Association between serum triglyceride level and severity of acute biliary pancreatitis.

BACKGROUND: Acute biliary pancreatitis (ABP) is the most common type of acute pancreatitis. However, the effect of serum triglyceride (TG) levels on the severity of ABP remains unclear. The aim of this study was to assess the correlation between serum TG levels and the severity of ABP. METHODS: Data from 526 ABP patients was analyzed in this study. The patients were divided into normal and elevated groups according to the TG level measured within 24 h after admission, and the elevated group was further divided into mild, moderate, and severe elevated groups. The demographic data and clinical outcomes of each group were compared. RESULTS: Of the 526 ABP patients, 394 were in the normal TG group and 132 were in the elevated TG group (36 mild, 57 moderate, and 39 severe). The elevated group was younger (51.5 ± 12.9 vs. 58.9 ± 13.9), predominantly male (66.7% vs. 45.2%), had more history of diabetes (22.7% vs. 12.4%) and hyperlipidemia (19.7% vs. 0.8%), and developed systemic inflammatory response syndrome (SIRS) (25.8% vs. 15.5%), persistent organ failure (POF) (11.4% vs. 2.8%), and local complications (62.9% vs. 42.1%) more frequently compared to the normal group (P < 0.05). The incidence of SIRS, POF, acute peripancreatic fluid collection (APFC), and acute necrotic collection (ANC) increased with increasing TG levels (Ptrend < 0.05). In multivariate analysis, TG was independently associated with POF, APFC, and ANC in increments of 100 mg/dl (P < 0.05), and there was a linear relationship between TG levels and POF, APFC, and ANC (non-linear P > 0.05, P overall <0.05). In addition, nonalcoholic fatty liver disease is not a risk factor for POF, ANC, and APFC in ABP patients. CONCLUSIONS: Elevated serum TG levels were independently associated with more severe ABP. The incidence of POF, APFC, and ANC in ABP patients increased with the increase of TG levels, with a linear relationship.

Relation between triglycerides and the severity of acute pancreatitis combined with nonalcoholic fatty liver disease: a retrospective study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) can exacerbate the severity of acute pancreatitis (AP), and this severity is worsened with increased severity of NAFLD. This study aimed to investigate the relation between serum triglyceride (TG) and the severity of AP with NAFLD by collecting clinical data from AP patients with NAFLD. METHODS: AP patients with NAFLD were divided into 2 groups according to TG levels: hypertriglyceridemia (HTG) group and non-hypertriglyceridemia (NHTG) group. RESULTS: In total, 598 AP patients with NAFLD were enrolled in this study, including 433 in the HTG group and 165 in the NHTG group. Compared with the NHTG group, AP patients in the HTG group were more serious (P < 0.05). The incidence of persistent organ failure (POF), especially persistent respiratory failure, and the ratio of acute peripancreatic fluid collection (APFC) were higher in the HTG group (P < 0.05). Higher TG levels were associated with a higher incidence of APFC (P < 0.05). Logistic regression analysis showed that the risk of APFC was significantly higher in moderate and severe NAFLD than in mild NAFLD. CONCLUSION: HTG may aggravate the severity and local complications of AP combined with NAFLD.

Enhancing chemotherapy sensitivity by targeting PcG via the ATM/p53 pathway.

Histone modification and chromatin remodeling are important events in response to DNA damage, and Polycomb group (PcG) proteins, catalyzing H3K27 methylation, are involved. However, the biological function and mechanism of PcG in DNA damage are not fully understood. Additionally, downstream effectors in hepatocellular carcinoma (HCC) remain unclear. The present study investigated the biological and mechanistic roles of PcG in the DNA damage response induced by chemotherapeutic drugs in HCC. It was found that chemotherapy drugs, such as epirubicin (EPB) and mitomycin C (MMC), effectively blocked expression of PcG in p53-wild-type HepG2 cells but not in PLC/PRF5 and Hep3B cells with p53 mutation or deletion. PcG-related target genes involved in DNA damage were identified, including p53, Ataxia telangiectasia mutated (ATM) and Forkhead box O3 (FOXO3). Moreover, targeting PcG-induced p53 expression was associated with increased drug sensitivity in HCC cells. shRNA targeting enhancer of zeste homolog 2 (EZH2) or its inhibitor GSK126 significantly promoted chemotherapeutic drug-induced genotoxicity and increased HepG2 cell chemosensitivity. Mechanistically, chromatin immunoprecipitation (ChIP) assays confirmed that PcG binds to the ATM promoter and inhibits its expression through covalent modification of H3K27me3. Herein, we establish a potential chemotherapy association with GSK126, and the findings suggest this link might represent a new strategy for increasing the sensitivity of HCC to chemotherapeutic agents.

EZH2 represses target genes through H3K27-dependent and H3K27-independent mechanisms in hepatocellular carcinoma.

UNLABELLED: Alterations of polycomb group (PcG) genes directly modulate the trimethylation of histone H3 lysine 27 (H3K27me3) and may thus affect the epigenome of hepatocellular carcinoma (HCC), which is crucial for controlling the HCC cell phenotype. However, the extent of downstream regulation by PcGs in HCC is not well defined. Using cDNA microarray analysis, we found that the target gene network of PcGs contains well-established genes, such as cyclin-dependent kinase inhibitors (CDKN2A), and genes that were previously undescribed for their regulation by PcG, including E2F1, NOTCH2, and TP53. Using chromatin immunoprecipitation assays, we demonstrated that EZH2 occupancy coincides with H3K27me3 at E2F1 and NOTCH2 promoters. Interestingly, PcG repress the expression of the typical tumor suppressor TP53 in human HCC cells, and an increased level of PcG was correlated with the downregulation of TP53 in certain HCC specimens. Unexpectedly, we did not find obvious H3K27me3 modification or an EZH2 binding signal at the TP53 promoters, suggesting that PcG regulates TP53 expression in an H3K27me3-independent manner. Finally, the reduced expression of PcGs effectively blocked the aggressive signature of liver cancer cells in vitro and in vivo. IMPLICATIONS: Taken together, our results establish the functional and mechanistic significance of certain gene regulatory networks that are regulated by PcGs in HCC.