HBV DNA Integration into Telomerase or MLL4 Genes and TERT Promoter Point Mutation as Three Independent Signatures in Subgrouping HBV-Related HCC with Distinct Features.

Introduction: A set of genetic mutations to classify hepatocellular carcinoma (HCC) useful to clinical studies is an unmet need. Hepatitis B virus-related HCC (HBV-HCC) harbors a unique genetic mutation, namely, the HBV integration, among other somatic endogenous gene mutations. We explored a combination of HBV DNA integrations and common somatic mutations to classify HBV-HCC by using a capture-sequencing platform. Methods: A total of 153 HBV-HCCs after surgical resection were subjected to capture sequencing to identify HBV integrations and three common somatic mutations in genomes. Three mutually exclusive mutations, HBV DNA integration into the TERT promoter, HBV DNA integration into MLL4, or TERT promoter point mutation, were identified in HBV-HCC. Results: They were used to classify HBV-HCCs into four groups: G1 with HBV-TERT integration (25.5%); G2 with HBV-MLL4 integration (10.5%); G3 with TERT promoter mutation (30.1%); and G4 without these three mutations (34.0%). Clinically, G3 has the highest male-to-female ratio, cirrhosis rate, and associated with higher early recurrence and mortality after resection, but G4 has the best outcome. Transcriptomic analysis revealed a grouping different from the published ones and G2 with an active immune profile related to immune checkpoint inhibitor response. Analysis of integrated HBV DNA provided clues for HBV genotype and variants in carcinogenesis of different HCC subgroup. This new classification was also validated in another independent cohort. Conclusion: A simple and robust genetic classification was developed to aid in understanding HBV-HCC and in harmonizing clinical studies.

Oxidized frying oil and its polar fraction fed to pregnant mice are teratogenic and alter mRNA expressions of vitamin A metabolism genes in the liver of dams and their fetuses.

We previously observed a higher incidence of congenital malformations in the fetuses of dams fed an oxidized frying oil (OFO)-containing diet during pregnancy. In this study, we hypothesized that, during pregnancy, maternal ingestion of OFO, specifically the oxidized components (i.e. the polar fraction), modulates peroxisome proliferator-activated receptor (PPARα) or aryl hydrocarbon receptor (AhR) transactivity, altering the metabolism of retinoic acid (RA), a well-characterized morphogen, resulting in teratogenesis. Pregnant C57BL/6J mice were divided into four groups which, from d1 (conception) to d18, were fed a diet containing 10 g/100 g of fresh soybean oil (SO), OFO or the non-polar (NP) or polar (PO) fraction of OFO. Reporter assays testing the transactivity of PPARα and AhR showed that free fatty acids from OFO, specifically the PO fraction, up-regulated PPARα transactivity and down-regulated AhR transactivity. In vivo study showed that the PO fraction group had a significantly higher number of dead fetuses and resorptions per litter than the SO and NP fraction groups. The incidence of abnormalities in terms of gross morphology and skeletal ossification of the fetus was greatest in the PO fraction group, followed by the OFO group, both values being significantly higher than in the other two groups. Hepatic expression of genes encoding enzymes associated with RA synthesis and catabolism in dams and fetuses was differentially affected by PO fraction assault. We conclude that OFO-mediated teratogenesis is associated with disturbed RA metabolism in the dams and fetuses caused, at least in part, by modulation of PPARα and AhR transactivity by the oxidized components in OFO.

Gestational ingestion of oxidized frying oil by C57BL/6J mice differentially affects the susceptibility of the male and female offspring to diet-induced obesity in adulthood.

The aim of this study was to investigate whether maternal ingestion of oxidized frying oil (OFO) during pregnancy influences the susceptibility to diet-induced obesity (DIO) of the adult offspring. Pregnant C57BL/6J mice were fed either a control diet [10% fresh soybean oil (SO)] or an OFO-containing diet (10% OFO) throughout the entire gestational period. After parturition, all pups were nursed by SO-fed dams for 3 wk, weaned onto a nonpurified standard diet for 4 wk, and shifted to a high-fat diet (29% butter + 1% SO) for 5 wk. Consequently, 4 groups of offspring were obtained, consisting of the male (m) or female (f) offspring of dams fed the OFO diet (OFO-m and OFO-f) or the SO diet (SO-m and SO-f). At pregnancy d 18, higher amounts (P < 0.05) of mRNA for PPARα target genes were found in the liver of the OFO-fed dams and their fetuses than in their SO controls. Although all pups were raised under the same conditions in postnatal life, a comparison based on the gender of pups from dams fed the different diets showed that adult OFO-f mice were prone to DIO, whereas adult OFO-m mice were resistant. The adult OFO-m mice also had higher expression of PPARα target genes in the liver and white adipose tissue (WAT) and of thermogenic genes in the WAT than adult SO-m mice, whereas adult OFO-f and SO-f mice did not differ. We conclude that uterine PPARα activation caused by maternal OFO ingestion affects hepatic PPARα activity and adipose thermogenic capacity and contributes to the differential susceptibility to DIO in the male and female offspring in adulthood.

[Factors associated with self-care behaviors in middle-aged adults and elderly with diabetes mellitus].

BACKGROUND: Adequate self-care behavior in diabetic individuals is essential to reduce the progress of the condition and reduce diabetes related complications. Continued research to understand the factors associated with self-care behaviors is needed in order to reduce health care costs and the social burdens associated with diabetes. PURPOSE: To investigate factors associated with self-care behaviors in individuals with diabetes in the community. METHODS: Researchers used secondary data analysis to assess survey data on diabetic individuals obtained from the Community Integrated Screening conducted by the Meishan Township Public Health Center and adult health examinations. Descriptive statistics and multiple linear regression analyses evaluated the independent factors associated with self-care behaviors. RESULTS: A total of ninety-seven individuals with Type 2 diabetes met the inclusion criteria. Mean age was 67.1 years and 37.1% was male. Results from multiple linear regression analysis indicated self-care behavior as poorer in individuals who drank alcohol during the past six months (p=.001), smoked cigarettes during the past six months (p=.015), and/or practiced religious or spiritual beliefs (p=.003). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Findings from this study can help understand factors affecting self-care behaviors in individuals with diabetes in the community. Medical and public health units should focus on providing effective advice on smoking and drinking cessation to individuals with diabetes. Units should also clarify potential conflicts between individuals' self-care behaviors and their religious or spiritual beliefs.