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https://www.readbyqxmd.com/read/29127353/clinicopathological-and-prognostic-significance-of-pkm2-protein-expression-in-cirrhotic-hepatocellular-carcinoma-and-non-cirrhotic-hepatocellular-carcinoma
#1
Yan Liu, Hao Wu, Ying Mei, Xiong Ding, Xiaoli Yang, Changping Li, Mingming Deng, Jianping Gong
Pyruvate kinase M2 (PKM2), a key protein in glucose and lipid metabolism, has been reported to be related to carcinogenesis in various malignancies. However, its roles in hepatocellular carcinoma with cirrhotic liver (CL) and hepatocellular carcinoma with non-cirrhoticliver (NCL) haves not been investigated. In our study western bloting, qRT-PCR and immunohistochemistry were performed to evaluate the clinical significance of PKM2 protein expression in CL and NCL. The results revealed that PKM2 protein expression was significantly higher in HCC tissues than in their adjacent non-tumour tissues...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29118118/n-myc-downstream-regulated-gene-1-restricts-hepatitis-c-virus-propagation-by-regulating-lipid-droplet-biogenesis-and-viral-assembly
#2
Cameron J Schweitzer, Fang Zhang, Audrey Boyer, Kristin Valdez, Maggie Cam, T Jake Liang
Host cells harbor various intrinsic mechanisms to restrict viral infections as a first line of antiviral defense. Viruses have evolved various countermeasures against these antiviral mechanisms. Here we show that N-Myc Downstream-Reguated Gene 1 (NDRG1) limits productive HCV infection by inhibiting viral assembly. Interestingly, HCV infection down-regulates NDRG1 protein and mRNA expression. Loss of NDRG1 increases the size and number of lipid droplets, which are the sites of HCV assembly. HCV suppresses NDRG1 expression by up-regulating MYC, which directly inhibits the transcription of NDRG1 Up-regulation of MYC also leads to reduced expression of NDRG1-specific kinase SGK1, resulting in markedly diminished phosphorylation of NDRG1...
November 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29109303/insulin-resistance-and-reduced-metabolic-flexibility-cause-or-consequence-of-nafld
#3
EDITORIAL
Amalia Gastaldelli
Whether non-alcoholic fatty liver disease (NAFLD) precedes insulin resistance (IR) or IR preludes/causes NAFLD has been long debated. Recent studies have shown that there are two phenotypes of NAFLD, 'genetic' vs 'metabolic' NAFLD. The former patients are more at risk of hepatocellular carcinoma and chronic liver disease the latter are more IR and at increased risk of type 2 diabetes (T2D). Even if they are not yet diabetics, from a metabolic point of view having NAFLD is equivalent to T2D with reduced peripheral glucose disposal and impaired suppression of hepatic glucose production, but without fasting hyperglycaemia...
November 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29097707/gp73-regulates-hepatic-steatosis-by-enhancing-scap-srebps-interaction
#4
Xiaoli Yang, Feixiang Wu, Jiankang Chen, Cui Wang, Yongjie Zhu, Feng Li, Qinfang Hao, Cuijuan Duan, Li Wang, Xueping Ma, Deyong Zou, Li Luo, Yiwen Zhao, Kai Guan, Yuan Cao, Pingping Zhang, Pengyu Zhou, Shengli Ma, Zhifeng Yan, Jia Li, Yanhong Zhang, Congwen Wei, Hui Zhong
Elevated Golgi phosphoprotein 2 (GP73, also known as GOLPH2 or GOLM1) expression in serum and liver, which can be induced by viral infection and cytokine treatments, is intimately connected with liver disease, including acute hepatitis, cirrhosis and hepatocellular carcinoma (HCC). However, its pathogenic roles in hepatic diseases have never been clarified in detail. Here, we showed that the upregulated GP73 is indispensable for SREBPs activation and lipogenesis. Notably, GP73 overexpression enhanced SCAP-SREBPs binding and its Golgi trafficking even under cholesterol sufficiency...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29074727/liver-reptin-ruvbl2-controls-glucose-and-lipid-metabolism-with-opposite-actions-on-mtorc1-and-mtorc2-signalling
#5
Joaquim Javary, Nathalie Allain-Courtois, Nicolas Saucisse, Pierre Costet, Capucine Heraud, Fadila Benhamed, Rémi Pierre, Corinne Bure, Nestor Pallares-Lupon, Marcio Do Cruzeiro, Catherine Postic, Daniela Cota, Pierre Dubus, Jean Rosenbaum, Samira Benhamouche-Trouillet
OBJECTIVE: The AAA+ ATPase Reptin is overexpressed in hepatocellular carcinoma and preclinical studies indicate that it could be a relevant therapeutic target. However, its physiological and pathophysiological roles in vivo remain unknown. This study aimed to determine the role of Reptin in mammalian adult liver. DESIGN AND RESULTS: We generated an inducible liver-specific Reptin knockout (Repin(LKO) ) mouse model. Following Reptin invalidation, mice displayed decreased body and fat mass, hypoglycaemia and hypolipidaemia...
October 26, 2017: Gut
https://www.readbyqxmd.com/read/29068700/silibinin-reduces-the-impact-of-obesity-on-invasive-liver-cancer
#6
C Miethe, H Nix, R Martin, A R Hernandez, R S Price
Obesity is associated with non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Obesity and metabolic abnormalities resulting in low-grade inflammation can increase the risk of developing NASH and HCC. NASH, a risk factor for HCC, is characterized by increased inflammation, lipid accumulation, and liver injury. Obesogenic proteins modulate signaling pathways that induce physiological changes including lipogenesis, ROS, and inflammation. Silibinin, a polyphenol in milk thistle seed, has been shown to have anti-inflammatory properties...
October 25, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/29066484/aminoguanidine-ag-induces-induced-both-pro-and-antioxidant-effect-in-ar42j-cells-a-rat-pancreatic-tumor-cell-line
#7
Parimal Chowdhury
Aminoguanidine (AG), a diamine oxidase and a nitric oxide synthase inhibitor, was used in diabetes, thyroid follicular carcinoma, hepatocellular carcinoma, pancreatic cancer xenografts and in breast cancer research. The effects of AG on these pathologic conditions may be related to its regulatory effects on cell proliferation, angiogenesis, and expression of antioxidant enzymes. However, its role as pro and/or anti-oxidant affecting signaling and function in pancreatic tumor cell lines has not been studied...
September 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/29058484/neurite-outgrowth-inhibitor-b-receptor-a-versatile-receptor-with-multiple-functions-and-actions
#8
Shuang-Lian Long, Yu-Kun Li, Yuan-Jie Xie, Zhi-Feng Long, Jin-Feng Shi, Zhong-Cheng Mo
Members of the reticulon protein family are predominantly distributed within the endoplasmic reticulum. The neurite outgrowth inhibitor (Nogo) has three subtypes, including Nogo-A (200 kDa), Nogo-B (55 kDa), and Nogo-C (25 kDa). Nogo-A and Nogo-C are potent Nogos that are predominantly expressed in the central nervous system. Nogo-B, the splice variant of reticulon-4, is expressed widely in multiple human organ systems, including the liver, lung, kidney, blood vessels, and inflammatory cells. Moreover, the Nogo-B receptor (NgBR) can interact with Nogo-B and can independently affect nervous system regeneration, the chemotaxis of endothelial cells, proliferation, and apoptosis...
October 23, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/29057834/non-alcoholic-fatty-liver-disease-and-nutritional-implications-special-focus-on-copper
#9
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/29056532/lamp3-regulates-hepatic-lipid-metabolism-through-activating-pi3k-akt-pathway
#10
Xiaoyu Liao, Lingyu Song, Linlin Zhang, Hui Wang, Qiang Tong, Jing Xu, Gangyi Yang, Shiming Yang, Hongting Zheng
Lysosome associated membrane protein 3 (LAMP3), a highly glycosylated protein, is one member of the LAMPs family. LAMPs family plays a critical role in the autolysosome fusion process. Autophagy was recently confirmed to regulate hepatic lipolysis. However, the physiological function of LAMP3 in lipid metabolism is not clear. In the current study, we discovered that the LAMP3 expression level was higher in the liver tissues of non-alcoholic fatty liver disease (NAFLD) patients and high-fat diet and ob/ob mice than in the matched control groups...
October 19, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29018509/circrna_0046367-prevents-hepatoxicity-of-lipid-peroxidation-an-inhibitory-role-against-hepatic-steatosis
#11
Xing-Ya Guo, Jian-Neng Chen, Fang Sun, Yu-Qin Wang, Qin Pan, Jian-Gao Fan
Hepatic steatosis reflects the miRNA-related pathological disorder with triglyceride accumulation and lipid peroxidation, which leads to nonalcoholic steatohepatitis, liver fibrosis/cirrhosis, and even hepatocellular carcinoma. Circular RNA (circRNA)/miRNA interaction reveals a novel layer of epigenetic regulation, yet the miRNA-targeting circRNA remains uncertain in hepatic steatosis. Here, we uncover circRNA_0046367 to be endogenous modulator of miR-34a that underlies hepatic steatosis. In contrast to its expression loss during the hepatocellular steatosis in vivo and in vitro, circRNA_0046367 normalization abolished miR-34a's inhibitory effect on peroxisome proliferator-activated receptor α (PPARα) via blocking the miRNA/mRNA interaction with miRNA response elements (MREs)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29018272/bile-acid-microbiota-crosstalk-in-gastrointestinal-inflammation-and-carcinogenesis
#12
REVIEW
Wei Jia, Guoxiang Xie, Weiping Jia
Emerging evidence points to a strong association between the gut microbiota and the risk, development and progression of gastrointestinal cancers such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Bile acids, produced in the liver, are metabolized by enzymes derived from intestinal bacteria and are critically important for maintaining a healthy gut microbiota, balanced lipid and carbohydrate metabolism, insulin sensitivity and innate immunity. Given the complexity of bile acid signalling and the direct biochemical interactions between the gut microbiota and the host, a systems biology perspective is required to understand the liver-bile acid-microbiota axis and its role in gastrointestinal carcinogenesis to reverse the microbiota-mediated alterations in bile acid metabolism that occur in disease states...
October 11, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28969053/induction-of-socs3-by-liver-x-receptor-suppresses-the-proliferation-of-hepatocellular-carcinoma-cells
#13
Haojun Xiong, Yan Zhang, Shan Chen, Zhenhong Ni, Jintao He, Xinzhe Li, Bo Li, Kai Zhao, Fan Yang, Yijun Zeng, Bingbo Chen, Fengtian He
Liver X receptor (LXR), a member of nuclear receptor superfamily, is involved in the regulation of glucose, lipid and cholesterol metabolism. Recently, it has been reported that LXR suppress different kinds of cancers including hepatocellular carcinoma (HCC). However, the corresponding mechanism is still not well elucidated. In the present study, we found that activation of LXR downregulated cyclin D1 while upregulated p21 and p27 by elevating the level of suppressor of cytokine signaling 3 (SOCS3), leading to the cell cycle arrest at G1/S phase and growth inhibition of HCC cells...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28954437/isocaloric-dietary-changes-and-non-alcoholic-fatty-liver-disease-in-high-cardiometabolic-risk-individuals
#14
REVIEW
Giuseppe Della Pepa, Claudia Vetrani, Gianluca Lombardi, Lutgarda Bozzetto, Giovanni Annuzzi, Angela Albarosa Rivellese
Non-alcoholic fatty liver disease (NAFLD) incorporates an extensive spectrum of histologic liver abnormalities, varying from simple triglyceride accumulation in hepatocytes non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), and it is the most frequent chronic liver disease in the industrialized world. Beyond liver related complications such as cirrhosis and hepatocellular carcinoma, NAFLD is also an emerging risk factor for type 2 diabetes and cardiovascular disease. Currently, lifestyle intervention including strategies to reduce body weight and to increase regular physical activity represents the mainstay of NAFLD management...
September 26, 2017: Nutrients
https://www.readbyqxmd.com/read/28941178/metabolomic-and-transcriptomic-profiling-of-hepatocellular-carcinomas-in-hras12v-transgenic-mice
#15
Tingting Fan, Zhuona Rong, Jianyi Dong, Juan Li, Kangwei Wang, Xinxin Wang, Huiling Li, Jun Chen, Fujin Wang, Jingyu Wang, Aiguo Wang
Activation of the Ras/MAPK pathway is prevalently involved in the occurrence and development of hepatocellular carcinoma (HCC). However, its effects on the deregulated cellular metabolic processes involved in HCC in vivo remain unknown. In this study, a mouse model of HCC induced by hepatocyte-specific expression of the Hras12V oncogene was investigated using an integrative analysis of metabolomics and transcriptomics data. Consistent with the phenotype of abundant lipid droplets in HCC, the lipid biosynthesis in HCC was significantly enhanced by (1) a sufficient supply of acetyl-CoA from enhanced glycolysis and citrate shuttle activity; (2) a sufficient supply of NADPH from enhanced pentose phosphate pathway (PPP) activity; (3) upregulation of key enzymes associated with lipid biosynthesis; and (4) downregulation of key enzymes associated with bile acid biosynthesis...
October 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28939830/lack-of-nlrp3-inflammasome-leads-to-gut-liver-axis-derangement-gut-dysbiosis-and-a-worsened-phenotype-in-a-mouse-model-of-nafld
#16
Pierantonelli Irene, Rychlicki Chiara, Agostinelli Laura, Giordano Debora Maria, Gaggini Melania, Fraumene Cristina, Saponaro Chiara, Manghina Valeria, Sartini Loris, Mingarelli Eleonora, Pinto Claudio, Buzzigoli Emma, Trozzi Luciano, Giordano Antonio, Marzioni Marco, De Minicis Samuele, Uzzau Sergio, Cinti Saverio, Amalia Gastalderi, Svegliati-Baroni Gianluca
Non-Alcoholic Fatty Liver Disease (NAFLD) represents the most common form of chronic liver injury and can progress to cirrhosis and hepatocellular carcinoma. A "multi-hit" theory, involving high fat diet and signals from the gut-liver axis, has been hypothesized. The role of the NLRP3-inflammasome, which senses dangerous signals, is controversial. Nlrp3(-/-) and wild-type mice were fed a Western-lifestyle diet with fructose in drinking water (HFHC) or a chow diet. Nlrp3(-/-)-HFHC showed higher hepatic expression of PPAR γ2 (that regulates lipid uptake and storage) and triglyceride content, histological score of liver injury and greater adipose tissue inflammation...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28938597/3-decylcatechol-induces-autophagy-mediated-cell-death-through-the-ire1%C3%AE-jnk-p62-in-hepatocellular-carcinoma-cells
#17
Da-Hye Go, Yu Geon Lee, Da-Hye Lee, Jin-A Kim, In-Hwa Jo, Yeon Soo Han, Yong Hun Jo, Kwang-Youn Kim, Young-Kyo Seo, Jae-Hak Moon, Chang Hwa Jung, Tae-Il Jeon
The natural, phenolic lipid urushiol exhibits both antioxidant and anticancer activities; however, its biological activity on hepatocellular carcinoma (HCC) has not been previously investigated. Here, we demonstrate that an urushiol derivative, 3-decylcatechol (DC), induces human HCC Huh7 cell death by induction of autophagy. DC initiates the autophagic process by activation of the mammalian target of rapamycin signaling pathway via Unc-51-like autophagy activating kinase 1, leading to autophagosome formation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938582/effect-of-hepatic-steatosis-on-the-progression-of-chronic-hepatitis-b-a-prospective-cohort-and-in-vitro-study
#18
Yangqin Chen, Chunlei Fan, Yuhan Chen, Hui Liu, Shanshan Wang, Peiling Dong, Lei Li, Huiguo Ding
AIM: To characterize the effect of hepatic steatosis (HS) on the progression of chronic hepatitis B. METHODS: A total of 162 chronic hepatitis B (CHB) patients confirmed by liver biopsy were involved in this study. All subjects were prospectively followed-up for 5 years in real-life clinical practice. Fibrosis stage was determined using aspartate aminotransferase-to-platelet ratio index (APRI). The end-point was cirrhosis, liver cancer or death. The effects of steatosis on the biological behavior of hepatocellular carcinoma cells were investigated using oleic acid-induced lipid accumulation in HepG2, HLE, PLC, and SMMC-7721 cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28932315/experimental-hepatic-carcinogenesis-oxidative-stress-and-natural-antioxidants
#19
REVIEW
Velid Unsal, Ergül Belge-Kurutaş
Hepatocellular carcinoma is one of the most common cancers in the world, and it is influenced by agents such as DEN, 2-AAF, phenobarbital, alcohol, aflatoxin B1 metabolite or hepatitis viruses (B and C). Oxidative stress is becoming recognized as a key factor in the progression of hepatocarcinogenesis. Reactive oxygen species can play a leading role in initiation and promotion of hepatic carcinogenesis. The metabolites of DEN Diethylnitrosamine (DEN) mediate the binding of tumour promoters by covalently binding to the DNA with one or two oxidation-providing electrons...
August 15, 2017: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28900935/metabolic-disorders-and-cancer-hepatocyte-store-operated-ca-2-channels-in-nonalcoholic-fatty-liver-disease
#20
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
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