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Hepatic stellate cell

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https://www.readbyqxmd.com/read/28424943/intestinal-alkaline-phosphatase-attenuates-alcohol-induced-hepatosteatosis-in-mice
#1
Sulaiman R Hamarneh, Byeong-Moo Kim, Kanakaraju Kaliannan, Sara A Morrison, Tyler J Tantillo, Qingsong Tao, Mussa M Rafat Mohamed, Juan M Ramirez, Aaron Karas, Wei Liu, Dong Hu, Abeba Teshager, Sarah Shireen Gul, Konstantinos P Economopoulos, Atul K Bhan, Madhu S Malo, Michael Y Choi, Richard A Hodin
BACKGROUND AND AIMS: Bacterially derived factors from the gut play a major role in the activation of inflammatory pathways in the liver and in the pathogenesis of alcoholic liver disease. The intestinal brush-border enzyme intestinal alkaline phosphatase (IAP) detoxifies a variety of bacterial pro-inflammatory factors and also functions to preserve gut barrier function. The aim of this study was to investigate whether oral IAP supplementation could protect against alcohol-induced liver disease...
April 19, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28424480/ketogenic-diet-attenuates-hepatopathy-in-mouse-model-of-respiratory-chain-complex-iii-deficiency-caused-by-a-bcs1l-mutation
#2
Janne Purhonen, Jayasimman Rajendran, Matthias Mörgelin, Kristiina Uusi-Rauva, Shintaro Katayama, Kaarel Krjutskov, Elisabet Einarsdottir, Vidya Velagapudi, Juha Kere, Matti Jauhiainen, Vineta Fellman, Jukka Kallijärvi
Mitochondrial disorders are among the most prevalent inborn errors of metabolism but largely lack treatments and have poor outcomes. High-fat, low-carbohydrate ketogenic diets (KDs) have shown beneficial effects in mouse models of mitochondrial myopathies, with induction of mitochondrial biogenesis as the suggested main mechanism. We fed KD to mice with respiratory chain complex III (CIII) deficiency and progressive hepatopathy due to mutated BCS1L, a CIII assembly factor. The mutant mice became persistently ketotic and tolerated the KD for up to 11 weeks...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423574/synergistic-anti-tumor-efficacy-of-sorafenib-and-fluvastatin-in-hepatocellular-carcinoma
#3
Yang Cheng, RongCheng Luo, Hang Zheng, Biao Wang, YaHui Liu, DingLi Liu, JinZhang Chen, WanFu Xu, AiMin Li, Yun Zhu
Drug resistance to sorafenib is common in patients with hepatocellular carcinoma(HCC). We examined the effects of a combination of sorafenib and fluvastatin on HCC using in vitro and in vivo models. The dual treatment induced apoptosis and reduced cellular viability in HCC more effectively than either drug alone. The combination treatment also inhibited activation of hepatic stellate cells, whereas single drug treatments did not. On a molecular level, combined treatment inhibited activation of the MAPK and NF-κB pathways via Toll-like receptor 4 in HCC cells...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423499/imidazoline-i2-receptor-inhibitor-idazoxan-regulates-the-progression-of-hepatic-fibrosis-via-akt-nrf2-smad2-3-signaling-pathway
#4
Li Xuanfei, Chen Hao, Yi Zhujun, Liu Yanming, Gong Jianping
Liver fibrosis is a global health problem and its relationship with imidazoline I2 receptor has not been reported. This study aimed to investigate the effects and underlying mechanisms of imidazoline I2 receptor (I2R) inhibitor idazoxan (IDA) on carbon tetrachloride (CCl4)-induced liver fibrosis. In vivo liver fibrosis in mice was induced by intraperitoneally injections of CCl4 for eight weeks, and in vitro studies were performed on activated LX2 cells treated with transforming growth factor-β (TGF-β). Our results showed that IDA significantly improved liver inflammation, ameliorated hepatic stellate cells activation and reduced collagen accumulation by suppressing the pro-fibrogenic signaling of TGF-β/Smad...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422322/pentraxin-3-modulates-lps-induced-inflammatory-response-and-attenuates-liver-injury
#5
Luis Perea, Mar Coll, Lucia Sanjurjo, Delia Blaya, Adil El Taghdouini, Daniel Rodrigo-Torres, José Altamirano, Isabel Graupera, Beatriz Aguilar-Bravo, Marta Llopis, Julia Vallverdú, Joan Caballeria, Leo A van Grunsven, Maria-Rosa Sarrias, Pere Ginès, Pau Sancho-Bru
Acute-on-chronic liver injury is characterized by an important inflammatory response frequently associated with endotoxemia. In this context, acute phase proteins such as Pentraxin-3 (PTX3) are released, however, little is known about their role in chronic liver disease. The aim of this study was to elucidate the role of PTX3 in liver injury. Role of PTX3 was evaluated in cultured human cells, liver tissue slices and mice with acute-on-chronic liver injury. PTX3 expression was assessed in tissue and serum samples from 54 patients with alcoholic hepatitis (AH)...
April 19, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28416697/small-molecule-mediated-inhibition-of-myofibroblast-transdifferentiation-for-the-treatment-of-fibrosis
#6
Michael J Bollong, Baiyuan Yang, Naja Vergani, Brittney A Beyer, Emily N Chin, Claudio Zambaldo, Danling Wang, Arnab K Chatterjee, Luke L Lairson, Peter G Schultz
Fibrosis, a disease in which excessive amounts of connective tissue accumulate in response to physical damage and/or inflammatory insult, affects nearly every tissue in the body and can progress to a state of organ malfunction and death. A hallmark of fibrotic disease is the excessive accumulation of extracellular matrix-secreting activated myofibroblasts (MFBs) in place of functional parenchymal cells. As such, the identification of agents that selectively inhibit the transdifferentiation process leading to the formation of MFBs represents an attractive approach for the treatment of diverse fibrosis-related diseases...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28414177/the-acitretin-and-methotrexate-combination-therapy-for-psoriasis-vulgaris-achieves-higher-effectiveness-and-less-liver-fibrosis
#7
Jingang An, Dingwei Zhang, Jiawen Wu, Jiong Li, Xiu Teng, Xiaomin Gao, Ruilian Li, Xiuying Wang, Linlin Xia, Yumin Xia
Both acitretin and methotrexate are effective in ameliorating psoriatic lesion. However, their combination has been seldom reported in the treatment of psoriasis because of the warning regarding the potential hepatotoxicity of the drug interactions. This study was designed to investigate the effectiveness of such combination therapy for psoriasis vulgaris, and the potential benefit as well as side effect during the treatment. Thirty-nine patients with psoriasis vulgaris were treated with acitretin, methotrexate or their combination or as control...
April 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28412299/toll-like-receptor-4-independent-carbon-tetrachloride-induced-fibrosis-and-lipopolysaccharide-induced-acute-liver-injury-in-mice-role-of-hepatic-stellate-cells
#8
Sudhir Kumar, Jiang Wang, Shiva Kumar Shanmukhappa, Chandrashekhar R Gandhi
Gram-negative bacterial endotoxin lipopolysaccharide (LPS) is implicated in acute and chronic liver injury; its effects are mediated predominantly via the membrane receptor Toll-like receptor 4 (TLR4). However, TLR4-independent effects of LPS may play important role in hepatic pathophysiology. We investigated carbon tetrachloride (CCl4)-induced fibrosis and LPS-induced acute liver injury in wild-type (WT) and B6.B10ScN-Tlr4(lps-del)/JthJ [TLR4-knockout (KO)] mice. Effects of LPS on fibrogenic hepatic stellate cells (HSCs) from WT and TLR4-KO mice were assessed in vitro...
April 12, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28411440/tweak-fn14-promotes-pro-inflammatory-cytokine-secretion-in-hepatic-stellate-cells-via-nf-%C3%AE%C2%BAb-stat3-pathways
#9
Aixiu Wang, Feng Zhang, Hui Xu, Mingcui Xu, Yu Cao, Chen Wang, Yuanyuan Xu, Min Su, Ming Zhang, Yuzheng Zhuge
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) have been associated with liver disease. Hepatic stellate cells (HSCs) play a critical role in the hepatic wound-healing response after liver injury, but there is little information available on the role of the TWEAK/Fn14 pathway in human HSCs. In this study, we explored the role of TWEAK/Fn14 in activated human HSCs. The LX-2 cells were treated with TWEAK, and the expression of pro-inflammatory cytokines was assayed by enzyme-linked immunosorbent assay (ELISA) and real-time PCR (RT-PCR)...
April 12, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28409388/diethylcarbamazine-attenuates-the-expression-of-pro-fibrogenic-markers-and-hepatic-stellate-cells-activation-in-carbon-tetrachloride-induced-liver-fibrosis
#10
Maria Eduarda Rocha de França, Sura Wanessa Santos Rocha, Wilma Helena Oliveira, Laise Aline Santos, Anne Gabrielle Vasconcelos de Oliveira, Karla Patrícia Sousa Barbosa, Ana Karolina Santana Nunes, Gabriel Barros Rodrigues, Deniele Bezerra Lós, Christina Alves Peixoto
BACKGROUND AND AIM: While diethylcarbamazine citrate (DEC) displays important anti-inflammatory effects in experimental models of liver injury, the mechanisms of its action remain poorly understood. The aim of the present study was to investigate the fibrolytic potential of DEC. METHODS: Mice receive two injections of carbon tetrachloride (CCl4) per week for 8 weeks. DEC 50 mg/kg body weight was administered through drinking water during the last 12 days of liver injury...
April 13, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28406452/suppression-of-hepatic-epithelial-to-mesenchymal-transition-by-melittin-via-blocking-of-tgf%C3%AE-smad-and-mapk-jnk-signaling-pathways
#11
Ji-Hyun Park, Byoungduck Park, Kwan-Kyu Park
Transforming growth factor (TGF)-β1 plays a crucial role in the epithelial-to-mesenchymal transition (EMT) in hepatocytes and hepatic stellate cells (HSC), which contributes to the pathogenesis of liver fibrosis. Melittin (MEL) is a major component of bee venom and is effective in rheumatoid arthritis, pain relief, cancer cell proliferation, fibrosis and immune modulating activity. In this study, we found that MEL inhibits hepatic EMT in vitro and in vivo, regulating the TGFβ/Smad and TGFβ/nonSmad signaling pathways...
April 13, 2017: Toxins
https://www.readbyqxmd.com/read/28405682/apamin-suppresses-biliary-fibrosis-and-activation-of-hepatic-stellate-cells
#12
Jung-Yeon Kim, Hyun-Jin An, Woon-Hae Kim, Yoon-Yub Park, Kyung Duck Park, Kwan-Kyu Park
Cholestatic liver disease is characterized by the progressive destruction of biliary epithelial cells (BECs) followed by fibrosis, cirrhosis and liver failure. Activated hepatic stellate cells (HSCs) and portal fibroblasts are the major cellular effectors of enhanced collagen deposition in biliary fibrosis. Apamin, an 18 amino acid peptide neurotoxin found in apitoxin (bee venom), is known to block Ca2+-activated K+ channels and prevent carbon tetrachloride-induced liver fibrosis. In the present study, we aimed to ascertain whether apamin inhibits biliary fibrosis and the proliferation of HSCs...
May 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28399886/levels-of-hepatic-th17-cells-and-regulatory-t-cells-upregulated-by-hepatic-stellate-cells-in-advanced-hbv-related-liver-fibrosis
#13
Xiaoyan Li, Yujie Su, Xuefeng Hua, Chan Xie, Jing Liu, Yuehua Huang, Liang Zhou, Min Zhang, Xu Li, Zhiliang Gao
BACKGROUND: Liver fibrosis which mainly occurs upon chronic hepatitis virus infection potentially leads to portal hypertension, hepatic failure and hepatocellular carcinoma. However, the immune status of Th17 and Treg cells in liver fibrosis is controversial and the exact mechanisms remain largely elusive. METHODS: Liver tissues and peripheral blood were obtained simultaneously from 32 hepatitis B virus infected patients undergoing surgery for hepatocellular carcinoma at the medical center of Sun Yat-sen University...
April 11, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28396867/carvedilol-attenuates-the-progression-of-hepatic-fibrosis-induced-by-bile-duct-ligation
#14
Xiaopeng Tian, Chunhong Zhao, Jinbo Guo, Shurui Xie, Fengrong Yin, Xiaoxia Huo, Xiaolan Zhang
Background. The sympathetic nervous system (SNS) is responsible for hepatic stellate cells (HSCs) activation and the accumulation of collagen that occurs in hepatic fibrogenesis. Carvedilol has been widely used for the complication of hepatic cirrhosis in the clinic. Furthermore, it has powerful antioxidant properties. We assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may further enhance its clinical benefits. Methods. Using a bile duct ligation rat model of hepatic fibrosis, we studied the effects of carvedilol on the fibrosis, collagen deposition, and oxidative stress based on histology, immunohistochemistry, western blot, and RT-PCR analyses...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28395572/protective-effects-of-ampelopsis-brevipedunculata-against-in-vitro-hepatic-stellate-cells-system-and-thioacetamide-induced-liver-fibrosis-rat-model
#15
Mun Jeong Yum, Sushruta Koppula, Jin Seoub Kim, Gwang Mo Shin, Yun Jin Chae, Tony Yoon, Chi Su Chun, Jae Dong Lee, MinDong Song
CONTEXT: Ampelopsis brevipedunculata Maxim (Vitaceae) is a traditional medicinal herb used for treating liver disorders. OBJECTIVE: The hepatoprotective effects of A. brevipedunculata ethanol extract (ABE) was investigated in experimental models of fibrosis. MATERIALS AND METHODS: Hepatic stellate cells (HSCs) system in vitro and thioacetamide (TAA)-induced liver fibrosis rat model in vivo were used. Sprague-Dawley rats were divided into five groups of eight each (control, TAA, TAA with ABE 10 mg/kg, ABE 100 mg/kg and silymarin 50 mg/kg groups, respectively)...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28395284/indole-3-carbinol-induces-apoptosis-of-hepatic-stellate-cells-through-k63-de-ubiquitination-of-rip1-in-rats
#16
Bin Li, Meng Cong, Yanan Zhu, Ying Xiong, Wenyi Jin, Yang Wan, Yunjiao Zhou, Ying Ao, Hui Wang
BACKGROUND/AIMS: The apoptosis of activated hepatic stellate cells (HSCs) is the central event in the reversal of liver fibrosis. K63 de-ubiquitinated receptor-interacting protein (RIP)1 promotes apoptosis in tumor necrosis factor (TNF)-α signaling pathway. In the previous study, we have proved that indole-3-carbinol (I3C) could reverse different models of liver fibrosis in rats, but the mechanism is still unclear. Thus, the present research aimed to demonstrate the induction of I3C on apoptosis of HSCs and the underlying molecular mechanism...
March 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28391277/lincrna-p21-inhibits-the-wnt-%C3%AE-catenin-pathway-in-activated-hepatic-stellate-cells-via-sponging-microrna-17-5p
#17
Fujun Yu, Yong Guo, Bicheng Chen, Liang Shi, Peihong Dong, Mengtao Zhou, Jianjian Zheng
BACKGROUND/AIMS: It is known that the activation of hepatic stellate cells (HSCs) is a pivotal step in the initiation and progression of liver fibrosis. Aberrant activated Wnt/β-catenin pathway is known to accelerate the development of liver fibrosis. microRNAs (miRNAs)-mediated Wnt/β-catenin pathway has been reported to be involved in HSC activation during liver fibrosis. However, whether long noncoding RNAs (lncRNAs) regulate Wnt/β-catenin pathway during HSC activation still remains unclear...
April 7, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28391159/inhibitory-effects-of-quercetin-on-the-progression-of-liver-fibrosis-through-the-regulation-of-nf-%C3%B0%C2%BAb-i%C3%B0%C2%BAb%C3%AE-p38-mapk-and-bcl-2-bax-signaling
#18
Rong Wang, Hai Zhang, Yuanyuan Wang, Fuxing Song, Yongfang Yuan
Quercetin, a natural flavonoid, has been used as a nutritional supplement for its anti-inflammatory and antioxidative properties. Quercetin was reported to exhibit a wide range of pharmacological properties, including its effect on anti-hepatic fibrosis. However, the anti-fibrotic mechanisms of quercetin have not been well-characterized to date. This study aimed to investigate the protective effects of quercetin on carbon tetrachloride (CCl4)-induced liver fibrosis in rats and to clarify its anti-hepatofibrotic mechanisms...
April 6, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28390947/expression-patterns-of-nuclear-receptors-in-parenchymal-and-non-parenchymal-mouse-liver-cells-and-their-modulation-in-cholestasis
#19
Ester Gonzalez-Sanchez, Delphine Firrincieli, Chantal Housset, Nicolas Chignard
Nuclear receptors (NR), the largest family of transcription factors, control many physiological and pathological processes. To gain insight into hepatic NR and their potential as therapeutic targets in cholestatis, we determined their expression in individual cell types of the mouse liver in normal and cholestatic conditions. Hepatocytes, cholangiocytes, hepatic stellate cells (HSC), sinusoidal endothelial cells (SEC) and Kupffer cells (KC) were isolated from the liver of mice with acute or chronic cholestasis (i...
April 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28390311/metformin-mitigates-carbon-tetrachloride-induced-tgf-%C3%AE-1-smad3-signaling-and-liver-fibrosis-in-mice
#20
Kerui Fan, Kejia Wu, Ling Lin, Pu Ge, Jie Dai, Xiaojiao He, Kai Hu, Li Zhang
Increasing evidence suggests that the widely used antidiabetic drug metformin have an extensive therapeutic range beyond hypoglycemic therapy. We previously found that metformin significantly attenuated acute hepatitis. The present study investigated the potential effects of metformin on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. The results indicated that treatment with metformin suppressed CCl4-induced elevation of liver index, formation of fibrotic septa, accumulation of connective tissue and upregulation of collagen I...
April 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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