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

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

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Efferocytosis: A new therapeutic target for stroke

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中华医学杂志(英文版) 2024年第23期

作者： Gao Li manaenko anatol Zeng Feng Li Jingchen Liu Lele Xie Ruichuan Zhang Xiaohua Zhang John H. Mei Qiyong Tang Jiping Hu Qin Department of Neurosurgery Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai China Department of Neurology Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai China Clinical Neuroanatomy Department of Neurology School of Medicine Ulm University Ulm Germany Department of Neurosurgery Changzheng Hospital Naval Medical University Shanghai China Department of Physiology and Pharmacology Loma Linda University Loma Linda CA USA Key Laboratory of Anesthesiology (Shanghai Jiao Tong University) Ministry of Education Shanghai China

Efferocytosis refers to the process that phagocytes recognize and remove the apoptotic cells, which is essential for maintaining tissue homeostasis both in physiological and pathological conditions. Numerous studies have demonstrated that efferocytosis can prevent secondary necrosis and proinflammatory factor release, leading to the resolution of inflammation and tissue immunological tolerance in numerous diseases such as stroke. Stroke is a leading cause of death and morbidity for adults worldwide. Persistent inflammation triggered by the dead cells or cell debris is a major contributor to post-stroke brain damage. Effective efferocytosis might be an efficient strategy to minimize inflammation and restore brain homeostasis for neuronal regeneration and function recovery. In this review, we will discuss the phagocytes in the brain, the molecular mechanisms underlying efferocytosis, the role of efferocytosis in inflammation resolution, and the potential therapeutic applications targeting efferocytosis in stroke.

关键词： Stroke Efferocytosis Inflammation resolution Apoptotic cell clearance

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大鼠蛛网膜下腔出血后SCH79797对血脑屏障的保护作用

大鼠蛛网膜下腔出血后SCH79797对血脑屏障的保护作用

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中国解剖学会2015年年会

作者：闫军浩 manaenko anatol Chen Sheng Klebe Damon Ma Qingyi Caner Basak Fujii Mutsumi Zhou Changman Zhang John H. 北京大学医学部解剖学系 Department of Physiology and Pharmacology Loma Linda University Medical Center

＜正＞蛛网膜下腔出血（subarachnoid hemorrhage,SAH）后,血浆凝血酶含量明显增加。但是,凝血酶受体（protease-activated receptor-1,PAR-1）对血脑屏障（blood-brain barrier,BBB）的影响还不清楚。本文欲探讨PAR-1抑制剂SCH79797是...

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重组Gas6在脑出血后促进Axl信号通路免疫调控作用的机制研究

重组Gas6在脑出血后促进Axl信号通路免疫调控作用的机制研究

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华东六省一市第二十三次神经病学学术会议暨2016年浙江省神经病学学术年会

作者：童璐莎邵安文欧一博郭珍妮 anatol manaenko Brandon J.Dixon 唐继平楼敏 John.H.Zhang 美国罗马琳达大学麻醉中心浙江大学医学院附属第二医院神经内科浙江大学医学院附属第二医院神经外科武汉同济医院神经外科吉林大学第一医院神经内科

目的:Axl,作为酪氨酸肌酶受体,近期被发现在固有免疫反应中发挥重要调控作用。SOCS1和SOCS3可被Axl激活,同时也是炎症信号通路中的重要负向调节因子。本研究揭示了Axl/SOCSs信号通路在脑出血后免疫重建过程中的变化和其中机制。方法:应...

目的:Axl,作为酪氨酸肌酶受体,近期被发现在固有免疫反应中发挥重要调控作用。SOCS1和SOCS3可被Axl激活,同时也是炎症信号通路中的重要负向调节因子。本研究揭示了Axl/SOCSs信号通路在脑出血后免疫重建过程中的变化和其中机制。方法:应用小鼠基底节自体血注射法建立脑出血模型。在模型前1小时分别给予Axl的激动剂(重组Gas6)或拮抗剂(R428)。通过模型前48小时侧脑室注射siRNA,实施Axl基因沉默或SOCSs基因沉默。研究中应用的其他实验手段包括神经功能评分,脑水肿测定,免疫沉淀,蛋白印迹法和免疫荧光染色。

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大鼠蛛网膜下腔出血后SCH79797对血脑屏障的保护作用

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中国民康医学 2015年第14期 121-121页

作者：闫军浩 manaenko anatol Chen Sheng Klebe Damon Ma Qingyi Caner Basak Fujii Mutsumi 周长满 Zhang John H 北京大学医学部解剖学系 Department of Physiology and Pharmacology Loma Linda University Medical Center

目的:蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后,血浆凝血酶含量明显增加。但是,凝血酶受体(protease-activated receptor-1,PAR-1)对血脑屏障(blood-brain barrier,BBB)的影响还不清楚。本文欲探讨PAR-1抑制剂SCH79797是否对大鼠SAH后BBB具有保护作用。方法:应用SD大鼠建立SAH模型,SCH79797腹腔注射。SAH后24h,对大鼠脑水含量、神经功能等进行评估。应用Western blot和免疫印迹等方法探讨SCH79797的作用机制。结果:经SCH79797治疗的SAH大鼠脑水含量明显下降,神经功能有所恢复。PAR-1水平下降,VE-Caderin表达增加。在SAH后,PAR-1下游蛋白c-Src和PAK-1使VE-Caderin磷酸化增加,与β-arrestin-2结合增多而被内噬,而SCH79797可以减轻上述病理过程。结论:在SAH后,SCH79797可以通过抑制PAR-1活性对BBB发挥保护作用。

关键词：蛛网膜下腔出血 SAH SCH79797 血脑屏障大鼠保护作用

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Liver fibrosis markers in alcoholic liver disease

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World Journal of Gastroenterology 2014年第25期20卷 8018-8023页

作者： Lech Chrostek anatol Panasiuk Department of Biochemical Diagnostics Medical University of Bialystok 15-540 Bialystok Poland Department of Infectious Diseases and Hepatology Medical University of Bialystok 15-540 BialystokPoland

Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease(ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have beenused to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index(PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients.

关键词： Liver fibrosis markers Alcoholic liver disease

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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 (P<0.03). Platelet-derived growth factor (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, P<0.05; NR: r=0.4, P<0,03). CONCLUSION: 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

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Definition of the Seismic Field of the Underground Sources in the Ambient Seismic Noise in the Tien Shan Region Using a Three-Component Gradient System

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Journal of Earth Science 2020年第5期31卷 988-992页

作者： anatoly Kuzmich Rybin Elena anatol'evna Bataleva Kseniia Sergeevna Nepeina Pavel Alexandrovich Kaznacheev Pavel Alexandrovich Matiukov Pavel Nikolaevich Aleksandrov Research Station of the Russian Academy of Sciences Bishkek 720049Kyrgyz Republic The Schmidt Institute of Physics of the Earth of the Russian Academy of Sciences Moscow 123242Russia Geoelectromagnetic Research Center of the Schmidt Institute of Physics of the Earth of the Russian Academy of Sciences Troitsk 108840Russia

This paper considers a new approach to solving the problem of quantitative estimation of the microseism energy for underground sources that is based on the synthesis of noise interferometry and the passive seismic method of the gradient system. The selection of a seismic field of the underground sources is considered in an experiment conducted in the Tien Shan region. The peculiarities of approach include the separation of vertical microseisms in the ambient seismic noise field structure according to the data of the seismic gradient system and a passive noise interferometry diagram, where microseisms from the underground sources are used as the seismic signal source. It is shown that the use of noise interferometry and passive seismic gradient system allows using the synchronous microseism recordings in a small number of points for passive medium sensing, and leads to the restoration of unknown energy parameters of the seismic field of underground sources.

关键词： gradient system passive seismic Tien Shan geodynamics

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Concentrations of gastric mucosal cytokines in children with food allergy and Helicobacterpylori infection

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World Journal of Gastroenterology 2005年第43期11卷 6751-6756页

作者： El(z|.)bieta Maciorkowska anatol Panasiuk Maciej Kaczmarski Department of Pediatric Nursing Department of Infectious Diseases 3rd Department of Children's Diseases

AIM： To measure the concentrations of chosen cytokines in the antrum mucosa depending on the kind of harmful pathogenic factors and to compare the concentrations with the values of controls without allergy and coexisting Helicobacter pylori （H pylori） infection. METHODS： The patients （97 children） were divided into three groups according to the data obtained from the case history, to the main cause of the disease and to the dominant clinical symptoms. Group Ⅰ： children with food allergy （Fa）; group Ⅱ： children infected with H pylori; group Ⅲ （control group）： children with functional disorders of the alimentary tract （without Fa and Hp infection）. H pylori infection was determined by the presence of anti-Hp antibodies in serum （ELISA method） and urease test performed during endoscopic examination. Cytokine concentration in homogenates of gastric mucosa was detected by ELISA method. RESULTS： The IL-2 concentration in gastric mucosa bioptates was the highest in children with Hp infection （116.5±179.5 pg/mg of the protein） and Fa and Hp infection （98.1±101.0 pg/mg）, while decreased in children with Fa （44.8±50.3 pg/mg） and controls （45.7±23.5 pg/mg）. The lowest mean concentration of IFN-y was observed in children with Hp infection （18.9±16.4 pg/mg）, with Fa and Hp infection （25.5±27.7 pg/mg）, with Fa （40.6±39.7 pg/mg） and controls （49.9±33.4 pg/mg）. The highest IL-4 concentrations were observed in children with Hp infection （35.3±52.8 pg/mg） and in children with Fa and Hp infection （37.2±51.7 pg/mg）, while lower IL-4 concentration （23.64-35.8 pg/mg） was found in children with Fa compared to the controls （22.7±13.8 pg/mg）. The analysis of IL-4 concentrations in children with Hp infection regarding the intensity of gastritis showed the highest value （62.2±61.2 pg/mg） in mild and moderate gastritis. The concentrations of IL-5 in the gastric mucosa of children with or without Fa did not differ significantly and were comparable to the control group. The highest mean IL-8 val

关键词： Mucosal cytokines Food allergy Helicobacterpylori dehydrogenase complex

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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

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