Brazilian Journal of Medical and Biological Research最新文献

Schistosomiasis remains a major global health concern, affecting approximately 260 million people, with 440 million experiencing morbidity and over 800 million at risk of infection. According to the World Health Organization (WHO), it ranks as the second most socioeconomically impactful infectious disease and the third most significant parasitic disease in terms of public health. This study aimed to improve immunodiagnostic tools for Schistosoma mansoni in resource-limited settings by developing monoclonal antibodies (MoAbs) using locally available materials. MoAbs were produced using hybridoma technology and assessed for specificity to soluble worm antigen preparation (SWAP) through ELISA. Immuno-phosphatase and immuno-peroxidase staining were employed to localize target antigens across various life cycle stages and assess cross-reactivity with related species. Four distinct MoAbs demonstrated strong phosphatase and peroxidase activity in the gut and tegumental tubercles of S. mansoni adult worms, with extreme (4+) phosphatase staining. The dorsal tubercles and oral/ventral suckers showed strong (3+) peroxidase staining. S. mansoni schistosomula showed positive staining in the oral sucker and penetration glands, while cercariae showed no reactivity. Cross-reactivity with S. haematobium was minimal, showing only weak (1+) peroxidase staining in gut and tegumental structures, as well as the intact worm's tegumental tubercles and suckers. In conclusion, the MoAbs developed exhibited high specificity for S. mansoni with limited cross-reactivity to S. haematobium, supporting their potential utility in locally produced, sensitive immunodiagnostic tools to strengthen schistosomiasis control and elimination efforts in endemic regions.

Biochanin A (BCA), a phytoestrogen with broad therapeutic potential, is a promising molecule for alleviating post-menopausal symptoms and treating disorders related to reproductive metabolism. Nevertheless, the effect of BCA on inflammatory changes caused by postmenopausal obesity is unclear. Thus, this study focused on investigating the impact of BCA on the adipose tissue and liver of ovariectomized (OVX) mice subjected to a high-fat diet (HFD). We found that BCA treatment reduced the crown-like structures (CLS), adipocyte area, and hypertrophic adipocyte distribution. This was accompanied by an increase in the anti-inflammatory cytokines interleukin (IL)-5 and IL-10 and the expression of Mrc1 (CD206), a marker for M2 macrophages. Furthermore, there was a reduction in the extent of hepatic steatosis, triglyceride content, and the expression of Nos2, the M1 marker. We concluded that BCA exerted an anti-inflammatory response in the tissues, promoting a resolving profile, although the metabolic profile of the animals was not altered. This study was the first to demonstrate the anti-inflammatory effect of BCA in ovariectomized animals with established obesity.

Colorectal cancer (CRC) is the fourth-leading cause of cancer-related mortality worldwide. Semaphorin 6A (SEMA6A) is a member of the semaphorin family, and its specific biological function in CRC progression remains unclear. Bioinformatics analysis revealed that SEMA6A expression was downregulated in CRC tissues and that low expression of SEMA6A was associated with a poor prognosis. Compared with those in normal colorectal epithelial cells, SEMA6A expression levels were lower in CRC cell lines. CACO2 and SW48 cells were chosen to construct stable SEMA6A-knockdown and SEMA6A-overexpressing cell lines. SEMA6A knockdown promoted CACO2 proliferation. Conversely, SEMA6A overexpression inhibited the proliferation and promoted the apoptosis of SW48 cells. Transwell and wound healing assays demonstrated that SEMA6A overexpression inhibited the invasion and migration ability of SW48 cells. SEMA6A overexpression might impede CRC cell migration and invasion by inhibiting the epithelial-to-mesenchymal transition, as evidenced by the downregulation of N-cadherin expression and the upregulation of E-cadherin expression in SW48 cells. To further validate the role of SEMA6A in CRC progression in vivo, transplanted tumor and liver metastasis mouse models were constructed in nude mice by injecting stable SEMA6A-overexpressing SW48 cell lines. SEMA6A overexpression inhibited tumor growth in SW48 tumor-bearing mice and the expression of Ki-67 in tumor tissues. In addition, SEMA6A overexpression resulted in a marked decrease in liver metastasis of CRC cells, with decreased numbers of hepatic metastatic nodules and infiltration of cancer cells. In summary, SEMA6A overexpression alleviated CRC progression by inhibiting tumor growth and metastasis both in vivo and in vitro.

The 2017 US guidelines for the prevention, detection, evaluation, and management of high blood pressure in adults proposed the diagnosis of hypertension at 130/80 mmHg, while the European Society of Cardiology and 2020 Brazilian Guidelines of Hypertension maintain the 140/90 mmHg cut-off. We aimed to evaluate how the cut-off established by the American Heart Association guidelines would impact the prevalence of hypertension in the ELSA-Brasil cohort and compare the clinical characteristics among these subgroups. The participants were part of the ongoing ELSA-Brasil multicenter cohort, with baseline data collected between 2008 and 2010, consisting of 15,105 public servants of both sexes aged 35 to 74 years. Hypertension (≥140 or ≥90 mmHg or use of antihypertensive drugs in the last two weeks if below these values) prevalence was 36.2% (95%CI: 35.4-36.9, n=5,456) with the Brazilian cut-off and 51.4% (95%CI: 50.6-52.1, n=7,756) when considering the US cut-off (SBP≥130 or DBP≥80 mmHg). In general, those with high blood pressure (HBP) presented an intermediate-risk profile compared to the hypertension group. Lowering the hypertension cut-off caused an absolute increase of 15.2% in the prevalence of hypertension in the sample of public servants studied. HBP individuals showed intermediate-risk profile between normal blood pressure and hypertension and represented a large fraction of the population who may benefit from treatment.

Delirium is a common complication in intensive care units (ICU). The PRE-DELIRIC model has shown promise in early delirium prediction, but its performance in Chinese ICU settings remains unclear. The objective of this study was to validate the PRE-DELIRIC model in a Chinese mixed medical-surgical ICU and evaluate its utility in guiding nursing interventions for delirium prevention. In this single-center retrospective cohort study, adult patients admitted to the ICU between January 2023 and October 2024 were included. The PRE-DELIRIC score was calculated within 24 h of admission. Delirium was assessed using Confusion Assessment Method for the ICU (CAM-ICU) every 8 h. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUROC). Among 580 patients, 176 (30.4%) developed delirium. The model showed good discrimination (AUROC 0.84; 95%CI: 0.81-0.87) and calibration (Hosmer-Lemeshow χ2=8.96, P=0.34). At the optimal cut-off point of 30%, sensitivity was 81.8% and specificity 78.2%, with 90.8% negative predictive value. Performance remained consistent across surgical (AUROC 0.84), medical (AUROC 0.86), and trauma patients (AUROC 0.85). Delirious patients had longer ICU stays (median 11.2 vs 7.1 days, P<0.001) and higher mortality (15.9 vs 10.4%, P=0.028). The PRE-DELIRIC model demonstrated reliable predictive performance in Chinese ICU settings. Integration into routine nursing assessment could guide individualized preventive interventions and optimize resource utilization.

Diabetic osteoporosis (DOP) is a complication of prolonged hyperglycemia. Hydrogen sulfide (H2S) has been identified as a protective factor in bone development. However, the mechanism by which H2S antagonizes the effects of high glucose (HG) on osteoblasts remains unclear. The effects of HG and H2S on osteoblasts were assessed through transcriptomic and metabolomic sequencing to identify key changes in gene expression and metabolism. Reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), alkaline phosphatase (ALP) activity, mineralization, iron ion levels, malondialdehyde (MDA) levels, cell proliferation, and protein expression were evaluated. Transcriptomic analysis revealed significant upregulation of the ferroptosis pathway in HG-treated osteoblasts. Fer-1 and H2S antagonized the HG-induced decrease in osteoblast cell proliferation, increase in ROS production, decrease in MMP, decrease in ALP, decrease in mineralized nodules, and increase in iron ions and MDA. Transcriptome analysis showed Fer-1 was involved in upregulating the synthesis, secretion, and action of parathyroid hormone and estrogen synthesis, while downregulating the mitogen-activated protein kinases (MAPK) pathway. Metabolomic analysis showed H2S restored glutathione metabolism, reducing pyroglutamic acid and L-5-oxoproline levels. Transcriptome sequencing identified downregulated genes (hmox1, ncoa4) and an upregulated gene (slc40a1) related to ferroptosis in the H2S + HG group compared with the HG group. Western blot analysis indicated H2S increased GPX4 and SLC7A11 levels while reducing ACSL4 expression compared with the HG group. Ferroptosis may be involved in the pathogenesis of DOP and H2S can effectively alleviate osteoblast injury by inhibiting ferroptosis in DOP.

This study aimed to investigate the impact of targeted nursing care combined with nutritional support on the clinical outcomes of diabetic nephropathy (DN) patients undergoing maintenance hemodialysis (HD). Clinical indicators such as serum creatinine (SCr), blood urea nitrogen (BUN), fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and K (urea clearance) × t (dialysis time) / V (volume of urea distribution) (Kt/V), as well as inflammatory indicators such as high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, and tumor necrosis factor-α (TNF-α), and nutritional indicators such as transferrin (TRF), albumin (ALB), and prealbumin (PA) were measured. SF-36 quality of life scale scores were assessed, and adverse events and patient satisfaction with care were recorded. Post-intervention, the experimental group exhibited lower SCr, BUN, FBG, HbA1c, hs-CRP, IL-6, and TNF-α, and higher body mass index, Kt/V, TRF, ALB, and PA than the control group (all P<0.05). Additionally, the experimental group demonstrated higher nursing satisfaction scores, and lower total incidence of adverse events compared to the control group (all P<0.05). Targeted nursing care combined with nutritional support applied to DN patients during HD helped improve residual renal function, reduce the body's inflammatory response, improve nutritional status and the quality of life, reduce adverse events, and at the same time, improve nursing satisfaction.

After SARS-CoV-2 infection, severe COVID-19 may develop with persistent sequelae, even after hospital discharge. This condition may result from tissue damage or immune alterations caused by the virus, including immune dysregulation, hyperinflammation, loss of immune tolerance, excessive neutrophil extracellular trap (NET) production, and antibody cross-reactivity (molecular mimicry), which can promote autoantibody development. This study evaluated autoantibody expression in patients with long COVID-19 and its potential relationship with symptoms. Conducted in Baixada Santista, São Paulo, Brazil, the study involved 55 participants aged 21-85 years who had tested positive for SARS-CoV-2. Blood samples were collected two years post-discharge, and serum was analyzed for inflammatory and autoimmune markers, including antinuclear antibody (ANA), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), procalcitonin (PCT), Venereal Disease Research Laboratory test (VDRL), and C-reactive protein (CRP). Results were compared to a control group of 21 individuals who never tested positive for COVID-19. Among severe COVID-19 patients, 26 reacted to ANA, 16 to VDRL, 2 had elevated RF, 12 had increased PCT, and 11 had high CRP, whereas the control group showed no reactive results. Anti-CCP values were not significant. Findings suggest that hyperinflammation may contribute to autoimmunity, particularly in cases of reactive ANA levels, linking COVID-19 symptoms to autoimmune responses.

A hallmark of COVID-19 patients is the reduction of the lymphocyte population accompanied by activation, senescence, and exhaustion markers. We investigated patients admitted to hospital wards who either recovered after a short hospitalization or progressed to critical illness. Patients (n=48) were recruited between May and September 2020; 19 healthy volunteers were enrolled as controls. Blood samples were collected on days 0, 3, and 7 of hospitalization and around 30 days after discharge (convalescence sample, CS30). Lymphocyte counts and extended immunophenotyping were performed by flow cytometry and analyzed using conventional and stochastic methods. At D0 and D7, total lymphocytes, natural killer cells, T cells, TCD4 cells, and TCD8 cells were lower in patients than in volunteers but were restored at CS30. The stochastic analysis identified 11 distinct clusters of lymphocytes, nine of them with significant differences between patients and healthy controls. Clusters of TCD8+ memory cells showing activation, senescence, and exhaustion were increased in patients during hospitalization and in the convalescence samples. In contrast, clusters 5 (TCD4+ Central Memory exhausted activated) and 7 (TCD4+ Central Memory exhausted) were decreased in patients during the disease compared to healthy controls. Overall, the conventional flow cytometry analyses corroborated the findings from the stochastic analysis, showing that effector memory (EM) and TEMRA subsets exhibited sustained markers of exhaustion and senescence, particularly in TCD8+ cells. Our findings reinforce lymphopenia, T cell activation, senescence, and exhaustion as essential immunological features of COVID-19; while cell counts fully recovered, lymphocytes remained dysfunctional in convalescent samples.

Sacha inchi oil (SIO) is characterized by its high content of polyunsaturated fatty acids (PUFAs), metabolites with beneficial properties on health. The objective was to evaluate the fatty acid (FA) profile of wild SIO and its effect on biochemical parameters of lipid metabolism under a high-fat diet. Twenty-four albino rats were grouped into groups I, II, III, and IV, which ingested ad libitum the following diets: conventional diet without supplementation (CDOS), conventional diet supplemented with SIO (CDWS), hyperlipidic diet without supplementation (HDOS), and hyperlipidic diet supplemented with SIO (HDWS) for 6 weeks. The FA content of SIO was assessed by gas chromatography-mass spectrometry. The lipid profile was analyzed by the enzymatic-spectrophotometric method, and cytokines and lipid mediator levels were measured via enzyme-linked immunosorbent assay (ELISA). Α-linolenic acid (ALA) and linoleic acid (LA) constitute 82% of this oil. Two-way ANOVA showed interaction effects between diet and supplement on interleukin (IL)-10 levels, and SIO-supplemented diet significantly decreased triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-C), and the TG/HDL-C ratio levels. Wild SIO is high in ALA and LA. SIO supplementation reduced TG, VLDL-C, and the TG/HDL-C ratio, modulated IL-10, and slightly improved leptin, resolvin-D1 (RvD1), and IL-6 levels.