Brazilian Journal of Medical and Biological Research最新文献

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

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

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

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

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

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

[This retracts the article doi: 10.1590/1414-431X20208885].

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

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

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