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Hepatocyte proliferation

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https://www.readbyqxmd.com/read/28231052/review-the-role-of-peroxisome-proliferator-activated-receptor-in-the-treatment-of-non-alcoholic-fatty-liver-disease
#1
Xin Sun, Yan Zhang, Meilin Xie
Non-alcoholic fatty liver disease (NAFLD) has been defined as a spectrum of histological abnormalities and is characterized by significant and excessive accumulation of triglycerides in the hepatocytes in patients without alcohol consumption or other diseases. Current studies are targeting new molecular mechanisms that underlie NAFLD and associated metabolic disorders. Many therapeutic targets have been found and used in clinical studies. Peroxisome proliferator-activated receptors (PPARs) are among the potential targets and have been demonstrated to exert a pivotal role in modulation of NAFLD...
March 1, 2017: Acta Pharmaceutica
https://www.readbyqxmd.com/read/28223311/single-tumor-initiating-cells-evade-immune-clearance-by-recruiting-type-ii-macrophages
#2
Xiaocan Guo, Yang Zhao, Huan Yan, Yingcheng Yang, Shuying Shen, Xiaoming Dai, Xinyan Ji, Fubo Ji, Xing-Guo Gong, Li Li, Xueli Bai, Xin-Hua Feng, Tingbo Liang, Junfang Ji, Lei Chen, Hongyang Wang, Bin Zhao
Tumor infiltrated type II (M2) macrophages promote tumorigenesis by suppressing immune clearance, promoting proliferation, and stimulating angiogenesis. Interestingly, macrophages were also found to enrich in small foci of altered hepatocytes containing liver tumor-initiating cells (TICs). However, whether and how TICs specifically recruit macrophages and the function of these macrophages in tumor initiation remain unknown due to technical difficulties. In this study, by generating genetically defined liver TICs, we demonstrate that TICs actively recruit M2 macrophages from as early as the single-cell stage...
February 21, 2017: Genes & Development
https://www.readbyqxmd.com/read/28220523/inflammation-is-independent-of-steatosis-in-a-murine-model-of-steatohepatitis
#3
Wei Wang, Ming-Jiang Xu, Yan Cai, Zhou Zhou, Haixia Cao, Partha Mukhopadhyay, Pal Pacher, Shusen Zheng, Frank J Gonzalez, Bin Gao
Obesity and alcohol consumption synergistically promote steatohepatitis, and neutrophil infiltration is believed to be associated with steatosis. However, the underlying mechanisms remain obscure. Peroxisome proliferator-activated receptor-gamma (PPARγ) plays a complex role in lipid metabolism and inflammation, therefore, the purpose of this study was to dissect its role in regulating steatosis and neutrophil infiltration in a clinically relevant mouse steatohepatitis model of 3-month high-fat diet (HFD) feeding plus a binge of ethanol (HFD -plus-binge ethanol)...
February 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28219158/-experimental-observation-on-the-histopathological-and-ultrastructural-pathology-of-great-gerbils-rhombomys-opimus-in-the-junggar-basin-by-subcutaneous-injecting-of-yersinia-pestis
#4
B Li, Rehemu Azhati, W W Meng, T Luo, B Li, Maituohuti Abulimiti, X H Wang, X Dai, Y J Zhang
Objective: To understand the histopathological and ultrastructural pathology changes of great gerbils in the Junggar Basin to Yersinia pestis infection. Methods: Forty captured great gerbils from the Junggar Basin that tested negative for anti-F1 antibodies were infected. The Y. pestis strain 2504, isolated from a live great gerbil in the natural plague foci of the Junggar Basin in 2005 with a median lethal dose (LD(50)) of <10 CFU/ml, was used in this study. Forty great gerbils were divided into seven infection groups and were subcutaneously infected with 7...
February 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/28217258/antioxidant-effects-of-aqueous-extract-of-salep-on-paraquat-induced-rat-liver-injury
#5
Shekoufeh Atashpour, Hossein Kargar Jahromi, Zahra Kargar Jahromi, Sanaz Zarei
AIM: To evaluate the effects of aqueous extract of Salep on Paraquat-mediated liver injury. METHODS: In this experimental study, 56 adult male Wistar rats were divided randomly to 7 groups as control, sham, and 5 experimental groups. In control group, rats did not receive any substance during experiment. In Sham group, rats were given distilled water according to their body weight and in experimental groups, Paraquat alone and with different doses of Salep aqueous extract (40, 80, 160 and 320 mg/kg) was given intraperitoneal daily for 14 d...
February 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28216578/tumor-microenvironment-a-paradigm-in-hepatocellular-carcinoma-progression-and-therapy
#6
REVIEW
Maryam Tahmasebi Birgani, Vinicio Carloni
Hepatocellular carcinoma (HCC) is among the most lethal and prevalent cancers in the human population. Different etiological factors such as hepatitis B and C virus, alcohol and diabetes cause liver injury followed by inflammation, necrosis and hepatocytes proliferation. Continuous cycles of this destructive-regenerative process culminates in liver cirrhosis which is characterized by regenerating nodules that progress to dysplastic nodules and ultimately HCC. Despite its significance, there is only an elemental understanding of the pathogenetic mechanisms, and there are only limited therapeutic options...
February 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28215170/derivatives-of-6-nitrobenzimidazole-inhibit-fructose-mediated-protein-glycation-and-intracellular-reactive-oxygen-species-production
#7
Humera Jahan, Muhammad Iqbal Choudhary, Zarbad Shah, Khalid M Khan, Atta-Ur-Rahman
BACKGROUND: Benzimidazoles are important pharmacophores in drug discovery. Several of them are currently used drugs, such as flubendazole, omeprazole, and astemizole for the treatment of anthelmintic, antiulcerative, and antihistaminic diseases, respectively. OBJECTIVES: The aim of the current study was to study the antiglycation activity of nitrobenzimidazole derivatives against fructose-mediated human serum albumin (HSA) glycation. The study was also aimed to investigate effects of newly identified antiglycation inhibitors on AGEs-induced intracellular reactive oxygen species production, and associated impaired proliferation of the hepatocytes...
February 16, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28214859/farnesoid-x-receptor-in-mice-prevents-severe-liver-immunopathology-during-lymphocytic-choriomeningitis-virus-infection
#8
Nadine Honke, Namir Shaabani, Cornelia Hardt, Caroline Krings, Dieter Häussinger, Philipp A Lang, Karl S Lang, Verena Keitel
BACKGROUND: Bile acids (BAs) are steroid molecules that are synthesized in the liver. In addition to their important role as a surfactant in solubilizing lipids and promoting the absorption of lipids in the gastrointestinal tract, they act as inflammagens. The role of BAs and their receptor farnesoid X receptor (FXR) during viral infection has not been studied in detail. METHODS: By using FXR-deficient mice, we investigated the role of bile acid receptor FXR during infection with lymphocytic choriomeningitis virus (LCMV)...
January 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214206/involvement-of-prolyl-isomerase-pin1-in-the-cell-cycle-progression-and-proliferation-of-hepatic-oval-cells
#9
Prabodh Risal, Nirajan Shrestha, Lokendra Chand, Karl G Sylvester, Yeon Jun Jeong
Liver regenerates remarkably after toxic injury or surgical resection. In the case of failure of resident hepatocytes to restore loss, repopulation is carried out by induction, proliferation, and differentiation of the progenitor cell. Although, some signaling pathways have been verified to contribute oval cell-mediated liver regeneration, role of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1(Pin1) in the oval cells proliferation is unknown. In the present study, we evaluate the role of Pin1 in oval cells proliferation...
January 18, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28213130/dipeptidyl-peptidase-4-impairs-insulin-signaling-and-promotes-lipid-accumulation-in-hepatocytes
#10
Kerstin Rufinatscha, Bernhard Radlinger, Jochen Dobner, Sabrina Folie, Claudia Bon, Elisabeth Profanter, Claudia Ress, Karin Salzmann, Gabriele Staudacher, Herbert Tilg, Susanne Kaser
Dipeptidyl-peptidase 4 [DPP-4) has evolved into an important target in diabetes therapy due to its role in incretin hormone metabolism. In contrast to its systemic effects, cellular functions of membranous DPP-4 are less clear. Here we studied the role of DPP-4 in hepatic energy metabolism. In order to distinguish systemic from cellular effects we established a cell culture model of DPP-4 knockdown in human hepatoma cell line HepG2. DPP-4 suppression was associated with increased basal glycogen content due to enhanced insulin signaling as shown by increased phosphorylation of insulin-receptor substrate 1 (IRS-1), protein kinase B/Akt and mitogen-activated protein kinases (MAPK)/ERK, respectively...
February 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28209758/atorvastatin-decreases-hbx-induced-phospho-akt-in-hepatocytes-via-p2x-receptors
#11
Aram Ghalali, Javier Martin-Renedo, Johan Hogberg, Ulla Stenius
: Hepatocellular carcinoma (HCC) is rated as the fifth most common malignancy and third in cancer related deaths worldwide. Statins, HMG-CoA reductase inhibitors, are potent cholesterol lowering drugs and recent epidemiological evidence suggests that statins prevent aggressive HCC development. Previous experiments revealed that statins downregulate phosphorylated Akt (pAkt). Here, it is demonstrated that atorvastatin decreases nuclear pAkt levels in pancreatic and lung cancer cell lines within minutes and this rapid effect is mediated by the purinergic P2X receptors...
February 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28209522/the-role-of-alkaline-phosphatase-in-intracellular-lipid-accumulation-in-the-human-hepatocarcinoma-cell-line-hepg2
#12
George M Chirambo, Chantal van Niekerk, Nigel J Crowther
Inhibition of tissue non-specific alkaline phosphatase (TNALP) decreases intracellular lipid accumulation in human preadipocytes and the murine preadipocyte cell line, 3T3-L1. Therefore, the current study was performed to determine if TNALP is required for intracellular lipid deposition in the human hepatocyte cell line, HepG2. Intracellular lipid accumulation, TNALP activity and peroxisome proliferator activated receptor (PPAR) γ gene expression were measured in HepG2 and 3T3-L1 cells in the presence and absence of the TNALP inhibitors levamisole and histidine...
February 13, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28197212/herbal-compound-jiedu-huayu-reduces-liver-injury-in-rats-via-regulation-of-il-2-tlr4-and-pcna-expression-levels
#13
Minggang Wang, Qinglan Shi, Rongzhen Zhang, Hua Qiu, Dewen Mao, Fuli Long
Aim of the Study. To investigate the preventative effects of Jiedu Huayu (JDHY) on D-galactosamine (D-GalN) and lipopolysaccharide-induced acute liver failure (ALF) and to evaluate the possible mechanisms of action. Materials and Methods. ALF was induced in Wistar rats by administrating D-GalN (900 mg/kg) and lipopolysaccharide (10 μg/kg). After treatment with JDHY granules, the levels of blood alanine aminotransferase, aspartate aminotransferase, total bilirubin, and prothrombin time were determined. Proliferating cell nuclear antigen was detected by immunohistochemistry staining...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28196117/the-transcriptional-activity-of-hepatocyte-nuclear-factor-4-alpha-is-inhibited-via-phosphorylation-by-erk1-2
#14
Borbála Vető, Dóra Bojcsuk, Caroline Bacquet, Judit Kiss, Szabolcs Sipeki, Ludovic Martin, László Buday, Bálint L Bálint, Tamás Arányi
Hepatocyte nuclear factor 4 alpha (HNF4α) nuclear receptor is a master regulator of hepatocyte development, nutrient transport and metabolism. HNF4α is regulated both at the transcriptional and post-transcriptional levels by different mechanisms. Several kinases (PKA, PKC, AMPK) were shown to phosphorylate and decrease the activity of HNF4α. Activation of the ERK1/2 signalling pathway, inducing proliferation and survival, inhibits the expression of HNF4α. However, based on our previous results we hypothesized that HNF4α is also regulated at the post-transcriptional level by ERK1/2...
2017: PloS One
https://www.readbyqxmd.com/read/28196027/mk2461-a-multitargeted-kinase-inhibitor-suppresses-the-progression-of-pancreatic-cancer-by-disrupting-the-interaction-between-pancreatic-cancer-cells-and-stellate-cells
#15
Koetsu Inoue, Hideo Ohtsuka, Masanori Tachikawa, Fuyuhiko Motoi, Masahiro Shijo, Daisuke Douchi, Shuhei Kawasaki, Kei Kawaguchi, Kunihiro Masuda, Koji Fukase, Takeshi Naitoh, Yu Katayose, Shinichi Egawa, Michiaki Unno, Tetsuya Terasaki
OBJECTIVES: Platelet-derived growth factor receptor beta (PDGFRβ) and hepatocyte growth factor receptor (MET) expressed on pancreatic stellate cells (PSCs) are suggested as important components modulating the interactions between pancreatic cancer cells (PCCs) and PSCs. The objective of this study is to clarify the effect of MK2461, a multikinase inhibitor targeting MET and PDGFRβ, on the interaction between PCCs and PSCs. METHODS: In this study, we profiled the expression of receptor tyrosine kinases (including PDGFRβ and MET) in pancreatic cancer with quantitative targeted absolute proteomics using liquid chromatography tandem mass spectrometry...
February 14, 2017: Pancreas
https://www.readbyqxmd.com/read/28195307/effect-of-obeticholic-acid-on-liver-regeneration-following-portal-vein-embolization-in-an-experimental-model
#16
P B Olthof, F Huisman, F G Schaap, K P van Lienden, R J Bennink, R F van Golen, M Heger, J Verheij, P L Jansen, S W Olde Damink, T M van Gulik
BACKGROUND: The bile salt-activated transcription factor farnesoid X receptor (FXR) is a key mediator of proliferative bile salt signalling, which is assumed to play a role in the early phase of compensatory liver growth. The aim of this study was to evaluate the effect of a potent FXR agonist (obeticholic acid, OCA) on liver growth following portal vein embolization (PVE). METHODS: Rabbits were allocated to receive daily oral gavage with OCA (10 mg/kg) or vehicle (control group) starting 7 days before PVE (n = 18 per group), and continued until 7 days after PVE...
February 13, 2017: British Journal of Surgery
https://www.readbyqxmd.com/read/28195035/pre-s2-mutant-induced-mammalian-target-of-rapamycin-signal-pathways-as-potential-therapeutic-targets-for-hepatitis-b-virus-associated-hepatocellular-carcinoma
#17
Chiao-Fang Teng, Han-Chieh Wu, Woei-Cherng Shyu, Long-Bin Jeng, Ih-Jen Su
Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Pre-S2 mutant represents an HBV oncoprotein that is accumulated in the endoplasmic reticulum (ER) and manifests as type II ground glass hepatocytes (GGHs). Pre-S2 mutant can induce ER stress and initiate multiple ER stress-dependent or -independent cellular signal pathways, leading to growth advantage of type II GGH. Importantly, the mammalian target of rapamycin (mTOR) signal pathways are consistently activated throughout the liver tumorigenesis in pre-S2 mutant transgenic mice and in human HCC tissues, leading to hepatocyte proliferation, metabolic disorders, and HCC tumorigenesis...
February 14, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28193226/hair-growth-promoting-effect-of-geranium-sibiricum-extract-in-human-dermal-papilla-cells-and-c57bl-6-mice
#18
William A Boisvert, Miri Yu, Youngbin Choi, Gi Hee Jeong, Yi-Lin Zhang, Sunghun Cho, Changsun Choi, Sanghyun Lee, Bog-Hieu Lee
BACKGROUND: Geranium sibiricum L. has been used as a medicinal plant to treat diarrhea, bacterial infection, and cancer in Bulgaria, Peru, and Korea. However, its hair growth-promoting effect was not investigated so far. This study examined the effects of Geranium sibiricum L. extract (GSE) on hair growth, using in vitro and in vivo models. METHODS: Antioxidant, proliferation and migration assay of GSE was performed with human dermal papilla cells (hDPCs). Hair-growth promoting effect was measured in animal model...
February 13, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28190927/hepatocellular-adenoma-with-severe-fatty-change-in-a-male-spontaneously-diabetic-torii-rat
#19
Eriko Taniai-Riya, Katsuhiro Miyajima, Kochi Kakimoto, Takeshi Ohta, Yuzo Yasui, Yusuke Kemmochi, Akiko Anagawa-Nakamura, Kaoru Toyoda, Akemi Takahashi, Toshiyuki Shoda
The Spontaneously Diabetic Torii (SDT) rat is a rat model of nonobese type 2 diabetes mellitus, and hepatocellular adenomas have not been reported in this model. We report a hepatocellular adenoma with severe fatty change in a male 42-week-old SDT rat fed a high-fat diet. At necropsy, the animal had a whitish nodular mass of approximately 2 cm in diameter in the right medial lobe. Histologically, the mass was well demarcated from the surrounding tissues, slightly compressing the adjacent hepatic parenchyma and widely compartmented by fibrous connective tissues...
January 2017: Journal of Toxicologic Pathology
https://www.readbyqxmd.com/read/28187190/widespread-gli-expression-but-limited-canonical-hedgehog-signaling-restricted-to-the-ductular-reaction-in-human-chronic-liver-disease
#20
Candice Alexandra Grzelak, Nicholas David Sigglekow, Janina Elke Eleonore Tirnitz-Parker, Elizabeth Jane Hamson, Alessandra Warren, Bharvi Maneck, Jinbiao Chen, Bramilla Patkunanathan, Jade Boland, Robert Cheng, Nicholas Adam Shackel, Devanshi Seth, David Geoffrey Bowen, Luciano Gastón Martelotto, D Neil Watkins, Geoffrey William McCaughan
Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations...
2017: PloS One
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