TAN (tannic acid) inhibits BPA-induced pyroptosis of L8824 (grass carp hepatocytes) by regulating PTEN/PI3K/AKT pathway.

Bisphenol A (BPA) and its analogues are still one of the most important substances that pollute aquatic systems and pose a threat to aquatic organisms. Tannic acid (TAN) is a kind of glycosyl compound, which has the functions of anti-oxidation, anti-inflammation and anti-apoptosis. However, it is unknown if BPA can regulate PTEN/PI3K/AKT pathway to induce pyroptosis of grass carp hepatocytes (L8824) and the antagonistic effect of tannic acid (TAN) through oxidative stress. Therefore, we established the grass carp hepatocytes (L8824) cell model treated with BPA. The oxidative stress indexes (SOD, CAT, GSH, H2O2 and T-AOC) were detected by oxidative stress kit, mRNA and protein expression of associated genes were examined using qRT-PCR and western blotting. The results showed that BPA treatment increased the content of hydrogen peroxide and decreased the activities of antioxidant enzymes and antioxidants (SOD, CAT, GSH, and T-AOC) in L8824 cells. We also found that PTEN/PI3K/AKT pathway was activated dramatically and the expression of pyroptosis-related genes (GSDMD, NLRP3, Caspase1, ASC and IL-1ß) was increased significantly. In addition, TAN could significantly reduce the toxicity of BPA on L8824 cells. After the addition of PTEN specific inhibitor SF1670, the activation of PTEN/PI3K/AKT pathway decreased by BPA was inhibited and the expression of scorch related genes was decreased. On the whole, TAN inhibits BPA-induced pyroptosis of L8824 by modulating the PTEN/PI3K/AKT pathway. The present study provides a novel perspective for toxicological mechanism of BPA, and new insights into the detoxification mechanism of TAN.

Global burden of stroke in adolescents and young adults (aged 15-39 years) from 1990 to 2019: a comprehensive trend analysis based on the global burden of disease study 2019.

INTRODUCTION: The incidence of stroke is rising among individuals aged 15-39. Insufficient research targeting this age group hampers the development of effective strategies. This study analyzes data from the Global Burden of Disease Study 2019 (GBD 2019) to examine trends from 1990 to 2019 and propose future interventions. METHODS: Data on ischemic strokes, intracerebral hemorrhage, and subarachnoid hemorrhage from 1990 to 2019 was collected from the Global Health Data Exchange (GHDx) platform. We used the Annual Average Percentage Change (AAPC) to assess global trends in incidence, prevalence, Disability-Adjusted Life Years (DALYs), and mortality rates across various stroke categories. Joinpoint models identified significant years of trend inflection. Trend analyses were segmented by age, gender, and Sociodemographic Index (SDI). FINDINGS: From 1990 to 2019, the global incidence of ischemic stroke within the adolescents and young adults (AYAs) cohort declined from 1990 to 1999, further decreased from 2000 to 2009, and then increased from 2010 to 2019. The overall AAPC p-value showed no significant difference. Mortality rates for ischemic strokes were consistently reduced during this period. The overall incidence rate of intracerebral hemorrhage has exhibited a downward trend. Meanwhile, the incidence rate of subarachnoid hemorrhage decreased from 1990 to 2009, yet saw a resurgence from 2010 to 2019. Male ischemic stroke incidence grew more than female incidence, but both absolute incidence and rates were higher for females. Differences in SDI levels were observed, with the fastest increase in incidence occurring in low-middle SDI regions, followed by high SDI regions, and the smallest increase in low SDI regions. Conversely, the most rapid decline was noted in high-middle SDI regions, with no significant change observed in middle SDI regions. CONCLUSION: A concerning trend of increasing ischemic stroke incidence, DALYs, and prevalence rates has emerged in the global 15-39 age group, especially among those aged 30-39. This increase is evident across regions with varying SDI classifications. To combat this alarming trend among adolescents and young adults, enhancing preventive efforts, promoting healthier lifestyles, strengthening the healthcare system's responsiveness, and maintaining vigilant epidemiological monitoring is essential.

Clinical application of four-dimensional flow cardiovascular magnetic resonance in Marfan syndrome: A systematic review and meta-analysis.

This study aims to fill this gap by assessing the application of 4D flow CMR in MFS through a systematic review and meta-analysis. We conducted a comprehensive search of databases from their inception to May 1, 2023. Eligibility criteria were established based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS), with studies scoring above five deemed high quality. Meta-analyses were performed using Stata 15.1 software. Nine studies were analyzed. Findings indicate MFS patients had increased vortex flow in the descending aorta (DAo), larger aortic root diameter (ARD) and Z-scores, lower inner wall shear stress (WSS) in the proximal descending aorta (pDAo), reduced in-plane rotational flow (IRF) in the aortic arch and proximal descending aorta (pDAo), and increased pulse wave velocity (PWV) in the ascending aorta (AAo) and DAo compared to healthy subjects. No significant difference in systolic flow reversal ratio was observed. Sensitivity analysis showed no heterogeneity and Egger's test revealed no publication bias. This meta-analysis underscores the effectiveness of 4D flow CMR in detecting MFS, particularly through indicators such as vortex flow, WSS, IRF, ARD, and PWV. The findings provide insights into diagnosing cardiovascular diseases and predicting cardiovascular events in MFS patients. Further case-control studies are needed to establish measurement standards and explore potential indicators for improved diagnosis and treatment of MFS.

Silicon dioxide particles induce DNA oxidative damage activating the AIM2-mediated PANoptosis in mice cerebellum.

Silicon dioxide (SiO2) particles are novel materials with wide-ranging applications across various fields, posing potential neurotoxic effects. This study investigates the toxicological mechanisms of SiO2 particles of different sizes on murine cerebellar tissue and cells. Six-week-old C57BL/6 mice were orally administered SiO2 particles of three sizes (1 µm, 300 nm, 50 nm) for 21 days to establish an in vivo model, and mice cerebellar astrocytes (C8-D1A cells) were cultured in vitro. Indicators of oxidative stress, DNA damage, and the PANoptosis pathway were detected using methods such as immunofluorescence staining, comet assay, western blotting, and qRT-PCR. The results show that SiO2 particles induce oxidative stress leading to DNA oxidative damage. The aberrant DNA is recognized by AIM2 (absent in melanoma 2), which activates the assembly of the PANoptosome complex, subsequently triggering PANoptosis. Furthermore, the extent of damage is inversely correlated with the size of SiO2 particles. This study elucidates the toxicological mechanism of SiO2 particles causing cerebellar damage via PANoptosis, extending research on PANoptosis in neurotoxicology, and aiding in the formulation of stricter safety standards and protective measures to reduce the potential toxic risk of SiO2 particles to humans.