Background and Aim Nonalcoholic fatty liver disease (NAFLD) has gradually become one of the most common chronic liver diseases in the world. More and more evidence shows that low skeletal muscle mass index (SMI) may play a role in the development of NAFLD. Our aim was to quantify the association between SMI, sarcopenia and the presence and severity of NAFLD. Methods We systematically searched English relevant studies from PubMed, Embase, the Web of Science and the Cochrane Library updated to December 20th, 2018. Studies in which SMI was compared between NAFLD cases and controls were included. So were studies concerning the odds ratio (OR) of NAFLD, non-alcoholic steatohepatitis (NASH) and significant fibrosis in sarcopenia patients. Pooled weighted mean differences and ORs were calculated. Results Of the 1331 retrieved studies, 19 articles were included. SMI level in NAFLD patients was 1.77 (95% CI 1.15, 2.39) lower than that in normal controls. We also found a significantly higher occurrence risk of NAFLD (OR = 1.33, 95% CI 1.20 to 1.48), NASH (OR = 2.42, 95% CI 1.27 to 3.57) and NAFLD-related significant fibrosis (OR = 1.56, 95% CI 1.34, 1.78) in sarcopenia subjects. Conclusions SMI level in patients with NAFLD was lower than healthy people, and patients with sarcopenia have higher occurrence risk of NAFLD, as well as its advanced stages including NASH or NAFLD-related significant fibrosis. Further well-designed prospective studies are required to strengthen the arguments.

Background: Methylation plays a significant role in the etiology and pathogenesis of hepatocellular carcinoma (HCC). The aim of the present study is to identify aberrantly methylated-diferentially expressed genes (DEGs) and dysregulated pathways associated with the development of HCC through integrated analysis of gene expression and methylation microarray.Method: Aberrantly methylated-DEGs were identified from gene expression microarrays (GSE62232, GSE74656) and gene methylation microarrays (GSE44909, GSE57958). Functional enrichment and pathway enrichment analyses were performed through the database of DAVID. Protein-protein interaction (PPI) network was established by STRING and visualized in Cytoscape. Subsequently, overall survival (OS) analysis of hub genes was performed by OncoLnc. Finally, we validated the expression level of CDCA5 by quantitative real-time PCR (qRT-PCR) and western blotting, and performed Immunohistochemical experiments utilizing a tissue microarray. Cell growth assay and flow cytometry were behaved to explore the function of CDCA5.Results: Aberrantly methylated-DEGs were enriched in biological process, molecular function, cellular component and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Among them, cell cycle was enriched most frequently, and some terms associated with cancer were enriched, such as p53 signaling pathway, pathways in cancers, PI3K-Akt signaling pathway and AMPK signaling pathway. After survival analysis and validation in TCGA database including methylation and gene expression status, 12 hub genes were identified. Furthermore, the expression level of new gene CDCA5 was validated in HCC cell lines and hepatic normal cell lines through qRT-PCR and western blotting. In additional, immunohistochemistry experiments revealed higher CDCA5 protein expression from HCC tumor tissues compared with paracancer tissues by tissue microarray. Finally, through loss of function, we demonstrated that CDCA5 promoted proliferation by regulating the cell cycle.Conclusions: In summary, the present study implied possible aberrantly methylated-differentially expressed genes and dysregulated pathways in HCC by bioinformatics analysis and experiments, which could be helpful in understanding the molecular mechanisms underlying the development and progression of HCC. Hub genes including CDC20, AURKB, BIRC5, RRM2, MCM2, PTTG1, CDKN2A, NEK2, CENPF, RACGAP1, GNA14 and especially the new gene CDCA5 may serve as biomarkers for diagnosis, treatment and prognosis of HCC.

BACKGROUNDIt is well known that nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR). LB100, a serine/threonine protein phosphatase 2A (PP2A) inhibitor, is closely related to IR. However, there is little data regarding its direct influence on NAFLD.AIMTo elucidate the effect and underlying mechanism of LB100 in NAFLD.METHODSAfter 10 wk of high fat diet (HFD) feeding, male C57BL/6 mice were injected intraperitoneally with vehicle or LB100 for an additional 6 wk (three times a week). The L02 cell line was treated with LB100 and free fatty acids (FFAs) for 24 h. Hematoxylin and eosin and oil red O staining were performed for histological examination. Western blot analysis was used to detect the protein expression of Sirtuin 1 (Sirt1), total and phosphorylated AMP-activated protein kinase α (AMPKα), and the proteins involved in lipogenesis and fatty acid oxidation. The mRNA levels were determined by qPCR. Pharmacological inhibition of AMPK was performed to further examine the exact mechanism of LB100 in NAFLD.RESULTSLB100 significantly ameliorated HFD-induced obesity, hepatic lipid accumulation and hepatic injury in mice. In addition, LB100 significantly downregulated the protein levels of acetyl-CoA carboxylase, sterol regulatory element-binding protein 1 and its lipogenesis target genes, including stearoyl-CoA desaturase-1 and fatty acid synthase, and upregulated the levels of proteins involved in fatty acid β-oxidation, such as peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), carnitine palmitoyltransferase 1α, acyl-CoA oxidase 1 and uncoupling protein 2, as well as the upstream mediators Sirt1 and AMPKα in the livers of HFD-fed mice. In vitro, LB100 alleviated FFA-induced lipid accumulation in L02 cells through the AMPK/Sirt1 signaling pathway. Further studies showed that the curative effect of LB100 on lipid accumulation was abolished by inhibiting AMPKα in L02 cells.CONCLUSIONPP2A inhibition by LB100 significantly ameliorates hepatic steatosis by regulating hepatic lipogenesis and fatty acid oxidation via the AMPK/Sirt1 pathway. LB100 may be a potential therapeutic agent for NAFLD.

Background and Aims. Recent studies have indicated that circulating miRNAs could serve as accurate biomarkers for diagnosing nonalcoholic fatty liver disease (NAFLD). We aimed to assess the evidence on the probability of circulating miRNAs as new diagnostic biomarkers in patients with NAFLD. Methods. We comprehensively retrieved relevant English literature from the databases of PubMed, Embase, and the Cochrane Library from 2000 to 1 January 2019. The diagnostic accuracy of circulating miRNAs as markers for NAFLD was analyzed. Moreover, we evaluated the methodological quality of the included article. STATA was applied to perform statistical analyses. Results. In this meta-analysis, 17 studies that enrolled 1408 patients of NAFLD and 926 healthy people from 6 articles were analyzed. We constructed a summary receiver-operating characteristic (SROC) curve of all circulating miRNAs, and the area under the curve (AUC) was 0.83, with the pooled sensitivity (SEN) 0.70 and the pooled specificity (SPE) 0.82 in distinguishing patients with NAFLD from healthy controls. Among them, miR-122 showed high diagnostic accuracy, with the diagnostic index of pooled SEN, SPE, and AUC being 0.88, 0.66, and 0.86, respectively. We then performed subgroup analyses based on the mode of miRNA regulation, countries, miRNA profiling, sample size, and male proportion. We then did a regression analysis and found the cause of heterogeneity might be miRNA profiling. Finally, publication bias was not found, and Fagan’s nomogram showed valuable clinical utility. Conclusion. Circulating miRNAs, especially miR-122, might be promising diagnostic biomarkers for NAFLD with high-accuracy, and more large-sample studies are required to support the above findings in the future.

Congenital tufting enteropathy (CTE), also named intestinal epithelial dysplasia, is a rare, autosomal recessive enteropathy with persistent and life-threatening intractable diarrhea early in life. Intractable diarrhea is present independent of breast or formula feeding. Most CTE patients require total parenteral nutrition (TPN), and in severe cases, small bowel transplantation is needed. In the last decade, we have seen remarkable progress in certain aspects, such as the pathogenesis and diagnostic methods of the disease. Rapidly developing molecular analysis techniques have improved the diagnostic methods for CTE and reduced invasive and expensive procedures. Mutations in the gene encoding human epithelial cell adhesion molecule (EpCAM) were identified in the typical form of CTE, which usually exhibits isolated refractory diarrhea. Moreover, the syndromic form of CTE features anal and choanal atresias as well as ophthalmologic signs, which are associated with mutations in the gene encoding Serine Peptidase Inhibitor Kunitz Type 2 (SPINT2). This article reviews CTE disease based on its clinical and histological presentation, etiology and pathogenesis, and management and outcome.