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https://www.readbyqxmd.com/read/28103636/limited-excessive-voluntary-alcohol-drinking-leads-to-liver-dysfunction-in-mice
#1
Scott A Wegner, Katherine A Pollard, Viktor Kharazia, David Darevsky, Luz Perez, Sanjoy Roychowdhury, Allison Xu, Dorit Ron, Laura E Nagy, Frederic Woodward Hopf
BACKGROUND: Liver damage is a serious and sometimes fatal consequence of long-term alcohol intake, which progresses from early-stage fatty liver (steatosis) to later-stage steatohepatitis with inflammation and fibrosis/necrosis. However, very little is known about earlier stages of liver disruption that may occur in problem drinkers, those who drink excessively but are not dependent on alcohol. METHODS: We examined how repeated binge-like alcohol drinking in C57BL/6 mice altered liver function, as compared with a single binge-intake session and with repeated moderate alcohol consumption...
January 19, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28102609/immunogenicity-of-hepatic-differentiated-human-umbilical-cord-mesenchymal-stem-cells-promoted-by-porcine-decellularized-liver-scaffolds
#2
Yi Li, Qiong Wu, Yujia Wang, Li Li, Fei Chen, Yujun Shi, Hong Bu, Ji Bao
Cell-based approaches, including hepatocyte transplantation and tissue-engineered livers, offer promising alternatives and are expected to help support patients with liver diseases until liver transplantation or recovery via regeneration of the damaged liver. However, the success of cell therapies remains dependent on how well the cells are accepted after transplantation and is directly related to their degree of immunogenicity. In this study, hepatic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) was induced in the traditional monolayer (2D) culture and newly established three-dimensional (3D) aggregation culture with the porcine decellularized liver scaffold (DLS) system (3D-DLS)...
January 19, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28101741/anti-hyperuricemic-effect-of-taxifolin-in-cultured-hepatocytes-and-model-mice
#3
Shin-Ichi Adachi, Ken-Ichi Nihei, Yoshiyuki Ishihara, Fumiaki Yoshizawa, Kazumi Yagasaki
Hyperuricemia is recognized as an important risk factor for gout. High dietary intake of purine-rich foods such as meats and sea foods increases uric acid (UA) levels in the blood. Taxifolin present in Siberian larch and strawberries has been reported to possess health promoting activities including anti-oxidant effect. In this study, we examined anti-hyperuricemic effect of taxifolin in both cultured hepatocytes and hyperuricemic model mice. In cultured AML12 hepatocytes, taxifolin significantly suppressed UA production dose- and time-dependently...
January 18, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28101713/macro-and-microelement-content-and-other-properties-of-chaenomeles-japonica-l-fruit-and-protective-effects-of-its-aqueous-extract-on-hepatocyte-metabolism
#4
Irena Baranowska-Bosiacka, Beata Bosiacka, Julita Rast, Izabela Gutowska, Jolanta Wolska, Ewa Rębacz-Maron, Kamila Dębia, Katarzyna Janda, Jan Korbecki, Dariusz Chlubek
This growing interest in the cultivation of Japanese quince Chaenomeles japonica L. results from the potentially beneficial properties of its fruit. Fresh fruits are very firm and too acidic to eat raw, but their bioactive components, distinctive aroma, and high amount of dietary fiber make the fruits well suited for industrial processing. However, not all the properties of the fruit have been investigated. For example, there are no comprehensive reports about the mineral content or potentially harmful effects on liver metabolism...
January 18, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28101470/protective-roles-of-n-acetyl-cysteine-and-or-taurine-against-sumatriptan-induced-hepatotoxicity
#5
Javad Khalili Fard, Hossein Hamzeiy, Mohammadreza Sattari, Mohammad Ali Eghbal
Purpose: Triptans are the drug category mostly prescribed for abortive treatment of migraine. Most recent cases of liver toxicity induced by triptans have been described, but the mechanisms of liver toxicity of these medications have not been clear. Methods: In the present study, we obtained LC50 using dose-response curve and investigated cell viability, free radical generation, lipid peroxide production, mitochondrial injury, lysosomal membrane damage and the cellular glutathione level as toxicity markers as well as the beneficial effects of taurine and/or N-acetyl cysteine in the sumatriptan-treated rat parenchymal hepatocytes using accelerated method of cytotoxicity mechanism screening...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28101459/venlafaxine-induced-cytotoxicity-towards-isolated-rat-hepatocytes-involves-oxidative-stress-and-mitochondrial-lysosomal-dysfunction
#6
Elham Ahmadian, Hossein Babaei, Alireza Mohajjel Nayebi, Aziz Eftekhari, Mohammad Ali Eghbal
Purpose: Depression is a public disorder worldwide. Despite the widespread use of venlafaxine in the treatment of depression, it has been associated with the incidence of toxicities. Hence, the goal of the current investigation was to evaluate the mechanisms of venlafaxine-induced cell death in the model of the freshly isolated rat hepatocytes. Methods: Collagenase-perfused rat hepatocytes were treated with venlafaxine and other agents. Cell damage, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential decline, lysosomal damage, glutathione (GSH) level were analyzed...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28100871/in-vivo-direct-reprogramming-of-liver-cells-to-insulin-producing-cells-by-virus-free-overexpression-of-defined-factors
#7
Xiao-Fei Yang, Li-Wei Ren, Lu Yang, Chun-Yan Deng, Fu-Rong Li
Direct reprogramming of autologous cells from diabetes patients to insulin producing cells is a new method for pancreatic cell replacement therapy. At present, transdifferentiation among mature cells is achieved mainly by introducing foreign genes into the starting tissue with viral vector, but there are potentical safety problems. In the present study, we delivered plasmids carrying Pdx1, Neurog3 and MafA genes (PNM) into mouse hepatocytes by hydrodynamics tail vein injection, investigated islet β cells markers in transfected cells from protein and mRNA level, and then observed the long-term control of blood glucose in diabetic mice...
January 18, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28100771/janus-kinase-2-jak2-dissociates-hepatosteatosis-from-hepatocellular-carcinoma-in-mice
#8
Sally Yu Shi, Stephanie A Schroer, Cynthia T Luk, Min Jeong Kim, David W Dodington, Lauren Lin, Tharini Sivasubramaniyam, Erica P Cai, Shun-Yan Lu, Kay-Uwe Wagner, Richard P Bazinet, Minna Woo
Hepatocellular carcinoma (HCC) is an end-stage complication of non-alcoholic fatty liver disease (NAFLD). Inflammation plays a critical role in the progression of non-alcoholic fatty liver disease and the development of hepatocellular carcinoma. However, whether steatosis per se promotes liver cancer and the molecular mechanisms that control the progression in this disease spectrum remain largely elusive. The Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway mediates signal transduction by numerous cytokines that regulate inflammation and may contribute to hepatocarcinogenesis...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100619/functional-analysis-of-hcv-envelope-protein-e1-using-a-trans-complementation-system-reveals-a-dual-role-of-a-putative-fusion-peptide-of-e1-in-both-hcv-entry-and-morphogenesis
#9
Yimin Tong, Xiaojing Chi, Wei Yang, Jin Zhong
: Hepatitis C virus (HCV) is an enveloped RNA virus belonging to the Flaviviridae family. It mainly infects human hepatocytes and causes chronic liver diseases including cirrhosis and cancer. HCV encodes two envelope proteins E1 and E2 that form a heterodimer and mediate virus entry. While E2 has been extensively studied, less has been done so for E1, and its role in HCV life cycle still needs to be elucidated. Here we developed a new cell culture model for HCV infection based on trans-complementation of E1...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28099843/human-carboxylesterase-2-reverses-obesity-induced-diacylglycerol-accumulation-and-glucose-intolerance
#10
Maxwell A Ruby, Julie Massart, Devon M Hunerdosse, Milena Schönke, Jorge C Correia, Sharon M Louie, Jorge L Ruas, Erik Näslund, Daniel K Nomura, Juleen R Zierath
Serine hydrolases are a large family of multifunctional enzymes known to influence obesity. Here, we performed activity-based protein profiling to assess the functional level of serine hydrolases in liver biopsies from lean and obese humans in order to gain mechanistic insight into the pathophysiology of metabolic disease. We identified reduced hepatic activity of carboxylesterase 2 (CES2) and arylacetamide deacetylase (AADAC) in human obesity. In primary human hepatocytes, CES2 knockdown impaired glucose storage and lipid oxidation...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28099758/melatonin-alleviates-cadmium-induced-liver-injury-by-inhibiting-the-txnip-nlrp3-inflammasome
#11
Zhengwang Cao, Yiliang Fang, Yonghui Lu, Dunxian Tan, Changhong Du, Yuming Li, Qinlong Ma, Junmei Yu, Mengyan Chen, Chao Zhou, Liping Pei, Lei Zhang, Haiying Ran, Mindi He, Zhengping Yu, Zhou Zhou
Cadmium (Cd) is a persistent environmental and occupational contaminant that accumulates in the liver and induces oxidative stress and inflammation. Melatonin possesses potent hepatoprotective properties against the development and progression of acute and chronic liver injury. Nevertheless, the molecular mechanism underlying the protective effects of melatonin against Cd-induced hepatotoxicity remains obscure. In the present study, we aimed to investigate the effects of melatonin on Cd-induced liver inflammation and hepatocyte death...
January 18, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28099338/liver-steatosis-in-children-with-chronic-hepatitis-b-and-c-prevalence-predictors-and-impact-on-disease-progression
#12
Maria Pokorska-Śpiewak, Barbara Kowalik-Mikołajewska, Małgorzata Aniszewska, Magdalena Pluta, Bożena Walewska-Zielecka, Magdalena Marczyńska
Only scarce data on liver steatosis in children with chronic hepatitis B and C (CHB and CHC) are available. The objective of this study was to evaluate the prevalence, predictors, and impact of hepatic steatosis on children with CHB and CHC. A total of 78 patients aged 11.5 ± 3.4 years were included: 30 (38%) had CHB, and 48 (62%) had CHC. Steatosis was scored on a 5-point scale, as follows: absent; minimal (≤5% hepatocytes affected), mild (6-33%), moderate (34-66%), and severe (>66%). Stepwise logistic regression was used to determine the factors associated with steatosis and moderate-to-severe steatosis...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28098910/hydrogen-rich-saline-improves-non%C3%A2-alcoholic-fatty-liver-disease-by-alleviating-oxidative-stress-and-activating-hepatic-ppar%C3%AE-and-ppar%C3%AE
#13
Xiao Zhai, Xiao Chen, Jiancan Lu, Yaping Zhang, Xuejun Sun, Qin Huang, Qijin Wang
Non-alcoholic fatty liver disease (NAFLD) comprises a range of liver diseases, between steatosis and non‑alcoholic steatohepatitis and liver cirrhosis, which are closely associated with diabetes mellitus. Previous studies have indicated that oxidative stress is a key factor in the development of NAFLD. Molecular hydrogen (H2) may ameliorate oxidative stress injuries by selectively neutralizing peroxynitrite and hydroxyl radicals. The present study evaluated the effects of H2 on NAFLD in rats and concluded that H2‑rich saline had significant therapeutic effects on NAFLD induced by hyperglycemia and hyperlipidemia, as demonstrated by hematoxylin and eosin and terminal deoxynucleotidyl-transferase‑mediated dUTP nick end labeling staining...
January 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28098909/biology-and-function-of-glypican-3-as-a-candidate-for-early-cancerous-transformation-of-hepatocytes-in-hepatocellular-carcinoma-review
#14
Mauro Montalbano, Jeremias Georgiadis, Ashlyn L Masterson, Joshua T McGuire, Janika Prajapati, Ali Shirafkan, Cristiana Rastellini, Luca Cicalese
Glypican-3 (GPC-3), a transmembrane heparan sulfate proteoglycan (HSPG), has recently been investigated as a player in tissue-dependent cellular signaling, specifically as a regulator of growth. Noteworthy, the regulatory protein has been implicated in both stimulatory and inhibitory pathways involving cell growth. Initially, GPC-3 was thought to act as a cell cycle regulator, as a loss-of-function mutation in the gene caused a hyper-proliferative state known as Simpson-Golabi-Behmel (SGB) overgrowth syndrome...
January 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098217/disrupting-hepatocyte-cyp51-from-cholesterol-synthesis-leads-to-progressive-liver-injury-in-the-developing-mouse-and-decreases-rorc-signalling
#15
Žiga Urlep, Gregor Lorbek, Martina Perše, Jera Jeruc, Peter Juvan, Madlen Matz-Soja, Rolf Gebhardt, Ingemar Björkhem, Jason A Hall, Richard Bonneau, Dan R Littman, Damjana Rozman
Development of mice with hepatocyte knockout of lanosterol 14α-demethylase (H(Cyp51-/-)) from cholesterol synthesis is characterized by the progressive onset of liver injury with ductular reaction and fibrosis. These changes begin during puberty and are generally more aggravated in the knockout females. However, a subgroup of (pre)pubertal knockout mice (runts) exhibits a pronounced male prevalent liver dysfunction characterized by downregulated amino acid metabolism and elevated Casp12. RORC transcriptional activity is diminished in livers of all runt mice, in correlation with the depletion of potential RORC ligands subsequent to CYP51 disruption...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097745/immature-core-protein-of-hepatitis-c-virus-induces-an-unfolded-protein-response-through-inhibition-of-erad-l-in-a-yeast-model-system
#16
Shota Takahashi, Naoko Sato, Junichi Kikuchi, Hideaki Kakinuma, Jun Okawa, Yukiko Masuyama, Singo Iwasa, Hayato Irokawa, Gi-Wook Hwang, Akira Naganuma, Michinori Kohara, Shusuke Kuge
The structural protein Core of hepatitis C virus (HCV), a cytosolic protein, induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in hepatocytes, and is responsible for the pathogenesis of persistent HCV infection. Using yeast as a model system, we evaluated mechanisms underlying Core-induced interference of ER homeostasis and UPR, and found that UPR is induced by the immature Core (aa 1-191, Core191) but not by the mature Core (aa 1-177, Core177). Interestingly, Core191 inhibits both ERAD-L, a degradation system responsible for misfolded/unfolded proteins in the ER lumen, and ERAD-M, a degradation system responsible for proteins carrying a misfolded/unfolded region in the ER membrane...
January 18, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28096572/current-and-emerging-treatments-for-hypercholesterolemia-a-focus-on-statins-and-proprotein-convertase-subtilisin-kexin-type-9-inhibitors-for-perioperative-clinicians
#17
REVIEW
Terrence L Trentman, Steven G Avey, Harish Ramakrishna
Statins are a mainstay of hyperlipidemia treatment. These drugs inhibit the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase and have beneficial effects on atherosclerosis including plaque stabilization, reduction of platelet activation, and reduction of plaque proliferation and inflammation. Statins also have a benefit beyond atherosclerotic plaque, including anticoagulation, vasodilatation, antioxidant effects, and reduction of mediators of inflammation. In the perioperative period, statins appear to contribute to improved outcomes via these mechanisms...
October 2016: Journal of Anaesthesiology, Clinical Pharmacology
https://www.readbyqxmd.com/read/28096505/the-neuropilin-2-isoform-nrp2b-uniquely-supports-tgf%C3%AE-mediated-progression-in-lung-cancer
#18
Robert M Gemmill, Patrick Nasarre, Joyce Nair-Menon, Federico Cappuzzo, Lorenza Landi, Armida D'Incecco, Hidetaka Uramoto, Takeshi Yoshida, Eric B Haura, Kent Armeson, Harry A Drabkin
Neuropilins (NRP1 and NRP2) are co-receptors for heparin-binding growth factors and class 3 semaphorins. Different isoforms of NRP1 and NRP2 are produced by alternative splicing. We found that in non-small cell lung cancer (NSCLC) cell lines, transforming growth factor-β (TGFβ) signaling preferentially increased the abundance of NRP2b. NRP2b and NRP2a differ only in their carboxyl-terminal regions. Although the presence of NRP2b inhibited cultured cell proliferation and primary tumor growth, NRP2b enhanced cellular migration, invasion into Matrigel, and tumorsphere formation in cultured cells in response to TGFβ signaling and promoted metastasis in xenograft mouse models...
January 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/28095508/the-smc5-6-complex-restricts-hbv-when-localized-to-nd10-without-inducing-an-innate-immune-response-and-is-counteracted-by-the-hbv-x-protein-shortly-after-infection
#19
Congrong Niu, Christine M Livingston, Li Li, Rudolf K Beran, Stephane Daffis, Dhivya Ramakrishnan, Dara Burdette, Leanne Peiser, Eduardo Salas, Hilario Ramos, Mei Yu, Guofeng Cheng, Michel Strubin, William E Delaney Iv, Simon P Fletcher
The structural maintenance of chromosome 5/6 complex (Smc5/6) is a restriction factor that represses hepatitis B virus (HBV) transcription. HBV counters this restriction by expressing HBV X protein (HBx), which targets Smc5/6 for degradation. However, the mechanism by which Smc5/6 suppresses HBV transcription and how HBx is initially expressed is not known. In this study we characterized viral kinetics and the host response during HBV infection of primary human hepatocytes (PHH) to address these unresolved questions...
2017: PloS One
https://www.readbyqxmd.com/read/28095353/liver-alpha-amylase-gene-expression-as-an-early-obesity-biomarker
#20
Marzieh Mojbafan, Zohreh Afsartala, Mahsa M Amoli, Mahdi Mahmoudi, Parichehreh Yaghmaei, Bagher Larijani, Azadeh Ebrahim-Habibi
BACKGROUND: Obesity is a major health problem worldwide, for which preventive and therapeutic means are still needed. Alpha-amylase is a digestive enzyme whose inhibition has been targeted as a potential anti-obesity strategy. However, alpha-amylase gene expression has not been particularly attended to, and in contrast with pancreatic and salivary amylases, fewer studies have focused on liver alpha-amylase. The present study aimed at investigating the expression of alpha-amylase gene in obese and normal mice at RNA and protein level as well as acarbose effect on this gene expression in hepatocyte cell culture...
November 5, 2016: Pharmacological Reports: PR
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