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https://www.readbyqxmd.com/read/28513320/crispr-cas9-based-pten-knock-out-and-sleeping-beauty-transposon-mediated-nras-knock-in-induces-hepatocellular-carcinoma-and-hepatic-lipid-accumulation-in-mice
#1
Mingming Gao, Dexi Liu
Both Pten and Nras are downstream mediators of receptor tyrosine kinase activation that plays important roles in controlling cell survival and proliferation. Here, we investigated whether and how Pten loss cross-talks with Nras activation in driving liver cancer development in mice. Somatic disruption of hepatic Pten and overexpression of Nras were achieved in out-bred immunocompetent CD-1 mice through a hydrodynamic delivery of plasmids carrying Sleeping Beauty transposon-based integration of Nras and the CRISPR/Cas9-mediated Pten knock-out system...
May 17, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28507299/the-fatty-acid-%C3%AE-oxidation-pathway-is-activated-by-leucine-deprivation-in-hepg2-cells-a-comparative-proteomics-study
#2
Guokai Yan, Xiuzhi Li, Ying Peng, Baisheng Long, Qiwen Fan, Zhichang Wang, Min Shi, Chunlin Xie, Li Zhao, Xianghua Yan
Leucine (Leu) is a multifunctional essential amino acid that plays crucial role in various cellular processes. However, the integral effect of Leu on the hepatic proteome remains largely unknown. Here, we for the first time applied an isobaric tags for relative and absolute quantification (iTRAQ)-based comparative proteomics strategy to investigate the proteome alteration induced by Leu deprivation in human hepatocellular carcinoma (HepG2) cells. A total of 4,111 proteins were quantified; 43 proteins were further identified as differentially expressed proteins between the normal and Leu deprivation groups...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28500841/effect-of-hepatic-steatosis-on-the-progression-of-chronic-hepatitis-b-a-prospective-cohort-and-in-vitro-study
#3
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...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28481866/critical-role-of-myc-activation-in-mouse-hepatocarcinogenesis-induced-by-the-activation-of-akt-and-ras-pathways
#4
B Xin, M Yamamoto, K Fujii, T Ooshio, X Chen, Y Okada, K Watanabe, N Miyokawa, H Furukawa, Y Nishikawa
MYC activation at modest levels has been frequently found in hepatocellular carcinoma. However, its significance in hepatocarcinogenesis has remained obscure. Here we examined the role of Myc activation in mouse liver tumours induced by hepatocytic expression of myristoylated AKT (AKT) and/or mutant HRAS(V12) (HRAS) via transposon-mediated gene integration. AKT or HRAS alone required 5 months to induce liver tumours, whereas their combination generated hepatocellular carcinoma within 8 weeks. Co-introduction of AKT and HRAS induced lipid-laden preneoplastic cells that grew into nodules composed of tumour cells with or without intracytoplasmic lipid, with the latter being more proliferative and associated with spontaneous Myc expression...
May 8, 2017: Oncogene
https://www.readbyqxmd.com/read/28467182/roles-of-silent-information-regulator-1-serine-arginine-rich-splicing-factor-10-lipin-1-axis-in-the-pathogenesis-of-alcohol-fatty-liver-disease
#5
Yuanyuan Li, Junying Zhou
Alcohol exposure is a major reason of morbidity and mortality all over the world, with much of detrimental consequences attributing to alcoholic liver disease (ALD). With the continued ethanol consumption, alcoholic fatty liver disease (AFLD, the earliest and reversible form of ALD) can further develop to more serious forms of alcoholic liver damage, including alcoholic steatohepatitis, fibrosis/cirrhosis, and even eventually progress to hepatocellular carcinoma and liver failure. Furthermore, cell trauma, inflammation, oxidative stress, regeneration, and bacterial translocation are crucial promoters of ethanol-mediated liver lesions...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28467181/pre-clinical-and-clinical-investigations-of-metabolic-zonation-in-liver-diseases-the-potential-of-microphysiology-systems
#6
Alejandro Soto-Gutierrez, Albert Gough, Lawrence A Vernetti, D L Taylor, Satdarshan P Monga
The establishment of metabolic zonation within a hepatic lobule ascribes specific functions to hepatocytes based on unique, location-dependent gene expression patterns. Recently, there have been significant developments in the field of metabolic liver zonation. A little over a decade ago, the role of β-catenin signaling was identified as a key regulator of gene expression and function in pericentral hepatocytes. Since then, additional molecules have been identified that regulate the pattern of Wnt/β-catenin signaling within a lobule and determine gene expression and function in other hepatic zones...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28462693/sarcopenia-in-patients-with-advanced-liver-disease
#7
Francesca Romana Ponziani, Antonio Gasbarrini
Sarcopenia is the loss of muscle mass and function, affecting up to 70% of patients with advanced liver disease. Liver cirrhosis is characterized by an altered glucose metabolism, lipid oxidation, ketogenesis and protein catabolism, leading to the loss of adipose and muscle tissue. The gastrointestinal dysfunction of cirrhotic patients results in inadequate nutrients intake and is responsible for muscle weakness thus limiting physical exercise and perpetuating the reduction of muscle mass. Recently, alterations of hormonal pathways involved in muscle growth, increased intestinal permeability and changes in the gut microbiota composition have been reported in cirrhotic patients...
April 28, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28448873/osthole-attenuates-lipid-accumulation-regulates-the-expression-of-inflammatory-mediators-and-increases-antioxidants-in-fl83b-cells
#8
Wen-Chung Huang, Po-Chen Liao, Chun-Hsun Huang, Sindy Hu, Shih-Chun Huang, Shu-Ju Wu
Osthole is found in Cnidium monnieri (L.) and has anti-inflammatory and anti-oxidative properties. It also inhibits the proliferation of hepatocellular carcinoma cells. This study aimed to evaluate the osthole suppressive nonalcoholic fatty liver disease effects in oleic acid (OA)-induced hepatic steatosis and if it can modulate inflammatory responses and oxidative stress. FL83B cells were pretreated with OA (250μΜ) for 24h, and then added different concentrations of osthole (3-100μM) for 24h. Subsequently, lipolysis and transcription factors of adipogenesis and phosphorylation of AMP-activated protein kinase proteins were measured...
April 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28442273/the-role-of-bile-acids-in-nonalcoholic-fatty-liver-disease-and-nonalcoholic-steatohepatitis
#9
REVIEW
Monica D Chow, Yi-Horng Lee, Grace L Guo
Nonalcoholic fatty liver disease is growing in prevalence worldwide. It is marked by the presence of macrosteatosis on liver histology but is often clinically asymptomatic. However, it can progress into nonalcoholic steatohepatitis which is a more severe form of liver disease characterized by inflammation and fibrosis. Further progression leads to cirrhosis, which predisposes patients to hepatocellular carcinoma or liver failure. The mechanism by which simple steatosis progresses to steatohepatitis is not entirely clear...
May 5, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28436449/metabolism-dysregulation-induces-a-specific-lipid-signature-of-nonalcoholic-steatohepatitis-in-patients
#10
Franck Chiappini, Audrey Coilly, Hanane Kadar, Philippe Gual, Albert Tran, Christophe Desterke, Didier Samuel, Jean-Charles Duclos-Vallée, David Touboul, Justine Bertrand-Michel, Alain Brunelle, Catherine Guettier, François Le Naour
Nonalcoholic steatohepatitis (NASH) is a condition which can progress to cirrhosis and hepatocellular carcinoma. Markers for NASH diagnosis are still lacking. We performed a comprehensive lipidomic analysis on human liver biopsies including normal liver, nonalcoholic fatty liver and NASH. Random forests-based machine learning approach allowed characterizing a signature of 32 lipids discriminating NASH with 100% sensitivity and specificity. Furthermore, we validated this signature in an independent group of NASH patients...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28430371/evaluation-of-circulating-zonulin-as-a-potential-marker-in-the-pathogenesis-of-nonalcoholic-fatty-liver-disease
#11
Olfat M Hendy, Maha M Elsabaawy, Mona M Aref, Fatma M Khalaf, Abdel Moaty A Oda, Helmy M El Shazly
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders ranging from simple hepatic steatosis up to nonalcoholic steatohepatitis (NASH) evolving to cirrhosis and hepatocellular carcinoma (HCC). Liver biopsy is still the gold standard modality for diagnosing and staging NAFLD. The linkage between intestinal microbiota and NAFLD, might suggest a potential role of serum zonulin in NAFLD diagnosis. To appraise the role of circulating zonulin in NAFLD pathogenesis, 56 subjects with proved NAFLD by ultrasonography and liver biopsy, as well as 20 healthy controls were tested...
April 21, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28422390/naringin-abates-adverse-effects-of-cadmium-mediated-hepatotoxicity-an-experimental-study-using-hepg2-cells
#12
Visesh Kumar Rathi, Shubhankar Das, Archana Parampalli Raghavendra, Bola Sadashiva Satish Rao
This study investigated the protective potential of Naringin (NIN) against cadmium chloride (CdCl2 ) mediated hepatotoxicity using human hepatocellular carcinoma (HepG2) cells. An optimal concentration of NIN (5 μM) was potent enough to confer cytoprotection against CdCl2 (50 μM) as was observed by MTT assay. Preconditioning with NIN maintained redox homeostasis, mitochondrial membrane potential, and reduced apoptosis as marked by decrease in the percentage sub-G0 /G1 and Annexin V-FITC/propidium iodide positive cells (apoptotic)...
April 19, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28421422/hepatitis-c-virus-genotype-3-update-on-current-and-emergent-therapeutic-interventions
#13
REVIEW
Steven W Johnson, Dorothea K Thompson, Brianne Raccor
PURPOSE OF REVIEW: Direct-acting antiviral agents (DAAs) have markedly improved the prognosis of hepatitis C virus (HCV)-genotype 3 (GT3), a highly prevalent infection worldwide. However, in patients with hepatic fibrosis, cirrhosis, or hepatocellular carcinoma (HCC), GT3 infection presents a treatment challenge compared with other genotypes. The dependence of the HCV life cycle on host lipid metabolism suggests the possible utility of targeting host cellular factors for combination anti-HCV therapy...
June 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28420094/nonalcoholic-fatty-liver-disease-and-insulin-resistance-new-insights-and-potential-new-treatments
#14
REVIEW
Hironori Kitade, Guanliang Chen, Yinhua Ni, Tsuguhito Ota
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide. It is associated with clinical states such as obesity, insulin resistance, and type 2 diabetes, and covers a wide range of liver changes, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. Metabolic disorders, such as lipid accumulation, insulin resistance, and inflammation, have been implicated in the pathogenesis of NAFLD, but the underlying mechanisms, including those that drive disease progression, are not fully understood...
April 14, 2017: Nutrients
https://www.readbyqxmd.com/read/28390113/regulation-of-acetate-utilization-by-monocarboxylate-transporter-1-mct1-in-hepatocellular-carcinoma-hcc
#15
Jeong Jeon, Misu Lee, Sang Whang, Jung-Whan Kim, Arthur Cho, Mijin Yun
Altered energy metabolism is a biochemical fingerprint of cancer cells. Hepatocellular carcinoma (HCC) shows reciprocal18F-Fluorodeoxyglucose (FDG) and 11C-acetate uptake, as revealed by positron emission tomography/computed tomography (PET/CT). Previous studies have focused on the role of FDG uptake in cancer cells; in this study, we evaluated the mechanism and roles of 11C-acetate uptake in human HCCs and cell lines. The expression of monocarboxylate transporters (MCTs) was assessed to determine the transporters of 11C-acetate uptake in HCC cell lines and human HCCs with different 11C-acetate uptake...
March 23, 2017: Oncology Research
https://www.readbyqxmd.com/read/28372475/in-vivo-antitumour-potential-of-camel-s-milk-against-hepatocellular-carcinoma-in-rats-and-its-improvement-of-cisplatin-renal-side-effects
#16
Hala M F El Miniawy, Kawkab A Ahmed, Sameeh A Mansour, Marwa M Salah Khattab
CONTEXT: Camel milk (CM) is recommended for liver disease patients in Egypt for a strong belief that it has a curative effect. OBJECTIVE: The effect of consumption of CM with or without chemotherapeutic drug cisplatin was evaluated on induced hepatocarcinogenesis in rats. MATERIALS AND METHODS: Wistar male rats (56) were divided into eight groups (7 rats each). Group I was control. Hepatocarcinogenesis was initiated by a single dose of intraperitoneal injection of diethylnitrosamine (DENA) (200 mg/kg BW) and promoted by phenobarbitone (500 ppm) in drinking water in groups V, VI, VII and VIII...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28371239/the-mediterranean-dietary-pattern-as-the-diet-of-choice-for-nafld-evidence-and-plausible-mechanisms
#17
Shira Zelber-Sagi, Federico Salomone, Liat Mlynarsky
Non-alcoholic fatty liver disease (NAFLD) has become a major global health burden, leading to increased risk for cirrhosis, hepatocellular carcinoma, type-2 diabetes and cardiovascular disease. Lifestyle intervention aiming at weight reduction is the most established treatment. However, changing the dietary composition even without weight loss can also reduce steatosis and improve metabolic alterations as insulin resistance and lipid profile. The Mediterranean diet (MD) pattern has been proposed as appropriate for this goal, and was recommended as the diet of choice for the treatment of NAFLD by the EASL-EASD-EASO Clinical Practice Guidelines...
April 2, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28359761/aspirin-suppresses-the-abnormal-lipid-metabolism-in-liver-cancer-cells-via-disrupting-an-nf%C3%AE%C2%BAb-acsl1-signaling
#18
Guang Yang, Yuan Wang, Jinyan Feng, Yunxia Liu, Tianjiao Wang, Man Zhao, Lihong Ye, Xiaodong Zhang
Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme...
March 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28352173/lipid-coated-iron-oxide-nanoparticles-for-dual-modal-imaging-of-hepatocellular-carcinoma
#19
Jinying Liang, Xinxin Zhang, Yunqiu Miao, Juan Li, Yong Gan
The development of noninvasive imaging techniques for the accurate diagnosis of progressive hepatocellular carcinoma (HCC) is of great clinical significance and has always been desired. Herein, a hepatocellular carcinoma cell-targeting fluorescent magnetic nanoparticle (NP) was obtained by conjugating near-infrared fluorescence to the surface of Fe3O4 (NIRF-Fe3O4) NPs, followed by coating the lipids consisting of tumoral hepatocytes-targeting polymer (Gal-P123). This magnetic NP (GPC@NIRF-Fe3O4) with superparamagnetic behavior showed high stability and safety in physiological conditions...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28345375/the-chemo-prophylactic-efficacy-of-an-ethanol-moringa-oleifera-leaf-extract-against-hepatocellular-carcinoma-in-rats
#20
Kadry M Sadek, Tarek K Abouzed, Reham Abouelkhair, Sherif Nasr
CONTEXT: Hepatocellular carcinoma (HCC) is among the most well-known threatening tumours around the world, and the outlook remains bleak. Moringa oleifera Lam. (Moringaceae) exhibits antitumor, antioxidant and hepatoprotective properties. OBJECTIVES: To assess the chemo-prophylactic proficiency and other likely activities of Moringa oleifera leaf ethanol extract (MOLEE) against diethyl nitrosamine (DEN)-induced HCC. MATERIALS AND METHODS: Wistar rats were gastrogavaged with MOLEE (500 mg/kg) for one week and then gastrogavaged with MOLEE and DEN (10 mg/kg) for the following 16 weeks...
December 2017: Pharmaceutical Biology
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