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Methylation of Septin9 Mediated by DNMT3a Enhances Hepatic Stellate Cells Activation and Liver Fibrogenesis.
Abstract Liver fibrosis, resulting from chronic and persistent injury to the liver, is a worldwide health problem. Advanced liver fibrosis results in cirrhosis, liver failure and even hepatocellular cancer (HCC), often eventually requiring liver transplantation, poses a huge health burden on the global community. However, the specific pathogenesis of liver fibrosis remains not fully understood. Numerous basic and clinical studies have provided evidence that epigenetic modifications, especially DNA methylation, might contribute to the activation of hepatic stellate cells (HSCs), the pivotal cell type responsible fo...
Source: Toxicology and Applied Pharmacology - December 5, 2016 Category: Toxicology Authors: Wu Y, Bu F, Yu H, Li W, Huang C, Meng X, Zhang L, Ma T, Li J Tags: Toxicol Appl Pharmacol Source Type: research

Calcineurin Inhibitors Downregulate HNF-1β and May Affect the Outcome of HNF1B Patients After Renal Transplantation
Conclusions: Because HNF1B-related disease is a heterozygous condition, CNIs used to prevent rejection may induce reduced expression of the nonmutated allele of HNF1B leading to a superimposed defect of HNF-1β transcriptional activity. Taking into account the specific risk of posttransplantation diabetes mellitus and liver disorders in HNF1B patients, these findings advocate for in-depth characterization of pathways that regulate HNF1B and plead for considering individually tailored graft management that may include a CNI-free immunosuppressive regimen. Interventional studies will have to confirm this individualized approach.
Source: Transplantation - August 24, 2016 Category: Transplant Surgery Tags: Original Clinical Science-General Source Type: research

The Myeloid HSF1 ‐Β‐Catenin Axis Regulates NLRP3 Inflammasome Activation in Mouse Liver Ischemia/Reperfusion Injury
Conclusions: The myeloid HSF1‐β‐catenin axis controlled NLRP3 activation by modulating the XBP1 signaling pathway. HSF1 activation promoted β‐catenin, which in turn inhibited XBP1, leading to NLRP3 inactivation and reduced IR‐induced liver injury. Our findings demonstrated that HSF1‐β‐catenin signaling is a novel regulator of innate immunity in liver inflammatory injury and implied the therapeutic potential for the management of sterile liver inflammation in transplant recipients. This article is protected by copyright. All rights reserved.
Source: Hepatology - July 29, 2016 Category: Internal Medicine Authors: Shi Yue, Jianjun Zhu, Ming Zhang, Changyong Li, Xingliang Zhou, Min Zhou, Michael Ke, Ronald W. Busuttil, Qilong Ying, Jerzy W. Kupiec ‐Weglinski, Qiang Xia, Bibo Ke Tags: Liver Injury and Regeneration Source Type: research

Bi-directional roles of IRF-1 on autophagy diminish its prognostic value as compared with Ki67 in liver transplantation for hepatocellular carcinoma.
Authors: Zhang HM, Li SP, Yu Y, Wang Z, He JD, Xu YJ, Zhang RX, Zhang JJ, Zhu ZJ, Shen ZY Abstract The prognostic values of IRF-1 and Ki-67 for liver transplantation (LT) of hepatocellular carcinoma (HCC) were investigated, as well as the mechanisms of IRF-1 in tumor suppression. Adult orthotropic liver transplantation cases (N = 127) were involved in the analysis. A significant decreased recurrence free survival (RFS) was found in the Ki-67 positive groups. Ki-67, tumor microemboli, the Milan and UCSF criteria were found to be independent risk factors for RFS. In LT for HCC beyond the Milan criteria, a significant...
Source: Oncotarget - May 20, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Identification of NUCKS1 as a putative oncogene and immunodiagnostic marker of hepatocellular carcinoma.
Abstract Although the molecular mechanisms underpinning hepatocellular carcinoma (HCC) are unknown, gene copy number and associated mRNA expression changes are frequently reported. Comparative genomic hybridization arrays spotted with 4041 bacterial artificial chromosome clones were used to assess copy number changes in 45 HCC tissues. Seventy more HCC tissues were used to validate candidate genes by using western blots and immunohistochemistry. A total of 259 clones were associated with copy number changes that significantly differed between normal liver and HCC samples. The chromosomal region 1q32.1 containing t...
Source: Gene - March 8, 2016 Category: Genetics & Stem Cells Authors: Cheong JY, Kim YB, Woo JH, Kim DK, Yeo M, Yang SJ, Yang KS, Soon SK, Wang HJ, Kim BW, Park JH, Cho SW Tags: Gene Source Type: research

New role and molecular mechanism of Gadd45a in hepatic fibrosis.
CONCLUSION: Gadd45a may counteract hepatic fibrosis by regulating the activation of HSCs via the inhibition of TGF-β/Smad signaling. PMID: 26973416 [PubMed - in process]
Source: World Journal of Gastroenterology : WJG - March 7, 2016 Category: Gastroenterology Authors: Hong L, Sun QF, Xu TY, Wu YH, Zhang H, Fu RQ, Cai FJ, Zhou QQ, Zhou K, Du QW, Zhang D, Xu S, Ding JG Tags: World J Gastroenterol Source Type: research

 IL-1β siRNA adenovirus benefits liver regeneration by improving mesenchymal stem cells survival after acute liver failure.
CONCLUSION: IL-1? siRNA adenovirus could enhance MSC ability of tissue regeneration through increasing its survival rate. Accordingly, combination of IL-1? siRNA adenovirus and MSC had a synergistic effect on acute liver failure. PMID: 26845604 [PubMed - as supplied by publisher]
Source: Annals of Hepatology - February 5, 2016 Category: Gastroenterology Tags: Ann Hepatol Source Type: research

Inhibition of human hepatocellular carcinoma tumor angiogenesis by siRNA silencing of VEGF via hepatic artery perfusion.
CONCLUSIONS: Our data demonstrated that VEGF silencing could suppress cells proliferation, promote cells apoptosis and reduce HCC angiogenesis through inactivation of VEGF/PI3K/AKT signaling pathway. PMID: 26744866 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - January 15, 2016 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

Preparation and evaluation of a non-viral gene vector for SiRNA: Multifunctional envelope-type nano device.
Authors: Zhang Y, Wei H, Xu L, Yan G, Ma C, Yu M, Wei C, Sun Y Abstract We prepared and evaluated a multifunctional envelope-type nano device (MEND) as a liver-targeting and long-circulation carrier for SiRNA. The polymer GA-PEG-Pp-DOPE was synthesized by modifying polyethylene glycol (PEG) with glycyrrhetinic acid (GA), peptide (Pp), and dioleoyl phosphoethanolamine (DOPE). The Pp is a substrate of matrix metalloproteinase 2. MEND was prepared with GA-PEG-Pp-DOPE and cationic phospholipids by the filming-rehydration method, and the orthogonal test was applied to optimize the prescription. The results of the biolog...
Source: Artificial Cells, Nanomedicine and Biotechnology - December 12, 2015 Category: Biotechnology Tags: Artif Cells Nanomed Biotechnol Source Type: research

HERC5 is a prognostic biomarker for post-liver transplant recurrent human hepatocellular carcinoma
Conclusions: HERC5 plays a crucial role in HCC immune evasion and has clinical relevance as a reproducible prognostic marker for risk of tumor recurrence and survival in patients.
Source: Journal of Translational Medicine - December 11, 2015 Category: Research Authors: Feng XueBrandon HiggsJiaqi HuangChris MorehouseWei ZhuXin YaoPhilip BrohawnZhan XiaoYinong SebastianZheng LiuYun XiaDong ShenMike KuzioraZhengwei DongHulin HanYi GuJianren GuQiang XiaYihong Yao Source Type: research

Theranostical nanosystem‐mediated identification of an oncogene and highly effective therapy in hepatocellular carcinoma
In conclusion, the theranostic siRNA nanomedicine examined here possesses great theranostic potential for combined gene therapy and MRI diagnosis of HCC. This article is protected by copyright. All rights reserved.
Source: Hepatology - December 1, 2015 Category: Internal Medicine Authors: Yu Guo, Jing Wang, Lu Zhang, Shunli Shen, Ruomi Guo, Yang Yang, Wenjie Chen, Yiru Wang, Guihua Chen, Xintao Shuai Tags: Hepatobiliary Malignancies Source Type: research

Hsp90 and hepatobiliary transformation during sea lamprey metamorphosis
Conclusions: HSP90 appears to play crucial roles in hepatobiliary transformation during sea lamprey metamorphosis. Sea lamprey is a useful animal model to study postembryonic development and mechanisms for hsp90-induced hepatobiliary transformation.
Source: BMC Developmental Biology - December 1, 2015 Category: Zoology Authors: Yu-Wen Chung-DavidsonChu-Yin YehUgo BussyKe LiPeter DavidsonKaben NanlohyC. BrownSteven WhyardWeiming Li Source Type: research

In vivo efficacy and off-target effects of locked nucleic acid (LNA) and unlocked nucleic acid (UNA) modified siRNA and small internally segmented interfering RNA (sisiRNA) in mice bearing human tumor xenografts.
We report that LNA and UNA modified siRNA and sisiRNA improve the efficacy in target knockdown as compared with unmodified siRNA in the tumor xenografts without formulation. However, the level of off-target gene regulation in both the tumor and the liver correlated with the increase in efficacy in target knockdown, unless the seed region of the siRNA was modified. PMID: 21687525 [PubMed - as supplied by publisher]
Source: Artificial DNA: PNA and XNA - November 19, 2015 Category: Genetics & Stem Cells Tags: Artif DNA PNA XNA Source Type: research

RNA Interference as a Therapeutic Strategy for the Treatment of Liver Diseases.
Abstract RNA interference has emerged as an innovative technology for gene silencing that degrades mRNAs complementary to the antisense strands of double-stranded, short interfering RNAs (siRNAs). Its therapeutic application has important advantages over small-molecule drugs since offers the possibility of targeting virtually all genes and allows selective silencing of one or several genes. So far, a relative small proportion of cellular proteins can bind and respond to chemical drugs. Based on that, RNA interference-mediated gene silencing is widely considered as a crucial breakthrough in molecular biology with a...
Source: Current Pharmaceutical Design - October 23, 2015 Category: Drugs & Pharmacology Authors: Gonzalez-Rodriguez A, Valverde AM Tags: Curr Pharm Des Source Type: research

Inhibition of Interferon Regulatory Factor 4 Attenuates Acute Liver Allograft Rejection in Mice
In conclusion, inhibition of IRF4 attenuates acute liver allograft rejection in mice, and this is associated with promoted M2 macrophage differentiation. This article is protected by copyright. All rights reserved.
Source: Scandinavian Journal of Immunology - June 12, 2015 Category: Allergy & Immunology Authors: Wei Zhao, Zhong Zhang, Qingjun Zhao, Mengjie Liu, Yuelan Wang Tags: Regular Article Source Type: research

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