Objective： To investigate the role of simultaneous blockade of CD40/CD40L and B7/CD28 pathways in the immune tolerance via co-expression of sCD40LIg and CTLA4Ig mediated by replication-defective adenovirus. Methods：...Objective： To investigate the role of simultaneous blockade of CD40/CD40L and B7/CD28 pathways in the immune tolerance via co-expression of sCD40LIg and CTLA4Ig mediated by replication-defective adenovirus. Methods： Ad-sCD40LIg- IRES2-CTLA4Ig, replication-defective adenovirus co-expressing sCD40LIg and CTLA4Ig, was constructed and identified. The co-expression of sCD40LIg and CTLA4Ig was evaluated with confocal laser scanning microscope and Western blotting. Skin transplantations of C57BL/6 to BALB/c mice were performed. PBS, Ad-Shuttle-CMV and Ad-sCD40LIg-IRES2-CTLA4Ig were administered. Skin graft survival was monitored and the mRNA expression of both genes was evaluated in the skin allografts. Results： Ad-sCD40LIg-IRESE-CTLA4Ig was constructed successfully and identified. The co-expression of sCD40LIg and CTLA4Ig was identified with confocal laser scanning microscopy and Western blotting. Compared to the skin graft mean survival time （MST） of non-treated group （（5.75±0.71） d） or Ad-Shuttle-CMV-treated group （（5.50±0.53） d）, the skin graft MST was dramatically prolonged in the Ad-sCD40LIg-IRESE-CTLA4Ig-treated group （（ 16.38± 1.19） d, P〈0.001）. The mRNA expression of both genes was detected. Conclusion： Ad-sCD40LIg-IRES2-CTLA4Ig, a replication-defective adenovirus carrying genes encoding sCD40LIg and CTLA4Ig, was constructed. Simultaneous blockade of CD40/CD40L and B7/CD28 costimulatory pathway mediated by replication-defective adenovirus significantly prolonged skin allografi survival in mice.展开更多
Anaphylaxis is a complex and dynamic condition,marked by a heterogeneity of triggers,pathophysiological pathways,and clinical presentations.Although IgE-mediated immune responses are the predominant drivers of anaphyl...Anaphylaxis is a complex and dynamic condition,marked by a heterogeneity of triggers,pathophysiological pathways,and clinical presentations.Although IgE-mediated immune responses are the predominant drivers of anaphylaxis,non-IgE-mediated mechanisms,including complement activation,engagement of the contact sys-tem,and IgG-mediated processes,also significantly contribute to its pathogenesis.Furthermore,non-immunemediated pathways,such as MRGPRX2 receptor activation,play a pivotal role in the initiation of anaphylactic reactions.The diagnosis of anaphylaxis predominantly hinges on the recognition of clinical manifestations.Nevertheless,biomarkers like tryptase and CPA3,as well as genetic markers,serve as critical adjuncts in con-firming the diagnosis,evaluating the severity of the reaction,and forecasting the prognosis.The accurate identification and avoidance of allergens are fundamental strategies for preventing recurrent anaphylactic epi-sodes.Provision of epinephrine auto-injectors empower patients with effective tools for self-management.Future research endeavors should concentrate on deepening the understanding of the multifaceted pathophysiology of anaphylaxis,advancing the development of precise diagnostic modalities,and refining therapeutic strategies.Enhancing patient education and management protocols is also essential.These collective efforts are aimed at diminishing the incidence and mortality associated with anaphylaxis,thereby enhancing the quality of life for affected individuals.展开更多
BACKGROUND IgE plays a critical role in allergic inflammation and asthma pathogenesis.This study investigates the involvement of IgE cells in asthma exacerbation and evaluates the effectiveness of targeted interventio...BACKGROUND IgE plays a critical role in allergic inflammation and asthma pathogenesis.This study investigates the involvement of IgE cells in asthma exacerbation and evaluates the effectiveness of targeted interventions.AIM To evaluate the role of IgE in the exacerbation of allergic asthma and to determine the clinical efficacy of anti-IgE therapy in improving disease outcomes.Specifically,the study investigates changes in serum IgE levels,lung function,asthma control scores,and the frequency of acute exacerbations among patients receiving standard therapy with or without anti-IgE intervention.METHODS A total of 200 patients diagnosed with moderate to severe asthma were enrolled in this experimental study conducted from April 2024 to April 2025.Participants were randomized to receive either standard asthma therapy or therapy combined with anti-IgE agents.IgE levels and asthma control parameters were monitored.RESULTS Participants receiving anti-IgE treatment demonstrated a significant reduction in serum IgE levels(P<0.001),improved Forced expiratory volume in one second scores,and fewer exacerbation episodes compared to the control group.CONCLUSION IgE cells significantly contribute to asthma severity,and targeted therapy against IgE can improve disease outcomes.These findings underscore the importance of immunomodulatory strategies in asthma management.展开更多
基金Project (No. 30371416) supported by the National Natural ScienceFoundation of China
文摘Objective： To investigate the role of simultaneous blockade of CD40/CD40L and B7/CD28 pathways in the immune tolerance via co-expression of sCD40LIg and CTLA4Ig mediated by replication-defective adenovirus. Methods： Ad-sCD40LIg- IRES2-CTLA4Ig, replication-defective adenovirus co-expressing sCD40LIg and CTLA4Ig, was constructed and identified. The co-expression of sCD40LIg and CTLA4Ig was evaluated with confocal laser scanning microscope and Western blotting. Skin transplantations of C57BL/6 to BALB/c mice were performed. PBS, Ad-Shuttle-CMV and Ad-sCD40LIg-IRES2-CTLA4Ig were administered. Skin graft survival was monitored and the mRNA expression of both genes was evaluated in the skin allografts. Results： Ad-sCD40LIg-IRESE-CTLA4Ig was constructed successfully and identified. The co-expression of sCD40LIg and CTLA4Ig was identified with confocal laser scanning microscopy and Western blotting. Compared to the skin graft mean survival time （MST） of non-treated group （（5.75±0.71） d） or Ad-Shuttle-CMV-treated group （（5.50±0.53） d）, the skin graft MST was dramatically prolonged in the Ad-sCD40LIg-IRESE-CTLA4Ig-treated group （（ 16.38± 1.19） d, P〈0.001）. The mRNA expression of both genes was detected. Conclusion： Ad-sCD40LIg-IRES2-CTLA4Ig, a replication-defective adenovirus carrying genes encoding sCD40LIg and CTLA4Ig, was constructed. Simultaneous blockade of CD40/CD40L and B7/CD28 costimulatory pathway mediated by replication-defective adenovirus significantly prolonged skin allografi survival in mice.
文摘Anaphylaxis is a complex and dynamic condition,marked by a heterogeneity of triggers,pathophysiological pathways,and clinical presentations.Although IgE-mediated immune responses are the predominant drivers of anaphylaxis,non-IgE-mediated mechanisms,including complement activation,engagement of the contact sys-tem,and IgG-mediated processes,also significantly contribute to its pathogenesis.Furthermore,non-immunemediated pathways,such as MRGPRX2 receptor activation,play a pivotal role in the initiation of anaphylactic reactions.The diagnosis of anaphylaxis predominantly hinges on the recognition of clinical manifestations.Nevertheless,biomarkers like tryptase and CPA3,as well as genetic markers,serve as critical adjuncts in con-firming the diagnosis,evaluating the severity of the reaction,and forecasting the prognosis.The accurate identification and avoidance of allergens are fundamental strategies for preventing recurrent anaphylactic epi-sodes.Provision of epinephrine auto-injectors empower patients with effective tools for self-management.Future research endeavors should concentrate on deepening the understanding of the multifaceted pathophysiology of anaphylaxis,advancing the development of precise diagnostic modalities,and refining therapeutic strategies.Enhancing patient education and management protocols is also essential.These collective efforts are aimed at diminishing the incidence and mortality associated with anaphylaxis,thereby enhancing the quality of life for affected individuals.
文摘BACKGROUND IgE plays a critical role in allergic inflammation and asthma pathogenesis.This study investigates the involvement of IgE cells in asthma exacerbation and evaluates the effectiveness of targeted interventions.AIM To evaluate the role of IgE in the exacerbation of allergic asthma and to determine the clinical efficacy of anti-IgE therapy in improving disease outcomes.Specifically,the study investigates changes in serum IgE levels,lung function,asthma control scores,and the frequency of acute exacerbations among patients receiving standard therapy with or without anti-IgE intervention.METHODS A total of 200 patients diagnosed with moderate to severe asthma were enrolled in this experimental study conducted from April 2024 to April 2025.Participants were randomized to receive either standard asthma therapy or therapy combined with anti-IgE agents.IgE levels and asthma control parameters were monitored.RESULTS Participants receiving anti-IgE treatment demonstrated a significant reduction in serum IgE levels(P<0.001),improved Forced expiratory volume in one second scores,and fewer exacerbation episodes compared to the control group.CONCLUSION IgE cells significantly contribute to asthma severity,and targeted therapy against IgE can improve disease outcomes.These findings underscore the importance of immunomodulatory strategies in asthma management.
