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https://www.readbyqxmd.com/read/29684031/computationally-identified-novel-agonists-for-gprc6a
#1
Min Pi, Karan Kapoor, Ruisong Ye, Dong-Jin Hwang, Duane D Miller, Jeremy C Smith, Jerome Baudry, L Darryl Quarles
New insights into G protein coupled receptor regulation of glucose metabolism by β-cells, skeletal muscle and liver hepatocytes identify GPRC6A as a potential therapeutic target for treating type 2 diabetes mellitus (T2D). Activating GPRC6A with a small molecule drug represents a potential paradigm-shifting opportunity to make significant strides in regulating glucose homeostasis by simultaneously correcting multiple metabolic derangements that underlie T2D, including abnormalities in β-cell proliferation and insulin secretion and peripheral insulin resistance...
2018: PloS One
https://www.readbyqxmd.com/read/29673755/understanding-liver-regeneration-from-mechanisms-to-regenerative-medicine
#2
REVIEW
Hélène Gilgenkrantz, Alexandra Collin de l'Hortet
Liver regeneration is a complex and unique process. When two-thirds of a mouse liver is removed, the remaining liver recovers its initial weight in approximately 10 days. The understanding of the mechanisms responsible for liver regeneration may help patients needing large liver resections or transplantation and may be applied to the field of regenerative medicine. All differentiated hepatocytes are capable of self-renewal, but different subpopulations of hepatocytes seem to have distinct proliferative abilities...
April 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29672920/targeting-hsp60-by-subcutaneous-injections-of-jetpei-hsp60-shrna-destabilizes-cytoplasmic-survivin-and-inhibits-hepatocellular-carcinoma-growth
#3
Ya-Hui Huang, Kwang-Huei Lin, Jao-Song Yu, Ting-Jung Wu, Wei-Chen Lee, Chuck C-K Chao, Tai-Long Pan, Chau-Ting Yeh
Heat shock protein 60 (HSP60) overexpresses in various types of cancer, but its expression levels and functions in hepatocellular carcinoma (HCC) are still in dispute. We aim to clarify this issue and examine whether HSP60 could be a therapeutic target for HCC. We found drastically enhanced cell apoptosis and suppressed cell proliferation in two HCC cell lines with HSP60-silencing, and also indicated survivin is involved in this regulatory process in vitro and in vivo. However, HSP60-silencing in normal human hepatocytes only resulted in a minimal reduction of cell proliferation but without effects on cell apoptosis...
April 19, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29672888/a-novel-fibroblast-growth-factor-15-dependent-and-bile-acid-independent-promotion-of-liver-regeneration-in-mice
#4
Bo Kong, Runbin Sun, Mingxing Huang, Monica D Chow, Xiao-Bo Zhong, Wen Xie, Yi-Horng Lee, Grace L Guo
The role of intestine-derived factors in promoting liver regeneration after partial hepatectomy (PHx) are not entirely known, but bile acids (BAs) and fibroblast growth factor 15 (Fgf15) that is highly expressed in the mouse ileum could promote hepatocyte proliferation. Fgf15 strongly suppresses the synthesis of BAs and emerging evidence indicates that Fgf15 is important for liver regeneration. The mechanisms by which Fgf15 promotes liver regeneration are unclear, but Fgf15 may do so indirectly by reducing BA levels and/or directly by promoting cell proliferation...
April 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29672850/ursolic-acid-ameliorates-ccl4-induced-liver-fibrosis-through-the-noxs-ros-pathway
#5
Dakai Gan, Wang Zhang, Chenkai Huang, Jiang Chen, Wenhua He, Anjiang Wang, Bimin Li, Xuan Zhu
Liver fibrosis is a reversible wound-healing response that occurs after liver injury. NADPH oxidases (NOXs) and reactive oxygen species (ROS) which are expressed in hepatocytes (HCs), hepatic stellate cells (HSCs), and Kupffer cells (KCs) play an important role in the development of hepatic fibrosis. In in vitro studies, we had shown that ursolic acid (UA) could reverse liver fibrosis by inhibiting the activation of NOX-mediated fibrotic signaling networks in HSCs. In this study, we verified that UA could alleviate CCl4-induced liver fibrosis by reducing the expression of NOXs/ROS in HCs, HSCs, KCs...
April 19, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29672235/interleukin-7-regulates-t-follicular-helper-cell-function-in-patients-with-chronic-hepatitis-c
#6
Zhi-Hong Zhang, Ben-Chun Jiang, Xiao-Hong Liu, Meng-Xuan Zhang, Zhen-Sheng-Nan Li, Guang-Ze Zhu
Signaling through interleukin (IL)-7 is essential and required for development, differentiation, proliferation, and homeostasis of T cells. However, the role of IL-7 in regulation of CD4+ T cells in chronic viral infections was not fully elucidated. Thus, the aim of the current study was to investigate the immunomodulatory activity of IL-7 to T follicular helper (Tfh) cells and its contribution to pathogenesis of chronic HCV, hepatitis C virus (HCV) infection. A total of 47 patients with chronic hepatitis C and 19 normal controls were enrolled...
April 19, 2018: Viral Immunology
https://www.readbyqxmd.com/read/29670525/mir-203-inhibits-alcohol-induced-hepatic-steatosis-by-targeting-lipin1
#7
Xiao-Yu Cheng, Jun-Da Liu, Xin-Yi Lu, Xing Yan, Cheng Huang, Xiao-Ming Meng, Jun Li
Alcoholic liver disease (ALD) is a global liver disease which characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Alcohol abuse is one of the main reasons for liver disease. Alcoholic fatty liver (AFL) disease is the early stage of ALD and associated with the excessive lipids accumulation in hepatocytes as well as oxidative stress. MicroRNA-203 (miR-203) is known to suppress the proliferation and metastasis of hepatocellular carcinoma, but the role in the progression of alcoholic liver disease is not clear and is warranted for further investigation...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29666296/phase-ii-study-to-evaluate-the-efficacy-and-safety-of-rilotumumab-and-bevacizumab-in-subjects-with-recurrent-malignant-glioma
#8
Mary Lou Affronti, Jennifer Gamboa Jackman, Frances McSherry, James E Herndon, Elwood C Massey, Eric Lipp, Annick Desjardins, Henry S Friedman, Gordana Vlahovic, James Vredenburgh, Katherine B Peters
LESSONS LEARNED: Due to evolving imaging criteria in brain tumors and variation in magnetic resonance imaging evaluation, it is not ideal to use response rate as a primary objective. Future studies involving antiangiogenic agents should use overall survival.Disease-expected toxicities should be considered when defining the clinical significance of an adverse event. For example, vascular thromboembolic events are common in brain tumor patients and should not be attributed to the study drug in the safety analysis...
April 17, 2018: Oncologist
https://www.readbyqxmd.com/read/29664235/mir-1-3p-and-mir-206-sensitizes-hgf-induced-gefitinib-resistant-human-lung-cancer-cells-through-inhibition-of-c-met-signalling-and-emt
#9
Demin Jiao, Jun Chen, Yu Li, Xiali Tang, Jian Wang, Wei Xu, Jia Song, You Li, Huimin Tao, Qingyong Chen
Hepatocyte growth factor (HGF) overexpression is an important mechanism in acquired epidermal growth factor receptor (EGFR) kinase inhibitor gefitinib resistance in lung cancers with EGFR activating mutations. MiR-1-3p and miR-206 act as suppressors in lung cancer proliferation and metastasis. However, whether miR-1-3p and miR-206 can overcome HGF-induced gefitinib resistance in EGFR mutant lung cancer is not clear. In this study, we showed that miR-1-3p and miR-206 restored the sensitivities of lung cancer cells PC-9 and HCC-827 to gefitinib in present of HGF...
April 17, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29658567/hepacam-inhibits-the-malignant-behavior-of-castration-resistant-prostate-cancer-cells-by-downregulating-notch-signaling-and-pf-3084014-a-%C3%AE-secretase-inhibitor-partly-reverses-the-resistance-of-refractory-prostate-cancer-to-docetaxel-and-enzalutamide-in-vitro
#10
Zhongbo Du, Luo Li, Wei Sun, Xiao Wang, Yao Zhang, Zhixiong Chen, Mengjuan Yuan, Zhen Quan, Nanjing Liu, Yanni Hao, Ting Li, Jinhua Wang, Chunli Luo, Xiaohou Wu
Castration-resistant prostate cancer (CRPC) continues to be a major challenge in the treatment of prostate cancer (PCa). The expression of hepatocyte cell adhesion molecule (HepaCAM), a novel tumor suppressor, is frequently downregulated or lost in PCa. Overactivated Notch signaling is involved in the development and progression of PCa, including CRPC. In this study, we found that the activities of Notch signaling were elevated, while HepaCAM expression was decreased in CRPC tissues compared with matched primary prostate cancer (PPC) tissues...
April 12, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29657405/immunomodulatory-effects-of-probiotics-and-prilled-fat-supplementation-on-immune-genes-expression-and-lymphocyte-proliferation-of-transition-stage-karan-fries-cows
#11
Meeti Punetha, A K Roy, H M Ajithakumar, Irshad Ahmed Para, Deepanshu Gupta, Mahendra Singh, Jaya Bharati
Background and Aim: Probiotics are the living microorganism which when administered improves the digestion and health of the animal. Saccharomyces cerevisiae (SC) improves the humoral and innate immunity of the animal. Prilled fat is a hydrogenated palm oil triglyceride which has been reported to promote the release of cytokines from macrophages. The aim of the study was to evaluate the immunomodulatory effect of probiotic and prilled fat during transition stage in Karan Fries (KF) cows...
February 2018: Veterinary World
https://www.readbyqxmd.com/read/29649779/activation-of-hepatic-stellate-cells-during-liver-carcinogenesis-requires-fibrinogen-integrin-%C3%AE-v%C3%AE-5-in-zebrafish
#12
Chuan Yan, Qiqi Yang, Zhiyuan Gong
Hepatocellular carcinoma (HCC) is one of the most common cancers and it usually develops from a background of liver fibrosis or inflammation. The crosstalk between tumor cells and stromal cells plays an important and stimulating role during tumor progression. Previously we found in a krasV12 -induced zebrafish HCC model that oncogenic hepatocytes activate hepatic stellate cells (HSCs) by up-regulation of serotonin and activate neutrophils and macrophages by up-regulation of cortisol. In the present study, we found a novel signaling transduction mechanism between oncogenic hepatocytes and HSCs...
April 9, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29627914/the-influence-of-feed-supplementation-with-probiotic-strain-lactobacillus-reuteri-ccm-8617-and-alginite-on-intestinal-microenvironment-of-spf-mice-infected-with-salmonella-typhimurium-ccm-7205
#13
Soňa Gancarčíková, Radomíra Nemcová, Miroslav Popper, Gabriela Hrčková, Ľuboslava Sciranková, Marián Maďar, Dagmar Mudroňová, Štefan Vilček, Rudolf Žitňan
Alginite is a non-ore raw material arising by fossilization of accumulated organic (algae) and inorganic material, particularly clay, carbonates, quartz, and amorphous modification of silicic acid in the aqueous environment. Humic acids as a component of organic portion of alginite are known for very good buffering ability which allows them to stabilise pH throughout the digestion system of animals, stimulate receptors of the immune system in intestinal villi against pathogenic bacteria, and support proliferation and activity of beneficial bacteria (lactobacilli, bifidobacteria, and similar)...
April 7, 2018: Probiotics and Antimicrobial Proteins
https://www.readbyqxmd.com/read/29626562/a-human-relevance-investigation-of-ppar%C3%AE-mediated-key-events-in-the-hepatocarcinogenic-mode-of-action-of-propaquizafop-in-rats
#14
Christian Strupp, Werner H Bomann, François Spézia, Frédéric Gervais, Roy Forster, Lysiane Richert, Pramila Singh
Propaquizafop is an herbicide with demonstrated hepatocarcinogenic activity in rodents. A rodent-specific mode of action (MOA) in the liver via activation of peroxisome proliferator-activated receptor α (PPARα) has been postulated based on existing data. Experience with PPARα-inducing pharmaceuticals indicates a lack of human relevance of this MOA. The objective of the present investigation was to evaluate the dependency of early key events leading to liver tumors on PPARα activation in wildtype (WT) compared to PPARα-knockout (KO) rats following 2 weeks exposure to 75, 500 and 1000 ppm propaquizafop in the diet...
April 4, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29616122/plasmodium-circumsporozoite-protein-suppresses-the-growth-of-a549-cells-via-inhibiting-nuclear-transcription-factor-%C3%AE%C2%BAb
#15
Xu-Feng Deng, Dong Zhou, Quan-Xing Liu, Hong Zheng, Yan Ding, Wen-Yue Xu, Jia-Xin Min, Ji-Gang Dai
Blocking the activation of nuclear factor κB (NF-κB) is a promising strategy for the treatment of non-small cell lung cancer. The circumsporozoite protein (CSP), a key component of the sporozoite stage of the malaria parasite, was previously reported to block NF-κB activation in hepatocytes. Therefore, in the present study, the effect of CSP on the growth of the human lung cancer cell line, A549, was investigated. It was demonstrated that transfection with a recombinant plasmid expressing CSP was able to inhibit the proliferation of A549 cells in a dose-dependent manner and induce the apoptosis of A549 cells...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29603076/effects-of-rhizoma-alismatis-extract-on-biochemical-indices-and-adipose-gene-expression-in-oleic-acid-induced-hepatocyte-injury-in-jian-carp-cyprinus-carpio-var-jian
#16
Jinliang Du, Rui Jia, Li-Ping Cao, Weidong Ding, Pao Xu, Guojun Yin
Fatty liver is an increasingly serious disease of fish in aquaculture. However, the mechanisms responsible for the occurrence of fatty liver remain unclear, and no effective methods for the prevention and treatment of this disease have yet been found. In the present study, we aimed to develop an in vitro model of hepatocyte injury using oleic acid as hepatotoxicant and evaluate the protective effects of Rhizoma Alismatis extract (RAE) in Jian carp using this model. Primary hepatocytes from Jian carp were isolated and purified and cultured in vitro...
March 30, 2018: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/29602237/nefa-induced-ros-impaired-insulin-signalling-through-the-jnk-and-p38mapk-pathways-in-non-alcoholic-steatohepatitis
#17
Wenwen Gao, Xiliang Du, Lin Lei, Heyuan Wang, Min Zhang, Zhe Wang, Xiaobing Li, Guowen Liu, Xinwei Li
The aim of this study was to investigate the changes in hepatic oxidative phosphorylation (OXPHOS) complexes (COs) in patients and cows with non-alcoholic steatohepatitis (NASH) and to investigate the mechanism that links mitochondrial dysfunction and hepatic insulin resistance induced by non-esterified fatty acids (NEFAs). Patients and cows with NASH displayed high blood NEFAs, TNF-α and IL-6 concentrations, mitochondrial dysfunction and insulin resistance. The protein levels of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), mitofusin-2 (Mfn-2) and OXPHOS complexes (human: COI and COIII; cow: COI-IV) were significantly decreased in patients and cows with NASH...
March 30, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29589872/cigarette-smoking-impairs-adipose-stromal-cell-vasculogenic-activity-and-abrogates-potency-to-ameliorate-ischemia
#18
Daria Barwinska, Dmitry O Traktuev, Stephanie Merfeld-Clauss, Todd G Cook, Hongyan Lu, Irina Petrache, Keith L March
Cigarette smoking (CS) adversely affects the physiologic function of endothelial progenitor, hematopoietic stem and progenitor cells. However, the effect of CS on the ability of adipose stem/stromal cells (ASC) to promote vasculogenesis and rescue perfusion in the context of ischemia is unknown. To evaluate this, ASC from nonsmokers (nCS-ASC) and smokers (CS-ASC), and their activity to promote perfusion in hindlimb ischemia models, as well as endothelial cell (EC) survival and vascular morphogenesis in vitro were assessed...
March 28, 2018: Stem Cells
https://www.readbyqxmd.com/read/29588626/epistructured-catechins-egcg-and-ec-facilitate-apoptosis-induction-through-targeting-de-novo-lipogenesis-pathway-in-hepg2-cells
#19
Phuriwat Khiewkamrop, Pattamaphron Phunsomboon, Lysiane Richert, Dumrongsak Pekthong, Piyarat Srisawang
Background: Abnormally high expression of the mammalian de novo lipogenesis (DNL) pathway in various cancer cells promotes cell over-proliferation and resistance to apoptosis. Inhibition of key enzymes in the DNL pathway, namely, ATP citrate lyase, acetyl-CoA carboxylase, and fatty acid synthase (FASN) can increase apoptosis without cytotoxicity to non-cancerous cells, leading to the search for and presentation of novel selective and powerful targets for cancer therapy. Previous studies reported that epistructured catechins, epigallocatechin gallate (EGCG) and epicatechin (EC) exhibit different mechanisms regarding a strong inducer of apoptosis in various cancer cell lines...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29581770/targeting-hepatocarcinogenesis-model-in-c56bl6-mice-with-pan-aurora-kinase-inhibitor-danusertib
#20
Paschalis Gavriilidis, Theofilos Poutahidis, Alexander Giakoustidis, Kali Makedou, Katerina Angelopoulou, Alexander Hardas, Paola Andreani, Argyro Zacharioudaki, George Saridis, Athanasios Gargavanis, Eleni Louri, Nikolaos Antoniadis, Eleftheria Karampela, Nikolaos Psychalakis, Antonios Michalopoulos, Apostolos Papalois, Stavros Iliadis, Satvinder Mudan, Daniel Azoulay, Dimitrios Giakoustidis
Background : To elucidate the expression of Aurora kinases (AURK) and the anticancer effects of pan-aurora kinase inhibitor Danusertib in hepatocarcinogenesis model in C56Bl6 mice. Methods : Thirty mice C56Bl6 were randomly divided into Group A or control, Group B animals who underwent experimental hepatocarcinogenesis with diethylnitrosamine (DEN), and Group C animals with DEN-induced hepatocarcinogenenesis that treated with pan-aurora kinase inhibitor Danusertib. Primary antibodies for immunochistochemistry (IHC) included rabbit antibodies against Ki-67, DKK1, INCENP, cleaved caspase-3, NF-κB p65, c-Jun, β-catenin...
2018: Journal of Cancer
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