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https://www.readbyqxmd.com/read/28346483/effect-of-mir-146-targeted-hdmcp-up-regulation-in-the-pathogenesis-of-nonalcoholic-steatohepatitis
#1
Xi Jin, Jiang Liu, Yi-Peng Chen, Zun Xiang, Jie-Xia Ding, You-Ming Li
BACKGROUNDS/AIMS: Mitochondrial dysfunction plays an important role inthe pathogenesis of nonalcoholic steatohepatitis (NASH), where uncoupling protein (UCP) is actively involved. We previously reported the uncoupling activity of HDMCP and its role in liver steatosis. We now aim to investigate the degree and therapeutic effect of HDMCP in NASH and the regulatory role of miR-146 on HDMCP. METHODS: NASH animal model was established by feeding BALB/c mice with MCD diet while L02 cell was cultured with high concentration of fatty acid (HFFA) for 72h to mimic the steatosis and inflammation of NASH in-vitro appearance...
2017: PloS One
https://www.readbyqxmd.com/read/28341344/propofol-affinity-to-mitochondrial-membranes-does-not-alter-mitochondrial-function
#2
Luís M Félix, Fernando Correia, Pedro A Pinto, Sónia P Campos, Telma Fernandes, Romeu Videira, M M Oliveira, Francisco P Peixoto, Luís M Antunes
The molecular mechanisms of hepatotoxicity after propofol anaesthesia have not been fully elucidated, although there is a relation with mitochondrial dysfunction. The action of propofol on mitochondrial hepatic functions in a rat model was evaluated by infusion for 4h with 25 and 62.5mg/kg/h propofol or 3.125ml/kg/h (vehicle). Liver mitochondrial respiratory rates were evaluated as well as mitochondrial transmembrane potential (ΔΨ), calcium fluxes, mitochondrial enzymatic activities (Complex I-V) and oxidative stress biomarkers (superoxide dismutase, catalase, glutathione reductase, glutathione S-transferase, lipid peroxidation and the oxidised/reduced glutathione ratio)...
March 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28339712/effect-of-chinese-herbal-medicine-treatment-on-plasma-lipid-profile-and-hepatic-lipid-metabolism-in-hetian-broiler
#3
Z Xie, J Zhang, S Ma, X Huang, Y Huang
The purpose of this study was to investigate whether adding a Chinese herbal hedicine (CHM, including astragalus membranaceus, codonopsis pilosula, poria cocos, bighead atractylodes rhizome, fructus crataegi, folium epimedii, radix saposhnikoviae, and pericarpium citri reticulatae) diet has effects on lipid metabolism in the liver of the broiler. Six-hundred-thirty Hetian broilers were divided into 3 groups including base diet (control), 0.3%, or 1% CHM diets, for 130 days. The results showed that CHM treatment significantly increased the slaughter performance...
February 21, 2017: Poultry Science
https://www.readbyqxmd.com/read/28337346/therapeutic-effect-of-green-tea-extract-on-alcohol-induced-hepatic-mitochondrial-dna-damage-in-albino-wistar-rats
#4
Hymavathi Reddyvari, Suresh Govatati, Sumanth Kumar Matha, Swapna Vahini Korla, Sravanthi Malempati, Sreenivasa Rao Pasupuleti, Manjula Bhanoori, Varadacharyulu Nallanchakravarthula
The present study principally sought to investigate the effect of green tea extract (GTE) supplementation on hepatic mitochondrial DNA (mtDNA) damage in alcohol receiving rats. MtDNA was isolated from hepatic tissues of albino wistar rats after alcohol treatment with and without GTE supplementation. Entire displacement loop (D-loop) of mtDNA was screened by PCR-Sanger's sequencing method. In addition, mtDNA deletions and antioxidant activity were measured in hepatic tissue of all rats. Results showed increased frequency of D-loop mutations in alcoholic rats (ALC)...
May 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/28337244/rat-liver-enzyme-release-depends-on-blood-flow-bearing-physical-forces-acting-in-endothelium-glycocalyx-rather-than-on-liver-damage
#5
Julieta A Díaz-Juárez, Rolando Hernández-Muñoz
We have found selective elevation of serum enzyme activities in rats subjected to partial hepatectomy (PH), apparently controlled by hemodynamic flow-bearing physical forces. Here, we assess the involvement of stretch-sensitive calcium channels and calcium mobilization in isolated livers, after chemical modifications of the endothelial glycocalyx and changing perfusion directionality. Inhibiting in vivo protein synthesis, we found that liver enzyme release is influenced by de novo synthesis of endothelial glycocalyx components, and released enzymes are confined into a liver "pool...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28332314/the-mitochondrial-hinge-protein-uqcrh-is-a-novel-prognostic-factor-for-hepatocellular-carcinoma
#6
Eun-Ran Park, Sang-Bum Kim, Jee-San Lee, Yang-Hyun Kim, Dong-Hyoung Lee, Eung-Ho Cho, Sun-Hoo Park, Chul Ju Han, Bu-Yeo Kim, Dong Wook Choi, Young Do Yoo, Ami Yu, Jae Won Lee, Ja June Jang, Young Nyun Park, Kyung-Suk Suh, Kee-Ho Lee
Alterations in mitochondrial respiration contribute to the development and progression of cancer via abnormal biogenesis, including generation of reactive oxygen species. Ubiquinol-cytochrome c reductase hinge protein (UQCRH) consists of the cytochrome bc1 complex serving respiration in mitochondria. In the present study, we analyzed UQCRH abnormalities in hepatocellular carcinoma (HCC) and its association with clinical outcomes of patients. UQCRH expression in HCC was determined via semiquantitative and quantitative real-time reverse transcriptase polymerase chain reaction of 96 surgically resected HCC tissues positive for hepatitis B virus surface antigen...
March 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28330852/a-controlled-release-mitochondrial-protonophore-reverses-hypertriglyceridemia-nonalcoholic-steatohepatitis-and-diabetes-in-lipodystrophic-mice
#7
Abudukadier Abulizi, Rachel J Perry, João Paulo G Camporez, Michael J Jurczak, Kitt Falk Petersen, Patricia Aspichueta, Gerald I Shulman
Lipodystrophy is a rare disorder characterized by complete or partial loss of adipose tissue. Patients with lipodystrophy exhibit hypertriglyceridemia, severe insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). Efforts to ameliorate NASH in lipodystrophies with pharmacologic agents have met with limited success. We examined whether a controlled-release mitochondrial protonophore (CRMP) that produces mild liver-targeted mitochondrial uncoupling could decrease hypertriglyceridemia and reverse NASH and diabetes in a mouse model (fatless AZIP/F-1 mice) of severe lipodystrophy and diabetes...
March 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28329914/ginsenoside-rg3-restores-hepatitis-c-virus-induced-aberrant-mitochondrial-dynamics-and-inhibits-virus-propagation
#8
Seong-Jun Kim, Jae Young Jang, Eun-Jung Kim, Eun Kyung Cho, Dae Gyun Ahn, Chonsaeng Kim, Han Seul Park, Soung Won Jeong, Sae Hwan Lee, Sang Gyune Kim, Young Seok Kim, Hong Soo Kim, Boo Sung Kim, Ji-Hyung Lee, Aleem Siddiqui
Hepatitis C virus (HCV) alters mitochondrial dynamics associated with persistent viral infection and suppression of innate immunity. Mitochondrial dysfunction is also a pathologic feature of direct-acting antiviral (DAA) treatment. Despite the high efficacy of DAAs, their treatment of patients with chronic hepatitis C in interferon-sparing regimens occasionally produces undesirable side effects such as fatigue, migraine and other conditions, which may be linked to mitochondrial dysfunction. Here we show that clinically prescribed DAAs, including Sofosbuvir, affect mitochondrial dynamics...
March 22, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28322544/graphene-oxide-quantum-dots-as-novel-nanozymes-for-alcohol-intoxication
#9
Anqi Sun, Li Mu, Xiangang Hu
Alcohol overconsumption as a worldwide issue results in alcoholic liver disease (ALD), such as steatosis, alcoholic hepatitis and cirrhosis. The treatment of ALD has been widely investigated but remains challenging. In this work, the protective effects of graphene oxide quantum dots (GOQDs) as novel nanozymes against alcohol overconsumption are discovered, and the specific mechanisms underlying these effects are elucidated via omics analysis. GOQDs dramatically alleviate the reduction of cell viability induced by ethanol and can act as nanozymes to accelerate ethanol metabolism and avoid the accumulation of toxic intermediates in cells...
March 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28322010/cholesterol-can-modulate-mitochondrial-aquaporin-8-expression-in-human-hepatic-cells
#10
Mauro Danielli, Alejo M Capiglioni, Julieta Marrone, Giuseppe Calamita, Raúl A Marinelli
Hepatocyte mitochondrial aquaporin-8 (mtAQP8) works as a multifunctional membrane channel protein that facilitates the uptake of ammonia for its detoxification to urea as well as the mitochondrial release of hydrogen peroxide. Since early oligonucleotide microarray studies in liver of cholesterol-fed mice showed an AQP8 downregulation, we tested whether alterations of cholesterol content per se modulate mtAQP8 expression in human hepatocyte-derived Huh-7 cells. Cholesterol loading with methyl-β-cyclodextrin (mβCD):cholesterol complexes downregulated the proteolytic activation of cholesterol-responsive sterol regulatory element-binding protein (SREBP) transcriptions factors 1 and 2, and the expression of the target gene 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)...
March 20, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28317891/hepatic-mitochondrial-dysfunction-is-a-feature-of-glycogen-storage-disease-type-ia-gsdia
#11
Benjamin L Farah, Rohit A Sinha, Yajun Wu, Brijesh K Singh, Andrea Lim, Masahiro Hirayama, Dustin J Landau, Boon Huat Bay, Dwight D Koeberl, Paul M Yen
Glycogen storage disease type Ia (GSDIa, von Gierke disease) is the most common glycogen storage disorder. It is caused by the deficiency of glucose-6-phosphatase, an enzyme which catalyses the final step of gluconeogenesis and glycogenolysis. Clinically, GSDIa is characterized by fasting hypoglycaemia and hepatic glycogen and triglyceride overaccumulation. The latter leads to steatohepatitis, cirrhosis, and the formation of hepatic adenomas and carcinomas. Currently, little is known about the function of various organelles and their impact on metabolism in GSDIa...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28314476/polydatin-alleviates-alcohol-induced-acute-liver-injury-in-mice-relevance-of-matrix-metalloproteinases-mmps-and-hepatic-antioxidants
#12
Meghana Koneru, Bidya Dhar Sahu, Sagarika Gudem, Madhusudana Kuncha, Halley Gora Ravuri, Jerald Mahesh Kumar, Eswar Kumar Kilari, Ramakrishna Sistla
BACKGROUND: Alcohol, a most commonly consumed beverage, is the foremost cause of liver injury throughout the world. Polydatin, a stilbenoid glucoside, was known to possess antioxidant and anti-inflammatory properties and is being investigated for use in various disorders. PURPOSE: The present study was intended at investigating the hepatoprotective efficacy of polydatin against acute-alcohol induced liver injury model in mice. STUDY DESIGN: C57BL/6 mice were fed with five doses of 50% ethyl alcohol (10ml/kg body weight) to induce acute liver injury...
April 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28301072/pre-conditions-for-eliminating-mitochondrial-dysfunction-and-maintaining-liver-function-after-hepatic-ischaemia-reperfusion
#13
REVIEW
Chenxia Hu, Lanjuan Li
The liver, the largest organ with multiple synthesis and secretion functions in mammals, consists of hepatocytes and Kupffer, stem, endothelial, stellate and other parenchymal cells. Because of early and extensive contact with the external environment, hepatic ischaemia reperfusion (IR) may result in mitochondrial dysfunction, autophagy and apoptosis of cells and tissues under various pathological conditions. Because the liver requires a high oxygen supply to maintain normal detoxification and synthesis functions, it is extremely susceptible to ischaemia and subsequent reperfusion with blood...
March 16, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28298638/pnaktide-attenuates-steatohepatitis-and-atherosclerosis-by-blocking-na-k-atpase-ros-amplification-in-c57bl6-and-apoe-knockout-mice-fed-a-western-diet
#14
Komal Sodhi, Krithika Srikanthan, Perrine Goguet-Rubio, Alexandra Nichols, Amrita Mallick, Athar Nawab, Rebecca Martin, Preeya T Shah, Muhammad Chaudhry, Saroj Sigdel, Mehiar El-Hamdani, Jiang Liu, Zijian Xie, Nader G Abraham, Joseph I Shapiro
We have previously reported that the α1 subunit of sodium potassium adenosine triphosphatase (Na/K-ATPase), acts as a receptor and an amplifier for reactive oxygen species, in addition to its distinct pumping function. On this background, we speculated that blockade of Na/K-ATPase-induced ROS amplification with a specific peptide, pNaKtide, might attenuate the development of steatohepatitis. To test this hypothesis, pNaKtide was administered to a murine model of NASH: the C57Bl6 mouse fed a "western" diet containing high amounts of fat and fructose...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28295449/hepatic-mtdna-tlr9-microrna-223-forms-a-negative-feedback-loop-to-limit-neutrophil-over-activation-and-acetaminophen-hepatotoxicity
#15
Yong He, Dechun Feng, Man Li, Yanhang Gao, Teresa Ramirez, Haixia Cao, Seung-Jin Kim, Yang Yang, Yan Cai, Cynthia Ju, Hua Wang, Jun Li, Bin Gao
Acetaminophen (APAP) overdose is a leading cause of acute liver failure worldwide, in which mitochondrial DNA (mtDNA) released by damaged hepatocytes activates neutrophils via the binding of TLR9, further aggravating liver injury. Here, we demonstrated that mtDNA/TLR9 also activates a negative feedback pathway via the induction of microRNA-223 (miR-223) to limit neutrophil over-activation and liver injury. After injection of APAP in mice, levels of miR-223, the most abundant miRNAs in neutrophils, were highly elevated in neutrophils...
March 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28295448/drug-rechallenge-following-drug-induced-liver-injury
#16
REVIEW
Christine M Hunt, Julie I Papay, Vid Stanulovic, Arie Regev
Drug induced hepatocellular injury is identified internationally by ALT 5x upper limits normal (ULN) appearing within 3 months of drug initiation, after alternative causes are excluded. Upon withdrawing the suspect drug, ALT generally decreases by 50% or more. With drug readministration, a positive rechallenge has recently been defined by an ALT 3-5xULN or greater. Nearly 50 drugs are associated with positive rechallenge after drug-induced liver injury (DILI): antimicrobials, central nervous system, cardiovascular and oncology therapeutics...
March 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28292679/evaluation-of-cytotoxicity-genotoxicity-and-apoptosis-of-wastewater-before-and-after-disinfection-with-performic-acid
#17
Patrizia Ragazzo, Donatella Feretti, Silvano Monarca, Luca Dominici, Elisabetta Ceretti, Gaia Viola, Valentina Piccolo, Nicoletta Chiucchini, Milena Villarini
Disinfection with performic acid (PFA) represents an emerging technology in wastewater treatment. Many recent studies indicate its effectiveness and suitability as a disinfectant for different applications; several have demonstrated its reliability as an alternative to chlorine for disinfecting secondary effluents from urban wastewater treatment plants (WWTPs). Some disinfection technologies, in relation to their oxidative power, lead to the formation of disinfection by-products (DBPs), some of which are of concern for their toxic and carcinogenic potential...
March 7, 2017: Water Research
https://www.readbyqxmd.com/read/28290602/ajs1669-a-novel-small-molecule-muscle-glycogen-synthase-activator-improves-glucose-metabolism-and-reduces-body-fat-mass-in-mice
#18
Kazuhiro Nakano, Sen Takeshita, Noriko Kawasaki, Wataru Miyanaga, Yoriko Okamatsu, Mizuki Dohi, Tadakiyo Nakagawa
Impaired glycogen synthesis and turnover are common in insulin resistance and type 2 diabetes. As glycogen synthase (GS) is a key enzyme involved in the synthetic process, it presents a promising therapeutic target for the treatment of type 2 diabetes. In the present study, we identified a novel, potent and orally available GS activator AJS1669 {sodium 2-[[5-[[4-(4,5-difluoro-2-methylsulfanyl-phenyl)phenoxy] methyl]furan-2-carbonyl]-(2-furylmethyl)amino] acetate}. In vitro, we performed a glycogen synthase 1 (GYS1) activation assay for screening GS activators and identified that the activity of AJS1669 was further potentiated in the presence of glucose-6-phosphate (G6P)...
March 7, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28289714/bile-acids-initiate-cholestatic-liver-injury-by-triggering-a-hepatocyte-specific-inflammatory-response
#19
Shi-Ying Cai, Xinshou Ouyang, Yonglin Chen, Carol J Soroka, Juxian Wang, Albert Mennone, Yucheng Wang, Wajahat Z Mehal, Dhanpat Jain, James L Boyer
Mechanisms of bile acid-induced (BA-induced) liver injury in cholestasis are controversial, limiting development of new therapies. We examined how BAs initiate liver injury using isolated liver cells from humans and mice and in-vivo mouse models. At pathophysiologic concentrations, BAs induced proinflammatory cytokine expression in mouse and human hepatocytes, but not in nonparenchymal cells or cholangiocytes. These hepatocyte-specific cytokines stimulated neutrophil chemotaxis. Inflammatory injury was mitigated in Ccl2(-/-) mice treated with BA or after bile duct ligation, where less hepatic infiltration of neutrophils was detected...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28283651/tfe3-regulates-whole-body-energy-metabolism-in-cooperation-with-tfeb
#20
Nunzia Pastore, Anna Vainshtein, Tiemo J Klisch, Andrea Armani, Tuong Huynh, Niculin J Herz, Elena V Polishchuk, Marco Sandri, Andrea Ballabio
TFE3 and TFEB are members of the MiT family of HLH-leucine zipper transcription factors. Recent studies demonstrated that they bind overlapping sets of promoters and are post-transcriptionally regulated through a similar mechanism. However, while Tcfeb knockout (KO) mice die during early embryonic development, no apparent phenotype was reported in Tfe3 KO mice. Thus raising the need to characterize the physiological role of TFE3 and elucidate its relationship with TFEB TFE3 deficiency resulted in altered mitochondrial morphology and function both in vitro and in vivo due to compromised mitochondrial dynamics...
March 10, 2017: EMBO Molecular Medicine
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