Immunity, Inflammation and Disease最新文献_第5页

Neohesperidin Dihydrochalcone Alleviates Lipopolysaccharide-Induced Vascular Endothelium Dysfunction by Regulating Antioxidant Capacity 新橙皮苷二氢查尔酮通过调节抗氧化能力减轻脂多糖诱导的血管内皮功能障碍。

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-19 DOI: 10.1002/iid3.70107

Yuxin Nong, Junquan Lu, Danqing Yu, Xuebiao Wei

Background

Endothelial dysfunction is one of the important mechanisms of organ and tissue damage in sepsis. In this study, we evaluated the effects of neohesperidin dihydrochalone (NHDC) on lipopolysaccharide (LPS)-induced vascular dysfunction and explored the potential mechanisms.

Methods

In vivo, we assessed vascular leakage in mice by injecting Evans blue dye. In vitro, cell counting kit-8 (CCK-8) assay and flow cytometry were used to assess the activity of HUVEC and apoptosis. The effect of LPS on HUVEC barrier was assessed using FITC-extend membrane assay. The adhesion ability of HUVEC was tested by THP-1 cell adhesion assay. The antioxidant capacity of cells was measured by detecting the level of mitochondrial membrane potential, ROS, and content of CAT, SOD, GSH, and MDA within the cells. Furthermore, the release of endothelial IL-1β, IL-6, and TNF-α were detected by ELISA, and the expression level of TAK1, ERK1/2, and NFκB were detected by western blot.

Results

Treatment with NHDC effectively alleviated LPS-induced endothelial permeability and organ damage by reducing reactive oxygen species production and enhancing the antioxidant response. Further investigation suggested that NHDC may exert its protective effects by inhibiting the release of IL-1β, IL-6, and TNF-α, and by decreasing the phosphorylation of key inflammatory signaling molecules, including transforming growth factor-β-activated kinase 1 (TAK1), extracellular signal-regulated kinases 1/2 (ERK1/2), and nuclear factor kappa B (NFκB).

Conclusions

Our study indicate that pretreatment with NHDC may provide protection against LPS-induced vascular dysfunction by reducing oxidative stress and activation of inflammatory signaling pathways.

背景：内皮功能障碍是脓毒症中器官和组织损伤的重要机制之一。在本研究中，我们评估了新橙皮苷二氢氯酮（NHDC）对脂多糖（LPS）诱导的血管功能障碍的影响，并探讨了其可能的机制。方法：采用Evans蓝染色法观察小鼠体内血管渗漏情况。体外采用细胞计数试剂盒-8 （CCK-8）法和流式细胞术检测HUVEC活性和细胞凋亡。采用fitc延伸膜法评价LPS对HUVEC屏障的影响。采用THP-1细胞粘附法检测HUVEC的粘附能力。通过检测细胞内线粒体膜电位、ROS水平及CAT、SOD、GSH、MDA含量，检测细胞抗氧化能力。ELISA法检测内皮细胞IL-1β、IL-6、TNF-α的释放，western blot法检测TAK1、ERK1/2、NFκB的表达水平。结果：NHDC通过减少活性氧的产生和增强抗氧化反应，有效缓解lps诱导的内皮通透性和器官损伤。进一步研究表明，NHDC可能通过抑制IL-1β、IL-6和TNF-α的释放，以及降低转化生长因子β活化激酶1 （TAK1）、细胞外信号调节激酶1/2 （ERK1/2）和核因子κB （NFκB）等关键炎症信号分子的磷酸化来发挥其保护作用。结论：我们的研究表明，NHDC预处理可能通过减少氧化应激和激活炎症信号通路，对lps诱导的血管功能障碍提供保护。

{"title":"Neohesperidin Dihydrochalcone Alleviates Lipopolysaccharide-Induced Vascular Endothelium Dysfunction by Regulating Antioxidant Capacity","authors":"Yuxin Nong, Junquan Lu, Danqing Yu, Xuebiao Wei","doi":"10.1002/iid3.70107","DOIUrl":"10.1002/iid3.70107","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Endothelial dysfunction is one of the important mechanisms of organ and tissue damage in sepsis. In this study, we evaluated the effects of neohesperidin dihydrochalone (NHDC) on lipopolysaccharide (LPS)-induced vascular dysfunction and explored the potential mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In vivo, we assessed vascular leakage in mice by injecting Evans blue dye. In vitro, cell counting kit-8 (CCK-8) assay and flow cytometry were used to assess the activity of HUVEC and apoptosis. The effect of LPS on HUVEC barrier was assessed using FITC-extend membrane assay. The adhesion ability of HUVEC was tested by THP-1 cell adhesion assay. The antioxidant capacity of cells was measured by detecting the level of mitochondrial membrane potential, ROS, and content of CAT, SOD, GSH, and MDA within the cells. Furthermore, the release of endothelial IL-1β, IL-6, and TNF-α were detected by ELISA, and the expression level of TAK1, ERK1/2, and NFκB were detected by western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Treatment with NHDC effectively alleviated LPS-induced endothelial permeability and organ damage by reducing reactive oxygen species production and enhancing the antioxidant response. Further investigation suggested that NHDC may exert its protective effects by inhibiting the release of IL-1β, IL-6, and TNF-α, and by decreasing the phosphorylation of key inflammatory signaling molecules, including transforming growth factor-β-activated kinase 1 (TAK1), extracellular signal-regulated kinases 1/2 (ERK1/2), and nuclear factor kappa B (NFκB).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study indicate that pretreatment with NHDC may provide protection against LPS-induced vascular dysfunction by reducing oxidative stress and activation of inflammatory signaling pathways.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"12 12","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853964","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

Expression of Major Basic Protein and Endothelial Adhesion Molecules in Chronically Inflamed Mucosa of the Ethmoid Labyrinth 筛迷宫慢性炎症黏膜中主要碱性蛋白和内皮粘附分子的表达。

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-19 DOI: 10.1002/iid3.70066

Tijana Vukadinović, Biserka Vukomanović Đurđević, Aleksandar Perić

Background/Objectives

Tissue remodeling, including dense eosinophil infiltration, is essential for forming inflammatory nasal polyps (NPs) and the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). Toxic eosinophil major basic protein (MBP) damages the sinus mucosa epithelium and lamina propria, which initiates reparative processes leading to tissue remodeling. MBP specifically binds to BMK-13 antibodies allowing immunohistochemical (IHC) tissue staining for eosinophils. This study evaluated the association between NP stromal BMK-13 and endothelial adhesion molecule staining, and clinical parameters of NP patients compared to IHC expression and clinical parameters in subjects with healthy nasal mucosa.

Methods

We included 30 patients with bilateral NPs who were selected for endoscopic ethmoidectomy. The control group was of 30 subjects with non-inflamed nasal mucosa but with middle turbinate aeration, chosen for surgery. All participants were clinically scored before surgery, according to quality of life (QoL) outcome and symptoms. The degree of disease extension on computed tomography scans of the paranasal sinuses was also evaluated. Tissue samples after surgery were IHC stained for BMK-13 and endothelial proliferation markers CD31 and CD34.

Results

Expression of BMK-13, CD31, and CD34 in tissues of NPs was higher than in healthy nasal mucosa. Positive correlations were observed between BMK-13 expression, impaired QoL, and radiologically assessed extension of inflammation in NP patients.

Conclusion

Apart from the fact that the NP tissue has, as expected, more intense eosinophilic infiltration, the proliferation of blood vessels is more pronounced in the NP tissue than in the tissue of healthy nasal mucosa. Expression of MBP in the tissue of ethmoidal NPs could serve as a potential marker of the degree of expansion of CRSwNP and indicate the severity of the disease.

Clinical Trial Registration

None, because it was a cross-sectional study.

背景/目的：组织重塑，包括密集的嗜酸性粒细胞浸润，是炎症性鼻息肉（NPs）形成和慢性鼻窦炎伴鼻息肉（CRSwNP）发病的必要条件。毒性嗜酸性粒细胞大碱性蛋白（MBP）损害窦黏膜上皮和固有层，启动修复过程导致组织重塑。MBP特异性结合BMK-13抗体，允许免疫组化（IHC）组织染色嗜酸性粒细胞。本研究比较了NP间质BMK-13与内皮粘附分子染色、NP患者临床参数与健康鼻黏膜IHC表达和临床参数的关系。方法：我们选择30例双侧NPs患者行内镜下筛切除术。对照组为30例鼻黏膜无炎症但经中鼻甲通气的患者，选择手术治疗。所有参与者在手术前根据生活质量（QoL）结果和症状进行临床评分。我们还评估了鼻窦计算机断层扫描的疾病扩展程度。术后组织标本进行免疫组化染色，检测BMK-13和内皮细胞增殖标志物CD31和CD34。结果：NPs组织中BMK-13、CD31和CD34的表达高于正常鼻黏膜组织。在NP患者中，BMK-13表达、生活质量受损和放射学评估的炎症扩展之间存在正相关。结论：除了NP组织如预期的那样有更强烈的嗜酸性粒细胞浸润外，NP组织中血管的增殖比健康鼻黏膜组织更明显。筛状NPs组织中MBP的表达可作为CRSwNP扩增程度的潜在标志，提示疾病的严重程度。临床试验注册：没有，因为这是一项横断面研究。

{"title":"Expression of Major Basic Protein and Endothelial Adhesion Molecules in Chronically Inflamed Mucosa of the Ethmoid Labyrinth","authors":"Tijana Vukadinović, Biserka Vukomanović Đurđević, Aleksandar Perić","doi":"10.1002/iid3.70066","DOIUrl":"10.1002/iid3.70066","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/Objectives</h3>\u0000 \u0000 <p>Tissue remodeling, including dense eosinophil infiltration, is essential for forming inflammatory nasal polyps (NPs) and the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). Toxic eosinophil major basic protein (MBP) damages the sinus mucosa epithelium and <i>lamina propria</i>, which initiates reparative processes leading to tissue remodeling. MBP specifically binds to BMK-13 antibodies allowing immunohistochemical (IHC) tissue staining for eosinophils. This study evaluated the association between NP stromal BMK-13 and endothelial adhesion molecule staining, and clinical parameters of NP patients compared to IHC expression and clinical parameters in subjects with healthy nasal mucosa.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included 30 patients with bilateral NPs who were selected for endoscopic ethmoidectomy. The control group was of 30 subjects with non-inflamed nasal mucosa but with middle turbinate aeration, chosen for surgery. All participants were clinically scored before surgery, according to quality of life (QoL) outcome and symptoms. The degree of disease extension on computed tomography scans of the paranasal sinuses was also evaluated. Tissue samples after surgery were IHC stained for BMK-13 and endothelial proliferation markers CD31 and CD34.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Expression of BMK-13, CD31, and CD34 in tissues of NPs was higher than in healthy nasal mucosa. Positive correlations were observed between BMK-13 expression, impaired QoL, and radiologically assessed extension of inflammation in NP patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Apart from the fact that the NP tissue has, as expected, more intense eosinophilic infiltration, the proliferation of blood vessels is more pronounced in the NP tissue than in the tissue of healthy nasal mucosa. Expression of MBP in the tissue of ethmoidal NPs could serve as a potential marker of the degree of expansion of CRSwNP and indicate the severity of the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Clinical Trial Registration</h3>\u0000 \u0000 <p>None, because it was a cross-sectional study.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"12 12","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853962","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 Efficacy of 11 SARS-CoV-2 Serological Assays for COVID-19: A Meta-Analysis and Adjusted Indirect Comparison of Diagnostic Test Accuracy 11种SARS-CoV-2血清学检测对COVID-19的诊断效果：荟萃分析和诊断检测准确性的调整间接比较

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-19 DOI: 10.1002/iid3.70114

Ying Zhao, Minjie Zhang, Weiwei Liang, Lijiang Fang

<div> <section> <h3> Objective</h3> <p>In the past 5 years, a large number of serological assays for large-scale detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen emerged. Serological assays for SARS-CoV-2 were needed to support clinical diagnosis and epidemiological investigations. However, there were limited data on the diagnostic accuracy of these serological assays. We aimed to compare the diagnostic accuracy of 11 commercial serological assays for coronavirus disease-2019 (COVID-19) by taking the reverse transcriptase polymerase chain reaction (RT-PCR) assays as the reference standard, which served as the control arm to conduct an indirect comparison of diagnostic accuracy for 11 different SARS-CoV-2 serological assays.</p> </section> <section> <h3> Methods</h3> <p>This meta-analysis was conducted following the PRISMA 2020 reporting guideline. Electronic searches were performed using the Cochrane Library, PubMed, Embase, Web of Science, Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI), WANFANG, and Chinese Weipu (VIP) databases. Fifty-seven articles, including 11 serologic-based IgG, IgM, and total antibodies assays for SARS-CoV-2, published before June 2024, were included in this meta-analysis. The main outcome of this meta-analysis used to evaluate the performance of 11 assays included pooled diagnostic odds ratio (DOR), area under the summary receiver operating characteristic (AUC), and summary receiver operating characteristic curve (SROC). The R software was used for adjusted indirect comparison to calculate the relative diagnostic odds ratio (RDOR) with corresponding 95% confidence intervals (CIs), and indirect comparison forest plots showed the results.</p> </section> <section> <h3> Results</h3> <p>A total of 57 articles met the eligibility criteria for inclusion in our meta-analysis. The pooled DOR and the AUC for access SARS-CoV-2 IgG were 564.28 (95% CI 229.58−1386.91) and 1.00, and as for EDI novel coronavirus COVID-19 IgG those were 85.27 (95% CI 53.99−134.68) and 0.95, for EDI novel coronavirus COVID-19 IgM were 49.42 (95% CI 16.47−148.30) and 0.86, for iFlash-SARS-CoV-2 IgG were 652.31 (95% CI 362.32−1174.41) and 0.97, for iFlash-SARS-CoV-2 IgM were 36.72 (95% CI 12.42−108.54) and 0.76, for MAGLUMI 2019-nCoV IgG were 145.44 (95% CI 59.37−356.30) and 0.90, for MAGLUMI 2019-nCoV IgM were 21.59 (95% CI 14.27−32.67) and 0.59, for ortho-clinical anti-SARS-CoV-2 IgG were 719.46 (95% CI 262.34−1973.13) and 1.00, for ortho-clinical anti-SARS-CoV-2 total were 1104.60 (95% CI 395.64−3083.99) and 1.00, for Siemens SARS-CoV-2 total (COV2T) were 1143.

目的：近5年来，出现了大量大规模检测SARS-CoV-2抗原抗体的血清学检测方法。需要对SARS-CoV-2进行血清学检测，以支持临床诊断和流行病学调查。然而，这些血清学分析的诊断准确性数据有限。我们以逆转录酶聚合酶链反应（RT-PCR）检测为参比标准，以RT-PCR为对照，对11种不同的SARS-CoV-2血清学检测方法的诊断准确性进行间接比较，比较11种商业化血清学检测方法对2019冠状病毒病（COVID-19）的诊断准确性。方法：本荟萃分析遵循PRISMA 2020报告指南进行。电子检索使用Cochrane Library、PubMed、Embase、Web of Science、中国生物医药数据库（CBM）、中国知网（CNKI）、万方和中国卫普数据库（VIP）。这项荟萃分析纳入了在2024年6月之前发表的57篇文章，包括11篇基于血清学的SARS-CoV-2 IgG、IgM和总抗体测定。该荟萃分析的主要结果用于评估11项试验的性能，包括合并诊断优势比（DOR）、总体受试者工作特征下面积（AUC）和总体受试者工作特征曲线（SROC）。采用R软件进行校正间接比较，计算相对诊断优势比（RDOR）和相应的95%置信区间（ci），间接比较森林图显示结果。结果：共有57篇文章符合纳入meta分析的资格标准。汇集金龟子和AUC访问SARS-CoV-2免疫球蛋白是564.28 (95% CI 229.58 - -1386.91)和1.00,至于EDI小说冠状病毒COVID-19免疫球蛋白这是85.27 (95% CI 53.99 - -134.68)和0.95,对EDI小说冠状病毒COVID-19 IgM分别为49.42 (95% CI 16.47 - -148.30)和0.86,为iFlash-SARS-CoV-2免疫球蛋白是652.31 (95% CI 362.32 - -1174.41)和0.97,为iFlash-SARS-CoV-2 IgM分别为36.72 (95% CI 12.42 - -108.54)和0.76,MAGLUMI 2019 - ncov免疫球蛋白是145.44 (95% CI 59.37 - -356.30)和0.90,MAGLUMI 2019-nCoV IgM分别为21.59 （95% CI 14.27 ~ 32.67）和0.59，抗SARS-CoV-2 IgG分别为719.46 （95% CI 262.34 ~ 1973.13）和1.00，抗SARS-CoV-2 IgG总抗体分别为1104.60 （95% CI 395.64 ~ 3083.99）和1.00，西门子SARS-CoV-2总抗体（COV2T）分别为1143.37 （95% CI 316.49 ~ 4130.62）和0.99，万泰SARS-CoV-2总抗体分别为1014.98 （95% CI 618.48 ~ 1665.66）和1.00。基于检测的IgG （n = 43）、基于检测的总抗体（n = 35）和基于检测的IgM （n = 20）的合并DOR分别为242.88 （95% CI 157.66-374.16）、1215.90 （95% CI 547.14-2702.07）和40.99 （95% CI 22.63-74.25）。总抗体检测的诊断准确率优于IgG和IgM检测；IgG检测法优于IgM检测法。结论：本研究提示Siemens SARS-CoV-2 total （COV2T）、orthoclinical anti- cov -2 total和Wantai SARS-CoV-2 total具有最佳的综合诊断准确性。基于elisa的总抗体诊断COVID-19的准确率高于基于elisa的IgG和基于elisa的IgM。

{"title":"Diagnostic Efficacy of 11 SARS-CoV-2 Serological Assays for COVID-19: A Meta-Analysis and Adjusted Indirect Comparison of Diagnostic Test Accuracy","authors":"Ying Zhao, Minjie Zhang, Weiwei Liang, Lijiang Fang","doi":"10.1002/iid3.70114","DOIUrl":"10.1002/iid3.70114","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In the past 5 years, a large number of serological assays for large-scale detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen emerged. Serological assays for SARS-CoV-2 were needed to support clinical diagnosis and epidemiological investigations. However, there were limited data on the diagnostic accuracy of these serological assays. We aimed to compare the diagnostic accuracy of 11 commercial serological assays for coronavirus disease-2019 (COVID-19) by taking the reverse transcriptase polymerase chain reaction (RT-PCR) assays as the reference standard, which served as the control arm to conduct an indirect comparison of diagnostic accuracy for 11 different SARS-CoV-2 serological assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This meta-analysis was conducted following the PRISMA 2020 reporting guideline. Electronic searches were performed using the Cochrane Library, PubMed, Embase, Web of Science, Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI), WANFANG, and Chinese Weipu (VIP) databases. Fifty-seven articles, including 11 serologic-based IgG, IgM, and total antibodies assays for SARS-CoV-2, published before June 2024, were included in this meta-analysis. The main outcome of this meta-analysis used to evaluate the performance of 11 assays included pooled diagnostic odds ratio (DOR), area under the summary receiver operating characteristic (AUC), and summary receiver operating characteristic curve (SROC). The R software was used for adjusted indirect comparison to calculate the relative diagnostic odds ratio (RDOR) with corresponding 95% confidence intervals (CIs), and indirect comparison forest plots showed the results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 57 articles met the eligibility criteria for inclusion in our meta-analysis. The pooled DOR and the AUC for access SARS-CoV-2 IgG were 564.28 (95% CI 229.58−1386.91) and 1.00, and as for EDI novel coronavirus COVID-19 IgG those were 85.27 (95% CI 53.99−134.68) and 0.95, for EDI novel coronavirus COVID-19 IgM were 49.42 (95% CI 16.47−148.30) and 0.86, for iFlash-SARS-CoV-2 IgG were 652.31 (95% CI 362.32−1174.41) and 0.97, for iFlash-SARS-CoV-2 IgM were 36.72 (95% CI 12.42−108.54) and 0.76, for MAGLUMI 2019-nCoV IgG were 145.44 (95% CI 59.37−356.30) and 0.90, for MAGLUMI 2019-nCoV IgM were 21.59 (95% CI 14.27−32.67) and 0.59, for ortho-clinical anti-SARS-CoV-2 IgG were 719.46 (95% CI 262.34−1973.13) and 1.00, for ortho-clinical anti-SARS-CoV-2 total were 1104.60 (95% CI 395.64−3083.99) and 1.00, for Siemens SARS-CoV-2 total (COV2T) were 1143.","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"12 12","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853885","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 Trial With a Depigmented, Polymerized Mite Mixture Extract at Maximum Concentrations 临床试验与脱色，聚合螨虫混合物提取物在最大浓度。

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-19 DOI: 10.1002/iid3.70090

Carmen Vidal, Laura Romero, Sara Lopez-Freire, Francisco Carballada-Gonzalez, José Carlos Garcia-Robaina, Teresa Gonzalez-Fernandez, Paula Mendez-Brea, Eva Nieto, Mónica Ruiz-Garcia

Background

Efficacy of allergen immunotherapy is dose-dependent; however, high doses of allergen may imply a greater risk of adverse reactions.

Objective

To assess the safety and tolerability of subcutaneous immunotherapy (SCIT) with mixtures of mite allergen extracts, Dermatophagoides pteronyssinus/Blomia tropicalis (Dpt/Bt) and Dermatophagoides pteronyssinus/Lepidoglyphus destructor (Dpt/Ld) at maximum concentrations, in adult patients with allergic rhinitis or rhinoconjunctivitis, and controlled allergic asthma due to a clinically relevant sensitisation to these mites.

Methods

An open-label, noncontrolled, nonrandomised, phase IIb clinical trial was carried out in three hospitals in Spain between September 2014 and May 2018. Patients received SCIT of either Dpt/Bt (100/1000 DPP/mL) or Dpt/Ld (100/100 DPP/mL) in two phases: a rush build-up phase on the first day (0.2 mL and 0.3 mL with a 30-min interval) and a monthly maintenance phase administration (0.5 mL) up to 48 months.

Results

Forty patients were recruited for the study, seven allocated to the Dpt/Bt group and 33 to the Dpt/Ld. None experienced immediate or delayed systemic Grade ≥ 2 reactions (EAACI classification) (systemic reactions were mostly Grade 1) nor died during the study. Local reactions were mostly mild (0‒10 cm). Thirty-nine patients (97.5%) experienced at least one adverse event (AE). Of the 283 reported AEs, eight (2.8%) were systemic reactions experienced by six (15%) subjects and 14 (4.9%) were local reactions sustained by ten (25%) subjects.

Conclusions

SCIT treatment of patients with allergic rhinitis or rhinoconjunctivitis and controlled asthma with mixtures of Dpt/Bt and Dpt/Ld allergen extracts at maximum concentrations showed a favourable safety profile.

背景：过敏原免疫治疗的疗效是剂量依赖性的；然而，高剂量的过敏原可能意味着更大的不良反应风险。目的：评估螨虫过敏原提取物、翼螨/热带褐虫（Dpt/Bt）和翼螨/毁鳞螨（Dpt/Ld）混合物在最大浓度下皮下免疫治疗（SCIT）对变应性鼻炎或鼻结膜炎的成人患者的安全性和耐受性，并控制过敏性哮喘，因为这些螨具有临床相关的致敏性。方法：2014年9月至2018年5月，在西班牙的三家医院进行了一项开放标签、非对照、非随机的IIb期临床试验。患者分两个阶段接受Dpt/Bt （100/1000 DPP/mL）或Dpt/Ld （100/100 DPP/mL）的SCIT治疗：第一天的快速积累阶段（0.2 mL和0.3 mL，间隔30分钟）和每月维持阶段（0.5 mL），直至48个月。结果：40例患者被纳入研究，7例分配到Dpt/Bt组，33例分配到Dpt/Ld组。在研究期间，没有发生立即或延迟的系统性≥2级反应（EAACI分级）（系统性反应大多为1级），也没有死亡。局部反应多为轻度（0 ~ 10 cm）。39例（97.5%）患者至少发生一次不良事件（AE）。在283例报告的不良反应中，8例（2.8%）为6例（15%）受试者的全身反应，14例（4.9%）为10例（25%）受试者的局部反应。结论：最大浓度Dpt/Bt和Dpt/Ld过敏原提取物的混合物在SCIT治疗变应性鼻炎或鼻结膜炎和控制哮喘患者中显示出良好的安全性。

{"title":"Clinical Trial With a Depigmented, Polymerized Mite Mixture Extract at Maximum Concentrations","authors":"Carmen Vidal, Laura Romero, Sara Lopez-Freire, Francisco Carballada-Gonzalez, José Carlos Garcia-Robaina, Teresa Gonzalez-Fernandez, Paula Mendez-Brea, Eva Nieto, Mónica Ruiz-Garcia","doi":"10.1002/iid3.70090","DOIUrl":"10.1002/iid3.70090","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Efficacy of allergen immunotherapy is dose-dependent; however, high doses of allergen may imply a greater risk of adverse reactions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To assess the safety and tolerability of subcutaneous immunotherapy (SCIT) with mixtures of mite allergen extracts, <i>Dermatophagoides pteronyssinus</i>/<i>Blomia tropicalis</i> (Dpt/Bt) and <i>Dermatophagoides pteronyssinus</i>/<i>Lepidoglyphus destructor</i> (Dpt/Ld) at maximum concentrations, in adult patients with allergic rhinitis or rhinoconjunctivitis, and controlled allergic asthma due to a clinically relevant sensitisation to these mites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An open-label, noncontrolled, nonrandomised, phase IIb clinical trial was carried out in three hospitals in Spain between September 2014 and May 2018. Patients received SCIT of either Dpt/Bt (100/1000 DPP/mL) or Dpt/Ld (100/100 DPP/mL) in two phases: a rush build-up phase on the first day (0.2 mL and 0.3 mL with a 30-min interval) and a monthly maintenance phase administration (0.5 mL) up to 48 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Forty patients were recruited for the study, seven allocated to the Dpt/Bt group and 33 to the Dpt/Ld. None experienced immediate or delayed systemic Grade ≥ 2 reactions (EAACI classification) (systemic reactions were mostly Grade 1) nor died during the study. Local reactions were mostly mild (0‒10 cm). Thirty-nine patients (97.5%) experienced at least one adverse event (AE). Of the 283 reported AEs, eight (2.8%) were systemic reactions experienced by six (15%) subjects and 14 (4.9%) were local reactions sustained by ten (25%) subjects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SCIT treatment of patients with allergic rhinitis or rhinoconjunctivitis and controlled asthma with mixtures of Dpt/Bt and Dpt/Ld allergen extracts at maximum concentrations showed a favourable safety profile.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"12 12","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853943","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

Blood Inflammatory Markers and Cytokines in COVID-19 Patients With Bacterial Coinfections COVID-19细菌性共感染患者血液炎症标志物和细胞因子

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-18 DOI: 10.1002/iid3.70105

Qingqing Bi, Jie Zhu, Jinju Zheng, Qingyun Xu, Juan Chen, Lei Zhang, Xiaofeng Mu

Background

Bacterial coinfection in patients with SARS-CoV-2 infection is an important risk factor for death. This study investigated whether there were differences in levels of serum inflammatory markers in COVID-19 patients with bacterial coinfections compared with those without bacterial infection.

Methods

A total of 235 inpatients with SARS-CoV-2 infection admitted to Qingdao Central Hospital from December 7, 2022, to August 7, 2024, were included. Patients were divided into a bacteria-positive group (115 cases) and a bacteria-negative group (120 cases) according to whether they had bacterial coinfections. PCT, CRP, and 12 kinds of cytokines were compared between groups, and the distribution of bacterial species in the positive group was statistically analyzed.

Results

The serum levels of CRP (Z = 8.94, p < 0.001), PCT (Z = 5.59, p < 0.001), IL-1β (t = 4.863, p < 0.001), IL-2 (t = 5.810, p < 0.001), IL-5 (t = 3.837, p < 0.001), IL-6 (t = 4.910, p < 0.001), IL-8 (t = 3.325, p < 0.001), ILIL-12p70 (t = 4.722, p < 0.001), IL-17 (t = 3.315, p = 0.001) and TNF-α (t = 4.251, p < 0.001) between the two groups were significantly different. IL-4, IL-10, IFN-α, and IFN-γ were not statistically significant (p > 0.05). Among the 115 bacteria-positive patients, 56 patients were positive for one species and 59 patients were multiple infections. Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae were common species.

Conclusions

Serum PCT and CRP levels in COVID-19 patients with bacterial coinfection are higher than those without bacterial infection. Cytokines such as IL-1β, IL-2, IL-5, IL-6, IL-8, IL-12p70, IL-17, and TNF-α may be involved in the progression of COVID-19 combined with bacterial infection. They can be used as potential markers to evaluate the disease condition and prognosis.

背景：细菌合并感染是SARS-CoV-2感染患者死亡的重要危险因素。本研究探讨了合并细菌感染的COVID-19患者与未感染的患者血清炎症标志物水平是否存在差异。方法：选取青岛市中心医院2022年12月7日至2024年8月7日收治的235例SARS-CoV-2住院患者。根据有无细菌共感染分为细菌阳性组（115例）和细菌阴性组（120例）。比较各组间PCT、CRP及12种细胞因子水平，并对阳性组细菌种类分布进行统计分析。结果：血清CRP水平（Z = 8.94, p 0.05）。115例细菌阳性患者中，一种细菌阳性56例，多重感染59例。鲍曼不动杆菌、肺炎克雷伯菌、铜绿假单胞菌、金黄色葡萄球菌和流感嗜血杆菌是常见的菌种。结论：合并细菌感染的COVID-19患者血清PCT和CRP水平高于未合并细菌感染的患者。IL-1β、IL-2、IL-5、IL-6、IL-8、IL-12p70、IL-17和TNF-α等细胞因子可能参与了COVID-19合并细菌感染的进展。它们可作为评估疾病状况和预后的潜在标志物。

{"title":"Blood Inflammatory Markers and Cytokines in COVID-19 Patients With Bacterial Coinfections","authors":"Qingqing Bi, Jie Zhu, Jinju Zheng, Qingyun Xu, Juan Chen, Lei Zhang, Xiaofeng Mu","doi":"10.1002/iid3.70105","DOIUrl":"10.1002/iid3.70105","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bacterial coinfection in patients with SARS-CoV-2 infection is an important risk factor for death. This study investigated whether there were differences in levels of serum inflammatory markers in COVID-19 patients with bacterial coinfections compared with those without bacterial infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 235 inpatients with SARS-CoV-2 infection admitted to Qingdao Central Hospital from December 7, 2022, to August 7, 2024, were included. Patients were divided into a bacteria-positive group (115 cases) and a bacteria-negative group (120 cases) according to whether they had bacterial coinfections. PCT, CRP, and 12 kinds of cytokines were compared between groups, and the distribution of bacterial species in the positive group was statistically analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The serum levels of CRP (<i>Z</i> = 8.94, <i>p</i> < 0.001), PCT (<i>Z</i> = 5.59, <i>p</i> < 0.001), IL-1β (<i>t</i> = 4.863, <i>p</i> < 0.001), IL-2 (<i>t</i> = 5.810, <i>p</i> < 0.001), IL-5 (<i>t</i> = 3.837, <i>p</i> < 0.001), IL-6 (<i>t</i> = 4.910, <i>p</i> < 0.001), IL-8 (<i>t</i> = 3.325, <i>p</i> < 0.001), ILIL-12p70 (<i>t</i> = 4.722, <i>p</i> < 0.001), IL-17 (<i>t</i> = 3.315, <i>p</i> = 0.001) and TNF-α (<i>t</i> = 4.251, <i>p</i> < 0.001) between the two groups were significantly different. IL-4, IL-10, IFN-α, and IFN-γ were not statistically significant (<i>p</i> > 0.05). Among the 115 bacteria-positive patients, 56 patients were positive for one species and 59 patients were multiple infections. <i>Acinetobacter baumannii</i>, <i>Klebsiella pneumoniae, Pseudomonas aeruginosa</i>, <i>Staphylococcus aureus,</i> and <i>Haemophilus influenzae</i> were common species.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Serum PCT and CRP levels in COVID-19 patients with bacterial coinfection are higher than those without bacterial infection. Cytokines such as IL-1β, IL-2, IL-5, IL-6, IL-8, IL-12p70, IL-17, and TNF-α may be involved in the progression of COVID-19 combined with bacterial infection. They can be used as potential markers to evaluate the disease condition and prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"12 12","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846585","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

D609 Suppresses Antituberculosis Response by Regulating Dendritic Cells Antigen Presentation D609通过调节树突状细胞抗原呈递抑制抗结核反应。

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-18 DOI: 10.1002/iid3.70103

Honglin Liu, Huimin Huang, Zhen Huang, Yingxuan Chen, Deyou Tan, Xiaoni Wang, Xiaoni Pang, Shuwen Chen, Lianhui Liang, Haihui Yang

<div> <section> <h3> Objective</h3> <p>To elucidate the role of phosphatidylcholine-specific phospholipase C (PC-PLC) in the antituberculosis (anti-TB) immune response mediated by dendritic cells (DCs).</p> </section> <section> <h3> Methods</h3> <p>In vivo, C57BL/6J mice infected with the <i>Mycobacterium tuberculosis</i> strain H37Rv. Before infection, the mice were pretreated with the PC-PLC inhibitor D609. Bacillary loads in lung and spleen tissues were quantified through colony-forming unit (CFU) assays. Hematoxylin and eosin (H&E) staining was performed to assess inflammatory infiltration and tissue damage. Levels of inflammatory mediators in peripheral venous blood were quantified using enzyme-linked immunosorbent assays (ELISAs). Flow cytometry was employed to determine the proportions of conventional DCs (cDCs) and their subsets, cDC1 and cDC2, within lung, spleen, and lymph node tissues. In vitro, mouse bone marrow-derived dendritic cells (BMDCs) pretreated with D609. The expression levels of chemokines and pro-inflammatory cytokines were assessed via quantitative polymerase chain reaction (qPCR) and ELISA. BMDCs were loaded with H37Rv expressing red fluorescent protein (RFP-H37Rv) or DQ-OVA, and flow cytometry was utilized to analyze the impact of D609 on antigen phagocytosis and processing. Furthermore, flow cytometry was employed to evaluate the effect of D609 pretreatment on the expression levels of costimulatory molecules on BMDCs. The capacity of D609-treated BMDCs to activate and proliferate T cells, as well as to induce interferon-gamma (IFN-γ) secretion, was assessed through a DC-T cell coculture system.</p> </section> <section> <h3> Results</h3> <p>In vivo analysis revealed that mice pretreated with D609 exhibited a marked increase in tissue bacterial load, enhanced inflammatory infiltration, and a reduction in pro-inflammatory mediator expression in peripheral venous blood. There was a notable decrease in the number of cDCs in lung and lymph node tissues, with a pronounced reduction in cDC1 in the lungs and cDC2 in the lymph nodes. In vitro studies demonstrated that D609 pretreated BMDCs displayed a significant decline in inflammatory mediator production, antigen phagocytosis, and antigen processing capabilities, potentially due to altered expression of costimulatory molecules. Coculture experiments indicated that D609 pretreated BMDCs showed a substantial reduction in their ability to stimulate T cell activation, proliferation, and IFN-γ secretion.</p> </section> <section> <h3> Conclusion</h3> <p>Our findings suggest that P

目的：探讨磷脂酰胆碱特异性磷脂酶C （PC-PLC）在树突状细胞介导的抗结核（anti-TB）免疫应答中的作用。方法：C57BL/6J小鼠体内感染H37Rv结核分枝杆菌。感染前用PC-PLC抑制剂D609对小鼠进行预处理。通过菌落形成单位（CFU）测定肺和脾组织中的细菌负荷。苏木精和伊红（H&E）染色评估炎症浸润和组织损伤。采用酶联免疫吸附法（elisa）测定外周静脉血中炎症介质的水平。流式细胞术测定肺、脾和淋巴结组织中常规dc （cdc）及其亚群cDC1和cDC2的比例。在体外，用D609预处理小鼠骨髓源性树突状细胞（bmdc）。采用定量聚合酶链反应（qPCR）和酶联免疫吸附法（ELISA）检测趋化因子和促炎因子的表达水平。分别转染表达红色荧光蛋白（RFP-H37Rv）或DQ-OVA的H37Rv，流式细胞术分析D609对抗原吞噬和加工的影响。采用流式细胞术检测D609预处理对BMDCs共刺激分子表达水平的影响。通过DC-T细胞共培养系统评估d609处理的BMDCs激活和增殖T细胞的能力，以及诱导干扰素γ (IFN-γ)分泌的能力。结果：体内分析显示，经D609预处理的小鼠组织细菌负荷显著增加，炎症浸润增强，外周静脉血促炎介质表达降低。肺和淋巴结组织中cDCs的数量明显减少，其中肺中cDC1和淋巴结中的cDC2明显减少。体外研究表明，D609预处理的BMDCs显示出炎症介质产生、抗原吞噬和抗原加工能力的显著下降，这可能是由于共刺激分子表达的改变。共培养实验表明，D609预处理的BMDCs刺激T细胞活化、增殖和IFN-γ分泌的能力显著降低。结论：我们的研究结果表明，PC-PLC在dc的功能中起着关键作用，包括趋化因子和促炎细胞因子的产生，向淋巴结的迁移和抗原向T细胞的递呈，这些共同促进T细胞的激活和有效清除结核分枝杆菌。对PC-PLC在dc中的调控机制的进一步研究可能为开发先进的抗结核治疗方法发现新的治疗靶点。

{"title":"D609 Suppresses Antituberculosis Response by Regulating Dendritic Cells Antigen Presentation","authors":"Honglin Liu, Huimin Huang, Zhen Huang, Yingxuan Chen, Deyou Tan, Xiaoni Wang, Xiaoni Pang, Shuwen Chen, Lianhui Liang, Haihui Yang","doi":"10.1002/iid3.70103","DOIUrl":"10.1002/iid3.70103","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To elucidate the role of phosphatidylcholine-specific phospholipase C (PC-PLC) in the antituberculosis (anti-TB) immune response mediated by dendritic cells (DCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In vivo, C57BL/6J mice infected with the <i>Mycobacterium tuberculosis</i> strain H37Rv. Before infection, the mice were pretreated with the PC-PLC inhibitor D609. Bacillary loads in lung and spleen tissues were quantified through colony-forming unit (CFU) assays. Hematoxylin and eosin (H&E) staining was performed to assess inflammatory infiltration and tissue damage. Levels of inflammatory mediators in peripheral venous blood were quantified using enzyme-linked immunosorbent assays (ELISAs). Flow cytometry was employed to determine the proportions of conventional DCs (cDCs) and their subsets, cDC1 and cDC2, within lung, spleen, and lymph node tissues. In vitro, mouse bone marrow-derived dendritic cells (BMDCs) pretreated with D609. The expression levels of chemokines and pro-inflammatory cytokines were assessed via quantitative polymerase chain reaction (qPCR) and ELISA. BMDCs were loaded with H37Rv expressing red fluorescent protein (RFP-H37Rv) or DQ-OVA, and flow cytometry was utilized to analyze the impact of D609 on antigen phagocytosis and processing. Furthermore, flow cytometry was employed to evaluate the effect of D609 pretreatment on the expression levels of costimulatory molecules on BMDCs. The capacity of D609-treated BMDCs to activate and proliferate T cells, as well as to induce interferon-gamma (IFN-γ) secretion, was assessed through a DC-T cell coculture system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In vivo analysis revealed that mice pretreated with D609 exhibited a marked increase in tissue bacterial load, enhanced inflammatory infiltration, and a reduction in pro-inflammatory mediator expression in peripheral venous blood. There was a notable decrease in the number of cDCs in lung and lymph node tissues, with a pronounced reduction in cDC1 in the lungs and cDC2 in the lymph nodes. In vitro studies demonstrated that D609 pretreated BMDCs displayed a significant decline in inflammatory mediator production, antigen phagocytosis, and antigen processing capabilities, potentially due to altered expression of costimulatory molecules. Coculture experiments indicated that D609 pretreated BMDCs showed a substantial reduction in their ability to stimulate T cell activation, proliferation, and IFN-γ secretion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that P","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"12 12","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846589","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

Upregulation of Peripheral Blood NLRP3 and IL-18 in Patients With Acute Kidney Injury in Sepsis and Its Clinical Significance 脓毒症急性肾损伤患者外周血NLRP3和IL-18表达上调及其临床意义

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-18 DOI: 10.1002/iid3.70113

Jing Zhou, Yibin Ye, Zhipeng Chen, Yong Liu, Baozheng Wu, Haiping Huang

Background

Sepsis-associated acute kidney injury (SA-AKI) is a common complication that can lead to renal failure in patients, significantly affecting the prognosis and survival of patients.

Objective

In this study, we aimed to evaluate the predictive value of NOD-like receptor protein 3 (NLRP3) and interleukin 18 (IL-18) in peripheral blood mononuclear cells (PBMCs) of SA patients for the occurrence of SA-AKI.

Material and Methods

We screened AKI-related data sets using the Gene Expression Omnibus (GEO) database and identified differentially expressed genes (DEGs) associated with AKI. KEGG and GO analysis were used to identify enriched molecular functions and pathways. The study included 62 SA patients admitted to the Department of Intensive Care Medicine of our hospital from February 2021 to June 2022, including 34 non-AKI cases and 28 AKI cases, and 25 healthy volunteers were used as the control group. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the levels of NLRP3 and IL-18 in PBMCs of the subjects.

Results

Bioinformatics analysis and experimental validation showed that the expression levels of NLRP3 and IL-18 were significantly upregulated in SA-AKI patients. In addition, the expressions of NLRP3 and IL-18 were positively correlated with APACHE II scores. ROC curve analysis revealed that NLRP3 and IL-18 have the potential to diagnose SA-AKI.

Conclusion

This study provides preliminary evidence for NLRP3 and IL-18 as potential diagnostic biomarkers for SA-AKI.

背景：脓毒症相关急性肾损伤（SA-AKI）是一种常见的并发症，可导致患者肾功能衰竭，严重影响患者的预后和生存。目的：本研究旨在评价SA患者外周血单个核细胞（PBMCs）中nod样受体蛋白3 （NLRP3）和白细胞介素18 （IL-18）对SA- aki发生的预测价值。材料和方法：我们使用Gene Expression Omnibus （GEO）数据库筛选AKI相关数据集，并鉴定与AKI相关的差异表达基因（DEGs）。KEGG和GO分析用于鉴定富集的分子功能和途径。本研究纳入我院重症医学科2021年2月至2022年6月收治的62例SA患者，其中非AKI患者34例，AKI患者28例，健康志愿者25例作为对照组。采用实时定量聚合酶链反应（RT-qPCR）检测受试者外周血NLRP3和IL-18水平。结果：生物信息学分析和实验验证表明，SA-AKI患者NLRP3和IL-18的表达水平显著上调。此外，NLRP3和IL-18的表达与APACHE II评分呈正相关。ROC曲线分析显示NLRP3和IL-18具有诊断SA-AKI的潜力。结论：本研究为NLRP3和IL-18作为SA-AKI的潜在诊断生物标志物提供了初步证据。

{"title":"Upregulation of Peripheral Blood NLRP3 and IL-18 in Patients With Acute Kidney Injury in Sepsis and Its Clinical Significance","authors":"Jing Zhou, Yibin Ye, Zhipeng Chen, Yong Liu, Baozheng Wu, Haiping Huang","doi":"10.1002/iid3.70113","DOIUrl":"10.1002/iid3.70113","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sepsis-associated acute kidney injury (SA-AKI) is a common complication that can lead to renal failure in patients, significantly affecting the prognosis and survival of patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In this study, we aimed to evaluate the predictive value of NOD-like receptor protein 3 (NLRP3) and interleukin 18 (IL-18) in peripheral blood mononuclear cells (PBMCs) of SA patients for the occurrence of SA-AKI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Methods</h3>\u0000 \u0000 <p>We screened AKI-related data sets using the Gene Expression Omnibus (GEO) database and identified differentially expressed genes (DEGs) associated with AKI. KEGG and GO analysis were used to identify enriched molecular functions and pathways. The study included 62 SA patients admitted to the Department of Intensive Care Medicine of our hospital from February 2021 to June 2022, including 34 non-AKI cases and 28 AKI cases, and 25 healthy volunteers were used as the control group. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the levels of NLRP3 and IL-18 in PBMCs of the subjects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Bioinformatics analysis and experimental validation showed that the expression levels of NLRP3 and IL-18 were significantly upregulated in SA-AKI patients. In addition, the expressions of NLRP3 and IL-18 were positively correlated with APACHE II scores. ROC curve analysis revealed that NLRP3 and IL-18 have the potential to diagnose SA-AKI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides preliminary evidence for NLRP3 and IL-18 as potential diagnostic biomarkers for SA-AKI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"12 12","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846593","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

Impaired Angiogenesis and Th1/Th17 Polarization: A Possible Explanation for the Decreased Incidence of Rosacea in the Aged 血管生成受损和Th1/Th17极化：老年人酒渣鼻发病率降低的可能解释。

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-18 DOI: 10.1002/iid3.70108

Juan Long, Zhili Deng, Mengting Chen, Tangxiele Liu

Background

Rosacea is a common inflammatory skin disorder characterized by frequent facial flushing, erythema, telangiectasia, and papules, with a higher incidence observed in individuals aged 30−50 years and a tendency to decrease in the elderly. This age-related decline in incidence drew our attention to further explore the relationship between rosacea pathogenesis and aging.

Methods

We analyzed the incidence of rosacea across 8340 individuals without systemic diseases. The effects of LL37-induced rosacea-like erythema and inflammation were evaluated in both young and aged mice. Immunofluorescence analysis was performed to assess microvessel density, whereas the expression levels of angiogenesis-related factors, including matrix metalloproteinases (MMPs) and vascular endothelial growth factor α (VEGFα), were quantified. Additionally, immune responses were assessed at both the cellular and systemic levels.

Results

Aged mice displayed milder LL37-induced rosacea-like erythema and inflammation compared to their young counterparts. Immunofluorescence analysis revealed a decrease in microvessel density in rosacea models of the aged group. The expression of angiogenesis-related factors, including MMPs and VEGFα, was decreased in aged mice compared to young mice, indicating a reduced responsiveness to LL37 stimulation. Furthermore, we found that suppressed Th1- and Th17-polarized immune responses, one of the major pathogenic mechanisms of rosacea, were reduced in aged mice in response to LL37 stimulation at both cellular and systemic levels.

Conclusion

The findings suggest that impaired angiogenesis and attenuated Th1/Th17 immune responses underlie the age-related decline in rosacea incidence.

背景：酒糟是一种常见的炎症性皮肤疾病，其特征是频繁的面部潮红、红斑、毛细血管扩张和丘疹，在30-50岁的人群中发病率较高，老年人有减少的趋势。这种与年龄相关的发病率下降引起了我们的注意，进一步探讨酒渣鼻发病与衰老的关系。方法：我们分析了8340例无全身性疾病的酒渣鼻的发病率。在年轻和老年小鼠中评估了ll37诱导的酒渣鼻样红斑和炎症的影响。免疫荧光分析评估微血管密度，同时定量血管生成相关因子，包括基质金属蛋白酶（MMPs）和血管内皮生长因子α (VEGFα)的表达水平。此外，在细胞和全身水平上评估免疫反应。结果：与年轻小鼠相比，老年小鼠表现出较轻的ll37诱导的酒渣鼻样红斑和炎症。免疫荧光分析显示老年组酒渣鼻模型微血管密度降低。与年轻小鼠相比，老年小鼠血管生成相关因子（包括MMPs和VEGFα）的表达降低，表明对LL37刺激的反应性降低。此外，我们发现抑制Th1-和th17极化的免疫反应是酒渣鼻的主要致病机制之一，在年老小鼠中，LL37刺激在细胞和全身水平上都降低了。结论：研究结果表明，血管生成受损和Th1/Th17免疫反应减弱是酒渣鼻发病率与年龄相关的下降的基础。

{"title":"Impaired Angiogenesis and Th1/Th17 Polarization: A Possible Explanation for the Decreased Incidence of Rosacea in the Aged","authors":"Juan Long, Zhili Deng, Mengting Chen, Tangxiele Liu","doi":"10.1002/iid3.70108","DOIUrl":"10.1002/iid3.70108","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Rosacea is a common inflammatory skin disorder characterized by frequent facial flushing, erythema, telangiectasia, and papules, with a higher incidence observed in individuals aged 30−50 years and a tendency to decrease in the elderly. This age-related decline in incidence drew our attention to further explore the relationship between rosacea pathogenesis and aging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed the incidence of rosacea across 8340 individuals without systemic diseases. The effects of LL37-induced rosacea-like erythema and inflammation were evaluated in both young and aged mice. Immunofluorescence analysis was performed to assess microvessel density, whereas the expression levels of angiogenesis-related factors, including matrix metalloproteinases (MMPs) and vascular endothelial growth factor α (VEGFα), were quantified. Additionally, immune responses were assessed at both the cellular and systemic levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Aged mice displayed milder LL37-induced rosacea-like erythema and inflammation compared to their young counterparts. Immunofluorescence analysis revealed a decrease in microvessel density in rosacea models of the aged group. The expression of angiogenesis-related factors, including MMPs and VEGFα, was decreased in aged mice compared to young mice, indicating a reduced responsiveness to LL37 stimulation. Furthermore, we found that suppressed Th1- and Th17-polarized immune responses, one of the major pathogenic mechanisms of rosacea, were reduced in aged mice in response to LL37 stimulation at both cellular and systemic levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The findings suggest that impaired angiogenesis and attenuated Th1/Th17 immune responses underlie the age-related decline in rosacea incidence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"12 12","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846591","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

Advancements in Molecular Diagnosis and Pharmacotherapeutic Strategies for Invasive Pituitary Adenomas 侵袭性垂体腺瘤的分子诊断与药物治疗策略研究进展。

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-17 DOI: 10.1002/iid3.70098

Dingkai Xu, Ling Wang, Maohua Zheng

Background

The overwhelming majority of pituitary tumors consist of pituitary adenomas (PAs), which have recently also been termed pituitary neuroendocrine tumors (PitNETs). Clinically significant PAs occur in approximately one in every 1000 individuals, while other types of pituitary tumors, such as craniopharyngiomas and pituicytomas, are significantly less common. Although PAs are generally benign, a subset of them exhibits malignant-like biological traits. They tend to infiltrate and grow aggressively into adjacent tissues and organs, including the dura mater, cavernous sinus, and sphenoid sinus. This invasive behavior often results in the destruction of the normal anatomical architecture of the sella turcica and skull base. Clinically, such tumors are classified as invasive PAs (IPAs), emphasizing their aggressive and destructive nature.

Objective and Significance

Currently, the diagnostic indicators for IPAs frequently suffer from suboptimal sensitivity and specificity. The invasiveness assessment of PAs lacks a definitive gold standard and instead serves as a predictive tool, with a greater number of indicators met suggesting a higher likelihood of invasiveness. Consequently, a comprehensive approach that integrates imaging, pathological, molecular biological, and other disciplinary metrics is crucial for accurate evaluation. Despite surgery being the primary treatment modality for IPAs, their malignant-like behavior complicates complete resection, resulting in lower resection rates and heightened postoperative recurrence, necessitating multiple surgeries. Therefore, adjunctive drug therapy is often necessary for IPA patients. Preoperative drug therapy can shrink tumor size, facilitating resection and postoperative recovery, mitigating hormone imbalances, delaying recurrence, and enhancing patients' quality of life.

Conclusions

This article comprehensively reviews the diagnostic criteria for assessing the invasiveness of PAs in the domains of imaging, pathology, and molecular biology, provides an overview of the current research status of drug therapy for these conditions, and deepens our insight into the biological and therapeutic aspects of the tumor microenvironment in PAs.

背景：绝大多数垂体瘤由垂体腺瘤（PA）组成，最近也被称为垂体神经内分泌肿瘤（PitNET）。具有临床意义的垂体腺瘤的发病率约为千分之一，而其他类型的垂体瘤（如颅咽管瘤和垂体细胞瘤）则要少得多。虽然 PA 通常是良性的，但其中一部分会表现出类似恶性肿瘤的生物学特征。它们倾向于向邻近组织和器官浸润和生长，包括硬脑膜、海绵窦和蝶窦。这种侵袭行为往往会破坏蝶鞍和颅底的正常解剖结构。在临床上，此类肿瘤被归类为侵袭性 PA（IPA），强调其侵袭性和破坏性：目前，IPA 的诊断指标往往存在敏感性和特异性不足的问题。PA 的侵袭性评估缺乏明确的金标准，而是作为一种预测工具，符合的指标越多，表明侵袭性的可能性越大。因此，整合成像、病理、分子生物学和其他学科指标的综合方法对于准确评估至关重要。尽管手术是 IPA 的主要治疗方式，但 IPA 的恶性行为使完全切除变得复杂，导致切除率降低，术后复发率升高，因而需要多次手术。因此，IPA 患者往往需要辅助药物治疗。术前药物治疗可以缩小肿瘤体积，促进切除和术后恢复，缓解激素失衡，延缓复发，提高患者的生活质量：本文全面回顾了影像学、病理学和分子生物学领域评估 PA 侵袭性的诊断标准，概述了这些疾病的药物治疗研究现状，加深了我们对 PA 肿瘤微环境的生物学和治疗学方面的认识。

{"title":"Advancements in Molecular Diagnosis and Pharmacotherapeutic Strategies for Invasive Pituitary Adenomas","authors":"Dingkai Xu, Ling Wang, Maohua Zheng","doi":"10.1002/iid3.70098","DOIUrl":"10.1002/iid3.70098","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The overwhelming majority of pituitary tumors consist of pituitary adenomas (PAs), which have recently also been termed pituitary neuroendocrine tumors (PitNETs). Clinically significant PAs occur in approximately one in every 1000 individuals, while other types of pituitary tumors, such as craniopharyngiomas and pituicytomas, are significantly less common. Although PAs are generally benign, a subset of them exhibits malignant-like biological traits. They tend to infiltrate and grow aggressively into adjacent tissues and organs, including the dura mater, cavernous sinus, and sphenoid sinus. This invasive behavior often results in the destruction of the normal anatomical architecture of the sella turcica and skull base. Clinically, such tumors are classified as invasive PAs (IPAs), emphasizing their aggressive and destructive nature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective and Significance</h3>\u0000 \u0000 <p>Currently, the diagnostic indicators for IPAs frequently suffer from suboptimal sensitivity and specificity. The invasiveness assessment of PAs lacks a definitive gold standard and instead serves as a predictive tool, with a greater number of indicators met suggesting a higher likelihood of invasiveness. Consequently, a comprehensive approach that integrates imaging, pathological, molecular biological, and other disciplinary metrics is crucial for accurate evaluation. Despite surgery being the primary treatment modality for IPAs, their malignant-like behavior complicates complete resection, resulting in lower resection rates and heightened postoperative recurrence, necessitating multiple surgeries. Therefore, adjunctive drug therapy is often necessary for IPA patients. Preoperative drug therapy can shrink tumor size, facilitating resection and postoperative recovery, mitigating hormone imbalances, delaying recurrence, and enhancing patients' quality of life.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This article comprehensively reviews the diagnostic criteria for assessing the invasiveness of PAs in the domains of imaging, pathology, and molecular biology, provides an overview of the current research status of drug therapy for these conditions, and deepens our insight into the biological and therapeutic aspects of the tumor microenvironment in PAs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"12 12","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835550","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

The Correlation Analysis Between m6A Methylation Modification and Ferroptosis Induced by Cigarette Smoke in Human Bronchial Epithelium m6A甲基化修饰与吸烟致人支气管上皮铁下垂的相关性分析。

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-17 DOI: 10.1002/iid3.70104

Xiaomei Duan, Tingting Hu, Lijuan Xu, Zheng Li, Jing Jing, Dan Xu, Jianbing Ding, Fengsen Li, Min Jiang, Jing Wang

Background

Chronic obstructive pulmonary disease (COPD), a prevalent respiratory condition, is characterized by long-term airway inflammation, which can lead to airway remodeling and persistent airflow restriction. Exposure to cigarette smoke is known as a major contributor to COPD development. Research has confirmed that ferroptosis and m6A modification are closely related to various inflammatory-related diseases. However, the correlation between m6A methylation and ferroptosis in COPD has not been confirmed. In this study, combined with bioinformatics analysis and molecular biology methods we investigated how m6A methylation was correlated to ferroptosis-associated genes (SLC7A11 and NQO-1) in cigarette smoke induced 16HBES cells.

Methods

Two microarray datasets (GSE30063 and GSE64614) were combined to identify differentially expressed genes (DEGs) through the application of bioinformatics techniques. A cigarette smoke (CS)-induced 16HBE cells model was established. The ROS, GSH, MDA, and total iron content were detected by relevant detection kits. The expression levels associated with ferroptosis and m6A methylation modification-related genes were determined via reverse transcription-quantitative polymerase chain reaction and western blot.

Results

Overall, 529 DEGs were identified in the above two databases. For COPD patients, significant changes were observed in FAGs (GCLC, NQO-1, SLC7A11) and m6A methylation-related genes (FTO). A negative correlation was also noted between the expression level of genes linked to ferroptosis (SLC7A11 and NQO-1) and that of the m6A methylation gene (FTO). The in vitro experiments results indicate that SLC7A11 and NQO-1 were significantly downregulated, and FTO were significantly upregulated. In addition, cigarette smoke stimulation increased the levels of MDA, LPO, and ROS, while reducing the content of GSH and total iron content in 16HBE cells.

Conclusion

Our findings explored the relationship between ferroptosis and m6A methylation in COPD, and screened out SLC7A11, NQO-1 and FTO may be critical in the pathogenesis of COPD.

背景：慢性阻塞性肺疾病（COPD）是一种常见的呼吸系统疾病，其特点是气道长期炎症，可导致气道重塑和持续气流受限。众所周知，接触香烟烟雾是导致慢性阻塞性肺病的主要因素。研究证实，铁蛋白沉积和 m6A 修饰与各种炎症相关疾病密切相关。然而，慢性阻塞性肺病中 m6A 甲基化与铁变态反应之间的相关性尚未得到证实。在本研究中，我们结合生物信息学分析和分子生物学方法，研究了在香烟烟雾诱导的 16HBES 细胞中，m6A 甲基化与铁变态反应相关基因（SLC7A11 和 NQO-1）的相关性：方法：结合两个微阵列数据集（GSE30063 和 GSE64614），应用生物信息学技术识别差异表达基因（DEGs）。建立了香烟烟雾（CS）诱导的 16HBE 细胞模型。通过相关检测试剂盒检测了ROS、GSH、MDA和总铁含量。通过逆转录-定量聚合酶链反应和免疫印迹法测定与铁变态反应和 m6A 甲基化修饰相关基因的表达水平：结果：上述两个数据库共鉴定出 529 个 DEGs。慢性阻塞性肺病患者的 FAGs（GCLC、NQO-1、SLC7A11）和 m6A 甲基化相关基因（FTO）发生了显著变化。此外，还发现与铁变态反应有关的基因（SLC7A11 和 NQO-1）的表达水平与 m6A 甲基化基因（FTO）的表达水平呈负相关。体外实验结果表明，SLC7A11 和 NQO-1 的表达明显下调，而 FTO 的表达明显上调。此外，香烟烟雾刺激增加了 16HBE 细胞中 MDA、LPO 和 ROS 的水平，同时降低了 GSH 和总铁的含量：结论：我们的研究结果探讨了慢性阻塞性肺病中的铁变态反应与 m6A 甲基化之间的关系，并筛选出 SLC7A11、NQO-1 和 FTO 可能在慢性阻塞性肺病的发病机制中起关键作用。

{"title":"The Correlation Analysis Between m6A Methylation Modification and Ferroptosis Induced by Cigarette Smoke in Human Bronchial Epithelium","authors":"Xiaomei Duan, Tingting Hu, Lijuan Xu, Zheng Li, Jing Jing, Dan Xu, Jianbing Ding, Fengsen Li, Min Jiang, Jing Wang","doi":"10.1002/iid3.70104","DOIUrl":"10.1002/iid3.70104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic obstructive pulmonary disease (COPD), a prevalent respiratory condition, is characterized by long-term airway inflammation, which can lead to airway remodeling and persistent airflow restriction. Exposure to cigarette smoke is known as a major contributor to COPD development. Research has confirmed that ferroptosis and m6A modification are closely related to various inflammatory-related diseases. However, the correlation between m6A methylation and ferroptosis in COPD has not been confirmed. In this study, combined with bioinformatics analysis and molecular biology methods we investigated how m6A methylation was correlated to ferroptosis-associated genes (SLC7A11 and NQO-1) in cigarette smoke induced 16HBES cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two microarray datasets (GSE30063 and GSE64614) were combined to identify differentially expressed genes (DEGs) through the application of bioinformatics techniques. A cigarette smoke (CS)-induced 16HBE cells model was established. The ROS, GSH, MDA, and total iron content were detected by relevant detection kits. The expression levels associated with ferroptosis and m6A methylation modification-related genes were determined via reverse transcription-quantitative polymerase chain reaction and western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 529 DEGs were identified in the above two databases. For COPD patients, significant changes were observed in FAGs (GCLC, NQO-1, SLC7A11) and m6A methylation-related genes (FTO). A negative correlation was also noted between the expression level of genes linked to ferroptosis (SLC7A11 and NQO-1) and that of the m6A methylation gene (FTO). The in vitro experiments results indicate that SLC7A11 and NQO-1 were significantly downregulated, and FTO were significantly upregulated. In addition, cigarette smoke stimulation increased the levels of MDA, LPO, and ROS, while reducing the content of GSH and total iron content in 16HBE cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings explored the relationship between ferroptosis and m6A methylation in COPD, and screened out SLC7A11, NQO-1 and FTO may be critical in the pathogenesis of COPD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"12 12","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835552","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