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Effect of interferon alpha2b plus ribavirin treatment on selected growth factors in respect to inflammation and fibrosis in chronic hepatitis c

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World Journal of Gastroenterology 2005年第12期11卷 1854-1858页

作者： Panasiuk anatol Flisiak Robert Prokopowicz Danuta Department of Infectious Diseases

AIM: Growth factors (GF) that participate in regeneration and apoptosis have an important role in chronic liver diseases. We analyzed serum GF concentration during antiviral treatment and correlated it with morphological liver failure in chronic hepatitis c. METHODS: The levels of GF were determined in sera by ELISA method in 0,16,32 and 48 wk of therapy in 40 patients treated with IFNα2b (9 MU sc/wk) and RBV (1.2 g/d) and in 25 healthy subjects. Blind liver biopsies were done before treatment with histological grading and staging examination. RESULTS: The hepatocyte growth factor (HGF) and epidermal growth factor (EGF) were markedly elevated prior the treatment and decreased during the therapy, although they did not reach the normal level. In non-responding (NR) patients, HGF and EGF were higher than that in responders (R), however differences were not significant. Before the treatment thrombopoietin (TPO) level was significantly lower in R than in NR (Pctor (PDGF) concentration was lower in chronic hepatitis c than in healthy subjects and decreased during the treatment. A significant positive correlation was observed between inflammatory activity in the liver tissue and the concentration of HGF (in R: r= 0.4, in NR: r= 0.5), TPO (R: r= 0.6), and a significant negative correlation between this activity and EGF (R: r = -0.6) and PDGF (R: r= -0.5). Serum HGF concentration was higher in more advanced fibrosis (R: r = 0.5, PcONcLUSION: The decrease in PDGF can be an effective prognostic marker of the treatment and HcV elimination. Decreasing HGF, EGF, and PDGF can influence the inhibition of inflammatory and fibrotic processes in the liver during the antiviral treatment.

关键词： Growth factor chronic hepatitis c Liver biopsy Interferon alfa 2b Ribivirin

Signal transduction pathways in liver and the influence of hepatitis c virus infection on their activities

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World Journal of Gastroenterology 2009年第18期15卷 2184-2189页

作者： Magdalena M Dabrowska anatol Panasiuk Robert Flisiak Department of Infectious Diseases and Hepatology Medical University of Bialystok14 Zurawia Str15-540 BialystokPoland

In liver,the most intensively studied transmembrane and intracellular signal transduction pathways are the Janus kinase signal transduction pathway,the mitogen-activated protein kinases signal transduction pathway,the transforming growth factor β signal transduction pathway,the tumor necrosis factor α signal transduction pathway and the recently discovered sphingolipid signal transduction *** of them are activated by many different cytokines and growth *** regulate specific cell mechanisms such as hepatocytes proliferation,growth,differentiation,adhesion,apoptosis,and synthesis and degradation of the extracellular *** replication cycle of hepatitis c virus(HcV) is intracellular and requires signal transduction to the nucleus to regulate transcription of its ***,HcV itself,by its structural and non-structural proteins,could influence the activity of the second signal ***,the inhibition of the transmembrane and intracellular signal transduction pathways could be a new therapeutic target in chronic hepatitis c treatment.

关键词： Liver Hepatitis c virus infection Signaltransduction pathway Proliferation Apoptosis

Expression of bcl-2 protein in chronic hepatitis c:Effect of interferon alpha 2b with ribavirin therapy

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World Journal of Gastroenterology 2005年第19期11卷 2949-2952页

作者： Panasiuk anatol Prokopowicz Danuta Dzieciol Janusz Panasiuk Bozena Department of Infectious Diseases Medical University of Bialystok Zurawia Str.1415-540 BialystokPoland Department of Human Anatomy Medical University of Bialystok Zurawia Str.1415-540 BialystokPoland

AIM: Mechanisms responsible for persistence of HcV infection and liver damage in chronic hepatitis c are not clear. Apoptosis is an important form of host immune response against viral infections. Anti-apoptotic protein bcl-2 expression on liver tissue as well as the influence of interferon alpha 2b (IFNa2b) and ribavirin (RBV) were analyzed in patients with chronic hepatitis c. METHODS: In 30 patients with chronic hepatitis c (responders - R and non-responders - NR) treated with IFNα2b+RBV, protein bcl-2 was determined in hepatocytes and in liver associated lymphocytes before and after the treatment. RESULTS: The treatment diminished bcl-2 protein accumulation in liver cells in_patients with hepatitis c (Pcted bcl-2 protein in R in 87±15% and 83±20% of hepatocytes and in 28±18% and 26±10% of liver-associated lymphocytes, respectively. In NR, the values before treatment decreased from 94±32% to 88±21% of hepatocytes and 39±29% to 28±12% of lymphocytes with bcl-2 expression. There was no statistical correlation between bcl-2 expression on liver tissue with inflammatory activity, fibrosis and biochemical parameters before and after the treatment. cONcLUSION: IFNα2b+RBV treatment, by bcl-2 protein expression decrease, enables apoptosis of hepatocytes and associated liver lymphocytes, which in turn eliminate hepatitis c viruses.

关键词： Bcl-2 chronic hepatitis c Interferon alpha Ribavirin Hepatitis c virus

Predictors of new-onset atrial fibrillation in elderly patients with coronary artery disease after coronary artery bypass graft

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Journal of Geriatric cardiology 2016年第5期13卷 444-449页

作者： Rubanenko O anatol'evna Fatenkov O Veniaminovic Khokhlunov S Mikhaylovich Department of Faculty Therapy Samara State Medical Universtty Samara Russia Samara Regional cardiology centre Samara Russia

Objective To identify the factors associated with the development of postoperative atrial fibrillation （POAF） after coronary artery bypass graft （cABG） in elderly patients with coronary artery disease （cAD）. Methods A total of 81 patients with cAD who underwent cABG were enrolled in the study. Patients were divided into two groups： Group 1, without postoperative atrial fibrillation （59 patients, 74.6% men, mean age 65.8 ~ 4.0 years）; Group 2, with early new-onset atrial fibrillation after cABG （22 patients, 90.9% men, mean age 67.7 ＋ 5.4 years）. Interleukin （IL）-6, IL-8, IL-10, c-reactive protein （cRP）, fibrinogen, superoxide dismutase （SOD）, N-terminal pro-B-type natriuretic peptide （NT-proBNP）, and troponin I were studied. Results During the observation period, atrial fibrillation occurred in 27.2% cases, an average of 4.9 ±3.8 days after surgery. In group 2, the left atrium （LA） dimension was larger than in group 1 （43.9 ± 3.4 mm vs. 37.6 ±3.9 rnm, P 〈 0.001）. Patients with POAF had significantly higher IL-6 （72.7 ±60.8 pg/mL vs. 38.0 ± 34.6 pg/mL, P = 0.04）, IL-8 （11.9 ± 6.0 pg/mL vs. 7.7± 5.4 pg/mL, P = 0.01） and SOD （2462.0 ± 2029.3 units/g vs. 1515.0 ± 1292.9 units/g, P = 0.04） compared with group without POAF. The multivariate analysis showed that the odds ratio （OR） for POAF development in patients with left atrium more than 39 mm was 2.1 [95% confidence interval （cI）： 1.2-3.8, P = 0.0004], IL-6 levels more than 65.18 pg/mL-1.4 （95% ch 1.1-2.7, P = 0.009）, IL-8 levels more than 9.67 pg/mL-1.2 （95% cI： 1.1-3.7, P ： 0.009）, SOD more than 2948 units/g-1.1 （95% ch 1.01-2.9, P = 0.04）. conclusions In our study, the independent predictors of postoperative atrial fibrillation after cABG in elderly patients were left atrium dimension and the increased postoperative concentration of IL-6, IL-8 and superoxide dismutase.

关键词： Antioxidant Atrial fibrillation coronary artery bypass graft Interleukins Troponin

Expression of β2-integrin on leukocytes in liver cirrhosis

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World Journal of Gastroenterology 2006年第38期12卷 6193-6197页

作者： anatol Panasiuk Janusz ■ak Elzbieta Maciorkowska Bozena Panasiuk Danuta Prokopowicz Department of Infectious Diseases Medical University of Bialystok Poland Department of Pediatrics Diagnostics Medical University of Bialystok Poland Department of Pediatric Nursing Medical University of Bialystok Poland

AIM： To analyze β2-integrin expression on blood leukocytes in liver drrhosis.METHODS： In 40 patients with liver cirrhosis and 20 healthy individuals, the evaluation of expression of cD11a （LFA-1α）, cD11b （Mac-1α）, cD11c （αX） and cD49d （VLA-4α） on peripheral blood leukocytes was performed using flow cytometry. The analysis was carried out in groups of patients divided into B and c according to child-Pugh＇s classification. RESULTS： An increased cDlla, cD11b, cD11c and cD49d integrin expression was observed on peripheral blood leukocytes in liver cirrhosis. The integrin levels were elevated as the advancement of liver failure progressed. The highest expression of integrins occurred predominantly on monocytes. A slight expression of VLA-4 was found on lymphocytes and granulocytes and it increased together with liver failure. A positive correlation was noted between median intensity of fluorescence （MIF） expression on polymorphonuclear cells of cD11a and cD11c and cD49d （r = 0.42, P 〈 0.01; r = 053, P 〈 0.01, respectively） in liver cirrhosis stage c. However, no correlation was observed between integrin expression on leukocytes. The concentrations of sIcAM-1, sVcAM-1, and TNFα, were significantly elevated in liver cirrhosis. cONcLUSION： β2-integrin expression on leukocytes increases in liver cirrhosis decornpensated as the stage of liver failure increases, which is a result of permanent activation of leukooytes circulating through the inflamed liver environment.β2-integrin expression on circulating leukocytes can intensify liver cirrhosis,

关键词： β2-integrin Liver cirrhosis Flow cytometry Leukocytes

Specific ssDNA concentration in liver tissue as an index of apoptosis in hepatitis c virus-infected patients

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World Journal of Gastroenterology 2005年第39期11卷 6130-6133页

作者： Tadeusz Wojciech Lapiski anatol Panasiuk Jerzy Jaroszewicz Oksana Kowalczuk Robert Flisiak Magdalena Rogalska Department of Infectious Diseases Medical University of Bialystok Poland Department of Infectious Diseases Medical University of BialystokPolandDepartment of Infectious Diseases Medical University of BialystokPolandInstitute of Molecular Biology Medical University of BialystokPolandDepartment of Infectious Diseases Medical University of BialystokPolandDepartment of Infectious Diseases Medical University of BialystokPoland

AIM. To evaluate bhe activity of apoptosis in liver tissue and explore its possible association with hepatic necroinflammarion and fibrosis as well as serum hepatitis c virus （HcV） load. METHODS： The studied population included 50 chronic hepatitis c patients （20 women and 30 men, aged 18-66 years）. HcV-RNA quantification was performed by two-step real-time quantitative RT-PcR mebhod using the TaqMan technology （reagents of Applera corporation firm, USA）. The morphology of liver tissue was assessed descriptively and scored （necroinflammatory activity and fibrosis）. The early apoptosis activity in liver tissue was examined by ssDNA apoptosis ELISA kit, （chemicon, Germany）. RESULTS： The correlation between apoptosis and fibrosis in liver tissue was observed. High intensification of apoptosis was proportional to the increase of fibrosis （ssDNA： 16.65×10^-5μg/g; 12.71×10^-5μg/g）, however, bhis difference was not statistically significant （P〉0.05）. Activity of apoptosis in the liver tissue, expressed by ssDNA concentration did not depend on hepatic necroinflammatory changes, HcVRNA viral load, ALT, and AST activity as well as prothrombin time and INR index. cONcLUSION： Fibrosis in the tissue is closely associated with early apoptosis in HcV-infected patients.

关键词： Apoptosis Hepatitis c virus ssDNA Fibrosis

KuiqpickTM:a low cost instrument for tissue microdissection and live single cell collection

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KuiqpickTM:a low cost instrument for tissue microdissection ...

microRNA-455-5p alleviates neuroinflammation in cerebral ischemia/reperfusion injury

中国神经科学学会第十届全国学术会议

作者： Zhong-cai Ma Lili c.Kudo anatol Bragin Stanislav Karsten Neurology David Geffen School of Medicine at UCLA

Objective The current work demonstrates the efficiency of Kuiqpick for brain tissue microdissection with follow-up RNA and protein isolation,dissection of hve brains for neural progenitor cultures,and collection of individual cells from various adherent cell *** Various subanatomical areas of hve,freshly frozen or sucrose-treated mouse brain were dissected,DNA,RNA and proteins were extracted and *** zones were isolated from fresh hve rat brain tissues,and used for neural progenitor cultures(NPc).Individual cells were collected from NPc,SH-SY5Y,cHO and MDA-MB-435 cultures based on morphology or fluorescent *** cells were tested for *** Kuiqpick efficiently collects specific areas of the brain at the cellular *** instrument works in a wide range of parameters and dissects brain sections of various thicknesses ranging from 10 to 500 μ***,fresh frozen and sucrose treated tissues can be used for the dissection of subanatomical regions or even individual *** quality RNA and proteins can be isolated from the collected samples for genomics and proteomics *** employed principle of a gentle vacuum suction has minimal impact on cellular viabihty;therefore,cells collected from cultures or native brain tissues may be used for downstream *** of cells can be performed based on their morphology or fluorescent *** We demonstrated several applications of Kuiqpick in neuroscience research,including(1) brain subanatomical region specific collection for-omics research;(2) collection of brain neurogenic areas for neural progenitor cultures and(3)collection of individual/single cells from in vitro cultures based on their morphology and fluorescent *** low cost of Kuiqpick,its accuracy,ease of use,compatibility with fluorescence,versatility,and compatibility with hve cells and tissues,make it a cell and tissue acquisition system of choice for high qualit

关键词： KuiqpickTM brain microdissection single cell analysis recultivation

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Neural Regeneration Research 2022年第8期17卷 1769-1775页

作者： Jian-Song Zhang Pin-Pin Hou Shuai Shao anatol Manaenko Zhi-Peng Xiao Yan chen Bing Zhao Feng Jia Xiao-Hua Zhang Qi-Yong Mei Qin Hu central Laboratory Renji HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurosurgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina Department of Medical Genetics Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurosurgery Changzheng Hospitalthe Second Military Medical UniversityShanghaiChina

Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/*** of microRNA(miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ***,the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been *** this study,mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by ***-455-5p,antagomir-455-5p,and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion(McAO).The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral ***-455-5p pretreatment increased miR-455-5p expression in the brain tissue,reduced the cerebral infarct volume,and improved neurological ***,primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/***-455-5p reduced c-c chemokine receptor type 5 mRNA and protein levels,inhibited microglia activation,and reduced the production of the inflammatory factors tumor necrosis factor-αand interleukin-1β.These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting c-c chemokine receptor type 5 expression and reducing the neuroinflammatory response.

关键词： agomiR-455-5p biomarker blood-brain barrier c-c chemokine receptor type 5 ischemia/reperfusion injury ischemic stroke microglia microRNA-455-5p neuroinflammation pretreatment

Distinct profiles of systemic biomarkers of oxidative stress in chronic human pathologies:cardiovascular,psychiatric,neurodegenerative,rheumatic,infectious,neoplasmic and endocrinological diseases

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Advances in Bioscience and Biotechnology 2013年第3期4卷 331-339页

作者： Michel Brack Olivier Brack Yves Menezo Dominique Bonnefont Rousselot Gerard Dreyfus MJohn chapman anatol Kontush Ge Sante et Retraite ParisFrance consultant en Statistiques EschesFrance Procrelys Maison Medicale Ambroise PareLyonFrance Laboratoire clement ParisFrance London Fertlity Associates LondonUK Department of Metabolic Biochemistry La Pitie Salpetriere-Charles Foix(AP-HP)ParisFrance Department of Biochemistry Faculty of PharmacyParis Descartes UniversityParisFrance Ecole Superieure de Physique et de chimie Industrielles ESPCIParisFrance (cNRS UMR 7084) Laboratoire d’electroniqueParisFrance Universite Pierre et Marie curie-Paris 6 ParisFrance UMR 939“Dyslipoproteinemia Inflammation and Atherosclerosis”INSERMParisFrance AP-HP Groupe hospitalier Pitie-SalpetriereParisFrance

Oxidative stress is involved in chronic and acute pathologies: cardiovascular, neurodegenerative, neoplastic, inflammatory and infectious diseases. clinical trials focused on prevention of cardiovascular and neoplastic diseases involving antioxidant supplementation have however provided predominantly negative obserations in large-scale studies. Screening of patient cohorts to assess baseline oxidative stress on the basis of a biomarker profile is decisive but lacking. For the first time, we evaluated the level of oxidative stress, testing more than 10 established biomarkers, in a comprehensive initial survey of 617 patients displaying chronic human pathologies. Multiple diseasespecific abnormalities were identified in plasma, whole blood and/or urine. This is the case for vitamins and oligo elements, vitamin c, vitamin E, β-carotene, selenium, zinc and copper;endogenous antioxidants such as reduced and oxidised glutathione, thiols, urate, and glutathione peroxidase activity, and a biomarker of oxidative DNA damage (8-hydroxy-2’-deoxy guanosine). The distinct biomarker profiles suggest the involvment of multiple forms of oxidative insults which arein some way partially specific to each pathological condition. This finding is in favor of the determination of an integrated score to combine contributions of distinct biomarkers, in order to screen patients presenting elevated levels of oxidative stress.

关键词： Vitamin c Vitamin E β-carotene Glutathione Thiols Urate 8-Hydroxy-2’-Deoxyguanosine