Review of recent research on hepatitis C therapy for 54th annual meeting of the American association for the study of liver diseases

This Clinical Practice Guideline (CPG) has been developed to assist physicians and other healthcare providers in the diagnosis and management of patients with Wilson's disease. The goal is to describe a number of generally accepted approaches for diagnosis, prevention, and treatment of Wilson's disease. Recommendations are based on a systematic literature review in the Medline (PubMed version), Embase (Dialog version), and the Cochrane Library databases using entries from 1966 to 2011. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system used in other EASL CPGs was used and set against the somewhat different grading system used in the AASLD guidelines (Table 1A and B). Unfortunately, there is not a single randomized controlled trial conducted in Wilson's disease which has an optimal design. Thus, it is impossible to assign a high or even a moderate quality of evidence to any of the questions dealt with in these guidelines. The evaluation is mostly based on large case series which have been reported within the last decades.

EASL Clinical Practice Guidelines: Wilson's disease

MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

Thioredoxins (Trxs), glutaredoxins (Grxs), and peroxiredoxins (Prxs) have been characterized as electron donors, guards of the intracellular redox state, and “antioxidants”. Today, these redox catalysts are increasingly recognized for their specific role in redox signaling. The number of publications published on the functions of these proteins continues to increase exponentially. The field is experiencing an exciting transformation, from looking at a general redox homeostasis and the pathological oxidative stress model to realizing redox changes as a part of localized, rapid, specific, and reversible redox-regulated signaling events. This review summarizes the almost 50 years of research on these proteins, focusing primarily on data from vertebrates and mammals. The role of Trx fold proteins in redox signaling is discussed by looking at reaction mechanisms, reversible oxidative post-translational modifications of proteins, and characterized interaction partners. On the basis of this analysis, th...

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Thioredoxins, glutaredoxins, and peroxiredoxins--molecular mechanisms and health significance: from cofactors to antioxidants to redox signaling.

Apoptosis is a form of cell death by which the body maintains the homeostasis of the internal environment. Apoptosis is an initiative cell death process that is controlled by genes and is mainly divided into endogenous pathways (mitochondrial pathway), exogenous pathways (death receptor pathway), and apoptotic pathways induced by endoplasmic reticulum (ER) stress. The homeostasis imbalance in ER results in ER stress. Under specific conditions, ER stress can be beneficial to the body; however, if ER protein homeostasis is not restored, the prolonged activation of the unfolded protein response may initiate apoptotic cell death via the up-regulation of the C/EBP homologous protein (CHOP). CHOP plays an important role in ER stress-induced apoptosis and this review focuses on its multifunctional roles in that process, as well as its role in apoptosis during microbial infection. We summarize the upstream and downstream pathways of CHOP in ER stress induced apoptosis. We also focus on the newest discoveries in the functions of CHOP-induced apoptosis during microbial infection, including DNA and RNA viruses and some species of bacteria. Understanding how CHOP functions during microbial infection will assist with the development of antimicrobial therapies.

The C/EBP Homologous Protein (CHOP) Transcription Factor Functions in Endoplasmic Reticulum Stress-Induced Apoptosis and Microbial Infection

Hepatocellular carcinoma (HCC) is well known as the sixth most common malignant tumor and the third leading cause of cancer-related deaths globally. LINC00152 was documented as an important long non-coding RNA (lncRNA) involved in the pathogenesis of gastric cancer; however, the detailed mechanism of action of LINC00152 remains unknown. Here, based on the increased level of LINC00152 in HCC tissues, we found that LINC00152 could promote cell proliferation in vitro and tumor growth in vivo. Furthermore, microarray-based analysis indicated that LINC00152 could activate the mechanistic target of rapamycin(mTOR) pathway by binding to the promoter of EpCAM through a cis-regulation, as confirmed by Gal4-λN/BoxB reporter system. Thus, LINC00152 might be involved in the oncogenesis of HCC by activating the mTOR signaling pathway and might be a novel index for clinical diagnosis in the future.

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LINC00152 promotes proliferation in hepatocellular carcinoma by targeting EpCAM via the mTOR signaling pathway.

We explored the role of microRNA-30a (miR-30a) and the mechanism involved in hepatic fibrosis. MiR-30a overexpression was achieved by miR-30a mimics transfection in hepatic stellate cells (HSCs) (HSC-T6, LX-2), and miR-30a agomir (ago-miR-30a) treatment in mice. MiR-30a levels were measured using TaqMan miRNA assay system, and the localization of miR-30a was detected by fluorescence in situ hybridization (FISH). The interaction of miR-30a and Beclin1 was confirmed by dual-luciferase reporter assay. Autophagic flux was analysed using tandem mRFP-GFP-LC3 fluorescence microscopy, electron microscopy and Western blot of LC3-II/I ratio. MiR-30a was notably down-regulated in activated HSCs and LX-2-exosomes induced by TGF-β1; overexpression of miR-30a down-regulated extracellular matrix (ECM), such as α-SMA, TIMP-1, and Collagen I expression, and suppressed cell viability in HSCs. MiR-30a was significantly down-regulated in hepatic fibrosis mice and overexpression of miR-30a prevented BDL-induced fibrogenesis, concomitant with the down-regulation of ECM. MiR-30a inhibited HSCs autophagy and increased lipid accumulation in HSCs and in mice fibrotic hepatic tissues. MiR-30a inhibited its downstream effector of Beclin1 by direct targeting its 3'-UTR region. Moreover, Knock-down of Beclin1 by small interfering RNA (siRNA) inhibited HSC autophagy and activation in LX-2 cells. In conclusion, miR-30a is down-regulated in hepatic fibrosis models and its overexpression prevents liver fibrogenesis by directly suppressing Beclin1-mediated autophagy; therefore, miR-30a may be a new potential therapeutic target for controlling hepatic fibrosis.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jcmm.13278

MicroRNA-30a ameliorates hepatic fibrosis by inhibiting Beclin1-mediated autophagy.

Mesenchymal stem cells over-expressing hepatocyte growth factor improve small-for-size liver grafts regeneration.

Gallstone ileus (GI) is characterized by occlusion of the intestinal lumen as a result of one or more gallstones. GI is a rare complication of gallstones that occurs in 1%-4% of all cases of bowel obstruction. The mortality associated with GI ranges between 12% and 27%. Classical findings on plain abdominal radiography include: (1) pneumobilia; (2) intestinal obstruction; (3) an aberrantly located gallstone; and (4) change of location of a previously observed stone. The optimal management of acute GI is controversial and can be: (1) enterotomy with stone extraction alone; (2) enterotomy, stone extraction, cholecystectomy and fistula closure; (3) bowel resection alone; and (4) bowel resection with fistula closure. We describe a case to highlight some of the pertinent issues involved in GI management, and propose a scheme to minimize recurrent disease and postoperative complications. We conclude that GI is a rare condition affecting mainly the older population with a female predominance. The advent of computed tomography and magnetic resonance imaging has made it easier to diagnose GI. Enterotomy with stone extraction alone remains the most common surgical method because of its low incidence of complications.

Gallstone ileus: Case report and literature review

Objectives: In this study, we characterized the expression of 32 other kinesin superfamily proteins (KIFs) and analyzed their association with the progression and prognosis of hepatocellular carcinoma (HCC). Materials and Methods: The data from 295 HCC patients from The Cancer Genome Atlas were included in the study. An independent t-test was used to compare the KIF levels in HCC and adjacent tissues. Pearson's Chi-square test was used to assess the relationships of KIF expression with tumor biomarkers and clinicopathological parameters. Kaplan–Meier plots and log-rank tests were used to analyze survival, and univariate and multivariate analyses were used to identify independent prognostic factors. Results: The expressions of 32 KIFs were compared between HCC and adjacent nontumor tissues. Among them, 12 KIFs showed no statistical significance, 17 KIFs were upregulated, and three KIFs were downregulated in tumor tissues. The levels of some KIFs were markedly correlated with that of biomarkers for the S phase and proliferation. KIF2A and KIFC3 expression was positively associated with biomarkers for cell invasion and migration. Some KIF overexpression was significantly associated with neoplastic pathological grade and tumor-node-metastasis staging. Furthermore, KIF2C, KIF4A, and KIF11 overexpression were significantly associated with shorter relapse-free survival times. KIF2A, KIF2C, KIF3A, KIF4B, KIF11, KIF15, KIFC1, and KIFC3 overexpression was associated with shorter overall survival (OS) times, whereas higher expression of KIF19 was associated with a longer OS time. Further multivariate analyses suggested that only KIF4B was an independent prognostic factor for HCC. Conclusions: Most overexpressions of abnormal KIFs were significantly associated with HCC progression and prognosis, indicating that KIFs could be prognostic and therapeutic biomarkers for HCC. However, it is necessary to further study the function of KIFs and their mechanisms involved in HCC.

Guoqiang Li

Papers

LINC00152 promotes proliferation in hepatocellular carcinoma by targeting EpCAM via the mTOR signaling pathway.

MicroRNA-30a ameliorates hepatic fibrosis by inhibiting Beclin1-mediated autophagy.

Mesenchymal stem cells over-expressing hepatocyte growth factor improve small-for-size liver grafts regeneration.

Gallstone ileus: Case report and literature review

Kinesin superfamily protein expression and its association with progression and prognosis in hepatocellular carcinoma