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https://www.readbyqxmd.com/read/29351395/macrophage-colony-stimulating-factor-increases-hepatic-macrophage-content-liver-growth-and-lipid-accumulation-in-neonatal-rats
#1
Clare Pridans, Kristin A Sauter, Katharine M Irvine, Gemma M Davis, Lucas Lefevre, Anna Raper, Rocio Rojo, Ajit J Nirmal, Philippa Beard, Michael Cheeseman, David A Hume
Signaling via the colony stimulating factor 1 receptor (CSF1R) controls the survival, differentiation and proliferation of macrophages. Mutations in CSF1, or CSF1R in mice and rats have pleiotropic effects on postnatal somatic growth. We tested the possible application of CSF1-Fc as a therapy for low birth weight (LBW) at term, using a model based upon maternal dexamethasone treatment in rats. Neonatal CSF1-Fc treatment did not alter somatic growth, and did not increase the blood monocyte count. Instead, there was a substantial increase in the size of liver in both control and LBW rats, and the treatment greatly exacerbated the lipid droplet accumulation seen in the dexamethasone LBW model...
December 21, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29351389/proliferation-of-hepatic-stellate-cells-mediated-by-yap-and-taz-contributes-to-liver-repair-and-regeneration-after-liver-ischemia-reperfusion-injury
#2
Takanori Konishi, Rebecca M Schuster, Alex B Lentsch
Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are key regulators of cell proliferation and organ size, however, their physiological contribution after liver injury has not been fully understood. In this study, we sought to determine the role of YAP and TAZ during liver recovery after ischemia-reperfusion (I/R). A murine model of partial (70%) I/R was used to induce liver injury and study the reparative and regenerative response. After liver injury, there was marked activation and proliferation of hepatic stellate cells...
January 11, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29350771/recombinant-relaxin-protects-liver-transplants-from-ischemia-damage-via-hepatocyte-glucocorticoid-receptor-from-bench-to-bedside
#3
Shoichi Kageyama, Kojiro Nakamura, Takehiro Fujii, Bibo Ke, Rebecca A Sosa, Elaine F Reed, Nakul Datta, Ali Zarrinpar, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Hepatic ischemia-reperfusion injury (IRI) represents a major risk factor of early graft dysfunction and acute/chronic rejection as well as a key obstacle to expanding the donor pool in orthotopic liver transplantation (OLT). Although glucocorticoid receptor (GR) signaling may enhance cytoprotective programs, clinical use of glucocorticoid is limited due to adverse effects, while clinical relevance of GR-facilitated cytoprotection in OLT remains unknown. We aimed to evaluate the significance of hepatic GR in clinical OLT and verify the impact of recombinant human relaxin (rhRLX), which may function as GR agonist in tissue/disease-specific manner...
January 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29350612/the-effects-of-betaine-on-the-nuclear-fractal-dimension-chromatin-texture-and-proliferative-activity-in-hepatocytes-in-mouse-model-of-nonalcoholic-fatty-liver-disease
#4
Milena Vesković, Milica Labudović-Borović, Ivan Zaletel, Jelena Rakočević, Dušan Mladenović, Bojan Jorgačević, Danijela Vučević, Tatjana Radosavljević
The effects of betaine on hepatocytes chromatin architecture changes were examined by using fractal and gray-level co-occurrence matrix (GLCM) analysis in methionine/choline-deficient (MCD) diet-induced, nonalcoholic fatty liver disease (NAFLD). Male C57BL/6 mice were divided into groups: (1) Control: standard diet; (2) BET: standard diet and betaine supplementation through drinking water (solution 1.5%); (3) MCD group: MCD diet for 6 weeks; (4) MCD+BET: fed with MCD diet + betaine for 6 weeks. Liver tissue was collected for histopathology, immunohistochemistry, and determination of fractal dimension and GLCM parameters...
January 19, 2018: Microscopy and Microanalysis
https://www.readbyqxmd.com/read/29350422/potency-of-polycyclic-aromatic-hydrocarbons-pahs-in-chicken-and-japanese-quail-embryos
#5
Cynthia D Franci, Angelika Aleksieva, Emily Boulanger, Jonas Brandenburg, Theresa Johnston, Asya Malinova, Jessica A Head
Birds are receptors of concern for polycyclic aromatic hydrocarbons (PAHs), and yet limited data describing the relative potency of PAH congeners are available for avian species. Here, we determine embryonic LD50 values for 5 PAH congeners in chicken (Gallus gallus) and one PAH congener in Japanese quail (Coturnix japonica). Graded concentrations of each test compound were injected into the air cell of chicken or quail eggs before incubation. Embryos were monitored through development (quail) or hatching (chicken)...
January 19, 2018: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/29348826/interaction-of-macrophages-with-apoptotic-cells-inhibits-transdifferentiation-and-invasion-of-lung-fibroblasts
#6
Yong-Bae Kim, Young-So Yoon, Youn-Hee Choi, Eun-Mi Park, Jihee Lee Kang
The invasion of activated fibroblasts is a key mechanism of tissue fibrosis pathology. The recognition and uptake of apoptotic cells can induce the anti-fibrogenic programming of macrophages. We demonstrate that after interacting with apoptotic cells, macrophages secrete bioactive molecules that antagonize TGF-β1-induced increases in myofibroblast (fibroproliferative) phenotypic markers and reduce the enhanced invasive capacity of TGF-β1- or EGF-treated mouse lung fibroblasts (MLg). Furthermore, numerous treatment strategies prevented the anti-fibrotic effects of conditioned media, including transfection of macrophages with COX-2 or RhoA siRNAs or treatment of MLg cells with receptor antagonists for prostaglandin E2 (PGE2), PGD2, or hepatocyte growth factor (HGF)...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348606/amp-activated-protein-kinase-agonist-n6-3-hydroxyphenyl-adenosine-protects-against-fulminant-hepatitis-by-suppressing-inflammation-and-apoptosis
#7
Jin Li, Bo Chen, Liping Zhong, Feng Gao, Haibo Zhu, Fengzhong Wang
Both AMP-activated protein kinase (AMPK) agonist and inhibitor have been reported to protect against fulminant hepatitis, implying that AMPK may play a complicated role in the development of fulminant hepatitis. In this study, we exploited whether the novel AMPK agonist N6-(3-hydroxyphenyl)adenosine (named as M1) exerted protective effects on fulminant hepatitis and whether its beneficial effects were AMPK-dependent. Results showed that intraperitoneal injection of M1 improved liver function, ameliorated liver injury and finally raised the survival rate in D-galactosamine/lipopolysaccharide (GalN/LPS)-treated mice...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348600/chinese-olive-extract-ameliorates-hepatic-lipid-accumulation-in-vitro-and-in-vivo-by-regulating-lipid-metabolism
#8
Yu-Te Yeh, Yan-Yu Cho, Shu-Chen Hsieh, An-Na Chiang
Chinese olive contains plenty of polyphenols, which possess a wide range of biological actions. In this study, we aimed to investigate the role of the ethyl acetate fraction of Chinese olive fruit extract (CO-EtOAc) in the modulation of lipid accumulation in vitro and in vivo. In cellular studies, CO-EtOAc attenuated oleic acid-induced lipid accumulation; we then elucidated the molecular mechanisms of CO-EtOAc in FL83B mouse hepatocytes. CO-EtOAc suppressed the mRNA levels of fatty acid transporter genes (CD36 and FABP) and lipogenesis genes (SREBP-1c, FAS, and ACC1), but upregulated genes that govern lipolysis (HSL) and lipid oxidation (PPARα, CPT-1, and ACOX)...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348487/h1-phgfk1-nanoparticles-exert-anti-tumoural-and-radiosensitising-effects-by-inhibition-of-met-in-glioblastoma
#9
Wenyan Zhang, Rui Duan, Jian Zhang, William K C Cheung, Xiaoge Gao, Raymond Zhang, Qing Zhang, Mengxue Wei, Gang Wang, Qian Zhang, Peng-Jin Mei, Hong-Lin Chen, Hsiangfu Kung, Marie C Lin, Zan Shen, Junnian Zheng, Longzhen Zhang, Hong Yao
BACKGROUND: The therapeutic resistance to ionising radiation (IR) and anti-angiogenesis mainly impair the prognosis of patients with glioblastoma. The primary and secondary MET aberrant activation is one crucial factor for these resistances. The kringle 1 domain of hepatocyte growth factor (HGFK1), an angiogenic inhibitor, contains a high-affinity binding domain of MET; however, its effects on glioblastoma remain elusive. METHODS: We formed the nanoparticles consisting of a folate receptor-targeted nanoparticle-mediated HGFK1 gene (H1/pHGFK1) and studied its anti-tumoural and radiosensitive activities in both subcutaneous and orthotopic human glioma cell-xenografted mouse models...
January 18, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29348414/microrna-146a-5p-attenuates-irradiation-induced-and-lps-induced-hepatic-stellate-cell-activation-and-hepatocyte-apoptosis-through-inhibition-of-tlr4-pathway
#10
Yuhan Chen, Zhifeng Wu, Baoying Yuan, Yinying Dong, Li Zhang, Zhaochong Zeng
Elevated toll-like receptor 4 (TLR4) expression is associated with a high risk of radiation-induced liver disease (RILD). MicroRNA (miR)-146a-5p is a key regulator of lipopolysaccharide (LPS)/TLR4 signaling, but its role in modulation of RILD remains unclear. Here, we found that irradiation and LPS stimulation induced TLR4 and miR-146a-5p expression in the human hepatic stellate cell (HSC) line LX2. Ectopic expression of miR-146a-5p in LX2 inhibited irradiation-induced and LPS-induced pro-inflammatory cytokine secretion and cell proliferation, and promoted cell apoptosis by down-regulating the expression levels of TLR4, interleukin-1 receptor associated kinase 1 (IRAK1), tumor necrosis factor receptor associated factor 6 (TRAF6) and phosphorylation of nuclear factor-kappa B...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348399/insulin-like-growth-factor-2-is-a-key-mitogen-driving-liver-repopulation-in-mice
#11
Min-Jun Wang, Fei Chen, Qing-Gui Liu, Chang-Cheng Liu, Hao Yao, Bing Yu, Hai-Bin Zhang, He-Xin Yan, Yibiao Ye, Tao Chen, Kirk J Wangensteen, Xin Wang, Yi-Ping Hu, Zhi-Ying He
Hepatocyte transplantation holds great promise as an alternative to orthotopic organ transplantation in the treatment of liver diseases. However, obtaining clinically meaningful levels of liver repopulation has not been achieved because the mechanisms regulating hepatocyte proliferation in recipient livers have not yet been well characterized. In the mouse model of Hereditary Tyrosinemia Type I, the fumarylacetoacetate hydrolase-deficient (Fah-/-) mouse, we found gradually increasing expression level of insulin-like growth factor 2 (IGF2) in the hepatocytes of host livers...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348288/budd-chiari-syndrome-a-rare-and-life-threatening-complication-of-crohn-s-disease
#12
Camila C Simoes, Yezaz A Ghouri, Shehzad N Merwat, Heather L Stevenson
Budd-Chiari syndrome (BCS) is characterised by obstruction of hepatic venous outflow and may be triggered by the prothrombotic state associated with inflammatory bowel disease (IBD). We reported a case of Crohn's disease (CD) that presented with anasarca, ascites, symptomatic hepatomegaly, elevated liver enzymes, increased prothrombin time and low albumin. Oesophagogastroduodenoscopy and colonoscopy confirmed active CD. Abdominal CT showed hepatic vein thrombosis. Liver biopsy revealed severe perivenular sinusoidal dilation with areas of hepatocyte dropout, bands of hepatocyte atrophy and centrizonal fibrosis, suggestive of BCS...
January 17, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29348125/metabolism-and-disposition-of-a-novel-selective-%C3%AE-7-neuronal-acetylcholine-receptor-agonist-abt-126-in-humans-characterization-of-the-major-roles-for-flavin-containing-monooxygenases-and-udp-glucuronosyl-transferase-1a4-and-2b10-in-catalysis
#13
Hong Liu, David M Stresser, Melissa J Michmerhuizen, XIaofeng Li, Ahmed A Othman, Aimee D Reed, Michael R Schrimpf, Jens Sydor, Anthony J Lee
Mass balance, metabolism and excretion of ABT-126, an α7 nAChRs agonist, were characterized in healthy male subjects (n=4) following a single 100 mg (100 μCi) oral dose. The total recovery of the administered radioactivity was 94.0% (±2.09%) with 81.5% (± 10.2%) in urine and 12.4% (± 9.3%) in feces. Metabolite profiling indicated that ABT-126 had been extensively metabolized with 6.6% of the dose remaining as unchanged parent drug in urine. Parent drug accounted for 12.2% of the administered radioactivity in feces...
January 18, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29348124/organic-anion-transporting-polypeptide-1a4-is-responsible-for-the-hepatic-uptake-of-cardiac-glycosides-in-mice
#14
Junichi Takano, Kazuya Maeda, Hiroyuki Kusuhara, Yuichi Sugiyama
Among organic anion transporting polypeptide (Oatp) family transporters expressed in the rodent liver, such as Oatp1a1, Oatp1a4, Oatp1b2, and Oatp2b1, Oatp1a4 has a unique character to recognize neutral cardiac glycosides as substrate in addition to organic anions. The relative contribution of Oatp1a4 to the substrate uptake into hepatocytes has not been clarified. In this study, we investigated the importance of Oatp1a4 in the hepatic uptake of its substrate drugs using Slco1a4-/- mice. The hepatic mRNA expression of Slco1a4 was decreased significantly in Slco1a4-/- mice, whereas no differences were seen in other hepatic transporters between wild-type and Slco1a4-/- mice...
January 18, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29346833/phase-1b-trial-of-ficlatuzumab-a-humanized-hepatocyte-growth-factor-inhibitory-monoclonal-antibody-in-combination-with-gefitinib-in-asian-patients-with-nsclc
#15
Eng-Huat Tan, Wan-Teck Lim, Myung-Ju Ahn, Quan-Sing Ng, Jin Seok Ahn, Daniel Shao-Weng Tan, Jong-Mu Sun, May Han, Francis C Payumo, Krista McKee, Wei Yin, Marc Credi, Shefali Agarwal, Jaroslaw Jac, Keunchil Park
Hepatocyte growth factor (HGF)/c-Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Ficlatuzumab (AV-299; SCH 900105), a humanized IgG1 κ HGF inhibitory monoclonal antibody, prevents HGF/c-Met pathway ligand-mediated activation. This phase 1b study assessed the safety/tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus gefitinib in Asian patients with previously treated advanced non-small cell lung cancer (NSCLC)...
January 18, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29346427/soluble-factors-from-adipose-tissue-derived-mesenchymal-stem-cells-promote-canine-hepatocellular-carcinoma-cell-proliferation-and-invasion
#16
Takahiro Teshima, Hirotaka Matsumoto, Hidekazu Koyama
The potential effects of adipose tissue-derived mesenchymal stem cells (AT-MSCs) on the growth and invasion of canine tumours including hepatocellular carcinoma (HCC) are not yet understood. Moreover in humans, the functional contribution of AT-MSCs to malignancies remains controversial. The purpose of this study was to investigate the effects of AT-MSCs on the proliferation and invasion of canine HCC cells in vitro. The effect of AT-MSCs on mRNA levels of factors related to HCC progression were also evaluated...
2018: PloS One
https://www.readbyqxmd.com/read/29346426/proliferation-and-survival-of-human-amniotic-epithelial-cells-during-their-hepatic-differentiation
#17
Julieta L Maymó, Rodrigo Riedel, Antonio Pérez-Pérez, Marta Magatti, Bernardo Maskin, José Luis Dueñas, Ornella Parolini, Víctor Sánchez-Margalet, Cecilia L Varone
Stem cells derived from placental tissues are an attractive source of cells for regenerative medicine. Amniotic epithelial cells isolated from human amnion (hAECs) have desirable and competitive characteristics that make them stand out between other stem cells. They have the ability to differentiate toward all three germ layers, they are not tumorigenic and they have immunosuppressive properties. Although liver transplantation is the best way to treat acute and chronic hepatic failure patients, there are several obstacles...
2018: PloS One
https://www.readbyqxmd.com/read/29345322/effect-of-substrate-stiffness-on-hepatocyte-migration-and-cellular-young-s-modulus
#18
Tingting Xia, Runze Zhao, Wanqian Liu, Qiping Huang, Peixing Chen, Yasinta Ningsih Waju, Mohanad Kh Al-Ani, Yonggang Lv, Li Yang
Hepatic fibrosis progress accompanied by an unbalanced extracellular matrix (ECM) degradation and deposition leads to an increased tissue stiffness. Hepatocytes interplay with all intrahepatic cell populations inside the liver. However, how hepatocytes migration and cellular Young's modulus influenced by the substrate stiffness are not well understood. Here, we established a stiffness-controllable in vitro cell culture model by using a polyvinyl alcohol (PVA) hydrogel that mimicked the same physical stiffness as a fibrotic liver...
January 18, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29345253/3-acetyl-oleanolic-acid-ameliorates-non-alcoholic-fatty-liver-disease-in-high-fat-diet-treated-rats-by-activating-ampk-related-pathways
#19
Qiong Ou-Yang, Chun-Xiao Xuan, Xue Wang, Han-Qiong Luo, Jin-E Liu, Lan-Lan Wang, Ting-Ting Li, Yu-Peng Chen, Jun Liu
3-Acetyl-oleanolic acid (3Ac-OA) is a derivative of oleanolic acid (OA), which has shown therapeutic beneficial effects on diabetes and metabolic syndrome. In this study we investigated whether 3Ac-OA exerted beneficial effect on non-alcoholic fatty liver disease (NAFLD) in rats and its potential underlying mechanisms. Treatment with 3Ac-OA (1-100 μmol/L) dose-dependently decreased the intracellular levels of total cholesterol (TC) and triglyceride (TG) in FFA-treated primary rat hepatocytes and human HepG2 cell lines in vitro...
January 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29344668/blocking-of-autocrine-igf-1-reduces-viability-of-human-umbilical-cord-mesenchymal-stem-cells-via-inhibition-of-the-akt-gsk-3%C3%AE-signaling-pathway
#20
Qi Wang, Fenxi Zhang, Yan Hong
Human umbilical cord mesenchymal stem cells (hUCMSCs) are able to secrete growth factors, such as hepatocyte growth factor, vascular endothelial growth factor and insulin‑like growth factor‑1 (IGF‑1). The secretion of these growth factors by transplanted hUCMSCs have been identified to stimulate the growth of the host cells in the target organs or tissues. The aim of the present study was to investigate the effect of autocrine IGF‑1 on cell viability of hUCMSCs. The expression levels of IGF‑1 and the IGF‑1 receptor (IGF‑1R) in hUCMSCs were identified using immunocytochemistry staining...
January 17, 2018: Molecular Medicine Reports
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