BACKGROUND:The effect of pituitary adenylate cyclase activating polypeptide(PACAP)during traumatic brain injury(TBI) and whether it can modulate secondary injury has not been reported previously.The present study eval...BACKGROUND:The effect of pituitary adenylate cyclase activating polypeptide(PACAP)during traumatic brain injury(TBI) and whether it can modulate secondary injury has not been reported previously.The present study evaluated the potential protective effects of ventricular infusion of PACAP in a rat model of TBI.METHODS:Male Sprague Dawley rats were randomly divided into 3 treatment groups(n=6,each):sham-operated,vehicle(normal saline)^+TBI,and PACAP^+TBI.Normal saline or PACAP(1 ug/5uL) was administered intracerebroventricularly 20 minutes before TBI.Right parietal cortical contusion was produced via a weight-dropping method.Brains were extracted 24 hours after trauma.Histological changes in brains were examined by HE staining.The numbers of CD4^+ and CD8^+ T cells in blood and the spleen were detected via flow cytometry.RESULTS:In injured brain regions,edema,hemorrhage,inflammatory cell infiltration,and swollen and degenerated neurons were observed under a light microscope,and the neurons were disorderly arrayed in the hippocampi.Compared to the sham group,average CD4^+ CD8" lymphocyte counts in blood and the spleen were significantly decreased in rats that received TBI^+vehicle,and CD4^+ CD8^+ were increased.In rats administered PACAP prior to TBI,damage was attenuated as evidenced by significantly increased CD4^+,and decreased CD8^+,T lymphocytes in blood and the spleen.CONCLUSION:Pretreatment with PACAP may protect against TBI by influencing periphery T cellular immune function.展开更多
Background: Adequate selection of a prospective whole blood donor protects his health and safety of the recipient. Objectives: The main objective of this study was to determine the haematology parameters of apparently...Background: Adequate selection of a prospective whole blood donor protects his health and safety of the recipient. Objectives: The main objective of this study was to determine the haematology parameters of apparently healthy prospective whole blood donors. Participants and Methods: This was a hospital based prospective study carried out from August to October 2020 at the blood transfusion unit of the Lagos State University Teaching Hospital (LASUTH), Ikeja, Nigeria. A structured pretested questionnaire was used for data collection. The socio demographic status and the haematology parameters of apparently healthy prospective whole blood donors who tested negative for HIV, hepatitis B and C markers were captured. Obtained data were analysed with the statistical package for the social scientist software version 20. Results: One hundred male (97.1%) and three female (2.9%) apparently healthy prospective whole blood donors were studied. The median age of study subjects was 30 years. Obtained median haematology parameter values were 13 g/dl, 40%, 4.9/nl and 203.9/nl for haemoglobin concentration, haematocrit, total white cell and platelet counts respectively. The median values for the mean corpuscular haemoglobin concentration (MCHC), mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV) of participants were 32.6 g/dl, 27.7 pg and 85.7 fl respectively. Observed prevalence of subnormal haematology parameters for haemoglobin concentration, total white cells, platelets were 12.6%, 25.2%, and 13.6% respectively. Also subnormal values for MCHC, MCH, MCV were 11.7%, 26.2%, and 16.5% respectively among prospective whole blood donors in this study. No higher than normal haematology parameter values were observed. Median values for erythrocyte sedimentation rate was 8.4 mm/hr. Conclusion: A significant percentage of apparently healthy prospective whole blood donors had subnormal haematology parameters values. Obtained normal values in our study are comparable with local reference range reports from previous studies in Nigeria and other parts of Africa. 124947 .展开更多
Graves*orbitopathy(GO),the most severe manifestation of Graves'hyperthyroidism(GH),is an autoimmune-mediated inflammatory disorder,and treatments often exhibit a low efficacy.CD4+T cells have been reported to play...Graves*orbitopathy(GO),the most severe manifestation of Graves'hyperthyroidism(GH),is an autoimmune-mediated inflammatory disorder,and treatments often exhibit a low efficacy.CD4+T cells have been reported to play vital roles in GO progression.To explore the pathogenic CD4-f T cell types that drive GO progression,we applied single-cell RNA sequencing(scRNA-Seq),T cell receptor sequencing(TCR-Seq),flow cytometry,immunofluorescence and mixed lymphocyte reaction(MLR)assays to evaluate CD4+T cells from GO and GH patients.scRNA-Seq revealed the novel GO-spedfic cell type CD4+cytotoxic T lymphocytes(CTLs),which are characterized by chemotactic and inflammatory features.The clonal expansion of this CD4+CTL population,as demonstrated by TCR-Seq,along with their strong cytotoxic response to autoantigens,localization in orbital sites,and potential relationship with disease relapse provide strong evidence for the pathogenic roles of GZMB and IFN-y-secreting CD4+CTLs in GO.Therefore,cytotoxic pathways may become potential therapeutic targets for GO.展开更多
activation.Therefore,engagement of the costimulatory CD27/CD70 pathway is solely dependent on upregulation of CD70.However,the T cell-intrinsic effect and function of human CD70 remain underexplored.Herein,we describe...activation.Therefore,engagement of the costimulatory CD27/CD70 pathway is solely dependent on upregulation of CD70.However,the T cell-intrinsic effect and function of human CD70 remain underexplored.Herein,we describe that CD70 expression distinguishes proinflammatory CD4^(+)T lymphocytes that display an increased potential to migrate into the central nervous system(CNS).Upregulation of CD70 on CD4^(+)T lymphocytes is induced by TGF-β1 and TGF-β3,which promote a pathogenic phenotype.In addition,CD70 is associated with a TH1 and TH17 profile of lymphocytes and is important for T-bet and IFN-γexpression by both T helper subtypes.Moreover,adoptive transfer of CD70−/−CD4^(+)T lymphocytes induced less severe experimental autoimmune encephalomyelitis(EAE)disease than transfer of WT CD4^(+)T lymphocytes.CD70+CD4^(+)T lymphocytes are found in the CNS during acute autoimmune inflammation in humans and mice,highlighting CD70 as both an immune marker and an important costimulator of highly pathogenic proinflammatory TH1/TH17 lymphocytes infiltrating the CNS.展开更多
文摘BACKGROUND:The effect of pituitary adenylate cyclase activating polypeptide(PACAP)during traumatic brain injury(TBI) and whether it can modulate secondary injury has not been reported previously.The present study evaluated the potential protective effects of ventricular infusion of PACAP in a rat model of TBI.METHODS:Male Sprague Dawley rats were randomly divided into 3 treatment groups(n=6,each):sham-operated,vehicle(normal saline)^+TBI,and PACAP^+TBI.Normal saline or PACAP(1 ug/5uL) was administered intracerebroventricularly 20 minutes before TBI.Right parietal cortical contusion was produced via a weight-dropping method.Brains were extracted 24 hours after trauma.Histological changes in brains were examined by HE staining.The numbers of CD4^+ and CD8^+ T cells in blood and the spleen were detected via flow cytometry.RESULTS:In injured brain regions,edema,hemorrhage,inflammatory cell infiltration,and swollen and degenerated neurons were observed under a light microscope,and the neurons were disorderly arrayed in the hippocampi.Compared to the sham group,average CD4^+ CD8" lymphocyte counts in blood and the spleen were significantly decreased in rats that received TBI^+vehicle,and CD4^+ CD8^+ were increased.In rats administered PACAP prior to TBI,damage was attenuated as evidenced by significantly increased CD4^+,and decreased CD8^+,T lymphocytes in blood and the spleen.CONCLUSION:Pretreatment with PACAP may protect against TBI by influencing periphery T cellular immune function.
文摘Background: Adequate selection of a prospective whole blood donor protects his health and safety of the recipient. Objectives: The main objective of this study was to determine the haematology parameters of apparently healthy prospective whole blood donors. Participants and Methods: This was a hospital based prospective study carried out from August to October 2020 at the blood transfusion unit of the Lagos State University Teaching Hospital (LASUTH), Ikeja, Nigeria. A structured pretested questionnaire was used for data collection. The socio demographic status and the haematology parameters of apparently healthy prospective whole blood donors who tested negative for HIV, hepatitis B and C markers were captured. Obtained data were analysed with the statistical package for the social scientist software version 20. Results: One hundred male (97.1%) and three female (2.9%) apparently healthy prospective whole blood donors were studied. The median age of study subjects was 30 years. Obtained median haematology parameter values were 13 g/dl, 40%, 4.9/nl and 203.9/nl for haemoglobin concentration, haematocrit, total white cell and platelet counts respectively. The median values for the mean corpuscular haemoglobin concentration (MCHC), mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV) of participants were 32.6 g/dl, 27.7 pg and 85.7 fl respectively. Observed prevalence of subnormal haematology parameters for haemoglobin concentration, total white cells, platelets were 12.6%, 25.2%, and 13.6% respectively. Also subnormal values for MCHC, MCH, MCV were 11.7%, 26.2%, and 16.5% respectively among prospective whole blood donors in this study. No higher than normal haematology parameter values were observed. Median values for erythrocyte sedimentation rate was 8.4 mm/hr. Conclusion: A significant percentage of apparently healthy prospective whole blood donors had subnormal haematology parameters values. Obtained normal values in our study are comparable with local reference range reports from previous studies in Nigeria and other parts of Africa. 124947 .
基金supported by the National Key R&D Program of China(Grant nos.2018YFC1311500(B.S.),2017YFC0907500(K.Y.)and 2018YFC0910400(K.Y.))National Science Foundation of China(NSFC)(Grant nos.81970679(B.S.),81500690(Y.W.),and 31671372(K.Y.))+3 种基金Natural Science Foundation of Shaanxi Province(2018JM70990(Y.W.))Key Research and Development Project of Shaanxi Province(Grant no.2017ZDXM-SF-060(B.S.))Fundamental Research Funds for the Central Universities(1191329875(Y.W.))the China Postdoctoral Science Foundation(224646(Y.W.)).
文摘Graves*orbitopathy(GO),the most severe manifestation of Graves'hyperthyroidism(GH),is an autoimmune-mediated inflammatory disorder,and treatments often exhibit a low efficacy.CD4+T cells have been reported to play vital roles in GO progression.To explore the pathogenic CD4-f T cell types that drive GO progression,we applied single-cell RNA sequencing(scRNA-Seq),T cell receptor sequencing(TCR-Seq),flow cytometry,immunofluorescence and mixed lymphocyte reaction(MLR)assays to evaluate CD4+T cells from GO and GH patients.scRNA-Seq revealed the novel GO-spedfic cell type CD4+cytotoxic T lymphocytes(CTLs),which are characterized by chemotactic and inflammatory features.The clonal expansion of this CD4+CTL population,as demonstrated by TCR-Seq,along with their strong cytotoxic response to autoantigens,localization in orbital sites,and potential relationship with disease relapse provide strong evidence for the pathogenic roles of GZMB and IFN-y-secreting CD4+CTLs in GO.Therefore,cytotoxic pathways may become potential therapeutic targets for GO.
基金T.D.holds a fellowship from the Fonds de Recherche du Québec-Santé(FRQS).L.T.holds scholarships from Universitéde Montréal and CRCHUM.E.P.holds a fellowship from the Multiple Sclerosis Society of Canada(MSSC)and the FRQS.S.Z.is supported by a fellowship from Biogen Canada.C.L.is supported by FRQS.A.P.holds the T1(senior)Canada Research Chair in Multiple Sclerosis.This work was funded by operating grants from the Canadian Institutes of Health Research(MOP 89885,PJI-153195)and from the MSSC(EGID 2382).We thank Jannie Borst for providing us with the CD70−/−mice.We thank Hartmut Wekerle for providing us with the TCR1640 mice.Special thanks to Magdalena Paterka and Volker Siffrin for providing the protocol for CD4+adoptive T cell transfer in RAG null mice.We would also like to thank the imaging platform,the pathology platform,and the flow cytometry platform from the CRCHUM for the excellent technical support and Alice M Roy and Elvia Gonzalez for their excellent technical animal support.
文摘activation.Therefore,engagement of the costimulatory CD27/CD70 pathway is solely dependent on upregulation of CD70.However,the T cell-intrinsic effect and function of human CD70 remain underexplored.Herein,we describe that CD70 expression distinguishes proinflammatory CD4^(+)T lymphocytes that display an increased potential to migrate into the central nervous system(CNS).Upregulation of CD70 on CD4^(+)T lymphocytes is induced by TGF-β1 and TGF-β3,which promote a pathogenic phenotype.In addition,CD70 is associated with a TH1 and TH17 profile of lymphocytes and is important for T-bet and IFN-γexpression by both T helper subtypes.Moreover,adoptive transfer of CD70−/−CD4^(+)T lymphocytes induced less severe experimental autoimmune encephalomyelitis(EAE)disease than transfer of WT CD4^(+)T lymphocytes.CD70+CD4^(+)T lymphocytes are found in the CNS during acute autoimmune inflammation in humans and mice,highlighting CD70 as both an immune marker and an important costimulator of highly pathogenic proinflammatory TH1/TH17 lymphocytes infiltrating the CNS.
