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Qingqing Wei, Ruiqi Li, Liang Zhong, Haiyuan Mu, Shaopeng Zhang, Liang Yue, Jinzhu Xiang, Enhong Li, Minglei Zhi, Suying Cao, Jianyong Han
After zygotic genome activation and lineage specification, zygotes develop into late blastocysts comprising three distinct cell types. The molecular mechanisms underlying this progress are largely unknown in pigs. Here, we intended to analyze an extensive set of regulators at the single-cell level to define the events involved in the development of the porcine blastocysts. Using a quantitative microfluidics approach in single cells, we detected mRNA levels of 96 genes known to function in early embryonic development and maintenance of stem cell pluripotency simultaneously in 480 individual cells derived from porcine preimplantation embryos...
March 13, 2018: Biology of Reproduction
Wan-Angkan Poolsri, Phornpun Phokrai, Somrudee Suwankulanan, Narinthorn Phakdeeto, Pattamaphorn Phunsomboon, Dumrongsak Pekthong, Lysiane Richert, Sutatip Pongcharoen, Piyarat Srisawang
Increased expression levels of both mitochondrial citrate transporter (CTP) and plasma membrane citrate transporter (PMCT) proteins have been found in various cancers. The transported citrates by these two transporter proteins provide acetyl-CoA precursors for the de novo lipogenesis (DNL) pathway to support a high rate of cancer cell viability and development. Inhibition of the DNL pathway promotes cancer cell apoptosis without apparent cytotoxic to normal cells, leading to the representation of selective and powerful targets for cancer therapy...
2018: BioMed Research International
Koji Yamamoto, Makiko Kawaguchi, Takeshi Shimomura, Aya Izumi, Kazuomi Konari, Arata Honda, Chen-Yong Lin, Michael D Johnson, Yoshihiro Yamashita, Tsuyoshi Fukushima, Hiroaki Kataoka
Hepatocyte growth factor activator inhibitor (HAI)-1/ SPINT1 and HAI-2/ SPINT2 are membrane-anchored protease inhibitors having homologous Kunitz-type inhibitor domains. They regulate membrane-anchored serine proteases, such as matriptase and prostasin. Whereas HAI-1 suppresses the neoplastic progression of keratinocytes to invasive squamous cell carcinoma (SCC) through matriptase inhibition, the role of HAI-2 in keratinocytes is poorly understood. In vitro homozygous knockout of the SPINT2 gene suppressed the proliferation of two oral SCC (OSCC) lines (SAS and HSC3) but not the growth of a non-tumorigenic keratinocyte line (HaCaT)...
February 20, 2018: Oncotarget
Shi Cheng, Yan Yang, Yong Zhou, Wei Xiang, Hua Yao, Ling Ma
The development of nonalcoholic fatty liver disease (NAFLD) is caused by the steatosis of hepatocytes, which induces oxidative stress (OS). Thus, OS has an important role in the development of NAFLD. In the present study, the L-02 hepatocyte cell line was used to develop a steatosis cell model. The best model was determined using an MTT assay and the triglyceride levels. Model cells were treated with high concentrations of uric acid (UA; 0, 5, 10, 20 and 30 mg/dl) for 24, 48, 72 and 96 h. Indicators of oxidation were then measured, which included total superoxide dismutase (SOD), malonaldehyde (MDA) and reduced glutathione (GSH), and the transcriptional and translational levels of SOD1 and γ-glutamate-cysteine ligase (γ-GCLC) were also determined...
April 2018: Experimental and Therapeutic Medicine
Xueliang Yang, Yunru Chen, Jian Zhang, Tiantian Tang, Ying Kong, Feng Ye, Xi Zhang, Xiaojing Liu, Shumei Lin
The present study aimed to evaluate whether thymosin α1 (Tα1) increases survival rates through the improvement of immunofunction and inhibition of hepatocyte apoptosis in rats with acute liver failure (ALF). A total of 25 rats were randomly divided into the control group (CG), the model group (MG) and the treatment group (TG). The CG received an intraperitoneal injection of saline (2 ml). The ALF rat model was established by the intraperitoneal injection of D-galactosamine (700 mg/kg) and lipopolysaccharide (10 µg/kg)...
April 2018: Experimental and Therapeutic Medicine
Marwa M Abu-Serie
Liver cancer is mainly originated by cancer stem cells (CSCs). Due to difference in pH between normal and tumor cell microenvironments, targeting hepatic CSCs exploiting pH-dependent charge switchable nanoparticles (NPs) is extremely required to limit nonselective toxicity to normal hepatocytes (NHCs) and to completely eliminate the root of cancer origin. In this study, NPs were prepared from cationic chitosan and then coated with anionic albumin namely uncoated and coated NPs, respectively. Both NPs were loaded with diethyldithiocarbamate (DDC) which is an inhibitor of the critical enzyme, aldehyde dehydrogenase (ALDH) 1A1, for CSCs survival...
March 15, 2018: Scientific Reports
Jingxiao Wang, Mingjie Dong, Zhong Xu, Xinhua Song, Shanshan Zhang, Yu Qiao, Li Che, John Gordan, Kaiwen Hu, Yan Liu, Diego F Calvisi, Xin Chen
Liver cancer comprises a group of malignant tumors, among which hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common. ICC is especially pernicious and associated with poor clinical outcome. Studies have shown that a subset of human ICCs may originate from mature hepatocytes. However, the mechanisms driving the trans-differentiation of hepatocytes into malignant cholangiocytes remain poorly defined. We adopted lineage tracing techniques and an established murine hepatocyte-derived ICC model by hydrodynamic injection of activated forms of AKT (myr-AKT) and Yap (YapS127A) proto-oncogenes...
March 16, 2018: Oncogene
Jacquelyn O Russell, Sungjin Ko, Harvinder S Saggi, Sucha Singh, Minakshi Poddar, Donghun Shin, Satdarshan P Monga
Bromodomain and extraterminal (BET) proteins recruit key components of basic transcriptional machinery to promote gene expression. Aberrant expression and mutations in BET genes have been identified in many malignancies. Small molecule inhibitors of BET proteins like JQ1 have shown efficacy in preclinical cancer models including affecting growth of hepatocellular carcinoma. BET proteins also regulate cell proliferation in nontumor settings. We recently showed that BET proteins regulate cholangiocyte-driven liver regeneration...
March 12, 2018: American Journal of Pathology
Zhanni Gu, Lingyan Wu, Yanan Duan, Jiang Wang, Shengbin Zhou, Jingya Li, Kaixian Chen, Jia Li, Hong Liu
To discover more derivatives with better glucose-lowering efficacy compared with berberine, twenty-three novel compounds with 4,7,12,12a-tetrahydro-5H-thieno[3',2':3,4]pyrido[1,2-b]isoquinoline or 5,8,12,12a-tetrahydro-6H-thieno[2',3':4,5]pyrido[2,1-a]isoquinoline cores were designed, synthesized, and biologically evaluated in vitro in continuation of our previous work on indirect activators of adenosine 5'-monophosphate-activated protein kinase (AMPK). Nine compounds effectively stimulated glucose consumption (>2...
March 12, 2018: Bioorganic & Medicinal Chemistry
Shenglin Fang, Zhao Zhuo, Xiaonan Yu, Haichao Wang, Jie Feng
The aim of this study was to determine the toxicological effects of excess iron in a liquid iron preparation (especially on intestinal barrier function) and the possible etiology of side effects or diseases caused by the excess iron. In study 1, forty male Sprague-Dawley rats (4-5 wk old) were subjected to oral gavage with 1 ml vehicle (0.01 mol/L HCl) or 1 ml liquid iron preparation containing 8 mg, 16 mg or 24 mg of iron for 30 d. Iron status, oxidative stress, histology (H&E staining), ultrastructure (electron microscopy) and apoptosis (TUNEL assay) in the intestines and liver were assessed...
May 2018: Journal of Trace Elements in Medicine and Biology
Yu Wu, Ze-Yang Ding, Guan-Nan Jin, Yi-Xiao Xiong, Bin Yu, Yi-Min Sun, Wei Wang, Hui-Fang Liang, Bixiang Zhang, Xiao-Ping Chen
Hepatic progenitor cells (HPCs) are a subpopulation of cells which was usually expanded in chronic liver injury and are contributed to liver regeneration through differentiating into hepatocytes and cholangiocytes. Epithelial-mesenchymal transition is a dynamic process which is important for the progression of liver fibrosis and cancer initiation. This study demonstrated that LE/6 and WB-F344 cells, both of which were HPC derived cell lines, were undergoing partial epithelial-mesenchymal transition states, which was indicated by the co-expression of epithelial markers (E-cadherin and zona occludin 1), and mesenchymal markers (vimentin, fibronectin, collagen 1and α-SMA)...
March 12, 2018: Biochimie
Yasmine Baktash, Anisha Madhav, Kelly E Coller, Glenn Randall
Hepatitis C virus (HCV) enters hepatocytes via various entry factors, including scavenger receptor BI (SR-B1), cluster of differentiation 81 (CD81), epidermal growth factor receptor (EGFR), claudin-1 (CLDN1), and occludin (OCLN). As CLDN1 and OCLN are not readily accessible due to their tight junctional localization, HCV likely accesses them by either disrupting cellular polarity or migrating to the tight junction. In this study, we image HCV entry into a three-dimensional polarized hepatoma system and reveal that the virus sequentially engages these entry factors through actin-dependent mechanisms...
March 14, 2018: Cell Host & Microbe
Nora Freyer, Selina Greuel, Fanny Knöspel, Florian Gerstmann, Lisa Storch, Georg Damm, Daniel Seehofer, Jennifer Foster Harris, Rashi Iyer, Frank Schubert, Katrin Zeilinger
The accurate prediction of hepatotoxicity demands validated human in vitro models that can close the gap between preclinical animal studies and clinical trials. In this study we investigated the response of primary human liver cells to toxic drug exposure in a perfused microscale 3D liver bioreactor. The cellularized bioreactors were treated with 5, 10, or 30 mM acetaminophen (APAP) used as a reference substance. Lactate production significantly decreased upon treatment with 30 mM APAP ( p < 0.05) and ammonia release significantly increased in bioreactors treated with 10 or 30 mM APAP ( p < 0...
March 15, 2018: Bioengineering
Vahid Mirshafiee, Bingbing Sun, Chong Hyun Chang, Yu-Pei Liao, Wen Jiang, Jinhong Jiang, Xiangsheng Liu, Xiang Wang, Tian Xia, Andre E Nel
The liver and the mononuclear phagocyte system (MPS) is a frequent target for engineered nanomaterials (ENMs), either as a result of particle uptake and spread from primary exposure sites or systemic administration of therapeutic and imaging nanoparticles. In this study, we performed a comparative analysis of the toxicological impact of 29 metal oxide (MOx) nanoparticles (NPs), some commonly used in consumer products, in transformed or primary Kupffer cells (KCs) and hepatocytes. Not only did we observe differences between KC and hepatocytes, but also differences in the toxicological profiles of transition metal oxides (TMOs, e...
March 15, 2018: ACS Nano
Alexander Raven, Wei-Yu Lu, Tak Yung Man, Sofia Ferreira-Gonzalez, Eoghan O'Duibhir, Benjamin J Dwyer, John P Thomson, Richard R Meehan, Roman Bogorad, Victor Koteliansky, Yuri Kotelevtsev, Charles Ffrench-Constant, Luke Boulter, Stuart J Forbes
This corrects the article DOI: 10.1038/nature23015.
March 14, 2018: Nature
Pamela Orjuela-Sanchez, Zaira Hellen Villa, Marta Moreno, Carlos Tong-Rios, Stephan Meister, Gregory M LaMonte, Brice Campo, Joseph M Vinetz, Elizabeth A Winzeler
To develop new drugs and vaccines for malaria elimination, it will be necessary to discover biological interventions, including small molecules that act against Plasmodium vivax exoerythrocytic forms. However, a robust in vitro culture system for P. vivax is still lacking. Thus, to study exoerythrocytic forms, researchers must have simultaneous access to fresh, temperature-controlled patient blood samples, as well as an anopheline mosquito colony. In addition, researchers must rely on native mosquito species to avoid introducing a potentially dangerous invasive species into a malaria-endemic region...
March 15, 2018: ACS Infectious Diseases
Lin Cao, Jizheng Chen, Yaxin Wang, Yuting Yang, Jie Qing, Zihe Rao, Xinwen Chen, Zhiyong Lou
Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. Although several HCV protease/polymerase inhibitors were recently approved by U.S. FDA, the combination of antivirals targeting multiple processes of HCV lifecycle would optimize anti-HCV therapy and against potential drug-resistance. Viral entry is an essential target step for antiviral development, but FDA-approved HCV entry inhibitor remains exclusive. Here we identify serotonin 2A receptor (5-HT2A R) is a HCV entry factor amendable to therapeutic intervention by a chemical biology strategy...
March 14, 2018: Protein & Cell
Qian Chen, Mengyang Liu, Haiyang Yu, Jian Li, Sijian Wang, Yi Zhang, Feng Qiu, Tao Wang
Scutellaria baicalensis has been reported to improve the lipid metabolism of high-fat diet-induced liver dysfunction, but direct evidence is rare. This study aimed to explore the effects and mechanisms of S. baicalensis and its major constituent baicalin on hepatic lipotoxicity. KK-Ay mice and orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) rats were used to evaluate lipid metabolism regulatory effects. Sodium oleate-induced triglyceride-accumulated HepG2 cells were used for the mechanism study, pretreated with or without compound C or STO-609 or transfected with liver kinase B1 (LKB1) siRNA...
March 14, 2018: Journal of Natural Medicines
Liisa Ailanen, Natalia N Bezborodkina, Laura Virtanen, Suvi T Ruohonen, Anastasia V Malova, Sergey V Okovityi, Elizaveta Y Chistyakova, Eriika Savontaus
Hepatic insulin resistance and increased gluconeogenesis are known therapeutic targets of metformin, but the role of hepatic glycogen in the pathogenesis of diabetes is less clear. Mouse model of neuropeptide Y (NPY) overexpression in noradrenergic neurons (OE-NPYD βH ) with a phenotype of late onset obesity, hepatosteatosis, and prediabetes was used to study early changes in glycogen structure and metabolism preceding prediabetes. Furthermore, the effect of the anti-hyperglycemic agent, metformin (300 mg/kg/day/4 weeks in drinking water), was assessed on changes in glycogen metabolism, body weight, fat mass, and glucose tolerance...
April 2018: Pharmacology Research & Perspectives
Ursula J Lemberger, Claudia D Fuchs, Christian Schöfer, Andrea Bileck, Christopher Gerner, Tatjana Stojakovic, Makoto M Taketo, Michael Trauner, Gerda Egger, Christoph H Österreicher
Background: Wnt/β-catenin signaling plays a crucial role in embryogenesis, tissue homeostasis, metabolism and malignant transformation of different organs including the liver. Continuous β-catenin signaling due to somatic mutations in exon 3 of the Ctnnb1 gene is associated with different liver diseases including cancer and cholestasis. Results: Expression of a degradation resistant form of β-catenin in hepatocytes resulted in 100% mortality within 31 days after birth...
February 16, 2018: Oncotarget
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