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https://www.readbyqxmd.com/read/29311600/depdc5-deficiency-contributes-to-resistance-to-leucine-starvation-via-p62-accumulation-in-hepatocellular-carcinoma
#1
Yuki Mizuno, Shu Shimada, Yoshimitsu Akiyama, Shuichi Watanabe, Tomomi Aida, Kosuke Ogawa, Hiroaki Ono, Yusuke Mitsunori, Daisuke Ban, Atsushi Kudo, Shigeki Arii, Shoji Yamaoka, Minoru Tanabe, Shinji Tanaka
Decrease in blood concentration of branched-chain amino acids, especially leucine, is known to promote liver carcinogenesis in patients with chronic liver disease, but the mechanism is unclear. We herein established hepatocellular carcinoma (HCC) cells knocked out for DEPDC5 by using the CRISPR/Cas9 system, and elucidated that cell viability of the DEPDC5 knockout (DEPDC5-KO) cells was higher than that of the DEPDC5 wild-type (DEPDC5-WT) under leucine starvation. Considering that autophagy deficiency might be involved in acquired resistance to leucine deprivation, we observed reduction of LC3-II followed by accumulation of p62 in the DEPDC5-KO, which induced reactive oxygen species (ROS) tolerance...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29274197/increased-recurrence-rates-of-hepatocellular-carcinoma-after-daa-therapy-in-a-hepatitis-c-infected-egyptian-cohort-a-comparative-analysis
#2
Mohamed El Kassas, Anna L Funk, Mohamed Salaheldin, Yusuke Shimakawa, Mohammed Eltabbakh, Kévin Jean, Adel El Tahan, Ahmad T Sweedy, Shimaa Afify, Naglaa Fa Youssef, Gamal Esmat, Arnaud Fontanet
In Egypt, hepatocellular carcinoma (HCC) is the most common form of cancer and direct acting antivirals (DAA) are administered on a large scale to patients with chronic HCV infection to reduce the risk. In this unique setting, we aimed to determine the association of DAA exposure with early phase HCC recurrence in patients with a history of HCV-related liver cancer. This was a prospective cohort study of an HCV infected population from one Egyptian specialized HCC management center starting from the time of successful HCC intervention...
December 23, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29262485/-association-between-hair-cortisol-concentration-and-overweight-and-obesity-in-6-9-years-old-childhood
#3
J J Hu, X N Duan, J Fang, N Xu, Y H Wan, P Y Su, F B Tao, Y Sun
Objective: To determine the possible relations between hair cortisol concentration (HCC) as a biomarker of chronic stress and childhood overweight and obesity. Methods: Children from grade 1 to 3 from 2 primary schools in Bengbu were invited to participate in the study; and those who suffer from mental disorders, endocrine diseases and those who took hormone drugs were excluded. Parental questionnaire was implemented to collect information on physical activity, screen time, sleep duration, sugar-beverage consumption, as well as socio-economic status...
December 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/29228221/oncogenic-potential-of-hepatitis-b-virus-subgenotype-d1-surpasses-d3-significance-in-the-development-of-hepatocellular-carcinoma
#4
Somenath Datta, Debanjali Dasgupta, Alip Ghosh, Suchandrima Ghosh, Alak Manna, Simanti Datta, Mitali Chatterjee, Abhijit Chowdhury, Soma Banerjee
Despite widespread distribution of HBV-genotype D, the clinical implications of its 9 subgenotypes (D1-D9) have not been well documented. Here, we have investigated the impact of two major circulating HBV/D-subgenotypes, D1 and D3 in Eastern India towards pathogenesis of liver disease progression to hepatocellular carcinoma (HCC). HBV-subgenotypes were determined using full-length genome sequences of HBV isolates from patients with chronic hepatitis B (CHB), liver cirrhosis (LC) and HCC. Impact of D1 and D3 on viral lifecycle and disease progression was assessed by several invitro assays...
December 8, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29224736/a-natural-small-molecule-inhibitor-corilagin-blocks-hcv-replication-and-modulates-oxidative-stress-to-reduce-liver-damage
#5
B Uma Reddy, Ranajoy Mullick, Anuj Kumar, Geetika Sharma, Paromita Bag, Chaitrali Laha Roy, Govindarajan Sudha, Himani Tandon, Pratik Dave, Asutosh Shukla, Priyanka Srinivasan, Madhusudhan Nandhitha, Narayanaswamy Srinivasan, Saumitra Das
Hepatitis C virus (HCV) infection causes chronic liver disease, which often leads to hepatocellular carcinoma. Earlier, we have demonstrated anti-HCV property of the methanolic extract of Phyllanthus amarus, an age-old folk-medicine against viral hepatitis. Here, we report identification of a principal bioactive component 'corilagin', which showed significant inhibition of the HCV key enzymes, NS3 protease and NS5B RNA-dependent-RNA-polymerase. This pure compound could effectively inhibit viral replication in the infectious cell culture system, displayed strong antioxidant activity by blocking HCV induced generation of reactive oxygen species and suppressed up-regulation of NOX4 and TGF-β mRNA levels...
December 7, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29221184/hepatitis-b-virus-x-protein-inhibits-apoptosis-by-modulating-endoplasmic-reticulum-stress-response
#6
Jia Li, Jiang He, Yongming Fu, Xingwang Hu, Lun-Quan Sun, Yan Huang, Xuegong Fan
Chronic Hepatitis B virus (HBV) infection is a major risk of hepatocellular carcinoma (HCC) worldwide. Hepatitis B virus X protein (HBx) is encoded by one of the four open reading frames of HBV, and is well known as an important coactivator for HBV replication and HBV-associated hepatocellular carcinogenesis. However, its role in keeping cells from apoptosis to promote HCC proliferation remains controversial. Here, we used HBx expressing HCC cells as a model, to investigate the mechanism of HBx-mediated cellular response to endoplasmic reticulum (ER) stress...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29211299/endoplasmic-reticulum-stress-induced-lox-1-cd15-polymorphonuclear-myeloid-derived-suppressor-cells-in-hepatocellular-carcinoma
#7
Nan Jiang, Yan-Fang Xing, Bo Hu, Jian-Xin Tang, Hui-Min Dong, Yu-Mei He, Dan-Yun Ruan, Qing-Jian Ye, Jia-Rong Cai, Xiao-Kun Ma, Jie Chen, Xiu-Rong Cai, Ze-Xiao Lin, Xiang-Yuan Wu, Xing Li
AIM: A recent study indicated that Lectin-type oxidized LDL receptor-1 (LOX-1) was a distinct surface marker for human polymorphonuclears myeloid-derived suppressor cells (PMN-MDSC). The present study was aimed to investigate the existence LOX-1 PMN-MDSC in hepatocellular carcinoma (HCC) patients. METHODS: 127 HCC patients, 10 patients with mild active chronic hepatits B, 10 liver cirrhosis due to hepatitis B, 10 liver dysplastic node with hepatitis B and 50 health control were included...
December 6, 2017: Immunology
https://www.readbyqxmd.com/read/29209107/functional-interaction-of-endoplasmic-reticulum-stress-and-hepatitis-b-virus-in-the-pathogenesis-of-liver-diseases
#8
REVIEW
So Young Kim, Yi Yi Kyaw, Jaehun Cheong
Hepatitis B virus (HBV) is a non-cytopathic virus that causes acute and chronic inflammatory liver diseases, often leading to the pathogenesis of hepatocellular carcinoma (HCC). Although many studies for the roles of HBV on pathogenesis of the liver diseases, such as non-alcoholic fatty liver disease (NAFLD), hepatic inflammation, cirrhosis, and HCC, have been reported, the mechanisms are not fully understood. Endoplasmic reticulum (ER) and mitochondria have the protective mechanisms to restore their damaged function by intrinsic or extrinsic stresses, but their chronic dysfunctions are associated with the pathogenesis of the various diseases...
November 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29184085/diverse-changes-of-circulating-fibroblast-growth-factor-21-levels-in-hepatitis-b-virus-related-diseases
#9
Liang Wu, Qingchun Pan, Guangyu Wu, Lingling Qian, Jing Zhang, Lei Zhang, Qichen Fang, Guoqing Zang, Yudong Wang, George Lau, Huating Li, Weiping Jia
Fibroblast growth factor 21 (FGF21), a stress-induced hormone in the liver, has been shown the protective functions in pathological conditions. The study investigated the association of circulating FGF21 with hepatitis B virus (HBV) infection and its related diseases. Serum FGF21 levels were measured in 33 acute hepatitis B (AHB), 75 chronic hepatitis B (CHB) and 66 CHB patients with advanced liver diseases including liver cirrhosis, acute-on-chronic liver failure (ALCF) and hepatocellular carcinoma (HCC) together with 200 age- and BMI-matched healthy controls...
November 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29156655/the-role-of-glyoxalase-i-glo-i-advanced-glycation-endproducts-ages-and-their-receptor-rage-in-chronic-liver-disease-and-hepatocellular-carcinoma-hcc
#10
REVIEW
Marcus Hollenbach
Glyoxalase-I (Glo-I) and glyoxalase-II (Glo-II) comprise the glyoxalase system and are responsible for the detoxification of methylglyoxal (MGO). MGO is formed non-enzymatically as a by-product, mainly in glycolysis, and leads to the formation of advanced glycation endproducts (AGEs). AGEs bind to their receptor, RAGE, and activate intracellular transcription factors, resulting in the production of pro-inflammatory cytokines, oxidative stress, and inflammation. This review will focus on the implication of the Glo-I/AGE/RAGE system in liver injury and hepatocellular carcinoma (HCC)...
November 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29154569/the-social-transmission-of-risk-maternal-stress-physiology-synchronous-parenting-and-well-being-mediate-the-effects-of-war-exposure-on-child-psychopathology
#11
Galit Halevi, Amir Djalovski, Yaniv Kanat-Maymon, Karen Yirmiya, Orna Zagoory-Sharon, Lee Koren, Ruth Feldman
While chronic early stress increases child susceptibility to psychopathology, risk and resilience trajectories are shaped by maternal social influences whose role requires much further research in longitudinal studies. We examined the social transmission of risk by assessing paths leading from war-exposure to child symptoms as mediated by 3 sources of maternal social influence; stress physiology, synchronous parenting, and psychiatric disorder. Mothers and children living in a zone of continuous war were assessed in early childhood (1...
November 2017: Journal of Abnormal Psychology
https://www.readbyqxmd.com/read/29065770/salivary-cortisol-reactivity-in-preschoolers-is-associated-with-hair-cortisol-and-behavioral-problems
#12
Katie Kao, Stacey N Doan, Ashley M St John, Jerrold S Meyer, Amanda R Tarullo
The interplay between children's cortisol reactivity to challenge and cumulative cortisol exposure is not well understood. Examining the role of cortisol reactivity in early childhood may elucidate biological mechanisms that contribute to children's chronic physiological stress and behavioral dysregulation. In a sample of 65 preschool-aged children, we examined the relation between children's salivary cortisol reactivity to challenging tasks and their hair cortisol concentration (HCC). While both are biomarkers of the hypothalamic-pituitary-adrenal (HPA) axis, salivary cortisol reactivity reflects an acute cortisol response to a stressor and HCC reflects cumulative cortisol exposure...
October 24, 2017: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/29057834/non-alcoholic-fatty-liver-disease-and-nutritional-implications-special-focus-on-copper
#13
REVIEW
Laura Antonucci, Cristiana Porcu, Gino Iannucci, Clara Balsano, Barbara Barbaro
Non-alcoholic fatty liver disease (NAFLD) is characterized by excess lipids in hepatocytes, due to excessive fatty acid influx from adipose tissue, de novo hepatic lipogenesis, in addition to excessive dietary fat and carbohydrate intake. Chronic hepatic lipid overload induces mitochondrial oxidative stress and cellular damage leading the development of NAFLD into a more severe liver disease condition, non-alcoholic steato-hepatitis (NASH). In turn, this can progress to cirrhosis and hepatocellular carcinoma (HCC)...
October 18, 2017: Nutrients
https://www.readbyqxmd.com/read/29050312/non-alcoholic-steatohepatitis-related-liver-tumorigenesis-is-suppressed-in-mice-lacking-hepatic-retinoid-storage
#14
Takayasu Ideta, Yohei Shirakami, Masaya Ohnishi, Akinori Maruta, Koki Obara, Tsuneyuki Miyazaki, Takahiro Kochi, Hiroyasu Sakai, Hiroyuki Tomita, Takuji Tanaka, William S Blaner, Masahito Shimizu
Non-alcoholic fatty liver disease has become one of the most common causes of chronic liver disease that can develop into a more serious form, non-alcoholic steatohepatitis, leading to liver cirrhosis and hepatocellular carcinoma. Although hepatic retinoid stores are progressively lost during the development of liver disease, how this affects steatohepatitis and its related hepatocarcinogenesis is unknown. In order to investigate these, we used subcutaneous injection of streptozotocin (0.2 mg/body) and high-fat diet to induce steatohepatitis and hepatic tumorigenesis in lecithin:retinol acyltransferase -deficient mice (n = 10), which lack stored retinoid in the liver, and control mice (n = 12)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900935/metabolic-disorders-and-cancer-hepatocyte-store-operated-ca-2-channels-in-nonalcoholic-fatty-liver-disease
#15
Eunüs S Ali, Grigori Y Rychkov, Greg J Barritt
In steatotic hepatocytes, intracellular Ca(2+) homeostasis is substantially altered compared to normal. Decreased Ca(2+) in the endoplasmic reticulum (ER) can lead to ER stress, an important mediator of the progression of liver steatosis to nonalcoholic steatohepatitis, type 2 diabetes, and hepatocellular carcinoma. Store-operated Ca(2+) channels (SOCs) in hepatocytes are composed principally of Orai1 and STIM1 proteins. Their main role is the maintenance of adequate Ca(2+) in the lumen of the ER. In steatotic hepatocytes, store-operated Ca(2+) entry (SOCE) is substantially inhibited...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28898696/a-dual-role-of-caspase-8-in-triggering-and-sensing-proliferation-associated-dna-damage-a-key-determinant-of-liver-cancer-development
#16
Yannick Boege, Mohsen Malehmir, Marc E Healy, Kira Bettermann, Anna Lorentzen, Mihael Vucur, Akshay K Ahuja, Friederike Böhm, Joachim C Mertens, Yutaka Shimizu, Lukas Frick, Caroline Remouchamps, Karun Mutreja, Thilo Kähne, Devakumar Sundaravinayagam, Monika J Wolf, Hubert Rehrauer, Christiane Koppe, Tobias Speicher, Susagna Padrissa-Altés, Renaud Maire, Jörn M Schattenberg, Ju-Seong Jeong, Lei Liu, Stefan Zwirner, Regina Boger, Norbert Hüser, Roger J Davis, Beat Müllhaupt, Holger Moch, Henning Schulze-Bergkamen, Pierre-Alain Clavien, Sabine Werner, Lubor Borsig, Sanjiv A Luther, Philipp J Jost, Ricardo Weinlich, Kristian Unger, Axel Behrens, Laura Hillert, Christopher Dillon, Michela Di Virgilio, David Wallach, Emmanuel Dejardin, Lars Zender, Michael Naumann, Henning Walczak, Douglas R Green, Massimo Lopes, Inna Lavrik, Tom Luedde, Mathias Heikenwalder, Achim Weber
Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28874443/amelioration-of-diet-induced-steatohepatitis-in-mice-following-combined-therapy-with-aso-fsp27-and-fenofibrate
#17
Ananthi Rajamoorthi, Noemí Arias, Jeannine Basta, Richard G Lee, Ángel Baldán
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD progresses from benign steatosis to steatohepatitis (NASH) to cirrhosis and is linked to hepatocellular carcinoma. No targeted treatment is currently approved for NAFLD/NASH. We previously showed that fat-specific protein 27 (FSP27), a lipid droplet-associated protein that controls triglyceride turnover in the hepatocyte, is required for fasting- and diet-induced triglyceride accumulation in the liver. However, silencing Fsp27 with antisense oligonucleotides (ASOs) did not improve hepatosteatosis in genetic nor nutritional mouse models of obesity...
November 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28852124/oxidative-stress-and-immune-responses-during-hepatitis-c-virus-infection-in-tupaia-belangeri
#18
Mohammad Enamul Hoque Kayesh, Sayeh Ezzikouri, Takahiro Sanada, Haiying Chi, Yukiko Hayashi, Khadija Rebbani, Bouchra Kitab, Aya Matsuu, Noriaki Miyoshi, Tsunekazu Hishima, Michinori Kohara, Kyoko Tsukiyama-Kohara
Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. To address the molecular basis of HCV pathogenesis using tupaias (Tupaia belangeri), we characterized host responses upon HCV infection. Adult tupaias were infected with HCV genotypes 1a, 1b, 2a, or 4a. Viral RNA, alanine aminotransferase, anti-HCV core and anti-nonstructural protein NS3 antibody titres, reactive oxygen species (ROS), and anti-3β-hydroxysterol-Δ24reductase (DHCR24) antibody levels were measured at 2-week intervals from 0 to 41 weeks postinfection...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835697/activation-of-perk-nrf2-oncogenic-signaling-promotes-mdm2-mediated-rb-degradation-in-persistently-infected-hcv-culture
#19
Yucel Aydin, Milad Chedid, Srinivas Chava, Donkita Danielle Williams, Shuanghu Liu, Curt H Hagedorn, Suchitra Sumitran-Holgersson, Krzysztof Reiss, Krzysztof Moroz, Hua Lu, Luis A Balart, Srikanta Dash
The mechanism of how chronic hepatitis C virus (HCV) infection leads to such a high rate of hepatocellular carcinoma (HCC) is unknown. We found that the PERK axis of endoplasmic reticulum (ER) stress elicited prominent nuclear translocation of Nrf2 in 100% of HCV infected hepatocytes. The sustained nuclear translocation of Nrf2 in chronically infected culture induces Mdm2-mediated retinoblastoma protein (Rb) degradation. Silencing PERK and Nrf2 restored Mdm2-mediated Rb degradation, suggesting that sustained activation of PERK/Nrf2 axis creates oncogenic stress in chronically infected HCV culture model...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28802237/umbelliferon-%C3%AE-d-glucopyranosyl-2-i-%C3%A2-1-ii-%C3%AE-dglucopyranoside-ameliorates-diethylnitrosamine-induced-precancerous-lesion-development-in-liver-via-regulation-of-inflammation-hyperproliferation-and-antioxidant-at-pre-clinical-stage
#20
Vikas Kumar, Prakash Chandra Bhatt, Mahfoozur Rahman, Fahad A Al-Abbasi, Firoz Anwar, Amita Verma
It is well documented that anomalous production of inflammatory proteins linked with most of the toxic expression and genesis of diverse chronic disease including cancer. Diethylnitrosamine (DEN) a well-known hepatotoxin and hepatocarcinogen, can induce oxidative stress and inflammatory reaction in it. Umbelliferone, secondary metabolites, is present in different plants and widely consumed by humans as medicine and food supplements. The aim of the current study was to scrutinize the chemoprotective potential of umbelliferon-α-d-glucopyranosyl-(2(I)→1(II))-α-d-glucopyranoside (UFD) against DEN-induced hepatocellular carcinoma (HCC) in experimental rats...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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