Brazilian Journal of Medical and Biological Research最新文献

The global prevalence of overweight status and obesity has increased considerably. Obesity is the common pathological basis of numerous diseases and a crucial triggering factor for diabetes. This study aimed to investigate the role of activating transcription factor 3 (ATF3) in the adipogenic process of adipocytes and the related compounds of Chinese medicine potentially targeting ATF3. The differentially expressed genes (DEGs) in high-fat diet (HFD) or overweight patients were identified by analyzing Gene Expression Omnibus (GEO) data profiles GSE112999, GSE112740, and GSE48964. qRT-PCR and western blot were conducted to detect the expression levels of related genes. Oil-red O staining was conducted to detect lipid droplet formation within 3T3-L1 adipocytes. Compounds that interacted with ATF3 were screened through the pharmacological database and analysis platform of the traditional Chinese medicine system. Furthermore, the eugenol effect on ATF3 expression was evaluated. ATF3 expression was increased in the adipose tissues of HFD mice and in clinically obese patients. Knock down of ATF3 promoted adipocyte lipid droplet formation, upregulated the protein levels of adipocyte markers (Fabp4 and PPARγ), elevated intracellular triglyceride (TG) levels, and activated the AKT signaling pathway. Eugenol effectively promoted ATF3 expression and inhibited adipocyte differentiation and adipogenesis. ATF3 expression was found to be elevated within the adipose tissues of overweight patients, whereas ATF3 knockdown promoted adipocyte differentiation and lipid accumulation by activating the PI3K/AKT signaling pathway. Therefore, ATF3 overexpression or supplementation with eugenol may be a potential method for overcoming obesity.

Myocardial ischemia-reperfusion injury (MIRI), a common secondary complication of cardiovascular diseases (CVDs), leads to significant psychological and physiological distress in patients. Pathophysiological reactions including inflammatory response, oxidative stress injury, platelet aggregation, vascular endothelial dysfunction, and programmed cell death are involved in the pathogenesis of MIRI. Prolonged use of conventional therapies (e.g., NSAIDs, calcium channel blockers, beta-blockers, and antiplatelet agents) may exacerbate cardiovascular damage due to adverse effects. Thus, identifying complementary and alternative therapies with better efficacy and safety profile is imperative. Unlike single-target pharmacological approaches, Salvia miltiorrhiza Bunge exhibits pleiotropic effects by modulating multiple pathways, including inflammation, oxidative stress, and vascular function. This review summarizes the protective mechanisms of Salvia miltiorrhiza against MIRI, highlighting its potential as a translational therapy for MIRI and guiding future preclinical studies.

Postinduction hypotension (PIH), a common complication of general anesthesia, occurs more frequently in hypertensive patients. This hypotensive state may induce hypoxia in vital organs, potentially progressing to organ dysfunction or even death. In this prospective cohort study, the primary outcome was incidence of PIH. The preanesthesia baseline parameters included demographic characteristics (age, sex, and body mass index [BMI]) and laboratory biomarkers (serum uric acid, hemoglobin, and lipoprotein levels). Noninvasive blood pressure was systematically monitored at five time points: preinduction (T0), postinduction (T1), immediately postintubation (T2), 5 min postintubation (T3), and 10 min postintubation (T4). This study involved 271 hypertensive patients with a median age (interquartile range) of 56.0 (17.0) years. The cohort comprised 134 males (49.4%) with a mean BMI of 23.8±2.94 kg/m2. PIH occurred in 165 patients (60.8%) following general anesthesia. Univariate logistic regression revealed potential associations between PIH and serum uric acid levels, advanced age, elevated baseline systolic blood pressure, grade 3 hypertension, fasting duration, and ASA class III status. Multivariate logistic regression suggested that serum uric acid may exert a protective effect, whereas grade 3 hypertension, age, and baseline systolic blood pressure emerged as risk modulators. Notably, a composite model incorporating age, baseline systolic blood pressure, hypertension severity, and serum uric acid level demonstrated enhanced predictive capacity (AUC=0.863 vs 0.712 for serum uric acid level alone, both P<0.01). Serum uric acid level demonstrated a moderate inverse correlation with PIH, whereas grade 3 hypertension, age, and baseline systolic blood pressure emerged as potential risk factors for PIH occurrence.

This research aimed to evaluate the impact of stress at the end of the pregnancy on bone health and body composition of Wistar rats after the breastfeeding period. The 90-day pregnant Wistar rats were divided into 2 groups (n=7/group): the stress group (SG) and the control group (CG). The stress protocol was carried out over 8 days, with 4 different types of stressor stimuli during the third week of pregnancy. Serum corticosterone, osteoprotegerin (OPG), nuclear factor kappa beta ligand (RANKL), calcium, and phosphorus were measured by an ELISA kit and body composition by the carcass technique. Bone mineral density, content, and area were measured in the femur by dual-energy X-ray absorptiometry, and the maximum force, breaking force, and elastic modulus were measured using a flexural test with a load cell (50 kgf). Results with P<0.05 were considered significant and data are reported as means±SD. Corticosterone was higher in SG (P=0.04), showing the effectiveness of the protocol, but no differences were observed in OPG, RANKL, calcium, phosphorus, and body composition. SG had lower bone mineral density (P=0.01) and lower maximum strength (P=0.04). Stress during the gestational period promoted deleterious effects on maternal bone health after the lactation period, shown by the reduction of bone mineral density and maximum strength, affecting bone quality; no difference was found in body composition.

There are no international or Chinese guidelines for the management of dry eye disease that develops after corneal refractive surgery. Sodium hyaluronate is the first-line therapy for dry eye diseases but is not sufficient to treat severe conditions. This study aimed to compare three-month outcomes following treatment of dry eyes after corneal refractive surgery with 3% diquafosol against those with 0.1% sodium hyaluronate. In a retrospective study, 118 patients were treated with 3% diquafosol sodium six times/day (DQS cohort, n=118 eyes) and 184 patients were treated with 0.1% sodium hyaluronate four times/day (SH cohort, n=184 eyes) for three months. Before treatments (BT), the ocular surface damage score was between 5 and 9 per eye, the ocular surface disease index was between 64 and 70% per eye, and the subjective symptom questionnaire score was between 13 and 19 per eye. Wet length of Schirmer's I strip test, ocular surface damage score, ocular surface disease index, and subjective symptom questionnaire scores improved in both cohorts after 3 months of treatments (AT) compared to BT conditions (P<0.01 for all comparisons). However, improvement was greater in the DQS cohort than in the SH cohort in the AT condition (P<0.01 for all comparisons). Blurred vision, ocular discomfort, and foreign body sensations were observed in a few cases. Dry eye disease is a common complication after corneal refractive surgery, and there is a lack of international guidelines addressing its management. Three percent diquafosol showed superior improvement of dry eye parameters post-refractive surgery than 0.1% sodium hyaluronate.

Pregnancy feto-maternal complications (PFMCs) contribute significantly to morbidity and mortality, with placental hypoxia as a key factor. Current methods for detecting fetal hypoxia are limited. This study aimed to evaluate the roles and biomarker potential of hypoxia-inducible factor (HIF)-1α, erythropoietin (EPO), and cell-free fetal hemoglobin (cf-HbF) in PFMCs. In a cross-sectional study, we quantitatively immunoassayed plasma levels of these biomarkers in 136 healthy pregnant women (age 29.618±5.19 years) and 118 women with complications (age 30.53±5.46 years) who had voluntarily consented and were enrolled sequentially and anonymously. Results indicated significantly higher biomarker levels in complicated pregnancies (P<0.001), with worsening trends for preeclampsia, ectopic pregnancy, abortion, gestational diabetes, and preterm labor with premature rupture of membranes. Only EPO levels showed pregnancy duration-dependent changes in healthy controls (encompassing 6 to 41 weeks; r=0.230, P=0.015). Strong correlations among the three biomarkers were found in both groups (r=0.402/P<0.001; r=0.724/P<0.001), with HIF-1α correlating with body mass index (BMI) in healthy controls (r=0.204/P=0.032). ROC analysis demonstrated high sensitivity and specificity in differentiating between groups (P<0.001), with cf-HbF showing the highest performance (AUC=0.923), followed by HIF-1α (AUC=0.882) and EPO (AUC=0.826). In conclusion, HIF-1α, EPO, and cf-HbF were associated with PFMCs and showed promising potential as biomarkers for distinguishing healthy from complicated pregnancies, with cf-HbF being the most significant. Their high levels also pointed to hypoxic adaptation dysfunction and/or resistance, as a pathogenic culprit.

Cutaneous melanoma, a lethal neoplasm originating from epidermal melanocytes, stands out for its resistance to conventional therapies and high metastatic rate. Given the urgent need for new therapeutic approaches, this study focuses on the antitumor potential of natural compounds derived from plants, recognized as primary sources of antineoplastic chemotherapeutics. In this systematic review, we selected studies that evaluated the efficacy of such compounds in vivo, using the murine melanoma B16 model. The research was registered at the International Platform of Registered Systematic Review and Meta-Analysis Protocols under the number INPLASY202490019 and conducted using the PubMed, Science Direct, Scopus, and Embase databases, following predefined eligibility criteria and standardized terms from the MeSH and DeCS databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and data were extracted using a Microsoft Excel® spreadsheet. Of the 361 identified studies, 33 were deemed eligible for analysis. Parameters such as routes of treatment administration and induction of melanoma, duration of treatment, and others were collected. The SYRCLE tool was used to identify methodological gaps, such as the absence or insufficient description of randomization and blinding. The results indicated that natural products, especially terpenes, flavonoids, phenolic compounds, quinones, fatty acids, and plant sterols, have considerable antimelanoma activity, with tumor inhibition above 70% and antimetastatic properties. These findings underscore the importance of investigating the potential of these plant compounds as antineoplastic agents and establishing standardized experimental protocols to increase the reliability of the results.

Breast cancer is the most frequent neoplasm and has the highest mortality rate among women. In the Afro-descendant population, these tumors may appear earlier and assume a more aggressive behavior. This study aimed to assess the epidemiological and clinical behavior of breast cancer in a predominantly Afro-descendant population, identify risk and prognostic factors, and compare them with already available data. Clinical and sociodemographic data were obtained from medical records and interviews with the patients involved. The variables ethnicity, age, number of children, monthly income, and education were used to describe the epidemiological profile and the results of clinical evaluation and pathological anatomy study. The immunohistochemical analysis was used to correlate the clinical characteristics of the tumors and prognosis. Afro-descendant women represented 77% of the population and the mean age at diagnosis was 54.4 years. Approximately 75% had up to 2 children, 20.5% had low income, and 37.3% had a low level of education. Infiltrating ductal carcinoma was diagnosed in 91% of patients, 70.2% had a moderate degree of differentiation, luminal subtype A was the most prevalent (39%), and a higher than global average percentage had a triple negative profile (22.9%). Early stages were identified in 53.4% of patients and only 4.8% were diagnosed with metastatic disease. The recurrence rate was 11.6%, and the mortality rate was 6.8%. The present study showed that unfavorable sociodemographic and clinical aspects, such as the high prevalence of triple-negative tumors, were not associated with a worse prognosis.

The aim of this study was to investigate the correlation between pre-stroke frailty status and post-stroke cognitive impairment (PSCI) in patients with acute large artery atherosclerotic cerebral infarction. One hundred and eight patients with acute large artery atherosclerotic cerebral infarction admitted in our hospital from July 2020 to July 2023 were prospectively enrolled. Patients were stratified into frailty (46 cases) and non-frailty groups (62 cases) based on FRAIL scale scores. During the 6-month follow-up after the onset of cerebral infarction, patients were evaluated using the Chinese modified version of Montreal Cognitive Assessment (MoCA) scale for cognitive function and were divided into PSCI (52 cases) and non-PSCI (56 cases) groups. The frailty group showed significantly higher age, prevalence of hypertension and diabetes comorbidities, smoking and alcohol consumption rates, National Institutes of Health Stroke Scale (NHISS) score, and Modified Rankin Scale (mRS) score than those in the non-frailty group (P<0.05, P<0.01). The incidence of PSCI in the frailty group was also significantly higher than that in the non-frailty group (78.3 vs 25.8%, P<0.01). Compared to the non-PSCI group, the PSCI group had higher age, shorter education duration, fewer cases of reperfusion therapy, and greater frailty (P<0.05, P<0.01). Logistic regression analysis showed that pre-stroke frailty was an independent risk factor for PSCI (P<0.01). Timely assessment of the frailty status in patients with acute large artery atherosclerotic cerebral infarction is beneficial for preventing, delaying onset, and reducing the incidence of PSCI.

Glioblastoma (GBM) is the most prevalent tumor in the central nervous system in adults. Lactotransferrin (LTF) is a molecule involved in the growth of various tumors. However, the underlying mechanism of LTF in GBM progression and chemotherapy resistance remains unclear. In this study, the clinical and diagnostic value of LTF were evaluated. In vitro and in vivo experiments were performed to explore the functional role of LTF in GBM. Immunoprecipitation and immunofluorescence assays were performed to clarify the effect of LTF on nuclear factor-κB (NF-κB) activation. LTF was overexpressed in GBM and correlated with poor prognosis. LTF promoted GBM cell proliferation, invasion, and temozolomide (TMZ) resistance. Mechanism assay results indicated that LTF competitively binds to p65, rescuing the inhibited effect of PP2A on p65 phosphorylation, thereby activating the NF-κB signaling pathway. Our results confirmed that highly expressed LTF promoted GBM progression and TMZ resistance through the NF-κB signaling pathway.