BACKGROUND B56εis a regulatory subunit of the serine/threonine protein phosphatase 2A,which is abnormally expressed in tumors and regulates various tumor cell functions.At present,the application of B56εin pan-cance...BACKGROUND B56εis a regulatory subunit of the serine/threonine protein phosphatase 2A,which is abnormally expressed in tumors and regulates various tumor cell functions.At present,the application of B56εin pan-cancer lacks a comprehensive analysis,and its role and mechanism in hepatocellular carcinoma(HCC)are still unclear.The Cancer Genome Atlas,Genotype-Tissue Expression,Gene Expression Profiling Interactive Analysis,and Tumor Immune Estimation Resource databases were used to analyze B56εexpression,prognostic mutations,somatic copy number alterations,and tumor immune characteristics in 33 tumors.The relationships between B56εexpression levels and drug sensitivity,immuno-therapy,immune checkpoints,and human leukocyte antigen(HLA)-related genes were further analyzed.Gene Set Enrichment Analysis(GSEA)was performed to reveal the role of B56εin HCC.The Cell Counting Kit-8,plate cloning,wound healing,and transwell assays were conducted to assess the effects of B56εinterference on the malignant behavior of HCC cells.RESULTS In most tumors,B56εexpression was upregulated,and high B56εexpression was a risk factor for adrenocortical cancer,HCC,pancreatic adenocarcinoma,and pheochromocytoma and paraganglioma(all P<0.05).B56εexpression levels were correlated with a variety of immune cells,such as T helper 17 cells,B cells,and macro-phages.There was a positive correlation between B56εexpression levels with immune checkpoint genes and HLA-related genes(all P<0.05).The expression of B56εwas negatively correlated with the sensitivity of most chemotherapy drugs,but a small number showed a positive correlation(all P<0.05).GSEA analysis showed that B56εexpression was related to the cancer pathway,p53 downstream pathway,and interleukin-mediated signaling in HCC.Knockdown of B56εexpression in HCC cells inhibited the proliferation,migration,and invasion capacity of tumor cells.Core Tip:The expression of protein phosphatase 2A(PP2A)subunit B56εis up-regulated in most tumors,and its high expression is a risk factor for adrenocortical cancer,hepatocellular carcinoma(HCC),pancreatic adenocarcinoma,and pheochromocytoma and paraganglioma.B56εexpression levels correlate with immune cells,immune checkpoint genes,human leukocyte antigen-related genes,and the sensitivity of chemotherapy drugs.In HCC,B56εexpression is related to the cancer pathway.Knockdown of B56εexpression in HCC cells can inhibit the proliferation,migration and invasion capacity of tumor cells.Our study supports PP2A subunit B56εas a prognostic marker and potential therapeutic target for HCC.展开更多
BACKGROUND Progressive pancreaticβcell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus(T2DM).Recently,mesenchymal stem cell(MSC)transplantation has emerged as a new therapeuti...BACKGROUND Progressive pancreaticβcell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus(T2DM).Recently,mesenchymal stem cell(MSC)transplantation has emerged as a new therapeutic method due to its ability to promote the regeneration of pancreaticβcells.However,current studies have focused on its efficacy,and there are few clinical studies on its safety.AIM To evaluate the safety of human umbilical cord(hUC)-MSC infusion in T2DM treatment.METHODS An open-label and randomized phase 2 clinical trial was designed to evaluate the safety of hUC-MSC transplantation in T2DM in a Class A hospital.Ten patients in the placebo group received acellular saline intravenously once per week for 3 wk.Twenty-four patients in the hUC-MSC group received hUC-MSCs(1×106 cells/kg)intravenously once per week for 3 wk.Diabetic clinical symptoms and signs,laboratory findings,and imaging findings were evaluated weekly for the 1st mo and then at weeks 12 and 24 post-treatment.RESULTS No serious adverse events were observed during the 24-wk follow-up.Four patients(16.7%)in the hUC-MSC group experienced transient fever,which occurred within 24 h after the second or third infusion;this did not occur in any patients in the placebo group.One patient from the hUC-MSC group experienced hypoglycemic attacks within 1 mo after transplantation.Significantly lower lymphocyte levels(weeks 2 and 3)and thrombin coagulation time(week 2)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).Significantly higher platelet levels(week 3),immunoglobulin levels(weeks 1,2,3,and 4),fibrinogen levels(weeks 2 and 3),D-dimer levels(weeks 1,2,3,4,12,and 24),and neutrophil-to-lymphocyte ratios(weeks 2 and 3)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).There were no significant differences between the two groups for tumor markers(alpha-fetoprotein,carcinoembryonic antigen,and carbohydrate antigen 199)or blood fat.No liver damage or other side effects were observed on chest X-ray.CONCLUSION Our study suggested that hUC-MSC transplantation has good tolerance and high safety in the treatment of T2DM.It can improve human immunity and inhibit lymphocytes.Coagulation function should be monitored vigilantly for abnormalities.展开更多
BACKGROUND Progressive pancreaticβ-cell dysfunction is a fundamental part of the pathology of type 2 diabetes mellitus(T2DM).Cellular therapies offer novel opportunities for the treatment of T2DM to improve the funct...BACKGROUND Progressive pancreaticβ-cell dysfunction is a fundamental part of the pathology of type 2 diabetes mellitus(T2DM).Cellular therapies offer novel opportunities for the treatment of T2DM to improve the function of isletβ-cells.AIM To evaluate the effectiveness and safety of human umbilical cord-mesenchymal stem cell(hUC-MSC)infusion in T2DM treatment.METHODS Sixteen patients were enrolled and received 1×10^(6) cells/kg per week for 3 wk as intravenous hUC-MSC infusion.The effectiveness was evaluated by assessing fasting blood glucose,C-peptide,normal glycosylated hemoglobin A1c(HbA1c),insulin resistance index(homeostatic model assessment for insulin resistance),and isletβ-cell function(homeostasis model assessment ofβ-cell function).The dosage of hypoglycemic agents and safety were evaluated by monitoring the occurrence of any adverse events(AEs).RESULTS During the entire intervention period,the fasting plasma glucose level was significantly reduced[baseline:9.3400(8.3575,11.7725),day 14±3:6.5200(5.2200,8.6900);P<0.01].The HbA1c level was significantly reduced on day 84±3[baseline:7.8000(7.5250,8.6750),day 84±3:7.150(6.600,7.925);P<0.01].The patients’isletβ-cell function was significantly improved on day 28±3 of intervention[baseline:29.90(16.43,37.40),day 28±3:40.97(19.27,56.36);P<0.01].The dosage of hypoglycemic agents was reduced in all patients,of whom 6(50%)had a decrement of more than 50%and 1(6.25%)discontinued the hypoglycemic agents.Four patients had transient fever,which occurred within 24 h after the second or third infusion.One patient(2.08%)had asymptomatic nocturnal hypoglycemia after infusion on day 28±3.No liver damage or other side effects were reported.CONCLUSION The results of this study suggest that hUC-MSC infusion can improve glycemia,restore isletβ-cell function,and reduce the dosage of hypoglycemic agents without serious AEs.Thus,hUC-MSC infusion may be a novel option for the treatment of T2DM.展开更多
To the Editor:Malassezia located in the skin of patients with atopic dermatitis(AD)might be related to its pathogenesis,consisting of Malassezia globosa and Malassezia restricta as the dominant species.[1]However,the ...To the Editor:Malassezia located in the skin of patients with atopic dermatitis(AD)might be related to its pathogenesis,consisting of Malassezia globosa and Malassezia restricta as the dominant species.[1]However,the specific molecular mechanisms of Malassezia on host immune cells from AD patients are still unclear.In our study,the Affymetrix Human Prime View array was used to detect the effect of M.globosa on the gene expression of peripheral blood mononuclear cells(PBMCs)from AD patients,which was favorable to further understand the role of Malassezia colonization in the pathogenesis of AD.展开更多
基金National Natural Science Foundation of China,No.82060621,82060607,and 82260664Natural Science Foundation of Guangxi Province,No.2020GXNSFDA297010 and 2020GXNSFAA297142Key Science and Technology Research and Development Program Project of Guangxi,No.AB22035017。
文摘BACKGROUND B56εis a regulatory subunit of the serine/threonine protein phosphatase 2A,which is abnormally expressed in tumors and regulates various tumor cell functions.At present,the application of B56εin pan-cancer lacks a comprehensive analysis,and its role and mechanism in hepatocellular carcinoma(HCC)are still unclear.The Cancer Genome Atlas,Genotype-Tissue Expression,Gene Expression Profiling Interactive Analysis,and Tumor Immune Estimation Resource databases were used to analyze B56εexpression,prognostic mutations,somatic copy number alterations,and tumor immune characteristics in 33 tumors.The relationships between B56εexpression levels and drug sensitivity,immuno-therapy,immune checkpoints,and human leukocyte antigen(HLA)-related genes were further analyzed.Gene Set Enrichment Analysis(GSEA)was performed to reveal the role of B56εin HCC.The Cell Counting Kit-8,plate cloning,wound healing,and transwell assays were conducted to assess the effects of B56εinterference on the malignant behavior of HCC cells.RESULTS In most tumors,B56εexpression was upregulated,and high B56εexpression was a risk factor for adrenocortical cancer,HCC,pancreatic adenocarcinoma,and pheochromocytoma and paraganglioma(all P<0.05).B56εexpression levels were correlated with a variety of immune cells,such as T helper 17 cells,B cells,and macro-phages.There was a positive correlation between B56εexpression levels with immune checkpoint genes and HLA-related genes(all P<0.05).The expression of B56εwas negatively correlated with the sensitivity of most chemotherapy drugs,but a small number showed a positive correlation(all P<0.05).GSEA analysis showed that B56εexpression was related to the cancer pathway,p53 downstream pathway,and interleukin-mediated signaling in HCC.Knockdown of B56εexpression in HCC cells inhibited the proliferation,migration,and invasion capacity of tumor cells.Core Tip:The expression of protein phosphatase 2A(PP2A)subunit B56εis up-regulated in most tumors,and its high expression is a risk factor for adrenocortical cancer,hepatocellular carcinoma(HCC),pancreatic adenocarcinoma,and pheochromocytoma and paraganglioma.B56εexpression levels correlate with immune cells,immune checkpoint genes,human leukocyte antigen-related genes,and the sensitivity of chemotherapy drugs.In HCC,B56εexpression is related to the cancer pathway.Knockdown of B56εexpression in HCC cells can inhibit the proliferation,migration and invasion capacity of tumor cells.Our study supports PP2A subunit B56εas a prognostic marker and potential therapeutic target for HCC.
基金Shenzhen Science and Technology Innovation Committee Projects,No.JCYJ20170816105416349Shenzhen High-Level Hospital Construction Fund,Shenzhen Key Medical Discipline Construction Fund,No.SZXK010.
文摘BACKGROUND Progressive pancreaticβcell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus(T2DM).Recently,mesenchymal stem cell(MSC)transplantation has emerged as a new therapeutic method due to its ability to promote the regeneration of pancreaticβcells.However,current studies have focused on its efficacy,and there are few clinical studies on its safety.AIM To evaluate the safety of human umbilical cord(hUC)-MSC infusion in T2DM treatment.METHODS An open-label and randomized phase 2 clinical trial was designed to evaluate the safety of hUC-MSC transplantation in T2DM in a Class A hospital.Ten patients in the placebo group received acellular saline intravenously once per week for 3 wk.Twenty-four patients in the hUC-MSC group received hUC-MSCs(1×106 cells/kg)intravenously once per week for 3 wk.Diabetic clinical symptoms and signs,laboratory findings,and imaging findings were evaluated weekly for the 1st mo and then at weeks 12 and 24 post-treatment.RESULTS No serious adverse events were observed during the 24-wk follow-up.Four patients(16.7%)in the hUC-MSC group experienced transient fever,which occurred within 24 h after the second or third infusion;this did not occur in any patients in the placebo group.One patient from the hUC-MSC group experienced hypoglycemic attacks within 1 mo after transplantation.Significantly lower lymphocyte levels(weeks 2 and 3)and thrombin coagulation time(week 2)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).Significantly higher platelet levels(week 3),immunoglobulin levels(weeks 1,2,3,and 4),fibrinogen levels(weeks 2 and 3),D-dimer levels(weeks 1,2,3,4,12,and 24),and neutrophil-to-lymphocyte ratios(weeks 2 and 3)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).There were no significant differences between the two groups for tumor markers(alpha-fetoprotein,carcinoembryonic antigen,and carbohydrate antigen 199)or blood fat.No liver damage or other side effects were observed on chest X-ray.CONCLUSION Our study suggested that hUC-MSC transplantation has good tolerance and high safety in the treatment of T2DM.It can improve human immunity and inhibit lymphocytes.Coagulation function should be monitored vigilantly for abnormalities.
基金grants from the Key National Basic Research Program of China，Nature Science Foundation of China (81270941) to Ye P,and the Nature Science Foundation of China，the Beijing Nova Program (Z121107002513124) to Bai Y
基金Supported by Shenzhen Science and Technology Innovation Committee Projects,No.JCYJ20170816105416349Shenzhen High-level Hospital Construction FundShenzhen Key Medical Discipline Construction Fund,No.SZXK010.
文摘BACKGROUND Progressive pancreaticβ-cell dysfunction is a fundamental part of the pathology of type 2 diabetes mellitus(T2DM).Cellular therapies offer novel opportunities for the treatment of T2DM to improve the function of isletβ-cells.AIM To evaluate the effectiveness and safety of human umbilical cord-mesenchymal stem cell(hUC-MSC)infusion in T2DM treatment.METHODS Sixteen patients were enrolled and received 1×10^(6) cells/kg per week for 3 wk as intravenous hUC-MSC infusion.The effectiveness was evaluated by assessing fasting blood glucose,C-peptide,normal glycosylated hemoglobin A1c(HbA1c),insulin resistance index(homeostatic model assessment for insulin resistance),and isletβ-cell function(homeostasis model assessment ofβ-cell function).The dosage of hypoglycemic agents and safety were evaluated by monitoring the occurrence of any adverse events(AEs).RESULTS During the entire intervention period,the fasting plasma glucose level was significantly reduced[baseline:9.3400(8.3575,11.7725),day 14±3:6.5200(5.2200,8.6900);P<0.01].The HbA1c level was significantly reduced on day 84±3[baseline:7.8000(7.5250,8.6750),day 84±3:7.150(6.600,7.925);P<0.01].The patients’isletβ-cell function was significantly improved on day 28±3 of intervention[baseline:29.90(16.43,37.40),day 28±3:40.97(19.27,56.36);P<0.01].The dosage of hypoglycemic agents was reduced in all patients,of whom 6(50%)had a decrement of more than 50%and 1(6.25%)discontinued the hypoglycemic agents.Four patients had transient fever,which occurred within 24 h after the second or third infusion.One patient(2.08%)had asymptomatic nocturnal hypoglycemia after infusion on day 28±3.No liver damage or other side effects were reported.CONCLUSION The results of this study suggest that hUC-MSC infusion can improve glycemia,restore isletβ-cell function,and reduce the dosage of hypoglycemic agents without serious AEs.Thus,hUC-MSC infusion may be a novel option for the treatment of T2DM.
基金the Research Project of Sichuan Provincial Education Department(No.17ZA0127)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University,and the HX-Academician Project,West China Hospital,Sichuan University.
文摘To the Editor:Malassezia located in the skin of patients with atopic dermatitis(AD)might be related to its pathogenesis,consisting of Malassezia globosa and Malassezia restricta as the dominant species.[1]However,the specific molecular mechanisms of Malassezia on host immune cells from AD patients are still unclear.In our study,the Affymetrix Human Prime View array was used to detect the effect of M.globosa on the gene expression of peripheral blood mononuclear cells(PBMCs)from AD patients,which was favorable to further understand the role of Malassezia colonization in the pathogenesis of AD.
