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https://www.readbyqxmd.com/read/29155352/patient-reported-outcomes-following-treatment-of-chronic-hepatitis-c-virus-infection-with-sofosbuvir-and-velpatasvir-with-or-without-voxilaprevir
#1
Zobair M Younossi, Maria Stepanova, Stuart Gordon, Stefan Zeuzem, Michael P Mann, Ira Jacobson, Marc Bourliere, Curtis Cooper, Steven Flamm, K Rajender Reddy, Kris Kowdley, Issah Younossi, Sharon Hunt
BACKGROUND & AIMS: Chronic infection with hepatitis C virus (HCV) has many hepatic and extrahepatic manifestations, measured by patient-reported outcomes (PROs). We measured changes in PROs during HCV treatment with recently developed pangenotypic regimens and from a sustained virologic response 12 weeks after treatment ended (SVR12). METHODS: We collected PRO data from 2 multi-center, blinded, international phase 3 trials of sofosbuvir, velpatasvir, and voxilaprevir, from 748 patients previously treated with direct-acting antivirals for chronic infection with HCV of any genotype (59% HCV genotype 1, 43% with compensated cirrhosis) (POLARIS-1 and POLARIS-4)...
November 16, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29147129/the-effect-of-exercise-training-on-upregulation-of-molecular-markers-of-bile-acid-metabolism-in-the-liver-of-ovariectomized-rats-fed-a-cholesterol-rich-diet
#2
Zahra Farahnak, Luciane Magri Tomaz, Raynald Bergeron, Natalie Chapados, Jean-Marc Lavoie
BACKGROUND: Small heterodimer partner (SHP) is an important transcriptional factor involved in the regulation of glucose, lipid, and bile acid metabolism in the liver. SHP has been reported to be down-regulated in ovariectomized (Ovx) mice and up-regulated by estrogens suggesting a link between estrogens and SHP. The aim of the present study was to determine the effects of exercise training on SHP and key molecular markers of cholesterol and bile acid homeostasis in Ovx rats under cholesterol feeding...
July 2017: ARYA Atherosclerosis
https://www.readbyqxmd.com/read/29142166/fish-oil-feeding-reverses-hepatomegaly-and-disrupted-hepatic-function-due-to-the-lack-of-fxr-signaling
#3
Masaaki Miyata, Kouhei Shinno, Tomoki Kinoshita, Yuichi Kinoshita, Yoshimasa Sugiura
Mice lacking farnesoid X receptor (FXR) are used as a model for nonalcoholic fatty liver disease because their livers exhibit hepatomegaly, hepatic steatosis, and hepatic inflammation. The influence of fish oil feeding on hepatomegaly and disrupted hepatic function was investigated using female Fxr-null mice and wild-type mice fed a fish oil diet (2% fish oil and 2% corn oil) or a control diet (4% corn oil) for 4 weeks. Hepatic n-3 polyunsaturated fatty acid (PUFA) levels, including 22:6 n-3 docosahexaenoic acid (DHA) and 20:5 n-3 eicosapentaenoic acid (EPA) were significantly higher in the fish oil group than those in the control group of Fxr-null mice and wild-type mice...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29137913/neutrophil-cd16b-crosslinking-induces-lipid-raft-mediated-activation-of-shp-2-and-affects-cytokine-expression-and-retarded-neutrophil-apoptosis
#4
H Yang, H Jiang, Y Song, D J Chen, X J Shen, J H Chen
Two different types of FcRs for IgG are constitutively expressed on the surface of human neutrophils, namely, FcγRIIA (CD32a) and FcγRIIIB (CD16b). Unlike FcγRIIA, FcγRIIIb is GPI anchored to the cell membrane and its signal transduction is still ambiguous. To further understand the signal transduction of CD16b, we compared neutrophil cytokine expression and apoptosis by the cross-linking of CD32a and CD16b respectively. We found that both CD32a and CD16b crosslinking can activate neutrophils, but did not exactly share cytokine expression profiles...
November 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29113744/corrigendum-to-blockade-of-stat3-activation-by-sorafenib-derivatives-through-enhancing-shp-1-phosphatase-activity-eur-j-med-chem-55-2012-220-227
#5
Kuen-Feng Chen, Wei-Tien Tai, Cheng-Yi Hsu, Jui-Wen Huang, Chun-Yu Liu, Pei-Jer Chen, InKi Kim, Chung-Wai Shiau
No abstract text is available yet for this article.
November 4, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29113698/the-control-of-oligodendrocyte-bioenergetics-by-interferon-gamma-ifn-%C3%AE-and-src-homology-region-2-domain-containing-phosphatase-1-shp-1
#6
Scott B Minchenberg, Paul T Massa
Glycolysis and mitochondrial respiration are essential for oligodendrocyte metabolism in both the developing and adult CNS. Based on recent reports on the effects of the proinflammatory cytokine IFN-γ on metabolism and on oligodendrocytes, we addressed whether IFN-γ may affect oligodendrocyte bioenergetics in ways relevant to CNS disease. Oligodendrocytes of mice treated with IFN-γ showed significant reductions in aerobic glycolysis and mitochondrial respiration. As expected, IFN-γ treatment led to the induction of STAT1 in oligodendrocytes indicating active signaling into these cells...
October 28, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29113283/epigallocatechin-3-gallate-induces-apoptosis-in-acute-promyelocytic-leukemia-cells-via-a-shp-1-p38%C3%AE-mapk-bax-cascade
#7
Liugen Gan, Liang Zhong, Zhiling Shan, Chunlan Xiao, Ting Xu, Hao Song, Liu Li, Rong Yang, Beizhong Liu
Acute promyelocytic leukemia (APL) is characterized by a specific chromosomal translation, resulting in a fusion gene that affects the differentiation, proliferation and apoptosis of APL cells. Epigallocatechin-3-gallate (EGCG), a catechin, exhibits numerous biological functions, including antitumor activities. Previous studies have reported that EGCG induces apoptosis in NB4 cells. However, the molecular mechanism underlying EGCG-induced apoptosis remains unclear. The present study aimed to determine the molecular basis of EGCG-induced apoptosis in NB4 cells...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29112160/reclamation-of-marine-chitinous-materials-for-the-production-of-%C3%AE-glucosidase-inhibitors-via-microbial-conversion
#8
Van Bon Nguyen, San-Lang Wang
Six kinds of chitinous materials have been used as sole carbon/nitrogen (C/N) sources for producing α-glucosidase inhibitors (aGI) by Paenibacillus sp. TKU042. The aGI productivity was found to be highest in the culture supernatants using demineralized crab shell powder (deCSP) and demineralized shrimp shell powder (deSSP) as the C/N source. The half maximal inhibitory concentration (IC50) and maximum aGI activity of fermented deCSP (38 µg/mL, 98%), deSSP (108 µg/mL, 89%), squid pen powder (SPP) (422 µg/mL, 98%), and shrimp head powder (SHP) (455 µg/mL, 92%) were compared with those of fermented nutrient broth (FNB) (81 µg/mL, 93%) and acarbose (1095 µg/mL, 74%), a commercial antidiabetic drug...
November 7, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29111786/active-hexose-correlated-compound-ahcc-inhibits-the-proliferation-of-ovarian-cancer-cells-by-suppressing-signal-transducer-and-activator-of-transcription-3-stat3-activation
#9
Jin Young Choi, Seul Lee, Sun-Mi Yun, Dong Hoon Suh, Kidong Kim, Jae Hong No, Eun-Hwan Jeong, Yong Beom Kim
The purpose of this study was to investigate the antiproliferative effect of active hexose correlated compound (AHCC), derived from basidiomycete mushroom culture, on ovarian cancer cell lines. An in vitro growth inhibition assay was performed using AHCC in ovarian cancer cell lines. Western blotting was performed to investigate the mechanism of the observed antiproliferative effect of AHCC. We identified that ovarian cancer cell viability was significantly reduced through treatment with AHCC compared to that in the control...
November 7, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/29093677/levodopa-benserazide-loaded-microspheres-alleviate-l-dopa-induced-dyskinesia-through-preventing-the-over-expression-of-d1r-shp-2-erk1-2-signaling-pathway-in-a-rat-model-of-parkinson-s-disease
#10
Ying Wan, Na Wu, Lu Song, Xijin Wang, Zhenguo Liu, Weien Yuan, Jing Gan
Background: The long-term intermittent Levodopa (L-dopa) stimulation contributes to an aberrant activation of D1 receptor (D1R) mediated extracellular signal-regulated kinases1/2 (ERK1/2) in the striatal medium spiny neurons, resulting in the occurrence of L-dopa induced dyskinesia (LID). Recently, a novel signaling pathway, D1R/Shp-2/ERK1/2, was proposed to be required for the occurrence of LID. Here we designed the study in which two different methods of L-dopa delivery [continuous dopamine stimulation (CDS) vs...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29079885/therapeutic-potential-of-curcumin-for-multiple-sclerosis
#11
Munibah Qureshi, Ebtesam A Al-Suhaimi, Fazli Wahid, Omer Shehzad, Adeeb Shehzad
Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS), characterized by demyelination, neuronal injury, and breaching of the blood-brain barrier (BBB). Epidemiological studies have shown that immunological, genetic, and environmental factors contribute to the progression and development of MS. T helper 17 (Th17) cells are crucial immunological participant in the pathophysiology of MS. The aberrant production of IL-17 and IL-22 by Th17 cells crosses BBB promotes its disruption and interferes with transmission of nerve signals through activation of neuroinflammation in the CNS...
October 27, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/29074590/deletion-of-at2-receptor-prevents-shp-1-induced-vegf-inhibition-and-improves-blood-flow-reperfusion-in-diabetic-ischemic-hindlimb
#12
Judith Paquin-Veillette, Farah Lizotte, Stéphanie Robillard, Raphaël Béland, Marc-André Breton, Andréanne Guay, Marc-Antoine Despatis, Pedro Geraldes
OBJECTIVE: Ischemia caused by narrowing of femoral artery is a major cause of peripheral arterial disease and morbidity affecting patients with diabetes mellitus. We have previously reported that the inhibition of the angiogenic response to VEGF (vascular endothelial growth factor) in diabetic mice was associated with the increased expression of SHP-1 (SH2 domain-containing phosphatase 1), a protein that can be activated by the AT2 (angiotensin II type 2) receptor. Deletion of AT2 receptor has been shown to promote angiogenesis within the ischemic muscle...
October 26, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29068796/protein-phosphatases-and-podocyte-function
#13
Pedro Geraldes
PURPOSE OF REVIEW: Deregulation of protecting factor signaling actions in podocytes has emerged as an alternative pathway of podocyte injury mechanisms. Here, we review recent knowledge that highlighted how podocyte protecting factors are modulated by protein phosphatases. RECENT FINDINGS: Protein tyrosine kinases and phosphatases participate in many, if not all, aspects of cellular function by turning on or off multiple signaling cascades and podocytes are no exception...
October 23, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29053943/inflammation-status-of-healthy-young-men-initial-and-specific-responses-to-resistance-training
#14
Johanna K Ihalainen, Heikki Peltonen, Göran Paulsen, Juha P Ahtiainen, Ritva S Taipale, Mari Hämäläinen, Eeva Moilanen, Antti A Mero
PURPOSE: Our primary aim was to study the effects of a 4 wk preparatory resistance training (RT) period followed by 12 wks of two specific RT protocols (either hypertrophic-strength, HS, or strength-hypertrophy-power, SHP, training) on inflammation markers and the possible relationship of the changes in abdominal fat and lean mass to the changes in inflammation status. METHODS: A total of 82 healthy men were included in the study. Maximal concentric leg press strength (1RM), total body lean mass, total body and abdominal fat mass, circulating high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), monocyte chemoattractant protein 1 (MCP-1), and selected adipocytokines (resistin, adiponectin and leptin) concentrations were measured before (PRE) and after 4 (wk4) and 16 weeks (wk16) of RT...
October 20, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/29041942/patient-reported-health-related-quality-of-life-work-productivity-and-activity-impairment-during-treatment-with-alo-02-extended-release-oxycodone-and-sequestered-naltrexone-for-moderate-to-severe-chronic-low-back-pain
#15
Arnold J Weil, Elizabeth T Masters, Alexandra I Barsdorf, Almasa Bass, Glenn Pixton, Jacquelyn G Wilson, Gernot Wolfram
BACKGROUND: The efficacy of ALO-02, an abuse-deterrent formulation containing extended-release oxycodone and sequestered naltrexone, in the treatment of chronic low back pain (CLBP) was studied in a 12-week randomized controlled trial. Primary efficacy endpoint results have been published previously (Rauck et al., 2015). The current paper focuses on patient-reported outcomes for health-related quality of life (HRQL), work productivity, and activity impairment that were assessed during this study...
October 17, 2017: Health and Quality of Life Outcomes
https://www.readbyqxmd.com/read/29031599/interaction-of-dj-1-with-lyn-is-essential-for-ige-mediated-stimulation-of-human-mast-cells
#16
Do-Kyun Kim, Michael A Beaven, Dean D Metcalfe, Ana Olivera
BACKGROUND: DJ-1 is a redox-sensitive protein with multiple roles in cell homeostasis whose levels are altered in mast cell (MC)-related disorders. However, whether DJ-1 can regulate human MC function is unknown. OBJECTIVE: We sought to investigate the potential role of DJ-1 in the responses of human MCs to antigen stimulation. METHODS: DJ-1 was silenced in human CD34(+)-derived and LAD2 MCs using lentiviral sh-RNA constructs. Release of β-hexosaminidase, PGD2 and GM-CSF and changes in reactive oxygen species (ROS) levels were measured after FcεRI engagement...
October 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29029413/targeting-shp-1-stat3-signaling-a-promising-therapeutic-approach-for-the-treatment-of-cholangiocarcinoma
#17
Ming-Hung Hu, Li-Ju Chen, Yen-Lin Chen, Ming-Shen Tsai, Chung-Wai Shiau, Tzu-I Chao, Chun-Yu Liu, Jia-Horng Kao, Kuen-Feng Chen
Sorafenib is a multiple kinase inhibitor which targets Raf kinases, VEGFR, and PDGFR and is approved for the treatment of hepatocellular carcinoma (HCC). Previously, we found that p-STAT3 is a major target of SC-43, a sorafenib derivative. In this study, we report that SC-43-induced apoptosis in cholangiocarcinoma (CCA) via a novel mechanism. Three CCA cell lines (HuCCT-1, KKU-100 and CGCCA) were treated with SC-43 to determine their sensitivity to SC-43-induced cell death and apoptosis. We found that SC-43 activated SH2 domain-containing phosphatase 1 (SHP-1) activity, leading to p-STAT3 and downstream cyclin B1 and Cdc2 downregulation, which induced G2-M arrest and apoptotic cell death...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29028359/complex-interaction-between-circadian-rhythm-and-diet-on-bile-acid-homeostasis-in-male-rats
#18
Hannah M Eggink, Johanneke E Oosterman, Paul de Goede, Emmely M de Vries, Ewout Foppen, Martijn Koehorst, Albert K Groen, Anita Boelen, Johannes A Romijn, Susanne E la Fleur, Maarten R Soeters, Andries Kalsbeek
Desynchronization between the master clock in the brain, which is entrained by (day) light, and peripheral organ clocks, which are mainly entrained by food intake, may have negative effects on energy metabolism. Bile acid metabolism follows a clear day/night rhythm. We investigated whether in rats on a normal chow diet the daily rhythm of plasma bile acids and hepatic expression of bile acid metabolic genes is controlled by the light/dark cycle or the feeding/fasting rhythm. In addition, we investigated the effects of high caloric diets and time-restricted feeding on daily rhythms of plasma bile acids and hepatic genes involved in bile acid synthesis...
October 13, 2017: Chronobiology International
https://www.readbyqxmd.com/read/29025706/no-augments-endothelial-reactivity-by-reducing-myoendothelial-calcium-signal-spreading-a-novel-role-for-cx37-connexin-37-and-shp-2
#19
Kristin Pogoda, Hanna Mannell, Stephanie Blodow, Holger Schneider, Kai Michael Schubert, Jiehua Qiu, Andreas Schmidt, Axel Imhof, Heike Beck, Laurentia Irina Tanase, Alexander Pfeifer, Ulrich Pohl, Petra Kameritsch
OBJECTIVE: Because of its strategic position between endothelial and smooth muscle cells in microvessels, Cx37 (Connexin 37) plays an important role in myoendothelial gap junctional intercellular communication. We have shown before that NO inhibits gap junctional intercellular communication through gap junctions containing Cx37. However, the underlying mechanism is not yet identified. APPROACH AND RESULTS: Using channel-forming Cx37 mutants exhibiting partial deletions or amino acid exchanges in their C-terminal loops, we now show that the phosphorylation state of a tyrosine residue at position 332 (Y332) in the C terminus of Cx37 controls the gap junction-dependent spread of calcium signals...
October 12, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29016649/small-heterodimer-partner-shp-deficiency-protects-myocardia-from-lipid-accumulation-in-high-fat-diet-fed-mice
#20
Jung Hun Ohn, Ji Yeon Hwang, Min Kyong Moon, Hwa Young Ahn, Hwan Hee Kim, Young Do Koo, Kwang-Il Kim, Hyuk Jae Chang, Hye Seung Lee, Hak Chul Jang, Young Joo Park
The small heterodimer partner (SHP) regulates fatty acid oxidation and lipogenesis in the liver by regulating peroxisome proliferator-activated receptor (PPAR) γ expression. SHP is also abundantly expressed in the myocardium. We investigated the effect of SHP expression on myocardia assessing not only heart structure and function but also lipid metabolism and related gene expression in a SHP deletion animal model. Transcriptional profiling with a microarray revealed that genes participating in cell growth, cytokine signalling, phospholipid metabolism, and extracellular matrix are up-regulated in the myocardia of SHP knockout (KO) mice compared to those of wild-type (WT) mice (nominal p value < 0...
2017: PloS One
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