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Obesity is a complex chronic disease characterized by excess body fat (adipose) that is harmful to health and has been a major global health problem. It may be associated with several diseases, such as nonalcoholic fatty liver disease (NAFLD). Polyunsaturated fatty acids (PUFA) are lipid mediators that have anti-inflammatory characteristics and can be found in animals and plants, with capybara oil (CO) being a promising source. So, we intend to evaluate the hepatic pathophysiological alterations in C57Bl/6 mice with NAFLD, caused by obesity, and the possible beneficial effects of OC in the treatment of this disease. Eighteen 3-month-old male C57Bl/6 mice received a control or high-fat diet for 18 weeks. From the 15th to the 18th week, the animals received treatment—through orogastric gavage—with placebo or free capybara oil (5 g/kg). Parameters inherent to body mass, glucose tolerance, evaluation of liver enzymes, percentage of hepatic steatosis, oxidative stress, the process of cell death with the apoptotic biomarkers (Bax, Bcl2, and Cytochrome C), and the ultrastructure of hepatocytes were analyzed. Even though the treatment with CO was not able to disassemble the effects on the physiological parameters, it proved to be beneficial in reversing the morphological and ultrastructural damage present in the hepatocytes. Thus, demonstrating that CO has beneficial effects in reducing steatosis and the apoptotic pathway, it is a promising treatment for NAFLD.

Annexin-A1 (AnxA1) and its N-terminal derived peptide Ac2-26 regulate the inflammatory response in several experimental models of disorders. This study evaluated the effect of endogenous AnxA1 and its N-terminal peptide Acetyl 2-26 (Ac2-26) on allergic asthma triggered by house dust mite (HDM) extract in mice. ANXA1−/− and wildtype (WT) mice were exposed to intranasal instillation of HDM every other day for 3 weeks, with analyses performed 24 h following the last exposure. Intranasal administration of peptide Ac2-26 was performed 1 h before HDM, beginning 1 week after the initial antigen application. ANXA1−/− mice stimulated with HDM showed marked exacerbations of airway hyperreactivity (AHR), eosinophil accumulation, subepithelial fibrosis, and mucus hypersecretion, all parameters correlating with overexpression of cytokines (IL-4, IL-13, TNF-α, and TGF-β) and chemokines (CCL11/eotaxin-1 and CCL2/MCP-1). Intranasal treatment with peptide Ac2-26 decreased eosinophil infiltration, peribronchiolar fibrosis, and mucus exacerbation caused by the allergen challenge. Ac2-26 also inhibited AHR and mediator production. Collectively, our findings show that the AnxA1-derived peptide Ac2-26 protects against several pathological changes associated with HDM allergic reaction, suggesting that this peptide or related AnxA1-mimetic Ac2-26 may represent promising therapeutic candidates for the treatment of allergic asthma.

Cholesterol is a pivotal lipotoxic molecule that contributes to the progression of Non-Alcoholic Steatohepatitis NASH). Additionally, microcirculatory changes are critical components of Non-Alcoholic Fatty Liver Disease (NAFLD) pathogenesis. This study aimed to investigate the role of cholesterol as an insult that modulates microcirculatory damage in NAFLD and the underlying mechanisms. The experimental model was established in male C57BL/6 mice fed a high-fat high-carbohydrate (HFHC) diet for 39 weeks. Between weeks 31–39, 2% cholesterol was added to the HFHC diet in a subgroup of mice. Leukocyte recruitment and hepatic stellate cells (HSC) activation in microcirculation were assessed using intravital microscopy. The hepatic microvascular blood flow (HMBF) was measured using laser speckle flowmetry. High cholesterol levels exacerbated hepatomegaly, hepatic steatosis, inflammation, fibrosis, and leukocyte recruitment compared to the HFHC group. In addition, cholesterol decreased the HMBF—cholesterol-induced activation of HSC and increased HIF1A expression in the liver. Furthermore, cholesterol promoted a pro-inflammatory cytokine profile with a Th1-type immune response (IFN-γ/IL-4). These findings suggest cholesterol exacerbates NAFLD progression through microcirculatory dysfunction and HIF1A upregulation through hypoxia and inflammation. This study highlights the importance of cholesterol-induced lipotoxicity, which causes microcirculatory dysfunction associated with NAFLD pathology, thus reinforcing the potential of lipotoxicity and microcirculation as therapeutic targets for NAFLD.

Objective. To assess the clinical efficacy of flavonoid supplements on allergic diseases. Design. Systematic review. Data Sources. MEDLINE/PubMed, Scopus, Web of Science, and Embase databases were searched from inception to September 2021. Eligibility Criteria for Selecting Studies. Eligible study designs were randomized controlled trials that investigated the effect of flavonoids applied to allergic diseases. Results. This review included 15 randomized controlled trials, including allergic rhinitis/cedar pollinosis (n=10), asthma (n=3), and atopic dermatitis (n=2). A total of 990 participants aged 6 to 69 years were included in these studies. Globally, 12 studies (80%) revealed some benefits of flavonoids (isolate or combined with other compounds) in allergic patients, while three studies (20%) reported no statistically significant impact on symptom scores and/or lung function. No severe adverse events related to treatment were reported. According to the GRADE system, the outcomes evaluated were of low to moderate quality of evidence. Conclusions. Overall, this review suggests that the administration of flavonoids may provide a viable strategy for mitigating allergic symptoms. Future trials with high methodological quality are needed to establish definitive conclusions. This trial is registered with PROSPERO registration no. CRD42021237403.

BackgroundZika fever gained importance in Brazil in 2015 due to its association with congenital syndrome. Although Zika virus (ZIKV) crosses the placenta and infects the fetus, its pathogenesis remains incompletely understood. This study investigated the effects of ZIKV infection in HTR-8/SVneo trophoblast cells.MethodsCells were infected with ZIKV (MOI 0.1, 0.2, or 1) or Mock control for 24 or 48 hours. Infection rate and viability were assessed by immunofluorescence and flow cytometry. Ultrastructural changes were analyzed by transmission electron microscopy. Mitochondrial membrane potential was evaluated by flow cytometry. Gene expression related to mitochondrial dynamics, antioxidant response ( sod, cat, nrf2 ), was analyzed by RT-qPCR. Protein expression (SOD, CAT, NRF2), enzymatic activities (SOD, CAT), and oxidative damage markers (8-OHdG, MDA, NO) were assessed by immunofluorescence and/or colorimetric assays.ResultsMOI 1 for 24 hours produced the highest NS1 expression and infection rate (62.53%) and higher viability (89% vs. 28.1%), establishing this as the optimal condition. Infected cells exhibited mitochondrial damage, including ruptured membranes and loss of cristae, dilated endoplasmic reticulum, clusters of virus-like particles, and vesicle secretion. Mitochondrial membrane potential was reduced, along with decreased transcripts of genes involved in mitochondrial dynamics. Although sod, cat , and nrf2 transcripts were reduced, protein immunolabeling and SOD activity were increased, whereas CAT activity was decreased. Elevated levels of 8-OHdG, MDA, and NO confirmed oxidative stress.ConclusionZIKV infection induces mitochondrial dysfunction, oxidative stress, and impaired mitophagy in HTR-8/SVneo trophoblast cells, highlighting mitochondrial dysfunction as a major component of the cellular response to ZIKV infection in trophoblast cells.

Neutrophil extracellular traps (NETs) are chromatin-derived structures decorated with neutrophil enzymes such as elastase and myeloperoxidase. Our group has previously demonstrated that amyloid fibrils (AFs), regardless of their protein composition, induce NET release in vitro in human neutrophils through a process dependent on reactive oxygen species (ROS) generation by NADPH oxidase 2 (NOX-2). Moreover, the proteases embedded in NETs were shown to degrade AFs into smaller, potentially toxic species. The present study aimed to determine whether amyloid fibrils composed of α-synuclein (αSF) can induce NET formation in vivo and to investigate the role of NETs in modulating amyloid-associated pathology. To this end, we employed gp91phox knockout (KO) mice, which lack NOX-2 activity and are therefore unable to release NETs. αSF was instilled into the lungs of both WT and KO mice (males and females), leveraging the lung’s robust immune cell recruitment - particularly of neutrophils-as a model system. Eight hours after αSF instillation, both WT and KO animals exhibited marked neutrophil infiltration in the lungs causing inflammation. However, NET formation-evidenced by the presence of citrullinated histones and myeloperoxidase - was detected only in WT mice. Interestingly, while Congo red-positive amyloid-like structures persisted in the lungs of KO mice, they were absent in the lungs of WT animals, suggesting that NET-associated proteases facilitate the clearance of AFs from lung tissue. Lung function was assessed by measuring elastance and resistance. Our data showed that, while AFs were still present in the lungs of both WT and KO mice, elastance was impaired. As AFs were cleared from the lungs of WT mice, lung function recovered. In contrast, KO animals, in which AFs persisted, continued to exhibit compromised elastance. Together, our findings demonstrate that AFs impair lung function, and that NETs, induced in response to these fibrils, promote their degradation and thereby protect lung tissue from further damage.