Aflatoxin B1-Induced COX-2 Expression Promotes Mitophagy and Contributes to Lipid Accumulation in Hepatocytes In Vitro and In Vivo.

AIM: Aflatoxin B1 (AFB1) is hepatotoxic. Numerous studies have shown that mitochondria play an essential role in AFB1-induced steatosis. However, the mechanisms of AFB1-induced steatosis via mitochondria are still obscure. The present study aimed to confirm that AFB1 causes hepatocyte steatosis regulated by cyclooxygenase-2 (COX-2)-induced mitophagy, both in vivo and in vitro. METHODS: Adult male C57BL/6 mice were randomly divided into control group with the same volume of peanut oil and exposure group administered 0.6 mg/kg AFB1 once in 2 days for 1 month. HepG2 and Cas9-PTGS2 cells were treated with 5 µM AFB1 for 48 hours. Then, various indicators were evaluated. RESULTS: Aflatoxin B1 causes liver injury and steatosis with increased alanine aminotransferase, aspartate aminotransferase, total cholesterol, total triglyceride levels in vivo and in vitro, and elevated lipid droplets in HepG2 cells. Cyclooxygenase-2 and mitophagy pathway were induced by AFB1 in both liver tissues and cultured HepG2 cells. Further studies have shown that knockout of COX-2 with the CRISPR/Cas9 system inhibited the AFB1-induced mitophagy and steatosis in HepG2 cells. Also, the inhibition of PTEN-induced putative kinase with RNA interference attenuated the AFB1-induced steatosis. CONCLUSIONS: The results of the current study suggested that AFB1 increases the expression of COX-2, which, in turn, elevates the level of mitophagy, thereby disrupting the normal mitochondrial lipid metabolism and causing steatosis. Thus, this study implies that COX-2 may be a potential target for therapy against AFB1-induced steatosis.

Risk factors for sinistral portal hypertension and related variceal bleeding in patients with chronic pancreatitis.

OBJECTIVES: Sinistral portal hypertension (SPH) is an uncommon complication of chronic pancreatitis (CP) and can result in severe gastrointestinal bleeding. The aim of this study was to determine the prevalence and the potential risk factors for SPH and related gastrointestinal variceal bleeding in patients with CP. METHODS: We retrospectively reviewed all patients with SPH due to CP admitted to our hospital from July 2014 to June 2019 in this case-control study. Patients with CP without SPH were randomly selected as controls during the study period (case: control  =  1:2). The characteristics, medical history, course of CP, characteristics associated with SPH, and follow-up evaluations of the patients were documented in detail. The prevalence rate of SPH in patients with CP and related gastrointestinal bleeding was calculated. Risk factors for SPH and related variceal bleeding were analyzed using univariate or multivariate logistic regression analysis. RESULTS: The prevalence of SPH was 2.7% (89/3358) in patients with CP. Independent risk factors for SPH included alcohol consumption (P = 0.030), history of acute pancreatitis (P = 0.010), diabetes mellitus (P < 0.001), and pseudocysts (P < 0.001). Overall 17 (19.1%) patients suffered from related gastrointestinal bleeding. Between the bleeding and non-bleeding groups, there were significant differences in the types of CP, existence of stones, gastric varices diagnosed before bleeding, splenomegaly and hypersplenism by univariate analysis. CONCLUSION: SPH is a rare complication of CP that is associated with a relatively low risk of variceal bleeding.