Resumo em Inglês:

Chronic kidney disease (CKD) is one of the main chronic diseases affecting the world population due to its high prevalence and increasing morbidity. Similarly, obesity gained the interest of the scientific community as it directly or indirectly increases mortality from cardiovascular causes, and its prevalence characterizes a pandemic. The objective of this study was to investigate obesity measured by body mass index as a predictor for end-stage renal disease in the general adult population. A systematic review and meta-analysis was carried out by searching 10 databases for prospective or retrospective cohort studies, with no restrictions on the language of publication, including adults with obesity without previous renal disease and who evolved to CKD (diagnosed by estimated glomerular filtration rate below 60 mL&mac_middot;min-1&mac_middot;(1.73 m2)-1 over the follow-up period. The R software and Meta package were used for data analysis. After removing duplicates, 5431 studies were submitted to the steps of the systematic review, and 21 articles were included in the data analysis. In total, 3,504,303 patients, 521,216 with obesity, and an average follow-up time of 9.86 years were included. The relative risk of obese people for developing CKD in the random effects model was 1.81 (95%CI: 1.52-2.16). The evidence found in this meta-analysis confirmed that obese people are at higher risk of developing CKD that the non-obese population (1.81 times higher), with obesity being a priority risk factor in preventive actions.

Resumo em Inglês:

Vascular invasion and systemic immune-inflammation index (SII) are risk factors for the prognosis of patients with hepatocellular carcinoma. At present, the correlation between the two is not clear. This meta-analysis explored the relationship between preoperative SII and vascular invasion in patients with hepatocellular carcinoma. According to the search formula, the Pubmed, Embase, Cochrane, Web of Science, and CNKI databases were searched for the relevant research until March 2020. After the quality evaluation of the included literature, the odds ratio (OR) and its corresponding 95% confidence interval (CI) were used as the effect measure. Stata 15. 0 software was used for statistical analysis. The meta-analysis eventually included seven retrospective cohort studies of 3583 patients with hepatocellular carcinoma. The results showed that the choice of SII cut-off value affects SII's efficiency in predicting the risk of vascular invasion. In the cohort of studies with appropriate SII cut-off value, the high SII preoperative group had a higher risk of vascular invasion (OR=2.62; 95%CI: 2.07-3.32; P=0.000) and microvascular invasion (OR=1.82; 95%CI: 1.01-3.25; P=0.045) than the low SII group. The tumor diameter (OR=2.88; 95%CI: 1.73-4. 80; P=0.000) of the high SII group was larger than that of the low SII group. There was no publication bias in this study (Begg's test, P=0.368). As a routine, cheap, and easily available index, SII can provide a certain reference value for clinicians to evaluate vascular invasion before operation.

Resumo em Inglês:

Sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) and sarcolemmal Na+/Ca2+ exchanger (NCX1) structures are involved in heart cell Ca2+ homeostasis. Previous studies have shown discrepancies in their function and expression in heart failure. The goal of this study was to evaluate heart function and hypertrophied muscle Ca2+-handling protein behavior under pressure overload. Twenty male Wistar rats were divided into two groups: Aortic stenosis (AoS), induced by a clip placed at the beginning of the aorta, and Control (Sham). After 18 weeks, heart function and structure were evaluated by echocardiogram. Myocardial function was analyzed by isolated papillary muscle (IPM) at basal condition and Ca2+ protein functions were evaluated after post-pause contraction and blockage with cyclopiazonic acid in IPM. Ca2+-handling protein expression was studied by western blot (WB). Echocardiogram showed that AoS caused concentric hypertrophy with enhanced ejection fraction and diastolic dysfunction inferred by dilated left atrium and increased relative wall thickness. IPM study showed developed tension was the same in both groups. AoS showed increased stiffness revealed by enhanced resting tension, and changes in Ca2+ homeostasis shown by calcium elevation and SERCA2a blockage maneuvers. WB revealed decreased NCX1, SERCA2a, and phosphorylated phospholambam (PLB) on serine-16 in AoS. AoS had left ventricular hypertrophy and diastolic dysfunction compared to Sham; this could be related to our findings regarding calcium homeostasis behavior: deficit in NCX1, SERCA2a, and phosphorylated PLB on serine-16.

Resumo em Inglês:

An increasing number of elderly people in renal support is expected in the coming years. The objective of this study was to report the clinical and socio-demographic data of end-stage renal disease (ESRD) adult patients undergoing regular dialysis treatment comparing elderly (≥65 years old) and non-elderly subjects using data from the Brazilian Dialysis Registry database. The regional distribution of the sample was Southeast (48.8%), South (33.7), Northeast (13.1%), Midwest (5.1%), and North (0.1%). A total of 18,030 patients were included in the analysis with elderly patients accounting for 29.5% of the sample. The elderly patients were predominantly male, white, retired, and literate. Elderly ESRD patients had a slightly higher frequency of undernourishment and a lower frequency of obesity than the non-elderly adults. A higher frequency of elderly patients were from the South and Southeast regions. The dialysis treatment of patients from both groups was predominantly funded by the public system, but the percent of non-public funding was higher for the elderly group. The most used initial access in the elderly was the central venous catheter and hemodialysis was the main modality at the beginning of treatment (93.2%), as well as during maintenance therapy (91.8%). Advanced age was associated with greater use of central venous catheter in the first dialysis session. The survival of the elderly on dialysis was lower than that of the non-elderly early in the course of dialysis and this difference increased over time. This is yet the largest national epidemiological study of elderly people on chronic dialysis.

Resumo em Inglês:

The novel Coronavirus disease (COVID-19) is responsible for thousands of deaths worldwide, especially in Brazil, currently one of the leading countries in number of infections and deaths. The beginning of the COVID-19 epidemic in Brazil is uncertain due to the low number of tests done in the country. The excess number of deaths can suggest the beginning of the pandemic in this context. In this article, we used an autoregressive integrated moving average (ARIMA) model to investigate possible excesses in the number of deaths processed by the São Paulo Autopsy Service according to different causes of deaths: all-cause, cardiovascular, and pulmonary causes. We calculated the expected number of deaths using data from 2019 to 2020 (n=17,011), and investigated different seasonal patterns using harmonic dynamic regression with Fourier terms with residuals modeled by an ARIMA method. We did not find any abnormalities in the predicted number of deaths and the real values in the first months of 2020. We found an increase in the number of deaths only by March 20, 2020, right after the first COVID-19 confirmed case in the city of São Paulo, which occurred on March 16, 2020.

Resumo em Inglês:

The main movements of artistic swimming demand various physical capacities such as flexibility, strength, power, and muscular endurance. The use of ergogenic resources to potentialize performance in this sport, however, is underexplored and deserves investigation. In the present study, we tested whether caffeine ingestion would improve the execution of movements that are essential in a typical figure competition or routines in artistic swimming (i.e., amplitude in the Ariana, height in the Boost and Barracuda, and time maintained in the Stationary Scull techniques). Sixteen experienced female athlete artistic swimmers (17.4±3.2 years of age, 5.6±2.8 years of artistic swimming practice) performed several movements of artistic swimming after having ingested a capsule containing caffeine (5 mg/kg body mass) or cellulose (placebo). Compared to the placebo, caffeine improved latero-lateral amplitude during the Ariana (P=0.035), the height of the Boost and Barracuda (P=0.028 and 0.009), and maintained duration in Stationary Sculling (P=0.012). Bayes factor analysis, however, indicated substantial evidence of a positive effect of caffeine only on the Barracuda and Stationary Scull techniques. These findings indicated that caffeine improved performance during specific artistic swimming movements. Coaches and athletes should consider caffeine ingestion in their supplementation plans.

Resumo em Inglês:

Osteoarthritis (OA) is a chronic health condition. MicroRNAs (miRs) are critical in chondrocyte apoptosis in OA. We aimed to investigate the mechanism of miR-130b in OA progression. Bone marrow mesenchymal stem cells (BMSCs) and chondrocytes were first extracted. Chondrogenic differentiation of BMSCs was carried out and verified. Chondrocytes were stimulated with interleukin (IL)-1β to imitate OA condition in vitro. The effect of miR-130b on the viability, inflammation, apoptosis, and extracellular matrix of OA chondrocytes was studied. The target gene of miR-130b was predicted and verified. Rescue experiments were performed to further study the underlying downstream mechanism of miR-130b in OA. miR-130b first increased and drastically reduced during chondrogenic differentiation of BMSCs and in OA chondrocytes, respectively, while IL-1β stimulation resulted in increased miR-130b expression in chondrocytes. miR-130b inhibitor promoted chondrogenic differentiation of BMSCs and chondrocyte growth and inhibited the levels of inflammatory factors. miR-130b targeted SOX9. Overexpression of SOX9 facilitated BMSC chondrogenic differentiation and chondrocyte growth, while siRNA-SOX9 contributed to the opposite trends. Silencing of SOX9 significantly attenuated the pro-chondrogenic effects of miR-130b inhibitor on BMSCs. Overall, miR-130b inhibitor induced chondrogenic differentiation of BMSCs and chondrocyte growth by targeting SOX9.

Resumo em Inglês:

This study aimed to investigate the effect of WeChat-based education and rehabilitation program (WERP) on anxiety, depression, health-related quality of life (HRQoL), major adverse cardiac/cerebrovascular events (MACCE)-free survival, and loss to follow-up rate in unprotected left main coronary artery disease (ULMCAD) patients after coronary artery bypass grafting (CABG). In this randomized controlled study, 140 ULMCAD patients who underwent CABG were randomly assigned to WERP group (n=70) or control care (CC) group (n=70). During the 12-month intervention period, anxiety and depression (using hospital anxiety and depression scale (HADS)) and HRQoL (using 12-Item Short-Form Health Survey (SF-12)) were assessed longitudinally. During the total 36-month follow-up period (12-month intervention and 24-month non-intervention periods), MACCE and loss to follow-up were recorded. During the intervention period, HADS-anxiety score at month 9 (M9) (P=0.047) and month 12 (M12) (P=0.034), anxiety rate at M12 (P=0.028), and HADS-D score at M12 (P=0.048) were all reduced in WERP group compared with CC group. As for HRQoL, SF-12 physical component summary score at M9 (P=0.020) and M12 (P=0.010) and SF-12 mental component summary score at M9 (P=0.040) and M12 (P=0.028) were all increased in WERP group compared with CC group. During the total follow-up period, WERP group displayed a trend of longer MACCE-free survival than that in CC group but without statistical significance (P=0.195). Additionally, loss to follow-up rate was attenuated in WERP group compared with CC group (P=0.033). WERP serves as an effective approach in optimizing mental health care and promoting life quality in ULMCAD patients after CABG.

Resumo em Inglês:

Naringenin (NAR) is a major flavanone in citrus fruits that has multiple pharmacological attributes such as anticancer and antiatherogenic. This study aims to investigate the mechanism of NAR in high-fat-diet (HFD)-induced atherosclerosis (AS) in apolipoprotein E-knockout (ApoE-/-) mice. A HFD-induced AS ApoE-/- mouse model was established. The mice were treated with HFD, different doses of NAR and simvastatin (Simv). After drug treatment, the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), superoxide dismutase (SOD), and alanine aminotransferase (ALT) were determined. The expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was detected using qRT-PCR and enzyme-linked immunosorbent assay. The plaque area of the aorta of AS mice was determined using oil red O staining. Western blot analysis was applied to measure the levels of autophagy-related proteins [protein 1 light chain 3B (LC3B), beclin 1, and p62]. The TC, TG, LDL-C, TNF-α, ALT, and MDA levels were significantly increased while the HDL-C, SOD, and GSH-Px levels were decreased in the HFD-induced AS ApoE-/- mice. NAR treatment reversed the expression of the above indicators in mice. After they were treated with different doses of NAR, the LC3B and beclin 1 levels were improved while the p62 protein level was decreased. This study suggested that NAR could promote cell autophagy to improve HFD-induced AS in ApoE-/- mice.

Resumo em Inglês:

It is known that neuronal apoptosis contributes to pathology of cerebral ischemia injury. Zonisamide (ZNS) has shown anti-apoptosis effects in recent studies. The present study investigated whether the anti-apoptotic effect can account for the neuroprotective action of ZNS on cerebral ischemia. Neuronal cells were maintained under oxygen-glucose deprivation conditions to simulate cerebral ischemia and treated with ZNS simultaneously. The apoptosis of the cells and expression of apoptosis-related proteins were investigated by flow cytometry and western blot analysis, respectively. A cerebral ischemia mouse model was created via middle cerebral artery occlusion, and the mice were treated with ZNS. Neurological deficit scores and infarct volumes of the cerebral ischemia mice were measured. The apoptosis status of the neuronal cells was evaluated by TUNEL staining. In vitro, the ZNS treatment inhibited both the apoptosis of the neuronal cells and apoptosis-related protein expression (caspase-3, caspase-8, and calpain-1) induced by the oxygen-glucose deprivation. The anti-apoptosis effect of ZNS could occur through the blocking of reactive oxygen species. Moreover, ZNS treatment significantly ameliorated neurological deficits and reduced infarct volumes in the cerebral ischemia mice model. In this study, ZNS exerted neuroprotective effects by inhibition of apoptosis in neuronal cells in cerebral ischemia. Therefore, ZNS might be a promising therapy for cerebral ischemia.

Resumo em Inglês:

Respiratory syncytial virus (RSV) infection is the main cause of lower respiratory tract infection in children. However, there is no effective treatment for RSV infection. Here, we aimed to identify potential biomarkers to aid in the treatment of RSV infection. Children in the acute and convalescence phases of RSV infection were recruited and proteomic analysis was performed to identify differentially expressed proteins (DEPs). Subsequently, promising candidate proteins were determined by functional enrichment and protein-protein interaction network analysis, and underwent further validation by western blot both in clinical and mouse model samples. Among the 79 DEPs identified in RSV patient samples, 4 proteins (BPGM, TPI1, PRDX2, and CFL1) were confirmed to be significantly upregulated during RSV infection. Functional analysis showed that BPGM and TPI1 were mainly involved in glycolysis, indicating an association between RSV infection and the glycolysis metabolic pathway. Our findings provide insights into the proteomic profile during RSV infection and indicated that BPGM, TPI1, PRDX2, and CFL1 may be potential therapeutic biomarkers or targets for the treatment of RSV infection.

Resumo em Inglês:

The long noncoding RNA (lncRNA) H19 is involved in the pathogenesis of endometriosis by modulating the proliferation and invasion of ectopic endometrial cells in vitro, but related in vivo studies are rare. This study aimed to investigate the role of lncRNA H19 in a nude mouse model of endometriosis. Ectopic endometrial stromal cells (ecESCs) were isolated from ectopic endometrium of patients with endometriosis and infected with lentiviruses expressing short hairpin RNA (shRNA) negative control (LV-NC-shRNA) or lncRNA-H19 shRNA (LV-H19-shRNA). The ecESCs infected with LV-NC-shRNA and LV-H19-shRNA were subcutaneously implanted into forty 6- to 8-week-old female nude mice. The size and weight of the endometriotic implants were measured at 1, 2, 3, and 4 weeks after implantation and compared, and lncRNA H19 levels in endometriotic implants were evaluated using real-time polymerase chain reaction (RT-PCR). All nude mice survived the experimental period, and no significant differences in body weight were observed between the experimental group and the control group. All nude mice developed histologically confirmed subcutaneous endometriotic lesions with glandular structures and stroma after 1 week of implantation. The subcutaneous lesions in the LV-NC-shRNA group after 1, 2, 3, and 4 weeks of implantation were larger than those in the LV-H19-shRNA group, and lncRNA H19 levels in subcutaneous lesions in the LV-NC-shRNA group were significantly higher than those in the LV-H19-shRNA group. Knockdown of lncRNA H19 suppresses endometriosis in vivo. Further study is required to explore the underlying mechanism in the future.

Resumo em Inglês:

Tacrolimus (TAC), a calcineurin inhibitor, and everolimus (EVL), an mTOR inhibitor, have been used as immunosuppressive (ISS) drugs in post-kidney transplantation therapy. The objective of this study was to compare the efficacy of EVL vs TAC in the ISS maintenance triple therapy. Ninety-seven kidney transplant patients, who received triple maintenance therapy with TAC, mycophenolate mofetil (MMF), and methyl prednisone (PRED), were evaluated. After four months of post-kidney transplant therapy, 30 patients enrolled in a randomized controlled clinical trial, in which 16 patients received TAC+MMF+PRED (cohort 1), and 14 patients switched to EVL+MMF+PRED (cohort 2). The patients were followed-up for 36 months. Two patients from cohort 1 lost their grafts after one year due to non-adherence. Two patients from cohort 2 had intolerance to mTOR inhibitors and were switched back to TAC from EVL. One case (6.25%) in cohort 1 and three cases (21.43%) in cohort 2 of acute T-cell-mediated rejection was observed. Antibody-mediated acute rejection (ABMAR) was observed in four patients (25.0%) in cohort 1, and antibody-mediated chronic rejection (ABMCR) was observed in two patients (12.50%). One patient from cohort 2 lost the graft after 15 months due to polyomavirus infection. The graft survival rate was 87.50% in cohort 1 and 92.86% in cohort 2. This clinical trial showed that the EVL+MMF+PRED triple maintenance therapy was efficacious compared with TAC during 32 months of follow-up. However, further studies are needed to confirm the efficacy of this regimen for long-term graft survival.

Resumo em Inglês:

Fibrosis caused by the increase in extracellular matrix in cardiac fibroblasts plays an important role in the occurrence and development of atrial fibrillation (AF). The aim of this study was to investigate the role of hsa-miR-4443 in AF, human cardiac fibroblast (HCFB) proliferation, and extracellular matrix remodeling. TaqMan Stem-loop miRNA assay was used to measure hsa-miR-4443 expression in patients with persistent AF (n=123) and healthy controls (n=100). Patients with AF were confirmed to have atrial fibrosis by late gadolinium enhancement. At the cellular level, after hsa-miR-4443 mimic and inhibitor were transfected with HCFBs, proliferation, apoptosis, migration, and invasion were analyzed. Lastly, hsa-miR-4443-targeted gene and transforming growth factor (TGF)-β1/α-SMA/collagen pathway were evaluated by dual-luciferase reporter assay and western blot, respectively. In patients with AF, hsa-miR-4443 decreased significantly and collagen metabolism level increased significantly. Logistic regression analysis showed that low hsa-miR-4443 level was a risk factor of AF (P<0.001). The receiver operating characteristic curve revealed that hsa-miR-4443 was useful for predicting AF (area under the curve: 0.828, sensitivity: 0.71, specificity: 0.78, P<0.001). In HCFBs, hsa-miR-4443 targeted thrombospondin-1 (THBS1) and downregulated TGF-β1/α-SMA/collagen pathway. The inhibition of hsa-miR-4443 expression promoted HCFB proliferation, migration, invasion, myofibroblast differentiation, and collagen production. The significant reduction of hsa-miR-4443 can be used as a biomarker for AF. hsa-miR-4443 protected AF by targeting THBS1 and regulated TGF-β1/α-SMA/collagen pathway to inhibit HCFB proliferation and collagen synthesis.