Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeut...Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.展开更多
Background Because of the pivotal role of the human leukocyte antigen （HLA） class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II al...Background Because of the pivotal role of the human leukocyte antigen （HLA） class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II alleles have been implicated in susceptibility to allergic diseases and in restriction of the IgE responses to a variety of allergens. We investigated the relationship between HLA-DRB genotype and allergies to various penicillins and explored HLA-DRB restriction of IgE responses to these derivatives of penicillin.Methods Radioallergosorbent test was used to examine 8 kinds of specific IgE antibodies （4 major and 4 minor antigenic determinants） in the sera of 248 patients with an allergy to penicillins and 101 healthy subjects without any allergic reaction. Some （113 patients and 87 healthy control subjects） were chosen from all subjects to type for HLA-DRB alleles by sequence specific primer-polymerase chain reaction.Results Compared with control subjects, a sign/ficantly increased frequency of DR9 was present in 77 patients with allergic reactions, with immediate hypersensitive reaction and with urticaria （P = 0.011; P = 0.019; P = 0.005 respectively）. Conversely, a significantly decreased frequency of DR14.1 was found in 80 patients with positive IgE antibodies, with immediate reaction and with urticaria compared with control group （P = 0.024; P = 0.038; P = 0.038）. A possible excess of HLA-DR17 was found in subjects who were responsive to benzylpenicilloyl compared with those were not （X^2 = 5.134, P = 0.023）, and of HLA-DR4 was found in subjects responsive to phenoxomethylpenicillanyl （PVA, X^2 = 4.057, P = 0.044）.Conclusion I-ILA-DRB gene may be involved in allergy to pcnicillins through modulating spvcific serum IgE to penicillins.展开更多
文摘Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.
基金This study was supported by grants from the Science Foundation for Distinguished Young Scholars of Henan Province (No. 0312002100)the Nature Science Foundation of Henan Province (No. 0211040100).
文摘Background Because of the pivotal role of the human leukocyte antigen （HLA） class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II alleles have been implicated in susceptibility to allergic diseases and in restriction of the IgE responses to a variety of allergens. We investigated the relationship between HLA-DRB genotype and allergies to various penicillins and explored HLA-DRB restriction of IgE responses to these derivatives of penicillin.Methods Radioallergosorbent test was used to examine 8 kinds of specific IgE antibodies （4 major and 4 minor antigenic determinants） in the sera of 248 patients with an allergy to penicillins and 101 healthy subjects without any allergic reaction. Some （113 patients and 87 healthy control subjects） were chosen from all subjects to type for HLA-DRB alleles by sequence specific primer-polymerase chain reaction.Results Compared with control subjects, a sign/ficantly increased frequency of DR9 was present in 77 patients with allergic reactions, with immediate hypersensitive reaction and with urticaria （P = 0.011; P = 0.019; P = 0.005 respectively）. Conversely, a significantly decreased frequency of DR14.1 was found in 80 patients with positive IgE antibodies, with immediate reaction and with urticaria compared with control group （P = 0.024; P = 0.038; P = 0.038）. A possible excess of HLA-DR17 was found in subjects who were responsive to benzylpenicilloyl compared with those were not （X^2 = 5.134, P = 0.023）, and of HLA-DR4 was found in subjects responsive to phenoxomethylpenicillanyl （PVA, X^2 = 4.057, P = 0.044）.Conclusion I-ILA-DRB gene may be involved in allergy to pcnicillins through modulating spvcific serum IgE to penicillins.
