 individuals assessed, only 0.8% (3/372) tested positive for L. infantum, all from the same village (Urubu Branco). Despite the small number of infected individuals, this study demonstrates the first human cases of Leishmania infantum infection in this population, suggesting the need for regular monitoring of visceral leishmaniasis in the area and leading to a broad discussion on the planning and implementation of public health measures for the indigenous population, while respecting their distinctive territories and culture.
Abstract in English:The periaqueductal gray matter (PAG) is an essential structure involved in the elaboration of defensive responses, such as when facing predators and conspecific aggressors. Using a prey vs predator paradigm, we aimed to evaluate the PAG activation pattern evoked by unconditioned and conditioned fear situations. Adult male guinea pigs were confronted either by a Boa constrictor constrictor wild snake or by the aversive experimental context. After the behavioral test, the rodents were euthanized and the brain prepared for immunohistochemistry for Fos protein identification in different PAG columns. Although Fos-protein-labeled neurons were found in different PAG columns after both unconditioned and conditioned fear situations at the caudal level of the PAG, we found greater activation of the lateral column compared to the ventrolateral and dorsomedial columns after predator exposure. Moreover, the lateral column of the PAG showed higher Fos-labeled cells at the caudal level compared to the same area at the rostral level. The present results suggested that there are different activation patterns of PAG columns during unconditioned and conditioned fear in guinea pigs. It is possible to hypothesize that the recruitment of specific PAG columns depended on the nature of the threatening stimulus.
Abstract in English:The elevated gradient of aversion (EGA) is an apparatus for investigating the exploratory behavior of rats in 3-min sessions, consisting of three different sections of the same size: tunnel, closed arm, and open arm. Factorial analyses have defined three factors: exploration, impulsivity, and self-protection. In general, male rats are placed in the tunnel end and tend to hesitate leaving this starting point. Then, they hesitate leaving the tunnel and entering the closed arm, which they explore and tend to avoid entering the open arm or even just stick their head in and not enter it at all. Since females were not used for this test and are reported to be more explorative than male rats, the present work aimed to compare the behavior of male and female rats in the EGA. Thirty male and 34 female Wistar rats were submitted to 3-min sessions in the EGA. In general, results indicated that females were different from males: they explored more (Factor 1 - Exploration), are more impulsive (Factor 2 - Impulsivity), and are less anxious/fearful (Factor 3 - Self-protection). These results confirmed the results of other studies obtained with other apparatuses and show that females exhibit higher locomotion than males and are less anxious/fearful.
Abstract in English:Abstract Inflammatory cytokines are related to cognitive function and psychiatric disorders in patients with several diseases. However, few relevant studies have been performed on acute ischemic stroke (AIS) patients. Hence, this study aimed to investigate the correlation of common inflammatory cytokines with cognition impairment, anxiety, and depression in AIS patients. Common inflammatory cytokines of 176 AIS patients (including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-17) were measured using Human Enzyme Linked Immunosorbent Assay Kits. Cognition impairment (Mini-Mental State Examination (MMSE)), anxiety (Hospital Anxiety and Depression Scale for anxiety (HADS-A)), and depression (HADS-D) were evaluated. The incidence of cognition impairment, anxiety, and depression was 43.2, 39.2, and 31.2%, respectively. TNF-α and IL-6 were negatively associated with MMSE score, and high TNF-α, IL-1β, and IL-6 were correlated with cognition impairment occurrence. In addition, TNF-α, IL-1β, and IL-17 were positively associated with HADS-A score, while only high TNF-α was associated with anxiety occurrence. Furthermore, TNF-α, IL-1β, and IL-17 were positively associated with HADS-D score, while high IL-1β, IL-6, and IL-17 correlated with depression occurrence. Multivariate logistic regression revealed that TNF-α and National Institutes of Health Stroke Scale (NIHSS) score ≥5 were associated with high risk of cognition impairment; TNF-α, IL-17, unemployed before surgery, hypertension, and chronic kidney disease (CKD) correlated with high anxiety occurrence. Furthermore, IL-17, divorced/widowed/single status, diabetes, and NIHSS score ≥5 were associated with high risk of depression. In conclusion, common inflammatory cytokines including TNF-α, IL-1β, and IL-17 were related to cognition impairment, anxiety, or depression in AIS patients.
Abstract in English:Roflumilast, a highly selective oral phosphodiesterase IV inhibitor, exerts anti-inflammatory and anti-fibrotic effects. Oral roflumilast causes gastrointestinal side effects, especially vomiting, which could be reduced by administering roflumilast via off-label routes. Inhaled roflumilast reportedly improved inflammatory and histopathological changes in asthmatic mice. The current study investigated the effects of oral and rectal roflumilast on trinitrobenzenesulfonic acid (TNBS)-induced chronic colitis in rats, an experimental model resembling human Crohn's disease. Five groups of rats (n=8) were used: normal control, TNBS-induced colitis, and three TNBS-treated colitic groups, which received oral sulfasalazine (500 mg·kg-1·day-1), oral roflumilast (5 mg·kg-1·day-1), or rectal roflumilast (5 mg·kg-1·day-1) for 15 days after colitis induction. Then, the following were assessed: the colitis activity score, tumor necrosis factor (TNF)-α, interleukin (IL)-2, and IL-6 serum levels, colonic length, and myeloperoxidase, malonaldehyde, and glutathione levels. Histological examinations employed H&E, Masson trichrome, and PAS stains in addition to immunostaining for KI-67 and TNF-α. The TNBS-induced colitis rats showed significant increases in disease activity scores, serum TNF-α, IL-2, and IL-6 levels, and colonic myeloperoxidase and malonaldehyde content. They also showed significant decreases in colonic length and glutathione levels in addition to histopathological and immunohistochemical changes. All the treatments significantly improved all these changes. Sulfasalazine provided the greatest improvement, followed by oral roflumilast, and then rectal roflumilast. In conclusion, both oral and rectal roflumilast partially improved TNBS-induced chronic colitis, suggesting the potential of roflumilast as an additional treatment for Crohn's disease.
Abstract in English:Seizures are a disorder caused by structural brain lesions, life-threatening metabolic derangements, or drug toxicity. The present study describes the behavior related to proconvulsant activity induced by thiocolchicoside (TCC) in rats and investigates the electrocorticographic patterns of this behavior and the effectiveness of classic antiepileptic drugs used to control these seizures. Forty-nine adult male Wistar rats were used and divided into two phases of our experimental design: 1) evaluation of seizure-related behavior and electrocorticographic patterns induced by TCC and 2) evaluation of the efficacy of classical antiepileptic drugs to control the proconvulsive activity caused by TCC. Our results showed that TCC induced tonic-clonic seizures that caused changes in electrocorticographic readings, characteristic of convulsive activity, with average amplitude greater than that induced by pentylenetetrazole. Treatment with anticonvulsants, especially diazepam, reduced the electrocorticographic outbreaks induced by TCC. The results suggested that TCC caused seizures with increased power in brain oscillations up to 40 Hz and that diazepam may partially reverse the effects.
Abstract in English:The present study was designed to investigate the involvement of miR-23a-3p in the progression of sepsis-induced acute kidney injury (AKI). The expression levels of miR-23a-3p and wnt5a in sepsis-induced AKI patients and lipopolysaccharide (LPS)-treated HK-2 cells were detected by real-time PCR and western blotting. Then, the effects of miR-23a-3p overexpression on cell viability, apoptosis, and inflammatory cytokines secretion in LPS-stimulated HK-2 cells were investigated. Moreover, luciferase reporter assay was performed to confirm the regulatory relationship between miR-23a-3p and wnt5a. Whether miR-23a-3p regulated the activation of Wnt/β-catenin signaling was also explored. mR-23a-3p was lowly expressed in the serum of patients with sepsis-associated AKI and in LPS-treated HK-2 cells. In addition, the overexpression of miR-23a-3p restrained LPS-induced proliferation inhibition and promotion of apoptosis and cytokine production in HK-2 cells. Moreover, wnt5a was identified as a target of miR-23a-3p, which could be negatively regulated by miR-23a-3p. Overexpression of miR-23a-3p suppressed the activation of Wnt/β-catenin signaling in LPS-treated HK-2 cells, which was markedly reversed by wnt5a upregulation. Upregulation of miR-23a-3p may alleviate LPS-induced cell injury by targeting wnt5a and inactivating Wnt/β-catenin pathway, which may serve as a novel therapeutic target for sepsis-associated AKI.
Abstract in English:We examined whether endurance performance and neuromuscular fatigue would be affected by caffeine ingestion during closed- and open-loop exercises. Nine cyclists performed a closed-loop (4,000-m cycling time trial) and an open-loop exercise (work rate fixed at mean power of the closed-loop trial) 60 min after ingesting caffeine (CAF, 5 mg/kg) or placebo (PLA, cellulose). Central and peripheral fatigue was quantified via pre- to post-exercise decrease in quadriceps voluntary activation and potentiated twitch force, respectively. Test sensitivity for detecting caffeine-induced improvements in exercise performance was calculated as the mean change in time divided by the error of measurement. Caffeine ingestion reduced the time of the closed-loop trial (PLA: 375.1±14.5 s vs CAF: 368.2±14.9 s, P=0.024) and increased exercise tolerance during the open-loop trial (PLA: 418.2±99.5 s vs CAF: 552.5±106.5 s, P=0.001), with similar calculated sensitivity indices (1.5, 90%CI: 0.7-2.9 vs 2.8, 90%CI: 1.9-5.1). The reduction in voluntary activation was more pronounced (P=0.019) in open- (-6.8±8.3%) than in closed-loop exercises (-1.9±4.4%), but there was no difference between open- and closed-loop exercises for the potentiated twitch force reduction (-25.6±12.8 vs -26.6±12.0%, P>0.05). Caffeine had no effect on central and peripheral fatigue development in either mode of exercise. In conclusion, caffeine improved endurance performance in both modes of exercise without influence on post-exercise central and peripheral fatigue, with the open-loop exercise imposing a greater challenge to central fatigue tolerance.
Abstract in English:Evidence has shown that women with type 2 diabetes mellitus (T2DM) have a greater risk of cardiovascular complications compared with men, but this sex difference is not clearly understood. This study assessed the microvascular function and circulatory biomarkers in postmenopausal women (PMW) with T2DM compared with diabetic men and their non-diabetic counterparts. Sixty participants were divided into nondiabetic PMW, PMW with T2DM, non-diabetic men, and diabetic men. Microvascular function was assessed using non-invasive equipment (EndoPAT®) and reported as reactive hyperemia index (RHI). Anthropometric and cardiovascular parameters were also measured. Two-way ANOVA was performed using sex (women or men) and T2DM (non-diabetic and diabetic) as the two factors. RHI impairment (1.97±0.14) was detected in diabetic PMW compared with women without T2DM (2.5±0.13) accompanied by lower adiponectin levels (T2DM: 9.3±1.2 and CTL: 13.8±1.8 ug/mL, P<0.05). An increase in the Nε-carboxymethyllysine (CML), nitrate/nitrite, and C-reactive protein (CRP) levels were observed in diabetic PMW compared to the other groups. Although a poor glycemia control was seen in diabetic men, neither RHI nor circulatory biomarkers were affected by T2DM. Multiple linear regression stratified by sex and T2DM identified some variables with RHI only in PMW with T2DM: HbA1c (P=0.003), body mass index (P=0.029), CML (P=0.032), and CRP (P=0.006). Diabetic PMW were more susceptible to the deleterious effects of hyperglycemia than men, showing microvascular dysfunction with high levels of pro-inflammatory mediators (CML and CRP) and a lower adiponectin concentration.
Abstract in English:The non-enzymatic antioxidant system protects blood components from oxidative damage and/or injury. Herein, plasma non-enzymatic antioxidant capacity after acute strenuous swimming exercise (Exe) and exercise until exhaustion (Exh) was measured in rats. The experiments were carried out in never exposed (Nex) and pre-exposed (Pex) groups. The Nex group did not undergo any previous training before the acute strenuous swimming test and the Pex group was submitted to daily swimming for 10 min in the first week and 15 min per day in the second week before testing. Plasma glucose, lactate, and pyruvate were measured and plasma total protein sulfhydryl groups (thiol), trolox equivalent antioxidant capacity (TEAC), ferric reducing ability of plasma (FRAP), and total radical-trapping antioxidant parameter (TRAP) levels were evaluated. There were marked increases in plasma lactate concentrations (Nex-Control 1.31±0.20 vs NexExe 4.16±0.39 vs NexExh 7.19±0.67) and in thiol (Nex-Control 271.9±5.6 vs NexExh 314.7±5.7), TEAC (Nex-Control 786.4±60.2 vs NexExh 1027.7±58.2), FRAP (Nex-Control 309.2±17.7 vs NexExh 413.4±24.3), and TRAP (Nex-Control 0.50±0.15 vs NexExh 2.6±0.32) levels after acute swimming and/or exhaustion. Also, there were increased plasma lactate concentrations (Pex-Control 1.39±0.15 vs PexExe 5.22±0.91 vs PexExh 10.07±0.49), thiol (Pex-Control 252.9±8.2 vs PexExh 284.6±6.7), FRAP (Pex-Control 296.5±15.4 vs PexExh 445.7±45.6), and TRAP (Pex-Control 1.8±0.1 vs PexExh 4.6±0.2) levels after acute swimming and/or exhaustion. Lactate showed the highest percent of elevation in the Nex and Pex groups. In conclusion, plasma lactate may contribute to plasma antioxidant defenses, and the TRAP assay is the most sensitive assay for assessing plasma non-antioxidant capacity after strenuous exercise.
Abstract in English:Near-infrared spectroscopy (NIRS) could be a useful continuous, non-invasive technique for monitoring the effect of partial pressure of carbon dioxide (PaCO2) fluctuations in the cerebral circulation during ventilation. The aim of this study was to examine the efficacy of NIRS to detect acute changes in cerebral blood flow following PaCO2 fluctuations after confirming the autoregulation physiology in piglets. Fourteen piglets (<72 h of life) were studied. Mean arterial blood pressure, oxygen saturation, pH, glycemia, hemoglobin, electrolytes, and temperature were monitored. Eight animals were used to evaluate brain autoregulation, assessing superior cava vein Doppler as a proxy of cerebral blood flow changing mean arterial blood pressure. Another 6 animals were used to assess hypercapnia generated by decreasing ventilatory settings and complementary CO2 through the ventilator circuit and hypocapnia due to increasing ventilatory settings. Cerebral blood flow was determined by jugular vein blood flow by Doppler and continuously monitored with NIRS. A decrease in PaCO2 was observed after hyperventilation (47.6±2.4 to 29.0±4.9 mmHg). An increase in PaCO2 was observed after hypoventilation (48.5±5.5 to 90.4±25.1 mmHg). A decrease in cerebral blood flow after hyperventilation (21.8±10.4 to 15.1±11.0 mL/min) and an increase after hypoventilation (23.4±8.4 to 38.3±10.5 mL/min) were detected by Doppler ultrasound. A significant correlation was found between cerebral oxygenation and Doppler-derived parameters of blood flow and PaCO2. Although cerebral NIRS monitoring is mainly used to detect changes in regional brain oxygenation, modifications in cerebral blood flow following experimental PaCO2 changes were detected in newborn piglets when no other important variables were modified.
Abstract in English:Cervical vertigo is a common complication of atlantoaxial joint dislocation. However, there is no consensus on the effects of different therapies on the recovery of the patients suffering cervical vertigo. The objective of this randomized controlled trial was to investigate the effect of traction therapy on reducing cervical vertigo induced by atlantoaxial joint dislocation. A total of 96 patients were randomized to receive traction therapy or traditional therapy for two weeks. The overall clinical efficacy was measured based on the 30-point cervical vertigo symptom and function evaluation form. The therapeutic effects were also evaluated based on lateral atlantodental space (LADS), vertigo scale, neck and shoulder pain scale, headache scale, daily life and work scale, psychosocial adaptation scale, and quality of life. Compared with the traditional therapy group, the traction group demonstrated markedly higher overall clinical efficacy (P=0.038). Both the traction therapy group and the traditional therapy group showed significant decrease in LADS (P<0.001), but the traction therapy group had a greater reduction of LAD compared with the traditional group (P<0.01). Traction therapy consistently led to significantly greater relief of cervical vertigo symptoms, including dizziness, neck and shoulder pain, headache, inconvenience in daily living and work activities, impaired psychosocial adaptation, while improving quality of life. The efficacy of traction therapy for cervical vertigo surpasses that of traditional therapy, suggesting that traction therapy is potentially more clinically useful in treating these patients.
Abstract in English:Nephrotic syndrome is the most common clinical presentation of glomerular disease in elderly patients, and renal biopsy is an important diagnostic resource. The aim of this study was to describe nephrotic syndrome among elderly patients in Brazil, focusing on tubulointerstitial and vascular involvement. This was a retrospective study of patients over 65 years of age with nephrotic syndrome who underwent renal biopsy between January 2012 and December 2019. Of the 123 renal biopsies that occurred during the study period, 44 (35.8%) were performed for the investigation of nephrotic syndrome. Among those 44 cases, the main etiologies were membranous nephropathy in 13 cases (29.5%), amyloidosis in ten (22.7%), non-collapsing focal segmental glomerulosclerosis (FSGS) in four (9.1%), and collapsing FSGS in four (9.1%). Patients with minimal change disease (MCD) had the lowest degree of interstitial fibrosis compared with the other glomerulopathies, and histological signs of acute tubular necrosis (ATN) were less common among those with amyloidosis than among those with membranous nephropathy, FSGS, or MCD (P=0.0077). Of the patients with ATN, the frequency of acute kidney injury (AKI) was highest in those with MCD (P<0.001). All patients had some degree of vascular involvement, regardless of the type of glomerulopathy. In conclusion, the second most common cause of nephrotic syndrome in this population was amyloidosis, and acute interstitial tubule involvement was more marked in MCD. Vascular involvement is something that cannot be dissociated from the age of the patient and is not only due to the underlying glomerulopathy.
Abstract in English:Genome-wide analysis using microarrays has revolutionized breast cancer (BC) research. A substantial body of evidence supports the clinical utility of the 21-gene assay (Oncotype DX) and 70-gene assay (MammaPrint) to predict BC recurrence and the magnitude of benefit from chemotherapy. However, there is currently no genetic tool able to predict chemosensitivity and chemoresistance to neoadjuvant chemotherapy (NACT) during BC treatment. In this study, we explored the predictive value of DNA repair gene expression in the neoadjuvant setting. We selected 98 patients with BC treated with NACT. We assessed DNA repair expression in 98 formalin-fixed, paraffin-embedded core biopsy fragments used at diagnosis and in 32 formalin-fixed, paraffin-embedded post-NACT residual tumors using quantitative reverse transcription-polymerase chain reaction. The following genes were selected: BRCA1, PALB2, RAD51C, BRCA2, ATM, FANCA, MSH2, XPA, ERCC1, PARP1, and SNM1. Of 98 patients, 33 (33.7%) achieved pathologic complete response (pCR). The DNA expression of 2 genes assessed in pre-NACT biopsies (PALB2 and ERCC1) was lower in pCR than in non-pCR patients (P=0.005 and P=0.009, respectively). There was no correlation between molecular subtype and expression of DNA repair genes. The genes BRCA2 (P=0.009), ATM (P=0.004), FANCA (P=0.001), and PARP1 (P=0.011) showed a lower expression in post-NACT residual tumor samples (n=32) than in pre-NACT biopsy samples (n=98). The expression of 2 genes (PALB2 and ERCC1) was lower in pCR patients. These alterations in DNA repair could be considered suitable targets for cancer therapy.
Abstract in English:The human gut microbiota is a complex and dynamic community of microorganisms living in our intestines and has emerged as an important factor for colorectal adenocarcinoma (CRC). The purpose of our study was to investigate the microbiota composition in Brazilian CRC patients compared with a local control population (CTL) to find out which changes could be considered universal or regional features in CRC microbiota. Fecal samples were obtained from 28 CRC and 23 CTL individuals. The 16S rRNA gene was used for metagenomic analysis. In addition to the anthropometric variables, the clinical stage (TNM 2018) was considered. Patients with CRC had a significant increase in alpha diversity and a higher percentage of genus Prevotella and a decreased proportion of Megamonas and Ruminococcus. Additionally, the proportion of Faecalibacterium prausnitzii was associated with a better prognosis in the first stages of CRC, and Fusobacterium nucleatum proved to be an important marker of colorectal carcinogenesis and tumor aggressiveness. Although regional differences influence the composition of the microbiota, in the case of CRC, the microhabitat created by the tumor seems to be a major factor. Our results contribute to a better understanding of the carcinogenic process, and even in different environments, some factors appear to be characteristic of the microbiota of patients with CRC.
Abstract in English:Elastase-2 (ELA-2) is an angiotensin II-generating enzyme that participates in the cardiovascular system. ELA-2 is involved in hemodynamic and autonomic control and is upregulated in myocardial infarction and hypertension. The inhibition of angiotensin-converting enzyme (ACE) increased ELA-2 expression in the carotid arteries and heart of spontaneously hypertensive rats. In this study, we sought to investigate the role of ACE inhibition in hemodynamic and autonomic balance in elastase-2 knockout (ELA-2 KO) mice. Male ELA-2 KO and C57BL/6 mice were treated with the ACE inhibitor enalapril or saline for 10 days. After treatment, mice underwent surgery for cannulation of the femoral artery and arterial pressure recordings were made five days later in awake animals. The variability of systolic blood pressure (SBP) and pulse interval (PI) was evaluated in the time and frequency domain. Spontaneous baroreflex was assessed by the sequencing method. ACE inhibition caused a significant decrease in mean arterial pressure (117±2.2 vs 100±2.8 mmHg) and an increase in heart rate (570±32 vs 655±15 bpm) in ELA-2 KO mice. Despite a tendency towards reduction in the overall heart rate variability (standard deviation of successive values: 7.6±1.1 vs 4.7±0.6 ms, P=0.08), no changes were found in the root of the mean sum of squares or in the power of the high-frequency band. ACE inhibition did not change the spontaneous baroreflex indices (gain and baroreflex effectiveness index) in ELA-2 KO mice. Altogether, this data suggested that ACE played a role in the maintenance of hemodynamic function in ELA-2 KO mice.
Abstract in English:The aim of this study was to establish reference equations for the six-minute step test (6MST) based on demographic, anthropometric, body composition, and performance variables able to predict oxygen uptake (V̇O2) in obese individuals. Seventy-three obese adults (42±14 years old, body mass index >30 kg/m2) from both sexes were included. They underwent anamnesis, body composition evaluation, and the 6MST with expired gases registered simultaneously. Three equations were developed for the obese population (n=73; 59% female). The first equation was composed of the up-and-down step cycles (UDS), sex, and age as predictors; the second equation was composed of the UDS, age, and lean mass (LM). Both equations collectively explained 68.1% of the V̇O2 variance in the 6MST, while the third equation, composed of the UDS, age, and body mass, accounted for 67.7% of the V̇O2 variance. UDS, sex, age, LM, and body mass were important V̇O2 predictors of 6MST in these obese individuals. This study contributes to the dissemination of a simple, inexpensive, and fast evaluation method that can provide important indicators of cardiorespiratory fitness and guide strategies for rehabilitation.
Abstract in English:Aging is related to a decrease in physiological abilities, especially cognitive functions. To unravel further evidence of age-related cognitive decline, we analyzed which physical and functional variables are predictors of cognitive performance in a sample of 498 Brazilian elderly (67.26% women). To do so, we used the Stroop test as a tool to evaluate executive functions and the General functional fitness index (GFFI) to evaluate the functional fitness of the participants. A linear regression analysis revealed that female sex (β=-0.097; t=-2.286; P=0.023), younger age (β=0.205; t=4.606; P<0.0001), more years of education (β=-0.280; t=-6.358; P<0.0001), and higher GFFI (β=-0.101; t=-2.347; P<0.02) were predictors of better cognitive performance. Body mass index (kg/m2) and nutritional status (underweight, eutrophic, overweight, or obese) were not predictors of cognitive performance. Interestingly, among the GFFI tasks, muscle strength influenced the test execution time, both in upper and lower limbs (elbow flexion: β=-0.201; t=-4.672; P<0.0001; sit-to-stand: β=-0.125; t=-2.580; P<0.01). Our findings showed that: 1) women performed the Stroop test faster than men; 2) the older the person, the lower was the cognitive performance; 3) the higher the education, the better the test execution time; and 4) higher scores in the GFFI were associated with a better performance in the Stroop test. Therefore, gender, age, education, and functional fitness and capacity were predictors of cognitive performance in the elderly.
Abstract in English:The aim of the present study was to verify the role of lactate as a signaling molecule in cardiac tissue under physiological conditions. C57BL6/J male mice were submitted to acute running bouts on a treadmill at different exercise intensities (30, 60, and 90% of maximal speed - Smax) under the effect of two doses (0.5 and 5 mM) of α-cyano-4-hydroxycynnamate (CINN), a blocker of lactate transporters. Cardiac lactate levels, activity of the enzymes of glycolytic [hexokinase (HK) and lactate dehydrogenase (LDH)] and oxidative metabolism [citrate synthase (CS)], and expression of genes also related to metabolism [LDH, nuclear factor erythroid 2-related factor 2 (NRF-2), cytochrome oxidase IV (COX-IV), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)] were evaluated. Elevated cardiac lactate levels were observed after high intensity running at 90% of Smax, which were parallel to increased activity of the HK and CS enzymes and mRNA levels of PGC-1α and COX-IV. No changes were observed in cardiac lactate levels in mice running at lower exercise intensities. Interestingly, prior intraperitoneal administration (15 min) of CINN (0.5 mM) significantly reduced cardiac lactate concentration, activities of HK and CS, and mRNA levels of PGC-1α and COX-IV in mice that ran at 90% of Smax. In addition, cardiac lactate levels were significantly correlated to both PGC-1α and COX-IV cardiac gene expression. The present study provides evidence that cardiac lactate levels are associated to gene transcription during an acute bout of high intensity running exercise.
Abstract in English:Bidirectional selection is a procedure in which an arbitrary characteristic is chosen as a selection criterion and animals exhibiting more of this characteristic are bred in one group and animals exhibiting less are bred in another group. The procedure is repeated along generations until the selected characteristic becomes stable, resulting in two strains that are opposite in relation to the chosen characteristic. The present study aimed at selectively breeding rats exhibiting either a high or a low tendency to socialize by using the proximity test. We tested male and female Wistar rats in a square open field with a communicating birdcage, separated by a grid, containing a co-specific rat and coupled on the outside. Subjects that remained more time in front of the birdcage, interacting with the co-specific rat were bred in a group considered of high sociability (SOC+). Likewise, subjects that remained little time in front of the birdcage, with little interaction with the co-specific rat, were bred in a second group considered of low sociability (SOC–). By the 10th generation, the bidirectional selection resulted in SOC+ rats that spent a large amount of time in front of the cage sniffing and rearing in interaction with the co-specific rat and spent less time in the corners, exploring and grooming. It also resulted in SOC– rats that spent a small amount of time in front of the cage sniffing and rearing in interaction with the co-specific rat and spent more time in the corners and used most of their time grooming.
Abstract in English:Endometriosis (EMS) is one of the most prevalent causes for female infertility. Herein, we investigated the effect of the repaglinide (RG), L-carnitine (LC), and bone marrow mesenchymal stem cell-conditioned medium (BMSC-CM) supplementation during in vitro maturation (IVM) on the quality, maturation, and fertilization rates, as well as embryonic quality and development of oocytes derived from normal and EMS mouse model. Immature oocytes were collected from two groups of normal and EMS-induced female NMRI mice at 6-8 weeks of age. Oocytes were cultured in IVM medium unsupplemented (control group), or supplemented with 1 M RG, 0.3 and 0.6 mg/mL LC, and 25 and 50% BMSC-CM. After 24 h of oocyte incubation, IVM rate and antioxidant status were assessed. Subsequently, the rates of fertilization, cleavage, blastulation, and embryonic development were assessed. Our results demonstrated that supplementation of IVM medium with LC and BMSC-CM, especially 50% BMSC-CM, significantly enhanced IVM and fertilization rates, and markedly improved blastocyst development and total blastocyst cell numbers in EMS-induced mice compared to the control group (53.28±0.24 vs 18.09±0.10%). Additionally, LC and BMSC-CM were able to significantly modulate EMS-induced nitro-oxidative stress by boosting total antioxidant capacity (TAC) and mitigating nitric oxide (NO) levels. Collectively, LC and BMSC-CM supplementation improved oocyte quality and IVM rates, pre-implantation developmental competence of oocytes after in vitro fertilization, and enhanced total blastocyst cell numbers probably by attenuating nitro-oxidative stress and accelerating nuclear maturation of oocytes. These outcomes may provide novel approaches to refining the IVM conditions that can advance the efficiency of assisted reproductive technologies in infertile couples.
Abstract in English:Pancreatic cancer (PC) is one of the malignant tumors with the worst prognosis worldwide because of a lack of early diagnostic markers and efficient therapies. Integrin, beta-like 1 (ITGBL1) is a β-integrin-related extracellular matrix protein and is reported to promote progression of some types of cancer. Nevertheless, the function of ITGBL1 in PC is still not clear. Herein, we found that ITGBL1 was highly expressed in PC tissues compared to normal tissues (P<0.05) and PC patients with higher TGBL1 expression showed worse prognosis. PANC-1 and AsPC-1 cells were used for gain/loss-of-function experiments. We found that ITGBL1-silenced cells exhibited decreased proliferation, migration, and invasion abilities and delayed cell cycle, whereas ITGBL1 overexpression reversed these malignant behaviors. ITGBL1 was also demonstrated to activate the TGF-β/Smad pathway, a key signaling pathway in PC progression. Additionally, ITGBL1 expression was found to be suppressed by a suppressor of PC progression, c-Jun dimerization protein 2 (JDP2). Results of dual-luciferase assay indicated that transcription factor JDP2 could inhibit TGBL1 promoter activity. ITGBL1 overexpression inversed the effects of JDP2 up-regulation on cell function. Collectively, we concluded that ITGBL1 may be transcriptionally suppressed by JDP2 and promote PC progression through the TGF-β/Smad pathway, indicating that ITGBL1 may have therapeutic potential for the treatment of PC.
Abstract in English:Here we investigated the effects of physical training on cardiovascular autonomic control and cardiac morphofunctional parameters in spontaneously hypertensive rats (SHRs) subjected to ovarian hormone deprivation. Forty-eight 10-week-old SHRs were divided into two groups: ovariectomized (OVX, n=24) and sham (SHAM, n=24). Half of each group (n=12) was trained by swimming for 12 weeks (OVX-T and SHAM-T). Cardiac morphology and functionality were assessed using echocardiography, and autonomic parameters were assessed using double pharmacological autonomic block, baroreflex sensitivity (BRS), and analyses of heart rate variability (HRV) and blood pressure variability (BPV). Ovariectomy did not influence the cardiac autonomic tonus balance unlike physical training, which favored greater participation of the vagal autonomic tonus. Ovariectomy and aerobic physical training did not modify HRV and BRS, unlike BPV, for which both methods reduced low-frequency oscillations, suggesting a reduction in sympathetic vascular modulation. Untrained ovariectomized animals showed a reduced relative wall thickness (RWT) and increased diastolic and systolic volumes and left ventricular diameters, resulting in increased stroke volume. Trained ovariectomized animals presented reduced posterior wall thickness and RWT as well as increased final diastolic diameter, left ventricular mass, and stroke volume. Ovarian hormone deprivation in SHRs promoted morphofunctional adaptations but did not alter the evaluation of cardiac autonomic parameters. In turn, aerobic physical training contributed to a more favorable cardiac autonomic balance to the vagal autonomic component and promoted morphological adaptations but had little effect on cardiac functionality.
Abstract in English:Nonalcoholic fatty liver disease (NAFLD) is considered to be a manifestation of hepatic metabolic syndrome. Some studies on the pathogenesis of NAFLD by targeting gut microbiota have attracted wide attention. Previous studies have demonstrated the positive effects of berberine and evodiamine on metabolic diseases and gut microbiota dysbiosis. However, it is not known whether the combination of berberine and evodiamine (BE) can prevent the development of high-fat diet (HFD)-induced NAFLD. Therefore, we aimed to explore the protective effects of BE on the development of HFD-induced NAFLD from the perspective of the gut microbiota. Gut microbiota profiles were established by high throughput sequencing of the bacterial 16S ribosomal RNA gene. The effects of BE on liver and intestinal tissue, intestinal barrier integrity, and hepatic inflammation were also investigated. The results showed that the abundance and diversity of gut microbiota were enriched by BE treatment, with an increase in beneficial bacteria, such as Lactobacillus, Ruminococcus, and Prevotella, and a decrease in pathogenic bacteria such as Fusobacterium and Lachnospira. In addition, BE effectively improved liver fat accumulation and tissue damage, inhibited the apoptosis of intestinal epithelial cells, increased the contents of intestinal tight junction proteins, and decreased the expression of pro-inflammatory factors. Consequently, BE treatment could be an effective and alternative strategy for alleviating NAFLD by modulating gut microbiota and safeguarding the intestinal barrier.
Abstract in English:We aimed to evaluate whether the administration of riboflavin to septic animals reduces inflammation, oxidative stress, organ dysfunction, and mortality. C57BL/6 mice, 6-8 weeks old, were allocated to the study group (polymicrobial sepsis induced by cecal ligation and puncture (CLP) + antibiotic + iv riboflavin), control (CLP + antibiotic + iv saline), or naïve (non-operated controls). Serum concentrations of alanine aminotransferase (ALT), creatine kinase-MB (CK-MB), urea, and creatinine, and markers of inflammation [interleukin (IL)-6, tumor necrosis factor (TNF)-α, keratinocyte-derived chemokine (KC), and macrophage inflammatory protein (MIP)-2)], and oxidative stress (malondialdehyde (MDA) were measured 12 h after the experiment. Animal survival rates were calculated after 7 days. Means between groups were compared using linear regression models adjusted under the Bayesian approach. No significant difference was observed between control and study groups in serum concentrations of IL-6 (95% credible interval) (-0.35 to 0.44), TNF-α (-15.7 to 99.1), KC (-0.13 to 0.05), MIP-2 (-0.84 to 0.06), MDA (-1.25 to 2.53), or ALT (-6.6 to 11.5). Serum concentrations of CK-MB (-145.1 to -30.1), urea (-114.7 to -15.1), and creatinine (-1.14 to -0.01) were higher in the study group. Survival was similar in both groups (P=0.8). Therefore, the use of riboflavin in mice undergoing sepsis induced by CLP did not reduce inflammation, oxidative stress, organ dysfunction, or mortality compared with placebo.
Abstract in English:In preparation for tracheal intubation during induction of anesthesia, the patient may be ventilated with 100% oxygen. To investigate the impact of acute isocapnic hyperoxia on endothelial activation and vascular remodeling, ten healthy young men (24±3 years) were exposed to 5-min normoxia (21% O2) and 10-min hyperoxia trials (100% O2). During hyperoxia, intercellular adhesion molecules (ICAM-1) (hyperoxia: 4.16±0.85 vs normoxia: 3.51±0.84 ng/mL, P=0.04) and tissue inhibitor matrix metalloproteinase 1 (TIMP-1) (hyperoxia: 8.40±3.84 vs normoxia: 5.73±2.15 pg/mL, P=0.04) increased, whereas matrix metalloproteinase (MMP-9) activity (hyperoxia: 0.53±0.11 vs normoxia: 0.68±0.18 A.U., P=0.03) decreased compared to the normoxia trial. We concluded that even short exposure to 100% oxygen may affect endothelial activation and vascular remodeling.
Abstract in English:Diabetes is associated with a worse prognosis and a high risk of morbidity and mortality in COVID-19 patients. We aimed to evaluate the main factors involved in the poor prognosis in diabetic patients. A total of 984 patients diagnosed with COVID-19 admitted to the hospital were included in this study. Patients were first divided into type-2 diabetic (DM+) and non-diabetic (DM–) groups. The participants were analyzed based on the National Early Warning Score (NEWS) and on the Quick-Sequential Organ Failure Assessment (qSOFA) to find the best prognostic risk score for our study. The DM+ and DM– groups were divided into non-severe and severe groups. Comparative and correlative analyses were used to identify the physiological parameters that could be employed for creating a potential risk indicator for DM+ COVID-19 patients. We found a poorer prognosis for the DM+ COVID-19 patients with a higher ICU admission rate, mechanical ventilation rate, vasopressor use, dialysis, and longer treatment times compared with the DM– group. DM+ COVID-19 patients had increased plasma glucose, lactate, age, urea, NEWS, and D-dimer levels, herein referred to as the GLAUND set, and worse prognosis and outcomes when compared with infected DM– patients. The NEWS score was a better indicator for assessing COVID-19 severity in diabetic patients than the q-SOFA score. In conclusion, diabetic COVID-19 patients should be assessed with the NEWS score and GLAUND set for determining their prognosis COVID-19 prognosis.
Abstract in English:In early 2021, Brazil saw a dramatic recurrence in Covid-19 cases associated to the spread of a novel variant of the SARS-CoV-2 virus, the P1 variant. In light of previous reports showing that this variant is more transmissible and more likely to infect people who had recovered from previous infection, a retrospective analysis was conducted to assess if the early 2021 Covid-19 wave in Brazil was associated with an increase in the number of individuals presenting with a more severe clinical course. Fifty-one thousand and fourteen individuals who underwent telemedicine consultations were divided into two groups: patients seen on or before January 31, 2021, and on or after February 1, 2021. These dates were chosen based on the spread of the P1 variant in Brazil. Referral to the emergency department (ED) was used as a marker of a more severe course of the disease. No differences were seen in the proportion of patients referred to the ED in each group nor in the odds ratio of being referred to the ED from the 1st of February 2021 (OR=0.909; 95%CI: 0.81-1.01). Considering the entire cohort, age had an impact on the odds of being referred to the ED, with individuals older than 59 years showing twice the risk of the remaining population and those less than 19 years showing a lower risk.
Abstract in English:Constitutional genomic imbalances are known to cause malformations, disabilities, neurodevelopmental delay, and dysmorphia and can lead to dysfunctions in the cell cycle. In extremely rare genetic conditions such as small supernumerary marker chromosomes (sSMC), it is important to understand the cellular consequences of this extra marker, as well the factors that contribute to their maintenance or elimination through successive cell cycles and phenotypic impact. The study of chromosomal mosaicism provides a natural model to characterize the effect of aneuploidy on genome stability and compare cells with the same genetic background and environment exposure, but differing in the presence of sSMC. Here, we report the functional characterization of different cell lines from two familial patients with mosaic sSMC derived from chromosome 12. We performed studies of proliferation dynamics, stability, and variability of these cells using fluorescent in situ hybridization (FISH), sister chromatid exchanges (SCE), and conventional staining. We also quantified the telomere-related genomic instability of sSMC cells using 3D telomeric profile analysis by quantitative-FISH. sSMC cells exhibited differences in the cell cycle dynamics compared to normal cells. First, the sSMC cells exhibited lower proliferation index and higher frequency of SCE than normal cells, associated with a higher level of chromosomal instability. Second, sSMC cells exhibited more telomeric-related genomic instability. Lastly, the differences of sSMC cells distribution among tissues could explain different phenotypic repercussions observed in patients. These results will help in our understanding of the sSMC stability, maintenance during cell cycle, and the cell cycle variables involved in the different phenotypic manifestations.