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Yi Jhen Wu, Yu Chiuan Wu, I-Fen Chen, Yi-Lung Wu, Chin Wen Chuang, Han Hsiang Huang, Shyh Ming Kuo
Astaxanthin (Asta), a xanthophyll carotenoid, has been reported to be a strong antioxidative agent and has anti-inflammatory, antitumor and free radical-scavenging activities. However, inadequate stability and water solubility results in its low bioavailability. This study incorporated Asta into hydrophilic hyaluronan nanoparticles (HAn) to produce Asta-HAn aggregates (AHAna) using an electrostatic field system and investigated the restorative effects of AHAna on retrorsine-CCl₄-induced liver fibrosis in rats in vivo...
March 22, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Driele Tavares, Marcelo Gustavo Paulino, Ana Paula Terezan, João Batista Fernandes, Alessandra Giani, Marisa Narciso Fernandes
Cyanobacterial proliferation in river and lakes is the result of eutrophication. The cyanobacterium Radiocystis fernandoi strain R28 produces mostly two MC variants MC-RR and MC-YR and small amounts of other oligopeptides, but does not produce MC-LR. The present study investigated the hepatotoxic potential of the crude extract of the R. fernandoi strain R28 on the Neotropical fish, Piaractus mesopotamicus, at 3, 6, and 24 h after intraperitoneal injection (100 μg MC-LR equivalent per kg-1 body mass) using biochemical and morphological biomarkers of liver damage...
March 21, 2018: Environmental Science and Pollution Research International
Jia Liu, Li-Li Hou, Cui-Ying Zhao
The herbal medicine Yin Huang Mixture (YHHJ; patent no. 200910031240.7) is an aqueous extract composed from various herbs, including Artemisia capillaries Thunb, Hypericum japonicum Thunb, Eucommia ulmoides Oliver, Rheum officinale Baill, Gardenia jasminoides Ellis, Poria cocos Wolf and Dictamnus dasycarpus Turcz. Previous studies have indicated that YHHJ treatment has a beneficial effect on ameliorating itching and reducing serum bile acid levels in patients with intrahepatic cholestasis of pregnancy (ICP)...
April 2018: Experimental and Therapeutic Medicine
Yi-Fan Tong, Ning Meng, Miao-Qin Chen, Han-Ning Ying, Ming Xu, Billy Lu, Jun-Jie Hong, Yi-Fan Wang, Xiu-Jun Cai
AIM: To establish a rat model for evaluating the maturity of liver regeneration derived from associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). METHODS: In the present study, ALPPS, partial hepatecotmy (PHx), and sham rat models were established initially, which were validated by significant increase of proliferative markers including Ki-67, proliferating cell nuclear antigen, and cyclin D1. In the setting of accelerated proliferation in volume at the second and fifth day after ALPPS, the characteristics of newborn hepatocytes, as well as specific markers of progenitor hepatic cell, were identified...
March 14, 2018: World Journal of Gastroenterology: WJG
Maria E Moreno-Fernandez, Daniel A Giles, Traci E Stankiewicz, Rachel Sheridan, Rebekah Karns, Monica Cappelletti, Kristin Lampe, Rajib Mukherjee, Christian Sina, Anthony Sallese, James P Bridges, Simon P Hogan, Bruce J Aronow, Kasper Hoebe, Senad Divanovic
Nonalcoholic fatty liver disease (NAFLD), a metabolic predisposition for development of hepatocellular carcinoma (HCC), represents a disease spectrum ranging from steatosis to steatohepatitis to cirrhosis. Acox1, a rate-limiting enzyme in peroxisomal fatty acid β-oxidation, regulates metabolism, spontaneous hepatic steatosis, and hepatocellular damage over time. However, it is unknown whether Acox1 modulates inflammation relevant to NAFLD pathogenesis or if Acox1-associated metabolic and inflammatory derangements uncover and accelerate potential for NAFLD progression...
March 22, 2018: JCI Insight
Monica Serra, Michela Marongiu, Antonella Contini, Toshio Miki, Erika Cadoni, Ezio Laconi, Fabio Marongiu
Amniotic epithelial cells (AECs) represent a useful and noncontroversial source for liver-based regenerative medicine, as they can differentiate into hepatocytes upon transplantation into the liver. However, the possibility that AECs can differentiate into other liver cell types, such as hepatic sinusoidal endothelial cells (HSECs), has never been assessed. In order to test this hypothesis, rat- and human-derived AECs (rAECs and hAECs, respectively) were subjected to endothelial cell tube formation assay in vitro...
January 2018: Cell Transplantation
Alan Jiang, Qiufeng Liu, Ruifeng Wang, Peng Wei, Yang Dai, Xin Wang, Yechun Xu, Yuchi Ma, Jing Ai, Jingkang Shen, Jian Ding, Bing Xiong
Fibroblast growth factor receptors (FGFRs), a subfamily of receptor tyrosine kinases, are aberrant in various cancer types, and considered to be promising targets for cancer therapy. We started with a weak-active compound that was identified from our internal hepatocyte growth factor receptor (also called c-Met) inhibitor project, and optimized it with the guidance of a co-crystal structure of compound 8 with FGFR1. Through rational design, synthesis, and the biological evaluation of a series of 5 H -pyrrolo[2,3- b ]pyrazine derivatives, we discovered several potent FGFR kinase inhibitors...
March 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Giovanni Ciccarelli, Saverio D'Elia, Michele De Paulis, Paolo Golino, Giovanni Cimmino
The role of low-density lipoproteins (LDLs) as a major risk factor for cardiovascular disease has been demonstrated by several epidemiological studies. The molecular basis for LDLs in atherosclerotic plaque formation and progression is not completely unraveled yet. Pharmacological modulation of plasma LDL-C concentrations and randomized clinical trials addressing the impact of lipid-lowering interventions on cardiovascular outcome have clearly shown that reducing plasma LDL-C concentrations results in a significant decrease in major cardiovascular events...
March 17, 2018: Diseases (Basel)
Devram S Ghorpade, Lale Ozcan, Ze Zheng, Sarah M Nicoloro, Yuefei Shen, Emily Chen, Matthias Blüher, Michael P Czech, Ira Tabas
Obesity-induced metabolic disease involves functional integration among several organs via circulating factors, but little is known about crosstalk between liver and visceral adipose tissue (VAT). In obesity, VAT becomes populated with inflammatory adipose tissue macrophages (ATMs). In obese humans, there is a close correlation between adipose tissue inflammation and insulin resistance, and in obese mice, blocking systemic or ATM inflammation improves insulin sensitivity. However, processes that promote pathological adipose tissue inflammation in obesity are incompletely understood...
March 21, 2018: Nature
Na-Na Tao, Rui Gong, Xiang Chen, Lin He, Fang Ren, Hai-Bo Yu, Juan Chen, Ji-Hua Ren
Hepatitis B virus (HBV) infection is a major health problem worldwide. Interleukin-35 (IL-35) is a definite immunosuppressive cytokine belonging to the IL-12 family. Nevertheless, the role of IL-35 in HBV replication remains elusive. In this study, we found that the level of HBV DNA replicative intermediates detected by qPCR and Southern blotting analysis was significantly increased by rhIL-35 in a dose-dependent manner. Moreover, HBV 3.5 kb mRNA levels were up-regulated by rhIL-35. The HBV core protein level as well as the HBsAg and HBeAg secretion levels were also increased by rhIL-35...
March 21, 2018: Journal of General Virology
Yanjie Li, Nan Lin, Jianliang Xu, Yi Lu, Shuxian Chen, Chuzhi Pan, Chusi Wang, Mingxing Xu, Boxuan Zhou, Ruiyun Xu, Yong-Jiang Xu
BACKGROUND Most forms of cancer, including hepatocellular carcinoma (HCC), are associated with varying degrees of chronic inflammation. The association between the expression of eicosanoids, which are bioactive lipid mediators of inflammation, and HCC remains unknown. The aim of this study was to measure serum and hepatic eicosanoids in a mouse model of HCC with the delivery of c-Met and activated b-catenin by hepatocyte hydrodynamic injection. MATERIAL AND METHODS The HCC mouse model, and normal control mice, were used in this study with co-delivery of human c-Met combined with activated β-catenin into hepatocytes through hydrodynamic injection...
March 21, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Shuying He, Weihong Guo, Feihong Deng, Kequan Chen, Yonghong Jiang, Minyu Dong, Liang Peng, Xueqing Chen
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and precision therapeutic will be a benefit for the NAFLD regression. In this study, we observed low microRNA 146 b (miR-146 b) expression in NAFLD mice model induced by methionine-choline-deficient diet (MCD) compared with control group. Furthermore, miR-146b-/- mice induced MCD exhibited severe liver steatosis and hepatitis. A bio-distribution study showed that novel Lactosylated PDMAEMA nanoparticles effectively targeted hepatocytes Lac-PDMAEMA...
March 21, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Kadri Atay, Billur Canbakan, Emine Koroglu, Ibrahim Hatemi, Mustafa Canbakan, Nuray Kepil, Murat Tuncer, Hakan Senturk
BACKGROUNDS AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR). We evaluated whether IR contributes to hepatocyte apoptosis, inflammation, and fibrosis in NAFLD. METHODS: Forty-four teetotaller patients with biopsy-proven diagnosis of NAFLD were enrolled. Twenty-eight NAFLD patients with IR were compared with 16 subjects without IR. For apoptotic activity caspase 3 and 8, transcription nuclear factor kB (NF-kB), and anti-apoptotic Bcl-2 protein were determined through immunohistochemical methods...
April 2017: Acta Gastro-enterologica Belgica
Minako Nagatome, Yuki Kondo, Daisuke Kadowaki, Yusuke Saishyo, Mitsuru Irikura, Tetsumi Irie, Yoichi Ishitsuka
Acetaminophen, a common analgesic/antipyretic, is a frequent cause of acute liver failure in Western countries. The development of an effective cure against acetaminophen hepatotoxicity is crucial. Ethyl pyruvate, an ethyl ester derivative of pyruvic acid, has been identified as a possible candidate against acetaminophen hepatotoxicity in animal experiments. However, the mode of the hepatoprotective action of ethyl pyruvate remains unclear. We examined the hepatoprotective effect of ethyl pyruvate against hepatocyte injury and oxidative stress in a mouse model of acetaminophen hepatotoxicity...
February 2018: Heliyon
Youhei Okada, Ting Wang, Kazuhiro Kasai, Kazuyuki Suzuki, Yasuhiro Takikawa
Transforming growth factor-beta (TGF-β) is critical in cancer cell invasion and metastasis. The effects of a treatment that targets TGF-β using the combination of interferon alpha (IFNα)-2b and 5-fluorouracil (5-FU) are unknown. Here, we show that the serum levels of TGF-β1 prior to the therapy correlate with increased maximum tumor diameter, which is significantly ( p  < 0.01) decreased after the combination therapy. 5-FU increased both the expression and secretion levels of TGF-β1 in hepatoma cells, but not in normal hepatocytes...
2018: Cell Death Discovery
Kimihiro Nishino, Sayaka Koda, Naoya Kataoka, Shinji Takamatsu, Miyako Nakano, Shun Ikeda, Yuka Kamamatsu, Koichi Morishita, Kenta Moriwaki, Hidetoshi Eguchi, Eiko Yamamoto, Fumitaka Kikkawa, Yasuhiko Tomita, Yoshihiro Kamada, Eiji Miyoshi
We previously found that the serum level of fucosylated haptoglobin (Fuc-Hpt) was significantly increased in pancreatic cancer patients. To delineate the mechanism underlying this increase and develop a simple detection method, we set out to generate a monoclonal antibody (mAb) specific for Fuc-Hpt. After multiple screenings by enzyme-linked immunosorbent assay (ELISA), a 10-7G mAb was identified as being highly specific for Fuc-Hpt generated in a cell line as well as for Hpt derived from a pancreatic cancer patient...
February 27, 2018: Oncotarget
Pengming Sun, Lifang Xue, Yiyi Song, Xiaodan Mao, Lili Chen, Binhua Dong, Elena Loana Braicu, Jalid Sehouli
The effects of specific and non-specific regulation of matriptase on endometrial cancer cells in vitro were investigated. Messenger ribonucleic acid (mRNA) and protein expression of matriptase and hepatocyte growth factor activator inhibitor-1 (HAI-1) in RL-952, HEC-1A, and HEC-1B endometrial cancer cells were detected by real-time quantitative PCR (RT-qPCR) and western blot. The cells were infected with lentivirus-mediated small-interfering RNA (siRNA) targeted on matriptase (MA-siRNA) or treated with different cisplatin (DDP) concentrations...
February 27, 2018: Oncotarget
Romeo Papazyan, Xueqing Liu, Jingwen Liu, Bin Dong, Emily M Plummer, Ronald D Lewis, Jonathan D Roth, Mark A Young
Obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist that regulates bile acid and lipid metabolism. FXR activation induces distinct changes in circulating cholesterol among animal models and humans. The mechanistic basis of these effects has been elusive because of difficulties in studying lipoprotein homeostasis in mice, which predominantly package circulating cholesterol in high-density lipoproteins. Here, we tested the effects of OCA in chimeric mice whose livers are mostly composed (≥80%) of human hepatocytes...
March 20, 2018: Journal of Lipid Research
Hwi Young Kim, Dong Hyeon Lee, Jeong-Hoon Lee, Young Youn Cho, Eun Ju Cho, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon
BACKGROUND: Prediction of the outcome of sorafenib therapy using biomarkers is an unmet clinical need in patients with advanced hepatocellular carcinoma (HCC). The aim was to develop and validate a biomarker-based model for predicting sorafenib response and overall survival (OS). METHODS: This prospective cohort study included 124 consecutive HCC patients (44 with disease control, 80 with progression) with Child-Pugh class A liver function, who received sorafenib...
March 20, 2018: BMC Cancer
Ying Huang, Fang Liu, Fang Zhang, Pingsheng Liu, Tao Xu, Wenjun Ding
Numerous studies have demonstrated that vanadium compounds are able to improve lipemia and triglyceridemia in both humans and animals. However, the molecular mechanism remains elusive. The present study was conducted to investigate the anti-hyperlipidemic effect of vanadium(IV) complex with 4-chlorodipicolinic acid (VOdipic-Cl)-induced autophagy on hepatic lipid accumulation. To explore the possible underlying mechanisms, primary rat hepatocytes, human hepatoma cell line HepG2, and liver tissue from C57BL/6 mice fed a high-fat diet (HFD) were used...
March 14, 2018: Journal of Inorganic Biochemistry
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