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https://www.readbyqxmd.com/read/28808340/kr%C3%A3-ppel-like-factor-6-is-a-transcriptional-activator-of-autophagy-in-acute-liver-injury
#1
Svenja Sydor, Paul Manka, Jan Best, Sami Jafoui, Jan-Peter Sowa, Miguel Eugenio Zoubek, Virginia Hernandez-Gea, Francisco Javier Cubero, Julia Kälsch, Diana Vetter, Maria Isabel Fiel, Yujin Hoshida, C Billie Bian, Leonard J Nelson, Han Moshage, Klaas Nico Faber, Andreas Paul, Hideo A Baba, Guido Gerken, Scott L Friedman, Ali Canbay, Lars P Bechmann
Krüppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)-treated mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807240/role-of-exosomes-in-treatment-of-hepatocellular-carcinoma
#2
REVIEW
Demetrios Moris, Eliza W Beal, Jeffery Chakedis, Richard A Burkhart, Carl Schmidt, Mary Dillhoff, Xufeng Zhang, Stamatios Theocharis, Timothy M Pawlik
Exosomes are nanovesicles that may play a role in intercellular communication by acting as carriers of functional contents such as proteins, lipids, RNA molecules and circulating DNA from donor to recipient cells. In addition, exosomes may play a potential role in immunosurveillance and tumor pathogenesis and progression. Recently, research has increasingly focused on the role of exosomes in hepatocellular carcinoma (HCC), the most common primary liver malignancy. We herein review data on emerging experimental and clinical studies focused on the role of exosomes in the pathogenesis, diagnosis, progression and chemotherapy response of patients with HCC...
September 2017: Surgical Oncology
https://www.readbyqxmd.com/read/28802563/metabolic-circuit-involving-free-fatty-acids-microrna-122-and-triglyceride-synthesis-in-liver-and-muscle-tissues
#3
Chofit Chai, Mila Rivkin, Liav Berkovits, Alina Simerzin, Elina Zorde-Khvalevsky, Nofar Rosenberg, Shiri Klein, Dayana Yaish, Ronen Durst, Shoshana Shpitzen, Shiran Udi, Joseph Tam, Joerg Heeren, Anna Worthmann, Christoph Schramm, Johannes Kluwe, Revital Ravid, Eran Hornstein, Hilla Giladi, Eithan Galun
BACKGROUND & AIMS: Effective treatments are needed for hepatic steatosis characterized by accumulation of triglycerides in hepatocytes, which leads to hepatocellular carcinoma. MicroRNA 122 (MIR122) is expressed only in the liver, where it regulates lipid metabolism. We investigated the mechanism by which free fatty acids (FFAs) regulate MIR122 expression and the effect of MIR122 on triglyceride synthesis. METHODS: We analyzed MIR122 promoter activity and validated its target mRNAs by transfection of luciferase reporter plasmids into Huh7, BNL-1ME, and HEK293 cultured cell lines...
August 9, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28769563/delivery-of-mir-375-and-doxorubicin-hydrochloride-by-lipid-coated-hollow-mesoporous-silica-nanoparticles-to-overcome-multiple-drug-resistance-in-hepatocellular-carcinoma
#4
Huiying Xue, Zhaoyang Yu, Yong Liu, Weigang Yuan, Tan Yang, Jia You, Xingxing He, Robert J Lee, Lei Li, Chuanrui Xu
Multidrug resistance (MDR) due to overexpression of P-glycoprotein (P-gp) is a major obstacle that hinders the treatment of hepatocellular carcinoma (HCC). It has been shown that miR-375 inhibits P-gp expression via inhibition of astrocyte elevated gene-1 (AEG-1) expression in HCC, and induces apoptosis in HCC cells by targeting AEG-1 and YAP1. In this study, we prepared lipid-coated hollow mesoporous silica nanoparticles (LH) containing doxorubicin hydrochloride (DOX) and miR-375 (LHD/miR-375) to deliver the two agents into MDR HCC cells in vitro and in vivo...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28768434/metabolic-reprogramming-during-hepatitis-b-disease-progression-offers-novel-diagnostic-and-therapeutic-opportunities
#5
REVIEW
Jesse Jr Masson, Hugh Ww Billings, Clovis S Palmer
Metabolic remodeling occurs in immune cells during an infection. Host cells must upregulate energy production for growth, proliferation, and effector functions to limit the damage imposed by pathogens. One example, the hepatitis B virus, induces hepatic injury in human hepatocytes through dysregulation of aerobic glycolysis and lipid metabolism. Increased glycolytic metabolism mediated by elevated expression of Glut1, glucose influx, and lactate secretion is associated with this Warburg phenotype, a classic metabolic signature also observed in cancer cells...
August 2017: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/28767424/induction-of-socs3-by-liver-x-receptor-suppresses-the-proliferation-of-hepatocellular-carcinoma-cells
#6
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...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28756230/haloperidol-a-sigma-receptor-1-antagonist-promotes-ferroptosis-in-hepatocellular-carcinoma-cells
#7
Tao Bai, Shuai Wang, Yipu Zhao, Rongtao Zhu, Weijie Wang, Yuling Sun
Ferroptosis is a novel form of cell death, which is characterized by accumulation of reactive oxygen species (ROS). Sigma 1 receptor (S1R) has been suggested to function in oxidative stress metabolism. Both erastin and sorafenib significantly induced S1R protein expression. Haloperidol strongly promoted erastin- and sorafenib-induced cell death, which was blocked by ferrostatin-1 but not ZVAD-FMK or necrosulfonamide. During ferroptosis, haloperidol substantially increased the cellular levels of Fe(2+), GSH and lipid peroxidation...
July 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28747982/comparative-study-of-fatty-liver-induced-by-methionine-and-choline-deficiency-in-c57bl-6n-mice-originating-from-three-different-sources
#8
Sou Hyun Kim, Yong Lim, Ju Bin Park, Jae-Hwan Kwak, Keuk-Jun Kim, Joung-Hee Kim, HyunKeun Song, Joon Young Cho, Dae Youn Hwang, Kil Soo Kim, Young-Suk Jung
Non-alcoholic fatty liver disease (NAFLD) is believed to be the most prevalent liver disease worldwide and a major cause of chronic liver injury. It is characterized by lipid accumulation in the absence of significant alcohol consumption and frequently progresses to steatohepatitis, liver fibrosis, and hepatocellular carcinoma. Although many studies have been conducted to better understand NAFLD since it was first recognized, there are still many gaps in knowledge of etiology, prognosis, prevention and treatment...
June 2017: Laboratory Animal Research
https://www.readbyqxmd.com/read/28747506/hcv-induces-the-localization-of-lipid-rafts-to-autophagosomes-for-its-rna-replication
#9
Ja Yeon Kim, Linya Wang, Jiyoung Lee, Jing-Hsiung James Ou
Autophagy plays important roles in maintaining cellular homeostasis. It uses double- or multiple- membrane vesicles termed autophagosomes to remove protein aggregates and damaged organelles from the cytoplasm for recycling. Hepatitis C virus (HCV) has been shown to induce autophagy to enhance its own replication. Here we describe a procedure that combines membrane flotation and affinity chromatography for the purification of autophagosomes from cells that harbor a HCV subgenomic RNA replicon. The purified autophagosomes had double- or multiple- membrane structures with a diameter ranging from 200 nm to 600 nm...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28730823/pathophysiological-analysis-of-the-progression-of-hepatic-lesions-in-stam-mice
#10
T Saito, M Muramatsu, Y Ishii, Y Saigo, T Konuma, Y Toriniwa, K Miyajima, T Ohta
Nonalcoholic steatohepatitis (NASH) is a current health issue since the disease often leads to hepatocellular carcinoma; however, the pathogenesis of the disease has still not been fully elucidated. In this study, we investigated the pathophysiological changes observed in hepatic lesions in STAM mice, a novel NASH model. STAM mice, high fat-diet (HFD) fed mice, and streptozotocin (STZ) treated mice were prepared, and changes over time, such as biological parameters, mRNA expression, and histopathological findings, were evaluated once animal reached 5, 7, and 10 weeks of age...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28729862/rad51-interacts-with-non-structural-3-protein-of-hepatitis-c-virus-and-regulates-viral-production
#11
Kidong Son, Tram T T Nguyen, Jae-Woong Choi, Long V Pham, Trang T D Luong, Yun-Sook Lim, Soon B Hwang
Hepatitis C virus (HCV) is a leading cause of chronic liver disease affecting over 170 million people worldwide. Chronic infection with HCV progresses to liver fibrosis, cirrhosis, and hepatocellular carcinoma. HCV exploits host cellular factors for viral propagation. To investigate the cellular factors required for HCV propagation, we screened a siRNA library targeting human cell cycle genes using cell culture grown HCV-infected cells. In the present study, we selected and characterized a gene encoding Rad51...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28724908/design-and-discovery-of-novel-monastrol-1-3-5-triazines-as-potent-anti-breast-cancer-agent-via-attenuating-epidermal-growth-factor-receptor-tyrosine-kinase
#12
Jitendra Kumar Srivastava, Girinath G Pillai, Hans Raj Bhat, Amita Verma, Udaya Pratap Singh
A novel series of hybrid analogues of monastrol-1,3,5-triazine were designed and developed via one-pot synthesis using Bi(NO3)3 as a catalyst. Entire compounds were evaluated for their anticancer activity against HeLa (cervical cancer), MCF-7 (breast cancer), HL-60 (Human promyelocytic leukemia), HepG2 (Hepatocellular carcinoma) and MCF 12A (normal epithelial breast cell line) using MTT assay, where they showed highest inhibitory activity against MCF-7. The molecules were also found to be non-toxic to MCF 12A cells...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720429/stable-isotope-based-flux-studies-in-nonalcoholic-fatty-liver-disease
#13
REVIEW
Arthur McCullough, Stephen Previs, Takhar Kasumov
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is associated with the worldwide epidemics of obesity, diabetes and cardiovascular diseases. NAFLD ranges from benign fat accumulation in the liver (steatosis) to non-alcoholic steatohepatitis (NASH), and cirrhosis which can progress to hepatocellular carcinoma and liver failure. Mass spectrometry and magnetic resonance spectroscopy-coupled stable isotope-based flux studies provide new insights into the understanding of NAFLD pathogenesis and the disease progression...
July 15, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28718980/an-endogenous-dna-adduct-as-a-prognostic-biomarker-for-hepatocarcinogenesis-and-its-prevention-by-theaphenon-e-in-mice
#14
Ying Fu, Shana Silverstein, Justine N McCutcheon, Marcin Dyba, Raghu G Nath, Monika Aggarwal, Heidi Coia, Angela Bai, Jishen Pan, Jiji Jiang, Bhaskar Kallakury, Hongkun Wang, Yu-Wen Zhang, Giuseppe Giaccone, Aiwu Ruth He, Fung-Lung Chung
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, mainly because of its poor prognosis. A valid mechanism-based prognostic biomarker is urgently needed. γ-hydroxy-1,N(2) -propanodeoxyguanosine (γ-OHPdG) is an endogenously formed mutagenic DNA adduct derived from lipid peroxidation (LPO). We examined the relationship of γ-OHPdG with hepatocarcinogenesis in two animal models and its potential role as a prognostic biomarker for recurrence in HCC patients. Bioassays were conducted in the Xeroderma pigmentosum group A knockout mice (Xpa(-/-) ), and the diethylnitrosamine (DEN)-injected mice, both prone to HCC development...
July 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28703810/microrna-148a-deficiency-promotes-hepatic-lipid-metabolism-and-hepatocarcinogenesis-in-mice
#15
Li Cheng, Yahui Zhu, Han Han, Qiang Zhang, Kaisa Cui, Hongxing Shen, Jinxiang Zhang, Jun Yan, Edward Prochownik, Youjun Li
miRNAs are involved in many physiologic and disease processes by virtue of degrading specific mRNAs or inhibiting their translation. miR-148a has been implicated in the control of tumor growth and cholesterol and triglyceride homeostasis using in vitro or in vivo gene expression- and silencing-based approaches. Here miR-148a knockout (KO) mice were used to investigate the intrinsic role of miR-148a in liver physiology and hepatocarcinogenesis in mice. miR-148a downregulation was found to be correlated with poor clinical outcomes in hepatocellular carcinoma (HCC) patients...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28693796/regulatory-effects-of-berberine-on-micrornome-in-cancer-and-other-conditions
#16
REVIEW
Seyed Hasan Ayati, Badrieh Fazeli, Amir Abbas Momtazi-Borojeni, Arrigo F G Cicero, Matteo Pirro, Amirhossein Sahebkar
Berberine (BBR) is an isoquinoline alkaloid found in different plant families such as Berberidaceae, Ranunculaceae, and Papaveraceae. BBR is well-known for its anti-inflammatory, lipid-modifying, anticancer, anti-diabetic, antibacterial, antiparasitic and fungicide activities. Multiple pharmacological actions of BBR stem from different molecular targets of this phytochemical. MicroRNAs (miRs) are single-stranded, evolutionary conserved, small non-coding RNA molecules with a length of 19-23 nucleotides that are involved in RNA silencing and post-transcriptional regulation of gene expression through binding to the 3'-untranslated region (3'UTR) of target mRNA...
August 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28680813/silencing-of-fabp1-ameliorates-hepatic-steatosis-inflammation-and-oxidative-stress-in-mice-with-nonalcoholic-fatty-liver-disease
#17
Takako Mukai, Miki Egawa, Tamaki Takeuchi, Hitoshi Yamashita, Tatsuya Kusudo
Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide and has been identified as a risk factor for cirrhosis and hepatocellular carcinoma. However, there is no effective pharmacologic treatment for NAFLD. FABP1 is a liver-specific fatty acid-binding protein (FABP) that plays important roles in intracellular lipid metabolism in the liver. We investigated the effect of repression of FABP1 expression on NAFLD, using adenovirus-mediated silencing of FABP1. FABP1 knockdown in the liver decreased the liver weight and hepatic triglyceride (TG) accumulation...
July 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28668842/diagnostic-value-of-systemic-cholesteryl-ester-free-cholesterol-ratio-in-hepatocellular-carcinoma
#18
Sabrina Krautbauer, Thomas S Weiss, Reiner Wiest, Doris Schacherer, Gerhard Liebisch, Christa Buechler
BACKGROUND: Hepatocellular carcinoma (HCC) most commonly occurs in the setting of liver cirrhosis which is characterized by low serum lipids. We hypothesized that composition of lipoproteins and consequently lipid species ratios are mostly unchanged in patients with cirrhosis compared to controls. This approach may be appropriate to identify lipid ratios altered in HCC irrespective of liver dysfunction. PATIENTS AND METHODS: Lipids were measured in serum of 21 patients with HCC, 41 patients with liver cirrhosis and 22 controls...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28667706/an-autopsy-case-of-non-traumatic-fat-embolism-syndrome
#19
Mai Sakashita, Shingo Sakashita, Akiko Sakata, Noriko Uesugi, Kazunori Ishige, Ichinosuke Hyodo, Masayuki Noguchi
Fat embolism syndrome (FES) occurs after long bone fractures and the symptoms appear 24-72 h after the initial trauma. Fat emboli can affect both the pulmonary and systemic circulation. Apart from the most common type of FES that originates from bone fracture, non-traumatic FES has been also reported. We have experienced an autopsy case of non-traumatic FES. An 81-year-old man with hepatocellular carcinoma associated with alcoholic liver cirrhosis suddenly lost consciousness before transcatheter arterial chemoembolization treatment for his disease and died 5 h after the episode...
June 30, 2017: Pathology International
https://www.readbyqxmd.com/read/28663670/the-plasma-and-serum-metabotyping-of-hepatocellular-carcinoma-in-a-nigerian-and-egyptian-cohort-using-proton-nuclear-magnetic-resonance-spectroscopy
#20
Mohamed I F Shariff, Jin Un Kim, Nimzing G Ladep, Asmaa I Gomaa, Mary M E Crossey, Edith Okeke, Edmund Banwat, Imam Waked, I Jane Cox, Roger Williams, Elaine Holmes, Simon D Taylor-Robinson
BACKGROUND/AIMS: Previous studies have observed disturbances in the (1)H nuclear magnetic resonance (NMR) blood spectral profiles in malignancy. No study has metabotyped serum or plasma of hepatocellular carcinoma (HCC) patients from two diverse populations. We aimed to delineate the HCC patient metabotype from Nigeria (mostly hepatitis B virus infected) and Egypt (mostly hepatitis C virus infected) to explore lipid and energy metabolite alterations that may be independent of disease aetiology, diet and environment...
June 2017: Journal of Clinical and Experimental Hepatology
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