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Hepatocyte proliferation

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https://www.readbyqxmd.com/read/28342980/muscarinic-receptor-mediated-signaling-pathways-in-hepatocytes-from-ccl4-induced-liver-fibrotic-rat
#1
Lin Luo, Chenghao Xi, Tingting Xu, Gaoshan Zhang, E Qun, Wei Zhang
The pathological changes of parasympathetic nerves are considered as an independent prognostic factor of the survival rate for patients with chronic liver disease. The non-selective muscarinic acetylcholine receptors (mAchR) agonists and antagonists can affect the proliferation of hepatocytes, but little is known about the role of mAChR in hepatocytes and hepatic fibrosis and the signaling pathway of this receptor in regulation of hepatocytes remains elusive. Here, 3ml/kg 40% carbon tetrachloride (CCL4) was given to induce hepatic fibrosis in rats and the hepatocytes were isolated to investigate the expression of mAchR and the cell signaling pathways which were involved in...
March 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28337887/up-regulation-of-mir-888-5p-in-hepatocellular-carcinoma-cell-lines-and-its-effect-on-malignant-characteristics-of-cells
#2
E Hao, J Yu, S Xie, W Zhang, G Wang
MicroRNA (miRNA) expression has been linked to the molecular pathogenesis of hepatocellular carcinoma (HCC). The aberrant expression of miRNA is involved in the processes of tumorigenesis and cancer progression. According to the latest research, miR-888-5p is associated with strong cancer-promoting effect. For instance, miR-888-5p is up-regulated in prostate cancer and breast cancer. Nevertheless, the role of miR-888-5p in HCC has not been investigated to date. In this study, we found that miR-888-5p levels in four HCC cell lines (SMMC7721, HepG2, Huh-7 and Bel7402) were significantly up-regulated compared with human hepatocyte cell line (HHL-5)...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28336956/preclinical-development-of-a-humanized-neutralizing-antibody-targeting-hgf
#3
Hyori Kim, Sung Hee Hong, Jung Yong Kim, In-Chull Kim, Young-Whan Park, Song-Jae Lee, Seong-Won Song, Jung Ju Kim, Gunwoo Park, Tae Min Kim, Yun-Hee Kim, Jong Bae Park, Junho Chung, In-Hoo Kim
Hepatocyte growth factor (HGF) and its receptor, cMET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers. We therefore examined the anti-tumor activity of the humanized monoclonal anti-HGF antibody, YYB-101, in nude mice bearing human glioblastoma xenografts as a single agent or in combination with temozolomide. HGF neutralization, The extracellular signal-related kinases 1 and 2 (ERK1/2) phosphorylation, and HGF-induced scattering were assessed in HGF-expressing cell lines treated with YYB-101...
March 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28336518/bmp-9-interferes-with-liver-regeneration-and-promotes-liver-fibrosis
#4
Katja Breitkopf-Heinlein, Christoph Meyer, Courtney König, Haristi Gaitantzi, Annalisa Addante, Maria Thomas, Eliza Wiercinska, Chen Cai, Qi Li, Fengqi Wan, Claus Hellerbrand, Nektarios A Valous, Maximilian Hahnel, Christian Ehlting, Johannes G Bode, Stephanie Müller-Bohl, Ursula Klingmüller, Jutta Altenöder, Iryna Ilkavets, Marie-José Goumans, Lukas J A C Hawinkels, Se-Jin Lee, Matthias Wieland, Carolin Mogler, Matthias P Ebert, Blanca Herrera, Hellmut Augustin, Aránzazu Sánchez, Steven Dooley, Peter Ten Dijke
OBJECTIVE: Bone morphogenetic protein (BMP)-9, a member of the transforming growth factor-β family of cytokines, is constitutively produced in the liver. Systemic levels act on many organs and tissues including bone and endothelium, but little is known about its hepatic functions in health and disease. DESIGN: Levels of BMP-9 and its receptors were analysed in primary liver cells. Direct effects of BMP-9 on hepatic stellate cells (HSCs) and hepatocytes were studied in vitro, and the role of BMP-9 was examined in acute and chronic liver injury models in mice...
March 23, 2017: Gut
https://www.readbyqxmd.com/read/28332364/potential-antitumor-activity-of-sim-89-in-non-small-cell-lung-cancer-cells
#5
Jun Pei, Tianqing Chu, Minhua Shao, Jiajun Teng, Huifang Sha, Aiqing Gu, Rong Li, Jialin Qian, Weifeng Mao, Ying Li, Baohui Han
PURPOSE: c-Met and its ligand, hepatocyte growth factor (HGF), play a critical role in oncogenesis and metastatic progression. The aim of this study was to identify inhibited enzymogram and to test the antitumor activity of SIM-89 (a c-Met receptor tyrosine kinase inhibitor) in non-small cell lung cancer. MATERIALS AND METHODS: Z'-LYTE kinase assay was employed to screen the kinase enzymogram, and mechanism of action (MOA) analysis was used to identify the inhibited kinases...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28331449/cyclin-d1-in-the-liver-role-of-noncanonical-signaling-in-liver-steatosis-and-hormone-regulation
#6
Kelley G Núñez, Janet Gonzalez-Rosario, Paul T Thevenot, Ari J Cohen
BACKGROUND: Cyclin D1 is an important protein for cell cycle progression; however, functions independent of the cell cycle have been described in the liver. Cyclin D1 is also involved in DNA repair, is overexpressed in many cancers, and functions as a proto-oncogene. The lesser-known roles of Cyclin D1, specifically in hepatocytes, impact liver steatosis and hormone regulation in the liver. METHODS: A comprehensive search of PubMed was conducted using the keywords Cyclin D1, steatosis, lipogenesis, and liver transplantation...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28331445/negligible-oval-cell-proliferation-following-ischemia-reperfusion-injury-with-and-without-partial-hepatectomy
#7
Ek Khoon Tan, Maureen Shuh, Heather Francois-Vaughan, Jennifer A Sanders, Ari J Cohen
BACKGROUND: Hepatic oval cells proliferate to replace hepatocytes and restore liver function when hepatocyte proliferation is compromised or inadequate. Exposure to chemical carcinogens, severe liver steatosis, and partial hepatectomy has been used in animal models to demonstrate the role of oval cells in liver regeneration. Ischemia-reperfusion injury (IRI) causes hepatocellular damage and death in the absence of confounding chemical toxicity; however, oval cell induction by IRI has not been demonstrated in vivo...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28330992/localized-hepatic-lobular-regeneration-by-central-vein-associated-lineage-restricted-progenitors
#8
Jonathan M Tsai, Pang Wei Koh, Ania Stefanska, Liujing Xing, Graham G Walmsley, Nicolas Poux, Irving L Weissman, Yuval Rinkevich
The regeneration of organ morphology and function following tissue loss is critical to restore normal physiology, yet few cases are documented in mammalian postnatal life. Partial hepatectomy of the adult mammalian liver activates compensatory hepatocyte hypertrophy and cell division across remaining lobes, resulting in restitution of organ mass but with permanent alteration of architecture. Here, we identify a time window in early postnatal life wherein partial amputation culminates in a localized regeneration instead of global hypertrophy and proliferation...
March 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28330461/impaired-liver-regeneration-is-associated-with-reduced-cyclin-b1-in-natural-killer-t-cell-deficient-mice
#9
Ami Ben Ya'acov, Hadar Meir, Lydia Zolotaryova, Yaron Ilan, Eyal Shteyer
BACKGROUND: It has been shown that the proportion of natural killer T cells is markedly elevated during liver regeneration and their activation under different conditions can modulate this process. As natural killer T cells and liver injury are central in liver regeneration, elucidating their role is important. METHODS: The aim of the current study is to explore the role of natural killer T cells in impaired liver regeneration. Concanvalin A was injected 4 days before partial hepatectomy to natural killer T cells- deficient mice or to anti CD1d1-treated mice...
March 23, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28330111/effect-of-stat3-inhibitor-in-chronic-myeloid-leukemia-associated-signaling-pathway-a-mathematical-modeling-simulation-and-systems-biology-study
#10
Himansu Kumar, Swapnil Tichkule, Utkarsh Raj, Saurabh Gupta, Swati Srivastava, Pritish Kumar Varadwaj
Chronic myeloid leukemia (CML) is a hematopoietic stem-cell disorder which proliferates due to abnormal growth of basophil cells. Several proangiogenic molecules have been reported to be associated in CML progression, including the hepatocyte growth factor (HGF). However, detail mechanism about the cellular distribution and function of HGF in CML is yet to be revealed. The proliferation of hematopoietic cells are regulated by some of the growth factors like interleukin 3 (IL-3), IL-6, erythropoietin, thrombopoietin, etc...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28323980/hypoxia-inducible-lipid-droplet-associated-hilpda-is-not-a-direct-physiological-regulator-of-lipolysis-in-adipose-tissue
#11
Wieneke Dijk, Frits Mattijssen, Montserrat de la Rosa Rodriguez, Angel Loza Valdes, Anne Loft, Susanne Mandrup, Eric Kalkhoven, Ling Qi, Jan Willem Borst, Sander Kersten
Triglycerides are stored in specialized organelles called lipid droplets. Numerous proteins have been shown to be physically associated with lipid droplets and govern their function. Previously, hypoxia-inducible lipid droplet-associated (HILPDA) was localized to lipid droplets and was suggested to inhibit triglyceride lipolysis in hepatocytes. We confirm the partial localization of HILPDA to lipid droplets and show that HILPDA is highly abundant in adipose tissue, where its expression is controlled by the peroxisome proliferator-activated receptor γ and by β-adrenergic stimulation...
March 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323103/cr-vi-induces-cytotoxicity-in-vitro-through-activation-of-ros-mediated-endoplasmic-reticulum-stress-and-mitochondrial-dysfunction-via-the-pi3k-akt-signaling-pathway
#12
Yujing Zhang, Fang Xiao, Xinmin Liu, Kaihua Liu, Xiaoxin Zhou, Caigao Zhong
The occupational and environmental toxicant hexavalent chromium [Cr(VI)] can cause severe damage to the liver; however, the exact mechanisms associated with its toxicity have not been thoroughly demonstrated. In the present study, the underlying mechanisms of Cr(VI)-induced hepatotoxicity were investigated. Our results showed that Cr(VI) inhibited the growth and proliferation of L-02 hepatocytes. Further study revealed that Cr(VI) significantly induced S-phase cell cycle arrest and apoptosis accompanying with the overproduction of reactive oxygen species (ROS)...
March 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28322831/chemical-inhibitors-of-c-met-receptor-tyrosine-kinase-stimulate-osteoblast-differentiation-and-bone-regeneration
#13
Jung-Woo Kim, Mi Nam Lee, Byung-Chul Jeong, Sin-Hye Oh, Min-Suk Kook, Jeong-Tae Koh
The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), have been recently introduced to negatively regulate bone morphogenetic protein (BMP)-induced osteogenesis. However, the effect of chemical inhibitors of c-Met receptor on osteoblast differentiation process has not been examined, especially the applicability of c-Met chemical inhibitors on in vivo bone regeneration. In this study, we demonstrated that chemical inhibitors of c-Met receptor tyrosine kinase, SYN1143 and SGX523, could potentiate the differentiation of precursor cells to osteoblasts and stimulate regeneration in calvarial bone defects of mice...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28321271/parkin-in-cancer-mitophagy-related-unrelated-tasks
#14
EDITORIAL
Nabil Eid, Yoichi Kondo
Dysfunctional mitochondria may produce excessive reactive oxygen species, thus inducing DNA damage, which may be oncogenic if not repaired. As a major role of the PINK1-Parkin pathway involves selective autophagic clearance of damaged mitochondria via a process termed mitophagy, Parkin-mediated mitophagy may be a tumor-suppressive mechanism. As an alternative mechanism for tumor inhibition beyond mitophagy, Parkin has been reported to have other oncosuppressive functions such as DNA repair, negative regulation of cell proliferation and stimulation of p53 tumor suppressor function...
March 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28320485/mesenchymal-stem-cells-increase-expression-of-heme-oxygenase-1-leading-to-anti-inflammatory-activity-in-treatment-of-acute-liver-failure
#15
Zhi-Heng Zhang, Wei Zhu, Hao-Zhen Ren, Xin Zhao, Shuai Wang, Hu-Cheng Ma, Xiao-Lei Shi
BACKGROUND: Mesenchymal stem cells (MSCs) have been studied for the treatment of acute liver failure (ALF) for several years. MSCs may exert their effect via complex paracrine mechanisms. Heme oxygenase (HO) 1, a rate-limiting enzyme in heme metabolism, exerts a wide range of anti-inflammatory, anti-apoptotic and immunoregulatory effects in a variety of diseases. However, the relationship between MSCs and HO-1 in the treatment of ALF is still unclear. We investigated the preventive and therapeutic potential of intravenously administered BMSCs...
March 20, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28320463/hyaluronan-coating-improves-liver-engraftment-of-transplanted-human-biliary-tree-stem-progenitor-cells
#16
Lorenzo Nevi, Guido Carpino, Daniele Costantini, Vincenzo Cardinale, Olga Riccioni, Sabina Di Matteo, Fabio Melandro, Pasquale Bartolomeo Berloco, Lola Reid, Eugenio Gaudio, Domenico Alvaro
BACKGROUND: Cell therapy of liver diseases with human biliary tree stem cells (hBTSCs) is biased by low engraftment efficiency. Coating the hBTSCs with hyaluronans (HAs), the primary constituents of all stem cell niches, could facilitate cell survival, proliferation, and, specifically, liver engraftment given that HAs are cleared selectively by the liver. METHODS: We developed a fast and easy method to coat hBTSCs with HA and assessed the effects of HA-coating on cell properties in vitro and in vivo...
March 20, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28314274/increased-hgf-expression-induces-resistance-to-c-met-tyrosine-kinase-inhibitors-in-gastric-cancer
#17
So Yeong Ahn, Jin Kim, Min A Kim, Jiwoon Choi, Woo Ho Kim
BACKGROUND: Increased expression of hepatocyte growth factor (HGF) and MET proto-oncogene (c-MET) is associated with poor prognosis in various cancer types. Recently, it was reported that the expression of HGF induces resistance to tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor, human epidermal receptor receptor 2, and b-raf proto-oncogene. Here, we investigated the effects of HGF overexpression in gastric cancer cells in the absence or presence of c-MET TKIs...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28301981/alterations-of-hepatocyte-function-with-free-radical-generators-and-reparation-or-prevention-with-coffee-polyphenols
#18
Amel Saidi Merzouk, Merzouk Hafida, Amel Medjdoub, Bouchra Loukidi, Sabri Cherrak, Sid Ahmed Merzouk, Mourad Elhabiri
Liver diseases are linked in the majority of cases to oxidative stress that antioxidants could neutralize with reducing liver injury. Chlorogenic acid, a coffee polyphenol, possesses antioxidant prosperities. The aim of this study was to evaluate in vitro preventive and corrective effects of cholorogenic acid in hepatocyte toxicity induced by free radicals. Hepatocytes were isolated from adult male Wistar rats. To determine corrective effects and reparation, cells were first exposed to two free radical generators (Hydrogen peroxide/Iron sulfate for hydroxyl radical formation, and Phenazine methosulfate/Nicotinamide adenine dinucleotide for superoxide anion formation) for 12H and thereafter treated by chlorogenic acid (1 and 10 µM final concentration) for another 12H...
March 16, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28297588/oncostatin-m-preconditioned-mesenchymal-stem-cells-alleviate-bleomycin-induced-pulmonary-fibrosis-through-paracrine-effects-of-the-hepatocyte-growth-factor
#19
Ying-Wei Lan, Si-Min Theng, Tsung-Teng Huang, Kong-Bung Choo, Chuan-Mu Chen, Han-Pin Kuo, Kowit-Yu Chong
Mesenchymal stem cells (MSCs) are widely considered for treatment of pulmonary fibrosis based on the anti-inflammatory, antifibrotic, antiapoptotic, and regenerative properties of the cells. Recently, elevated levels of oncostatin M (OSM) have been reported in the bronchoalveolar lavage fluid of a pulmonary fibrosis animal model and in patients. In this work, we aimed to prolong engrafted MSC survival and to enhance the effectiveness of pulmonary fibrosis transplantation therapy by using OSM-preconditioned MSCs...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28294470/exome-sequencing-deciphers-a-germline-met-mutation-in-familial-epidermal-growth-factor-receptor-mutant-lung-cancer
#20
Naoki Tode, Toshiaki Kikuchi, Tomohiro Sakakibara, Taizou Hirano, Akira Inoue, Shinya Ohkouchi, Tsutomu Tamada, Tatsuma Okazaki, Akira Koarai, Hisatoshi Sugiura, Tetsuya Niihori, Yoko Aoki, Keiko Nakayama, Kunio Matsumoto, Yoichi Matsubara, Masayuki Yamamoto, Akira Watanabe, Toshihiro Nukiwa, Masakazu Ichinose
Lung cancer accompanied by somatic activating mutations in the epidermal growth factor receptor (EGFR) gene, which is associated with a significant clinical response to the targeted therapy, is frequently found in never-smoking Asian women with adenocarcinoma. Although this implies genetic factors underlying the carcinogenesis, the etiology remains unclear. To gain insight into the pathogenic mechanisms, we sequenced the exomes in the peripheral-blood DNA from six siblings, four affected and two unaffected siblings, of a kindred with familial EGFR-mutant lung adenocarcinoma...
March 13, 2017: Cancer Science
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