Brazilian Journal of Medical and Biological Research最新文献

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

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

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

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

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

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

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

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

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

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