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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
#1
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/28329705/sensing-of-bacterial-cyclic-dinucleotides-by-the-oxidoreductase-recon-promotes-nf-%C3%AE%C2%BAb-activation-and-shapes-a-proinflammatory-antibacterial-state
#2
Adelle P McFarland, Shukun Luo, Fariha Ahmed-Qadri, Meghan Zuck, Elizabeth F Thayer, Young Ah Goo, Kevin Hybiske, Liang Tong, Joshua J Woodward
Bacterial and host cyclic dinucleotides (cdNs) mediate cytosolic immune responses through the STING signaling pathway, although evidence suggests that alternative pathways exist. We used cdN-conjugated beads to biochemically isolate host receptors for bacterial cdNs, and we identified the oxidoreductase RECON. High-affinity cdN binding inhibited RECON enzyme activity by simultaneously blocking the substrate and cosubstrate sites, as revealed by structural analyses. During bacterial infection of macrophages, RECON antagonized STING activation by acting as a molecular sink for cdNs...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28328977/jmjd3-aids-in-reprogramming-of-bone-marrow-progenitor-cells-to-hepatic-phenotype-through-epigenetic-activation-of-hepatic-transcription-factors
#3
Veena Kochat, Zaffar Equbal, Prakash Baligar, Vikash Kumar, Madhulika Srivastava, Asok Mukhopadhyay
The strictly regulated unidirectional differentiation program in some somatic stem/progenitor cells has been found to be modified in the ectopic site (tissue) undergoing regeneration. In these cases, the lineage barrier is crossed by either heterotypic cell fusion or direct differentiation. Though studies have shown the role of coordinated genetic and epigenetic mechanisms in cellular development and differentiation, how the lineage fate of adult bone marrow progenitor cells (BMPCs) is reprogrammed during liver regeneration and whether this lineage switch is stably maintained are not clearly understood...
2017: PloS One
https://www.readbyqxmd.com/read/28327528/anti-obesity-effect-of-bombus-ignitus-queen-glycosaminoglycans-in-rats-on-a-high-fat-diet
#4
Mi Young Ahn, Ban Ji Kim, Ha Jeong Kim, Hyung Joo Yoon, Sang Duck Jee, Jae Sam Hwang, Kun-Koo Park
The mechanism of functional insect glycosaminoglycan (GAG) on obesity caused a high fat diet has not yet been elucidated. Therefore, insect glycosaminoglycans derived from Isaria sinclairii, Bombus ignitus (a type of bumblebee) queen, and Gryllus bimaculatus were purified and investigated as a potential functional food. 14-week old male Wistar rats were fed a high-fat diet (HFD) for 6 weeks. There were five groups that received daily intraperitoneal administration of phosphate buffered saline (PBS, control), GbG (GAG from Gryllus bimaculatus) 10 mg/kg, ISG (GAG from Isaria sinclairii) 10 mg/kg, IQG (GAG from Bombus ignites) 10 mg/kg, or Pravastatin (2 mg/kg)...
March 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28327356/type-2-inositol-trisphosphate-receptor-gene-expression-in-hepatocytes-is-regulated-by-cyclic-amp
#5
Emma Kruglov, M Ananthanarayanan, Pedro Sousa, Jittima Weerachayaphorn, Mateus T Guerra, Michael H Nathanson
The type 2 inositol 1,4,5-trisphosphate receptor (IP3R2) is the principal intracellular Ca(2+) release channel in hepatocytes, and so is important for bile secretion and other functions. IP3R2 activity is regulated in part by post-translational modifications but little is known about transcriptional regulation of its expression. We found that both IP3R2 mRNA and protein levels in liver were increased during fasting. Treatment of hepatocytes with forskolin or 8-CPT-cAMP also increased IP3R2, and this was reduced by actinomycin D...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28325853/deletion-of-macrophage-mineralocorticoid-receptor-protects-hepatic-steatosis-and-insulin-resistance-through-er%C3%AE-hgf-met-pathway
#6
Yu-Yao Zhang, Chao Li, Gao-Feng Yao, Lin-Juan Du, Yuan Liu, Xiao-Jun Zheng, Shuai Yan, Jian-Yong Sun, Yan Liu, Ming-Zhu Liu, Xiaoran Zhang, Gang Wei, Wenxin Tong, Xiaobei Chen, Yong Wu, Shuyang Sun, Suling Liu, Qiurong Ding, Ying Yu, Huiyong Yin, Sheng-Zhong Duan
Although the importance of macrophages in nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) has been recognized, it remains elusive how macrophages impact hepatocytes. Mineralocorticoid receptor (MR) has been implied to play important roles in NAFLD and T2DM. However, cellular and molecular mechanisms are largely unknown. Here we report that myeloid MR knockout (MRKO) improves glucose intolerance, insulin resistance, and hepatic steatosis in obese mice. Estrogen signaling is sufficient and necessary for such improvements...
March 21, 2017: Diabetes
https://www.readbyqxmd.com/read/28325141/effect-of-intranasal-administration-of-galanin-like-peptide-galp-on-body-weight-and-hepatic-lipids-accumulation-in-mice-with-diet-induced-obesity
#7
Satoshi Hirako, Nobuhiro Wada, Haruaki Kageyama, Fumiko Takenoya, Hyounju Kim, Yuzuru Iizuka, Akiyo Matsumoto, Mai Okabe, Seiji Shioda
Galanin-like peptide (GALP) is a neuropeptide involved in the regulation of food intake behavior, body weight and energy metabolism. In previous studies, we demonstrated that the intranasal administration of GALP has weight loss effects, although the mechanism of this action was not clarified. The aim of this study was to demonstrate the functional significance of GALP on lipid metabolism in the liver. Mice were fed a high fat diet to cause diet-induced obesity (DIO) and then administered GALP intranasally for 2 weeks (experimental), or vehicle (control)...
March 20, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28323980/hypoxia-inducible-lipid-droplet-associated-hilpda-is-not-a-direct-physiological-regulator-of-lipolysis-in-adipose-tissue
#8
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/28323964/dysregulated-autophagy-in-hepatocytes-promotes-bisphenol-a-bpa-induced-hepatic-lipid-accumulation-in-male-mice
#9
Shumin Yang, Ting Li, Aipin Zhang, Rufei Gao, Chuan Peng, Lulu Liu, Qingfeng Cheng, Mei Mei, Ying Song, Xiaojiao Xiang, Chaodong Wu, Xiaoqiu Xiao, Qifu Li
Context: Accumulating evidence suggests that bisphenol A (BPA) exposure is associated with nonalcoholic fatty liver disease. Disruption of autophagy causes lipid accumulation in hepatocytes. Whether and how BPA regulates autophagy remains to be explored. Objective: We investigated the effect of BPA on autophagy in hepatocytes and examined the influence of BPA-regulated autophagy on hepatic lipid accumulation. Design: Male CD1 mice were treated with BPA for eight weeks, followed by histological and biochemical evaluation of liver lipids and autophagy...
February 21, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323660/impact-of-rare-variants-in-autosomal-dominant-hypercholesterolemia-causing-genes
#10
Sebastiano Calandra, Patrizia Tarugi, Stefano Bertolini
PURPOSE OF REVIEW: The systematic analysis of the major candidate genes in autosomal dominant hypercholesterolemia (ADH) and the use of next-generation sequencing (NGS) technology have made possible the discovery of several rare gene variants whose pathogenic effect in most cases remains poorly defined. RECENT FINDINGS: One major advance in the field has been the adoption of a set of international guidelines for the assignment of pathogenicity to low-density lipoprotein receptor (LDLR) gene variants based on the use of softwares, complemented with data available from literature and public databases...
March 18, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28323124/cd44-is-a-key-player-in-non-alcoholic-steatohepatitis
#11
Stéphanie Patouraux, Déborah Rousseau, Stéphanie Bonnafous, Cynthia Lebeaupin, Carmelo Luci, Clémence M Canivet, Anne-Sophie Schneck, Adeline Bertola, Marie-Christine Saint-Paul, Antonio Iannelli, Jean Gugenheim, Rodolphe Anty, Albert Tran, Béatrice Bailly-Maitre, Philippe Gual
BACKGROUND: CD44 is expressed on many immune cells that contribute to inflammation. It has been shown, mainly through animal data, that CD44 regulates adipose tissue inflammation in obesity and hepatic leukocyte recruitment in a lithogenic context. However, its role in hepatic inflammation in a mouse model of steatohepatitis and its relevance in humans have not yet been investigated. METHODS: The role of CD44 was evaluated in CD44-/- mice and after injections of an αCD44 antibody in Wild-type mice challenged with a methionine- and choline-deficient diet (MCDD)...
March 16, 2017: Journal of Hepatology
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/28322895/baicalin-benefits-the-anti-hbv-therapy-via-inhibiting-hbv-viral-rnas
#13
Hai Huang, Wei Zhou, Haiyan Zhu, Pei Zhou, Xunlong Shi
BACKGROUND: Although current antiviral treatments (nucleoside analogs, NAs) for chronic hepatitis B virus (HBV) infection are effective in suppressing HBV-DNA replication, their clinical outcomes can be compromised by the increasing drug resistance and the inefficiency in promoting HBsAg/HBeAg seroconversion. OBJECTIVES: In this study, we will explore possible effects and mechanism of a natural product baicalin (BA) with the anti-HBV efficacy of entecavir (ETV), a first-line anti-HBV drug, in HBV-DNA, HBsAg/HBeAg seroconversion and drug-resistance...
March 18, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28322831/chemical-inhibitors-of-c-met-receptor-tyrosine-kinase-stimulate-osteoblast-differentiation-and-bone-regeneration
#14
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/28322826/apc-cdh1-controls-cell-cycle-entry-during-liver-regeneration
#15
Ranran Cheng, Xin Liang, Quancheng Zhao, Zhusheng Lian, Lichun Tang, Chen Qiu, Huan Chen, Pumin Zhang
Cdh1 is one of the two adaptor proteins of anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase controlling mitosis and DNA replication. To date, the in vivo functions of Cdh1 have not been fully explored. In order to characterize Cdh1 in liver regeneration, we generated a conditional knock-out mouse model. Our data showed that loss of Cdh1 leads to increased and extended S phase progression possibly due to the upregulation of cyclin D1. Moreover, the increased DNA replication resulted in activated DNA damage response...
March 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28322470/anti-inflammatory-and-antioxidant-actions-of-copaiba-oil-are-related-to-liver-cell-modifications-in-arthritic-rats
#16
Cristiane V de Castro Ghizoni, Ana P Arssufi Ames, Osmar A Lameira, Ciomar A Bersani Amado, Anacharis B de Sá Nakanishi, Lívia Bracht, Maria R Marçal Natali, Rosane M Peralta, Adelar Bracht, Jurandir F Comar
The present study investigated the action of copaiba oil (Copaifera reticulata) on the systemic inflammation, oxidative status and liver cell metabolism of rats with adjuvant-induced arthritis. The later is an experimental autoimmune pathology that shares many features with the human rheumatoid arthritis. Holtzman rats were distributed into the following groups: control (healthy) rats; control rats treated with copaiba oil at the doses of 0.58 and 1.15 g · Kg(-1) , arthritic rats, and arthritic rats treated with copaiba oil (0...
March 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28322389/alteration-of-pancreatic-carcinoma-and-promyeloblastic-cell-adhesion-in-liver-microvasculature-by-co-culture-of-hepatocytes-hepatic-stellate-cells-and-endothelial-cells-in-a-physiologically-relevant-model
#17
Mathieu Danoy, Marie Shinohara, Astia Rizki-Safitri, Dominique Collard, Vincent Senez, Yasuyuki Sakai
In vitro models of the liver microvasculature, especially with respect to cancer cell extravasation, should include not only endothelial and cancer cells but also surrounding cells to mimic the physiological situation. To this end, in the present study, we established a physiologically-relevant hierarchical co-culture model by stacking layers of primary rat hepatocytes (Hep), hepatic stellate cells embedded in collagen gel (LX-2) and endothelial cells (HUVECs) on a specially designed oxygen-permeable polydimethylsiloxane PDMS bottom plate...
March 21, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28322010/cholesterol-can-modulate-mitochondrial-aquaporin-8-expression-in-human-hepatic-cells
#18
Mauro Danielli, Alejo M Capiglioni, Julieta Marrone, Giuseppe Calamita, Raúl A Marinelli
Hepatocyte mitochondrial aquaporin-8 (mtAQP8) works as a multifunctional membrane channel protein that facilitates the uptake of ammonia for its detoxification to urea as well as the mitochondrial release of hydrogen peroxide. Since early oligonucleotide microarray studies in liver of cholesterol-fed mice showed an AQP8 downregulation, we tested whether alterations of cholesterol content per se modulate mtAQP8 expression in human hepatocyte-derived Huh-7 cells. Cholesterol loading with methyl-β-cyclodextrin (mβCD):cholesterol complexes downregulated the proteolytic activation of cholesterol-responsive sterol regulatory element-binding protein (SREBP) transcriptions factors 1 and 2, and the expression of the target gene 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)...
March 20, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28321271/parkin-in-cancer-mitophagy-related-unrelated-tasks
#19
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/28321157/hsa-mir-183-is-frequently-methylated-and-related-to-poor-survival-in-human-hepatocellular-carcinoma
#20
Sumadi Lukman Anwar, Till Krech, Britta Hasemeier, Elisa Schipper, Nora Schweitzer, Arndt Vogel, Hans Kreipe, Reena Buurman, Britta Skawran, Ulrich Lehmann
AIM: To screen clinically relevant microRNAs (miRNAs) silenced by DNA methylation in human hepatocellular carcinoma (HCC). METHODS: Knockdown of DNA methyltransferases (DNMTs) using siRNAs and miRNA profiling in HCC cell lines were performed to identify DNA hypermethylation-mediated miRNA downregulation. Confirmation using individual quantitative real-time PCR (qRT-PCR) assays was then performed followed by DNA methylation quantification at the promoter of the miRNA genes...
March 7, 2017: World Journal of Gastroenterology: WJG
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