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https://www.readbyqxmd.com/read/28550384/investigation-of-glycochenodeoxycholate-sulfate-and-chenodeoxycholate-glucuronide-as-surrogate-endogenous-probes-for-drug-interaction-studies-of-oatp1b1-and-oatp1b3-in-healthy-japanese-volunteers
#1
Issey Takehara, Hanano Terashima, Takeshi Nakayama, Takashi Yoshikado, Miwa Yoshida, Kenichi Furihata, Nobuaki Watanabe, Kazuya Maeda, Osamu Ando, Yuichi Sugiyama, Hiroyuki Kusuhara
PURPOSE: To assess the use of glycochenodeoxycholate-3-sulfate (GCDCA-S) and chenodeoxycholate 3- or 24-glucuronide (CDCA-3G or -24G) as surrogate endogenous substrates in the investigation of drug interactions involving OATP1B1 and OATP1B3. METHODS: Uptake of GCDCA-S and CDCA-24G was examined in HEK293 cells transfected with cDNA for OATP1B1, OATP1B3, and NTCP and in cryopreserved human hepatocytes. Plasma concentrations of bile acids and their metabolites (GCDCA-S, CDCA-3G, and CDCA-24G) were determined by LC-MS/MS in eight healthy volunteers with or without administration of rifampicin (600 mg, po)...
May 26, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28549910/naturally-acquired-immune-responses-to-thrombospondin-related-adhesion-protein-trap-of-plasmodium-vivax-in-patients-from-areas-of-unstable-malaria-transmission
#2
Saeed Nazeri, Sedigheh Zakeri, Akram Abouie Mehrizi, Navid Dinparast Djadid
A key tool for the control, elimination, and eradication of Plasmodium vivax is the development of an effective vaccine. The thrombospondin-related adhesion protein (TRAP) is one of the major sporozoite antigens that plays an important role in the invasion of mosquito salivary glands and hepatocytes by sporozoites. The main goal of this study was to evaluate the naturally acquired antibodies to the P. vivax TRAP (PvTRAP) in patients from malaria-endemic areas of Iran (n=116), Afghanistan (n=50), and Pakistan (n=50)...
May 23, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28549346/functional-heterogeneity-in-tumor-derived-human-pancreatic-stellate-cells-differential-expression-of-hgf-and-implications-for-mitogenic-signaling-and-migration-in-pancreatic-cancer-cells
#3
Vegard Tjomsland, Monica Aasrum, Thoralf Christoffersen, Ivar P Gladhaug
The pancreatic stellate cell (PSC) is the principal cell type of the desmoplastic stroma of pancreatic ductal adenocarcinoma (PDAC). PSCs interact with cancer cells and influence the progression of the disease through a complex network of signaling molecules including hepatocyte growth factor (HGF). Functional heterogeneity of PSCs within a tumor might conceivably influence tumor progression. We investigated PSC populations isolated from different human PDACs and examined the effects of PSC-conditioned medium on BxPC-3 and AsPC-1 pancreatic cancer cells...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548876/the-constitutive-lipid-droplet-protein-plin2-regulates-autophagy-in-liver
#4
Tsung-Huang Tsai, Elaine Chen, Lan Li, Pradip Saha, Hsiao-Ju Lee, Li-Shin Huang, Gregory S Shelness, Lawrence Chan, Benny Hung-Junn Chang
Excess triglyceride (TG) accumulation in the liver underlies fatty liver disease, a highly prevalent ailment. TG occurs in the liver sequestered in lipid droplets, the major lipid storage organelle. Lipid droplets are home to the lipid droplet proteins, the most abundant of which are the perilipins (PLINs), encoded by 5 different genes, Plin1 to Plin5. Of the corresponding gene products, PLIN2 is the only constitutive and ubiquitously expressed lipid droplet protein that has been used as a protein marker for lipid droplets...
May 26, 2017: Autophagy
https://www.readbyqxmd.com/read/28548045/3d-liver-membrane-system-by-co-culturing-human-hepatocytes-sinusoidal-endothelial-and-stellate-cells
#5
Haysam Mohamed Magdy Ahmed, Simona Salerno, Sabrina Morelli, Lidetta Giorno, Loredana De Bartolo
In this study, a designed approach has been utilized for the development of a 3D liver system. This approach makes use of primary human sinusoidal endothelial cells, stellate cells and hepatocytes that are seeded sequentially on hollow fiber membranes (HF) in order to mimic the layers of cells found in vivo. To this purpose modified polyethersulfone (PES) HF membranes were used for the creation of a 3D human liver system in static and dynamic conditions. In order to verify the positive effect of non-parenchymal cells on the maintenance of hepatocyte viability and functions, homotypic cultures of hepatocytes alone on the HF membranes were further investigated...
May 26, 2017: Biofabrication
https://www.readbyqxmd.com/read/28546505/role-of-cyp2b-in-phenobarbital-induced-hepatocyte-proliferation-in-mice
#6
Lei Li, Xiaochen Bao, Qing-Yu Zhang, Masahiko Negishi, Xinxin Ding
Phenobarbital (PB) promotes liver tumorigenesis in rodents, in part through activation of the constitutive androstane receptor (CAR) and the consequent changes in hepatic gene expression and increases in hepatocyte proliferation. A typical effect of CAR activation by PB is a marked induction of Cyp2b10 expression in the liver; the latter has been suspected to be vital for PB-induced hepatocellular proliferation. This hypothesis was tested here, by using a Cyp2a(4/5)bgs-null (null) mouse model, in which all Cyp2b genes are deleted...
May 25, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28546220/activation-of-adiponectin-receptor-regulates-proprotein-convertase-subtilisin-kexin-type-9-expression-and-inhibits-lesions-in-apoe-deficient-mice
#7
Lei Sun, Xiaoxiao Yang, Qi Li, Peng Zeng, Ying Liu, Lipei Liu, Yuanli Chen, Miao Yu, Chuanrui Ma, Xiaoju Li, Yan Li, Rongxin Zhang, Yan Zhu, Qing Robert Miao, Jihong Han, Yajun Duan
OBJECTIVE: The reduced adiponectin levels are associated with atherosclerosis. Adiponectin exerts its functions by activating adiponectin receptor (AdipoR). Proprotein convertase subtilisin kexin type 9 (PCSK9) degrades LDLR protein (low-density lipoprotein receptor) to increase serum LDL-cholesterol levels. PCSK9 expression can be regulated by PPARγ (peroxisome proliferator-activated receptor γ) or SREBP2 (sterol regulatory element-binding protein 2). The effects of AdipoR agonists on PCSK9 and LDLR expression, serum lipid profiles, and atherosclerosis remain unknown...
May 25, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28545547/clonorchis-sinensis-granulin-identification-immunolocalization-and-function-in-promoting-the-metastasis-of-cholangiocarcinoma-and-hepatocellular-carcinoma
#8
Caiqin Wang, Huali Lei, Yanli Tian, Mei Shang, Yinjuan Wu, Ye Li, Lu Zhao, Mengchen Shi, Xin Tang, Tingjin Chen, Zhiyue Lv, Yan Huang, Xiaoping Tang, Xinbing Yu, Xuerong Li
BACKGROUND: Long-term infections by Clonorchis sinensis are associated with cholangitis, cholecystitis, liver fibrosis, cirrhosis, and even liver cancer. Molecules from the worm play vital roles in disease progress. In the present study, we identified and explored molecular characterization of C. sinensis granulin (CsGRN), a growth factor-like protein from C. sinensis excretory/secretory products (CsESPs). METHODS: The encoding sequence and conserved domains of CsGRN were identified and analysed by bioinformatics tools...
May 25, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28545186/gallium-nanoparticle-mediated-reduction-of-brain-specific-serine-protease-4-in-an-experimental-metastatic-cancer-model
#9
Enas M Moustafa, Marwa Abdelhameed Mohamed, Noura M Thabet
Purpose: Tumor growth and metastasis depend on angiogenesis; therefore, efforts are being made to develop specific angiogenic inhibitors. Gallium (Ga) is the second most common metal ion, after platinum, used in cancer treatment. Its activities are numerous and various. In the present study, we aimed to investigate the effect of Ga on brain metastasis arising from hepatocellular carcinoma (HCC). Materials and methods: Forty experimental rats (divided into 4 groups) received diethylnitrosamine (DEN) at a dose (20 mg/kg...
April 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28545127/improvement-of-alt-decay-kinetics-by-all-oral-hcv-treatment-role-of-ns5a-inhibitors-and-differences-with-ifn-based-regimens
#10
Valeria Cento, Thi Huyen Tram Nguyen, Domenico Di Carlo, Elisa Biliotti, Laura Gianserra, Ilaria Lenci, Daniele Di Paolo, Vincenza Calvaruso, Elisabetta Teti, Maddalena Cerrone, Dante Romagnoli, Michela Melis, Elena Danieli, Barbara Menzaghi, Ennio Polilli, Massimo Siciliano, Laura Ambra Nicolini, Antonio Di Biagio, Carlo Federico Magni, Matteo Bolis, Francesco Paolo Antonucci, Velia Chiara Di Maio, Roberta Alfieri, Loredana Sarmati, Paolo Casalino, Sergio Bernardini, Valeria Micheli, Giuliano Rizzardini, Giustino Parruti, Tiziana Quirino, Massimo Puoti, Sergio Babudieri, Antonella D'Arminio Monforte, Massimo Andreoni, Antonio Craxì, Mario Angelico, Caterina Pasquazzi, Gloria Taliani, Jeremie Guedj, Carlo Federico Perno, Francesca Ceccherini-Silberstein
BACKGROUND: Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. STUDY DESIGN: Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR...
2017: PloS One
https://www.readbyqxmd.com/read/28544244/branched-chain-amino-acids-supplementation-modulates-tgf-%C3%AE-1-smad-signaling-pathway-and-interleukins-in-ccl4-induced-liver-fibrosis
#11
Naglaa F Khedr, Eman G Khedr
The alterations and low levels of circulating branched chain amino acids (BCAAs), leucine, isoleucine and valine, are associated with liver diseases. The study was designed to evaluate hepatoprotective effect of BCAAs on CCl4 -induced liver fibrosis and to investigate the molecular mechanisms underlying these effects in rats. Thirty male rats were divided into three groups. Control group (n=10), CCl4 group (n=10); rats were injected with CCl4 (1 mL/kg of 0.5:1 v/v injected i.p. twice weekly for 12 weeks). CCl4 +BCAAs group (n=10); rats were injected with similar doses of CCl4 and supplemented with a mixture of 600 mg/kg BCAAs (2: 1: 1...
May 23, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28543181/loss-of-l-selectin-guided-cd8-but-not-cd4-cells-protects-against-ischemia-reperfusion-injury-in-a-steatotic-liver
#12
Vasantha L Kolachala, Sirish Palle, Ming Shen, Alayna Feng, Dmitry Shayakhmetov, Nitika A Gupta
BACKGROUND & AIMS: Steatotic liver responds with increased hepatocellular injury when exposed to an ischemic-reperfusion insult. Increasing evidence supports the role of immune cells as key mediators of this injury in a normal (lean) state, but data about their role in a steatotic liver are practically non-existent. The objective of the current study was to delineate contribution of specific phenotypes of T cells and adhesion molecules in exacerbated cell death in steatotic liver injury...
May 20, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28543100/syndecan-1-limits-the-progression-of-liver-injury-and-promotes-liver-repair-in-acetaminophen-induced-liver-injury
#13
Eon Jeong Nam, Kazutaka Hayashida, Rafael S Aquino, John R Couchman, Rosemary A Kozar, Jian Liu, Pyong Woo Park
Accidental or intentional misuse of acetaminophen (APAP) is the leading cause of acute liver failure in the Western world. While mechanisms that trigger APAP-induced liver injury are well known, those that halt the progression of APAP liver disease and facilitate liver recovery are less understood. Heparan sulfate proteoglycans (HSPGs) bind to and regulate various tissue injury factors through their heparan sulfate (HS) chains, but the importance of HSPGs in liver injury in vivo remains unknown. Here, we examined the role of syndecan-1, the major cell surface HSPG of hepatocytes, in APAP-induced liver injury...
May 22, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28542705/a-pump-free-microfluidic-3d-perfusion-platform-for-the-efficient-differentiation-of-human-hepatocyte-like-cells
#14
Louis Jun Ye Ong, Lor Huai Chong, Lin Jin, Pawan Kumar Singh, Poh Seng Lee, Hanry Yu, Abhishek Ananthanarayanan, Hwa Liang Leo, Yi-Chin Toh
The practical application of microfluidic liver models for in vitro drug testing is partly hampered by their reliance on human primary hepatocytes, which are limited in number and have batch-to-batch variation. Human stem cell-derived hepatocytes offer an attractive alternative cell source, although their 3D differentiation and maturation in a microfluidic platform have not yet been demonstrated. We develop a pump-free microfluidic 3D perfusion platform to achieve long-term and efficient differentiation of human liver progenitor cells into hepatocyte-like cells (HLCs)...
May 20, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28542544/development-and-characterization-of-an-experimental-model-of-diet-induced-metabolic-syndrome-in-rabbit
#15
Oscar Julián Arias-Mutis, Vannina G Marrachelli, Amparo Ruiz-Saurí, Antonio Alberola, Jose Manuel Morales, Luis Such-Miquel, Daniel Monleon, Francisco J Chorro, Luis Such, Manuel Zarzoso
Metabolic syndrome (MetS) has become one of the main concerns for public health because of its link to cardiovascular disease. Murine models have been used to study the effect of MetS on the cardiovascular system, but they have limitations for studying cardiac electrophysiology. In contrast, the rabbit cardiac electrophysiology is similar to human, but a detailed characterization of the different components of MetS in this animal is still needed. Our objective was to develop and characterize a diet-induced experimental model of MetS that allows the study of cardiovascular remodeling and arrhythmogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28542387/lncrna-af113014-promotes-the-expression-of-egr2-by-interaction-with-mir-20a-to-inhibit-proliferation-of-hepatocellular-carcinoma-cells
#16
Tao Zeng, Dan Wang, Juan Chen, Yuanyuan Tian, Xuefei Cai, Hong Peng, Liying Zhu, Ailong Huang, Hua Tang
Long non-coding RNAs (lncRNAs), tentatively identified as non-protein coding RNA, are transcripts more than 200nt in length and accounting for 98% of the whole genome of human being. Accumulating evidence showed aberrant expressions of lncRNAs are strongly correlated to the development of cancers. In this study, AF113014 is a new lncRNA identified from Microarray. We found AF113014 is differentially expressed between HCC cell lines and normal hepatocytes. Functionally, AF113014 inhibited proliferation of HCC cells both in vitro and in vivo, whereas the opposite effect was observed when AF113014 knockdown...
2017: PloS One
https://www.readbyqxmd.com/read/28542148/modulation-of-liver-regeneration-via-myeloid-pten-deficiency
#17
Wen-Tao Ma, Yan-Jie Jia, Qing-Zhi Liu, Yan-Qing Yang, Jing-Bo Yang, Zhi-Bin Zhao, Zhen-Ye Yang, Qing-Hua Shi, Hong-Di Ma, M Eric Gershwin, Zhe-Xiong Lian
Molecular mechanisms that modulate liver regeneration are of critical importance for a number of hepatic disorders. Kupffer cells and natural killer (NK) cells are two cell subsets indispensable for liver regeneration. We have focused on these two populations and, in particular, the interplay between them. Importantly, we demonstrate that deletion of the myeloid phosphatase and tensin homolog on chromosome 10 (PTEN) leading to an M2-like polarization of Kupffer cells, which results in decreased activation of NK cells...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28542142/deletion-of-pdcd5-in-mice-led-to-the-deficiency-of-placenta-development-and-embryonic-lethality
#18
Ge Li, Chentong Xu, Xin Lin, Liujing Qu, Dan Xia, Beiqi Hongdu, Yan Xia, Xiaokun Wang, Yaxin Lou, Qihua He, Dalong Ma, Yingyu Chen
Programmed cell death 5 (PDCD5) is an apoptosis promoter molecule that displays multiple biological activities. However, the function of PDCD5 in vivo has not yet been investigated. Here, we generated a Pdcd5 knockout mouse model to study the physiological role of PDCD5 in vivo. Knockout of the Pdcd5 gene resulted in embryonic lethality at mid-gestation. Histopathological analysis revealed dysplasia in both the LZs and JZs in Pdcd5(-/-) placentas with defects in spongiotrophoblasts and trophoblast giant cells...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28541126/oxidative-stress-and-hepatotoxicity-in-the-frog-rana-chensinensis-when-exposed-to-low-doses-of-trichlorfon
#19
Bo Li, Yu Ma, Yu H Zhang
Trichlorfon is an organophosphate insecticide that is widely used in aquaculture and agriculture against parasitic infestations and has caused aquatic toxicity to non-target organisms. To evaluate the effects of low doses of trichlorfon on the oxidative stress and hepatotoxicity in amphibians, Chinese brown frogs (Rana chensinensis) were exposed to trichlorfon at concentrations of 0, 0.01, 0.1, and 1.0 mg/L for 2 and 4 weeks. Then, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and the content of malondialdehyde (MDA) in hepatic tissue were examined to evaluate the effects of oxidative stress and lipid peroxidation...
May 25, 2017: Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes
https://www.readbyqxmd.com/read/28540984/inverse-relationship-between-hepatic-steatosis-and-alanine-aminotransferase-with-sex-hormone-binding-globulin-in-men
#20
In Ho Seo, Hyung Bin Lee, Shinhye Kim, Yong Jae Lee, Dong Hyuk Jung
PURPOSE: Sex hormone-binding globulin (SHBG) is a serum glycoprotein produced predominantly in hepatocytes. As such, the synthesis of SHBG could be associated with liver function and metabolic syndrome. Alanine aminotransferase (ALT) levels could reflect hepatocellular injury and insulin resistance; however, the relationship between hepatic steatosis and ALT with SHBG has not been investigated in humans. The objective of this study was to investigate the associations between SHBG and hepatocyte damage among Korean male patients with hepatic steatosis enrolled in a health examination program...
July 2017: Yonsei Medical Journal
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