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https://www.readbyqxmd.com/read/28638224/inhibitory-effect-of-oxymatrine-on-hepatocyte-apoptosis-via-tlr4-pi3k-akt-gsk-3%C3%AE-signaling-pathway
#1
Xian Zhang, Wei Jiang, Ai-Ling Zhou, Min Zhao, Dao-Rong Jiang
AIM: To evaluate the effect of oxymatrine (OMT) on hepatocyte apoptosis in rats with lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver failure (ALF). METHODS: LPS/D-GalN was used to establish a model of ALF in rats. To evaluate the effect of OMT, we assessed apoptosis by transmission electron microscopy, and the pathological changes in the liver by light microscopy with hematoxylin and eosin staining. An automated biochemical analyzer was used to measure serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)...
June 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28638086/wnt2b-attenuates-hscs-activation-and-liver-fibrosis-through-negative-regulating-tlr4-signaling
#2
Yi Yuan, Qiuju Han, Siyu Li, Zhigang Tian, Jian Zhang
The Wingless-type MMTV integration site family member 2b (Wnt2b) has been found to be a principal mediator of liver development and regeneration. However, the significance of Wnt2b in the pathogenesis of fibrosis-related liver diseases remains undefined. Here, we report that Wnt2b was highly expressed in the fibrotic liver tissues, exhibiting protective effects against activation of hepatic stellate cells (HSCs) and fibrosis progression. We identified a negative regulation of Wnt2b on the toll-like receptor 4 (TLR4) activation-mediated pro-fibrogenic effects...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634394/the-roles-of-toll-like-receptor-4-in-the-pathogenesis-of-pathogen-associated-biliary-fibrosis-caused-by-clonorchis-sinensis
#3
Chao Yan, Bo Li, Fang Fan, Ying Du, Rui Ma, Xiao-Dan Cheng, Xiang-Yang Li, Bo Zhang, Qian Yu, Yu-Gang Wang, Ren-Xian Tang, Kui-Yang Zheng
Pathogen-associated biliary fibrosis (PABF) is a type of liver fibrosis characterized by injuries of cholangiocytes and extra cellular matrix (ECM) deposition around bile ducts caused by various bacteria, fungi, virus and parasites. Recent studies show that TLR4 plays an important role in several other types of liver fibrosis, but the mechanism of TLR4 in PABF is yet really unclear. In the present study, a PABF mouse model was established by a trematode infection-Clonorchis sinensis which dwells in the bile ducts and causes severe biliary fibrosis of mice...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28632732/fructo-oligosaccharides-and-intestinal-barrier-function-in-a-methionine-choline-deficient-mouse-model-of-nonalcoholic-steatohepatitis
#4
Kotaro Matsumoto, Mayuko Ichimura, Koichi Tsuneyama, Yuki Moritoki, Hiromichi Tsunashima, Katsuhisa Omagari, Masumi Hara, Ichiro Yasuda, Hiroshi Miyakawa, Kentaro Kikuchi
Impairments in intestinal barrier function, epithelial mucins, and tight junction proteins have been reported to be associated with nonalcoholic steatohepatitis. Prebiotic fructo-oligosaccharides restore balance in the gastrointestinal microbiome. This study was conducted to determine the effects of dietary fructo-oligosaccharides on intestinal barrier function and steatohepatitis in methionine-choline-deficient mice. Three groups of 12-week-old male C57BL/6J mice were studied for 3 weeks; specifically, mice were fed a methionine-choline-deficient diet, a methionine-choline-deficient diet plus 5% fructo-oligosaccharides in water, or a normal control diet...
2017: PloS One
https://www.readbyqxmd.com/read/28628927/curcumin-promotes-apoptosis-of-activated-hepatic-stellate-cells-by-inhibiting-protein-expression-of-the-myd88-pathway
#5
Ya-Jun He, Kenny Kuchta, Yan-Mei Deng, Silke Cameron, Yu Lin, Xu-You Liu, Guo-Ron Ye, Xia Lv, Yuta Kobayashi, Jian-Chang Shu
Activation and proliferation of hepatic stellate cells (HSC) play an important role in the progress of liver fibrosis. HSC activation occurs in response to inflammatory cytokines, cellular interactions with immune cells, and morphogenetic signals. The literature hints to a role of the adaptor protein MyD88 in fibrosis. Although curcumin has been shown to exert inhibitory effects on the proliferation of HSC in vitro, its influence on the MyD88 pathway in HSC has remained unclear. Here, we investigated whether curcumin accelerates apoptosis of HSC through the MyD88 pathway...
June 19, 2017: Planta Medica
https://www.readbyqxmd.com/read/28627210/lactobacillus-rhamnosusgg-reduces-hepatic-fibrosis-in-a-model-of-chronic-liver-disease-in-rats
#6
Thais Ortiz Hammes, Renata Leke, Thayssa Dalla Costa Escobar, Laisa Beduschi Fracasso, Fabiola Schons Meyer, Michael Éverton Andrades, Themis Reverbel da Silveira
BACKGROUND: The intestinal dysbiosis is common in chronic liver disease and can induce to inflammatory responses and mediate the collagen deposition in the liver. AIM: To evaluate the probiotic Lactobacillus rhamnosus GG (LGG) for the treatment of liver fibrosis in a model of chronic cholestatic liver disease in rats. METHODS: Male adult Wistar rats (n = 29) were submitted to common bile duct ligation (BDL groups) or manipulation of common bile duct without ligation (Ctrl groups)...
June 5, 2017: Nutrición Hospitalaria: Organo Oficial de la Sociedad Española de Nutrición Parenteral y Enteral
https://www.readbyqxmd.com/read/28623125/chronic-intermittent-hypoxia-induces-liver-fibrosis-in-mice-with-diet-induced-obesity-via-tlr4-myd88-mapk-nf-kb-signaling-pathways
#7
Hyeon Hui Kang, In Kyoung Kim, Hye In Lee, Hyonsoo Joo, Jeong Uk Lim, Jongmin Lee, Sang Haak Lee, Hwa Sik Moon
Obstructive sleep apnea (OSA) is associated with nonalcoholic fatty liver disease (NAFLD), and causes chronic intermittent hypoxia (CIH) during sleep. Inflammation is associated with the development of metabolic complications induced by CIH. Research suggests that innate immune mechanisms are involved in the pro-inflammatory pathways of liver fibrosis. The purpose of this study was to investigate whether innate immune responses induce liver fibrosis, and to evaluate mechanisms underlying hepatic inflammation related to CIH in a murine diet-induced obesity (DIO) model...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28604704/thermoneutral-housing-exacerbates-nonalcoholic-fatty-liver-disease-in-mice-and-allows-for-sex-independent-disease-modeling
#8
Daniel A Giles, Maria E Moreno-Fernandez, Traci E Stankiewicz, Simon Graspeuntner, Monica Cappelletti, David Wu, Rajib Mukherjee, Calvin C Chan, Matthew J Lawson, Jared Klarquist, Annika Sünderhauf, Samir Softic, C Ronald Kahn, Kerstin Stemmer, Yoichiro Iwakura, Bruce J Aronow, Rebekah Karns, Kris A Steinbrecher, Christopher L Karp, Rachel Sheridan, Shiva K Shanmukhappa, Damien Reynaud, David B Haslam, Christian Sina, Jan Rupp, Simon P Hogan, Senad Divanovic
Nonalcoholic fatty liver disease (NAFLD), a common prelude to cirrhosis and hepatocellular carcinoma, is the most common chronic liver disease worldwide. Defining the molecular mechanisms underlying the pathogenesis of NAFLD has been hampered by a lack of animal models that closely recapitulate the severe end of the disease spectrum in humans, including bridging hepatic fibrosis. Here we demonstrate that a novel experimental model employing thermoneutral housing, as opposed to standard housing, resulted in lower stress-driven production of corticosterone, augmented mouse proinflammatory immune responses and markedly exacerbated high-fat diet (HFD)-induced NAFLD pathogenesis...
June 12, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28601590/hepatoprotective-effects-of-ethyl-pyruvate-against-ccl4-induced-hepatic-fibrosis-via-inhibition-of-tlr4-nf-%C3%AE%C2%BAb-signaling-and-up-regulation-of-mmps-timps-ratio
#9
Mingxiao Zhang, Xiaosong Hu, Shuai Li, Chen Lu, Juan Li, Yonghua Zong, Wenqian Qi, Huijun Yang
BACKGROUND AND AIM: Liver fibrosis is a worldwide clinical issue. It has been well established that liver fibrosis is characterized of excessive extracellular matrix (ECM) deposition in chronically damaged livers. Accumulating evidences have suggested that ethyl pyruvate (EP) is a potential useful agent for preventing from hepatic injury. The aim of this study was to evaluate the protective effects of the EP against liver fibrosis induced by carbon tetrachloride (CCl4) in rats. METHOD: Rats were randomly divided into control group, CCl4 group and CCl4+EP group, which with and without EP administration...
June 7, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28595383/cooperative-interactions-between-toll-like-receptor-2-and-toll-like-receptor-4-in-murine-klebsiella-pneumoniae-infections
#10
Hee-Yeon Jeon, Jong-Hyung Park, Jin-Il Park, Jun-Young Kim, Sun-Min Seo, Seung-Hoon Ham, Eui-Suk Jeong, Yang-Kyu Choi
Klebsiella pneumoniae is an opportunistic and clinically significant emerging pathogen. We investigated the relative roles of Toll-like receptor (TLR) 2 and TLR4 in initiating host defenses against K. pneumoniae. TLR2 knockout (KO), TLR4 KO, TLR2/4 double KO (DKO), and wild-type (WT) mice were inoculated with K. pneumoniae. Mice in each group were sacrificed after either 12 or 24 hours, and lungs, livers, and blood were harvested to enumerate bacterial colony-forming units (CFU). Cytokine and chemokine levels were analyzed using enzyme-linked immunosorbent assay and real-time PCR, and pneumonia severity was determined by histopathological analysis...
June 8, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28593786/characterization-of-liver-changes-in-zsf1-rats-an-animal-model-of-metabolic-syndrome
#11
Marta Borges Canha, José Pedro Portela-Cidade, Glória Conceição, Cláudia Sousa-Mendes, Sara Leite, Dulce Fontoura, Daniel Moreira-Gonçalves, Inês Falcão-Pires, André Lourenço, Adelino Leite-Moreira, Pedro Pimentel-Nunes
BACKGROUND: The non-alcoholic fatty liver disease is the hepatic counterpart of the metabolic syndrome. ZSF1 rats are a metabolic syndrome animal model in which liver changes have not been described yet. AIM: The characterization of liver histological and innate immunity changes in ZSF1 rats. METHODS: Five groups of rats were included (n = 7 each group): healthy Wistar-Kyoto control rats (Ctrl), hypertensive ZSF1 lean (Ln), ZSF1 obese rats with a normal diet (Ob), ZSF1 obese rates with a high-fat diet (Ob-HFD), and ZSF1 obese rats with low-intensity exercise training (Ob-Ex)...
June 8, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28584078/alcohol-induced-mir-155-and-hdac11-inhibit-negative-regulators-of-the-tlr4-pathway-and-lead-to-increased-lps-responsiveness-of-kupffer-cells-in-alcoholic-liver-disease
#12
Shashi Bala, Timea Csak, Karen Kodys, Donna Catalano, Aditya Ambade, Istvan Furi, Patrick Lowe, Yeonhee Cho, Arvin Iracheta-Vellve, Gyongyi Szabo
Inflammation promotes the progression of alcoholic liver disease. Alcohol sensitizes KCs to gut-derived endotoxin (LPS); however, signaling pathways that perpetuate inflammation in alcoholic liver disease are only partially understood. We found that chronic alcohol feeding in mice induced miR-155, an inflammatory miRNA in isolated KCs. We hypothesized that miR-155 might increase the responsiveness of KCs to LPS via targeting the negative regulators of LPS signaling. Our results revealed that KCs that were isolated from alcohol-fed mice showed a decrease in IRAK-M, SHIP1, and PU...
June 5, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28575583/the-critical-role-played-by-endotoxin-induced-liver-autophagy-in-the-maintenance-of-lipid-metabolism-during-sepsis
#13
Ki Wung Chung, Kyung Mok Kim, Yeon Ja Choi, Hye Jin An, Bonggi Lee, Dae Hyun Kim, Eun Kyeong Lee, Eunok Im, Jaewon Lee, Dong Soon Im, Byung Pal Yu, Hae Young Chung
Macroautophagy/autophagy is a central mechanism by which cells maintain integrity and homeostasis, and endotoxin-induced autophagy plays important roles in innate immunity. Although TLR4 stimulation mediated by lipopolysaccharide (LPS) also upregulates autophagy in hepatocytes and liver, its physiological role remains elusive. The objective of this study was to determine the role of LPS-induced autophagy in the regulation of liver lipid metabolism. LPS treatment (5 mg/kg) increased autophagy, as detected by LC3 conversion and transmission electron microscopy (TEM) analysis in C57BL6 mouse livers...
June 2, 2017: Autophagy
https://www.readbyqxmd.com/read/28562479/sepsis-up-regulates-cd14-expression-in-a-myd88-dependent-and-trif-independent-pathway
#14
Zhixia Chen, Zhenzhen Shao, Shuya Mei, Zhengzheng Yan, Xibing Ding, Timothy Billiar, Quan Li
An overwhelming immune response, particularly from macrophages, plays a critical role in survival and organ damage in sepsis patients. TLRs are important receptors to recognize the conserved motifs expressed by invading bacteria. The TLRs except TLR3 signal via a MyD88 dependent pathway. TLR3 uses a TRIF dependent pathway, while TLR4 uses both MyD88 and TRIF dependent pathways. Previous studies indicated that CD14 was necessary for TLRs dependent production of pro-inflammatory cytokines. Blocking CD14 protected against the deleterious systemic inflammatory response associated with sepsis...
May 29, 2017: Shock
https://www.readbyqxmd.com/read/28559049/attenuation-of-thioacetamide-induced-hepatocellular-injury-by-short-term-repeated-injections-associated-with-down-regulation-of-metabolic-enzymes-and-relationship-with-mhc-class-ii-presenting-cells
#15
Mizuki Kuramochi, Takeshi Izawa, Munmun Pervin, Alexandra Bondoc, Mitsuru Kuwamura, Jonathan LaMarre, Jyoji Yamate
The liver is the primary organ participating in the metabolism of xenobiotics and is therefore an important target in the safety assessment of drugs, chemicals and environmental toxins. Drug-induced liver injury (DILI) has recently become widely recognized in human medicine as an adverse event. The progression of DILI often involves "damage-associated molecular patterns" (DAMPs) of gene and protein expression such as high-mobility group boxes (HMGBs), S100 proteins and heat shock proteins (Hsp). DAMPs are released from injured or necrotic cells and are bound to Toll-like receptors (TLRs) and modulate inflammatory reactions...
May 27, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28551086/hmgb1-rage-pathway-drives-peroxynitrite-signaling-induced-ibd-like-inflammation-in-murine-nonalcoholic-fatty-liver-disease
#16
Varun Chandrashekaran, Ratanesh K Seth, Diptadip Dattaroy, Firas Alhasson, Jacek Ziolenka, James Carson, Franklin G Berger, Balaraman Kalyanaraman, Anna Mae Diehl, Saurabh Chatterjee
Recent clinical studies found a strong association of colonic inflammation and Inflammatory bowel disease (IBD)-like phenotype with NonAlcoholic Fatty liver Disease (NAFLD) yet the mechanisms remain unknown. The present study identifies high mobility group box 1 (HMGB1) as a key mediator of intestinal inflammation in NAFLD and outlines a detailed redox signaling mechanism for such a pathway. NAFLD mice showed liver damage and release of elevated HMGB1 in systemic circulation and increased intestinal tyrosine nitration that was dependent on NADPH oxidase...
May 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/28538192/hepatic-anti-inflammatory-effect-of-hexane-extracts-of-dioscorea-batatas-decne-possible-suppression-of-toll-like-receptor-4-mediated-signaling
#17
Hyun Jung Koo, SungRyul Lee, Kwang Jin Chang, Eunsoo Sohn, Eun-Hwa Sohn, Se Chan Kang, Suhkneung Pyo
The hepatic anti-inflammatory potential of hexane extracts of Dioscorea batatas Decne edible part (EDH-1e) and bark (EDH-2b) were investigated in Western-type diet-fed apolipoprotein E null [ApoE (-/-)] mice and HepG2 cells. EDH-1e and EDH-2b suppressed the increased levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, transforming growth factor beta 1 (TGF-β1), vascular cell adhesion protein 1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1), and reduced infiltration of monocytes into liver tissue...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28536433/a-new-model-of-self-resolving-leptospirosis-in-mice-infected-with-a-strain-of-leptospira-interrogans-serovar-autumnalis-harboring-lps-signaling-only-through-tlr4
#18
Bili Xia, Le Sun, Xia Fan, Haihan Xiao, Yongzhang Zhu, Jinhong Qin, Chengsong Cai, Wei Zhao, Yung-Fu Chang, Yan Zhang, Xiaokui Guo, Ping He
Leptospirosis is an emerging worldwide zoonosis caused by pathogenic Leptospira spp. Our understanding of leptospirosis pathogenesis and host immune response remains limited, while mechanistic studies are hindered by a lack of proper animal models and immunological reagents. Here we established a murine model of acute and self-resolving leptospirosis by infecting 10-week-old C57BL/6 mice with Leptospira interrogans serovar Autumnalis strain 56606v, with characteristic manifestations including jaundice as well as subcutaneous and pulmonary bleeding, but no kidney lesions...
May 24, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28522898/the-protective-effect-of-cordycepin-on-d-galactosamine-lipopolysaccharide-induced-acute-liver-injury
#19
Jin Li, Liping Zhong, Haibo Zhu, Fengzhong Wang
As the major active ingredient of Cordyceps militaris, cordycepin (3'-deoxyadenosine) has been well documented to alleviate inflammation and oxidative stress both in vitro and in vivo. To explore the potential protective effect of cordycepin in fulminant hepatic failure, mice were pretreated with cordycepin for 3 weeks followed by D-galactosamine (GalN)/lipopolysaccharide (LPS) injection. Then we found cordycepin (200 mg/kg) administration elevated survival rate, improved liver function, and suppressed hepatocyte apoptosis and necrosis in mice with severe hepatic damage by GalN/LPS treatment...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28506763/neonatal-hyperoxia-disrupts-the-intestinal-barrier-and-impairs-intestinal-function-in-rats
#20
Hsiu-Chu Chou, Chung-Ming Chen
Animal studies have demonstrated that neonatal hyperoxia injures the distal small intestine and disrupts the intestinal barrier. This study evaluated the effects of brief hyperoxia exposure on intestinal function in newborn rats. Newborn Sprague-Dawley rat pups were exposed to room air or normobaric hyperoxia (85% O2) for 1week. The rats were euthanized on Postnatal Day 7, and their terminal ilea and sera were collected for histological analyses and intestinal permeability measurements, respectively. Bacterial translocation to the liver and spleen under aerobic and anaerobic conditions was determined...
May 12, 2017: Experimental and Molecular Pathology
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