Brazilian Journal of Medical and Biological Research最新文献

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

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

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

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

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

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

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

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

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

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