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hepatic fibrosis

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https://www.readbyqxmd.com/read/28334911/mertk-rs4374383-variant-predicts-incident-nonalcoholic-fatty-liver-disease-and-diabetes-role-of-mononuclear-cell-activation-and-adipokine-response-to-dietary-fat
#1
Giovanni Musso, Maurizio Cassader, Franco De Michieli, Elena Paschetta, Silvia Pinach, Francesca Saba, Daria Bongiovanni, Luciana Framarin, Mara Berrutti, Nicola Leone, Stefania Corvisieri, Renato Parente, Federica Molinaro, Antonio Sircana, Bo Simona, Roberto Gambino
The loss-of-function rs4374383 G>A variant in Myeloid-epithelial-reproductive Tyrosine Kinase (MERTK) gene has been linked to hepatic fibrosis in chronic liver diseases. MERTK is expressed by immune and non-immune cells involved in inflammation, metabolism and vascular homeostasis. We assessed the impact of MERTK rs4374383 G>A variant on nonalcoholic fatty liver disease (NAFLD) incidence and severity and on glucose and lipid metabolism.We followed-up 305 healthy nonobese nondiabetic, metabolic syndrome-free insulin sensitive participants in a population-based study, characterized for MERTK G>A polymorphism, adipokine profile and inflammatory markers...
March 8, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28333073/effects-of-melatonin-on-liver-injuries-and-diseases
#2
REVIEW
Jiao-Jiao Zhang, Xiao Meng, Ya Li, Yue Zhou, Dong-Ping Xu, Sha Li, Hua-Bin Li
Liver injuries and diseases are serious health problems worldwide. Various factors, such as chemical pollutants, drugs, and alcohol, could induce liver injuries. Liver diseases involve a wide range of liver pathologies, including hepatic steatosis, fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocarcinoma. Despite all the studies performed up to now, therapy choices for liver injuries and diseases are very few. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries and diseases remains a priority...
March 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28332306/impact-of-iatrogenic-iron-overload-on-the-course-of-hepatitis-c-in-dialysis-population-a-plea-for-caution
#3
Guy Rostoker, Nosratola D Vaziri
About 2.5% of the world population, corresponding to about 177 million individuals, are infected by hepatitis C virus (HCV), a small, single-stranded RNA virus. The prevalence of HCV infection among dialysis patients in Japan, Europe, and North America during the 2012 to 2015 period was found to be 8.7% in the DOPPS study. Nosocomial HCV spread in hemodialysis facilities still occurs. Increased hepatic tissue iron has been shown to play a deleterious role in the course of hepatitis C, favor development of fibrosis and cirrhosis and possibly increase the risk of liver cancer in the general population...
March 23, 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28332284/ezh2-mediated-repression-of-dkk1-promotes-hepatic-stellate-cell-activation-and-hepatic-fibrosis
#4
Yang Yang, Xiao-Xia Chen, Wan-Xia Li, Xiao-Qin Wu, Cheng Huang, Juan Xie, Yu-Xin Zhao, Xiao-Ming Meng, Jun Li
EZH2, a histone H3 lysine-27-specific methyltransferase, is involved in diverse physiological and pathological processes including cell proliferation and differentiation. However, the role of EZH2 in liver fibrosis is largely unknown. In this study, it was identified that EZH2 promoted Wnt pathway-stimulated fibroblasts in vitro and in vivo by repressing Dkk-1, which is a Wnt pathway antagonist. The expression of EZH2 was increased in CCl4 -induced rat liver and primary HSCs as well as TGF-β1-treated HSC-T6, whereas the expression of Dkk1 was reduced...
March 23, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28332100/expression-of-programmed-death-1-and-its-ligands-in-the-liver-of-biliary-atresia
#5
Pan-Liang Wang, Jun Wang, Ying Zhou, Xiao-Song Chen, Ke-Jun Zhou, Jie Wen, Jian-Jun Zhang, Wei Cai
BACKGROUND: An aberrant immune response is the predominant pathogenetic factor in biliary atresia (BA). Programmed death-1 (PD-1) and its two ligands, programmed death ligand-1 and programmed death ligand-2 (PD-L1 and PD-L2, respectively) play an important inhibitory role in immune reactions. We aimed to illustrate the expression of these molecules in BA. METHODS: Liver specimens were obtained from infants with BA during the Kasai procedure (early BA) and liver transplantation (late BA)...
March 22, 2017: World Journal of Pediatrics: WJP
https://www.readbyqxmd.com/read/28331563/%C3%A2-evaluation-of-serum-hbv-viral-load-transaminases-and-histological-features-in-chronic-hbeag-negative-hepatitis-b-patients
#6
Abbas Esmaeelzadeh, Hassan Saadatnia, Bahram Memar, Elham Mokhtari Amirmajdi, Azita Ganji, Ladan Goshayeshi, Zahra Meshkat, Alireza Pasdar, Hassan Vosoughinia, Mohammadreza Farzanehfar, Shahrzad Tehranian, Kamran Ghaffarzadehgan, Farnood Rajabzadeh, Mitra Ahadi
AIM: To evaluate the association between biochemical, virologic and histologic features in patients with HBeAg-negative chronic hepatitis B (CHB). BACKGROUND: Hepatitis-B e-antigen (HBeAg)-negative is common in Iran, is progressive with poor prognosis. Therefore, it seems necessary to perform a comprehensive evaluation of different spectrum of laboratory measurements accompanying histological findings. METHODS: HBeAg- negative CHB patients referring to two university hospitals during two years were enrolled...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28331224/enhanced-wnt-signalling-in-hepatocytes-is-associated-with-schistosoma-japonicum-infection-and-contributes-to-liver-fibrosis
#7
Qi Wang, Xin Chou, Fei Guan, Zhengming Fang, Shengjun Lu, Jiahui Lei, Yonglong Li, Wenqi Liu
Liver fibrosis is the most serious pathology caused by Schistosoma japonicum infection, which arises when schistosome eggs are deposited in the liver. Eosinophils, macrophages and hepatic stellate cells (HSCs) have been identified as major cellular contributors to the development of granulomas and fibrosis, but little is known about the effects of hepatocytes on granuloma formation. Here, we found that the levels of Wnt signalling-related molecules, transforming growth factor β (TGF-β) and connective tissue growth factor (CTGF) in hepatocytes were markedly elevated after S...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28329108/increased-mortality-among-persons-with-chronic-hepatitis-c-with-moderate-or-severe-liver-disease-a-cohort-study
#8
Javier A Cepeda, David L Thomas, Jacquie Astemborski, Mark S Sulkowski, Gregory D Kirk, Shruti H Mehta
Background: Despite the availability of curative treatment for hepatitis C virus (HCV) infection, because of cost, treatment is often denied until liver fibrosis has progressed to at least moderate fibrosis and in some cases cirrhosis. That practice is justified on assumptions that there are no medical consequences to having moderate disease and that disease stage transitions can be anticipated. Methods: We performed transient elastography on 964 people chronically infected with HCV with a history of injection drug use living in Baltimore, Maryland...
March 10, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28328941/cynomolgus-monkeys-are-successfully-and-persistently-infected-with-hepatitis-e-virus-genotype-3-hev-3-after-long-term-immunosuppressive-therapy
#9
Noemi Rovaris Gardinali, Juliana Rodrigues Guimarães, Juliana Gil Melgaço, Yohan Britto Kevorkian, Fernanda de Oliveira Bottino, Yasmine Rangel Vieira, Aline Campos de Azevedo da Silva, Douglas Pereira Pinto, Laís Bastos da Fonseca, Leandro Schiavo Vilhena, Edilson Uiechi, Maria Cristina Carlan da Silva, Julio Moran, Renato Sérgio Marchevsky, Oswaldo Gonçalves Cruz, Rodrigo Alejandro Arellano Otonel, Amauri Alcindo Alfieri, Jaqueline Mendes de Oliveira, Ana Maria Coimbra Gaspar, Marcelo Alves Pinto
Epidemiological studies found that hepatitis E virus genotype 3 (HEV-3) infection was associated with chronic hepatitis and cirrhosis in immunocompromised patients. Our study aimed to investigate the relationship between the host immunosuppressive status and the occurrence of HEV-related chronic hepatitis. Here we describe a successful experimental study, using cynomolgus monkeys previously treated with tacrolimus, a potent calcineurin inhibitor immunosuppressant, and infected with a Brazilian HEV-3 strain isolated from naturally infected pigs...
2017: PloS One
https://www.readbyqxmd.com/read/28328813/evaluation-of-apri-and-fib-4-for-noninvasive-assessment-of-significant-fibrosis-and-cirrhosis-in-hbeag-negative-chb-patients-with-alt%C3%A2-%C3%A2-%C3%A2-2-uln-a-retrospective-cohort-study
#10
Qiang Li, Xiaojing Ren, Chuan Lu, Weixia Li, Yuxian Huang, Liang Chen
To evaluate the performance of aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) to predict significant fibrosis and cirrhosis in hepatitis B virus e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with alanine transaminase (ALT) ≤ twice the upper limit of normal (2 ULN).Histologic and laboratory data of 236 HBeAg-negative CHB patients with ALT ≤ 2 ULN were analyzed. Predicted fibrosis stage, based on established scales and cut-offs for APRI and FIB-4, was compared with METAVIR scores obtained from liver biopsy...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28327812/platelet-derived-growth-factor-a-mrna-in-platelets-is-associated-with-the-degree-of-hepatic-fibrosis-in-chronic-hepatitis-c
#11
Aline Aki Tanikawa, Rejane Maria Tommasini Grotto, Giovanni Faria Silva, Adriana Camargo Ferrasi, Valéria Cristina Rodrigues Sarnighausen, Maria Inês de Moura Campos Pardini
INTRODUCTION: Transforming growth factor beta 1 (TGFB1) and platelet-derived growth factor (PDGF) are the main cytokines related to hepatic fibrogenesis. METHODS: RNA isolated from the platelets and hepatic tissue of 43 HCV carriers was used for quantitative polymerase chain reaction to determine TGFB1, PDGFA, and PDGFB RNA expression. RESULTS: The mRNA expression of PDGFA in platelets was significantly lower in the group with advanced fibrosis than in the group with early-stage fibrosis...
January 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28327670/global-identification-and-analysis-of-isozyme-specific-possible-substrates-crosslinked-by-transglutaminases-using-substrate-peptides-in-mouse-liver-fibrosis
#12
Hideki Tatsukawa, Yuji Tani, Risa Otsu, Haruka Nakagawa, Kiyotaka Hitomi
The transglutaminase (TG) family comprises eight isozymes that form the isopeptide bonds between glutamine and lysine residues and contribute to the fibrotic diseases via crosslinking-mediated stabilization of ECM and the activation of TGF-β in several tissues. However, despite a growing body of evidence implicating TG2 as a key enzyme in fibrosis, the causative role of TG2 and the involvement of the other isozymes have not yet been fully elucidated. Therefore, here we clarified the distributions of TG isozymes and their in situ activities and identified the isozyme-specific possible substrates for both TG1 and TG2 using their substrate peptides in mouse fibrotic liver...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327434/-99m-tc-3prgd2-scintigraphy-to-stage-liver-fibrosis-and-evaluate-reversal-after-fibrotic-stimulus-withdrawn
#13
Xin Zhang, Qiyong Guo, Yu Shi, Weina Xu, Shupeng Yu, Zhiguang Yang, Li Cao, Changping Liu, Zhoushe Zhao, Jun Xin
OBJECTIVE: Scintigraphy using 99mTc-3PRGD2 targeting integrin αvβ3 could assess activation of hepatic stellate cells (HSCs). Liver fibrogenesis is intimately associated with activation of HSCs, and the fibrolytic process is accompanied by the reduction of the activated HSCs. In this study, we aimed to evaluate the feasibility of this method to assess the severity of liver fibrosis and the reversal after the fibrotic stimulus withdrawal. METHODS: Liver fibrosis of different stages was induced by thioacetamide (TAA) injection for 2, 4 and 6 weeks (n = 6 for each time point)...
March 7, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28325896/egg-antigen-p40-of-schistosoma-japonicum-promotes-senescence-in-activated-hepatic-stellate-cells-via-skp2-p27-signaling-pathway
#14
Tianhua Xu, Jinling Chen, Dandan Zhu, Liuting Chen, Jianxin Wang, Xiaolei Sun, Bin Hu, Yinong Duan
Schistosomiasis is characterized by egg deposition, granulomatous inflammatory reaction and then subsequent hepatic fibrosis formation. Activated HSCs are regarded as the main effector cells in the progression of liver fibrosis and induction of senescence in hepatic stellate cells (HSCs) is vital to the reversion of hepatic fibrosis. Our previous work has showed that S. japonicum egg antigen p40 (Sjp40) could promote HSCs senescence via a STAT3/p53/p21 mechanism. In this paper, the major aim was to explore whether there are other signaling pathways in the process of Sjp40-induced HSCs aging and the underlying effect of SKP2/P27 signal pathway in this procedure...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28323868/-waiting-for-daas-a-retrospective-chart-review-of-patients-with-untreated-hepatitis-c-in-rwanda
#15
Neil Gupta, Jules Kabahizi, Constance Mukabatsinda, Timothy David Walker, Emmanuel Musabeyezu, Athanase Kiromera, Jennifer Ilo Van Nuil, Kevin Steiner, Joia Mukherjee, Sabin Nsanzimana, Aimable Mbituyumuremyi
BACKGROUND: Access to treatment for hepatitis C virus (HCV) in sub-Saharan Africa is extremely limited. With the advent of direct acting antivirals (DAAs), highly effective and easy-to-deliver oral regimens are now available on the global market. This study was conducted to understand the background and characteristics of a national cohort of patients with HCV infection enrolled in care and awaiting therapy with DAAs. METHODS AND FINDINGS: We conducted a retrospective chart review of all adult patients with confirmed HCV infection who were currently enrolled in care and treatment at the four existing hepatitis referral centers in Rwanda...
2017: PloS One
https://www.readbyqxmd.com/read/28323124/cd44-is-a-key-player-in-non-alcoholic-steatohepatitis
#16
Stéphanie Patouraux, Déborah Rousseau, Stéphanie Bonnafous, Cynthia Lebeaupin, Carmelo Luci, Clémence M Canivet, Anne-Sophie Schneck, Adeline Bertola, Marie-Christine Saint-Paul, Antonio Iannelli, Jean Gugenheim, Rodolphe Anty, Albert Tran, Béatrice Bailly-Maitre, Philippe Gual
BACKGROUND: CD44 is expressed on many immune cells that contribute to inflammation. It has been shown, mainly through animal data, that CD44 regulates adipose tissue inflammation in obesity and hepatic leukocyte recruitment in a lithogenic context. However, its role in hepatic inflammation in a mouse model of steatohepatitis and its relevance in humans have not yet been investigated. METHODS: The role of CD44 was evaluated in CD44-/- mice and after injections of an αCD44 antibody in Wild-type mice challenged with a methionine- and choline-deficient diet (MCDD)...
March 16, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28322865/palmitic-acid-elicits-hepatic-stellate-cell-activation-through-inflammasomes-and-hedgehog-signaling
#17
Na-Na Duan, Xue-Jing Liu, Jian Wu
AIMS: Activation of hepatic stellate cells (HSCs) plays a pivotal role at the center of the fibrogenic progression in nonalcoholic steatohepatitis (NASH). However, it is poorly understood that how various molecules interact within HSCs during the progression of NASH to fibrosis. The aim of the present study is to delineate how inflammasome molecules, hedgehog signaling and autophagy provoke HSC activation using palmitic acid (PA) as a major insult. MAIN METHODS: Inflammasome activation, hedgehog signaling activity and autophagy in PA-exposed HSCs were determined to investigate their role in activation of human and rodent HSC lines or primary HSCs...
March 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28322443/all-trans-retinoic-acid-ameliorates-hepatic-stellate-cell-activation-via-suppression-of-thioredoxin-interacting-protein-expression
#18
Hiroki Shimizu, Toshiaki Tsubota, Keita Kanki, Goshi Shiota
Activation of hepatic stellate cells (HSCs) is the effector factor of hepatic fibrosis and hepatocellular carcinoma (HCC) development. Accumulating evidence suggests that retinoic acids (RAs), derivatives of vitamin A, contribute to prevention of liver fibrosis and carcinogenesis, however, regulatory mechanisms of RAs still remain exclusive. To elucidate RA signaling pathway, we previously performed a genome-wide screening of RA-responsive genes by in silico analysis of RA-response elements, and identified 26 RA-responsive genes...
March 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28322315/quantitative-proteomic-analysis-on-activated-hepatic-stellate-cells-reversion-reveal-stat1-as-a-key-regulator-between-liver-fibrosis-and-recovery
#19
Hongyu Zhang, Fangyan Chen, Xu Fan, Cong Lin, Yunwei Hao, Handong Wei, Weiran Lin, Ying Jiang, Fuchu He
Understanding the changes of activated HSCs reversion is an essential step toward clarifying the potential roles of HSCs in the treatment of liver fibrosis. In this study, we chose adipocyte differentiation mixture to induce LX-2 cells for 2 days in vitro as reversion phase, comparing with normal cultured LX-2 cells as activation phase. Mass spectrometric-based SILAC technology was adopted to study differentially expressed proteome of LX-2 cells between reversion and activation. Compared with activated HSCs, 273 proteins showed significant differences in reverted HSCs...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322247/tricyclic-antidepressants-promote-ceramide-accumulation-to-regulate-collagen-production-in-human-hepatic-stellate-cells
#20
Jennifer Y Chen, Benjamin Newcomb, Chan Zhou, Joshua V Pondick, Sarani Ghoshal, Samuel R York, Daniel L Motola, Nicolas Coant, Jae Kyo Yi, Cungui Mao, Kenneth K Tanabe, Irina Bronova, Evgeny V Berdyshev, Bryan C Fuchs, Yusuf Hannun, Raymond T Chung, Alan C Mullen
Activation of hepatic stellate cells (HSCs) in response to injury is a key step in hepatic fibrosis, and is characterized by trans-differentiation of quiescent HSCs to HSC myofibroblasts, which secrete extracellular matrix proteins responsible for the fibrotic scar. There are currently no therapies to directly inhibit hepatic fibrosis. We developed a small molecule screen to identify compounds that inactivate human HSC myofibroblasts through the quantification of lipid droplets. We screened 1600 compounds and identified 21 small molecules that induce HSC inactivation...
March 21, 2017: Scientific Reports
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