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Comparative Studies of Different Organs of Nyctanthes arbortristis in Modulation of Cytokines in Murine Model of Arthritis

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Biomedical and Environmental Sciences 2007年第2期20卷 154-159页

作者： BRIJESH RATHORE BHOLANATH PAUL BHUSAN P CHAUDHURY ASHOK KUMAR SAXENA ANAND PRAKASH SAHU YOGENDRA KUMAR GUPTA immunobiology Laboratory Central Pathology Laboratory Preventive Toxicology Laboratory Industrial Toxicology Research centre M. G. MargLucknow 226001India

Objective To study the modulation effect of pro- and anti-inflammatory cytokines following long term use of water soluble ethanol extracts from different organs of Nyctanthes arbortristis （NAT） in mouse model of arthritis. Methods Arthritis was induced in mice by two injections of Freund＇s complete adjuvant on days 0 and 12 in the sub-planter surface of the right hind paw. Results Injection of adjuvant resulted in a maximum primary edema of the footpad with erythema, and edema and distortion of joints of the right hind paw after 24-48 hours. Second injection of FCA led to the formation of secondary swellings persisting more than four weeks that spread onto the other hind limb but to a lesser extent. Histological analysis of the ankle on day 47 showed marked evidence of cartilage destruction in association with pannus formation and moderate bone resorption. Proinfiammatory cytokine levels in the inflamed joint homogenate were elevated on days 2, 14, and 47. Oral administration of leaf and fruit extracts in arthritic mice reduced joint homogenate levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 on days 2, 14, and 47 in comparison to untreated arthritic mice. Intedeukin-10 level was elevated in the inflamed joint on days 2, 14, and 47 in comparisons to untreated arthritic mice. Confusion Evidence of lesser inflammation of the footpad and joint and associated histological observation support the therapeutic benefit of leaf and fruit extracts from Nyctanthes arbortristis. This study helps in understanding the mechanism of anti-inflammatory action of Nyctanthes arbortristis in the light of pro- and anti-inflammatory cytokine balance.

关键词： Nyctanthes arbortristis Arthritis TNF-α IL- 1β IL-6 IL-10

Revisiting the role of mesenchymal stem cells in tuberculosis and other infectious diseases

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Cellular & Molecular Immunology 2023年第6期20卷 600-612页

作者： Annu Devi Isha Pahuja Shashi Prakash Singh Akanksha Verma Debapriya Bhattacharya Ashima Bhaskar Ved Prakash Dwivedi Gobardhan Das Special centre for Molecular Medicine Jawaharlal Nehru UniversityNew DelhiIndia immunobiology Group International Centre for Genetic Engineering and Biotechnology New DelhiIndia Department of Molecular Medicine Jamia Hamdard UniversityNew DelhiIndia centre for Biotechnology Siksha O Anusandhan UniversityBhubneshwarOdishaIndia

Mesenchymal stem cells(MsCs)play diverse roles ranging from regeneration and wound healing to immune *** investigations have indicated the crucial role of these multipotent stem cells in regulating various aspects of the immune *** express unique signaling molecules and secrete various soluble factors that play critical roles in modulating and shaping immune responses,and in some other cases,MSCs can also exert direct antimicrobial effects,thereby helping with the eradication of invading ***,it has been demonstrated that MSCs are recruited at the periphery of the granuloma containing Mycobacterium tuberculosis and exert"Janus"-like functions by harboring pathogens and mediating host protective immune *** leads to the establishment of a dynamic balance between the host and the *** function through various immunomodulatory factors such as nitric oxide(NO),IDO,and immunosuppressive ***,our group has shown that *** uses MSCs as a niche to evade host protective immune surveillance mechanisms and establish *** also express a large number of ABC efflux pumps;therefore,dormant *** residing in MSCs are exposed to a suboptimal dose of ***,it is highly likely that drug resistance is coupled with dormancy and originates within *** this review,we discussed various immunomodulatory properties of MsCs,their interactions with important immune cells,and soluble *** also discussed the possible roles of MsCs in the outcome of multiple infections and in shaping the immune system,which may provide insight into therapeutic approaches using these cells in different infection models.

关键词： Mesenchymal Stem Cells(MsCs) Macrophages Tuberculosis Infectious Diseases T cells Immunomodulation Immunotherapy.

Hippocampal stem cells:so they are multipotent!

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Journal of Molecular Cell Biology 2011年第5期3卷 270-272页

作者： Verdon Taylor centre for Stem Cell Biology Department of Biomedical ScienceUniversity of SheffieldWestern BankSheffield S102TNUK Department of Molecular Embryology Max Planck Institute of Immunobiology and EpigeneticsStubeweg 51Freiburg D-79108Germany

Although neurogenesis continues throughout life in the mammalian brain,the issue of whether the stem cells that drive the process in vivo are self-renewing and multipotent remains *** a recent landmark paper by Bonaguidi et al.(2011)published in Cell,the authors provide clonal evidence that neural stem cells in the dentate gyrus of the adult hippocampus are indeed multipotent and undergo symmetric cell divisions.

关键词： al. potent stem

Silica Induced Early Fibrogenic Reaction in Lung of Mice Ameliorated by Nyctanthes arbortristis Extract

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Biomedical and Environmental Sciences 2002年第3期15卷 215-222页

作者： BHOLA NATH PAUL ANAND PRAKASH SIRISH KUMAR AJAY KYADAV UMANI ASHOK KSAXENA ANAND PRAKASH SAHU KEWAL LAL KALYAN KDUTTA immunobiology Laboratory Industrial Toxicology Research CentreM.G.MargLucknow 226001U.P.India Inhalation Toxicology Laboratory Industrial Toxicology Research CentreM.G.MargLucknow 226001U.P.India Preventive Toxicology Laboratory Industrial Toxicology Research CentreM.G.MargLucknow 226001U.P.India

Objective To investigate the pharmacological effect of Nyctanthes arbortristis (NAT) leaf extract in the prevention of lung injury induced by silica particles. Method Lung injury was induced in Swiss mice through inhalation exposure to silica particles (<5m) using a Flow Past Nose Only Inhalation Chamber at the rate of -10 mg/m3 respirable mass for 5 h. Lung bronchoalveolar lavage (BAL) fluid collected between 48 and 72 h was subjected to protein profiling by electrophoresis and cytokine evaluation by solid phase sandwich ELISA. Lung histopathology was performed to evaluate lung injury. Results Inhalation of silica increased the level of tumor necrosis factor-a (TNF-a), and of the 66 and 63 kDa peptides in the BAL fluid in comparison to sham-treated control. Pre-treatment of silica exposed mice with NAT leaf extract significantly prevented the accumulation of TNF-a in the BAL fluid, but the 66 and 63 kDa peptides remained unchanged. The extract was also effective in the prevention of silica-induced early fibrogenic reactions like congestion, edema and infiltration of nucleated cells in the interstitial alveolar spaces, and thickening of alveolar septa in mouse lung. Conclusion NAT leaf extract helps in bypassing silica induced initial lung injury in mice.

关键词： Nyctanthes arbortristis Lung-injury Silica Mice prevention

Platelets in hemostasis and thrombosis:Novel mechanisms of fibrinogen-independent platelet aggregation and fibronectin-mediated protein wave of hemostasis

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The Journal of Biomedical Research 2015年第6期29卷 437-444页

作者： Yan Hou Naadiya Carrim Yiming Wang Reid C.Gallant Alexandra Marshall Heyu Ni Department of Laboratory Medicine Keenan Research Centre for Biomedical ScienceLi Ka Shing Knowledge InstituteSt.Michael's Hospital and Toronto Platelet Immunobiology Group Jilin Provincial Center for Disease Control and Prevention Department of Laboratory Medicine and Pathobiology University of Toronto Canadian Blood Services Department of Medicine and Department of Physiology University of Toronto

Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet genera- tion, maturation, and clearance are still not fully understood, significant progress has been made in the last 1-2 dec- ades. In blood circulation, platelets can quickly adhere and aggregate at sites of vascular injury, forming the platelet plug （i.e. the first wave of hemostasis）. Activated platelets can also provide negatively charged phosphatidylserine- rich membrane surface that enhances cell-based thrombin generation, which facilitates blood coagulation （i.e. the second wave of hemostasis）. Platelets therefore play central roles in hemostasis. However, the same process of hemostasis may also cause thrombosis and vessel occlusion, which are the most common mechanisms leading to heart attack and stroke following ruptured atherosclerotic lesions. In this review, we will introduce the classical mechanisms and newly discovered pathways of platelets in hemostasis and thrombosis, including fibrinogen-inde- pendent platelet aggregation and thrombosis, and the plasma fibronectin-mediated ＂protein wave＂ of hemostasis that precedes the classical first wave of hemostasis. Furthermore, we briefly discuss the roles of platelets in inflam- marion and atherosclerosis and the potential strategies to control atherothrombosis.

关键词： platelets thrombosis and hemostasis integrin αIIbβ3 fibrinogen fibronectin

Platelets and platelet alloantigens:Lessons from human patients and animal models of fetal and neonatal alloimmune thrombocytopenia

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Genes & Diseases 2015年第2期2卷 173-185页

作者： Brian Vadasz Pingguo Chen Issaka Yougbare Darko Zdravic June Li Conglei Li Naadiya Carrim Heyu Ni Toronto Platelet immunobiology Group TorontoONCanada Department of Laboratory Medicine Keenan Research Centre for Biomedical ScienceSt.Michael’s HospitalTorontoONCanada Department of Laboratory Medicine and Pathobiology University of TorontoTorontoONCanada Canadian Blood Services TorontoONCanada Department of Physiology University of TorontoTorontoONCanada Department of Medicine University of TorontoTorontoONCanada

Platelets play critical roles in hemostasis and *** evidence indicates that they are versatile cells and also involved in many other physiological processes and disease *** and neonatal alloimmune thrombocytopenia(FNAIT)is a life threatening bleeding disorder caused by fetal platelet destruction by maternal alloantibodies developed during *** polymorphisms cause platelet surface protein incompatibilities between mother and fetus,and ultimately lead to maternal *** is the most common cause of intracranial hemorrhage in full-term infants and can also lead to intrauterine growth retardation and *** diagnosis,prevention and treatment of FNAIT is challenging due to insufficient knowledge of the disease and a lack of routine screening as well as its frequent occurrence in first *** the ethical difficulties in performing basic research on human fetuses and neonates,animal models are essential to improve our understanding of the pathogenesis and treatment of *** aim of this review is to provide an overview on platelets,hemostasis and thrombocytopenia with a focus on the advancements made in FNAIT by utilizing animal models.

关键词： Fetal and neonatal alloimmune thrombocytopenia Integrins and GPIb complex Platelets and platelet receptors Thrombosis and hemostasis and Animal models of human disease

Combination therapy with saxagliptin and vitamin D for the preservation ofβ-cell function in adult-onset type 1 diabetes:a multi-center,randomized,controlled trial

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2354-2362页

作者： Xiang Yan Xia Li Bingwen Liu Jiaqi Huang Yufei Xiang Yuhang Hu Xiaohan Tang Ziwei Zhang Gan Huang Zhiguo Xie Houde Zhou Zhenqi Liu Xiangbing Wang Richard David Leslie Zhiguang Zhou National Clinical Research Center for Metabolic Diseases Key Laboratory of Diabetes Immunology(Central South University)Ministry of Educationand Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina Division of Endocrinology and Metabolism Department of MedicineUniversity of Virginia Health SystemCharlottesvilleVAUSA Division of Endocrinology Metabolism and NutritionRutgers University-Robert Wood Johnson Medical SchoolNew BrunswickNJUSA centre for immunobiology Blizard InstituteQueen Mary University of LondonLondonUK

Disease modifying therapies aiming to preserveβ-cell function in patients with adult-onset autoimmune type 1 diabetes are ***,we conducted a multi-centre,randomized,controlled trial to assess theβ-cell preservation effects of saxagliptin alone and saxagliptin combined with vitamin D as adjunctive therapies in adult-onset autoimmune type 1 *** this 3-arm trial,301 participants were randomly assigned to a 24-month course of the conventional therapy(metformin with or without insulin)or adjunctive saxagliptin or adjunctive saxagliptin plus vitamin D to the conventional *** primary endpoint was the change from baseline to 24 months in the fasting *** secondary endpoints included the area under the concentration-time curve(AUC)for C-peptide level in a 2-h mixed-meal tolerance test,glycemic control,total daily insulin use and safety,*** primary endpoint was not achieved in saxagliptin plus vitamin D group(P=0.18)and saxagliptin group(P=0.26).However,compared with the conventional therapy,2-h C-peptide AUC from 24 months to baseline decreased less with saxagliptin plus vitamin D(-276 pmol/L vs.-419 pmol/L;P=0.01),and not to the same degree with saxagliptin alone(-314 pmol/L;P=0.14).Notably,for participants with higher glutamic acid decarboxylase antibody(GADA)levels,the decline ofβ-cell function was much lower in saxagliptin plus vitamin D group than in the conventional therapy group(P=0.001).Insulin dose was significantly reduced in both active treatment groups than in the conventional therapy group despite all groups having similar glycemic *** conclusion,the combination of saxagliptin and vitamin D preserves pancreaticβ-cell function in adult-onset autoimmune type 1 diabetes,an effect especially efficacious in individuals with higher GADA *** results provide evidence for a novel adjunct to insulin and metformin as potential initial treatment for adult-onset type 1 diabetes.(*** identifier:NCT024

关键词： vitamin alone treatment

T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway

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Cellular & Molecular Immunology 2017年第6期14卷 497-510页

作者： Jose-Ignacio Rodriguez-Barbosa Carlos Fernandez-Renedo Ana Maria Bravo Moral Leo Biihler Maria-Luisa del Rio Transplantation immunobiology Section Institute of Biomedicine University of Leon and Castilla and Leon Regional Transplantation Coordination Leon University Hospital Leon Spain Department of Veterinary Clinical Sciences University of Santiago de Compostela Veterinary Faculty Lugo Spain Visceral and Transplantation Surgery Department of Surgery University Hospitals of Geneva and Faculty of Medicine Geneva Switzerland

The molecular pathways contributing to humoral-mediated allograft rejection are poorly defined. In this study, we assessed the role of the herpesvirus entry mediator/B- and T-lymphocyte attenuator （HVEM/BTLA） signalling pathway in the context of antibody-mediated allograft rejection. An experimental setting was designed to elucidate whether the blockade of HVEM/BTLA interactions could modulate de novo induction of host antidonor-specific antibodies during the course of graft rejection. To test this hypothesis, fully allogeneic major histocompatibility complex-mismatched skin grafts were transplanted onto the right flank of recipient mice that were treated with isotype control, anti-CD40L or modulatory antibodies of the HVEM/BTLA signalling pathway. The frequencies of CD4 T follicular helper （Tfh） cells （B220-, CD4＋ CXCR5＋ PD-lhigh）, extrafollicular helper cells （B220-, CD4＋ CXCR5- PD-1＋ and PD-1-） and germinal centre （GC） B cells （B220＋Fas＋ GL7＋） were analysed by flow cytometry in draining and non-draining lymph nodes at day 10 post transplantation during the acute phase of graft rejection. The host antidonor isotype-specific humoral immune response was also assessed. Whereas blockade of the CD40/CD40L pathway was highly effective in preventing the allogeneic humoral immune response, antibody-mediated blockade of the HVEM/BTLA-interacting pathway affected neither the expansion of Tfh cells nor the expansion of GC B cells. Consequently, the course of the host antidonor antibody-mediated response proceeded normally, without detectable evidence of impaired development. In summary, these data indicate that HVEM/BTLA interactions are dispensable for the formation of de novo host antidonor isotype-specific antibodies in transplantation.

关键词： BTLA (CD272) humoral immunity HVEM (TNFRSF14, CD270) T follicular helper cells transplantation

COMPARATIVE STUDIES OF DIFFERENT ORGANS OF N. arbor tristis IN MODULATION OF LIPID PEROXIDE LEVELS, ANTI-OXIDANT CONTENT, CYTOKINES AND EFFECT ON HEPATIC AND RENAL MARKER ENZYMES IN EXPERIMENTAL RHEUMATOID ARTHRITIS

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COMPARATIVE STUDIES OF DIFFERENT ORGANS OF N. arbor tristis ...