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https://www.readbyqxmd.com/read/28526886/fk866-attenuates-acute-hepatic-failure-through-c-jun-n-terminal-kinase-jnk-dependent-autophagy
#1
Enshuang Guo, Renlong Li, Jiankun Yang, Jun Zhang, Anyi Li, Yan Yang, Shenpei Liu, Anding Liu, Xiaojing Jiang
FK866 exhibits a protective effect on D-galactosamine (GaIN)/lipopolysaccharide (LPS) and concanavalin A (ConA)-induced acute liver failure (ALF), but the mechanism by which FK866 affords this benefit has not yet been elucidated. Autophagy has a protective effect on acute liver injury. However, the contribution of autophagy to FK866-conferred hepatoprotection is still unclear. This study aimed to investigate whether FK866 could attenuate GaIN/LPS and ConA-induced ALF through c-jun-N-terminal kinase (JNK)-dependent autophagy...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28488390/mesenchymal-stem-cells-protect-from-acute-liver-injury-by-attenuating-hepatotoxicity-of-liver-nkt-cells-in-inos-and-ido-dependent-manner
#2
Marina Gazdic, Bojana Simovic Markovic, Ljubica Vucicevic, Tamara Nikolic, Valentin Djonov, Nebojsa Arsenijevic, Vladimir Trajkovic, Miodrag L Lukic, Vladislav Volarevic
The effects of mesenchymal stem cells (MSCs) on phenotype and function of natural killer T (NKT) cells, is not understood. We used concanavalin A (ConA) - and α-galactosylceramide (α-GalCer)-induced liver injury to evaluate effects of MSCs on NKT-dependent hepatotoxicity. Mouse MSCs (mMSCs) significantly reduced Con A- and α-GalCer-mediated hepatitis in C57Bl/6 mice, as demonstrated by histopathological and biochemical analysis, attenuated influx of inflammatory (T-bet(+) TNF-α, IFN-γ producing and GATA3(+) , IL-4-producing) liver NKT cells and down-regulated TNF-α, IFN-γ and IL-4 levels in the sera...
May 9, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28482408/-protective-effect-of-intraperitoneal-transplantation-of-human-liver-derived-stem-cells-at-different-times-against-concanavalin-a-induced-acute-liver-injury-in-mice
#3
Y Z Bi, Z Fan, D F Chen, S S Li, Q Y Wang, P F Gao, Q Q Wang, Z P Duan, Y Chen, L B Kong, Y B Wang, F Hong
Objective: To investigate the protective effect of intraperitoneal transplantation of human liver-derived stem cells at different times against concanavalin A (ConA)-induced acute liver injury in mice. Methods: A total of 88 male C57BL/6 mice were randomly divided into normal control group (group C), ConA model group (group M), and human liver-derived stem cells (HYX1)+ConA group (group E); according to the interval between phosphate buffer/HYX1 injection and ConA injection, Groups M and E were further divided into 3-hour groups (M1 and E1 groups), 6-hour groups (M2 and E2 groups), 12-hour groups (M3 and E3 groups), 24-hour groups (M4 and E4 groups), and 48-hour groups (M5 and E5 groups)...
March 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28450923/expression-and-roles-of-tipe2-in-autoimmune-hepatitis
#4
Jinhua Qian, Zongde Meng, Jiachang Guan, Zhiwei Zhang, Yangang Wang
Tumor necrosis factor, alpha-induced protein 8-like 2 (TIPE2) is associated with the development of hepatic inflammatory diseases. However, to date, the possible role of TIPE2 in autoimmune hepatitis (AIH) has not been reported. The present study aimed to investigate the expression of TIPE2 in peripheral blood mononuclear cells (PBMCs) of mice with AIH. Furthermore, the liver function, pro-inflammatory cytokine production and hepatic histopathology were examined in TIPE2-deficient mice in order to evaluate whether TIPE2 is involved in the pathogenesis of AIH...
March 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28416868/a-synergistic-effect-of-cremophor-and-beta-glucosylceramide-to-exert-liver-and-sugar-protection
#5
Yehudit Shabat, Yaron Ilan
Many commonly used drugs carry the potential to induce hepatotoxicity, and a large number of foods and beverages induce an increase in blood sugar levels. A change in lifestyle by omitting these compounds is not applicable in many circumstances. β-Glucosylceramide (GC) is a naturally occurring glycosphingolipid that exerts an effect on the immune system. Cremophor EL (CrEL) is a synthetic, nonionic surfactant that is used as a vehicle for the administration of water-insoluble compounds. The aim of the present study was to determine the synergistic effect of oral administration of the combination of GC and CrEL (GCC) when added to potential toxic substrates or to sugar-enriched compounds...
April 2017: Journal of Food Science and Technology
https://www.readbyqxmd.com/read/28377718/sophocarpine-protects-mice-from-cona-induced-hepatitis-via-inhibition-of-the-ifn-gamma-stat1-pathway
#6
Xiu-Xiu Sang, Rui-Lin Wang, Cong-En Zhang, Shi-Jing Liu, Hong-Hui Shen, Yu-Ming Guo, Ya-Ming Zhang, Ming Niu, Jia-Bo Wang, Zhao-Fang Bai, Xiao-He Xiao
Sophocarpine is the major pharmacologically active compound of the traditional Chinese herbal medicine Radix Sophorae Subprostratae which has been used in treating hepatitis for years in China. It has been demonstrated that Sophocarpine exerts an activity in immune modulation and significantly decreases the production of inflammatory cytokines. However, the protective effects of Sophocarpine in T cell-dependent immune hepatitis remained unknown. The aim of this study was to determine the protective effects and pharmacological mechanisms of Sophocarpine on Concanavalin A (ConA)-induced hepatitis, an experimental model of T cell-mediated liver injury...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28330461/impaired-liver-regeneration-is-associated-with-reduced-cyclin-b1-in-natural-killer-t-cell-deficient-mice
#7
Ami Ben Ya'acov, Hadar Meir, Lydia Zolotaryova, Yaron Ilan, Eyal Shteyer
BACKGROUND: It has been shown that the proportion of natural killer T cells is markedly elevated during liver regeneration and their activation under different conditions can modulate this process. As natural killer T cells and liver injury are central in liver regeneration, elucidating their role is important. METHODS: The aim of the current study is to explore the role of natural killer T cells in impaired liver regeneration. Concanvalin A was injected 4 days before partial hepatectomy to natural killer T cells- deficient mice or to anti CD1d1-treated mice...
March 23, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28261494/radioprotective-effects-of-cimetidine-on-rats-irradiated-by-long-term-low-dose-rate-neutrons-and-60-co-%C3%AE-rays
#8
Ding-Wen Jiang, Qing-Rong Wang, Xian-Rong Shen, Ying He, Tian-Tian Qian, Qiong Liu, Deng-Yong Hou, Yu-Ming Liu, Wei Chen, Xin Ren, Ke-Xian Li
BACKGROUND: Cimetidine, an antagonist of histamine type II receptors, has shown protective effects against γ-rays or neutrons. However, there have been no reports on the effects of cimetidine against neutrons combined with γ-rays. This study was carried out to evaluate the protective effects of cimetidine on rats exposed to long-term, low-dose-rate neutron and γ-ray combined irradiation (n-γ LDR). METHODS: Fifty male Sprague-Dawley (SD) rats were randomly divided into 5 groups: the normal control group, radiation model group, 20 mg/(kg · d) cimetidine group, 80 mg/(kg · d) cimetidine group and 160 mg/(kg · d) cimetidine group (10 rats per group)...
2017: Military Medical Research
https://www.readbyqxmd.com/read/28246592/stellate-cell-activation-and-imbalanced-expression-of-tgf-%C3%AE-1-tgf-%C3%AE-3-in-acute-autoimmune-liver-lesions-induced-by-cona-in-mice
#9
Liyun Wang, Lei Tu, Jinping Zhang, Keshu Xu, Wei Qian
Objective. To study the pathogenic feature of liver injury, activation of hepatic stellate cells, and dynamic expression of TGF-β1/TGF-β3 to reveal their role in liver injury induced by ConA. Methods. Mice were randomly divided into control group and ConA treatment group. ConA (20 mg/kg) was injected through vena caudalis in ConA treatment group; the controls received the same volume of saline injection. After injection for 2 h, 8 h, 24 h, and 48 h, animals were terminated. Blood, liver, and spleen were harvested...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28174672/immunomodulatory-effects-of-adipose-tissue-derived-stem-cells-on-concanavalin-a-induced-acute-liver-injury-in-mice
#10
Yasuma Yoshizumi, Hiroshi Yukawa, Ryoji Iwaki, Sanae Fujinaka, Ayano Kanou, Yuki Kanou, Tatsuya Yamada, Shingo Nakagawa, Tomomi Ohara, Kenta Nakagiri, Yusuke Ogihara, Yoko Tsutsui, Yumi Hayashi, Masatoshi Ishigami, Yoshinobu Baba, Tetsuya Ishikawa
Cell therapy with adipose tissue-derived stem cells (ASCs) is expected to be a candidate for the treatment of fulminant hepatic failure (FHF), which is caused by excessive immune responses. In order to evaluate the therapeutic effects of ASCs on FHF, the in vitro and in vivo immunomodulatory effects of ASCs were examined in detail in the mouse model. The in vitro effects of ASCs were examined by assessing their influence on the proliferation of lymphomononuclear cells (LMCs) stimulated with three kinds of mitogens: phorbol 12-myristate 13-acetate (PMA) plus ionomycin, concanavalin A (ConA), and lipopolysaccharide (LPS)...
January 8, 2017: Cell Medicine
https://www.readbyqxmd.com/read/28109817/salecan-protected-against-concanavalin-a-induced-acute-liver-injury-by-modulating-t-cell-immune-responses-and-nmr-based-metabolic-profiles
#11
Qi Sun, Xi Xu, Xiao Yang, Dan Weng, Junsong Wang, Jianfa Zhang
Salecan, a water-soluble extracellular β-glucan produced by Agrobacterium sp. ZX09, has been reported to exhibit a wide range of biological effects. The aims of the present study were to investigate the protective effect of salecan against Concanavalin A (ConA)-induced hepatitis, a well-established animal model of immune-mediated liver injury, and to search for possible mechanisms. C57BL/6 mice were pretreated with salecan followed by ConA injection. Salecan treatment significantly reduced ConA-induced acute liver injury, and suppressed the expression and secretion of inflammatory cytokines including interferon (IFN)-γ, interleukin (IL)-6 and IL-1β in ConA-induced liver injury model...
January 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28092402/%C3%AE-%C3%AE-t-cells-are-indispensable-for-interleukin-23-mediated-protection-against-concanavalin-a-induced-hepatitis-in-hepatitis-b-virus-transgenic-mice
#12
Ziyu Meng, Jingya Wang, Yifang Yuan, Guangchao Cao, Shuobing Fan, Chao Gao, Li Wang, Zheng Li, Xiaoli Wu, Zhenzhou Wu, Liqing Zhao, Zhinan Yin
Hepatitis B virus surface antigen (HBsAg) carriers are highly susceptible to liver injury triggered by environmental biochemical stimulation. Previously, we have reported an inverse correlation between γδ T cells and liver damage in patients with hepatitis B virus (HBV). However, whether γδ T cells play a role in regulating the hypersensitivity of HBsAg carriers to biochemical stimulation-induced hepatitis is unknown. In this study, using HBV transgenic (HBs-Tg) and HBs-Tg T-cell receptor-δ-deficient (TCR-δ(-/-) ) mice, we found that mice genetically deficient in γδ T cells exhibited more severe liver damage upon Concanavalin A (Con A) treatment, as indicated by substantially higher serum alanine aminotransferase levels, further elevated interferon-γ (IFN-γ) levels and more extensive necrosis...
May 2017: Immunology
https://www.readbyqxmd.com/read/28065940/cd24-aggravates-acute-liver-injury-in-autoimmune-hepatitis-by-promoting-ifn-%C3%AE-production-by-cd4-t-cells
#13
Chenhong Zheng, Shulei Yin, Yang Yang, Yizhi Yu, Xiaohua Xie
The T-cell-mediated immune response is implicated in many clinical hepatic injuries, such as autoimmune hepatitis and acute virus hepatitis. CD24 is widely expressed by different immune cells and plays an important role in the pathogenesis of many autoimmune diseases. However, the role of CD24 in T-cell-mediated liver injury has not been elucidated until now. Here we showed that CD24 deficiency protects mice from concanavalin A (ConA)-induced fulminant liver injury by reducing serum interferon-γ (IFN-γ) levels...
January 9, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28032440/magnolol-attenuates-concanavalin-a-induced-hepatic-fibrosis-inhibits-cd4-t-helper-17-th17-cell-differentiation-and-suppresses-hepatic-stellate-cell-activation-blockade-of-smad3-smad4-signalling
#14
Hongjun Zhang, Baoling Ju, Xiaoli Zhang, Yanfei Zhu, Ying Nie, Yuanhong Xu, Qiuxia Lei
Magnolol is a pharmacological biphenolic compound extracted from Chinese herb Magnolia officinalis, which displays anti-inflammatory and antioxidant effects. This study was aimed at exploring the potential effect of magnolol on immune-related liver fibrosis. Herein, BALB/c mice were injected with concanavalin A (ConA, 8 mg/kg/week) up to 6 weeks to establish hepatic fibrosis, and magnolol (10, 20, 30 mg/kg/day) was given to these mice orally throughout the whole experiment. We found that magnolol preserved liver function and attenuated liver fibrotic injury in vivo...
June 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27832933/a-plant-cell-expressed-recombinant-anti-tnf-fusion-protein-is-biologically-active-in-the-gut-and-alleviates-immune-mediated-hepatitis-and-colitis
#15
Yaron Ilan, Svetlana Gingis-Velitski, Ami Ben Ya'aco, Yehudit Shabbat, Lidya Zolotarov, Einat Almon, Yoseph Shaaltiel
The orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) (n=6) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human antibody IgG1 domain. AIM: To evaluate the immune modulatory effect of the oral administration of plant cells expressing PRX-106. METHODS: Mice treated with Concanavalin A (ConA) to induce immune hepatitis was orally treated with cells expressing PRX-106 containing 0...
November 4, 2016: Immunobiology
https://www.readbyqxmd.com/read/27831558/ripk1-protects-from-tnf-%C3%AE-mediated-liver-damage-during-hepatitis
#16
Aveline Filliol, Claire Piquet-Pellorce, Jacques Le Seyec, Muhammad Farooq, Valentine Genet, Catherine Lucas-Clerc, John Bertin, Peter J Gough, Marie-Thérèse Dimanche-Boitrel, Peter Vandenabeele, Mathieu Jm Bertrand, Michel Samson
Cell death of hepatocytes is a prominent characteristic in the pathogenesis of liver disease, while hepatolysis is a starting point of inflammation in hepatitis and loss of hepatic function. However, the precise molecular mechanisms of hepatocyte cell death, the role of the cytokines of hepatic microenvironment and the involvement of intracellular kinases, remain unclear. Tumor necrosis factor alpha (TNF-α) is a key cytokine involved in cell death or survival pathways and the role of RIPK1 has been associated to the TNF-α-dependent signaling pathway...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27821872/enterogenous-bacterial-glycolipids-are-required-for-the-generation-of-natural-killer-t-cells-mediated-liver-injury
#17
Yingfeng Wei, Benhua Zeng, Jianing Chen, Guangying Cui, Chong Lu, Wei Wu, Jiezuan Yang, Hong Wei, Rufeng Xue, Li Bai, Zhi Chen, Lanjuan Li, Kazuya Iwabuchi, Toshimitsu Uede, Luc Van Kaer, Hongyan Diao
Glycolipids are potent activator of natural killer T (NKT) cells. The relationship between NKT cells and intestinal bacterial glycolipids in liver disorders remained unclear. We found that, in sharp contrast to specific pathogen-free (SPF) mice, germ-free (GF) mice are resistant to Concanavalin A (ConA)-induced liver injury. ConA treatment failed to trigger the activation of hepatic NKT cells in GF mice. These defects correlated with the sharply reduced levels of CD1d-presented glycolipid antigens in ConA-treated GF mice compared with SPF counterparts...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27760053/a-murder-mystery-in-the-liver-who-done-it-and-how
#18
Lily Dara, Zhang-Xu Liu, Neil Kaplowitz
Hepatocyte death, which can be apoptosis or necrosis depending on the context, is a prominent feature of liver disease. The lectin concanavalin A (ConA) activates immune cells, resulting in inflammatory liver injury and hepatocyte necrosis. In this issue of the JCI, Günther et al. demonstrate that the pseudokinase mixed lineage kinase domain-like protein (MLKL) participates in hepatocyte death in ConA injury and that MLKL-mediated death is independent of the receptor-interacting protein kinase RIPK3. RIPK3 was absent in hepatocytes, and MLKL-deficient mice, but not RIPK3-deficient mice, were protected from ConA-induced liver injury...
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27714757/the-protective-effect-of-the-natural-compound-hesperetin-against-fulminant-hepatitis-in-vivo-and-in-vitro
#19
Xueting Bai, Peixuan Yang, Qiaoling Zhou, Bozhi Cai, Manon Buist-Homan, He Cheng, Jiyang Jiang, Daifei Shen, Lijun Li, Xiajiong Luo, Klaas Nico Faber, Han Moshage, Ganggang Shi
BACKGROUND AND PURPOSE: Liver diseases are mostly accompanied by inflammation and hepatocyte death. Therapeutic approaches targeting both hepatocyte injury and inflammation are not available. Natural compounds are considered as potential treatment for inflammatory liver diseases. Hesperetin, a flavonoid component of citrus fruits, has been reported to have anti-inflammatory properties. The aim of this study was to evaluate the cytoprotective and anti-inflammatory properties of hesperetin both in vitro and in models of fulminant hepatitis...
January 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27685635/circulating-histones-are-major-mediators-of-systemic-inflammation-and-cellular-injury-in-patients-with-acute-liver-failure
#20
Zongmei Wen, Zhen Lei, Lu Yao, Ping Jiang, Tao Gu, Feng Ren, Yan Liu, Chunyan Gou, Xiuhui Li, Tao Wen
Acute liver failure (ALF) is a life-threatening systemic disorder. Here we investigated the impact of circulating histones, recently identified inflammatory mediators, on systemic inflammation and liver injury in murine models and patients with ALF. We analyzed histone levels in blood samples from 62 patients with ALF, 60 patients with chronic liver disease, and 30 healthy volunteers. We incubated patients' sera with human L02 hepatocytes and monocytic U937 cells to assess cellular damage and cytokine production...
2016: Cell Death & Disease
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