Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency and sickle cell disease are common genetic defects of red blood cells that lead to hemolytic anemia. The prevalence of G6PD deficiency in sickle cell pat...Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency and sickle cell disease are common genetic defects of red blood cells that lead to hemolytic anemia. The prevalence of G6PD deficiency in sickle cell patients is unknown in Benin. Objective: This study aimed to determine the prevalence of G6PD deficiency in sickle cell patients at the CNHU-HKM of Cotonou. Methods: This prospective study was conducted from April to November 2022 at the blood-related diseases teaching clinic and included sickle cell patients in the stationary phase. G6PD determination was performed using the enzymatic method on a Mindray BS 200 machine following the Herz method. Hematological parameters were determined using the XT 4000i analyzer and supplemented by a blood smear stained with May Grunwald Giemsa. Data were analyzed using Epi Info 3.5.4 software. Results: One hundred and sixty-four sickle cell patients (80 SS homozygotes and 84 SC heterozygotes) in the intercritical phase, with a mean age of 26.30 ± 10.76 years, were included. The prevalence of G6PD deficiency was 9.1% (15 cases found in 7 SS patients and 8 SC patients). In G6PD-deficient patients, the mean concentration of the enzyme was lower in Hb SC heterozygotes than in Hb SS homozygotes: 3.56 IU/g Hb versus 4.98 IU/g Hb. The mean reticulocyte count was 231.43 G/L in the deficient group, compared to 216.32 G/L in the non-deficient group. Conclusion: The preliminary results of our study reveal a high prevalence of G6PD deficiency in sickle cell patients. The impact of this association on hematologic and biological parameters should be evaluated for better management of sickle cell disease.展开更多
Natural killer(NK)cells are innate cytotoxic lymphoid cells(ILCs)involved in the killing of infected and tumor cells.Among human and mouse NK cells from the spleen and blood,we previously identified by single-cell RNA...Natural killer(NK)cells are innate cytotoxic lymphoid cells(ILCs)involved in the killing of infected and tumor cells.Among human and mouse NK cells from the spleen and blood,we previously identified by single-cell RNA sequencing(scRNAseq)two similar major subsets,NK1 and NK2.Using the same technology,we report here the identification,by single-cell RNA sequencing(scRNAseq),of three NK cell subpopulations in human bone marrow.Pseudotime analysis identified a subset of resident CD56^(bright) NK cells,NK0 cells,as the precursor of both circulating CD56dim NK1-like NK cells and CD56^(bright) NK2-like NK cells in human bone marrow and spleen under physiological conditions.Transcriptomic profiles of bone marrow NK cells from patients with acute myeloid leukemia(AML)exhibited stress-induced repression of NK cell effector functions,highlighting the profound impact of this disease on NK cell heterogeneity.Bone marrow NK cells from AML patients exhibited reduced levels of CD160,but the CD160high group had a significantly higher survival rate.展开更多
Arsenic trioxide(As2O3)is recently found to have therapeutic potential in systemic sclerosis(SSc),a life-threatening multi-system fibrosing autoimmune disease with type I interferon(IFN-I)signature.Chronically activat...Arsenic trioxide(As2O3)is recently found to have therapeutic potential in systemic sclerosis(SSc),a life-threatening multi-system fibrosing autoimmune disease with type I interferon(IFN-I)signature.Chronically activated plasmacytoid dendritic cells(pDCs)are responsible for IFN-I secretion and are closely related with fibrosis establishment in SSc.In this study,we showed that high concentrations of As2O3 induced apoptosis of pDCs via mitochondrial pathway with increased BAX/BCL-2 ratio,while independent of reactive oxygen species generation.Notably,at clinical relevant concentrations,As2O3 preferentially inhibited IFN-αsecretion as compared to other cytokines such as TNF-α,probably due to potent down-regulation of the total protein and mRNA expression,as well as phosphorylation of the interferon regulatory factor7(IRF7).In addition,As2O3 induced a suppressive phenotype,and in combination with cytokine inhibition,it down-regulated pDCs’capacity to induce CD4+T cell proliferation,Thl/Th22 polarization,and B cell differentiation towards plasmablasts.Moreover,chronically activated pDCs from SSc patients were not resistant to the selective IFN-αinhibition,and regulatory phenotype induced by As2O3.Collectively,our data suggest that As2O3 could target pDCs and exert its treatment efficacy in SSc,and more autoimmune disorders with IFN-I signature.展开更多
Correction to:Cellular&Molecular Immunology https://doi.org/10.1038/S41423-020-00574-8,published online 25 November 2020 In the version of this article initially published,two unintended errors were made during ma...Correction to:Cellular&Molecular Immunology https://doi.org/10.1038/S41423-020-00574-8,published online 25 November 2020 In the version of this article initially published,two unintended errors were made during manuscript preparation.(1)The figure legend for Panel 3B was missing;the correct legend is as follows.展开更多
Aim:Angiogenesis is observed in acute myeloid leukemia(AML).AML cells abnormally proliferate and are resistant to death.Positive regulators of angiogenesis,VEGF-A and matrix metalloproteinases(MMPs)2 and 9 are markers...Aim:Angiogenesis is observed in acute myeloid leukemia(AML).AML cells abnormally proliferate and are resistant to death.Positive regulators of angiogenesis,VEGF-A and matrix metalloproteinases(MMPs)2 and 9 are markers of disease status in AML.The natural phloroglucinol hyperforin(HF)displays antitumoral properties of potential pharmacological interest.Herein,we investigated the effects of HF on MMP-2/9 and VEGF-A expression and survival of primary AML cells.Methods:Blood and bone marrow samples were collected in 45 patients with distinct subtypes defined by French American British classification,i.e.,M0,M1,M2,M3,M4,and M5.Levels of MMPs and VEGF-A in leukemic blood cells and culture supernatants were determined by RT-PCR,ELISA,and gelatin zymography(MMPs).The balance between cell death and survival was assessed by flow cytometry with analysis of phosphatidylserine externalization and caspase-3 activation.Results:The administration of HF promoted a caspase-associated apoptosis in primary AML blasts(from blood and bone marrow),but not normal blood cells and monocytes.In addition,HF inhibited the levels of secreted proMMP-2,proMMP-9,and VEGF-A without altering transcripts.The induction of apoptosis by HF significantly paralleled the inhibition of MMP-2/9 and VEGF-A release by HF.No differences were seen in response to the deleterious effects of HF between AML cells of distinct subtypes.Conclusion:Our results suggest that HF,through its proapoptotic and potential antiangiogenic properties(by inhibiting MMP-2/9 and VEGF-A)on primary AML cells,might be a useful experimental agent,in combination with existing drugs,for new therapeutic approaches in the treatment of this incurable disease.展开更多
文摘Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency and sickle cell disease are common genetic defects of red blood cells that lead to hemolytic anemia. The prevalence of G6PD deficiency in sickle cell patients is unknown in Benin. Objective: This study aimed to determine the prevalence of G6PD deficiency in sickle cell patients at the CNHU-HKM of Cotonou. Methods: This prospective study was conducted from April to November 2022 at the blood-related diseases teaching clinic and included sickle cell patients in the stationary phase. G6PD determination was performed using the enzymatic method on a Mindray BS 200 machine following the Herz method. Hematological parameters were determined using the XT 4000i analyzer and supplemented by a blood smear stained with May Grunwald Giemsa. Data were analyzed using Epi Info 3.5.4 software. Results: One hundred and sixty-four sickle cell patients (80 SS homozygotes and 84 SC heterozygotes) in the intercritical phase, with a mean age of 26.30 ± 10.76 years, were included. The prevalence of G6PD deficiency was 9.1% (15 cases found in 7 SS patients and 8 SC patients). In G6PD-deficient patients, the mean concentration of the enzyme was lower in Hb SC heterozygotes than in Hb SS homozygotes: 3.56 IU/g Hb versus 4.98 IU/g Hb. The mean reticulocyte count was 231.43 G/L in the deficient group, compared to 216.32 G/L in the non-deficient group. Conclusion: The preliminary results of our study reveal a high prevalence of G6PD deficiency in sickle cell patients. The impact of this association on hematologic and biological parameters should be evaluated for better management of sickle cell disease.
基金supported by a grant from the Fondation de France(DDS Cancer 2017)P.‐Y.D.received a Fondation de France research fellowship.
文摘Natural killer(NK)cells are innate cytotoxic lymphoid cells(ILCs)involved in the killing of infected and tumor cells.Among human and mouse NK cells from the spleen and blood,we previously identified by single-cell RNA sequencing(scRNAseq)two similar major subsets,NK1 and NK2.Using the same technology,we report here the identification,by single-cell RNA sequencing(scRNAseq),of three NK cell subpopulations in human bone marrow.Pseudotime analysis identified a subset of resident CD56^(bright) NK cells,NK0 cells,as the precursor of both circulating CD56dim NK1-like NK cells and CD56^(bright) NK2-like NK cells in human bone marrow and spleen under physiological conditions.Transcriptomic profiles of bone marrow NK cells from patients with acute myeloid leukemia(AML)exhibited stress-induced repression of NK cell effector functions,highlighting the profound impact of this disease on NK cell heterogeneity.Bone marrow NK cells from AML patients exhibited reduced levels of CD160,but the CD160high group had a significantly higher survival rate.
基金China Scholarship Council for financial support(CSC No.201606320257,China)
文摘Arsenic trioxide(As2O3)is recently found to have therapeutic potential in systemic sclerosis(SSc),a life-threatening multi-system fibrosing autoimmune disease with type I interferon(IFN-I)signature.Chronically activated plasmacytoid dendritic cells(pDCs)are responsible for IFN-I secretion and are closely related with fibrosis establishment in SSc.In this study,we showed that high concentrations of As2O3 induced apoptosis of pDCs via mitochondrial pathway with increased BAX/BCL-2 ratio,while independent of reactive oxygen species generation.Notably,at clinical relevant concentrations,As2O3 preferentially inhibited IFN-αsecretion as compared to other cytokines such as TNF-α,probably due to potent down-regulation of the total protein and mRNA expression,as well as phosphorylation of the interferon regulatory factor7(IRF7).In addition,As2O3 induced a suppressive phenotype,and in combination with cytokine inhibition,it down-regulated pDCs’capacity to induce CD4+T cell proliferation,Thl/Th22 polarization,and B cell differentiation towards plasmablasts.Moreover,chronically activated pDCs from SSc patients were not resistant to the selective IFN-αinhibition,and regulatory phenotype induced by As2O3.Collectively,our data suggest that As2O3 could target pDCs and exert its treatment efficacy in SSc,and more autoimmune disorders with IFN-I signature.
文摘Correction to:Cellular&Molecular Immunology https://doi.org/10.1038/S41423-020-00574-8,published online 25 November 2020 In the version of this article initially published,two unintended errors were made during manuscript preparation.(1)The figure legend for Panel 3B was missing;the correct legend is as follows.
基金supported by the French National Institute of Health and Medical Research(INSERM).This research received no external funding.
文摘Aim:Angiogenesis is observed in acute myeloid leukemia(AML).AML cells abnormally proliferate and are resistant to death.Positive regulators of angiogenesis,VEGF-A and matrix metalloproteinases(MMPs)2 and 9 are markers of disease status in AML.The natural phloroglucinol hyperforin(HF)displays antitumoral properties of potential pharmacological interest.Herein,we investigated the effects of HF on MMP-2/9 and VEGF-A expression and survival of primary AML cells.Methods:Blood and bone marrow samples were collected in 45 patients with distinct subtypes defined by French American British classification,i.e.,M0,M1,M2,M3,M4,and M5.Levels of MMPs and VEGF-A in leukemic blood cells and culture supernatants were determined by RT-PCR,ELISA,and gelatin zymography(MMPs).The balance between cell death and survival was assessed by flow cytometry with analysis of phosphatidylserine externalization and caspase-3 activation.Results:The administration of HF promoted a caspase-associated apoptosis in primary AML blasts(from blood and bone marrow),but not normal blood cells and monocytes.In addition,HF inhibited the levels of secreted proMMP-2,proMMP-9,and VEGF-A without altering transcripts.The induction of apoptosis by HF significantly paralleled the inhibition of MMP-2/9 and VEGF-A release by HF.No differences were seen in response to the deleterious effects of HF between AML cells of distinct subtypes.Conclusion:Our results suggest that HF,through its proapoptotic and potential antiangiogenic properties(by inhibiting MMP-2/9 and VEGF-A)on primary AML cells,might be a useful experimental agent,in combination with existing drugs,for new therapeutic approaches in the treatment of this incurable disease.