The effects of aB-crystallin on mitochondrial death pathway during hydrogen peroxide induced apoptosis

aB-crystallin, a major small heat shock protein, has recently been shown to exert inhibitory effects on apoptosis, while the responsible mechanisms remain largely unknown. In the present study, we discovered that aB-crystallin protected mouse myoblast C2C12 cells against oxidative stress-induced apoptosis. During hydrogen peroxide-induced apoptosis, aBcrystallin showed that it decreased the redistribution level of phosphatidylserine (PS), reduced the release of cytochrome C and Smac/Diablo from mitochondria into cytoplasm, and decreased the cleavage of Bid. Interestingly, immunoprecipitation experiments with anti-aBcrystallin and anti-myc-tag antibodies demonstrated respectively an interaction between aBcrystallin and p53 during hydrogen peroxide induced apoptosis. Both the NH2-terminal and COOH-terminal regions of aB-crystallin could interact with p53, suggesting two domains of aB-crystallin are necessary for the interaction. Electrophoresis mobility shift assay (EMSA) and luciferase assay further demonstrated that aB-crystallin inhibited the upregulation of the DNA-binding, as well as the transactivation activity of p53 induced by hydrogen peroxide. Our results show that aB-crystallin has a protective role in oxidative stress induced apoptosis by interference with the mitochondrial death pathway

The anti-resection activity of the X protein encoded by Hepatitis Virus B

Chronic infection of hepatitis virus B (HBV) is associated with an increased incidence of hepatocellular carcinoma (HCC). HBV encodes an oncoprotein (HBx) that is crucial for viral replication and interferes with multiple cellular activities including gene expression, histone modifications and genomic stability. To date, it remains unclear how disruption of these activities contributes to hepatocarcinogenesis. Here, we report that HBV exhibits a novel anti‐resection activity by disrupting DNA end resection, thus impairing the initial steps of homologous recombination (HR). This anti‐resection activity occurs in primary human hepatocytes (PHHs) undergoing a natural viral infection‐replication cycle, as well as in cells with integrated HBV genomes. Among the seven HBV‐encoded proteins, we identified HBx as the sole viral factor that inhibits resection. By disrupting an evolutionarily conserved Cullin4A‐DDB1‐RING type of E3 ligase, CRL4WDR70, via its H‐box, we show that HBx inhibits H2B monoubiquitylation at lysine 120 (uH2B) at double strand breaks, thus reducing the efficiency of long‐range resection. We further show that directly impairing H2B monoubiquitylation elicited tumorigenesis upon engraftment of deficient cells in athymic mice, confirming that the impairment of CRL4WDR70 function by HBx is sufficient to promote carcinogenesis. Finally, we demonstrated that lack of H2B monoubiquitylation is manifest in human HBV‐associated HCC (HBVHCC) when compared with HBV‐free HCC, implying corresponding defects of epigenetic regulation and end resection. We conclude that the anti‐resection activity of HBx induces an HR defect and genome instability and contributes to tumorigenesis of host hepatocytes

The association of exogenous dietary antioxidant micronutrient intake and consumption timing with urinary albumin excretion among U.S. adults

BackgroundOxidative stress plays a central role in the pathogenesis of chronic kidney disease (CKD) and is closely linked to glomerular injury and microvascular endothelial dysfunction. Urinary albumin excretion (UAE) is a sensitive early marker of renal damage and systemic inflammation. Although dietary antioxidants are recognized to modulate oxidative stress, the impact of both their cumulative intake and timing on UAE remains unclear.ObjectivesTo investigate the association between the Composite Dietary Antioxidant Index (CDAI)—including both total daily intake and intake at different meals—and the incidence of elevated UAE among adults in the United States. We also aimed to evaluate whether the timing of antioxidant intake, particularly in the evening, modifies this relationship.MethodsWe analysed data from 23,214 adults aged ≥20 years in the U.S. National Health and Nutrition Examination Survey (NHANES) 2009–2018. CDAI was determined using dietary intakes of six antioxidants (vitamins E, A, C, carotenoids, selenium, and zinc) across breakfast, lunch, and dinner. UAE was defined as a urinary albumin-to-creatinine ratio (ACR) >30 mg/g. Weighted multivariable logistic regression, restricted cubic spline analysis, component-independent effect analysis, and analysis of subgroups were used to evaluate the associations and interactions.ResultsHigher CDAI was greatly connected to reduced odds of UAE (fully adjusted OR per SD increase: 0.98; 95% CI: 0.97–0.99; P = 0.041). Antioxidant intake during dinner showed the strongest inverse association with UAE (P < 0.01), while breakfast and lunch intake were not significantly related. The difference between dinner and breakfast CDAI (ΔCDAI) was also inversely associated with UAE. Subgroup analysis revealed effect modification by BMI: the protective association was attenuated in participants with obesity (BMI ≥ 30).ConclusionsBoth the quantity and timing of dietary antioxidant intake are associated with urinary albumin excretion. Evening antioxidant consumption and a higher ΔCDAI may offer enhanced renal protection, potentially via circadian modulation of oxidative stress and inflammation. These findings support a chrononutrition-based approach to kidney health and warrant further interventional studies