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Long-Term Follow-Up of Patients With Positive Antiphospholipid Antibodies After Fetal Death: Five Typical Cases From a Prospective Cohort Study
IF 3.1 4区 医学
Immunity, Inflammation and Disease Pub Date : 2025-02-13 DOI: 10.1002/iid3.70158
Anxia Xie, Zhanmei Liu, Shenglan Wang, Mingqian Yuan, Ling Xie, Shengdong Liu, Xiaoxing Wei
{"title":"Long-Term Follow-Up of Patients With Positive Antiphospholipid Antibodies After Fetal Death: Five Typical Cases From a Prospective Cohort Study","authors":"Anxia Xie,&nbsp;Zhanmei Liu,&nbsp;Shenglan Wang,&nbsp;Mingqian Yuan,&nbsp;Ling Xie,&nbsp;Shengdong Liu,&nbsp;Xiaoxing Wei","doi":"10.1002/iid3.70158","DOIUrl":"https://doi.org/10.1002/iid3.70158","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Testing of antiphospholipid antibodies (aPLs) has attracted increasing attention for its association with thrombosis and pregnancy loss. However, few studies reported long-term monitoring outcomes of patients who experienced pregnancy loss and exhibited positivity for aPLs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We investigated the causes of fetal death in five cases with positive aPLs and traced the patients for changes in aPLs, subsequent pregnancy outcomes, and thrombotic events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a report of five typical cases from a prospective cohort study on the diagnosis of antiphospholipid syndrome (APS) in patients who were hospitalized for fetal death in Xining, China. Long-term follow-up was conducted and repeat aPL testing was recommended when the patients were confirmed or suspect APS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All five patients had subsequent pregnancies that resulted in term livebirths. None of the patients experienced thrombotic events. One showed progression of aPL serostatus from alone IgM of aβ2GP-1 to both IgM and IgG of aβ2GP-1, two exhibited fluctuation of aPL serostatus, and one had negative conversion, and the other one had not retested aPLs and did not receive any intervention with uneventful subsequent pregnancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The aPLs of a patient with APS may develop or may disappear, so long-term monitoring cannot be discounted. Also, a woman who has experienced fetal death and exhibits positivity for aPLs may not necessarily be a patient with APS, as there are a variety of conditions in which aPLs appear.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396888","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}
引用次数: 0
Single-Cell Analysis of Endothelial Cell Injury in IgA Nephropathy IgA 肾病内皮细胞损伤的单细胞分析
IF 3.1 4区 医学
Immunity, Inflammation and Disease Pub Date : 2025-02-13 DOI: 10.1002/iid3.70149
Yong-Chang Yang, Lin Zhu, Jing-Ying Zhao, Bo Zhang, Xiao-Meng Wang, Wai W. Cheung, Cheng-Guang Zhao, Ping Zhou
{"title":"Single-Cell Analysis of Endothelial Cell Injury in IgA Nephropathy","authors":"Yong-Chang Yang,&nbsp;Lin Zhu,&nbsp;Jing-Ying Zhao,&nbsp;Bo Zhang,&nbsp;Xiao-Meng Wang,&nbsp;Wai W. Cheung,&nbsp;Cheng-Guang Zhao,&nbsp;Ping Zhou","doi":"10.1002/iid3.70149","DOIUrl":"https://doi.org/10.1002/iid3.70149","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The precise mechanisms responsible for renal injury in IgA nephropathy (IgAN) are not fully understood. Our study employed an extensive scRNA-seq analysis of kidney biopsies obtained from individuals with IgAN, with a specific emphasis on investigating the involvement of renal endothelial cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We obtained data from the Gene Expression Omnibus database and conducted bioinformatics analysis, which included enrichment analysis of differentially expressed genes, AUCell analysis, and high-dimensional weighted gene co-expression network analysis (hdWGCNA). The results of these analyses were further validated using human renal glomerular endothelial cells (HRGECs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The ScRNA-seq data uncovered notable variations in gene expression between IgAN and control kidney tissues. The enrichment analysis using AUCell demonstrated a high presence of adhesion molecules and components related to the mitogen-activated protein kinase signaling pathway within the renal endothelial cells. Furthermore, through hdWGCNA analysis, it was discovered that interleukin (IL)-6, Rac1, and cadherin exhibited associations with the renal endothelial cells. Stimulation of HRGECs with IL-6/IL-6 receptor resulted in a significant reduction in VE-cad expression while inhibiting Rac1 led to a substantial decrease in Rac1-GTP levels and an increase in VE-cad expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study presents novel findings regarding the contribution of renal endothelial cells to the development of IgAN, as it demonstrates that IL-6 negatively regulates VE-cad expression in HRGECs via Rac1. These results highlight the significant involvement of renal endothelial cells in the pathogenesis of IgAN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396887","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}
引用次数: 0
Porphyromonas gingivalis and Its Outer Membrane Vesicles Induce Neuroinflammation in Mice Through Distinct Mechanisms
IF 3.1 4区 医学
Immunity, Inflammation and Disease Pub Date : 2025-02-11 DOI: 10.1002/iid3.70135
Yu Qiu, Yueyang Zhao, Guiqiong He, Deqin Yang
{"title":"Porphyromonas gingivalis and Its Outer Membrane Vesicles Induce Neuroinflammation in Mice Through Distinct Mechanisms","authors":"Yu Qiu,&nbsp;Yueyang Zhao,&nbsp;Guiqiong He,&nbsp;Deqin Yang","doi":"10.1002/iid3.70135","DOIUrl":"https://doi.org/10.1002/iid3.70135","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is the most common chronic neurodegenerative disorder, with neuroinflammation playing an important role in its progression to become a major research focus. The role of <i>Porphyromonas gingivalis</i> (<i>Pg</i>) and its outer membrane vesicles (<i>Pg</i> OMVs) in AD development is uncertain, particularly regarding their effects on neuroinflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The cognition of mice injected with <i>Pg</i>, <i>Pg</i> OMVs, or PBS via the tail vein was assessed by the Morris water maze test. Pathological changes in the mouse brain were analyzed via immunohistochemistry, immunofluorescence and hematoxylin‒eosin (H&amp;E) staining, and the ultrastructure of the hippocampus was observed via transmission electron microscopy (TEM). Plasma levels of inflammatory factors were assessed by enzyme-linked immunosorbent assay (ELISA). Protein levels of brain inflammatory factor, occludin, and NLRP3 inflammasome-related proteins were assessed by western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Memory impairment; notable neuroinflammation, including astrocyte and microglial activation; and elevated protein levels of IL-1β, TNF-α, and IL-6 in the hippocampus were detected in the <i>Pg</i> and <i>Pg</i> OMV groups. However, <i>Pg</i> induced weight loss and systemic inflammation, such as splenomegaly and increased IL-1β and TNF-α levels in plasma, whereas <i>Pg</i> OMVs had minimal impact. In addition, <i>Pg</i> induced more pronounced activation of the NLRP3 inflammasome compared to <i>Pg</i> OMVs. In contrast, only the <i>Pg</i> OMV group exhibited blood−brain barrier (BBB) disruption characterized by reduced integrity of tight junctions and lower levels of occludin protein.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p><i>Pg</i> is associated with a significant immune response and systemic inflammation, which in turn exacerbates neuroinflammation via activating NLRP3 inflammasome. However, <i>Pg</i> OMVs might elude the systemic immune response and disrupt tight junctions, thereby entering the brain and directly triggering neuroinflammation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380622","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}
引用次数: 0
Omalizumab Treated Urticaria Patients Display T Cell and Thrombocyte-Associated Gene Regulation
IF 3.1 4区 医学
Immunity, Inflammation and Disease Pub Date : 2025-02-11 DOI: 10.1002/iid3.70132
Anna Smola, Heike C. Hawerkamp, Péter Oláh, Andreas Kislat, Nicole Duschner, Bernhard Homey, Stephan Meller
{"title":"Omalizumab Treated Urticaria Patients Display T Cell and Thrombocyte-Associated Gene Regulation","authors":"Anna Smola,&nbsp;Heike C. Hawerkamp,&nbsp;Péter Oláh,&nbsp;Andreas Kislat,&nbsp;Nicole Duschner,&nbsp;Bernhard Homey,&nbsp;Stephan Meller","doi":"10.1002/iid3.70132","DOIUrl":"https://doi.org/10.1002/iid3.70132","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic spontaneous urticaria (CSU) is a debilitating inflammatory skin disease with a prevalence of approximately 1% of the population. It is characterized by recurrent itchy wheals and/or angioedema for more than 6 weeks without known triggers leading to a high quality of life impairment. The pathogenesis of CSU remains not fully understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to explore the pathomechanism of CSU beyond mast cells and IgE-dependent histamine release and to identify possible biomarkers for the disease and its treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We investigated a patient cohort in the first month of omalizumab treatment regarding the IgE levels and changes in gene and miRNA expression in peripheral blood. The cohort was divided into responders and nonresponders (depending on the score of the urticaria control test) and compared to a group of healthy controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our messenger RNA and microRNA microarray analyses revealed the greatest changes in expression levels on Day 2 after the first omalizumab dose.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We identified several genes and miRNAs of interest, most of which have not been described to be linked to CSU so far, underlining, for example, to T cell involvement or even suggesting platelet involvement.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389247","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}
引用次数: 0
Construction of the Single-Cell Landscape of Hashimoto's Thyroiditis Tissue and Peripheral Blood by Single-Cell RNA Sequencing
IF 3.1 4区 医学
Immunity, Inflammation and Disease Pub Date : 2025-02-11 DOI: 10.1002/iid3.70153
Kaiyu Song, Xiaojie Wang, Wenjie Yao, Yuantao Wang, Qinling Zhang, Yuxiao Tang, Yakui Mou, Xicheng Song, Jin Zhou
{"title":"Construction of the Single-Cell Landscape of Hashimoto's Thyroiditis Tissue and Peripheral Blood by Single-Cell RNA Sequencing","authors":"Kaiyu Song,&nbsp;Xiaojie Wang,&nbsp;Wenjie Yao,&nbsp;Yuantao Wang,&nbsp;Qinling Zhang,&nbsp;Yuxiao Tang,&nbsp;Yakui Mou,&nbsp;Xicheng Song,&nbsp;Jin Zhou","doi":"10.1002/iid3.70153","DOIUrl":"https://doi.org/10.1002/iid3.70153","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease, and its etiology may be related to genetic, environmental, and epigenetic factors. However, its exact pathogenesis remains elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, single-cell transcriptomic sequencing and bioinformatics analysis were performed on the thyroid tissues of six HT patients, peripheral blood mononuclear cells (PBMCs) of four HT patients, and normal thyroid tissue of one healthy control. A panoramic single-cell atlas of HT was constructed to explore changes in the abundance of different cell subsets in the states of the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A single-cell atlas of HT was constructed, and eight cell types were defined based on the marker genes. Subsequent clustering analysis of T cells, B cells, myeloid, and thyroid follicular cells revealed that the abundance rates of the CD8<sup>+</sup>T_CCL4L2, B_MEF2B_BCL6, Mac_APOE, Mac_IL1B, and TFC_PAX8_NKX2-1 subgroups were elevated in thyroid tissues of HT patients. However, the abundance rate of the NKT_KLRD1_KLRC2 subgroup was risen in the PBMCs of HT patients. Ig-producing plasma cells were specifically enriched in the B-cell subgroup.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The present study further validated the role of immune cells in the pathogenesis of HT at the cellular level. In addition, a new cell subset B_MEF2B_BCL6 was found. It could be speculated that MEF2B mainly transactivates the expression level of the transcriptional repressor BCL6, leading to the development of HT. A new cell subset TFC_PAX8_NKX2-1 was also identified, in which the specific transcription factors PAX8 and NKX2-1 were highly expressed in HT tissues.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380621","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}
引用次数: 0
Clinical and Laboratory Risk Factors of Early Poor Outcome in Patients With Childhood-Onset Lupus Nephritis—A Single-Center Retrospective Study
IF 3.1 4区 医学
Immunity, Inflammation and Disease Pub Date : 2025-02-11 DOI: 10.1002/iid3.70146
Wei Qijiao, Huang Fujia, Yang Bing, Wang Changyan, Zhong Linqing, Dong Yanqing, Wang Wei, Song Hongmei
{"title":"Clinical and Laboratory Risk Factors of Early Poor Outcome in Patients With Childhood-Onset Lupus Nephritis—A Single-Center Retrospective Study","authors":"Wei Qijiao,&nbsp;Huang Fujia,&nbsp;Yang Bing,&nbsp;Wang Changyan,&nbsp;Zhong Linqing,&nbsp;Dong Yanqing,&nbsp;Wang Wei,&nbsp;Song Hongmei","doi":"10.1002/iid3.70146","DOIUrl":"https://doi.org/10.1002/iid3.70146","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;&lt;i&gt;Childhood-onset&lt;/i&gt; lupus nephritis (LN) tends to be more severe than in adults. A significant correlation between remission at 3 months of induction therapy and remission after 3 years was found in adults. While few studies on the risk factors of poor early prognosis in children with LN were made. Thus, this study investigated the risk factors of early poor response to help doctors develop effective treatment strategies.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A total of 99 LN children at Peking Union Medical College Hospital from January 2012 to January 2018 were evaluated and clinical data were retrospectively collected. In the study, a complete remission (CR) was defined as laboratory test results were completely normal, including blood routine, renal function, albumin, complement, and erythrocyte sedimentation rate, and the 24-h urinary total protein (24 h UTP) was less than 150 mg. After 3 months of treatment, 15 children achieved CR, and they were in good prognosis group (&lt;i&gt;n&lt;/i&gt; = 15). While 84 did not achieve CR, and they were in poor prognosis group (&lt;i&gt;n&lt;/i&gt; = 84). We compared the differences of clinical and laboratory indicators between the two groups.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;According to inclusion and exclusion criteria, 99 of 116 children with LN were included in this study. And 15 LN children were in good prognosis group. While 84 patients were in poor prognosis group. The incidence of rash (32.1% vs. 6.7%, &lt;i&gt;p&lt;/i&gt; = 0.036) and oral ulcer (81.0% vs. 53.3%, &lt;i&gt;p&lt;/i&gt; = 0.027) in poor prognosis group is higher than that in the good prognosis group. The 24 h UTP (g) [2.46 (1.41, 4.86) vs. 0.56 (0.30, 0.66), &lt;i&gt;p&lt;/i&gt; &lt; 0.001] and the serum creatinine (umol/L) [53.0 (40.3, 65.0) vs. 39.0 (29.8, 51.5), &lt;i&gt;p&lt;/i&gt; = 0.017] were higher in poor prognosis group. The albumin (g/L) (28.7 ± 8.1 vs. 34.5 ± 5.3, &lt;i&gt;p&lt;/i&gt; = 0.003) is lower in poor prognosis group. Logistic regression analysis showed that rash (&lt;i&gt;p&lt;/i&gt; = 0.036), oral ulcer (&lt;i&gt;p&lt;/i&gt; = 0.027), high 24 h UTP (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), high creatinine (&lt;i&gt;p&lt;/i&gt; = 0.017), and low serum albumin (&lt;i&gt;p&lt;/i&gt; = 0.003) were significantly associated with poor early prognosis in childhood-onset LN.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The occurrence of rash cannot be ignored, especially for children with oral ulcers, a comprehensive evaluation of each system should be carried out, so as not to cause inactive treatment and affect the prognosis. High 24 h UTP have a positive predictive value for the early poor outcome ","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389246","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}
引用次数: 0
Jian Pi Hua Tan Fang Reverses Trastuzumab Resistance of HER2-Positive Gastric Cancer Through PI3K/AKT/mTOR Pathway: Integrating Network Pharmacology, Molecular Docking and Experimental Validation
IF 3.1 4区 医学
Immunity, Inflammation and Disease Pub Date : 2025-02-07 DOI: 10.1002/iid3.70154
Jia Hu, Wenjing Bu, Yongfang Ding, Xin Li, Bo Zhang, Bo Shen, Cong Wu, Youqi Xu, Xiaoyang Zhang
{"title":"Jian Pi Hua Tan Fang Reverses Trastuzumab Resistance of HER2-Positive Gastric Cancer Through PI3K/AKT/mTOR Pathway: Integrating Network Pharmacology, Molecular Docking and Experimental Validation","authors":"Jia Hu,&nbsp;Wenjing Bu,&nbsp;Yongfang Ding,&nbsp;Xin Li,&nbsp;Bo Zhang,&nbsp;Bo Shen,&nbsp;Cong Wu,&nbsp;Youqi Xu,&nbsp;Xiaoyang Zhang","doi":"10.1002/iid3.70154","DOIUrl":"https://doi.org/10.1002/iid3.70154","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Currently, trastuzumab resistance significantly impacts the treatment outcome for individuals with HER2-positive gastric cancer. In clinical practice, Jian Pi Hua Tan Fang (JPHTF) has been shown to be effective in preventing recurrences and metastases caused by gastric cancer. Yet, the treatment process remains unknown. We aim to evaluate the potential pharmacological mechanism of JPHTF in interfering with resistance to trastuzumab in HER2-positive gastric cancer (GC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, network pharmacology and molecular docking techniques were used to forecast the potential active ingredients, pathways, and targets of JPHTF in overcoming trastuzumab resistance in HER2-positive GC. Then, in vitro models of NCI-N87/TR was developed, and JPHTF-containing serum was utilized for intervention to confirm these crucial targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Network pharmacology showed that 92 potential active compounds and 420 therapeutic targets of JPHTF. SRC, EGFR, TP53, and AKT1 were identified as the main targets associated with the PI3K/Akt, MAPK, and Ras pathways, playing crucial roles in angiogenesis, cell apoptosis, cell proliferation, and resistance to chemotherapy in the GC microenvironment. Molecular docking analysis showed that quercetin, formononetin, and luteolin, which are the main active ingredients, exhibit high binding affinity to the central targets PI3K, AKT, and mTOR. In vitro experiment, the JPHTF-containing serum has a significant alleviating effect on reversing trastuzumab resistance and cell apoptotic and proliferation of NCI-N87/TR. Further molecular biological experiments showed that JPHTF could regulate the expression of PI3K/AKT/mTOR pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>JPHTF has the ability to overcome trastuzumab resistance in NCI-N87 cells through the regulation of the PI3K/AKT/mTOR pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362622","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}
引用次数: 0
Role of miRNAs in Apoptosis Pathways of Immune Cells in Systemic Lupus Erythematosus
IF 3.1 4区 医学
Immunity, Inflammation and Disease Pub Date : 2025-02-06 DOI: 10.1002/iid3.70124
Amin Azizan, Elham Farhadi, Seyedeh Tahereh Faezi, Ahmadreza Jamshidi, Majid Alikhani, Mahdi Mahmoudi
{"title":"Role of miRNAs in Apoptosis Pathways of Immune Cells in Systemic Lupus Erythematosus","authors":"Amin Azizan,&nbsp;Elham Farhadi,&nbsp;Seyedeh Tahereh Faezi,&nbsp;Ahmadreza Jamshidi,&nbsp;Majid Alikhani,&nbsp;Mahdi Mahmoudi","doi":"10.1002/iid3.70124","DOIUrl":"https://doi.org/10.1002/iid3.70124","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by dysregulated immune responses and multi-organ involvement. Dysregulation of apoptosis, a key process for maintaining immune homeostasis, plays a critical role in the pathogenesis of SLE. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, have emerged as important modulators of apoptosis in immune cells, influencing the balance between immune tolerance and autoimmunity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This review aims to comprehensively summarize recent advancements in understanding the roles of miRNAs in apoptosis regulation within immune cells in SLE, highlighting their therapeutic potential for restoring immune balance and mitigating disease progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Aberrant expression of specific miRNAs contributes to the dysregulation of apoptosis in SLE immune cells. Pro-apoptotic miRNAs, such as miR-125b and miR-150, are often downregulated, leading to enhanced survival of autoreactive immune cells. Conversely, anti-apoptotic miRNAs, including miR-21, are upregulated, further disrupting the delicate balance of immune cell apoptosis. Dual-function miRNAs, such as miR-155, exhibit context-dependent roles based on cellular environments and target gene interactions. This dysregulation promotes the persistence of autoreactive immune cells and the development of autoimmunity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>miRNAs play critical roles in modulating apoptosis pathways, making them promising therapeutic targets for SLE. Restoring the balance of pro-apoptotic and anti-apoptotic miRNAs could help reinstate immune tolerance and reduce tissue damage. Future research should focus on elucidating miRNA targetomes, improving delivery systems, and addressing off-target effects to fully harness their therapeutic potential.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248687","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}
引用次数: 0
Diagnostic and Prognostic Value of Serum Golgi Protein 73 in Patients With Hepatitis B Virus-Associated Acute-on-Chronic Liver Failure
IF 3.1 4区 医学
Immunity, Inflammation and Disease Pub Date : 2025-02-06 DOI: 10.1002/iid3.70120
Zheng-ju Xu, Tao Xu, Qiao-xia Ye, Yong-fei Li, Tian-huang Yang, Xiao-man Zhang, Hui Lin, Hui-guo Liu, Zhi-jie Huang, Jian-kun Shen
{"title":"Diagnostic and Prognostic Value of Serum Golgi Protein 73 in Patients With Hepatitis B Virus-Associated Acute-on-Chronic Liver Failure","authors":"Zheng-ju Xu,&nbsp;Tao Xu,&nbsp;Qiao-xia Ye,&nbsp;Yong-fei Li,&nbsp;Tian-huang Yang,&nbsp;Xiao-man Zhang,&nbsp;Hui Lin,&nbsp;Hui-guo Liu,&nbsp;Zhi-jie Huang,&nbsp;Jian-kun Shen","doi":"10.1002/iid3.70120","DOIUrl":"https://doi.org/10.1002/iid3.70120","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The prognosis and severity of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) cannot be well-identified by serum biomarkers. The present study aims to determine the role of serum Golgi protein 73 (GP73) in predicting the prognosis and severity of liver necrotizing inflammation induced by HBV-ACLF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 427 chronic HBV-infected patients were included for the present study. Among these patients, 179 patients had chronic hepatitis B (CHB), 96 patients had HBV-related liver cirrhosis (LC), and 152 patients had HBV-ACLF. The baseline and dynamic changes in serum GP73 levels were measured and compared in CHB, LC and HBV-ACLF patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The serum GP73 levels were significantly greater in HBV-ACLF patients when compared to CHB and LC patients. Furthermore, serum GP73 demonstrated excellent performance in distinguishing HBV-ACLF from CHB and LC, with an area under the curve of 0.969 and 0.824, respectively. In the logistic regression analysis, a high GP73 level was identified as an independent risk factor associated with death within 3 months, and the optimal cut-off level was 274.59 ng/mL. The serum GP73 levels significantly decreased and remained stable at approximately 6 months for survivors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Serum GP73 may serve as a valuable biomarker for the diagnosis and prognosis prediction of HBV-ACLF patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248790","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}
引用次数: 0
Integrated Metabolomics and Proteomics Analysis of the Myocardium in a Mouse Model of Acute Viral Myocarditis
IF 3.1 4区 医学
Immunity, Inflammation and Disease Pub Date : 2025-02-06 DOI: 10.1002/iid3.70151
Yimin Xue, Jiuyun Zhang, Mingguang Chen, Qiaolian Fan, Tingfeng Huang, Jun Ke, Feng Chen
{"title":"Integrated Metabolomics and Proteomics Analysis of the Myocardium in a Mouse Model of Acute Viral Myocarditis","authors":"Yimin Xue,&nbsp;Jiuyun Zhang,&nbsp;Mingguang Chen,&nbsp;Qiaolian Fan,&nbsp;Tingfeng Huang,&nbsp;Jun Ke,&nbsp;Feng Chen","doi":"10.1002/iid3.70151","DOIUrl":"https://doi.org/10.1002/iid3.70151","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Acute viral myocarditis (AVMC) is a common inflammatory disease affecting the myocardium and is often accompanied by severe metabolic disturbances. The molecular mechanisms underlying this disease are complex and not yet fully understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Coxsackievirus B3 (CVB3)-induced AVMC mouse models were established. By integrating ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)-based metabolomics and data-independent acquisition (DIA)-based proteomics, we aimed to investigate the global influence of CVB3 infection on the myocardial metabolome and proteome in mice. Based on the criterion of OPLS-DA VIP &gt; 1.0 and <i>p</i> value &lt; 0.05, a total of 149 differential metabolites (DMs) were identified, including 64 upregulated and 85 downregulated metabolites. Bioinformatics analysis revealed that these DMs were mostly enriched in Global and overview maps (Metabolic pathways), Energy metabolism (Sulfur metabolism and Nitrogen metabolism), Amino acid metabolism (Taurine and hypotaurine metabolism, Lysine degradation, and Arginine and proline metabolism), and Carbohydrate metabolism (Propanoate metabolism). Differential analysis also identified 1385 differential proteins (DPs) between the two groups (|Fold Change| &gt;1.5 and <i>p</i> value &lt; 0.05), including 1092 upregulated and 293 downregulated proteins. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DPs indicated that metabolism-related pathways were significant components of the AVMC process. Next, we mined many DPs engaged in the above metabolic pathways through an integrated analysis of KEGG pathway-based metabolomics and proteomics data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our integrated metabolomics and proteomics analysis revealed characteristic alterations in metabolites and proteins in the myocardium of AVMC, as well as the associations between them. This not only extends the existing understanding of the molecular basis of the pathogenesis and progression of AVMC but also suggests new directions for its treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248789","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}
引用次数: 0
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