Brazilian Journal of Medical and Biological Research最新文献

During the climacteric period, the decline in ovarian hormones leads to changes in the lipid profile. Physical exercise is the main non-pharmacological recommendation for controlling lipid levels. However, the effects on the lipid profile in perimenopausal and postmenopausal women are incipient and inconclusive. In this context, we searched the Embase, PubMed, Scopus, and Web of Science databases for randomized clinical trials on the effects of exercise on the lipid profile of these women. We excluded studies that did not specify criteria for classifying the climacteric phase, that involved women undergoing hormone replacement therapy, or that examined combined treatments or acute effects of physical exercise. The meta-analysis indicated that general physical exercise increased high-density lipoprotein cholesterol (HDL-C) levels (mean difference [MD]=4.89; 95% confidence interval [95%CI]=0.97 to 8.81) in perimenopausal women. For obese postmenopausal women, 16 weeks of aerobic training increased HDL-C levels (MD=3.88; 95%CI=0.56 to 7.20) and reduced total cholesterol (MD=-22.36; 95%CI=-29.67 to -15.05) and low-density lipoprotein cholesterol (LDL-C) levels (MD=-17.86; 95%CI=-25.97 to -9.75), whereas 12 weeks of resistance training increased HDL-C levels (MD=4.20; 95%CI=1.16 to 7.23) and decreased triglycerides (MD=-14.86; 95%CI=-26.62 to -3.09) and LDL-C levels (MD=-16.36; 95%CI=-28.05 to -4.67). Overall, the results showed that physical exercise regulated lipid profiles in perimenopausal and postmenopausal women. Specifically, 12 weeks of resistance exercise and 16 weeks of aerobic exercise improved the lipid profile of obese postmenopausal women.

1α,25-Dihydroxyvitamin D3 (VD3), the active form of vitamin D, plays a crucial role in wound healing. In this study, we aimed to investigate the effect of VD3 on the proliferation and differentiation of epidermal stem cells (EpSCs) and monitor its impact on re-epithelialization. We established a murine full-thickness skin defect model and applied four doses of VD3 (0, 5, 50, and 250 ng/mouse/day) to the wounds topically for three days. Immunostaining and flow cytometry confirmed the effect of VD3 on the proliferation and differentiation of EpSCs in wounds. This effect of VD3 (0, 1, 10, and 50 nM) on EpSCs and its possible mechanism were further confirmed in vitro by CCK8, westen blot, immunostaining, and flow cytometry. We found that on day five post-wounding, the means±SD length of the neo-epidermis was 195.88±11.57, 231.84±16.45, 385.80±17.50, and 268.00±8.22 μm in the control, 5, 50, and 250 ng groups, respectively, with a significant difference from the control (all P<0.05). Immunostaining and flow cytometry showed that VD3 improved the proliferation and differentiation of K15+ EpSC (vs control, all P<0.05), K14+ epidermal progenitor cells (vs control, all P<0.05), and K10+ epidermal terminal cells (vs control, all P<0.05) in vivo and in vitro. The PI3K signaling pathway appeared to underlie this response because significant inhibition of the response was found when inhibitors were used to inhibit PI3K. Our study demonstrated that VD3 is a potent promoter of cutaneous wound healing by stimulating EpSC proliferation and differentiation through PI3K activation.

Alpinia zerumbet, a plant native to East Asia, is widely found on the Brazilian coast, where it is used in folk medicine as an antihypertensive, diuretic, and anxiolytic. This study investigated the effects of the hydroalcoholic extract obtained from Alpinia zerumbet leaves (AZE) on cardiovascular changes and oxidative status in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto male rats, 90 days old, treated or not with AZE (50 mg/kg/day in drinking water) for six weeks, were used in this study. Blood pressure (BP) was assessed weekly by tail plethysmography. At the end of treatment, the animals were anesthetized with thiopental (70 mg/kg, ip), blood was collected through abdominal aorta puncture, the thoracic aorta and left ventricle were isolated for morphometric analysis and immunostaining of NOX-4, SOD-2, 8-isoprostane, and angiotensin II AT1 receptors (AT1R), and the mesenteric arterial bed (MAB) was isolated for the assessment of vascular function. Oxidative damage in lipids and proteins and the enzymatic antioxidant activity were evaluated in plasma samples by spectrophotometry. AZE normalized BP in SHR. Although the treatment did not improve the MAB vascular dysfunction, it reversed the cardiovascular remodeling in the aorta and left ventricle. In addition, AZE improved antioxidant activity in plasma and SOD-2 immunostaining in the thoracic aorta and left ventricle, decreased protein carbonylation in plasma, and reduced 8-isoprostane, NOX-4, and AT1R immunostaining in the cardiovascular system. The results suggested that AZE reversed hypertension and cardiovascular remodeling in SHR, which was associated with lower oxidative stress and AT1R.

The stiffening of the conductance arteries is a hallmark of ageing and increases drastically after menopause. Therefore, the augmentation index (AIx), a surrogate for arterial stiffness, could be related to the decline in baroreflex sensitivity. We sought to investigate the relationship between resting AIx and spontaneous cardiac baroreflex sensitivity (cBRS) during handgrip exercise in ageing women. Thirteen young women (YW: 24±5 years; 24±2 kg/m2) and nine postmenopausal women (PMW: 60±5 years; 26±3 kg/m2) underwent the protocol, which consisted of 10 min of supine resting followed by 3 min of static handgrip exercise at 40% of the maximal voluntary force. The AIx was provided by the aortic pressure waveform and cBRS was calculated using the sequence technique, and vagal activity was accessed via heart rate variability using the root mean square of successive differences (RMSSD) index. Resting AIx was higher in PMW compared to YW (YW: 8±10%; PMW: 23±8%; P<0.01), while the cBRS (YW: 16±12 ms/mmHg; PMW: 10±5 ms/mmHg; P=0.08) and RMSSD (YW: 46±35 ms; PMW: 34±12 ms; P=0.26) were similar in YW and PMW. At rest, there was no significant (P>0.05) relationship between the AIx and cBRS in YW and PMW. However, in PMW, a negative (slope=-0.22) and strong (r=-0.70; P=0.03) relationship was observed between AIx and cBRS for the increment of blood pressure during the handgrip exercise. The stiffening of the arterial tree is one possible mechanism to explain the decrease of spontaneous cardiac baroreflex sensitivity during exercise in postmenopausal women.

It has been confirmed that the expression of miR-501-3p is closely related to the behavior of several cancers. This study aimed to elucidate the effects of miR-501-3p/SPC24 axis on the behavior of renal cancer cells and to identify its prognostic value in renal cancer. First, the expression of miR-501-3p in the renal cell carcinoma (RCC) cell line was detected using real-time quantitative polymerase chain reaction (RT-qPCR). Second, cell function identification experiments were performed, including CCK-8, scratch, transwell invasion, and flow cytometry assays. Several databases were applied to explore the possible mechanism of miR-501-3p tumor suppressor effect in RCC. To explore the value of miR-501-3p/SPC24 axis in predicting renal cancer patient overall survival (OS), GEPIA (http://gepia.cancer-pku.cn/index.html) was used. Finally, western blot was performed to detect the expression level of SPC24 in renal cancer cells predicted by bioinformatics analysis. Dual-Luciferase Reporter Assay was used to verify if SPC24 is a target of mir-501-3p. MiR-501-3p was found to be down-regulated in cancer cells and tissues and to play a role in suppressing tumor cell proliferation, cell viability, cell migration, and cell invasion, while promoting apoptosis. We also found that high expression levels of SPC24 were associated with shorter OS time in patients diagnosed with renal cell carcinoma. In addition, the results of TCGA data analysis and western blot showed that the tumor suppressor effect of miR-501-3p may be achieved by targeting SPC24. The MiR-501-3p/SPC24 axis affects cell proliferation, migration, invasion, apoptosis, and prognosis in renal cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumor that poses a major hazard to people's health. ZC3H12D, which belongs to the family of CCCH-type zinc finger-containing proteins, is a negative regulator with a key function in immune modulation. However, it is still unclear how ZC3H12D affects the immune infiltration and prognosis of HNSCC. In this study, the data obtained from various databases were used to assess ZC3H12D expression in HNSCC and in various tumors under the HNSCC classification. The association between clinical features and ZC3H12D expression in HNSCC was evaluated using the UALCAN database. Additionally, a ROC curve was employed to analyze the diagnostic value of ZC3H12D. The effect of ZC3H12D on prognosis was assessed using Kaplan-Meier curves, Cox analysis, and the nomogram model. Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were employed to investigate the underlying role of ZC3H12D in HNSCC. The association between ZC3H12D expression and the tumor microenvironment and immune checkpoints were investigated by TIMER2 and Tumor Immune Single Cell Hub 2 databases and various packages in R. The findings demonstrated a significant up-regulation of ZC3H12D expression in HNSCC, while ZC3H12D expression was found to be associated with clinical parameters. Our study also demonstrated that ZC3H12D could act as a potential prognostic biomarker for HNSCC, especially oral squamous cell carcinoma. Additional analyses have shown that ZC3H12D was associated with common immune checkpoint genes and may be related to immune infiltration in HNSCC.

Bone fractures must undergo a complex healing process involving intricate cellular and molecular mechanisms. They require a suitable biological environment to restore skeletal stability and resolve inflammation. Scaffolds play a vital role in bone regeneration, thus reducing disease burden. Autologous bone graft represents the gold standard of therapy. However, its application is limited due to various reasons. Nanotechnology, in the form of nanomaterials and nano-drug delivery systems, has been proven to increase the potency of active substances in mimicking extracellular matrix (ECM), thereby providing physical support benefits and enhancing therapeutic effectiveness. Various materials, including protein, metal oxide, hydroxyapatite, and silica are modified with nanoparticle technology for the purposes of tissue regeneration therapy. Moreover, the properties of nanomaterials such as size, seta potential, and surface properties will affect their effectiveness in bone regeneration therapy. This review provides insights that deepen the knowledge of the manufacturing and application of nanomaterials as a therapeutic agent for bone regeneration.

Although correlated to peak oxygen uptake (VO2), the six-minute walk test (6MWT) alone cannot provide precise physiological insight regarding the specific cause(s) of exercise limitations. We aimed to analyze whether 6MWT is able to properly detect differences in the cardiorespiratory responses between patients with stable coronary artery disease (SCAD) and those with ischemic cardiomyopathy (IC) and determine whether the degree of abnormality in ejection fraction is related with impaired submaximal exercise capacity. Twenty-two subjects with SCAD and 19 subjects with IC underwent a 6MWT while simultaneously using a mobile telemetric cardiopulmonary monitor to assess cardiorespiratory responses. VO2 response at exercise onset was used to obtain VO2 on-kinetics, and the slope of ventilation vs carbon dioxide output (VE/VCO2) was calculated. IC subjects exhibited significantly delayed VO2 on-kinetics compared with the SCAD group (P<0.01) and higher VE/VCO2 slope (IC=40.45 [95%CI: 39.76 to 41.1] vs SCAD=34.36 [95%CI: 34.03 to 34.69], P=0.001). The left ventricular ejection fraction (LVEF) was moderately correlated with VO2 on-kinetics in the SCAD group, but no relationship was found in the IC group. Pulmonary function was correlated with the VE/VCO2 slope only in the IC group. Subjects with IC presented slower VO2 on-kinetics during the 6MWT than those with SCAD. Once reduction in left ventricular function is achieved, LVEF had no association with exercise capacity. Pulmonary function could help identify IC patients at risk of ventilatory inefficiency and may add diagnostic power to the 6MWT.

Hepatic ischemia reperfusion injury (HIRI) is a pathophysiological and complex systemic process involving multiple tissues and organs. Gastrodin (GSTD), a natural compound from Gastrodia elata, displays a variety of interesting pharmacological activities. Heme oxygenase-1 (HO-1), a stress-responsive protein, has a cytoprotective defense response against oxidative and inflammatory injuries. The aim of this investigation was to elucidate whether GSTD plays a protective role against HIRI by regulating HO-1 expression. GSTD (100 mg/kg) or zinc protoporphyrin (15 mg/kg; an HO-1 inhibitor) was administered to HIRI C57 male mice. GSTD decreased glutamic pyruvic transaminase and glutamic oxaloacetic transaminase levels in HIRI mice. Inflammatory (TNF-α and IL-6) and oxidative-stress (malondialdehyde, MDA) markers of HIRI mice were decreased by GSTD. GSTD up-regulated HO-1 protein and mRNA expression in HIRI mice but decreased caspase-3 and -9 protein expression. GSTD lowered mRNA expression of apoptosis-related genes (caspase-3, -9, -12, and Bax) in the liver of HIRI mice but enhanced mRNA level of the anti-apoptotic Bcl-2 gene. Consistent with in vivo results, GSTD displayed a similar regulatory effect on the expression of mRNA (HO-1, caspase-3, -9, -12, Bax, and Bcl-2) and protein (HO-1, caspase-3 and -9) as well as inflammatory (TNF-α and IL-6) and on oxidative stress factors (superoxide dismutase and MDA) in BRL-3A cells transfected with small interfering HO-1 RNA in a hypoxia-reperfusion model. In conclusion, GSTD up-regulated HO-1 expression to play a protective role in HIRI by anti-apoptotic, anti-inflammatory, and antioxidant effects. GSTD is a promising natural compound that alleviated HIRI in liver surgery.

Nasopharyngeal carcinoma (NPC) is a malignant tumor predominantly influenced by Epstein-Barr virus infection and genetic factors. The transforming growth factor-beta (TGF-β) superfamily is implicated in various cellular processes, including tumorigenesis. This study aimed to detect the role of one TGF-β superfamily member activin receptor type IIB (ACTRIIB) in NPC. This study analyzed NPC datasets, including GSE12452, GSE102349, and GSE53819. ACTRIIB expression and N-glycosylation levels were assessed by western blot, real-time PCR, immunofluorescence, and immunohistochemistry in NPC cells and tissues. As indicated by the datasets, ACTRIIB was significantly upregulated in NPC tissues, and the up-regulation was associated with poor prognosis. This study confirmed the N-glycosylation of ACTRIIB primarily at the forty-second amino acid, an asparagine. The N-glycosylation of ACTRIIB promoted the localization of ACTRIIB to the cell membrane and prevented the degradation of the protein by lysosomes, through which ACTRIIB activated the downstream Smard1/2 to promote tumor cell proliferation and invasion. Inhibition of N-glycosylation or knockdown of ACTRIIB resulted in reduced cell proliferation and invasion and increased the cell sensitivity to docetaxel. In conclusion, N-glycosylation of ACTRIIB was a critical post-translational modification that enhanced protein stability and induced membrane localization, which facilitates the functions of ACTRIIB in cell proliferation and invasion in NPC. Inhibition of ACTRIIB N-glycosylation could potentially serve as a therapeutic strategy to improve the efficacy of chemotherapy in NPC.