Jose-Reynaldo Homen Fernandez, Inés Armenteros, Adrián Valls Carbó, Julia Barrado, Carolina Olmos-Mata, Ana Muñoz, Juncal Pérez-Somarriba, Noemí Cabello, María José Núñez, Vicente Estrada
Background
Lower respiratory tract infections (LRTIs) impose a significant global burden, with over 400 million cases annually. This study compares the clinical features of adults hospitalized with respiratory syncytial virus (RSV) and COVID-19, two viral pathogens with similar presentations but differing epidemiology.
Methods
This cross-sectional study analyzed 100 adult cases with PCR-confirmed RSV or COVID-19, admitted to the hospital from January 2022 to March 2023. Data on clinical, sociodemographic, radiological, treatment, and laboratory variables were extracted from records.
Results
Both cohorts consisted of elderly patients (> 70 years) with multiple comorbidities. Notably, the RSV group had a higher prevalence of CHF (24% vs. 10%, p = 0.014) and COPD (29% vs. 9%, p = 0.001). Radiologically, 51% of RSV patients had normal findings, whereas 48% of COVID-19 patients exhibited bilateral pneumonia (p = 0.001). Antimicrobial treatment was administered to 75% of RSV patients compared to 41% of COVID-19 patients (p < 0.001). RSV patients had marginally higher leukocyte and neutrophil counts, while COVID-19 patients showed significantly elevated CRP, ferritin, LDH, ALT, and potassium levels.
Conclusions
Distinct profiles were identified between hospitalized RSV and COVID-19 patients. RSV patients, mostly older with CHF and COPD, were more likely to receive antibiotics, possibly reflecting the lack of targeted therapies. In contrast, COVID-19 patients exhibited higher inflammation and lung involvement. These findings highlight the need to refine treatment protocols, enhance antimicrobial stewardship, and develop specific RSV therapies alongside preventive strategies for high-risk groups.
{"title":"Respiratory Syncytial Virus and COVID-19 in Hospitalized Adults in Spain: Clinical, Radiological Features and Antimicrobial Use","authors":"Jose-Reynaldo Homen Fernandez, Inés Armenteros, Adrián Valls Carbó, Julia Barrado, Carolina Olmos-Mata, Ana Muñoz, Juncal Pérez-Somarriba, Noemí Cabello, María José Núñez, Vicente Estrada","doi":"10.1002/iid3.70281","DOIUrl":"10.1002/iid3.70281","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lower respiratory tract infections (LRTIs) impose a significant global burden, with over 400 million cases annually. This study compares the clinical features of adults hospitalized with respiratory syncytial virus (RSV) and COVID-19, two viral pathogens with similar presentations but differing epidemiology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study analyzed 100 adult cases with PCR-confirmed RSV or COVID-19, admitted to the hospital from January 2022 to March 2023. Data on clinical, sociodemographic, radiological, treatment, and laboratory variables were extracted from records.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both cohorts consisted of elderly patients (> 70 years) with multiple comorbidities. Notably, the RSV group had a higher prevalence of CHF (24% vs. 10%, <i>p</i> = 0.014) and COPD (29% vs. 9%, <i>p</i> = 0.001). Radiologically, 51% of RSV patients had normal findings, whereas 48% of COVID-19 patients exhibited bilateral pneumonia (<i>p</i> = 0.001). Antimicrobial treatment was administered to 75% of RSV patients compared to 41% of COVID-19 patients (<i>p</i> < 0.001). RSV patients had marginally higher leukocyte and neutrophil counts, while COVID-19 patients showed significantly elevated CRP, ferritin, LDH, ALT, and potassium levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Distinct profiles were identified between hospitalized RSV and COVID-19 patients. RSV patients, mostly older with CHF and COPD, were more likely to receive antibiotics, possibly reflecting the lack of targeted therapies. In contrast, COVID-19 patients exhibited higher inflammation and lung involvement. These findings highlight the need to refine treatment protocols, enhance antimicrobial stewardship, and develop specific RSV therapies alongside preventive strategies for high-risk groups.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70281","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Taiyuan Guan, Peixin Li, Sijian Su, Liang Ao, Xin Zhou
Background
Patients with osteoarthritis (OA) exhibit an elevated risk for major depressive disorder (MDD), primarily due to chronic pain and associated disability. However, the shared molecular mechanisms underlying these conditions remain poorly understood.
Methods
This study employs bioinformatics and systems biology approaches to identify common gene signatures and elucidate the shared pathogenesis of OA and MDD.
Results
We identified 22 common differentially expressed genes between the two diseases, which were predominantly associated with the positive regulation of reactive oxygen species metabolic processes, immune and inflammatory responses, efferocytosis, the PI3K-Akt signaling pathway, the TGF-beta receptor signaling pathway, and immune system-related pathways. Notably, CXCR6, GZMK, and KLRG1 were identified as key genes, showing positive correlations with CD8+ T cells and negative correlations with naïve CD4+ T cells and monocytes in both OA and MDD. Competitive endogenous RNA regulatory network analysis revealed that the KCNQ1OT1-miR-92a/miR-132/miR-19b/miR-145-CXCR6/GZMK/KLRG1 and XIST1-miR-92a/miR-132/miR-19b-CXCR6/GZMK/KLRG1 regulatory axes may play critical roles in the pathogenesis of OA and MDD.
Conclusion
These findings provide novel insights into the comorbidity mechanism of OA and MDD and may guide the development of individualized therapeutic strategies for patients with comorbid conditions.
{"title":"Identification of Potential Common Pathogenic Mechanisms Underlying Osteoarthritis and Major Depressive Disorder Using Bioinformatics Analysis","authors":"Taiyuan Guan, Peixin Li, Sijian Su, Liang Ao, Xin Zhou","doi":"10.1002/iid3.70293","DOIUrl":"10.1002/iid3.70293","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with osteoarthritis (OA) exhibit an elevated risk for major depressive disorder (MDD), primarily due to chronic pain and associated disability. However, the shared molecular mechanisms underlying these conditions remain poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study employs bioinformatics and systems biology approaches to identify common gene signatures and elucidate the shared pathogenesis of OA and MDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 22 common differentially expressed genes between the two diseases, which were predominantly associated with the positive regulation of reactive oxygen species metabolic processes, immune and inflammatory responses, efferocytosis, the PI3K-Akt signaling pathway, the TGF-beta receptor signaling pathway, and immune system-related pathways. Notably, CXCR6, GZMK, and KLRG1 were identified as key genes, showing positive correlations with CD8+ T cells and negative correlations with naïve CD4+ T cells and monocytes in both OA and MDD. Competitive endogenous RNA regulatory network analysis revealed that the KCNQ1OT1-miR-92a/miR-132/miR-19b/miR-145-CXCR6/GZMK/KLRG1 and XIST1-miR-92a/miR-132/miR-19b-CXCR6/GZMK/KLRG1 regulatory axes may play critical roles in the pathogenesis of OA and MDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings provide novel insights into the comorbidity mechanism of OA and MDD and may guide the development of individualized therapeutic strategies for patients with comorbid conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70293","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shujing Ma, Xiaoxin Xie, Yanhua Fu, Lin Gan, Xiaoyan Yang, Qing Wang, Hai Long
Background
Long-term outcome data from real-world studies of the bictegravir emtricitabine tenofovir alafenamide fumarate (B/F/TAF) regimen in the treatment of elderly patients with HIV/AIDS are still limited. This study evaluated the real-world effectiveness and safety of B/F/TAF in elderly HIV-infected individuals in southwest China.
Methods
This was an observational, single-center, retrospective study that enrolled antiretroviral therapy (ART)-naïve (n = 149) and ART-experienced (n = 143) patients with HIV infection between January 2021 and April 2024. The main endpoint was the viral suppression rate of HIV RNA < 50 copies/ml at 48 weeks, and change in CD4 cell count, CD4/CD8 ratio, body weight, blood lipid and safety were secondary endpoints.
Results
The proportions of ART-naïve and ART-experienced HIV-infected cases with VL < 50 copies/mL at 48 weeks were 93.1% and 92.9%, respectively. CD4 cell counts and CD4/CD8 ratios increased significantly from baseline at 48 weeks (p < 0.001). In the treatment-naive group, ALT, AST, eGFR, and Glu decreased significantly from baseline at 48 weeks, while body weight, Scr, TC, HDL, and LDL increased significantly. Among patients previously administered ART, eGFR increased significantly from baseline at 48 weeks, while AST, LDL, and Scr decreased significantly; other indicators showed no significant changes from baseline. The incidence rates of adverse events were 11.7% and 4.3% in treatment-naïve and treatment-experienced, respectively.
Conclusions
For elderly HIV/AIDS patients, B/F/TAF is a safe option to achieve and maintain virological suppression and immune recovery. In terms of lipid metabolism, the metabolic effects of BIC/FTC/TAF in the treated patients are not significant, and the effects in untreated patients require longer follow-up.
{"title":"Clinical Efficacy and Safety of BIC/TAF/FTC in Elderly HIV-Infected Individuals in Southwest China: A Retrospective Observation Study","authors":"Shujing Ma, Xiaoxin Xie, Yanhua Fu, Lin Gan, Xiaoyan Yang, Qing Wang, Hai Long","doi":"10.1002/iid3.70264","DOIUrl":"10.1002/iid3.70264","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Long-term outcome data from real-world studies of the bictegravir emtricitabine tenofovir alafenamide fumarate (B/F/TAF) regimen in the treatment of elderly patients with HIV/AIDS are still limited. This study evaluated the real-world effectiveness and safety of B/F/TAF in elderly HIV-infected individuals in southwest China.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was an observational, single-center, retrospective study that enrolled antiretroviral therapy (ART)-naïve (<i>n</i> = 149) and ART-experienced (<i>n</i> = 143) patients with HIV infection between January 2021 and April 2024. The main endpoint was the viral suppression rate of HIV RNA < 50 copies/ml at 48 weeks, and change in CD4 cell count, CD4/CD8 ratio, body weight, blood lipid and safety were secondary endpoints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The proportions of ART-naïve and ART-experienced HIV-infected cases with VL < 50 copies/mL at 48 weeks were 93.1% and 92.9%, respectively. CD4 cell counts and CD4/CD8 ratios increased significantly from baseline at 48 weeks (<i>p</i> < 0.001). In the treatment-naive group, ALT, AST, eGFR, and Glu decreased significantly from baseline at 48 weeks, while body weight, Scr, TC, HDL, and LDL increased significantly. Among patients previously administered ART, eGFR increased significantly from baseline at 48 weeks, while AST, LDL, and Scr decreased significantly; other indicators showed no significant changes from baseline. The incidence rates of adverse events were 11.7% and 4.3% in treatment-naïve and treatment-experienced, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>For elderly HIV/AIDS patients, B/F/TAF is a safe option to achieve and maintain virological suppression and immune recovery. In terms of lipid metabolism, the metabolic effects of BIC/FTC/TAF in the treated patients are not significant, and the effects in untreated patients require longer follow-up.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In winter 2024/2025, one of the most severe U.S. influenza epidemics since 2017, with 82 million illnesses and ~ 130,000 deaths, eclipsed a comparatively subdued SARS-CoV-2 wave (~ 20 million infections, ~540,000 hospitalizations, ~63,000 COVID-19 deaths), a hypothesis supported by existing CDC data and virological models.
Hypothesis
Influenza's robust interferon response might have contributed to suppression of SARS-CoV-2 replication, creating an antiviral environment that delayed COVID-19's winter surge.
Evidence
In vitro studies demonstrate influenza interference with SARS-CoV-2, reversible by oseltamivir, supporting this hypothesis. Thus, the decline in influenza activity in spring 2025 may have contributed to the observed increase in SARS-CoV-2 hospitalizations, driven by the NB.1.8.1 variant, a JN.1 derivative with enhanced transmissibility and reduced neutralization. Although this did not evolve into a pandemic-scale wave, the resultant burden on healthcare services was clinically meaningful. Alternative explanations, including behavioral changes and Omicron-induced herd immunity, are considered but less compelling.
Implication
The global health implications are critical: lapsed COVID-19 preparedness, limited surveillance, and low vaccine uptake threaten effective responses.
Recommandations
We advocate enhanced surveillance, adopting wastewater monitoring as demonstrated in the U.S., and integrated vaccination campaigns with combined influenza-COVID-19 vaccines, currently in phase III trials, to boost immunity. Resource allocation, informed by the 2024/2025 hospital overload, is essential to manage surges. This article underscores the need for global coordination to understand viral interference and prepare for shifting respiratory virus dynamics, offering actionable strategies to mitigate future epidemics, including those caused by other viruses.
{"title":"The Unprecedented Influenza Epidemic of 2024/2025: Overshadowing the COVID-19 Winter Wave and Exploring Viral Interference","authors":"Benjamin Davido","doi":"10.1002/iid3.70300","DOIUrl":"10.1002/iid3.70300","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In winter 2024/2025, one of the most severe U.S. influenza epidemics since 2017, with 82 million illnesses and ~ 130,000 deaths, eclipsed a comparatively subdued SARS-CoV-2 wave (~ 20 million infections, ~540,000 hospitalizations, ~63,000 COVID-19 deaths), a hypothesis supported by existing CDC data and virological models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Hypothesis</h3>\u0000 \u0000 <p>Influenza's robust interferon response might have contributed to suppression of SARS-CoV-2 replication, creating an antiviral environment that delayed COVID-19's winter surge.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Evidence</h3>\u0000 \u0000 <p>In vitro studies demonstrate influenza interference with SARS-CoV-2, reversible by oseltamivir, supporting this hypothesis. Thus, the decline in influenza activity in spring 2025 may have contributed to the observed increase in SARS-CoV-2 hospitalizations, driven by the NB.1.8.1 variant, a JN.1 derivative with enhanced transmissibility and reduced neutralization. Although this did not evolve into a pandemic-scale wave, the resultant burden on healthcare services was clinically meaningful. Alternative explanations, including behavioral changes and Omicron-induced herd immunity, are considered but less compelling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Implication</h3>\u0000 \u0000 <p>The global health implications are critical: lapsed COVID-19 preparedness, limited surveillance, and low vaccine uptake threaten effective responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Recommandations</h3>\u0000 \u0000 <p>We advocate enhanced surveillance, adopting wastewater monitoring as demonstrated in the U.S., and integrated vaccination campaigns with combined influenza-COVID-19 vaccines, currently in phase III trials, to boost immunity. Resource allocation, informed by the 2024/2025 hospital overload, is essential to manage surges. This article underscores the need for global coordination to understand viral interference and prepare for shifting respiratory virus dynamics, offering actionable strategies to mitigate future epidemics, including those caused by other viruses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70300","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145563861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Subarachnoid fibrosis is the key pathology of hydrocephalus, but its underlying mechanisms remains poorly understood. In the present study, we aim to verify the hypothesis that neutrophil extracellular traps (NETs), released by neutrophils infiltrated into the subarachnoid space following hemorrhage and infection, might be a crucial culprits in promoting subarachnoid fibrosis in hydrocephalus.
Methods
Firstly, NETs in cerebrospinal fluid (CSF) specimens from patients and subarachnoid fibrosis of kaolin-induced hydrocephalus rat model were detected by assay kit and immunofluorescence, respectively. Secondly, kaolin-induced hydrocephalus rats were treated by peptidylarginine deiminase 4 (PAD4) inhibitor and DNase I. NETs, subarachnoid fibrosis, reactive gliosis, proliferation and differentiation of meningeal fibroblasts were detected by immunofluorescence and Western Blot (WB), ventricular volumes were evaluated by magnetic resonance imaging (MRI). Finally, primary meningeal fibroblasts were stimulated with NET, and their proliferation and differentiation were measured by flow cytometer, WB and immunofluorescence, respectively.
Results
Combining with CSF specimens from patients and hydrocephalus rat model, we found that infiltrating neutrophils release NETs in the subarachnoid space after subarachnoid hemorrhage and hydrocephalus. Further, combining with in vivo animal experiments and in vitro experiments, we demonstrated that NETs aggravate subarachnoid fibrosis to promote hydrocephalus via stimulating the proliferation and differentiation of meningeal fibroblasts. What′s more, both inhibiting NETs production with PAD4 inhibitor and degrading NETs with DNase I significantly prevent the development of hydrocephalus by attenuating subarachnoid fibrosis.
Conclusion
NETs aggravate subarachnoid fibrosis to promote hydrocephalus via stimulating the proliferation and differentiation of meningeal fibroblasts, and restricting NETs significantly prevents the development of hydrocephalus through attenuating subarachnoid fibrosis. It indicates that NETs might be a promising potential target for clinical hydrocephalus treatment.
{"title":"Neutrophil Extracellular Traps Activate Meningeal Fibroblast to Aggravate Subarachnoid Fibrosis in Kaolin-Induced Hydrocephalus in Rats","authors":"Chao Ma, Zhou Feng, Binyuan Xiong, Liang Liang, Shengyan Liu, Lingxia Min, Qiang Zhang, Peiwen Guo, Jingyu Chen, Liang Tan, Jingming Hou, Zhi Chen","doi":"10.1002/iid3.70268","DOIUrl":"10.1002/iid3.70268","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>Subarachnoid fibrosis is the key pathology of hydrocephalus, but its underlying mechanisms remains poorly understood. In the present study, we aim to verify the hypothesis that neutrophil extracellular traps (NETs), released by neutrophils infiltrated into the subarachnoid space following hemorrhage and infection, might be a crucial culprits in promoting subarachnoid fibrosis in hydrocephalus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Firstly, NETs in cerebrospinal fluid (CSF) specimens from patients and subarachnoid fibrosis of kaolin-induced hydrocephalus rat model were detected by assay kit and immunofluorescence, respectively. Secondly, kaolin-induced hydrocephalus rats were treated by peptidylarginine deiminase 4 (PAD4) inhibitor and DNase I. NETs, subarachnoid fibrosis, reactive gliosis, proliferation and differentiation of meningeal fibroblasts were detected by immunofluorescence and Western Blot (WB), ventricular volumes were evaluated by magnetic resonance imaging (MRI). Finally, primary meningeal fibroblasts were stimulated with NET, and their proliferation and differentiation were measured by flow cytometer, WB and immunofluorescence, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Combining with CSF specimens from patients and hydrocephalus rat model, we found that infiltrating neutrophils release NETs in the subarachnoid space after subarachnoid hemorrhage and hydrocephalus. Further, combining with in vivo animal experiments and in vitro experiments, we demonstrated that NETs aggravate subarachnoid fibrosis to promote hydrocephalus via stimulating the proliferation and differentiation of meningeal fibroblasts. What′s more, both inhibiting NETs production with PAD4 inhibitor and degrading NETs with DNase I significantly prevent the development of hydrocephalus by attenuating subarachnoid fibrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>NETs aggravate subarachnoid fibrosis to promote hydrocephalus via stimulating the proliferation and differentiation of meningeal fibroblasts, and restricting NETs significantly prevents the development of hydrocephalus through attenuating subarachnoid fibrosis. It indicates that NETs might be a promising potential target for clinical hydrocephalus treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chimeric antigen receptor T-cell (CAR-T) therapy, a revolutionary immunotherapy originally developed for hematologic malignancies, has recently gained attention for its potential in treating autoimmune diseases. Increasing evidence suggests that CAR-T cells can precisely target pathogenic immune populations, offering durable remission and immune homeostasis restoration in neuroimmunological disorders such as myasthenia gravis (MG), neuromyelitis optica spectrum disorder (NMOSD), and multiple sclerosis (MS).
Methods
Relevant publications and clinical trial data up to September 2025 were systematically reviewed to summarize the mechanisms, therapeutic targets, safety profiles, and translational applications of CAR-T therapy in autoimmune diseases of the nervous system.
Results
Preclinical and early clinical studies demonstrate that CD19- and BCMA-directed CAR-T therapies effectively deplete autoreactive B cells with significant symptom improvement and minimal cytokine release syndrome or neurotoxicity. Novel constructs such as chimeric autoantibody receptor (CAAR)-T and CAR-regulatory T (CAR-Treg) cells enhance specificity and immune tolerance. Innovations including allogeneic “off-the-shelf” CAR-T, in vivo CAR engineering, and CRISPR-based safety switches further optimize therapeutic potential and accessibility.
Conclusion
CAR-T therapy represents a promising frontier for refractory neuroautoimmune diseases. By precisely modulating immune networks, it offers a pathway toward long-term remission and personalized immunotherapy in clinical neuroimmunology.
{"title":"Chimeric Antigen Receptor T-Cell Therapy and Autoimmune Diseases in the Nervous System","authors":"Shun-yu Yao, Miao-qiao Du, Huan Yang, Qiu-ming Zeng, Hao Zhou, Xiuli Zhang, Sugimoto Kazuo, Jia Liu, Lan-xin Lin, Xu-hui Kang, Dai-yi Jiang, Yong Peng","doi":"10.1002/iid3.70298","DOIUrl":"10.1002/iid3.70298","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Chimeric antigen receptor T-cell (CAR-T) therapy, a revolutionary immunotherapy originally developed for hematologic malignancies, has recently gained attention for its potential in treating autoimmune diseases. Increasing evidence suggests that CAR-T cells can precisely target pathogenic immune populations, offering durable remission and immune homeostasis restoration in neuroimmunological disorders such as myasthenia gravis (MG), neuromyelitis optica spectrum disorder (NMOSD), and multiple sclerosis (MS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Relevant publications and clinical trial data up to September 2025 were systematically reviewed to summarize the mechanisms, therapeutic targets, safety profiles, and translational applications of CAR-T therapy in autoimmune diseases of the nervous system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Preclinical and early clinical studies demonstrate that CD19- and BCMA-directed CAR-T therapies effectively deplete autoreactive B cells with significant symptom improvement and minimal cytokine release syndrome or neurotoxicity. Novel constructs such as chimeric autoantibody receptor (CAAR)-T and CAR-regulatory T (CAR-Treg) cells enhance specificity and immune tolerance. Innovations including allogeneic “off-the-shelf” CAR-T, in vivo CAR engineering, and CRISPR-based safety switches further optimize therapeutic potential and accessibility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CAR-T therapy represents a promising frontier for refractory neuroautoimmune diseases. By precisely modulating immune networks, it offers a pathway toward long-term remission and personalized immunotherapy in clinical neuroimmunology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12598406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qiuyu Dai, Jie Zheng, Meng Fu, Song Qin, Xiaoyun Fu
Background
Annexin A1 (ANXA1), a calcium-dependent phospholipid-binding protein, plays a critical role in regulating inflammation, apoptosis, immune responses, and vascular remodeling. It is increasingly recognized for its potential as a therapeutic target and diagnostic biomarker in various circulatory diseases, including sepsis, hypertension, coronary heart disease, myocardial ischemia-reperfusion injury, heart failure, and cerebrovascular disorders. ANXA1 and its derived peptides exert protective effects by modulating key signaling pathways and cellular processes involved in disease pathogenesis.
Aim
This review summarizes the current research progress on ANXA1 and its derived peptides in the diagnosis and treatment of circulatory diseases, highlighting their mechanisms of action and therapeutic potential.
Method
A comprehensive literature search was conducted using PubMed, Web of Science, and other relevant databases. Articles published up to 2024 were included, with a focus on experimental studies, clinical reports, and reviews addressing the role of ANXA1 in circulatory diseases. Key themes included anti-inflammatory mechanisms, apoptosis regulation, immune modulation, and vascular protection.
Result
ANXA1 and its mimetic peptides like Ac2-26, ANXA1sp, RTP-026 and so on demonstrate significant protective effects across multiple circulatory diseases. They attenuate inflammation, oxidative stress, apoptosis, and ferroptosis, while promoting mitochondrial biosynthesis and immune regulation. These effects are mediated through receptors such as FPR2/ALX and pathways involving SIRT3, PI3K/Akt, and AMPK/mTOR. However, the role of ANXA1 can be context-dependent, exhibiting both protective and detrimental effects in specific conditions such as gestational hypertension and transient ischemic attack.
Conclusion
ANXA1 represents a promising diagnostic biomarker and therapeutic target for circulatory diseases. Further research is needed to elucidate its complex regulatory networks and validate its clinical applicability through multi-omics approaches and large-scale trials.
背景：膜联蛋白A1 （ANXA1）是一种钙依赖性磷脂结合蛋白，在调节炎症、细胞凋亡、免疫反应和血管重构中起关键作用。越来越多的人认识到它作为各种循环系统疾病的治疗靶点和诊断生物标志物的潜力，包括败血症、高血压、冠心病、心肌缺血-再灌注损伤、心力衰竭和脑血管疾病。ANXA1及其衍生肽通过调节关键信号通路和参与疾病发病的细胞过程发挥保护作用。目的：综述ANXA1及其衍生肽在循环系统疾病诊断和治疗中的研究进展，重点介绍其作用机制和治疗潜力。方法：利用PubMed、Web of Science等相关数据库进行综合文献检索。纳入了截至2024年发表的文章，重点是实验研究、临床报告和综述，讨论了ANXA1在循环系统疾病中的作用。主要主题包括抗炎机制、细胞凋亡调节、免疫调节和血管保护。结果：ANXA1及其类似肽Ac2-26、ANXA1sp、RTP-026等对多种循环系统疾病具有明显的保护作用。它们减轻炎症、氧化应激、细胞凋亡和铁下垂，同时促进线粒体生物合成和免疫调节。这些作用是通过受体如FPR2/ALX和涉及SIRT3、PI3K/Akt和AMPK/mTOR的途径介导的。然而，ANXA1的作用可能是情境依赖的，在妊娠高血压和短暂性脑缺血发作等特定情况下表现出保护和有害作用。结论：ANXA1是一种有前景的循环系统疾病诊断生物标志物和治疗靶点。需要进一步研究阐明其复杂的调控网络，并通过多组学方法和大规模试验验证其临床适用性。
{"title":"Research Progress of Annexin A1 and Its Derived Peptides in the Diagnosis and Treatment of Circulatory Diseases","authors":"Qiuyu Dai, Jie Zheng, Meng Fu, Song Qin, Xiaoyun Fu","doi":"10.1002/iid3.70249","DOIUrl":"10.1002/iid3.70249","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Annexin A1 (ANXA1), a calcium-dependent phospholipid-binding protein, plays a critical role in regulating inflammation, apoptosis, immune responses, and vascular remodeling. It is increasingly recognized for its potential as a therapeutic target and diagnostic biomarker in various circulatory diseases, including sepsis, hypertension, coronary heart disease, myocardial ischemia-reperfusion injury, heart failure, and cerebrovascular disorders. ANXA1 and its derived peptides exert protective effects by modulating key signaling pathways and cellular processes involved in disease pathogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This review summarizes the current research progress on ANXA1 and its derived peptides in the diagnosis and treatment of circulatory diseases, highlighting their mechanisms of action and therapeutic potential.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>A comprehensive literature search was conducted using PubMed, Web of Science, and other relevant databases. Articles published up to 2024 were included, with a focus on experimental studies, clinical reports, and reviews addressing the role of ANXA1 in circulatory diseases. Key themes included anti-inflammatory mechanisms, apoptosis regulation, immune modulation, and vascular protection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>ANXA1 and its mimetic peptides like Ac2-26, ANXA1sp, RTP-026 and so on demonstrate significant protective effects across multiple circulatory diseases. They attenuate inflammation, oxidative stress, apoptosis, and ferroptosis, while promoting mitochondrial biosynthesis and immune regulation. These effects are mediated through receptors such as FPR2/ALX and pathways involving SIRT3, PI3K/Akt, and AMPK/mTOR. However, the role of ANXA1 can be context-dependent, exhibiting both protective and detrimental effects in specific conditions such as gestational hypertension and transient ischemic attack.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ANXA1 represents a promising diagnostic biomarker and therapeutic target for circulatory diseases. Further research is needed to elucidate its complex regulatory networks and validate its clinical applicability through multi-omics approaches and large-scale trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12598408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rong Wang, Keying Jing, Huijuan Zhao, Guoguang Zheng, Jun Cai
Introduction
Acute myeloid leukemia (AML) is known for its unfavorable prognosis, prompting research efforts of cytokines in the microenvironment to explore new therapeutic targets. Here, we investigated the complex cytokine networks in both AML mice and AML patients to reveal the role of cytokines in AML pathogenesis.
Methods
As a basis for further studies on human, the patterns of cytokines were detected in AML mice by cytokine array panel, and the patterns of cytokines were detected in AML patients by Luminex liquid suspension chip and ELISA. Leukocyte subpopulations in human were analyzed by flow cytometry. Additionally, the associations of cytokine levels with the outcome of AML patients were analyzed by Cox regression analysis, the overall survival curve was assessed by Kaplan-Meier method. Furthermore, Pearson correlation analysis was used for the correlation analysis of continuous variables.
Results
The imbalanced patterns of cytokines were observed in AML mice. Furthermore, higher levels of CCL3, CCL4 and CXCL10, independent of sex, age, FAB phenotype, patient status and risk molecular, were associated with the poor outcome of AML patients recruited in our study by Cox regression analysis. Additionally, the survival analysis demonstrated that the CCL3high group had a shorter overall survival than the CCL3low group, and a similar result was observed in the analysis of CXCL10. The correlation analysis revealed that Treg cells may be related to the increase of CCL3, while B cell may be associated with for the changes of CXCL10 in AML microenvironment.
Conclusion
The imbalanced patterns of cytokines were observed in both AML mice and AML patients. Interestingly, 3 cytokines (CCL3, CCL4 and CXCL10) were related to the outcome of AML patients, suggesting they are valuable for AML prognosis. Furthermore, the change of leukocyte subpopulations, either as causes or as consequences, may partially account for the change of cytokines in AML condition.
{"title":"The Imbalanced Patterns and Clinical Significance of Cytokines in Acute Myeloid Leukemia Microenvironment","authors":"Rong Wang, Keying Jing, Huijuan Zhao, Guoguang Zheng, Jun Cai","doi":"10.1002/iid3.70290","DOIUrl":"10.1002/iid3.70290","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Acute myeloid leukemia (AML) is known for its unfavorable prognosis, prompting research efforts of cytokines in the microenvironment to explore new therapeutic targets. Here, we investigated the complex cytokine networks in both AML mice and AML patients to reveal the role of cytokines in AML pathogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>As a basis for further studies on human, the patterns of cytokines were detected in AML mice by cytokine array panel, and the patterns of cytokines were detected in AML patients by Luminex liquid suspension chip and ELISA. Leukocyte subpopulations in human were analyzed by flow cytometry. Additionally, the associations of cytokine levels with the outcome of AML patients were analyzed by Cox regression analysis, the overall survival curve was assessed by Kaplan-Meier method. Furthermore, Pearson correlation analysis was used for the correlation analysis of continuous variables.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The imbalanced patterns of cytokines were observed in AML mice. Furthermore, higher levels of CCL3, CCL4 and CXCL10, independent of sex, age, FAB phenotype, patient status and risk molecular, were associated with the poor outcome of AML patients recruited in our study by Cox regression analysis. Additionally, the survival analysis demonstrated that the CCL3<sup>high</sup> group had a shorter overall survival than the CCL3<sup>low</sup> group, and a similar result was observed in the analysis of CXCL10. The correlation analysis revealed that Treg cells may be related to the increase of CCL3, while B cell may be associated with for the changes of CXCL10 in AML microenvironment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The imbalanced patterns of cytokines were observed in both AML mice and AML patients. Interestingly, 3 cytokines (CCL3, CCL4 and CXCL10) were related to the outcome of AML patients, suggesting they are valuable for AML prognosis. Furthermore, the change of leukocyte subpopulations, either as causes or as consequences, may partially account for the change of cytokines in AML condition.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12598404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lili Tang, Shanshan He, Buguo Ma, Zeli Tang, Tingzheng Zhan, Suyu Xiao, Jilong Wang, Jinmin Zhao, Jiake Xu, Yunliang Shi
<div> <section> <h3> Background</h3> <p><i>Clonorchis sinensis</i> crude antigen (<i>Cs</i>CA) is recognized for its immunomodulatory capacity in host-pathogen interactions and immune-related pathologies, its direct impact on bone remodeling cells remains underexplored. Although prior studies demonstrate <i>Cs</i>CA-mediated suppression of inflammatory bone formation in ankylosing spondylitis, the specific regulatory effects on osteoclastogenesis and associated molecular mechanisms remain elusive. This study aimed to investigate the impact of <i>Cs</i>CA on osteoclast differentiation and its potential molecular mechanisms.</p> </section> <section> <h3> Methods</h3> <p>The cytotoxicity of <i>Cs</i>CA on mouse bone marrow–derived macrophages (BMMs) was evaluated using the CCK-8 assay. At the established non-cytotoxic dose, the effects of <i>Cs</i>CA on osteoclast morphology and activity were observed via TRAcP staining and F-actin ring formation assay. Expression of osteoclast differentiation-related genes and proteins was analyzed by combined RT-qPCR and Western Blot. RNA-seq was performed to identify <i>Cs</i>CA-regulated signaling pathways during osteoclast differentiation, followed by validation of key pathway components through Western Blot and immunofluorescence.</p> </section> <section> <h3> Results</h3> <p><i>Cs</i>CA exhibited no significant cytotoxicity on BMMs at concentrations ≤ 40 μg/mL. TRAcP staining revealed a significant reduction in osteoclast numbers in <i>Cs</i>CA-treated groups. F-actin ring formation assays demonstrated abnormal cytoskeletal structures. RT-PCR results showed significantly downregulated expression of osteoclast differentiation-related genes, including <i>NFATc1</i>, <i>c-Fos</i>, <i>Acp5</i>, <i>CTSK</i> and <i>MMP-9</i>. Western Blot confirmed reduced protein expression levels of NFATc1 and c-Fos. RNA-seq analysis combined with experimental validation by Western Blot and immunofluorescence confirmed that <i>Cs</i>CA primarily inhibits osteoclast differentiation through the NF-κB and MAPK signaling pathways.</p> </section> <section> <h3> Conclusions</h3> <p><i>Cs</i>CA inhibits the formation and function of osteoclasts by suppressing the expression of key genes involved in osteoclast differentiation through the inhibition of the NF-κB and MAPK signaling pathways. This study elucidates the mechanism by which <i>Cs</i>CA regulates osteoclasts and suggests its translational potential in preventing and treating hyper-resorptive bone diseases such as osteoporosis and bone metastasis.</p> </section>
{"title":"Clonorchis sinensis Crude Antigen Suppresses Osteoclast Differentiation via Modulation of the NF-κB and MAPK Signaling Pathway","authors":"Lili Tang, Shanshan He, Buguo Ma, Zeli Tang, Tingzheng Zhan, Suyu Xiao, Jilong Wang, Jinmin Zhao, Jiake Xu, Yunliang Shi","doi":"10.1002/iid3.70292","DOIUrl":"https://doi.org/10.1002/iid3.70292","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>Clonorchis sinensis</i> crude antigen (<i>Cs</i>CA) is recognized for its immunomodulatory capacity in host-pathogen interactions and immune-related pathologies, its direct impact on bone remodeling cells remains underexplored. Although prior studies demonstrate <i>Cs</i>CA-mediated suppression of inflammatory bone formation in ankylosing spondylitis, the specific regulatory effects on osteoclastogenesis and associated molecular mechanisms remain elusive. This study aimed to investigate the impact of <i>Cs</i>CA on osteoclast differentiation and its potential molecular mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The cytotoxicity of <i>Cs</i>CA on mouse bone marrow–derived macrophages (BMMs) was evaluated using the CCK-8 assay. At the established non-cytotoxic dose, the effects of <i>Cs</i>CA on osteoclast morphology and activity were observed via TRAcP staining and F-actin ring formation assay. Expression of osteoclast differentiation-related genes and proteins was analyzed by combined RT-qPCR and Western Blot. RNA-seq was performed to identify <i>Cs</i>CA-regulated signaling pathways during osteoclast differentiation, followed by validation of key pathway components through Western Blot and immunofluorescence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>Cs</i>CA exhibited no significant cytotoxicity on BMMs at concentrations ≤ 40 μg/mL. TRAcP staining revealed a significant reduction in osteoclast numbers in <i>Cs</i>CA-treated groups. F-actin ring formation assays demonstrated abnormal cytoskeletal structures. RT-PCR results showed significantly downregulated expression of osteoclast differentiation-related genes, including <i>NFATc1</i>, <i>c-Fos</i>, <i>Acp5</i>, <i>CTSK</i> and <i>MMP-9</i>. Western Blot confirmed reduced protein expression levels of NFATc1 and c-Fos. RNA-seq analysis combined with experimental validation by Western Blot and immunofluorescence confirmed that <i>Cs</i>CA primarily inhibits osteoclast differentiation through the NF-κB and MAPK signaling pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p><i>Cs</i>CA inhibits the formation and function of osteoclasts by suppressing the expression of key genes involved in osteoclast differentiation through the inhibition of the NF-κB and MAPK signaling pathways. This study elucidates the mechanism by which <i>Cs</i>CA regulates osteoclasts and suggests its translational potential in preventing and treating hyper-resorptive bone diseases such as osteoporosis and bone metastasis.</p>\u0000 </section>\u0000 ","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70292","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145442994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jinyu Qu, Yingchun Peng, Xuefang Shen, Jin Xiong, Huan Wang, Xiang Xiao, Yili Wang
Objective
To investigate the underlying mechanisms through which electroacupuncture (EA) at the Guanyuan (CV4) acupoint inhibits sympathetic activity and neurogenic inflammatory responses to relieve pain in rats with pelvic inflammatory disease (PID).
Methods
Escherichia coli and Staphylococcus aureus were used to establish a PID rat model. EA was evaluated at frequencies of 2, 100, and 2/100 Hz, and 2/100 Hz was selected for subsequent investigation. The rats were randomly divided into the control, model, EA-guanyuan (2/100 Hz), and EA-nonsensitized groups (n = 6). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were assessed using von Frey filaments. Hematoxylin and eosin staining was performed to evaluate the histopathology. The tyrosine hydroxylase (TH) expression was analyzed using immunofluorescence (IF) staining. The levels of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), transforming growth factor-β1 (TGF-β1), intercellular cell adhesion molecule-1 (ICAM-1), 5-hydroxytryptamine receptor 3 (5-HT3R), substance P (SP), hyaluronic acid (HA), and bradykinin (BK) were measured using an enzyme-linked immunosorbent assay (ELISA). Western blot analysis was performed to measure the expression of 5-HT3R, calcitonin gene-related peptide (CGRP), HA, Kininogen 1 (KNG1), prostaglandin I2 (PGI2), and trefoil factor 2 (TFF2). Transmission electron microscopy (TEM) was used to observe synaptic connections.
Results
EA at CV4 reduced the behavioral pain score (p < 0.05), increased MWT and TWL, and alleviated uterine tissue pathological damage in rats. EA at CV4 reduced the levels of 5-HT3R, CGRP, BK, HA, KNG1, PGI2SP, TGF-β1, ICAM-1, and TNF-α, and increased IL-2 levels (p < 0.05). Furthermore, EA at CV4 inhibited sympathetic activity by decreasing TH expression (p < 0.05). Additionally, EA at CV4 restored the synaptic connections between the pelvic nerves of the dorsal commissural neuron (DCN).
Conclusion
EA at CV4 alleviated the pathological damage and pain sensitization of uterine tissue in rats with PID by inhibiting sympathetic activity and neurogenic inflammatory response.
{"title":"Electroacupuncture of Guanyuan (CV4) Acupoint Improved Pelvic Inflammatory Disease Pain by Inhibiting Neuroinflammation and Sympathetic Activity","authors":"Jinyu Qu, Yingchun Peng, Xuefang Shen, Jin Xiong, Huan Wang, Xiang Xiao, Yili Wang","doi":"10.1002/iid3.70299","DOIUrl":"https://doi.org/10.1002/iid3.70299","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate the underlying mechanisms through which electroacupuncture (EA) at the Guanyuan (CV4) acupoint inhibits sympathetic activity and neurogenic inflammatory responses to relieve pain in rats with pelvic inflammatory disease (PID).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p><i>Escherichia coli</i> and <i>Staphylococcus aureus</i> were used to establish a PID rat model. EA was evaluated at frequencies of 2, 100, and 2/100 Hz, and 2/100 Hz was selected for subsequent investigation. The rats were randomly divided into the control, model, EA-guanyuan (2/100 Hz), and EA-nonsensitized groups (<i>n</i> = 6). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were assessed using von Frey filaments. Hematoxylin and eosin staining was performed to evaluate the histopathology. The tyrosine hydroxylase (TH) expression was analyzed using immunofluorescence (IF) staining. The levels of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), transforming growth factor-β1 (TGF-β1), intercellular cell adhesion molecule-1 (ICAM-1), 5-hydroxytryptamine receptor 3 (5-HT3R), substance P (SP), hyaluronic acid (HA), and bradykinin (BK) were measured using an enzyme-linked immunosorbent assay (ELISA). Western blot analysis was performed to measure the expression of 5-HT3R, calcitonin gene-related peptide (CGRP), HA, Kininogen 1 (KNG1), prostaglandin I2 (PGI2), and trefoil factor 2 (TFF2). Transmission electron microscopy (TEM) was used to observe synaptic connections.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>EA at CV4 reduced the behavioral pain score (<i>p</i> < 0.05), increased MWT and TWL, and alleviated uterine tissue pathological damage in rats. EA at CV4 reduced the levels of 5-HT3R, CGRP, BK, HA, KNG1, PGI2SP, TGF-β1, ICAM-1, and TNF-α, and increased IL-2 levels (<i>p</i> < 0.05). Furthermore, EA at CV4 inhibited sympathetic activity by decreasing TH expression (<i>p</i> < 0.05). Additionally, EA at CV4 restored the synaptic connections between the pelvic nerves of the dorsal commissural neuron (DCN).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>EA at CV4 alleviated the pathological damage and pain sensitization of uterine tissue in rats with PID by inhibiting sympathetic activity and neurogenic inflammatory response.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70299","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145442992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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