Brazilian Journal of Medical and Biological Research最新文献

Malaria is a parasitic disease of great relevance in global public health. The development of new sensitive and specific diagnostic high-throughput methods remains a challenge in the eradication of this disease. In this study, we developed a flow cytometry test using latex microbeads and polyclonal antibodies obtained from rabbits and mice for the detection of the P. vivax lactate dehydrogenase (PvLDH) antigen. We processed 50 samples from Brazilian patients diagnosed with malaria caused by P. vivax and 40 samples from healthy individuals. The assay presented sensitivity of 64%, specificity of 97%, a positive predictive value of 97%, and a negative predictive value of 57% when analyzed using the fluorescent labeling method. Using the mean fluorescence intensity (MFI) analysis method, the sensitivity was 53%, specificity was 89%, the positive predictive value was 95%, and the negative predictive value was 33%. In both methods of analysis, we observed significant statistical differences between the analyzed groups (P-value <0.0001). A high correlation (0.60) between the two methods and a low correlation between PvLDH concentration and parasite density was found. The test was able to detect the PvLDH protein with high specificity, but its sensitivity should be improved. More promising results were observed when the samples were analyzed according to the percentage of fluorescent labeling. Improvement of this assay would enable its application as a serological test for the detection of asymptomatic patients and for the validation of rapid diagnostic tests.

The aim of the present study was to describe the use of tapering, carbohydrate (CHO) supercompensation, and supplementation strategies self-reported by athletes in the Olympic triathlon category. A total of 72 triathletes (61 males and 11 females) answered an online questionnaire about their training and performance, supercompensation strategies, carbohydrate supplementation, and use of supplements and other ergogenic substances. The information was summarized and subjected to descriptive analysis. Shapiro-Wilk test was applied to check data normality. The t-test was used to investigate differences in the analyzed variables between sexes. Almost all triathletes reported to have performed tapering (93.05%) and approximately half of them adopted a CHO supercompensation strategy (48.61%); updated CHO supercompensation was the most used strategy (27.77%). Most participants (86.11%) used CHO supplementation during competitions, but in amounts below the 60 g/h recommended for most athletes (96.77%). Thus, since few triathletes performed supercompensation, in addition to the insufficient amount of supplemented carbohydrate taken by them, it could be concluded that triathletes were not sufficiently aware of nutritional recommendations or did not adopt them.

Osteosarcoma (OS) remains the most common bone tumor and the prognosis for many patients remains stagnant due to the unsatisfactory therapeutic effect of conventional treatment regimens. This research explored the effect and mechanism of a novel natural product, Eriocalyxin B (EB), in pathogenesis and immunotherapy in OS. Cell Count Kit 8 assay, colony formation assay, and wound healing assay were employed to detect the proliferative, colony-forming, and migratory abilities of human OS cells following EB treatment. Moreover, xenograft growth assay was performed to assess the effect of EB on OS in vivo. Subcutaneous OS models constructed in immunocompetent mice were employed to evaluate the effect of EB treatment in combination with immune checkpoint blockades (ICBs) PD1ab and CTLA4ab. Immunohistochemistry (IHC) staining was utilized to detect the level of CD8+ T cells infiltration and Ki67 expression. TARGET database, RNA interference technology, and qPCR assay were employed to explore the mechanism of EB on OS. EB inhibited the proliferative, colony-forming, and migratory abilities of the human OS cells MG63 and U2OS both in vitro and in vivo. TARGET data analysis demonstrated that up-regulation of TCEA3 was significantly negatively correlated with overall survival in OS patients. EB exerted anti-tumor activity via downregulation of TCEA3. EB, in conjunction with ICBs, synergistically optimized anti-tumorigenic activity against OS in immunocompetent mice. EB may promote infiltration of CD8+ T cells and down-regulate Ki67 expression. These results signaled that EB may have a role as a candidate therapeutic or preventive agent for the treatment of OS.

Frailty is a significant risk factor for adverse outcomes in elderly surgical patients. Gait speed assessment is a new tool recently used to stratify risk for these pre-operative adverse outcomes. In this prospective study of 392 frail elderly patients undergoing abdominal surgery, we investigated the predictive value of preoperative gait speed for postoperative outcomes. Patients were divided into two groups based on their 6-meter gait speed: normal (≥0.8 m/s, n=184) and slow (<0.8 m/s, n=208). The slow group was older, had more comorbidities, and higher American Society of Anesthesiologists (ASA) grades (P<0.05). They also had significantly higher rates of 30-day overall complications (38.9 vs 18.5%, P<0.01), severe complications (12.0 vs 4.3%, P<0.01), and 1-year mortality (15.4 vs 6.5%, P=0.008) compared to the normal group. Pulmonary infection, wound infection, and delirium were the most common complications. Multivariate logistic regression confirmed slow gait speed as an independent risk factor for 30-day complications (OR=2.38, 95%CI: 1.41-4.01) and 1-year mortality (OR=2.19, 95%CI: 1.07-4.48). Our findings demonstrated that preoperative 6-meter gait speed effectively predicted short-term complications and mid-term mortality in frail elderly patients undergoing abdominal surgery. This suggests the need for individualized perioperative management strategies for high-risk patients with slow gait speed to potentially improve their prognosis.

Cancer is the second leading cause of death worldwide. Cancer cachexia is a multifactorial catabolic syndrome responsible for almost one third of cancer-related deaths. Drug repurposing has been used in oncological research and drugs like clenbuterol and metformin seem to be reasonable candidates in the context of cancer cachexia, because the former is a β2-agonist that stimulates muscle gain and the latter has anti-inflammatory properties. The aim of this study was to assess the effects of a short-term treatment with metformin and clenbuterol, isolated or combined, on tumor growth and cancer cachexia parameters in Walker 256 tumor-bearing rats, a model of cancer cachexia. To this end, Wistar rats were separated into 8 groups and 4 of them were injected with Walker 256 tumor cells (W groups). Control (C) and W groups received the following treatments: metformin (M), clenbuterol (Cb), or metformin combined with clenbuterol (MCb). Body and tumor weight, metabolic parameters, and oxidative damage in the tumor were assessed. Compared to the C group, the W group showed body weight loss, hypoglycemia, hyperlactatemia, and hypertriacylglycerolemia. None of the treatments could reverse body weight loss, although they reversed the alterations of the assessed plasma metabolic parameters. Surprisingly, only clenbuterol alone reduced tumor weight. Hydrogen peroxide production and lipid peroxidation in tumor tissue was increased in this group. In conclusion, metformin and clenbuterol ameliorated metabolic cachexia parameters in Walker tumor-bearing rats, but only clenbuterol reduced the tumor weight, probably, through a lipid peroxidation-dependent cell death.

This systematic review of inception prospective cohort studies aimed to investigate whether autoantibodies are potential prognostic factors for short- and long-term clinical outcomes of COVID-19. Searches were conducted in MEDLINE, EMBASE, AMED, GLOBAL HEALTH, and COCHRANE databases from 2019 to 2022. When possible, meta-analysis was conducted, otherwise findings from individual studies were reported using odds ratios (OR) with 95% confidence intervals (CI). Quality of evidence was summarized using the GRADE criteria. We identified 2292 references, 18 inception prospective cohort studies (3178 patients) were included in the systematic review, and 12 studies reached criteria for meta-analysis. Studies achieved, in general, low to moderate risk of bias. Moderate quality of evidence showed that anti-interferon (IFN) was associated with increased risk of severity (OR=7.75; CI=1.79-33.61) and mechanical ventilation (OR=4.19; CI=2.06-8.53), but not with COVID-19 mortality (OR=1.68; CI=0.63-4.44). Antiphospholipids were not associated with COVID-19 mortality (OR=1.42; CI=0.85-2.37; P=0.18; I2=3.21) nor with thrombosis risk (OR=1.41; CI: 0.71-2.8; P=0.33). Antinuclear antibody level was not associated with risk of mortality or severity (risk for mortality: OR=3.8; CI=0.78-18.6; P=0.1; I2: 32.3; severity: OR=1.74; CI=0.96-3.16; P=0.07). Evidence currently available is insufficient for a quantitative analysis of autoantibodies association with long COVID-19. Anti-IFN measurement should be considered in COVID-19 follow-up. In a population-based rational, optimized vaccination strategies should be considered for individuals with anti-IFN antibodies since it could represent a risk for a worse prognosis. High-quality prospective studies for short- and long-term disease effects and autoantibody evaluation are still needed.

Sirtuins (SIRTs) are key regulators of cellular metabolism, involved in a wide range of physiological and pathological processes. However, there is scarce knowledge about the effect of sugar consumption and physical activity on SIRTs in kidney disorders. Here, we evaluated the impact of prolonged consumption of an isocaloric high-sugar diet (HSD) and physical training on the modulation of renal Sirts and the link between these alterations and possible obesity-associated kidney damage. Newly weaned male Wistar rats were fed a standard chow diet (STD) or HSD ad libitum and then subjected or not to regular workload swimming training for 18 weeks. Morphometric and biochemical parameters were analyzed, and the kidneys were removed for lipid quantification, histological analysis, and for Sirts1-7 expression. HSD led to the development of obesity, increased serum triglyceride levels, and glucose intolerance, regardless of higher caloric consumption. However, training was able to partially inhibit the HSD-induced obesogenic effect. No changes were identified in kidney mass, lipid content, histology, and creatinine clearance among the groups; these results were associated with a decrease in the renal expression of Sirt2-3 and Sirt7; however, training was able to reverse this modulation. The interaction between HSD and training led to an increase in Sirt4-7. However, Sirt1 remained constant among experimental groups. In conclusion, our results indicated that the transcriptional modulation of Sirts precedes HSD-induced damage and loss of kidney function, as well as a possible protective adaptive response of physical exercise on long-term Sirts expression.

Necrotizing enterocolitis (NEC) is a severe intestinal disease of multifactorial origin that primarily affects premature infants. Approximately 27% of NEC babies develop short gut (SG) secondary to extensive intestinal resection, and 10% will have chronic dependence on total parenteral nutrition. We evaluated the Botox treatment in SG model rats. Twenty-day-old weanling male rats (weight range 38-70 g, n=72) were divided into four groups (n=18 each): 1) Control (fed a regular liquid diet); 2) Botox (Control submitted to laparotomy and intestinal injection of Botox®); 3) SG (short gut); and 4) SG and Botox (SG+Botox®). After seven post-operative days, samples were collected for biometrics [body weight (BW), intestine weight (IW) and IW/BW ratio (IBR), and intestine length (IL) and height (IH)], histometric analysis [villous height (VH), crypt depth (CD), muscular thickness (MT), and PCNA index)], and intestinal transit time (ITT). BW, IW, and IL decreased in SG (P<0.05). IH, VH, and PCNA index increased in Botox groups [Control = SG < Botox and SG+Botox (P<0.05)], CD increased in Botox, SG, and SG+Botox (P<0.005), and MT was higher in SG and SG+Botox. Botox groups had lower ITT (P<0.05). Botox provided dilatation and histological changes in SG. These findings suggested that Botox improved adaptation and might be applied in SG with promising results.

[This retracts the article doi: 10.1590/1414-431X20209346].

Phosphodiesterase 2A (PDE2A) plays a pivotal role in modulating cyclic nucleotide metabolism. Recent studies have shown that PDE2A is associated with some tumors, but its expression profiles, prognostic significance, and immunological roles in diverse cancer types remain unclear. Utilizing advanced bioinformatics tools, we performed a comprehensive analysis of PDE2A gene expression in multiple human cancers. Our study revealed that PDE2A expression was significantly reduced in the majority of cancer types and clinicopathological stages (I to IV) compared to normal tissues. Additionally, PDE2A expression was closely related to the prognosis of cancers such as stomach adenocarcinoma (STAD), ovarian serous cystadenocarcinoma (OV), and liver hepatocellular carcinoma (LIHC). Cox regression analyses indicated that PDE2A can act as an independent prognostic factor for these cancers. The level of PDE2A DNA methylation was significantly decreased in most cancers. Genetic alterations in PDE2A predominantly manifest in the form of amplifications. Moreover, infiltrating cells and immune checkpoint genes, including PDCD1, exhibited notable correlations with PDE2A expression. Significant associations were observed between PDE2A expression and tumor mutation burden as well as microsatellite instability. Single cell sequencing revealed PDE2A's crucial role in regulating differentiation and angiogenesis of cancer cells. Functional enrichment analysis emphasized the important role of PDE2A in synaptic transmission and tumor development. Aberrant expression of PDE2A influenced the sensitivity of various antitumor and chemotherapy drugs. This research provided a comprehensive analysis of PDE2A in human cancers, highlighting its potential as both a prognostic marker and an immunotherapy target for future research.