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https://www.readbyqxmd.com/read/28641031/treatment-options-for-nonalcoholic-steatohepatitis-a-safety-evaluation
#1
Danny Issa, Julia Wattacheril, Arun J Sanyal
Introduction There is an urgent as yet unmet need to develop highly effective and safe therapeutics for nonalcoholic fatty liver disease (NAFLD). The remarkable progress in understanding NAFLD pathogenesis allowed the identification of injury pathways which may be recruited as therapy targets. Areas covered This article reviews the safety and tolerability data of the NAFLD therapies and explains the mechanistic basis for each of the established and investigational drugs. Treatment targets include: weight loss, anti-metabolic agents such as lipid lowering and anti-diabetic drugs, inflammation, fibrosis and others such as targeting gut microbiota, immune modulation and apoptosis...
June 22, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28640790/microrna-155-deficiency-in-kupffer-cells-ameliorates-liver-ischemia-reperfusion-injury-in-mice
#2
Yakun Li, Dongxia Ma, Zhimin Wang, Jun Yang
BACKGROUND: MicroRNA-155 (miR-155) is known to be involved in autoimmune diseases, inflammation, and transplantation. However, its role in a warm hepatic ischemia-reperfusion (IR) model has not been fully elucidated. METHODS: Partial hepatic IR was performed in wild-type and miR-155-deficient mice treated with or without GdCl3, and then the serum transaminase concentration and histology were analyzed. Kupffer cells (KCs) were isolated from the liver after IR, and immunohistochemistry was used to evaluate activation and polarization...
July 2017: Transplantation
https://www.readbyqxmd.com/read/28637102/-the-progression-of-liver-fibrosis-in-non-alcoholic-fatty-liver-disease
#3
REVIEW
Moon Young Kim
Understanding the pathogenesis of non-alcoholic steatohepatitis (NASH) and its fibrosis progression is still evolving. Nonetheless, current evidence suggests that mechanisms involved are very complex parallel processes with multiple metabolic factors. Lipotoxicity related with excess saturated free fatty acids, obesity, and insulin resistance acts as the central driver of cellular injury via oxidative stress. Hepatocyte apoptosis and/or senescence are also contribute to the activation of inflammasome via various intra- and inter-cellular signaling mechanisms that lead to fibrosis...
June 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28636830/attenuation-of-hepatic-steatosis-by-purple-sweet-potato-color-is-associated-with-blocking-src-erk-c-ebp%C3%AE-signalling-in-high-fat-diet-treated-mice
#4
Xin Wang, Zi-Feng Zhang, Gui-Hong Zheng, Ai-Min Wang, Chun-Hui Sun, Su-Ping Qin, Juan Zhuang, Jun Lu, Dai-Fu Ma, Yuan-Lin Zheng
Our previous work showed that purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, effectively improved hepatic glucose metabolic dysfunction in high-fat diet (HFD)-treated mice. This study investigated the effects of PSPC on HFD-induced hepatic steatosis and the signalling events associated with these effects. Mice were divided into four groups: Control group, HFD group, HFD+PSPC group and PSPC group. PSPC was administered daily for 20 weeks at oral doses of 700 mg/kg/day. Our results showed that PSPC significantly improved obesity and related metabolic parameters, as well as liver injury in HFD-treated mice...
June 21, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28636533/microrna-149-suppresses-hepatic-inflammatory-response-through-antagonizing-stat3-signaling-pathway
#5
Qiqi Zhang, Jia Su, Ziwei Wang, Hui Qi, Zeyong Ge, Zhijun Li, Wei-Dong Chen, Yan-Dong Wang
Chronic inflammation is increasingly recognized as an important component of tumorigenesis and metabolic diseases. The roles of microRNA149* (miRNA149*) in inflammation remain poorly understood. Here, we demonstrate that miR-149* is a suppressor of STAT3-mediated inflammation. MiR-149*-/- mice were generated with CRISPR/CAS9 technique. In a lipopolysaccharide (LPS)-induced inflammation model, miR-149*-/- mice show more severe liver injury and inflammation, compared with wild-type (WT) mice. MiR-149*-/- mice also displayed elevated messenger RNA (mRNA) levels of interleukin (IL)-6, inducible nitric oxide synthase (iNOS), complement C3 (C3) and IL-4 in response to LPS...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636309/quantitative-chemical-proteomic-profiling-of-the-in-vivo-targets-of-reactive-drug-metabolites
#6
Landon R Whitby, R Scott Obach, Gabriel M Simon, Matthew M Hayward, Benjamin F Cravatt
Idiosyncratic liver toxicity represents an important problem in drug research and pharmacotherapy. Reactive drug metabolites that modify proteins are thought to be a principal factor in drug-induced liver injury. Here, we describe a quantitative chemical proteomic method to identify the targets of reactive drug metabolites in vivo. Treating mice with clickable analogues of four representative hepatotoxic drugs, we demonstrate extensive covalent binding that is confined primarily to the liver. Each drug exhibited a distinct target profile that, in certain cases, showed strong enrichment for specific metabolic pathways (e...
June 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28636071/the-role-of-homocysteine-in-seminal-vesicles-remodeling-in-rat
#7
Adel Ghoul, Elara Moudilou, Mohamed El Hadi Cherifi, Fouzia Zerrouk, Billel Chaouad, Anissa Moulahoum, Souhila Aouichat-Bouguerra, Khira Othmani, Jean-Marie Exbrayat, Yasmina Benazzoug
INTRODUCTION: Elevated plasma homocysteine (Hcy) levels have been associated with several tissue injuries including heart and liver fibrosis. In these diseases, hyperhomocysteinemia (Hhcy) plays a major role in modulating the alteration of the balance between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMPs), leading to the pathological accumulation of extracellular matrix (ECM) proteins. Since the effect of Hhcy on ECM of seminal vesicle was not studied, the aim of our research was to check if Hcy can induce a remodeling within seminal vesicles ECM...
June 21, 2017: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/28635176/genetic-loss-of-the-muscarinic-m3-receptor-m3-r-markedly-alters-bile-formation-and-cholestatic-liver-injury-in-mice
#8
Franziska Durchschein, Elisabeth Krones, Marion J Pollheimer, Gernot Zollner, Martin Wagner, Jean-Pierre Raufman, Peter Fickert
Hepatic innervation represents a potentially underestimated regulator of liver function and regeneration. The muscarinic 3 receptor (M3 -R) is the primary cholangiocyte receptor for the afferent parasympathetic innervation of bile ducts. We aimed to determine the specific role of the M3 -R in bile formation and models for cholestatic liver disease in mice. We compared bile flow and composition in M3 -R knock-out mice (M3 -R(-/-) ) and wild type littermates (WT). M3 -R(-/-) mice showed significantly reduced bile flow compared to WT mice, most likely due to decreased biliary HCO3(-) secretion...
June 21, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28634823/a-nationwide-study-of-the-incidence-rate-of-herb-induced-liver-injury-in-korea
#9
Jung-Hyo Cho, Dal-Seok Oh, Sang-Hoon Hong, Heung Ko, Nam-Hun Lee, Sang-Eun Park, Chang-Woo Han, Seung-Mo Kim, Young-Chul Kim, Kang-San Kim, Chang-Won Choi, Seon-My Shin, Ki-Tae Kim, Hong-Sik Choi, Jang-Hoon Lee, Jun-Young Kim, Ji-Young Kang, Dong-Soo Lee, Yo-Chan Ahn, Chang-Gue Son
Discrepant incidence has been reported regarding the incidence of herb-induced liver injury (HILI). To address the growing worldwide concern of HILI, we evaluated the risk of HILI in a nationwide prospective study. Between April 2013 and January 2016, 1001 inpatients (360 males and 641 females) from 10 tertiary hospitals throughout South Korea were treated with herbal drugs and had their liver enzymes periodically measured. A total of six patients met the criteria for HILI with RUCAM scores ranging from 4 to 7...
June 20, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28634578/neonatal-venous-thromboembolism
#10
REVIEW
Kristina M Haley
Neonates are the pediatric population at highest risk for development of venous thromboembolism (VTE), and the incidence of VTE in the neonatal population is increasing. This is especially true in the critically ill population. Several large studies indicate that the incidence of neonatal VTE is up almost threefold in the last two decades. Central lines, fluid fluctuations, sepsis, liver dysfunction, and inflammation contribute to the risk profile for VTE development in ill neonates. In addition, the neonatal hemostatic system is different from that of older children and adults...
2017: Frontiers in Pediatrics
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
#11
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/28634393/a-small-molecule-ds44170716-inhibits-ca-2-induced-mitochondrial-permeability-transition
#12
Naohiro Kon, Atsushi Satoh, Naoki Miyoshi
Mitochondria are involved in a variety of physiological and pathological processes. Ca(2+) uptake is one of the important functions of the organelle for maintenance of cellular Ca(2+) homeostasis. In pathological conditions such as ischemia reperfusion injury, Ca(2+) overload into mitochondria induces mitochondrial permeability transition (MPT), a critical step for cell death. Because inhibition of MPT is a promising approach to protecting cells and organs, it is important for drug discovery to identify novel chemicals or mechanisms to inhibit MPT...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634377/hepatoprotective-and-in-vitro-antioxidant-effects-of-native-depolymerised-exopolysaccharides-derived-from-termitomyces-albuminosus
#13
Huajie Zhao, Juan Li, Jianjun Zhang, Xiuxiu Wang, Min Liu, Chen Zhang, Le Jia
In this study, native depolymerised-exopolysaccharides (DEPS) were successfully derived from the exopolysaccharides (EPS) of Termitomyces albuminosus, and its hepatoprotective effects against a high-fat emulsion and in vitro antioxidant activities were investigated. Based on the results of in vitro assays, DEPS showed superior antioxidant activities compared with EPS dose-dependently. According to the in vivo assays both EPS and DEPS significantly decreased the lipid levels, improved the enzymatic activities, and reduced lipid peroxidation in both serum and hepatic homogenates...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28633873/elental%C3%A2-amino-acid-component-has-protective-effects-on-primary-cultured-hepatocytes-and-a-rat-model-of-acute-liver-injury
#14
Hirokazu Miki, Katsuji Tokuhara, Masaharu Oishi, Yoshito Tanaka, Richi Nakatake, Yosuke Ueyama, Masaki Kaibori, Mikio Nishizawa, Tadayoshi Okumura, Masanori Kon
Amino acids can exert protective effects on the liver either when administered as a medication or following an operation. In this study, we examined the protective effects of amino acids on the liver using in vitro and in vivo models by studying their influence on the induction of inducible nitric oxide synthase (iNOS) and nitric oxide production as a liver injury marker in cultured hepatocytes and liver-protective effects in d-galactosamine and lipopolysaccharide (GalN/LPS)-treated rats, respectively. Primary cultured rat hepatocytes were treated with interleukin (IL)-1β in the presence or absence of Elental® amino acid component (EleAA; 17 amino acids)...
June 2017: Nutrition Research
https://www.readbyqxmd.com/read/28633644/risk-factors-for-pulmonary-complications-after-hepatic-resection-role-of-intraoperative-hemodynamic-instability-and-hepatic-ischemia
#15
Victoria Lepere, Antoine Vanier, Yann Loncar, Louis Lemoine, Jean Christophe Vaillant, Antoine Monsel, Eric Savier, Pierre Coriat, Daniel Eyraud
BACKGROUND: Postoperative operative pulmonary complications (PPCs) after hepatic surgery are associated with increased length of hospital stays. Intraoperative blood transfusion, extensive resection and different comorbidities have been identified. Other parameters, like time of hepatic ischemia, have neither been clinically studied, though experimental studies show that hepatic ischemia can provide lung injury. The objective of this study was to determinate the risk factors of postoperative pulmonary complications (PPCs) after hepatic resection within 7 postoperative days...
June 20, 2017: BMC Anesthesiology
https://www.readbyqxmd.com/read/28633424/three-dimensional-3d-heparg-spheroid-model-with-physiologically-relevant-xenobiotic-metabolism-competence-and-hepatocyte-functionality-for-liver-toxicity-screening
#16
Sreenivasa C Ramaiahgari, Suramya Waidyanatha, Darlene Dixon, Michael J DeVito, Richard S Paules, Stephen S Ferguson
Effective prediction of human responses to chemical and drug exposure is of critical importance in environmental toxicology research and drug development. While significant progress has been made to address this challenge using in vitro liver models, these approaches often fail due to inadequate tissue model functionality. Herein, we describe the development, optimization, and characterization of a novel three-dimensional (3D) spheroid model using differentiated HepaRG cells that achieve and maintain physiologically-relevant levels of xenobiotic metabolism (CYP1A2, CYP2B6, and CYP3A4/5)...
June 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28632657/role-of-computed-tomography-in-the-classification-of-pediatric-pelvic-fractures-revisited
#17
Melissa A Bent, William L Hennrikus, Johan E Latorre, Douglas G Armstrong, Brian Shaw, Kerwyn C Jones, Lee S Segal
OBJECTIVES: To determine the need for computerized tomography (CT) scans in the assessment of pediatric pelvic fractures. DESIGN: Retrospective Chart Review. SETTING: Level-1 Pediatric Trauma Center. PATIENTS/PARTICIPANTS: Thirty pediatric trauma patients with pelvic fractures who have obtained both a radiograph and CT scan. MAIN OUTCOME MEASUREMENTS: Fleiss Kappa coefficient to compare interreliability...
July 2017: Journal of Orthopaedic Trauma
https://www.readbyqxmd.com/read/28631096/a-case-of-nivolumab-related-cholangitis-and-literature-review-how-to-look-for-the-right-tools-for-a-correct-diagnosis-of-this-rare-immune-related-adverse-event
#18
Francesco Gelsomino, Giovanni Vitale, Andrea Ardizzoni
Anti-programmed cell death-1 (PD-1) monoclonal antibodies, such as nivolumab, used for the treatment of several tumors, can trigger effector T-cells against tumor- and self-antigens, leading to the occurrence of different immune-related adverse events. Among them, liver injuries are rare and usually transient. To date, only four cases of immune-related cholangitis in non-small cell lung cancer (NSCLC) patients have been described during nivolumab treatment. Here, we describe laboratory tests, imaging and liver biopsy features that confirm this diagnosis as opposed to other forms of autoimmune liver disease; nevertheless, we also provide evidence of the presence of different clinical-pathological patterns of immune-related cholangitis...
June 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28630953/distribution-of-acetylated-histone-4-in-normal-liver-and-acetaminophen-induced-liver-damage
#19
N Nakamura, Chang C-W, X Yang, Q Shi, W F Salminen, A Suzuki
To describe cell-specific acetylation of histones and their zonal localization in normal mouse liver and characterize their changes in acetaminophen (APAP)-damaged mouse liver 24 hr after APAP exposure, we performed an immunohistochemical study using normal and APAP-injured mouse livers. Cell-specific expression of acetylated H4 was observed in normal mouse liver. The highest acetylated H4 expression levels were found in bile duct epithelial cells, followed by sinusoidal non-parenchymal cells, venous endothelial cells, and hepatocytes...
2017: SM J Biol
https://www.readbyqxmd.com/read/28630645/the-use-of-laparoscopy-in-managing-penetrating-thoracoabdominal-injuries-in-africa-83-cases-reviewed
#20
Zach M Koto, Fusi Mosai, Oleh Y Matsevych
BACKGROUND: The use of laparoscopy in managing haemodynamically stable patients with penetrating thoracoabdominal injuries in developed countries is wildly practiced, but in Africa, the use of laparoscopy is still in its infancy stage. We reviewed a single centre experience in using laparoscopy in Africa for management of patients with both isolated diaphragmatic injuries as well as diaphragmatic injuries associated with intra-abdominal injuries requiring intervention. METHODS: A retrospective analysis of prospectively collected data of patients presenting with penetrating thoracoabdominal injuries was done...
2017: World Journal of Emergency Surgery: WJES
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