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https://www.readbyqxmd.com/read/29457838/bax-inhibitor-1-protects-from-non-alcoholic-steatohepatitis-by-limiting-ire1%C3%AE-signaling
#1
Cynthia Lebeaupin, Déborah Vallée, Déborah Rousseau, Stéphanie Patouraux, Stéphanie Bonnafous, Gilbert Adam, Frederic Luciano, Carmelo Luci, Rodolphe Anty, Antonio Iannelli, Sandrine Marchetti, Guido Kroemer, Sandra Lacas-Gervais, Albert Tran, Philippe Gual, Béatrice Bailly-Maitre
Endoplasmic reticulum (ER) stress is activated in non-alcoholic fatty liver disease (NAFLD), raising the possibility that ER stress-dependent metabolic dysfunction, inflammation and cell death underlie the transition from steatosis to steatohepatitis (NASH). Bax inhibitor-1 (BI-1), a negative regulator of the ER stress sensor IRE1α, has yet to be explored in NAFLD as a hepatoprotective agent. We hypothesized that the genetic ablation of BI-1 would render the liver vulnerable to NASH due to unrestrained IRE1α signaling...
February 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29456412/performance-of-transient-elastography-in-assessing-liver-fibrosis-in-patients-with-autoimmune-hepatitis-primary-biliary-cholangitis-overlap-syndrome
#2
Hui-Min Wu, Li Sheng, Qi Wang, Han Bao, Qi Miao, Xiao Xiao, Can-Jie Guo, Hai Li, Xiong Ma, De-Kai Qiu, Jing Hua
AIM: To investigate the performance of transient elastography (TE) for diagnosis of fibrosis in patients with autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap syndrome. METHODS: A total of 70 patients with biopsy-proven AIH-PBC overlap syndrome were included. Spearman correlation test was used to analyze the correlation of liver stiffness measurement (LSM) and fibrosis stage. Independent samples Student's t -test or one-way analysis of variance was used to compare quantitative variables...
February 14, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29456362/joubert-syndrome-with-orofacial-digital-features
#3
Parveen Bhardwaj, Minoo Sharma, Karan Ahluwalia
Joubert syndrome (JS) is an autosomal recessive inherited disorder characterized by hypotonia, cerebellar vermis hypoplasia, ocular abnormalities (e.g., pigmentary retinopathy, oculomotor apraxia, and nystagmus), renal cysts, and hepatic fibrosis. Respiratory abnormalities, as apnea and hyperpnea, may be present, as well as mental retardation. Since the clinical findings of JS are quite heterogeneous, determination of radiological findings is essential.
January 2018: Journal of Neurosciences in Rural Practice
https://www.readbyqxmd.com/read/29455190/a-novel-paraneoplastic-syndrome-with-acquired-lipodystrophy-and-chronic-inflammatory-demyelinating-polyneuropathy-in-an-adolescent-male-with-craniopharyngioma
#4
Hillary Elizabeth Lockemer, Kathryn Maria Sumpter, Sandy Cope-Yokoyama, Abhimanyu Garg
BACKGROUND: Acquired lipodystrophy, craniopharyngioma and chronic inflammatory demyelinating polyneuropathy (CIDP) are individually rare disorders, and have never before been reported in a single patient. CASE PRESENTATION: A 15-year-7 month old Caucasian male presented with lower extremity weakness, frequent falls and abnormal fat distribution occurring over the previous 1 year. He was diagnosed with CIDP, craniopharyngioma and acquired lipodystrophy. The patient underwent tumor debulking and cranial irradiation for the craniopharyngioma, and received monthly intravenous immunoglobulin for the CIDP...
February 19, 2018: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/29455124/combination-effects-of-airborne-particulate-matter-exposure-and-high-fat-diet-on-hepatic-fibrosis-through-regulating-the-ros-endoplasmic-reticulum-stress-tgf%C3%AE-smads-axis-in-mice
#5
Shibin Ding, Lanlan Yu, Baijie An, Guofu Zhang, Pengxin Yu, Zhe Wang
BACKGROUND: Hepatic fibrosis, characterized by an excessive accumulation of extracellular matrix, is associated with toxic substance exposure, chronic infections, mechanical injury, airborne fine particulate matter (PM2.5 ) exposure and metabolic disease. This study aimed to investigate the effect and mechanism of long-term, real-world airborne particulate matter (PM) exposure on hepatic fibrosis and further explored whether combination treatment of PM exposure and high-fat diet (HFD) aggravate the adverse effects in mice...
February 14, 2018: Chemosphere
https://www.readbyqxmd.com/read/29454797/alterations-in-intestinal-microbiota-lead-to-production-of-interleukin-17-by-intrahepatic-%C3%AE-%C3%AE-t-cell-receptor-positive-cells-and-pathogenesis-of-cholestatic-liver-disease
#6
Dana Tedesco, Manoj Thapa, Chui-Yoke Chin, Yong Ge, Minghao Gong, Jing Li, Sanjeev Gumber, Patrick Speck, Elizabeth J Elrod, Eileen M Burd, William H Kitchens, Joseph F Magliocca, Andrew B Adams, David S Weiss, Mansour Mohamadzadeh, Arash Grakoui
BACKGROUND & AIMS: Variants at the ATP binding cassette subfamily B member 4 gene (ABCB4 or MDR2) locus, which encodes a biliary transport protein, are associated with a spectrum of cholestatic liver diseases. Exacerbation of liver disease has been linked to increased hepatic levels of interleukin 17 (IL17), yet the mechanisms of this increase are not understood. We studied mice with disruption of Mdr2 to determine how defects in liver and alteration in the microbiota contribute to production of IL17 by intrahepatic γδ T cells...
February 15, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29454793/p300-acetyltransferase-mediates-stiffness-induced-activation-of-hepatic-stellate-cells-into-tumor-promoting-myofibroblasts
#7
Changwei Dou, Zhikui Liu, Kangsheng Tu, Hongbin Zhang, Chen Chen, Usman Yaqoob, Yuanguo Wang, Jialing Wen, Jan van Deursen, Delphine Sicard, Daniel Tschumperlin, Hongzhi Zou, Wei-Chien Huang, Raul Urrutia, Vijay H Shah, Ningling Kang
BACKGROUND & AIMS: Hepatic stellate cells (HSCs) contribute to desmoplasia and stiffness of liver metastases by differentiating into matrix-producing myofibroblasts. We investigated whether stiffness due to the presence of tumors increases activation of HSCs into myofibroblasts and their tumor-promoting effects, as well as the role of E1A binding protein p300 (EP300 or p300), a histone acetyltransferase that regulates transcription, in these processes. METHODS: HSCs were isolated from liver tissues of patients, mice in which the p300 gene was flanked by 2 loxP sites (p300F/F mice), and p300+/+ mice (controls)...
February 15, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29454753/protein-s-exacerbates-chronic-liver-injury-and-fibrosis
#8
Toshiaki Totoki, Corina N D' Alessandro-Gabazza, Masaaki Toda, Prince Baffour Tonto, Atsuro Takeshita, Taro Yasuma, Kota Nishihama, Motoh Iwasa, Noriyuki Horiki, Yoshiyuki Takei, Esteban C Gabazza
Protein S is a vitamin K-dependent glycoprotein produced mainly in the liver with anticoagulant, anti-inflammatory, immune-modulatory, and anti-apoptotic properties. Protein S exacerbates acute liver injury by prolonging the survival of liver immune cells. However, the effect of protein S on chronic liver injury and fibrosis is unknown. Here we investigated whether human protein S can affect chronic liver injury and fibrosis. Liver injury/fibrosis was induced by carbon tetrachloride injection in mice overexpressing human protein S and in wild-type mice...
February 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29454647/dynamic-plasticity-of-macrophage-functions-in-diseased-liver
#9
Thomas Ritz, Oliver Krenkel, Frank Tacke
Liver macrophages attract increasing interest due to their crucial roles in homeostasis and hepatic diseases. Recent findings in mice and man suggest a remarkable phenotypic and functional diversity of liver macrophages. Kupffer cells, the subset of tissue resident macrophages with sentinel functions in liver, mainly arise from embryogenic precursors, whereas in injury, liver tissue is engrafted by monocyte-derived macrophages. Both principal macrophage populations respond to local or systemic signals and have substantial effects on reduction as well as aggravation of hepatic diseases...
December 20, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29451178/involvement-of-epithelial-mesenchymal-transition-in-liver-fibrosis
#10
REVIEW
Kangkang Yu, Qian Li, Guangfeng Shi, Ning Li
Fibrosis of the liver is an inherent wound healing response to chronic liver injury. Regeneration of liver epithelium and restoration of normal liver structure were generally involved in this process. Although the liver has a striking capacity to adapt to damage through tissue repair, excessive accumulation of extracellular matrix during this process often leads to scar tissue formation and subsequent fibrosis. Epithelial to mesenchymal transition (EMT) enables a polarized epithelial cell to undergo multiple changes biochemically and to bear a mesenchymal cell phenotype...
January 2018: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
https://www.readbyqxmd.com/read/29451090/study-of-changes-in-lipid-profile-and-insulin-resistance-in-egyptian-patients-with-chronic-hepatitis-c-genotype-4-in-the-era-of-daas
#11
Ghada El Sagheer, Elwy Soliman, Asmaa Ahmad, Lamiaa Hamdy
Chronic hepatitis C virus (HCV) infection is associated with altered metabolism, including dyslipidemia and insulin resistance. These contribute to disease progression and influences the response to therapy. To investigate the relationships of new direct-acting antiviral drugs, simeprevir/sofosbuvir, with lipid profile and insulin resistance (IR). Eighty chronic hepatitis C genotype 4 patients were included; they were divided into four groups according to the severity of fibrosis as detected by fibroscan. Forty healthy persons volunteered as a control group...
December 2018: Libyan Journal of Medicine
https://www.readbyqxmd.com/read/29450869/long-term-observation-of-acute-onset-autoimmune-hepatitis-presenting-clinically-and-radiologically-as-acute-hepatitis
#12
Keiichi Fujiwara, Yoshihiro Fukuda, Katsushi Seza, Masaya Saito, Shin Yasui, Masayuki Nakano, Osamu Yokosuka, Naoya Kato
BACKGROUND: There is yet no gold standard for the diagnosis of acute-onset autoimmune hepatitis (A-AIH), especially histologically acute AIH. As a result, long-term observation of A-AIH has been difficult and the nature is not well known. We retrospectively analyzed the clinicopathological features of A-AIH over a long prospective follow-up period. METHODS: Clinical, biochemical, immunological and pathological features of 30 patients (21 female, mean age 55.1 ± 13...
February 15, 2018: Hepatology International
https://www.readbyqxmd.com/read/29448843/cenicriviroc-for-the-treatment-of-non-alcoholic-steatohepatitis-and-liver-fibrosis
#13
Frank Tacke
Nonalcoholic fatty liver disease (NAFLD) has an increasing prevalence worldwide. At present, no specific pharmacotherapy is approved for NAFLD. Simple steatosis and nonalcoholic steatohepatitis (NASH) can progress to liver fibrosis that is associated with mortality in NAFLD. The recruitment of inflammatory monocytes and macrophages via chemokine receptor CCR2 as well as of lymphocytes and hepatic stellate cells via CCR5 promote the progression of NASH to fibrosis. Areas covered: I summarize preclinical and clinical data on the efficacy and safety of the dual CCR2/CCR5 inhibitor cenicriviroc (CVC, also TBR-652 or TAK-652) for the treatment of NASH and fibrosis...
February 16, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29448021/risk-assessment-of-silica-nanoparticles-on-liver-injury-in-metabolic-syndrome-mice-induced-by-fructose
#14
Jianmei Li, Xiwei He, Yang Yang, Mei Li, Chenke Xu, Rong Yu
This study aims to assess the effects and the mechanisms of silica nanoparticles (SiNPs) on hepatotoxicity in both normal and metabolic syndrome mouse models induced by fructose. Here, we found that SiNPs exposure lead to improved insulin resistance in metabolic syndrome mice, but markedly worsened hepatic ballooning, inflammation infiltration, and fibrosis. Moreover, SiNPs exposure aggravated liver injury in metabolic syndrome mice by causing serious DNA damage. Following SiNPs exposure, liver superoxide dismutase and catalase activities in metabolic syndrome mice were stimulated, which is accompanied by significantly increased malondialdehyde and 8-hydroxy-2-deoxyguanosine levels as compared to normal mice...
February 12, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29445243/quantitative-assessment-of-liver-fibrosis-qfibrosis-reveals-precise-outcomes-in-ishak-stable-patients-on-anti-hbv-therapy
#15
Yameng Sun, Jialing Zhou, Xiaoning Wu, Yongpeng Chen, Hongxin Piao, Lungen Lu, Huiguo Ding, Yuemin Nan, Wei Jiang, Tailing Wang, Hui Liu, Xiaojuan Ou, Aileen Wee, Neil D Theise, Jidong Jia, Hong You
Current widely used semiquantitative histological assessment methods are insensitive to identify subtle changes of liver fibrosis. Therefore, to precisely assess therapeutic efficacy on chronic hepatitis B (CHB), we explored the utility of qFibrosis (a fully-quantitative morphometric method employing second harmonic generation/two photon excitation fluorescence) in liver fibrosis evaluation. Fibrosis changes were evaluated by Ishak fibrosis scoring and qFibrosis in CHB patients with paired liver biopsies before and after 78 weeks' antiviral therapy...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29444470/effect-of-sirolimus-on-liver-cirrhosis-and-hepatic-encephalopathy-of-common-bile-duct-ligated-rats
#16
Kuo-Cheng Wu, Hui-Chun Huang, Ting Chang, Wen-Shin Lee, Chiao-Lin Chuang, I-Fang Hsin, Shao-Jung Hsu, Fa-Yauh Lee, Ching-Chih Chang, Shou-Dong Lee
Cirrhosis is often associated with portal hypertension and portal-systemic collateral vessels formation attributed to angiogenesis, which leads to severe complications as hepatic encephalopathy. Sirolimus has anti-fibrosis and anti-angiogenesis effects, but whether it influences the severity of portal-systemic collaterals and hepatic encephalopathy is unknown. This study was thus designed to address this issue in rats with common bile duct ligation-induced liver cirrhosis. Sham-operated rats were surgical controls...
February 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29444417/a-study-on-the-regenerative-effect-of-platelets-rich-plasma-on-experimentally-induced-hepatic-damage-in-albino-rats
#17
Heba Mamdoh Shoeib, Walaa Arafa Keshk, Abdallah Mahmoud Foda, Saad El-Deen Abd Elfatah Abo El Noeman
Hepatic fibrosis is a worldwide health problem with significant morbidity and mortality. Currently, there is no effective therapy for hepatic fibrosis. So that the present study was aimed to evaluate the possible regenerative effect of Platelet-rich plasma (PRP) against thioacetamide (TAA) induced hepatic damage. Eighty albino rats were included; 40 were used for PRP preparation and 40 were randomly divided into four groups. Group I (control group); group II (PRP control); group III (TAA- intoxicated in a dose of 200 mg ∕ kg body weight/twice weekly for 7 weeks, intra-peritoneal and group IV (TAA-intoxicated+ PRP treated)...
February 14, 2018: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29444136/ly2405319-an-analog-of-fibroblast-growth-factor-21-ameliorates-%C3%AE-smooth-muscle-actin-production-through-inhibition-of-the-succinate-g-protein-couple-receptor-91-gpr91-pathway-in-mice
#18
Cong Thuc Le, Giang Nguyen, So Young Park, Dae Hee Choi, Eun-Hee Cho
Fibroblast growth factor 21 (FGF21) is an important metabolic regulator expressed predominantly in the liver. In this study, we evaluated the role of LY2405319, an analogue of FGF21, in hepatic stellate cell (HSC) activation and in a methionine and choline-deficient (MCD)-diet induced mouse model of liver fibrosis. During liver injury, HSCs trans-differentiate into activated myofibroblasts which produce alpha-smooth muscle actin (α-SMA) and become a major cell type in hepatic fibrogenesis. Succinate and succinate receptor (GPR91) signaling has emerged as a regulator to promote α-SMA production in MCD diet- induced mice...
2018: PloS One
https://www.readbyqxmd.com/read/29443924/identification-of-key-pathways-and-genes-in-the-dynamic-progression-of-hcc-based-on-wgcna
#19
Li Yin, Zhihui Cai, Baoan Zhu, Cunshuan Xu
Hepatocellular carcinoma (HCC) is a devastating disease worldwide. Though many efforts have been made to elucidate the process of HCC, its molecular mechanisms of development remain elusive due to its complexity. To explore the stepwise carcinogenic process from pre-neoplastic lesions to the end stage of HCC, we employed weighted gene co-expression network analysis (WGCNA) which has been proved to be an effective method in many diseases to detect co-expressed modules and hub genes using eight pathological stages including normal, cirrhosis without HCC, cirrhosis, low-grade dysplastic, high-grade dysplastic, very early and early, advanced HCC and very advanced HCC...
February 14, 2018: Genes
https://www.readbyqxmd.com/read/29442483/quantification-of-ultrasound-imaging-in-the-staging-of-hepatic-fibrosis
#20
Paolo Borro, Silvana G Dellepiane, Rinaldo Pellicano, Laura Gemme, Sharmila Fagoonee, Gianni Testino
OBJECTIVE: The need for a staging of hepatic fibrosis has become particularly urgent in the last few years in order to start new therapeutic treatments. The objective of this study is to identify ultrasound descriptors and achieve a staging of hepatic fibrosis with non-invasive, rapid and inexpensive methods, both as an alternative and a support to the ultrasound elastography examination. MATERIALS AND METHODS: This study evaluated 196 patients under treatment at the Alcohological Regional Center...
February 13, 2018: Panminerva Medica
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