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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
#1
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/29343773/mitochondrial-mutations-in-cholestatic-liver-disease-with-biliary-atresia
#2
Hong Koh, Gun-Seok Park, Sun-Mi Shin, Chang Eon Park, Seung Kim, Seok Joo Han, Huy Quang Pham, Jae-Ho Shin, Dong-Woo Lee
Biliary atresia (BA) results in severe bile blockage and is caused by the absence of extrahepatic ducts. Even after successful hepatic portoenterostomy, a considerable number of patients are likely to show progressive deterioration in liver function. Recent studies show that mutations in protein-coding mitochondrial DNA (mtDNA) genes and/or mitochondrial genes in nuclear DNA (nDNA) are associated with hepatocellular dysfunction. This observation led us to investigate whether hepatic dysfunctions in BA is genetically associated with mtDNA mutations...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343698/correlations-between-mitochondrial-dna-haplogroup-d5-and-chronic-hepatitis-b-virus-infection-in-yunnan-china
#3
Xiao Li, Tai-Cheng Zhou, Chang-Hui Wu, Li-Lin Tao, Rui Bi, Li-Jun Chen, De-Yao Deng, Chang Liu, Newton O Otecko, Yang Tang, Xin Lai, Liang Zhang, Jia Wei
Mitochondrial abnormality is frequently reported in individuals with hepatitis B virus (HBV) infection, but the associated hosts' mitochondrial genetic factors remain obscure. We hypothesized that mitochondria may affect host susceptibility to HBV infection. In this study, we aimed to detect the association between chronic HBV infection and mitochondrial DNA in Chinese from Yunnan, Southwest China. A total of 272 individuals with chronic HBV infection (CHB), 310 who had never been infected by HBV (healthy controls, HC) and 278 with a trace of HBV infection (spontaneously recovered, SR) were analysed for mtDNA sequence variations and classified into respective haplogroups...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29341879/mechanisms-of-mitochondrial-toxicity-of-the-kinase-inhibitors-ponatinib-regorafenib-and-sorafenib-in-human-hepatic-hepg2-cells
#4
Franziska Paech, Cécile Mingard, David Grünig, Vanessa F Abegg, Jamal Bouitbir, Stephan Krähenbühl
Previous studies have shown that certain kinase inhibitors are mitochondrial toxicants. In the current investigation, we determined the mechanisms of mitochondrial impairment by the kinase inhibitors ponatinib, regorafenib, and sorafenib in more detail. In HepG2 cells cultured in galactose and exposed for 24 hours, all three kinase inhibitors investigated depleted the cellular ATP pools at lower concentrations than cytotoxicity occurred, compatible with mitochondrial toxicity. The kinase inhibitors impaired the activity of different complexes of the respiratory chain in HepG2 cells exposed to the toxicants for 24 hours and in isolated mouse liver mitochondria exposed acutely...
January 13, 2018: Toxicology
https://www.readbyqxmd.com/read/29335519/metabolic-reprogramming-by-pck1-promotes-tca-cataplerosis-oxidative-stress-and-apoptosis-in-liver-cancer-cells-and-suppresses-hepatocellular-carcinoma
#5
Meng-Xi Liu, Lei Jin, Si-Jia Sun, Peng Liu, Xu Feng, Zhou-Li Cheng, Wei-Ren Liu, Kun-Liang Guan, Ying-Hong Shi, Hai-Xin Yuan, Yue Xiong
Phosphoenolpyruvate carboxykinase (PEPCK or PCK) catalyzes the first rate-limiting step in hepatic gluconeogenesis pathway to maintain blood glucose levels. Mammalian cells express two PCK genes, encoding for a cytoplasmic (PCPEK-C or PCK1) and a mitochondrial (PEPCK-M or PCK2) isoforms, respectively. Increased expressions of both PCK genes are found in cancer of several organs, including colon, lung, and skin, and linked to increased anabolic metabolism and cell proliferation. Here, we report that the expressions of both PCK1 and PCK2 genes are downregulated in primary hepatocellular carcinoma (HCC) and low PCK expression was associated with poor prognosis in patients with HCC...
January 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29331880/preventive-effects-of-indole-3-carbinol-against-alcohol-induced-liver-injury-in-mice-via-antioxidant-anti-inflammatory-and-anti-apoptotic-mechanisms-role-of-gut-liver-adipose-tissue-axis
#6
Youngshim Choi, Mohamed A Abdelmegeed, Byoung-Joon Song
Indole-3-carbinol (I3C), found in Brassica family vegetables, exhibits antioxidant, anti-inflammatory, and anti-cancerous properties. Here, we aimed to evaluate the preventive effects of I3C against ethanol (EtOH)-induced liver injury and study the protective mechanism(s) by using the well-established chronic-plus-binge alcohol exposure model. The preventive effects of I3C were evaluated by conducting various histological, biochemical, and real-time PCR analyses in mouse liver, adipose tissue, and colon, since functional alterations of adipose tissue and intestine can also participate in promoting EtOH-induced liver damage...
December 10, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29329795/omega-3-fatty-acids-and-adipose-tissue-biology
#7
REVIEW
Ondrej Kuda, Martin Rossmeisl, Jan Kopecky
This review provides evidence for the importance of white and brown adipose tissue (i.e. WAT and BAT) function for the maintenance of healthy metabolic phenotype and its preservation in response to omega-3 polyunsaturated fatty acids (omega-3 PUFA), namely in the context of diseased states linked to aberrant accumulation of body fat, systemic low-grade inflammation, dyslipidemia and insulin resistance. More specifically, the review deals with (i) the concept of immunometabolism, i.e. how adipose-resident immune cells and adipocytes affect each other and define the immune-metabolic interface; and (ii) the characteristic features of "healthy adipocytes" in WAT, which are relatively small fat cells endowed with a high capacity for mitochondrial oxidative phosphorylation, triacylglycerol/fatty acid (TAG/FA) cycling and de novo lipogenesis (DNL)...
January 9, 2018: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29328482/cytisine-induces-endoplasmic-reticulum-stress-caused-by-calcium-overload-in-hepg2-cells
#8
Lei Yu, Bo Jiang, Zhifeng Chen, Xin Wang, Dongxue Shang, Xiaopo Zhang, Yongxue Sun, Jinghui Yang, Yubin Ji
Cytisine, a quinolizidine alkaloid, is one of the major bioactive components found in the small tree Sophora Alopecuraides L., and is a traditional Chinese medicine that is used for treating hepatitis and liver cancer. In the 1960s, quinolizidine alkaloids were reported to exhibit inhibitory effects on tumour cell proliferation in several types of cancer cells. However, few studies have investigated the effect of cytisine on liver cancer. Our team confirmed that cytisine induced apoptosis in HepG2 cells via a mitochondrial pathway...
January 8, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29326365/disruption-of-mitochondria-associated-endoplasmic-reticulum-membranes-mams-integrity-contributes-to-muscle-insulin-resistance-in-mice-and-humans
#9
Emily Tubbs, Stéphanie Chanon, Maud Robert, Nadia Bendridi, Gabriel Bidaux, Marie-Agnès Chauvin, Jingwei Ji-Cao, Christine Durand, Daphné Gauvrit-Ramette, Hubert Vidal, Etienne Lefai, Jennifer Rieusset
Modifications of the interactions between endoplasmic reticulum (ER) and mitochondria, defined as mitochondria-associated membranes (MAMs), were recently involved in the control of hepatic insulin action and glucose homeostasis, but with conflicting results. Whereas skeletal muscle is the primary site of insulin-mediated glucose uptake and the main target for alterations in insulin resistant states, the relevance of MAM integrity in muscle insulin resistance is unknown. Deciphering the importance of MAMs on muscle insulin signaling could help to clarify this controversy...
January 11, 2018: Diabetes
https://www.readbyqxmd.com/read/29325178/modulation-of-o-glcnac-levels-in-the-liver-impacts-acetaminophen-induced-liver-injury-by-affecting-protein-adduct-formation-and-glutathione-synthesis
#10
Steven R McGreal, Bharat Bhushan, Chad Walesky, Mitchell R McGill, Margitta Lebofsky, Sylvie E Kandel, Robert D Winefield, Hartmut Jaeschke, Natasha E Zachara, Zhen Zhang, Ee Phie Tan, Chad Slawson, Udayan Apte
Overdose of acetaminophen (APAP) results in acute liver failure. We have investigated the role of a post-translational modification of proteins called O-GlcNAcylation, where the O-GlcNAc transferase (OGT) adds and O-GlcNAcase (OGA) removes a single β-D-N-acetylglucosamine (O-GlcNAc) moiety, in the pathogenesis of APAP-induced liver injury. Hepatocyte specific OGT knockout mice (OGT KO), which have reduced O-GlcNAcylation, and WT controls were treated with 300 mg/kg APAP and the development of injury was studied over a time course from 0-24 hr...
January 9, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29310441/dihydromyricetin-ameliorates-nonalcoholic-fatty-liver-disease-by-improving-mitochondrial-respiratory-capacity-and-redox-homeostasis-through-modulation-of-sirt3-signaling
#11
Xianglong Zeng, Jining Yang, Ou Hu, Juan Huang, Li Ran, Mengting Chen, Yu Zhang, Xi Zhou, Jundong Zhu, Qianyong Zhang, Long Yi, Mantian Mi
AIMS: Our previous clinical trial indicated that the flavonoid dihydromyricetin (DHM) could improve hepatic steatosis in patients with NAFLD, altough the potential mechanisms of these effects remained elusive. Here, we investigated the hepatoprotective role of DHM on high-fat diet (HFD)-induced NAFLD. RESULTS: DHM supplementation could effectively ameliorate the development of NAFLD by inhibiting hepatic lipids accumulation both in HFD-fed wild type mice and in palmitic acid (PA)-induced hepatocytes...
January 8, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29305935/hedgehog-yap-signaling-pathway-regulates-glutaminolysis-to-control-hepatic-stellate-cell-activation
#12
Kuo Du, Jeongeun Hyun, Richard T Premont, Steve S Choi, Gregory A Michelotti, Marzena Swiderska-Syn, George D Dalton, Eric Thelen, Bahar Salimian Rizi, Youngmi Jung, Anna Mae Diehl
BACKGROUND & AIMS: Cirrhosis results from accumulation of myofibroblasts derived from quiescent hepatic stellate cells (Q-HSCs); it regresses when myofibroblastic HSCs are depleted. Hedgehog signaling promotes transdifferentiation of HSCs by activating Yes-associated protein 1 (YAP1 or YAP) and inducing aerobic glycolysis. However, increased aerobic glycolysis alone cannot meet the high metabolic demands of myofibroblastic HSCs. Determining the metabolic processes of these cells could lead to strategies to prevent progressive liver fibrosis, so we investigated whether glutaminolysis (conversion of glutamine to alpha-ketoglutarate) sustains energy metabolism and permits anabolism when Q-HSCs become myofibroblastic, and whether this is controlled by hedgehog signaling to YAP...
January 3, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29304478/differential-mitochondrial-dinitrosyliron-complex-formation-by-nitrite-and-nitric-oxide
#13
Douglas D Thomas, Catherine Corey, Jason Hickok, Yinna Wang, Sruti Shiva
Nitrite represents an endocrine reserve of bioavailable nitric oxide (NO) that mediates a number of physiological responses including conferral of cytoprotection after ischemia/reperfusion (I/R). It has long been known that nitrite can react with non-heme iron to form dinitrosyliron complexes (DNIC). However, it remains unclear how quickly nitrite-dependent DNIC form in vivo, whether formation kinetics differ from that of NO-dependent DNIC, and whether DNIC play a role in the cytoprotective effects of nitrite...
December 23, 2017: Redox Biology
https://www.readbyqxmd.com/read/29302508/alpers-huttenlocher-syndrome-first-presented-with-hepatic-failure-can-liver-transplantation-be-considered-as-treatment-option
#14
Sowon Park, Hoon-Chul Kang, Jin-Sung Lee, Young Nyun Park, Seung Kim, Hong Koh
Mitochondria play essential role in eukaryotic cells including in the oxidative phosphorylation and generation of adenosine triphosphate via the electron-transport chain. Therefore, defects in mitochondrial DNA (mtDNA) can result in mitochondrial dysfunction which leads to various mitochondrial disorders that may present with various neurologic and non-neurologic manifestations. Mutations in the nuclear gene polymerase gamma (POLG) are associated with mtDNA depletions, and Alpers-Huttenlocher syndrome is one of the most severe manifestations of POLG mutation characterized by the clinical triad of intractable seizures, psychomotor regression, and liver failure...
December 2017: Pediatric Gastroenterology, Hepatology & Nutrition
https://www.readbyqxmd.com/read/29300782/the-paradox-of-hbv-evolution-as-revealed-from-a-16th-century-mummy
#15
Zoe Patterson Ross, Jennifer Klunk, Gino Fornaciari, Valentina Giuffra, Sebastian Duchêne, Ana T Duggan, Debi Poinar, Mark W Douglas, John-Sebastian Eden, Edward C Holmes, Hendrik N Poinar
Hepatitis B virus (HBV) is a ubiquitous viral pathogen associated with large-scale morbidity and mortality in humans. However, there is considerable uncertainty over the time-scale of its origin and evolution. Initial shotgun data from a mid-16th century Italian child mummy, that was previously paleopathologically identified as having been infected with Variola virus (VARV, the agent of smallpox), showed no DNA reads for VARV yet did for hepatitis B virus (HBV). Previously, electron microscopy provided evidence for the presence of VARV in this sample, although similar analyses conducted here did not reveal any VARV particles...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29291263/overexpression-of-anthocyanidin-synthase-ans-gene-in-strawberry-enhances-antioxidant-capacity-and-cytotoxic-effects-on-human-hepatic-cancer-cells
#16
Francesca Giampieri, Massimiliano Gasparrini, Tamara Yuliett Forbes-Hernandez, Luca Mazzoni, Franco Capocasa, Silvia Sabbadini, José M Alvarez-Suarez, Sadia Afrin, Carlo Rosati, Tiziana Pandolfini, Barbara Molesini, José F Sanchez-Villa, Iraida Amaya, Bruno Mezzetti, Maurizio Battino
Food fortification through the increase and/or modulation of bioactive compounds has become a major goal for preventing several diseases, including cancer. Here, strawberry lines of cv. Calypso transformed with a construct containing an anthocyanidin synthase (ANS) gene were produced to study the effects on anthocyanin biosynthesis, metabolism and transcriptome. Three strawberry ANS transgenic lines (ANS L5, ANS L15 and ANS L18) were analysed for phytochemical composition and total antioxidant capacity (TAC), and their fruit extracts assessed for cytotoxic effects on hepatocellular carcinoma...
January 1, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29290907/morphological-alterations-and-redox-changes-associated-with-hepatic-warm-ischemia-reperfusion-injury
#17
Rim Jawad, Melroy D'souza, Lisa Arodin Selenius, Marita Wallenberg Lundgren, Olof Danielsson, Greg Nowak, Mikael Björnstedt, Bengt Isaksson
AIM: To study the effects of warm ischemia-reperfusion (I/R) injury on hepatic morphology at the ultrastructural level and to analyze the expression of the thioredoxin (TRX) and glutaredoxin (GRX) systems. METHODS: Eleven patients undergoing liver resection were subjected to portal triad clamping (PTC). Liver biopsies were collected at three time points; first prior to PTC (baseline), 20 min after PTC (post-ischemia) and 20 min after reperfusion (post-reperfusion)...
December 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/29288054/mitochondria-in-non-alcoholic-fatty-liver-disease
#18
Inês C M Simões, Adriana Fontes, Paolo Pinton, Hans Zischka, Mariusz R Wieckowski
NAFLD is a common disease in Western society and ranges from steatosis to steatohepatitis and to end-stage liver disease. The molecular mechanisms that cause the progression of steatosis to severe liver damage are not fully understood. One suggested mechanism involves the oxidation of biomolecules by mitochondrial ROS which initiates a vicious cycle of exacerbated mitochondrial dysfunction and increased hepatocellular oxidative damage. This may ultimately pave the way for hepatic inflammation and liver failure...
December 26, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29285026/corrigendum-hepatic-s6k1-partially-regulates-lifespan-of-mice-with-mitochondrial-complex-i-deficiency
#19
Takashi K Ito, Chenhao Lu, Jacob Khan, Quy Nguyen, Heather Z Huang, Dayae Kim, James J Phillips, Jo Tan, Yenna Lee, Tuyet Nguyen, Samy Khessib, Natalie Lim, Surapat Mekvanich, Joshua Oh, Victor V Pineda, Weirong Wang, Alessandro Bitto, Jonathan Y An, John F Morton, Mitsutoshi Setou, Warren C Ladiges, Matt Kaeberlein
[This corrects the article on p. 113 in vol. 8, PMID: 28919908.].
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/29282788/mpv17-related-mitochondrial-dna-maintenance-defect-new-cases-and-review-of-clinical-biochemical-and-molecular-aspects
#20
Ayman W El-Hattab, Julia Wang, Hongzheng Dai, Mohammed Almannai, Christian Staufner, Majid Alfadhel, Michael J Gambello, Pankaj Prasun, Saleem Raza, Hernando J Lyons, Manal Afqi, Mohammed A M Saleh, Eissa A Faqeih, Hamad I Alzaidan, Abduljabbar Alshenqiti, Leigh Anne Flore, Jozef Hertecant, Stephanie Sacharow, Deborah S Barbouth, Kei Murayama, Amit A Shah, Henry C Lin, Lee-Jun C Wong
Mitochondrial DNA (mtDNA) maintenance defects are a group of diseases caused by deficiency of proteins involved in mtDNA synthesis, mitochondrial nucleotide supply, or mitochondrial dynamics. One of the mtDNA maintenance proteins is MPV17, which is a mitochondrial inner membrane protein involved in importing deoxynucleotides into the mitochondria. In 2006, pathogenic variants in MPV17 were first reported to cause infantile-onset hepatocerebral mtDNA depletion syndrome and Navajo neurohepatopathy. To date, 75 individuals with MPV17-related mtDNA maintenance defect have been reported with 39 different MPV17 pathogenic variants...
December 27, 2017: Human Mutation
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