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https://www.readbyqxmd.com/read/28343379/hepatitis-c-virus-nonstructural-5a-protein-hcv-ns5a-inhibits-hepatocyte-apoptosis-through-the-nf-kappab-mir-503-bcl-2-pathway
#1
Xie Zheng Yuan, Xiao Zhi Hua, Wang Fen Fen
The nonstructural protein 5A (NS5A) encoded by the human hepatitis C virus (HCV) RNA genome is a multifunctional phosphoprotein. To analyse the influence of NS5A on apoptosis, we established an Hep-NS5A cell line (HepG2 cells that stably express NS5A) and induced apoptosis using tumour necrosis factor (TNF)-alpha. We utilised the MTT assay to detect cell viability, real-time quantitative polymerase chain reaction and Western blot to analyse gene and protein expression, and a luciferase reporter gene experiment to investigate the targeted regulatory relationship...
March 27, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28343127/direct-immobilization-of-manganese-chelates-on-silica-nanospheres-for-mri-applications
#2
Marcell Pálmai, Adrienn Pethő, Lívia Naszályi Nagy, Szilvia Klébert, Zoltán May, Judith Mihály, András Wacha, Katalin Jemnitz, Zsuzsanna Veres, Ildikó Horváth, Krisztián Szigeti, Domokos Máthé, Zoltán Varga
The development of tissue specific magnetic resonance imaging (MRI) contrast agents (CAs) is very desirable to achieve high contrast ratio combined with excellent anatomical details. To this end, we introduce a highly effective manganese(II) containing silica material, with the aim to shorten the longitudinal (T1) relaxation time. The microporous silica nanospheres (MSNSs) with enlarged porosity and specific surface area were prepared by a surfactant assisted aqueous method. Subsequently, the surface silanol groups were amino-functionalized, reacted with diethylenetriaminepentaacetic (DTPA) dianhydride and finally deposited with Mn(2+)...
March 14, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28343019/a-new-opportunity-for-nanomedicines-micellar-cytochrome-p450-inhibitors-to-improve-drug-efficacy-in-a-cancer-therapy-model
#3
Marion Paolini, Laurence Poul, Audrey Darmon, Matthieu Germain, Agnès Pottier, Laurent Levy, Eric Vibert
Nanomedicines are mainly used as drug delivery systems; here we evaluate a new application - to inhibit a drug's metabolism thereby enhancing its effective dose. Micelles containing the natural furanocoumarin 6',7'-dihydroxybergamottin (DHB), a known CYP450 inhibitor, were developed to transiently block hepatic CYP450-mediated drug metabolism and increase the bioavailability of the oncology drug docetaxel. Administered in mice 24hours prior to the drug, DHB-micelles enhanced antitumor efficacy in the tumor xenograft models HT-29 and MDA-MB-231, when compared to the drug alone...
March 22, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28342980/muscarinic-receptor-mediated-signaling-pathways-in-hepatocytes-from-ccl4-induced-liver-fibrotic-rat
#4
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/28342842/protectin-dx-suppresses-hepatic-gluconeogenesis-through-ampk-ho-1-mediated-inhibition-of-er-stress
#5
Tae Woo Jung, Hyung-Chun Kim, Ji Hoon Jeong
Several studies have shown that protectins, which are ω-3 fatty acid-derived proresolution mediators, may improve insulin resistance. Recently, protectin DX (PDX) was documented to attenuate insulin resistance by stimulating IL-6 expression in skeletal muscle, thereby regulating hepatic gluconeogenesis. These findings made us investigate the direct effects of PDX on hepatic glucose metabolism in the context of diabetes. In the current study, we show that PDX regulates hepatic gluconeogenesis in a manner distinct from its indirect glucoregulatory activity via IL-6...
March 22, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28340340/selective-chemical-inhibition-of-pgc-1%C3%AE-gluconeogenic-activity-ameliorates-type-2-diabetes
#6
Kfir Sharabi, Hua Lin, Clint D J Tavares, John E Dominy, Joao Paulo Camporez, Rachel J Perry, Roger Schilling, Amy K Rines, Jaemin Lee, Marc Hickey, Melissa Bennion, Michelle Palmer, Partha P Nag, Joshua A Bittker, José Perez, Mark P Jedrychowski, Umut Ozcan, Steve P Gygi, Theodore M Kamenecka, Gerald I Shulman, Stuart L Schreiber, Patrick R Griffin, Pere Puigserver
Type 2 diabetes (T2D) is a worldwide epidemic with a medical need for additional targeted therapies. Suppression of hepatic glucose production (HGP) effectively ameliorates diabetes and can be exploited for its treatment. We hypothesized that targeting PGC-1α acetylation in the liver, a chemical modification known to inhibit hepatic gluconeogenesis, could be potentially used for treatment of T2D. Thus, we designed a high-throughput chemical screen platform to quantify PGC-1α acetylation in cells and identified small molecules that increase PGC-1α acetylation, suppress gluconeogenic gene expression, and reduce glucose production in hepatocytes...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340295/response-of-catalase-of-the-mouse-primary-hepatocytes-to-sodium-dodecylbenzene-sulfonate-and-the-underlying-molecular-mechanisms
#7
Jing Wang, Jiaxi Wang, Lu Zhang, Rutao Liu, Wansong Zong
This study investigated the adverse effects of sodium dodecylbenzene sulfonates (SDBS) on the mouse primary hepatocytes by conducting cell viability, intracellular oxidative stress level and catalase (CAT) activity assays. It was shown that SDBS altered CAT activities, triggered oxidative stress, and thus exhibited cytotoxicity to the hepatocytes. Both the stimulation of intracellular CAT production and the inhibition of molecular CAT activity contributed to intracellular CAT activity change. Molecular mechanisms underlying CAT activity inhibition and structural changes were explored by isothermal titration calorimetry, multi-spectroscopy and molecular docking studies...
March 24, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28339025/cerebral-hemorrhage-therapy-by-targeting-vegf-and-hgf-in-a-preclinical-trial-in-rats
#8
Xueqing Li, Ruiqi Cao, Huaihai Lu, Wenbin Tian, Ning Yu, Pei Zhang, Zhenming Dong
Cerebral hemorrhage is the most common type of human cerebrovascular disease and frequently causes paralysis, vegetative state and mortality. The modulatory actions of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are vital in the human nervous system. The present study investigated the association between cerebral hemorrhage and the expression of VEGF and HGF in a rat model of cerebral hemorrhage. The therapeutic potential of cerebral hemorrhage was also evaluated using targeted drugs for VEGF and HGF in the cerebral hemorrhage rat model...
March 22, 2017: Molecular Medicine Reports
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
#9
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/28337527/phase-ii-study-of-the-c-met-inhibitor-tivantinib-arq-197-in-patients-with-relapsed-or-relapsed-refractory-multiple-myeloma
#10
Muhamed Baljevic, Shadia Zaman, Veerabhadran Baladandayuthapani, Yan Heather Lin, Claudia Morales de Partovi, Zuzana Berkova, Behrang Amini, Sheeba K Thomas, Jatin J Shah, Donna M Weber, Min Fu, Charles S Cleeland, Xin Shelley Wang, Christine M Stellrecht, Richard E Davis, Varsha Gandhi, Robert Z Orlowski
The hepatocyte growth factor/c-MET pathway has been implicated in the pathobiology of multiple myeloma, and c-MET inhibitors induce myeloma cell apoptosis, suggesting that they could be useful clinically. We conducted a phase II study with the c-MET inhibitor tivantinib in patients with relapsed, or relapsed and refractory myeloma whose disease had progressed after one to four prior therapies. Tivantinib, 360 mg orally per dose, was administered twice daily continuously over a 4-week treatment cycle without a cap on the number of allowed cycles, barring undue toxicities or disease progression...
March 23, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28337452/teratogenic-effect-of-usnic-acid-from-cladonia-substellata-vainio-during-organogenesis
#11
C R Silva, K S N Marinho, T D S Silva, D K S Ferreira, G M Aguiar, M C B Martins, K R P Santos, F C A Aguiar Júnior, N P S Santos, E C Pereira, N H Silva
Studies about toxicological potential of usnic acid are limited. This way, the vast majority of data available in the literature are related only to biological activities. This is the first study that aimed to evaluate the oral toxicity of usnic acid during the period of organogenesis. Females rats were distributed in the control groups, treated I and II, at doses of 15 and 25 mg/kg, administered by gavage during the 6° to 15° days of pregnancy. After 20 days the fetuses were removed and analyzed. A reduction in weight gain during pregnancy, increased resorption, reduction in the number of viable fetuses, and their body weight were observed...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28337307/effects-of-microrna-29a-on-retinopathy-of-prematurity-by-targeting-agt-in-a-mouse-model
#12
Xin-Ke Chen, Li-Juan Ouyang, Zheng-Qin Yin, Yuan-You Xia, Xiu-Rong Chen, Hui Shi, Yan Xiong, Lian-Hong Pi
BACKGROUND: This study aimed to explore the effects of microRNA-29a (miR-29a) on retinopathy of prematurity (ROP) by targeting angiotensinogen (AGT) expression in a mouse model. METHODS: Ninety-six C57BL/6J mice were selected and divided into the normal control group (n = 12) and the oxygen-induced retinopathy (OIR) group (n = 84). All the mice in the OIR group were assigned to the following seven groups (12 mice in each group): the blank, miR-29a mimics, miR-29a inhibitors, empty plasmid, miR-29a mimics + si-AGT, miR-29a inhibitors + si-AGT and si-AGT groups...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337145/dioscin-protects-anit-induced-intrahepatic-cholestasis-through-regulating-transporters-apoptosis-and-oxidative-stress
#13
Hong Yao, Youwei Xu, Lianhong Yin, Xufeng Tao, Lina Xu, Yan Qi, Xu Han, Pengyuan Sun, Kexin Liu, Jinyong Peng
Intrahepatic cholestasis, a clinical syndrome, is caused by excessive accumulation of bile acids in body and liver. Proper regulation of bile acids in liver cells is critical for liver injury. We previously reported the effects of dioscin against α-naphthylisothio- cyanate (ANIT)-induced cholestasis in rats. However, the pharmacological and mechanism data are limited. In our work, the animals of rats and mice, and Sandwich-cultured hepatocytes (SCHs) were caused by ANIT, and dioscin was used for the treatment...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28336956/preclinical-development-of-a-humanized-neutralizing-antibody-targeting-hgf
#14
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/28336955/progress-of-antibody-based-inhibitors-of-the-hgf-cmet-axis-in-cancer-therapy
#15
REVIEW
Ki-Hyun Kim, Hyori Kim
Dysregulated receptor tyrosine kinase signaling in human cancer cells leads to tumor progression, invasion and metastasis. The receptor tyrosine kinase cMET is frequently overexpressed in cancer tissue, and activation of cMET signaling is related to drug resistance and the processes of carcinogenesis, invasion and metastasis. For that reason, cMET and its ligand, hepatocyte growth factor (HGF), are considered prime targets for the development of anticancer drugs. At least eight anti-cMET and four anti-HGF antibodies have been tested or are being tested in clinical trials...
March 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28336578/quantitative-prediction-of-cyp3a4-induction-impact-of-measured-free-and-intracellular-perpetrator-concentrations-from-human-hepatocyte-induction-studies-on-drug-drug-interaction-predictions
#16
Yongkai Sun, Paresh P Chothe, Jennifer Sager, Hong Tsao, Amanda Moore, Leena Laitinen, Niresh Hariparsad
Typically, concentration-response curves are generated based upon nominal new chemical entity (NCE) concentrations for in-vitro-to-in-vivo extrapolation of CYP3A4 induction. These data are then used to determine the induction risk of an NCE employing various modeling approaches. The limitation to this practice is that it assumes the hepatocyte culture model to be a static system. In the current study, we assessed whether correcting for; 1) changes in perpetrator concentration in the induction medium during the assay incubation period, 2) perpetrator binding to proteins in the induction medium and 3) non-specific binding of perpetrator can improve the accuracy of CYP3A4 induction predictions...
March 23, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28336556/human-microrna-548p-decreases-hepatic-apolipoprotein-b-secretion-and-lipid-synthesis
#17
Liye Zhou, M Mahmood Hussain
OBJECTIVE: MicroRNAs (miRs) play important regulatory roles in lipid metabolism. Apolipoprotein B (ApoB), as the only essential scaffolding protein in the assembly of very-low-density lipoproteins, is a target to treat hyperlipidemia and atherosclerosis. We aimed to find out miRs that reduce apoB expression. APPROACH AND RESULTS: Bioinformatic analyses predicted that hsa-miR-548p can interact with apoB mRNA. MiR-548p or control miR was transfected in human and mouse liver cells to test its role in regulating apoB secretion and mRNA expression levels...
March 23, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28336518/bmp-9-interferes-with-liver-regeneration-and-promotes-liver-fibrosis
#18
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/28336330/requirement-of-cytosolic-phospholipase-a2-gamma-in-lipid-droplet-formation
#19
Xi Su, Shuhui Liu, Xianwen Zhang, Sin Man Lam, Xue Hu, Yuan Zhou, Jizheng Chen, Yun Wang, Chunchen Wu, Guanghou Shui, Mengji Lu, Rongjuan Pei, Xinwen Chen
Lipid droplet (LD) accumulation in hepatocytes is a typical character of steatosis. Hepatitis C virus (HCV) infection, one of the risk factors related to steatosis, induced LD accumulation in cultured cells. However, the mechanisms of which HCV induce LD formation are not fully revealed. Previously we identified cytosolic phospholipase A2 gamma (PLA2G4C) as a host factor upregulated by HCV infection and involved in HCV replication. Here we further revealed that PLA2G4C plays an important role in LD biogenesis and refined the functional analysis of PLA2G4C in LD biogenesis and HCV assembly...
March 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28336227/aqueous-calyxes-extract-of-roselle-or-hibiscus-sabdariffa-linn-supplementation-improves-liver-morphology-in-streptozotocin-induced-diabetic-rats
#20
Akhtar Husin Nazratun Nafizah, Siti Balkis Budin, Abd Hamid Zaryantey, Abd Rahman Mariati, Raj Louis Santhana, Mohamad Osman, Md Idris Muhd Hanis, Mohamed Jamaludin
BACKGROUND AND STUDY AIMS: The complex series of deleterious events among diabetes patients leads to multiple organ failure. Therefore, a holistic approach of treatment is urgently required to prevent worsening of complications. The present investigation was carried out to study the possible protective effects of Roselle or Hibiscus sabdariffa Linn (HSL) calyxes aqueous extract, as an antidiabetic and antioxidant agent against oxidative liver injury in streptozotocin-induced diabetic rats...
March 20, 2017: Arab Journal of Gastroenterology: the Official Publication of the Pan-Arab Association of Gastroenterology
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