High-intensity interval training alleviates liver inflammation by regulating the TLR4/NF-κB signaling pathway and M1/M2 macrophage balance in female rats with cisplatin hepatotoxicity.

Cisplatin (CDDP) is an antineoplastic drug whose adverse effects include hepatotoxicity. The inflammatory process is crucial in the progression of liver injuries. Exercise is known for its anti-inflammatory effects, but the influence of different training modalities on hepatoprotection is still unclear. This study aims to compare the impacts between preconditioning with high-intensity interval training (HIIT) and traditional continuous training of low (LT) and moderate (MT) intensities on inflammatory markers in Wistar female rats with CDDP-induced hepatotoxicity. Thirty-five rats were divided into five groups: control and sedentary (C + Sed), treated with CDDP and sedentary (CDDP + Sed), treated with CDDP and subjected to LT (CDDP + LT), treated with CDDP and subjected to MT (CDDP + MT), and treated with CDDP and subjected to HIIT (CDDP + HIIT). The training protocols consisted of treadmill running for 8 weeks before CDDP treatment. The rats were euthanized 7 days after the treatment. Liver samples were collected to evaluate the expression of various inflammatory markers and types of macrophages. Our results indicated that HIIT was the only protocol to prevent the increase in all analyzed pro-inflammatory cytokines and reduce the number of ED-1-positive cells, attenuating the TLR4/NF-κB signaling pathway in the liver. Additionally, HIIT increased the anti-inflammatory cytokine IL-10 and regulated M1/M2 macrophage polarization. Thus, this study suggests that preconditioning with HIIT is more effective in promoting hepatoprotective effects than LT and MT, regulating inflammatory markers through modulation of the TLR4/NF-κB signaling pathway and M2 macrophage polarization in the hepatic tissue of female rats treated with CDDP.

Benefits of high-intensity interval training compared to continuous training to reduce apoptotic markers in female rats with cisplatin nephrotoxicity - possible modulatory role of IL-11.

Apoptotic signaling pathways are involved in acute kidney injury (AKI) induced by the antineoplastic drug cisplatin (Cis). Mechanical stress is known to increase interleukin (IL) -11, a pleiotropic cytokine with antiapoptotic and antinecrotic effects. We compared the impact of high-intensity interval training (HIIT) with low-intensity continuous training (LICT) and moderate-intensity continuous training (MICT) on renal levels of IL-11 and the expression of apoptotic markers in female rats with nephrotoxicity induced by Cis. For that, the animals were divided into five groups (n = 7): control and sedentary (C + S); Cis and sedentary (Cis + S); Cis and LICT (Cis + LICT); Cis and MICT (Cis + MICT) and Cis and HIIT (Cis + HIIT). At the end of 8 weeks of treadmill running, the rats received a single injection of Cis (5 mg/kg), and 7 days later they were euthanized. Serum and kidney samples were collected to assess the blood urea nitrogen (BUN), gene expression of TNF receptor 1 (TNFR1) and 2 (TNFR2), caspase-3, (p38) MAPK (MAPK14), p53, Bax, Bak, Bcl-2, and Bcl-xL, renal levels of IL-11, IL-8, and p53, and immunolocalization of cleaved caspase-3, Bax, Bcl-2, and (p38) MAPK in renal tissue. Our data indicate that all trained groups showed a significant intensity-dependent increase in renal levels of IL-11 associated with reduced local expression of proapoptotic and increased antiapoptotic markers, but these effects were more pronounced with HIIT. So, HIIT appears to provide superior renoprotection than traditional continuous training by modulating apoptotic signaling pathways, and this effect can be related to the increase in renal levels of IL-11.

Renoprotective mechanisms of exercise training against acute and chronic renal diseases - A perspective based on experimental studies.

Regular exercise training can lead to several health benefits, reduce mortality risk, and increase life expectancy. On the other hand, a sedentary lifestyle is a known risk factor for chronic diseases and increased mortality. Acute kidney injury (AKI) and chronic kidney disease (CKD) represent a significant global health problem, affecting millions of people worldwide. The progression from AKI to CKD is well-recognized in the literature, and exercise training has emerged as a potential renoprotective strategy. Thus, this article aims to review the main molecular mechanisms underlying the renoprotective actions of exercise training in the context of AKI and CKD, focusing on its antioxidative, anti-inflammatory, anti-apoptotic, anti-fibrotic, and autophagy regulatory effects. For that, bibliographical research was carried out in Medline/PubMed and Scielo databases. Although the pathophysiological mechanisms involved in renal diseases are not fully understood, experimental studies demonstrate that oxidative stress, inflammation, apoptosis, and dysregulation of fibrotic and autophagic processes play central roles in the development of tissue damage. Increasing evidence has suggested that exercise can beneficially modulate these mechanisms, potentially becoming a safe and effective non-pharmacological strategy for kidney health protection and promotion. Thus, the evidence base discussed in this review suggests that an adequate training program emerges as a valuable tool for preserving renal function in experimental animals, mainly through the production of antioxidant enzymes, nitric oxide (NO), irisin, IL-10, and IL-11. Future research can continue to explore these mechanisms to develop specific guidelines for the prescription of exercise training in different populations of patients with kidney diseases.

Role of the Microbiome in Aedes spp. Vector Competence: What Do We Know?

Aedes aegypti and Aedes albopictus are the vectors of important arboviruses: dengue fever, chikungunya, Zika, and yellow fever. Female mosquitoes acquire arboviruses by feeding on the infected host blood, thus being able to transmit it to their offspring. The intrinsic ability of a vector to infect itself and transmit a pathogen is known as vector competence. Several factors influence the susceptibility of these females to be infected by these arboviruses, such as the activation of the innate immune system through the Toll, immunodeficiency (Imd), JAK-STAT pathways, and the interference of specific antiviral response pathways of RNAi. It is also believed that the presence of non-pathogenic microorganisms in the microbiota of these arthropods could influence this immune response, as it provides a baseline activation of the innate immune system, which may generate resistance against arboviruses. In addition, this microbiome has direct action against arboviruses, mainly due to the ability of Wolbachia spp. to block viral genome replication, added to the competition for resources within the mosquito organism. Despite major advances in the area, studies are still needed to evaluate the microbiota profiles of Aedes spp. and their vector competence, as well as further exploration of the individual roles of microbiome components in activating the innate immune system.

High-intensity interval training is more effective than continuous training to reduce inflammation markers in female rats with cisplatin nephrotoxicity.

AIMS: Cisplatin (CP) is an antineoplastic widely used in the treatment of various solid tumors, however, its clinical application is limited by nephrotoxicity. Here, we compared the impact of preconditioning with high-intensity interval training (HIIT) with continuous training of low (LIT) and moderate (MIT) intensity on innate immunity markers in female rats with CP-induced acute kidney injury. MATERIALS AND METHODS: The rats were divided into five groups (n = 7): saline control and sedentary (C + S); CP and sedentary (CP + S); CP and LIT (CP + LIT); CP and MIT (CP + MIT) and CP and HIIT (CP + HIIT). The training intensity was determined by a maximum running test. At the end of training, the rats received a single dose of CP (5 mg/kg), and 7 days later they were euthanized. We evaluated renal function parameters (serum creatinine, glomerular filtration rate and proteinuria), renal structure, macrophage tissue infiltration, immunolocalization of nuclear transcription factor kappa B (NF-κB), renal levels of tumor necrosis factor-alpha (TNF-α), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6), and gene expression of monocyte chemoattractant protein-1 (MCP-1), toll-like receptor 4 (TLR4), and NF-κB in renal tissue. KEY FINDINGS: Although both MIT and HIIT attenuated the degree of renal injury, only the HIIT prevented changes in renal function. The three training protocols mitigated the increase in expression of all inflammatory markers, however, this effect was more pronounced in HIIT. SIGNIFICANCE: All training protocols promoted renoprotective actions, but HIIT was more effective in mitigating CP-induced acute kidney injury, in part by modulation of important markers of the innate immune response.

Influence of exercise training on diabetic kidney disease: A brief physiological approach.

IMPACT STATEMENT: Diabetic kidney disease (DKD) is associated with increased mortality in diabetic patients and has a negative impact on public health. The identification of potential therapies that help the management of DKD can contribute to the improvement of health and quality of life of patients. Thus, this paper is timely and relevant because, in addition to presenting a concise review of the pathogenesis and major pathophysiological mechanisms of DKD, it addresses the most recent findings on the impact of exercise training on this disease. Thus, since non-pharmacological interventions have gained increasing attention in the fight against chronic diseases, this paper appears as an important tool to increase knowledge and stimulate innovative research on the impact of exercise on kidney disease.

Previous Exercise Training Reduces Markers of Renal Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Female Rats.

The aim of this study is to evaluate the effects of regular moderate exercise training initiated previously or after induction of diabetes mellitus on renal oxidative stress and inflammation in STZ-induced diabetic female rats. For this purpose, Wistar rats were divided into five groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD), trained diabetic (TD), and previously trained diabetic (PTD). Only the PTD group was submitted to treadmill running for 4 weeks previously to DM induction with streptozotocin (40 mg/kg, i.v). After confirming diabetes, the PTD, TD, and TC groups were submitted to eight weeks of exercise training. At the end of the training protocol, we evaluated the following: glycosuria, body weight gain, plasma, renal and urinary levels of nitric oxide and thiobarbituric acid reactive substances, renal glutathione, and immunolocalization of lymphocytes, macrophages, and nuclear factor-kappa B (NF-κB/p65) in the renal cortex. The results showed that exercise training reduced glycosuria, renal TBARS levels, and the number of immune cells in the renal tissue of the TD and PTD groups. Of note, only previous exercise increased weight gain and urinary/renal NO levels and reduced NF-κB (p65) immunostaining in the renal cortex of the PTD group. In conclusion, our study shows that exercise training, especially when initiated previously to diabetes induction, promotes protective effects in diabetic kidney by reduction of renal oxidative stress and inflammation markers in female Wistar rats.

Ovariectomy exacerbates glycerol-induced acute kidney injury in rats / A ovariectomia intensifica a lesão renal aguda induzida pelo glicerol em ratas

Objective: This study aimed to evaluate the effects of ovariectomy on glycerol-induced renal changes in rats. Methods: Twenty-four female Wistar rats were submitted to ovariectomized (OVX) or sham surgery. One week after surgery, the animals received an intramuscular injection (8ml/kg) of 50% glycerol or saline (0.15 M) solution. These animals were divided into the following groups (n=6 per group): Sham, sham-operated female rats injected with saline; OVX, ovariectomized female rats injected with saline; Sham+Gly, sham-operated female rats injected with glycerol; OVX+Gly, ovariectomized female rats injected with glycerol. All rats were euthanized 3 days after the injections and the kidneys were removed for histological and immunohistochemical studies. Blood and urine samples were also collected for renal function studies. Results: The OVX+Gly group presented higher creatinine serum levels, as well as greater fractional excretion of sodium and urinary flow than the Sham+Gly group. Histological lesions and tubulointerstitial staining for macrophages, nuclear factor-kappa B, and nitrotyrosine were more pronounced in the renal cortex of the OVX+Gly group compared to the Sham+Gly group. Conclusion: We conclude that ovariectomy aggravated changes in renal function and structure in glycerol-induced acute kidney injury by the intensification of the proinflammatory tissue response.

Objetivo: Avaliar os efeitos da ovariectomia nas alterações renais induzidas pelo glicerol em ratas. Métodos: Vinte e quatro ratas Wistar foram submetidas à ovariectomia (OVX) ou cirurgia sham (intervenção falsa). Uma semana após a cirurgia, os animais receberam injeção intramuscular (8ml/kg) de glicerol a 50% ou solução salina (0,15 M). As ratas foram divididas nos seguintes grupos (n=6 por grupo): Sham, fêmeas sham-operadas e injetadas com solução salina; OVX, fêmeas ovariectomizadas e injetadas com solução salina; Sham+Gly, fêmeas sham-operadas e injetados com glicerol; OVX+Gly, fêmeas ovariectomizadas e injetadas com glicerol. Todas as ratas foram eutanasiadas 3 dias após as injeções e os rins foram removidos para estudos histológicos e imuno-histoquímicos. Amostras de sangue e urina também foram coletadas para estudos de função renal. Resultados: O grupo OVX+Gly apresentou maiores níveis séricos de creatinina, assim como maiores fração de excreção de sódio e fluxo urinário do que o grupo Sham+Gly. As lesões histológicas e imunomarcação tubulointersticial para macrófagos, fator nuclear-kappa B e nitrotirosina foram mais pronunciadas no córtex renal do grupo OVX+Gly em comparação ao grupo Sham+Gly. Conclusão: Concluímos que a ovariectomia agravou as alterações na função e estrutura renal, na lesão renal aguda induzida por glicerol, pela intensificação da resposta tecidual pró-inflamatória.

Predicting increased blood pressure using machine learning.

The present study investigates the prediction of increased blood pressure by body mass index (BMI), waist (WC) and hip circumference (HC), and waist hip ratio (WHR) using a machine learning technique named classification tree. Data were collected from 400 college students (56.3% women) from 16 to 63 years old. Fifteen trees were calculated in the training group for each sex, using different numbers and combinations of predictors. The result shows that for women BMI, WC, and WHR are the combination that produces the best prediction, since it has the lowest deviance (87.42), misclassification (.19), and the higher pseudo R (2) (.43). This model presented a sensitivity of 80.86% and specificity of 81.22% in the training set and, respectively, 45.65% and 65.15% in the test sample. For men BMI, WC, HC, and WHC showed the best prediction with the lowest deviance (57.25), misclassification (.16), and the higher pseudo R (2) (.46). This model had a sensitivity of 72% and specificity of 86.25% in the training set and, respectively, 58.38% and 69.70% in the test set. Finally, the result from the classification tree analysis was compared with traditional logistic regression, indicating that the former outperformed the latter in terms of predictive power.