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https://www.readbyqxmd.com/read/28339471/expression-quantitative-trait-loci-for-pax8-contributes-to-the-prognosis-of-hepatocellular-carcinoma
#1
Shijie Ma, Jianshui Yang, Ci Song, Zijun Ge, Jing Zhou, Guoxin Zhang, Zhibin Hu
Paired-box family member PAX8 encodes a transcription factor that has a role in cell differentiation and cell growth and may participate in the prognosis of hepatocellular carcinoma (HCC). By bioinformatics analysis, we identified several single nucleotide polymorphisms (SNPs) within a newly identified long non-coding RNA (lncRNA) AC016683.6 as expression quantitative trait loci (eQTLs) for PAX8. Hence, we hypothesized that PAX8eQTLs in lncRNA AC016683.6 may influence the HCC prognosis. We then performed a case-only study to assess the association between the two SNPs as well as the prognosis of HCC in 331 HBV-positive HCC patients without surgical treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28339466/in-silico-search-for-modifier-genes-associated-with-pancreatic-and-liver-disease-in-cystic-fibrosis
#2
Pascal Trouvé, Emmanuelle Génin, Claude Férec
Cystic Fibrosis is the most common lethal autosomal recessive disorder in the white population, affecting among other organs, the lung, the pancreas and the liver. Whereas Cystic Fibrosis is a monogenic disease, many studies reveal a very complex relationship between genotype and clinical phenotype. Indeed, the broad phenotypic spectrum observed in Cystic Fibrosis is far from being explained by obvious genotype-phenotype correlations and it is admitted that Cystic Fibrosis disease is the result of multiple factors, including effects of the environment as well as modifier genes...
2017: PloS One
https://www.readbyqxmd.com/read/28334911/mertk-rs4374383-variant-predicts-incident-nonalcoholic-fatty-liver-disease-and-diabetes-role-of-mononuclear-cell-activation-and-adipokine-response-to-dietary-fat
#3
Giovanni Musso, Maurizio Cassader, Franco De Michieli, Elena Paschetta, Silvia Pinach, Francesca Saba, Daria Bongiovanni, Luciana Framarin, Mara Berrutti, Nicola Leone, Stefania Corvisieri, Renato Parente, Federica Molinaro, Antonio Sircana, Bo Simona, Roberto Gambino
The loss-of-function rs4374383 G>A variant in Myeloid-epithelial-reproductive Tyrosine Kinase (MERTK) gene has been linked to hepatic fibrosis in chronic liver diseases. MERTK is expressed by immune and non-immune cells involved in inflammation, metabolism and vascular homeostasis. We assessed the impact of MERTK rs4374383 G>A variant on nonalcoholic fatty liver disease (NAFLD) incidence and severity and on glucose and lipid metabolism.We followed-up 305 healthy nonobese nondiabetic, metabolic syndrome-free insulin sensitive participants in a population-based study, characterized for MERTK G>A polymorphism, adipokine profile and inflammatory markers...
March 8, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28333016/predictors-of-liver-toxicity-following-stereotactic-body-radiation-therapy-for-hepatocellular-carcinoma
#4
Michael Velec, Carol R Haddad, Tim Craig, Lisa Wang, Patricia Lindsay, James Brierley, Anthony Brade, Jolie Ringash, Rebecca Wong, John Kim, Laura A Dawson
PURPOSE: To identify risk factors associated with a decline in liver function after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma. METHODS AND MATERIALS: Data were analyzed from patients with hepatocellular carcinoma treated on clinical trials of 6-fraction SBRT. Liver toxicity was defined as an increase in Child-Pugh (CP) score ≥2 three months after SBRT. Clinical factors, SBRT details, and liver dose-volume histogram (DVH) parameters were tested for association with toxicity using logistic regression...
April 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28330786/investigating-acetaminophen-hepatotoxicity-in-multi-cellular-organotypic-liver-models
#5
Sophia M Orbach, Margaret E Cassin, Marion F Ehrich, Padmavathy Rajagopalan
In vivo studies clearly demonstrate the participation and subsequent death of non-parenchymal liver cells (NPCs) with corresponding hepatocyte effects. This results in a critical need to investigate how major liver cell types function cohesively during hepatotoxicity. However, virtually no studies replicate these phenomena in vitro. We report the design of multi-cellular three-dimensional (3D) organotypic liver models of primary rat hepatocytes, liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs)...
March 19, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28327528/anti-obesity-effect-of-bombus-ignitus-queen-glycosaminoglycans-in-rats-on-a-high-fat-diet
#6
Mi Young Ahn, Ban Ji Kim, Ha Jeong Kim, Hyung Joo Yoon, Sang Duck Jee, Jae Sam Hwang, Kun-Koo Park
The mechanism of functional insect glycosaminoglycan (GAG) on obesity caused a high fat diet has not yet been elucidated. Therefore, insect glycosaminoglycans derived from Isaria sinclairii, Bombus ignitus (a type of bumblebee) queen, and Gryllus bimaculatus were purified and investigated as a potential functional food. 14-week old male Wistar rats were fed a high-fat diet (HFD) for 6 weeks. There were five groups that received daily intraperitoneal administration of phosphate buffered saline (PBS, control), GbG (GAG from Gryllus bimaculatus) 10 mg/kg, ISG (GAG from Isaria sinclairii) 10 mg/kg, IQG (GAG from Bombus ignites) 10 mg/kg, or Pravastatin (2 mg/kg)...
March 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28324021/endogenous-calcitonin-gene-related-peptide-regulates-lipid-metabolism-and-energy-homeostasis-in-male-mice
#7
Tian Liu, Akiko Kamiyoshi, Takayuki Sakurai, Yuka Ichikawa-Shindo, Hisaka Kawate, Lei Yang, Megumu Tanaka, Xian Xian, Akira Imai, Liuyu Zhai, Kazutaka Hirabayashi, Kun Dai, Keiya Tanimura, Teng Liu, Nanqi Cui, Kyoko Igarashi, Akihiro Yamauchi, Takayuki Shindo
Calcitonin gene-related peptide (CGRP) is a bioactive peptide produced by alternative splicing of the primary transcript of the calcitonin/CGRP gene. CGRP is largely distributed in the cardiovascular and nervous systems, where it acts as a regulatory factor. CGRP is also expressed in organs and tissues involved in metabolic regulation, including white adipose tissue (WAT), where its function is largely unknown. In this study, we examined the effects of endogenous CGRP on metabolic function. When we administered a high-fat diet to CGRP knockout (CGRP-/-) and wild-type (WT) mice for 10 weeks, we observed that food intake did not differ between the two groups, but body weight and visceral fat weight were significantly lower in CGRP-/- mice...
January 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322318/12-o-tetradecanoylphorbol-13-acetate-tpa-is-anti-tumorigenic-in-liver-cancer-cells-via-inhibiting-yap-through-amot
#8
Guoqing Zhu, Yan Chen, Xiao Zhang, Qi Wu, Yinghui Zhao, Yuxin Chen, Fenyong Sun, Yongxia Qiao, Jiayi Wang
TPA stimulates carcinogenesis in various types of cancers. However, we found that TPA inhibits transformative phenotypes in liver cancer cells via the translocation of YAP from the nucleus, where it functions as a transcriptional co-factor, to the cytoplasm. Such effects led to a separation of YAP from its dependent transcription factors. The inhibitory effects of TPA on YAP were AMOT dependent. Without AMOT, TPA was unable to alter YAP activity. Importantly, the depletion of YAP and AMOT blocked the TPA-reduced transformative phenotypes...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28321091/azacitidine-therapy-for-low-risk-myelodysplastic-syndrome-developing-after-solid-organ-transplantation
#9
Hiroaki Inoue, Yasuyoshi Morita, Shinya Rai, Hiroaki Kakutani, Yasuyo Ohyama, Yasuhiro Taniguchi, Hirokazu Tanaka, Takahiro Shimada, Yoichi Tatsumi, Takashi Ashida, Itaru Matsumura
Immunosuppressive therapy after solid organ transplantation is known to be a risk factor for the development of myelodysplastic syndromes (MDS). Herein, we report 2 patients, both of whom developed low-risk MDS after solid organ transplantation and were successfully treated with azacitidine (AZA). The 1st case was a 74-year-old man who had received liver transplantation. The initial immunosuppressive therapy consisted of cyclosporine and prednisolone. Nine years after transplantation, he was diagnosed as having MDS (RCMD)...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28320485/mesenchymal-stem-cells-increase-expression-of-heme-oxygenase-1-leading-to-anti-inflammatory-activity-in-treatment-of-acute-liver-failure
#10
Zhi-Heng Zhang, Wei Zhu, Hao-Zhen Ren, Xin Zhao, Shuai Wang, Hu-Cheng Ma, Xiao-Lei Shi
BACKGROUND: Mesenchymal stem cells (MSCs) have been studied for the treatment of acute liver failure (ALF) for several years. MSCs may exert their effect via complex paracrine mechanisms. Heme oxygenase (HO) 1, a rate-limiting enzyme in heme metabolism, exerts a wide range of anti-inflammatory, anti-apoptotic and immunoregulatory effects in a variety of diseases. However, the relationship between MSCs and HO-1 in the treatment of ALF is still unclear. We investigated the preventive and therapeutic potential of intravenously administered BMSCs...
March 20, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28319169/high-meld-score-and-extended-operating-time-predict-prolonged-initial-icu-stay-after-liver-transplantation-and-influence-the-outcome
#11
Panagiota Stratigopoulou, Andreas Paul, Dieter P Hoyer, Stylianos Kykalos, Fuat H Saner, Georgios C Sotiropoulos
BACKGROUND: The aim of the present study is to determine the incidence of a prolonged (>3 days) initial ICU-stay after liver transplantation (LT) and to identify risk factors for it. PATIENTS AND METHODS: We retrospectively analyzed data of adult recipients who underwent deceased donor first-LT at the University Hospital Essen between 11/2003 and 07/2012 and showed a primary graft function. RESULTS: Of the 374 recipients, 225 (60.16%) had prolonged ICU-stay...
2017: PloS One
https://www.readbyqxmd.com/read/28319060/the-anti-diabetic-drug-exenatide-a-glucagon-like-peptide-1-receptor-agonist-counteracts-hepatocarcinogenesis-through-camp-pka-egfr-stat3-axis
#12
M Zhou, M T S Mok, H Sun, A W Chan, Y Huang, A S L Cheng, G Xu
Epidemiological studies have demonstrated a close association of type 2 diabetes and hepatocellular carcinoma (HCC). Exenatide (Ex-4), a potent diabetes drug targeting glucagon-like peptide-1 receptor (GLP-1R), is protective against non-alcoholic fatty liver disease (NAFLD). However, the Ex-4 function and GLP-1R status have yet been explored in HCC. Herein we investigated the effect of Ex-4 in diethylnitrosamine (DEN)-treated mice consuming control or high-fat high-carbohydrate diet. Administration of Ex-4 significantly improved obesity-induced hyperglycemia and hyperlipidemia and reduced HCC multiplicity in obese DEN-treated mice, in which suppressed proliferation and induced apoptosis were confined to tumor cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28317840/association-between-liver-function-and-metabolic-syndrome-in-chinese-men-and-women
#13
Sen Wang, Jie Zhang, Li Zhu, Linlin Song, Zhaowei Meng, Qiang Jia, Xue Li, Na Liu, Tianpeng Hu, Pingping Zhou, Qing Zhang, Li Liu, Kun Song, Qiyu Jia
Metabolic syndrome (MS) could be associated with liver function. Our study aimed to investigate the association between liver function and MS in a large cohort of Chinese men and women. We enrolled 32,768 ostensibly healthy participants. The associations between liver function and MS of both genders were analyzed separately after dividing total bilirubin (TBIL), gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) into quartiles. Young males had significantly higher MS prevalence than females, yet after menopause, females had higher MS prevalence...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317482/nutraceuticals-as-an-important-part-of-combination-therapy-in-dyslipidaemia
#14
Angelo Maria Patti, Peter P Toth, Rosaria Vincenza Giglio, Maciej Banach, Marcello Noto, Dragana Nikolic, Giuseppe Montalto, Manfredi Rizzo
Several risk factors such as abnormality of lipid metabolism (e.g. high levels of low-density lipoprotein cholesterol (LDL-C), elevated triglycerides and low levels of high-density lipoprotein cholesterol (HDL-C)) play a central role in the aetiology of cardiovascular disease (CVD). Nutraceutical combination together with a cholesterol-lowering action, when associated with suitable lifestyle, should furnish an alternative to pharmacotherapy in patients reporting statin-intolerance and in subjects at low cardiovascular risk...
March 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28315901/the-effect-of-sitagliptin-on-lipid-metabolism-of-fatty-liver-mice-and-related-mechanisms
#15
Bilin Xu, Tian Shen, Lin Chen, Juan Xia, Cuiping Zhang, Hongping Wang, Ming Yu, Tao Lei
BACKGROUND In clinics, patients with type 2 diabetes complicated with non-alcoholic fatty liver disease (NAFLD) have been shown to receive significant improvements in blood glucose levels, lipid levels, and liver function after sitagliptin treatment, although the mechanism of drug action remains poorly understood. This study investigated the possible mechanism of sitagliptin on lipid metabolism of NAFLD mice. MATERIAL AND METHODS Male C57/BL6 mice were induced for NAFLD via 16 weeks of a high-fat diet, and were treated with 15 mg/kg/day sitagliptin for 16 consecutive weeks...
March 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28314773/glucocorticoid-receptor-signaling-represses-the-antioxidant-response-by-inhibiting-histone-acetylation-mediated-by-the-transcriptional-activator-nrf2
#16
Md Morshedul Alam, Keito Okazaki, Linh Thi Thao Nguyen, Nao Ota, Hiroshi Kitamura, Shohei Murakami, Hiroki Shima, Kazuhiko Igarashi, Hiroki Sekine, Hozumi Motohashi
NRF2 (nuclear factor erythroid 2-related factor 2) is a key transcriptional activator that mediates the inducible expression of antioxidant genes. NRF2 is normally ubiquitinated by KEAP1 (Kelch-like ECH-associated protein 1) and subsequently degraded by proteasomes. Inactivation of KEAP1 by oxidative stress or electrophilic chemicals allows NRF2 to activate transcription through binding to antioxidant response elements (AREs) and recruiting histone acetyltransferase CBP (CREB-binding protein). While KEAP1-dependent regulation is a major determinant of NRF2 activity, NRF2-mediated transcriptional activation varies from context to context, suggesting other intracellular signaling cascades may impact NRF2 function...
March 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28314735/non-alcoholic-fatty-liver-disease-and-its-relationship-with-cardiovascular-disease-and-other-extrahepatic-diseases
#17
REVIEW
Leon A Adams, Quentin M Anstee, Herbert Tilg, Giovanni Targher
Key physiological functions of the liver, including glucose and lipid metabolism, become disturbed in the setting of non-alcoholic fatty liver disease (NAFLD) and may be associated with a systemic inflammatory 'milieu' initiated in part by liver-secreted cytokines and molecules. Consequently, the pathophysiological effects of NAFLD extend beyond the liver with a large body of clinical evidence demonstrating NAFLD to be independently associated with both prevalent and incident cardiovascular disease (CVD), chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM)...
March 17, 2017: Gut
https://www.readbyqxmd.com/read/28297787/-umbilical-cord-mesenchymal-stem-cells-and-their-association-with-liver-fibrosis
#18
L Tuo, W Z Zeng, H L Xue, X L Wu
At present, the most effective therapeutic method for end-stage liver fibrosis is liver transplantation. However, the application of liver transplantation is limited by a shortage of liver donors, a high incidence rate of surgical complications, graft-versus-host disease, and high medical costs. Umbilical cord mesenchymal stem cell (UC-MSC) transplantation may become a promising method for the treatment of liver diseases. UC-MSCs are adult stem cells which exhibit multipotential differentiation and can differentiate into hepatic parenchymal cells...
January 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28295976/insulin-like-growth-factor-1-deficiency-exacerbates-hypertension-induced-cerebral-microhemorrhages-in-mice-mimicking-the-aging-phenotype
#19
Stefano Tarantini, Noa M Valcarcel-Ares, Andriy Yabluchanskiy, Zsolt Springo, Gabor A Fulop, Nicole Ashpole, Tripti Gautam, Cory B Giles, Jonathan D Wren, William E Sonntag, Anna Csiszar, Zoltan Ungvari
Clinical and experimental studies show that aging exacerbates hypertension-induced cerebral microhemorrhages (CMHs), which progressively impair neuronal function. There is growing evidence that aging promotes insulin-like growth factor 1 (IGF-1) deficiency, which compromises multiple aspects of cerebromicrovascular and brain health. To determine the role of IGF-1 deficiency in the pathogenesis of CMHs, we induced hypertension in mice with liver-specific knockdown of IGF-1 (Igf1(f/f)  + TBG-Cre-AAV8) and control mice by angiotensin II plus l-NAME treatment...
March 14, 2017: Aging Cell
https://www.readbyqxmd.com/read/28295475/downregulation-of-hnf-4%C3%AE-and-defective-zonation-in-livers-expressing-mutant-z-%C3%AE-1-antitrypsin
#20
Pasquale Piccolo, Patrizia Annunziata, Leandro R Soria, Sergio Attanasio, Anna Barbato, Raffaele Castello, Annamaria Carissimo, Luca Quagliata, Luigi M Terracciano, Nicola Brunetti-Pierri
α1 -antitrypsin (AAT) deficiency is one of the most common genetic disorders and the liver disease due to the Z mutant of α1 -antitrypsin (ATZ) is a prototype of conformational disorder due to misfolding of protein with consequent aberrant intermolecular protein aggregation. In the present study, we found that livers of PiZ transgenic mice expressing the human ATZ have altered expression of a network of hepatocyte transcriptional factors including HNF4-α, that is early downregulated and induces a transcriptional repression of ATZ expression...
March 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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