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Macrophage secretory products induce an inflammatory phenotype in hepatocytes

World Journal of Gastroenterology 2012年第15期18卷 1732-1744页

作者： Michelle Melino Victoria L Gadd Gene V Walker Richard Skoien Helen D Barrie Dinesh Jothimani leigh horsfall Alun Jones Matthew J Sweet Gethin P Thomas Andrew D Clouston Julie R Jonsson Elizabeth E Powell Centre for Liver Disease Research School of MedicineThe University of QueenslandPrincess Alexandra HospitalBrisbane 4102QueenslandAustralia Department of Gastroenterology and Hepatology Princess Alexandra HospitalBrisbane 4102QueenslandAustralia Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre The University of QueenslandBrisbane 4072QueenslandAustralia Diamantina Institute The University of QueenslandBrisbane 4102QueenslandAustralia

AIM:To investigate the influence of macrophages on hepatocyte phenotype and ***:Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophageconditioned medium on HepG2 mRNA and protein expression *** in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus(HCV)***:Conditioned media from macrophages,but not monocytes,induced a transient morphological change in hepatocytes associated with upregulation of vimentin(7.8±2.5-fold,P=0.045)and transforming growth factor(TGF)-β1(2.6±0.2-fold,P<0.001)and downregulation of epithelial cadherin(1.7±0.02-fold,P=0.017)mRNA *** analysis revealed significant upregulation of lipocalin-2(17-fold,P <0.001)and pathways associated with inflammation,and substantial downregulation of pathways related to hepatocyte *** patients with chronic HCV,realtime polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA(F0 1.0 ±0.3,F1 2.2±0.2,F2 3.0±9.3,F3/4 4.0±0.8,P= 0.003)and protein expression(F1 1.0±0.5,F2 1.3± 0.4,F3/4 3.6±0.4,P=0.014)with increasing liver *** performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase(MMP)-9 in macrophageconditioned medium,and a chemical inhibitor of MMP-9 attenuated the change in morphology and mRNA expression of TGF-β1(2.9±0.2 vs 1.04±0.1,P<0.001) in macrophage-conditioned media treated HepG2 *** patients with chronic HCV infection,hepatic mRNA expression of CD163(F0 1.0±0.2,F1/2 2.8±0.3,F3/4 5.3±1.0,P=0.001)and MMP-9(F0 1.0±0.4,F1/2 2.8±0.3,F3/4 4.1±0.8,P=0.011)was significantly associated with increasing stage of ***:Secreted macrophage products alter the phenotype and function of hepatocytes,with increased expression of inflammatory mediators,suggesting that hepatocytes actively participat

关键词： Macrophages Hepatic fibrosis Lipocalin-2 Transforming growth factor-β1 Matrix metalloproteinase-9

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Medication beliefs predict medication adherence in ambulatory patients with decompensated cirrhosis

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World Journal of Gastroenterology 2017年第40期23卷 7321-7331页

作者： Kelly L Hayward Patricia C Valery Jennifer H Martin Antara Karmakar Preya J Patel leigh U horsfall Caroline J Tallis Katherine A Stuart Penny L Wright David D Smith Katharine M Irvine Elizabeth E Powell W Neil Cottrell Pharmacy Department Princess Al-exandra Hospital The Centre for Liver Disease Research Translational Research Institute The University of Queensland Cancer and Chronic Disease Research Group QIMR Berghofer Medical Research Institute School of Medicine and Public Health The University of Newcastle The Centre for Liver Disease Research Translational Research Institute The University of Queensland Department of Gastroenterology and Hepatology Princess Alexandra Hospital The Centre for Liver Disease Research Translational Research Institute The University of Queensland Department of Gastroenterology and Hepatology Princess Alexandra Hospital Statistics Unit QIMR Berghofer Medical Research Institute School of Pharmacy The University of Queensland

AIM To investigate the impact of medication beliefs, illness perceptions and quality of life on medication adherence in people with decompensated *** One hundred adults with decompensated cirrhosis completed a structured questionnaire when they attended for routine outpatient hepatology review. Measures of self-reported medication adherence(Morisky Medication Adherence Scale), beliefs surrounding medications(Beliefs about Medicines Questionnaire), perceptions of illness and medicines(Brief Illness Perception Questionnaire), and quality of life(Chronic Liver Disease Questionnaire) were examined. Clinical data were obtained via patient history and review of medical records. Least absolute shrinkage and selection operator and stepwise backwards regression techniques were used to construct the multivariable logistic regression model. Statistical significance was set at alpha = *** Medication adherence was " High " in 42 % o f participants, "Medium" in 37%, and "Low" in 21%. Compared to patients with "High" adherence, those with "Medium" or "Low" adherence were more likely to report difficulty affording their medications(P < 0.001), lower perception of treatment helpfulness(P = 0.003) and stronger medication concerns relative to medication necessity beliefs(P = 0.003). People with "Low" adherence also experienced greater symptom burden and poorer quality of life, including more frequent abdominal pain(P = 0.023), shortness of breath(P = 0.030), and emotional disturbances(P = 0.050). Multivariable analysis identified having stronger medication concerns relative to necessity beliefs(Necessity-Concerns Differential ≤ 5, OR = 3.66, 95%CI: 1.18-11.40) and more frequent shortness of breath(shortness of breath score ≤ 3, OR = 3.87,95%CI: 1.22-12.25) as independent predictors of "Low"*** The association between "Low" adherence and patients having strong concerns or doubting the necessity or helpfulness of their medications should be explor

关键词： Medication adherence Medication beliefs Illness perceptions Quality of life Liver cirrhosis

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