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Liver injury

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https://www.readbyqxmd.com/read/29352225/a-humanized-mouse-model-of-liver-fibrosis-following-expansion-of-transplanted-hepatic-stellate-cells
#1
Daniel Benten, Johannes Kluwe, Jan W Wirth, Nina D Thiele, Antonia Follenzi, Kuldeep K Bhargava, Christopher J Palestro, Michael Koepke, Reni Tjandra, Tassilo Volz, Marc Lutgehetmann, Sanjeev Gupta
Hepatic stellate cells (HSCs) are major contributors to liver fibrosis, as hepatic injuries may cause their transdifferentiation into myofibroblast-like cells capable of producing excessive extracellular matrix proteins. Also, HSCs can modulate engraftment of transplanted hepatocytes and contribute to liver regeneration. Therefore, understanding the biology of human HSCs (hHSCs) is important, but effective methods have not been available to address their fate in vivo. To investigate whether HSCs could engraft and repopulate the liver, we transplanted GFP-transduced immortalized hHSCs into immunodeficient NOD/SCID mice...
January 19, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29352069/identification-of-ketene-reactive-intermediate-of-erlotinib-possibly-responsible-for-inactivation-of-p450-enzymes
#2
Huimin Zhao, Siyuan Li, Zixin Yang, Ying Peng, Xiaohui Chen, Jiang Zheng
Erlotinib (ELT), a tyrosine kinase inhibitor, is widely used for the treatment of non-small-cell lung cancer in clinic. Unfortunately, severe drug-induced liver injury and other adverse effects occurred during the treatment. Meanwhile, ELT has been reported to be a mechanism-based inactivator of CYPs 3A4 and 3A5. The objectives of this study were to identify ketene intermediate of ELT and investigate the association of the acetylenic bioactivation with the enzyme inactivation caused by ELT. A ketene intermediate was detected in human microsomal incubations of ELT, using 4-bromobenzylamine as a trapping agent...
January 19, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29352068/maternal-fetal-disposition-and-metabolism-of-retrorsine-in-pregnant-rats
#3
Xia Li, Xiaojing Yang, E Xiang, Jinyuan Luo, Shuaikai Qiu, Yan Fang, Li Zhang, Yu Guo, Jiang Zheng, Hui Wang
Pyrrolizidine alkaloids (PAs) are extensively synthesized by plants and are commonly present in herbs and foodstuffs, which exhibit hepatotoxicity requiring metabolic activation by cytochrome P450 (CYP) 3A to form the electrophilic metabolites-pyrrolic ester. PAs also cause embryo toxicity, but the metabolic profiles of PAs in fetus and placenta have been far from clear. In this study, we determined the basal metabolic activation of retrorsine (RTS) in rat maternal liver, placenta and fetal liver in vitro, and examined the fetal toxicity and bioactivation of RTS in vivo...
January 19, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29351922/activation-of-constitutive-androstane-receptor-ameliorates-renal-ischemia-reperfusion-induced-liver-and-kidney-injury
#4
You-Jin Choi, Dong Zhou, Anne Barbosa, Yongdong Niu, Xiudong Guan, Meishu Xu, Songrong Ren, Thomas Nolin, Yiuhua Liu, Wen Xie
Acute kidney injury (AKI) is associate with high mortality. Despite the evidence of AKI-induced distant organ injury, a relationship between AKI and liver injury has not been clearly established. The goal of this study is to investigate whether renal ischemia-reperfusion (IR) can affect liver pathophysiology. We showed that renal IR in mice induced fatty liver and compromised liver function through the down-regulation of constitutive androstane receptor (CAR; -90.4%) and inhibition of hepatic very low-density lipoprotein-triglyceride (VLDL-TG) secretion (-28...
January 19, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29351389/proliferation-of-hepatic-stellate-cells-mediated-by-yap-and-taz-contributes-to-liver-repair-and-regeneration-after-liver-ischemia-reperfusion-injury
#5
Takanori Konishi, Rebecca M Schuster, Alex B Lentsch
Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are key regulators of cell proliferation and organ size, however, their physiological contribution after liver injury has not been fully understood. In this study, we sought to determine the role of YAP and TAZ during liver recovery after ischemia-reperfusion (I/R). A murine model of partial (70%) I/R was used to induce liver injury and study the reparative and regenerative response. After liver injury, there was marked activation and proliferation of hepatic stellate cells...
January 11, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29351251/compatibility-with-panax-notoginseng-and-rehmannia-glutinosa-alleviates-the-hepatotoxicity-and-nephrotoxicity-of-tripterygium-wilfordii-via-modulating-the-pharmacokinetics-of-triptolide
#6
Qichun Zhang, Yiqun Li, Mengzhu Liu, Jinao Duan, Xueping Zhou, Huaxu Zhu
Tripterygium wilfordii (TW) and the representative active component triptolide show positive therapeutic effect on the autoimmune disorders and simultaneously ineluctable hepatotoxicity and nephrotoxicity. Combinational application of Panax notoginseng (PN) and Rehmannia glutinosa (RG) weakens the toxicity of TW according the clinical application of traditional Chinese medicine. This article was aimed at the mechanism of decreasing toxicity of TW by the combinational application of PN and RG. Biochemical and pathohistological analysis were utilized to assess the toxicity on liver and kidney in rats administrated with TW, TW-PN, TW-RG and TW-PN-RG for 3 and 7 days...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29351246/addition-of-berberine-to-preservation-solution-in-an-animal-model-of-ex-vivo-liver-transplant-preserves-mitochondrial-function-and-bioenergetics-from-the-damage-induced-by-ischemia-reperfusion
#7
Rui Miguel Martins, Anabela Pinto Rolo, João Soeiro Teodoro, Emanuel Furtado, Rui Caetano Oliveira, José Guilherme Tralhão, Carlos Marques Palmeira
Liver transplantation is a therapeutic regimen to treat patients with non-malignant end-stage liver diseases and malignant tumors of hepatic origin. The ischemia/reperfusion (I/R) injury in liver transplantation is associated with disruption of mitochondrial function in the hepatic parenchyma. Several studies have been conducted in animal models to identify pharmacological therapeutic strategies to minimize the injury induced by the cold/warm I/R in liver transplantation. Most of these studies were conducted in unrealistic conditions without the potential to be translated to clinical usage...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29351226/curcumin-attenuates-on-carbon-tetrachloride-induced-acute-liver-injury-in-mice-via-modulation-of-the-nrf2-ho-1-and-tgf-%C3%AE-1-smad3-pathway
#8
Xinyan Peng, Chongshan Dai, Quanwen Liu, Junke Li, Jingru Qiu
This study aimed to investigate the protective effect of curcumin against carbon tetrachloride (CCl₄)-induced acute liver injury in a mouse model, and to explain the underlying mechanism. Curcumin at doses of 50, 100 and 200 mg/kg/day were administered orally once daily for seven days prior to CCl₄ exposure. At 24 h, curcumin-attenuated CCl₄ induced elevated serum transaminase activities and histopathological damage in the mouse's liver. Curcumin pre-treatment at 50, 100 and 200 mg/kg significantly ameliorated CCl₄-induced oxidative stress, characterized by decreased malondialdehyde (MDA) formations, and increased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) content, followed by a decrease in caspase-9 and -3 activities...
January 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29350771/recombinant-relaxin-protects-liver-transplants-from-ischemia-damage-via-hepatocyte-glucocorticoid-receptor-from-bench-to-bedside
#9
Shoichi Kageyama, Kojiro Nakamura, Takehiro Fujii, Bibo Ke, Rebecca A Sosa, Elaine F Reed, Nakul Datta, Ali Zarrinpar, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Hepatic ischemia-reperfusion injury (IRI) represents a major risk factor of early graft dysfunction and acute/chronic rejection as well as a key obstacle to expanding the donor pool in orthotopic liver transplantation (OLT). Although glucocorticoid receptor (GR) signaling may enhance cytoprotective programs, clinical use of glucocorticoid is limited due to adverse effects, while clinical relevance of GR-facilitated cytoprotection in OLT remains unknown. We aimed to evaluate the significance of hepatic GR in clinical OLT and verify the impact of recombinant human relaxin (rhRLX), which may function as GR agonist in tissue/disease-specific manner...
January 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29350757/hepatoprotective-effects-of-sophoricoside-against-fructose-induced-liver-injury-via-regulating-lipid-metabolism-oxidation-and-inflammation-in-mice
#10
Wenfeng Li, Yalong Lu
The dried fruit of Sophora japonica L. is a traditional Chinese herb tea rich in sophoricoside that is an isoflavone glycoside. The aim of current study was to investigate the hepatic protective effect of sophoricoside in high fructose (HF) diet fed mice. Healthy male mice were fed 30% fructose water and treated 80 and 160 mg/kg·bw sophoricoside continuously for 8 wk. Our data showed that administration of sophoricoside at 80 and 160 mg/kg·bw observably decreased the body weight and liver weight in HF-fed mice...
January 19, 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29350750/the-hepatoprotective-effect-of-selenium-enriched-yeast-and-gum-arabic-combination-on-carbon-tetrachloride-induced-chronic-liver-injury-in-rats
#11
Mohammed Hamid, Yassin Abdulrahim, Dandan Liu, Gang Qian, Alamzeb Khan, Kehe Huang
The antioxidant and anti-inflammatory effects of selenium-enriched yeast (SY) and Gum Arabic (GA) have been reported. This study aimed to determine the hepatoprotective effect of SY and GA combination on carbon tetrachloride (CCl4 )-induced chronic liver injury in rats and to explore their synergistic mechanisms of action. Forty adult male Wistar rats randomly allotted to 5 groups: (A) worked as control, (B) was administered CCl4 , (C-E) were fed daily by GA, SY, and GA+SY respectively after mixing with basal diet, following CCl4 -intoxication...
January 19, 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29350370/operative-and-non-operative-management-of-children-with-abdominal-gunshot-injuries
#12
Mehmet Şerif Arslan, Hikmet Zeytun, Serkan Arslan, Erol Basuguy, Mehmet Hanifi Okur, Bahattin Aydoğdu, Cemil Göya, İbrahim Uygun, Selçuk Otçu
BACKGROUND: Non-operative management (NOM) is a standard treatment method for solid organ injuries worldwide. There is no consensus on the management of gunshot wounds (GSW) because of the higher frequency of hollow viscus injuries (HVI) and the unpredictable depth of tissue damage produced by kinetic energy transfer during retardation of the bullet. Here we aimed to reevaluate indications for surgery and NOM based on our pediatric patients with abdominal GSW. METHODS: We performed a retrospective analysis of patients evaluated and treated for abdominal GSW at University of Dicle between January 2010 and October 2016...
January 2018: Ulusal Travma Ve Acil Cerrahi Dergisi, Turkish Journal of Trauma & Emergency Surgery: TJTES
https://www.readbyqxmd.com/read/29350250/-abdominal-injuries-in-polytraumatized-adults-systematic-review
#13
C E M Pothmann, K Sprengel, H Alkadhi, G Osterhoff, F Allemann, T Jentzsch, G Jukema, H C Pape, H-P Simmen, V Neuhaus
Abdominal injuries are potentially life-threatening and occur in 20-25% of all polytraumatized patients. Blunt trauma is the main mechanism. The liver and spleen are most commonly injured and much less often the intestines. The clinical evaluation proves equivocal in many cases; therefore, the gold standard is computed tomography (CT), which has been increasingly used even in hemodynamically weakly stable or sometimes even unstable patients because it promptly provides precise diagnostic findings, which present the basis for successful therapy...
January 19, 2018: Der Unfallchirurg
https://www.readbyqxmd.com/read/29349567/hbeag-induces-the-expression-of-macrophage-mir-155-to-accelerate-liver-injury-via-promoting-production-of-inflammatory-cytokines
#14
Wenwen Wang, Hongjun Bian, Feifei Li, Xiao Li, Di Zhang, Shuohuan Sun, Shouyang Song, Qiang Zhu, Wanhua Ren, Chengyong Qin, Jianni Qi
Activation of Kupffer cells (KCs) induced that inflammatory cytokine production plays a central role in the pathogenesis of HBV infection. The previous studies from our and other laboratory demonstrated miRNAs can regulate TLR-inducing inflammatory responses to macrophage. However, the involvement of miRNAs in HBV-associated antigen-induced macrophage activation is still not thoroughly understood. Here, we evaluated the effects and mechanisms of miR-155 in HBV-associated antigen-induced macrophage activation...
January 18, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29348818/high-cyp2e1-activity-correlates-with-hepatofibrogenesis-induced-by-nitrosamines
#15
Jie Gao, Gao-Ju Wang, Zhao Wang, Na Gao, Jing Li, Yun-Fei Zhang, Jun Zhou, Hong-Xin Zhang, Qiang Wen, Han Jin, Hai-Ling Qiao
Hepatofibrosis, which leads to cirrhosis and eventual hepatocellular carcinoma, is a common response to chronic toxin-mediated liver injury. Nitrosamines are potent hepatotoxic agents that cause necrosis and subsequent fibrosis in the liver as a result of cytochrome P450 2E1 (CYP2E1)-dependent metabolism, which generates toxic metabolites that form adducts with nucleic acids, leading to hepatotoxicity and mutagenesis. Herein, CYP2E1 activity and content were determined in fibrotic liver tissue from patients with hepatocellular carcinoma...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348606/amp-activated-protein-kinase-agonist-n6-3-hydroxyphenyl-adenosine-protects-against-fulminant-hepatitis-by-suppressing-inflammation-and-apoptosis
#16
Jin Li, Bo Chen, Liping Zhong, Feng Gao, Haibo Zhu, Fengzhong Wang
Both AMP-activated protein kinase (AMPK) agonist and inhibitor have been reported to protect against fulminant hepatitis, implying that AMPK may play a complicated role in the development of fulminant hepatitis. In this study, we exploited whether the novel AMPK agonist N6-(3-hydroxyphenyl)adenosine (named as M1) exerted protective effects on fulminant hepatitis and whether its beneficial effects were AMPK-dependent. Results showed that intraperitoneal injection of M1 improved liver function, ameliorated liver injury and finally raised the survival rate in D-galactosamine/lipopolysaccharide (GalN/LPS)-treated mice...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348414/microrna-146a-5p-attenuates-irradiation-induced-and-lps-induced-hepatic-stellate-cell-activation-and-hepatocyte-apoptosis-through-inhibition-of-tlr4-pathway
#17
Yuhan Chen, Zhifeng Wu, Baoying Yuan, Yinying Dong, Li Zhang, Zhaochong Zeng
Elevated toll-like receptor 4 (TLR4) expression is associated with a high risk of radiation-induced liver disease (RILD). MicroRNA (miR)-146a-5p is a key regulator of lipopolysaccharide (LPS)/TLR4 signaling, but its role in modulation of RILD remains unclear. Here, we found that irradiation and LPS stimulation induced TLR4 and miR-146a-5p expression in the human hepatic stellate cell (HSC) line LX2. Ectopic expression of miR-146a-5p in LX2 inhibited irradiation-induced and LPS-induced pro-inflammatory cytokine secretion and cell proliferation, and promoted cell apoptosis by down-regulating the expression levels of TLR4, interleukin-1 receptor associated kinase 1 (IRAK1), tumor necrosis factor receptor associated factor 6 (TRAF6) and phosphorylation of nuclear factor-kappa B...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348399/insulin-like-growth-factor-2-is-a-key-mitogen-driving-liver-repopulation-in-mice
#18
Min-Jun Wang, Fei Chen, Qing-Gui Liu, Chang-Cheng Liu, Hao Yao, Bing Yu, Hai-Bin Zhang, He-Xin Yan, Yibiao Ye, Tao Chen, Kirk J Wangensteen, Xin Wang, Yi-Ping Hu, Zhi-Ying He
Hepatocyte transplantation holds great promise as an alternative to orthotopic organ transplantation in the treatment of liver diseases. However, obtaining clinically meaningful levels of liver repopulation has not been achieved because the mechanisms regulating hepatocyte proliferation in recipient livers have not yet been well characterized. In the mouse model of Hereditary Tyrosinemia Type I, the fumarylacetoacetate hydrolase-deficient (Fah-/-) mouse, we found gradually increasing expression level of insulin-like growth factor 2 (IGF2) in the hepatocytes of host livers...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29347961/relevant-pericardial-effusion-caused-by-cytomegalovirus-infection-in-an-immunocompetent-patient-a-case-report
#19
Tabea Hutter, Dirk Springe, Lukas Ebnöther, Marcos Delgado
BACKGROUND: Cytomegalovirus infection is known to cause symptomatic disease in immunocompromised patients, while an infection in immunocompetent individuals normally causes few or no symptoms. We present the case of an immunocompetent adult patient with unexpected severe evolution. CASE PRESENTATION: An otherwise healthy, 72-year-old Caucasian woman presented with complaints of progressive shoulder pain and dyspnoea on exertion. The blood test results showed elevated inflammation parameters and elevated hepatic transaminase levels...
January 19, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29346429/the-farnesoid-x-receptor-agonist-obeticholic-acid-upregulates-biliary-excretion-of-asymmetric-dimethylarginine-via-mate-1-during-hepatic-ischemia-reperfusion-injury
#20
Andrea Ferrigno, Laura Giuseppina Di Pasqua, Clarissa Berardo, Veronica Siciliano, Vittoria Rizzo, Luciano Adorini, Plinio Richelmi, Mariapia Vairetti
BACKGROUND: We previously showed that increased asymmetric dimethylarginine (ADMA) biliary excretion occurs during hepatic ischemia/reperfusion (I/R), prompting us to study the effects of the farnesoid X receptor (FXR) agonist obeticholic acid (OCA) on bile, serum and tissue levels of ADMA after I/R. MATERIAL AND METHODS: Male Wistar rats were orally administered 10mg/kg/day of OCA or vehicle for 5 days and were subjected to 60 min partial hepatic ischemia or sham-operated...
2018: PloS One
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