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https://www.readbyqxmd.com/read/28820612/the-potential-of-signal-peptide-peptidase-as-a-therapeutic-target-for-hepatitis-c
#1
Kohji Moriishi
Chronic infection with hepatitis C virus (HCV) causes liver steatosis, cirrhosis, metabolic syndrome with inflammation, and eventually leads to hepatocellular carcinoma. HCV core protein is a well-known capsid protein and pathogenic factor related to lipid accumulation, type 2 diabetes mellitus, and carcinogenesis. Cleavage of the C-terminal transmembrane region by signal peptide peptidase (SPP) is required for maturation of the core protein. Areas covered: Herein, this review details the general aspects of the structure, lifecycle, pathogenesis, and maturation of the HCV core protein, the function of SPP, and clinically available direct-acting antivirals (DAAs)...
August 18, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28820447/comprehensive-study-of-multiple-stages-progressing-to-nonalcoholic-steatohepatitis-with-subsequent-fibrosis-in-sd-rats
#2
Lulu Wang, Susu Wu, Minxuan Cai, Ji Ma, Shengcun Li, Maoru Li, Yan Xu, Lixin Wei, Jing Shang
Because of the absence of the time course of histological nonalcoholic fatty hepatitis with subsequent fibrotic progression, the effective approaches available for controlling the onset and progression of non-alcoholic steatohepatitis (NASH) remain limited. Therefore, we detected the serum and liver tissue related lipid metabolism disorder, liver pathology and relative molecular makers alteration dynamically in a high fat-sucrose diet during different time points. High fat-sucrose diet significantly increased the serum lipid level on day 10...
August 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28820393/fibroblast-growth-factor-21-and-omentin-1-hepatic-mrna-expression-and-serum-levels-in-morbidly-obese-women-with-non-alcoholic-fatty-liver-disease
#3
M Waluga, M Kukla, M Zorniak, M Kajor, L Liszka, M Dyaczynski, G Kowalski, D Zadlo, E Waluga, P Olczyk, R J Buldak, A Berdowska, M Hartleb
Fibroblast growth factor-21 (FGF21) and omentin-1 have been recognized as potent antidiabetic agents with potential hepatoprotective activity. The aim of this study was to evaluate hepatic FGF21 and omentin-1 mRNA expression as well as their serum levels as predictive markers of liver injury and insulin resistance in morbidly obese women with non-alcoholic fatty liver disease (NAFLD). This study included 56 severely obese women who underwent intraoperative wedge liver biopsy during the bariatric surgery. Hepatic FGF21 and omentin-1 mRNA were assessed by quantitative real-time PCR, while their serum concentrations were measured with commercially available enzyme-linked immunosorbent assays...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28817690/resveratrol-and-caloric-restriction-prevent-hepatic-steatosis-by-regulating-sirt1-autophagy-pathway-and-alleviating-endoplasmic-reticulum-stress-in-high-fat-diet-fed-rats
#4
Shibin Ding, Jinjin Jiang, Guofu Zhang, Yongjun Bu, Guanghui Zhang, Xiangmei Zhao
BACKGROUND: Studies have demonstrated that resveratrol (a natural polyphenol) and caloric restriction activate Sirtuin-1 (SIRT1) and induce autophagy. Furthermore, autophagy is induced by the SIRT1-FoxO signaling pathway and was recently shown to be a critical protective mechanism against non-alcoholic fatty liver disease (NAFLD) development. We aimed to compare the effects of resveratrol and caloric restriction on hepatic lipid metabolism and elucidate the mechanism by which resveratrol supplementation and caloric restriction alleviate hepatosteatosis by examining the molecular interplay between SIRT1 and autophagy...
2017: PloS One
https://www.readbyqxmd.com/read/28814531/patients-with-nonalcoholic-fatty-liver-disease-have-a-low-response-rate-to-vitamin-d-supplementation
#5
Jaividhya Dasarathy, Rony Varghese, Abram Feldman, Amer Khiyami, Arthur J McCullough, Srinivasan Dasarathy
Background: Hypovitaminosis D is associated with an increased severity of nonalcoholic fatty liver disease (NAFLD), but reports on the response to cholecalciferol (vitamin D3) supplementation are conflicting.Objective: The objective of this study was to determine if standard vitamin D3 supplementation is effective in NAFLD with hypovitaminosis D.Methods: Sixty-five well-characterized adults [age (mean ± SD): 51.6 ± 12.3 y] with biopsy-proven NAFLD were screened. Forty-two patients (the ratio of men to women was 13:29) had hypovitaminosis D (plasma 25-hydroxyvitamin D [25(OH)D] <30 ng/mL)...
August 16, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28813448/a-prospective-comparative-assessment-of-the-accuracy-of-the-fibroscan-in-evaluating-liver-steatosis
#6
Baek Gyu Jun, Won Young Park, Eui Ju Park, Jae Young Jang, Soung Won Jeong, Sae Hwan Lee, Sang Gyune Kim, Sang-Woo Cha, Young Seok Kim, Young Deok Cho, Hong Soo Kim, Boo Sung Kim, So Young Jin, Suyeon Park
BACKGROUND/AIMS: Recent studies have demonstrated the utility of the FibroScan® device in diagnosing liver steatosis, but its usefulness has not been thoroughly appraised. We investigated the usefulness of the controlled attenuation parameter (CAP) in detecting and quantifying liver steatosis. METHODS: A prospective analysis was applied to 79 chronic liver disease patients who underwent a liver biopsy, a FibroScan investigation, ultrasonography, and hepatic steatosis index (HSI)...
2017: PloS One
https://www.readbyqxmd.com/read/28812326/effect-of-dietary-components-from-antarctic-krill-on-atherosclerosis-in-apoe-deficient-mice
#7
Cinzia Parolini, Bodil Bjorndal, Marco Busnelli, Stefano Manzini, Giulia S Ganzetti, Federica Dellera, Marie Ramsvik, Inge Bruheim, Rolf Kristian Berge, Giulia Chiesa
SCOPE: Antarctic krill is a great source of n-3 fatty acids and high-quality proteins. Aim of the study was to evaluate the effect of Antarctic krill components on plasma lipids and atherosclerosis development. METHODS AND RESULTS: Sixty apoEKO mice were divided into four groups and fed Western diet (CONTROL) or Western-like diets, differing for protein or fat content. Specifically, casein or fat in CONTROL was partially replaced by krill proteins (PRO), krill oil (KRILL OIL), or both (KRILL OIL+PRO)...
August 15, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28811860/the-apelin-receptor-apj-in-hematopoietic-stem-cells-progenitor-cells-in-the-early-stage-of-non-alcoholic-steatohepatitis
#8
Wataru Ando, Hiroaki Yokomori, Katsuya Otori, Masaya Oda
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis and inflammation with or without fibrosis. The apelin receptor (APJ) is related to angiotensin-like-receptor 1 (AGTRL1). The present study aimed to evaluate APJ as an indicator of the pathophysiology of early-stage NASH. METHODS: APJ expression was evaluated in six tissue samples with histologically proven early-stage NASH using immunohistochemistry (IHC) and immunoelectron microscopy (IEM)...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28811651/inkt-cells-prevent-obesity-induced-hepatic-steatosis-in-mice-in-a-c-c-chemokine-receptor-7-dependent-manner
#9
H M Kim, R Lee, E S Lee, M H Kwon, J H Huh, B-E Kwon, E-K Park, S-Y Chang, M-N Kweon, P-H Kim, H-J Ko, C H Chung
Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease, and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism...
August 16, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28811294/dihydrocapsiate-improved-age-associated-impairments-in-mice-by-increasing-energy-expenditure
#10
Kana Ohyama, Katsuya Suzuki
Metabolic dysfunction is associated with aging and results in age-associated chronic diseases, including type 2 diabetes mellitus, cardiovascular disease, and stroke. Hence, there has been a focus on increasing energy expenditure in aged populations to protect them from age-associated diseases. Dihydrocapsiate (DCT) is a compound that belongs to the capsinoid family. Capsinoids are capsaicin analogs that are found in non-pungent peppers and increase whole-body energy expenditure. However, their effect on energy expenditure has been reported only in young populations, and to date the effectiveness of DCT in increasing energy expenditure in aged populations has not been investigated...
August 15, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28811292/dapagliflozin-slows-the-progression-of-the-renal-and-liver-fibrosis-associated-with-type-2-diabetes
#11
Li Tang, Yuanyuan Wu, Mi Tian, C David Sjostrom, Ulrika Johansson, Xiao-Rong Peng, David M Smith, Yufeng Huang
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic oral agents indicating promising effects on cardiovascular and renal end points. However, the renoprotective effects of SGLT2 inhibitors are not fully understood. Also, metabolic effects of SGLT2 inhibition on other organ systems such as effects on hepatic steatosis are not fully understood. This study sought to address these questions by treating 18week-old uninephrectomized db/db mice with a selective SGLT2 inhibitor dapagliflozin...
August 15, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28811064/evaluation-of-non-alcoholic-fatty-liver-disease-using-acoustic-radiation-force-impulse-imaging-elastography-in-rat-models
#12
Yanrong Guo, Changfeng Dong, Haoming Lin, Xinyu Zhang, Huiying Wen, Yuanyuan Shen, Tianfu Wang, Siping Chen, Yingxia Liu, Xin Chen
The aim of this study is to evaluate the utility of acoustic radiation force impulse (ARFI) elastography for assessing hepatic fibrosis stage and non-alcoholic fatty liver disease (NAFLD) severity, as well as the relationship among hepatic histologic changes using shear wave velocity (SWV). Animal models with various degrees of NAFLD were established in 110 rats. The right liver lobe was processed and embedded in a fabricated gelatin solution (porcine skin). Liver mechanics were measured using SWV induced by acoustic radiation force...
August 12, 2017: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/28809727/models-of-non-alcoholic-fatty-liver-disease-and-potential-translational-value-the-effects-of-3-5-l-diiodothyronine
#13
Elena Grasselli, Laura Canesi, Piero Portincasa, Adriana Voci, Laura Vergani, Ilaria Demori
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in industrialized countries and is associated with increased risk of cardiovascular, hepatic and metabolic diseases. Molecular mechanisms on the root of the disrupted lipid homeostasis in NAFLD and potential therapeutic strategies can benefit of in vivo and in vitro experimental models of fatty liver. Here, we describe the high fat diet (HFD)-fed rat in vivo model, and two in vitro models, the primary cultured rat fatty hepatocytes or the FaO rat hepatoma fatty cells, mimicking human NAFLD...
August 8, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28808064/obesity-and-aging-diminish-sirt1-mediated-deacetylation-of-sirt3-leading-to-hyperacetylation-and-decreased-activity-and-stability-of-sirt3
#14
Sanghoon Kwon, Sunmi Seok, Peter Yau, Xiaoling Li, Byron Kemper, Jongsook Kim Kemper
Sirtuin 3 (SIRT3) deacetylates and regulates many mitochondrial proteins to maintain health, but its functions are depressed in aging and obesity. The best-studied sirtuin, SIRT1, counteracts aging- and obesity-related diseases by deacetylating many proteins, but whether SIRT1 has a role in deacetylating and altering the function of SIRT3 is unknown. Here we show that SIRT3 is reversibly acetylated in the mitochondria and unexpectedly is a target of SIRT1 deacetylation. SIRT3 is hyperacetylated in aged and obese mice, in which SIRT1 activity is low, and SIRT3 acetylation at K57 inhibits its deacetylase activity and promotes protein degradation...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28807209/induction-of-autophagy-reduces-ischemia-reperfusion-injury-in-steatotic-rat-livers
#15
Chunyi Kan, Anding Liu, Haoshu Fang, Olaf Dirsch, Uta Dahmen, Michael Boettcher
BACKGROUND: Steatotic livers are particularly vulnerable to ischemia/reperfusion injury (IRI). One of the reasons is an underlying impairment of autophagy. Autophagy is regulated by glycogen synthase kinase 3b (GSK3b) and extracellular signal-regulated kinases (ERK1/2) pathways. Both of them are target proteins of a cell-protective drug, lithium chloride. Lithium chloride treatment reduces IRI in many organs including liver. Therefore, we aimed to investigate the effect of lithium chloride treatment on autophagy induction in steatotic rat livers...
August 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28804621/development-of-gene-polymorphisms-in-meditators-of-nonalcoholic-fatty-liver-disease
#16
Chun Wang, Jianping Gong, Hao Wu
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, the morbidity of which closely correlates with diversity of ethnicity, minority, family and location. Its histology spans from simple steatosis, to nonalcoholic steatohepatitis, which ultimately results in fibrosis, cirrhosis and hepatocellular carcinoma. The accelerating prevalence of NAFLD is due to an incremental incidence of metabolic syndrome that is distinguished by dyslipidemia, glucose impairment, obesity, excessive oxidative stress and adipocytokine impairment...
August 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28803762/apigenin-protects-against-alcohol-induced-liver-injury-in-mice-by-regulating-hepatic-cyp2e1-mediated-oxidative-stress-and-ppar%C3%AE-mediated-lipogenic-gene-expression
#17
Feng Wang, Jin-Cheng Liu, Rui-Jun Zhou, Xi Zhao, Mei Liu, Hua Ye, Mei-Lin Xie
Alcohol is a major cause of liver injury, and there are currently no ideal pharmacological reagents that can prevent or reverse this disease. Apigenin is one of the most common flavonoids present in numerous plants and has many beneficial effects. But whether or not apigenin may protect against alcohol-induced liver injury remains unknown. Our aim was to examine the effect and potential mechanisms. The experimental mice were given 56% erguotou wine or simultaneously given apigenin 150-300 mg/kg by gavage for 30 days...
August 10, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28803504/the-pharmacological-management-of-nafld-in-children-and-adolescents
#18
Savinda Liyanagedera, Robert Patrick Williams, Silvio Veraldi, Valerio Nobili, Jake P Mann
Non-alcoholic fatty liver disease (NAFLD) represents a spectrum, including 'simple' steatosis, non-alcoholic steatohepatitis (NASH), and fibrosis. Increasing prevalence of NAFLD has followed the international rise in obesity and lifestyle modification is the mainstay therapy for children. To date, pharmacological trials have had varying efficacy but a large number of new agents are in early phase trials for adults. Areas covered: This review explores the effect of current and potential future paediatric NAFLD treatments in terms of histological and biochemical endpoints...
August 14, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28802563/metabolic-circuit-involving-free-fatty-acids-microrna-122-and-triglyceride-synthesis-in-liver-and-muscle-tissues
#19
Chofit Chai, Mila Rivkin, Liav Berkovits, Alina Simerzin, Elina Zorde-Khvalevsky, Nofar Rosenberg, Shiri Klein, Dayana Yaish, Ronen Durst, Shoshana Shpitzen, Shiran Udi, Joseph Tam, Joerg Heeren, Anna Worthmann, Christoph Schramm, Johannes Kluwe, Revital Ravid, Eran Hornstein, Hilla Giladi, Eithan Galun
BACKGROUND & AIMS: Effective treatments are needed for hepatic steatosis characterized by accumulation of triglycerides in hepatocytes, which leads to hepatocellular carcinoma. MicroRNA 122 (MIR122) is expressed only in the liver, where it regulates lipid metabolism. We investigated the mechanism by which free fatty acids (FFAs) regulate MIR122 expression and the effect of MIR122 on triglyceride synthesis. METHODS: We analyzed MIR122 promoter activity and validated its target mRNAs by transfection of luciferase reporter plasmids into Huh7, BNL-1ME, and HEK293 cultured cell lines...
August 9, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28802559/absence-of-subchronic-oral-toxicity-and-genotoxicity-of-rice-koji-with-aspergillus-terreus
#20
Jun-Won Yun, Seung-Hyun Kim, Yun-Soon Kim, Ji-Ran You, Eun-Young Cho, Jung-Hee Yoon, Euna Kwon, Sang Ju Lee, Seong Pil Kim, Jae Hoon Seo, Jae Pyung In, Jae Hun Ahn, Ja-June Jang, Jin-Sung Park, Jeong-Hwan Che, Byeong-Cheol Kang
Koji products have been considered as an effective fermented food consumed in East Asia with many health benefits. Particularly, rice koji with Aspergillus terreus (RAT) has been reported to be able to prevent hyperlipidemia and hepatic steatosis through regulating cholesterol synthesis. Despite its biological activities, there is a lack of comprehensive information to give an assurance of its safety. Therefore, the objective of this study was to perform a series of toxicological studies (repeated dose oral toxicity and genotoxicity) according to test guidelines published by the Organization for Economic Cooperation and Development...
August 9, 2017: Regulatory Toxicology and Pharmacology: RTP
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