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The Complex Relationship Between Chronic Obstructive Pulmonary Disease With Cardiovascular Disease and Their Interactions With COVID-19 Vaccination: A Retrospective Study 慢性阻塞性肺病与心血管疾病之间的复杂关系及其与接种 COVID-19 疫苗的相互作用:一项回顾性研究
IF 3.1 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-18 DOI: 10.1002/iid3.70068
Muhammad Muneeb Hassan, Sheikh Muhammad Sikandar, Farrukh Jamal, Muhammad Ameeq, Alpha Kargbo

Background

Previously, most researchers explored the association between chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD). This study investigates the distinct influence of COVID-19 vaccination status on patients with both conditions.

Objective

We investigate the relationship between COPD and CVD in a cohort of 838 individuals who presented with both conditions. Our aim is to understand how these conditions interact and how COVID-19 vaccination status affects patient outcomes.

Methods

A retrospective analysis was conducted on 838 patients with COPD and CVD treated at DHQ Hospital in Muzaffargarh, Punjab, Pakistan, from November 2022 to April 2023. We employed multiple logistic regression and the Wilcoxon signed-rank test to assess the odds ratio and relative risk of COPD in patients with-CVD under various conditions. Additionally, we analyzed time-to-death and survival using Kaplan–Meier methods.

Results

Findings reveal a 7.95 times higher risk of death in patients without COVID-19 vaccination compared with those who were vaccinated (95% CI, 6.12–10.33). Conversely, COVID-19-vaccinated patients exhibited a 0.221 times lower risk of recovery than their nonvaccinated counterparts (95% CI, 0.08–0.60). We also observed significant differences in time-to-death and recovery based on the presence of COPD and CVD, with vaccinated patients generally experiencing milder disease.

Conclusion

Our study assessed the impact of COVID-19 vaccination status on patient outcomes in patients with overlapping COPD and CVD. Individuals diagnosed with COPD and CVD display significant differences in terms of their probability of survival, with those who have received vaccinations.

背景:以前,大多数研究人员探讨的是慢性阻塞性肺疾病(COPD)与心血管疾病(CVD)之间的关联。本研究调查了 COVID-19 疫苗接种情况对这两种疾病患者的不同影响:我们调查了同时患有慢性阻塞性肺病和心血管疾病的 838 名患者。我们的目的是了解这两种疾病如何相互作用,以及 COVID-19 疫苗接种情况如何影响患者的预后:我们对 2022 年 11 月至 2023 年 4 月期间在巴基斯坦旁遮普省穆扎法尔加尔 DHQ 医院接受治疗的 838 名慢性阻塞性肺病和心血管疾病患者进行了回顾性分析。我们采用多元 Logistic 回归和 Wilcoxon 符号秩检验来评估慢性阻塞性肺病和心血管疾病患者在不同情况下的几率比例和相对风险。此外,我们还采用 Kaplan-Meier 方法分析了死亡时间和存活率:结果:研究结果显示,未接种 COVID-19 疫苗的患者死亡风险是接种疫苗患者的 7.95 倍(95% CI,6.12-10.33)。相反,接种 COVID-19 疫苗的患者康复风险比未接种者低 0.221 倍(95% CI,0.08-0.60)。我们还观察到,慢性阻塞性肺病和心血管疾病患者的死亡时间和康复时间存在明显差异,接种疫苗的患者一般病情较轻:我们的研究评估了 COVID-19 疫苗接种情况对合并慢性阻塞性肺病和心血管疾病患者预后的影响。确诊患有慢性阻塞性肺病和心血管疾病的患者与接种过疫苗的患者在生存概率方面存在显著差异。
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引用次数: 0
The Impact of Food Specific IgG Antibodies on Migraine and Its Comorbidities 食物特异性 IgG 抗体对偏头痛及其并发症的影响
IF 3.1 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-17 DOI: 10.1002/iid3.70056
Zhi-Ming Zhao, Mei-Mei Yang, Xian-Shu Zhao, Fu-Jun Wan, Bao-Li Ning, Li-Ming Zhang, Jun Fu

Objective

To investigate the differences in headache and comorbidity symptoms between migraine patients with negative and positive food specific IgG antibodies, and explore the correlation between these symptoms with food specific IgG antibodies.

Methods

A total of 129 migraine patients were enrolled. Seven questionnaires were used to gather information regarding the symptoms of migraine, gastrointestinal, depression, anxiety, and sleep. Serum specific IgG antibodies against 14 kinds of food were detected using enzyme-linked immunosorbent assays.

Results

Patients with migraine diagnosis who had positive food specific IgG antibodies had significantly worse headaches, gastrointestinal and anxiety symptoms, compared to the patients with negative IgG antibodies. Patients with more IgG positive foods and higher total positive IgG concentration generally had worse migraine conditions, anxiety, depression, and gastrointestinal symptoms.

Conclusion

The effect of food specific IgG antibodies on severity of migraine and its comorbidities were antibody-quantity and IgG-concentration dependent. Future studies are warranted to explore the mechanism underlying such relationship.

目的研究食物特异性 IgG 抗体阴性和阳性偏头痛患者在头痛和合并症症状方面的差异,并探讨这些症状与食物特异性 IgG 抗体之间的相关性:方法:共招募了 129 名偏头痛患者。方法:共招募了 129 名偏头痛患者,使用 7 份问卷调查偏头痛、胃肠道、抑郁、焦虑和睡眠症状。使用酶联免疫吸附试验检测血清中针对 14 种食物的特异性 IgG 抗体:结果:与 IgG 抗体阴性的患者相比,食物特异性 IgG 抗体阳性的偏头痛患者的头痛、胃肠道和焦虑症状明显加重。IgG阳性食物越多、IgG总阳性浓度越高的患者,偏头痛症状、焦虑、抑郁和胃肠道症状普遍越严重:结论:食物特异性 IgG 抗体对偏头痛严重程度及其合并症的影响与抗体数量和 IgG 浓度有关。未来的研究需要探索这种关系的内在机制。
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引用次数: 0
Analysis of genotype resistance and HIV-1 transmission risk in HIV-1-infected men who have sex with men in Guiyang, China 中国贵阳男男性行为者中 HIV-1 感染者的基因型耐药性和 HIV-1 传播风险分析。
IF 3.1 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-17 DOI: 10.1002/iid3.70029
Dawen Qin, Zhangping Hong, Yi Wang, Nan Meng, Xueyu Yang, Du Shen, Yong Hu, Xinglin Yang
<div> <section> <h3> Background</h3> <p>As the social economy has developed and population mobility has increased, differences in the Human immunodeficiency virus type 1 (HIV-1) genotype distribution among men who have sex with men (MSM) have become apparent in the provinces and cities across China. The high variability and drug resistance characteristics of HIV-1 can lead to the widespread spread of resistant strains, which may also result in antiretroviral therapy failure and an increase in the mortality rate.</p> </section> <section> <h3> Objective</h3> <p>The genotypic drug resistance characteristics and HIV-1 transmission risks among HIV-1-infected MSM in Guiyang, Guizhou Province were analyzed in the current study. The aim of the study was to provide a scientific basis for preventing the spread of HIV-1 strains among MSM and develop intervention measures.</p> </section> <section> <h3> Method</h3> <p>A cross-sectional study was conducted at the Guiyang Public Health Clinical Center. A total of 181 HIV-1-infected MSM who not received treatment at the center between 1 January 2020 and 31 December 2022 were selected. The HIV-1 <i>pol</i> region gene fragment, including the protease and reverse transcriptase regions, was amplified by nested PCR and RT-PCR. The maximum likelihood method was used to construct a phylogenetic tree for analyzing the HIV-1 genotypes in MSM. HIV-1 genotypic resistance was evaluated using the Stanford University HIV drug resistance database. A molecular transmission network of HIV was constructed and the risk of HIV-1 transmission was determined.</p> </section> <section> <h3> Results</h3> <p>We successfully amplified 173 <i>pol</i> gene sequences from blood samples obtained from 181 patients. The main subtype was CRF07_BC (60.69% [105/173]), followed by CRF01_AE (26.59% [46/173]), CRF08_BC (4.05% [7/173]), CRF55_01B (4.62% [8/173]), B (3.47% [6/173]), and C (0.58% [1/173]). The distribution of HIV-1 genotypes in MSM showed that there was a significant difference in the genotype composition of HIV-1-infected MSM according to registered residences and ages (<i>p</i> < .05). The CRF55_01B subtype accounted for the lowest proportion in Guiyang City and individuals >30 years of age. Multivariate logistic regression analysis of risk factors for drug resistance in HIV-1-infected MSM showed that the overall prevalence of pretreatment drug-resistant species was 12.72% (22/173), and age >30 years, CRF55_01B subtype, and CD4<sup>+</sup> T lymphocyte count >350 cells/mm<sup>3</sup> were risk factors for drug resistance in
背景:随着社会经济的发展和人口流动的增加,全国各省市男男性行为者(MSM)中1型人类免疫缺陷病毒(HIV-1)基因型分布差异明显。HIV-1 的高变异性和耐药性特征会导致耐药株的广泛传播,也可能导致抗逆转录病毒治疗失败和死亡率上升:本研究分析了贵州省贵阳市感染 HIV-1 的男男性行为者的耐药性基因型特征和 HIV-1 传播风险。研究旨在为预防 HIV-1 株系在男男性行为者中传播提供科学依据,并制定干预措施:方法:在贵阳市公共卫生临床中心进行了一项横断面研究。方法:在贵阳市公共卫生临床中心进行横断面研究,选取 2020 年 1 月 1 日至 2022 年 12 月 31 日期间未在该中心接受治疗的 181 名 HIV-1 感染男男性行为者。通过巢式 PCR 和 RT-PCR 扩增 HIV-1 pol 区基因片段,包括蛋白酶区和逆转录酶区。采用最大似然法构建系统发生树,分析 MSM 中的 HIV-1 基因型。利用斯坦福大学 HIV 耐药性数据库对 HIV-1 基因型耐药性进行了评估。构建了 HIV 分子传播网络,并确定了 HIV-1 传播的风险:我们从 181 名患者的血液样本中成功扩增出 173 个 pol 基因序列。主要亚型为 CRF07_BC(60.69% [105/173]),其次为 CRF01_AE(26.59% [46/173])、CRF08_BC(4.05% [7/173])、CRF55_01B(4.62% [8/173])、B(3.47% [6/173])和 C(0.58% [1/173])。MSM 中 HIV-1 基因型的分布显示,根据登记的居住地和年龄(P 30 岁),感染 HIV-1 的 MSM 的基因型构成存在显著差异。对感染 HIV-1 的 MSM 耐药风险因素的多变量 logistic 回归分析显示,治疗前耐药菌株的总患病率为 12.72%(22/173),年龄大于 30 岁、CRF55_01B 亚型和 CD4+ T 淋巴细胞计数大于 350 cells/mm3 是 MSM HIV-1 菌株耐药的风险因素。在治疗前耐药菌株中,非核苷类逆转录酶抑制剂耐药菌株≥1株的占9.25%(16/173),其次是蛋白酶抑制剂4.05%(7/173)和核苷类逆转录酶抑制剂1.73%(3/173)。对 CRF07_BC 和 CRF01_AE 基因型耐药的非核苷类逆转录酶抑制剂占多数。CRF55_01B 基因型最有可能携带 V179E 突变。分子网络包括 CRF07_BC 和 B 基因型。对影响加入网络比率的因素进行的多因素逻辑回归分析结果显示,年龄大于 30 岁的个体与结论中的个体相比,加入网络的可能性较低:贵阳男男性行为者的 HIV-1 基因型分布多样而复杂。主要基因型为 CRF07_BC 和 CRF01_AE。耐药突变率较高,治疗前耐药种类处于中等流行水平,NNRTIs是耐药突变的最常见部位。CRF07_BC 亚型和患者
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引用次数: 0
Analysis of Nirmatrelvir Entry into Pulmonary Lining Fluid in Patients with COVID-19: A Unique Perspective to Explore and Understand the Target Plasma Concentration of 292 ng/mL in Antiviral Activity 分析COVID-19患者体内Nirmatrelvir进入肺内衬液的情况:探索和理解抗病毒活性目标血浆浓度 292 纳克/毫升的独特视角
IF 3.1 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-15 DOI: 10.1002/iid3.70075
Wenjing Zhang, Lin Xia, Zhilong Yuan, Yang Jiao, Zhuo Wang

Background

Currently, the applicant has chosen a target plasma trough concentration for nirmatrelvir, which is adjusted to 292 ng/mL based on the drug's molecular weight (499.54 Daltons), its binding to human plasma proteins (69%), and the in vitro antiviral EC90 value (181 nM). However, the current exposure-effect relationships (ER) analysis of viral load in patients enrolled in the EPIC-HR study has not revealed clinically significant trends in the ER. Given that the lungs are the primary site of COVID-19 infection, we aim to further understand this exposure relationship by exploring and analyzing the penetration characteristics of nirmatrelvir in the lungs.

Objectives

To explore and understand the target plasma concentration of 292 ng/mL in antiviral activity.

Methods

We identified all critically ill patients with coronavirus disease 2019 who received nirmatrelvir/ritonavir treatment in the respiratory intensive care unit of Changhai hospital between January 2023 and October 2023. Samples of plasma and bronchoalveolar lavage fluid were obtained at pre-dose trough concentrations after administration of nirmatrelvir (NMV). The relationship between NMV levels in plasma and the epithelial lining fluid (ELF) was assessed by determining concentrations of NMV.

Results

There was a significant relationship between NMV levels in plasma and ELF (ELF = 0.4976*PLASMA- 204; R = 0.96), with a correlation whose slope (0.4976) suggested that the blood-to-ELF ratio of drug penetration was 2:1. A negative value from the equation indicates that NMV requires to reach baseline concentration to penetrate the ELF.

Conclusions

The relationship between NMV levels in plasma and ELF with low permeability and a negative baseline value suggests that the target plasma concentration of 292 ng/mL is insufficient for antiviral activity. This study provides a unique perspective to explore and understand no clinically meaningful trend of exposure-response relationships in patients enrolled in EPIC-HR.

背景:目前,申请人已为 nirmatrelvir 选择了目标血浆谷浓度,并根据该药物的分子量(499.54 道尔顿)、与人体血浆蛋白的结合率(69%)和体外抗病毒 EC90 值(181 nM)将其调整为 292 ng/mL。然而,目前对 EPIC-HR 研究入组患者病毒载量的暴露-效应关系(ER)分析并未显示出具有临床意义的 ER 趋势。鉴于肺部是 COVID-19 感染的主要部位,我们希望通过探索和分析 nirmatrelvir 在肺部的渗透特性来进一步了解这种暴露关系:探索并理解292纳克/毫升的血浆目标浓度在抗病毒活性中的作用:我们确定了2023年1月至2023年10月期间在长海医院呼吸重症监护室接受过尼马瑞韦/利托那韦治疗的所有2019年冠状病毒病重症患者。研究人员在服用尼尔马特韦(NMV)后,以用药前的谷值浓度采集血浆和支气管肺泡灌洗液样本。通过测定 NMV 的浓度,评估了血浆中 NMV 水平与上皮内衬液 (ELF) 之间的关系:血浆中的 NMV 水平与 ELF 之间存在明显关系(ELF = 0.4976*PLASMA- 204;R = 0.96),其斜率(0.4976)表明血液与 ELF 的药物渗透比为 2:1。等式中的负值表示 NMV 需要达到基线浓度才能穿透 ELF:血浆中的 NMV 水平与 ELF 之间的关系、低渗透性和负基线值表明,292 纳克/毫升的目标血浆浓度不足以产生抗病毒活性。这项研究提供了一个独特的视角,以探索和了解 EPIC-HR 登记患者中无临床意义的暴露-反应关系趋势。
{"title":"Analysis of Nirmatrelvir Entry into Pulmonary Lining Fluid in Patients with COVID-19: A Unique Perspective to Explore and Understand the Target Plasma Concentration of 292 ng/mL in Antiviral Activity","authors":"Wenjing Zhang,&nbsp;Lin Xia,&nbsp;Zhilong Yuan,&nbsp;Yang Jiao,&nbsp;Zhuo Wang","doi":"10.1002/iid3.70075","DOIUrl":"10.1002/iid3.70075","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Currently, the applicant has chosen a target plasma trough concentration for nirmatrelvir, which is adjusted to 292 ng/mL based on the drug's molecular weight (499.54 Daltons), its binding to human plasma proteins (69%), and the in vitro antiviral EC<sub>90</sub> value (181 nM). However, the current exposure-effect relationships (ER) analysis of viral load in patients enrolled in the EPIC-HR study has not revealed clinically significant trends in the ER. Given that the lungs are the primary site of COVID-19 infection, we aim to further understand this exposure relationship by exploring and analyzing the penetration characteristics of nirmatrelvir in the lungs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To explore and understand the target plasma concentration of 292 ng/mL in antiviral activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We identified all critically ill patients with coronavirus disease 2019 who received nirmatrelvir/ritonavir treatment in the respiratory intensive care unit of Changhai hospital between January 2023 and October 2023. Samples of plasma and bronchoalveolar lavage fluid were obtained at pre-dose trough concentrations after administration of nirmatrelvir (NMV). The relationship between NMV levels in plasma and the epithelial lining fluid (ELF) was assessed by determining concentrations of NMV.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There was a significant relationship between NMV levels in plasma and ELF (ELF = 0.4976*PLASMA- 204; <i>R</i> = 0.96), with a correlation whose slope (0.4976) suggested that the blood-to-ELF ratio of drug penetration was 2:1. A negative value from the equation indicates that NMV requires to reach baseline concentration to penetrate the ELF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The relationship between NMV levels in plasma and ELF with low permeability and a negative baseline value suggests that the target plasma concentration of 292 ng/mL is insufficient for antiviral activity. This study provides a unique perspective to explore and understand no clinically meaningful trend of exposure-response relationships in patients enrolled in EPIC-HR.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"12 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638841","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
Leukocyte Platelet-Rich Plasma-Derived Exosomes Restrained Macrophages Viability and Induced Apoptosis, NO Generation, and M1 Polarization 白细胞富血小板血浆衍生的外泌体抑制巨噬细胞活力并诱导凋亡、NO生成和M1极化
IF 3.1 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-15 DOI: 10.1002/iid3.70064
Xiong Li, Feifei Guo, Jiehua Deng, Jiasong Li, Jie Zhang, Ming Fu, Hui Fan

Background

Chronic refractory wounds refer to wounds that cannot be repaired timely. Platelet-rich plasma (PRP) has significant potential in chronic wound healing therapy. The exosomes isolated from PRP were proved to exhibit more effectiveness than PRP. However, the therapeutic potential of exosomes from PRP on chronic refractory wounds remained elusive. Hence, this study aimed to clarify the action of exosomes from PRP on chronic refractory wounds by evaluating the response of macrophages to exosomes.

Methods

Pure platelet-rich plasma (P-PRP) and leukocyte platelet-rich plasma (L-PRP) were prepared from the fasting venous blood of healthy volunteers. Exosomes were extracted from P-PRP and L-PRP using ultracentrifugation and identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot. Macrophages were obtained by inducing THP-1 cells with phorbol-12-myristate-13 acetate (PMA). The internalization of exosomes into macrophages was observed utilizing confocal laser scanning microscopy after being labeled with PKH67. Cell viability was determined by CCK-8 assay. Cell apoptosis was measured utilizing a flow cytometer. The polarization status of M1 and M2 macrophages were evaluated by detecting their markers. Nitric oxide (NO) detection was conducted using the commercial kit.

Results

Exosomes from P-PRP and L-PRP were absorbed by macrophages. Exosomes from L-PRP restrained viability and induced apoptosis of macrophages. Besides, exosomes from P-PRP promoted M2 polarization, and exosomes from L-PRP promoted M1 polarization. Furthermore, exosomes from L-PRP promoted NO generation of macrophages.

Conclusion

Exosomes from L-PRP restrained viability, induced apoptosis and NO generation of macrophages, and promoted M1 polarization, while exosomes from P-PRP increased M2 polarization. The exosomes from L-PRP presented a more effective effect on macrophages than that from P-PRP, making it a promising strategy for chronic refractory wound management.

背景:慢性难治性伤口是指无法及时修复的伤口。富血小板血浆(PRP)在慢性伤口愈合治疗中具有巨大潜力。事实证明,从血小板丰富血浆中分离出的外泌体比血小板丰富血浆更有效。然而,从 PRP 中分离出的外泌体对慢性难治性伤口的治疗潜力仍然难以捉摸。因此,本研究旨在通过评估巨噬细胞对外泌体的反应,阐明从血小板丰富血浆中提取的外泌体对慢性难治性伤口的作用:方法:从健康志愿者的空腹静脉血中制备富含血小板的纯血浆(P-PRP)和富含白细胞的血小板血浆(L-PRP)。使用超速离心法从P-PRP和L-PRP中提取外泌体,并通过透射电子显微镜(TEM)、纳米颗粒追踪分析(NTA)和Western印迹进行鉴定。用光滑醇-12-肉豆蔻酸-13 乙酸酯(PMA)诱导 THP-1 细胞获得巨噬细胞。用 PKH67 标记外泌体后,利用激光扫描共聚焦显微镜观察外泌体在巨噬细胞中的内化情况。细胞活力通过 CCK-8 试验测定。细胞凋亡用流式细胞仪测定。通过检测 M1 和 M2 巨噬细胞的标记物来评估它们的极化状态。使用商业试剂盒检测一氧化氮(NO):结果:P-PRP和L-PRP的外泌体被巨噬细胞吸收。L-PRP 的外泌体抑制巨噬细胞的活力并诱导其凋亡。此外,P-PRP 的外泌体可促进 M2 极化,L-PRP 的外泌体可促进 M1 极化。此外,L-PRP的外泌体还能促进巨噬细胞产生NO:结论:L-PRP的外泌体抑制了巨噬细胞的活力,诱导了巨噬细胞的凋亡和NO生成,并促进了M1极化,而P-PRP的外泌体增加了M2极化。L-PRP的外泌体对巨噬细胞的作用比P-PRP的外泌体更有效,因此L-PRP有望成为慢性难治性伤口治疗的一种策略。
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引用次数: 0
Macrophage polarization and metabolic reprogramming in abdominal aortic aneurysm 腹主动脉瘤中的巨噬细胞极化和代谢重编程。
IF 3.1 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-12 DOI: 10.1002/iid3.1268
Ningxin Hou, Hongmin Zhou, Jun Li, Xiaoxing Xiong, Hongping Deng, Sizheng Xiong

Background

Abdominal aortic aneurysm (AAA) is a macrovascular disease with high morbidity and mortality in the elderly. The limitation of the current management is that most patients can only be followed up until the AAA diameter increases to a threshold, and surgical intervention is recommended. The development of preventive and curative drugs for AAA is urgently needed. Macrophage-mediated immune inflammation is one of the key pathological links in the occurrence and development of AAA.

Aims

This review article aims to evaluate the impact of immunometabolism on macrophage biology and its role in AAA.

Methods

We analyze publications focusing on the polarization and metabolic reprogramming in macrophages as well as their potential impact on AAA, and summarize the potential interventions that are currently available to regulate these processes.

Results

The phenotypic and functional changes in macrophages are accompanied by significant alterations in metabolic pathways. The interaction between macrophage polarization and metabolic pathways significantly influences the progression of AAA.

Conclusion

Macrophage polarization is a manifestation of the gross dichotomy of macrophage function into pro-inflammatory killing and tissue repair, that is, classically activated M1 macrophages and alternatively activated M2 macrophages. Macrophage functions are closely linked to metabolic changes, and the emerging field of immunometabolism is providing unique insights into the role of macrophages in AAA. It is essential to further investigate the precise metabolic changes and their functional consequences in AAA-associated macrophages.

背景:腹主动脉瘤(AAA)是一种大血管疾病,在老年人中发病率和死亡率都很高。目前治疗的局限性在于,大多数患者只能接受随访,直到 AAA 直径增大到临界值,才建议进行手术治疗。目前急需开发预防和治疗 AAA 的药物。目的:这篇综述文章旨在评估免疫代谢对巨噬细胞生物学的影响及其在 AAA 中的作用:我们分析了有关巨噬细胞极化和代谢重编程及其对 AAA 潜在影响的出版物,并总结了目前可用于调节这些过程的潜在干预措施:结果:巨噬细胞的表型和功能变化伴随着代谢途径的显著改变。结果:巨噬细胞的表型和功能变化伴随着代谢途径的显著改变,巨噬细胞极化和代谢途径之间的相互作用对 AAA 的进展有重大影响:巨噬细胞极化是巨噬细胞功能严重二分化的表现,即经典活化的 M1 巨噬细胞和交替活化的 M2 巨噬细胞,分为促炎症杀伤和组织修复两种功能。巨噬细胞的功能与新陈代谢的变化密切相关,新兴的免疫代谢领域为了解巨噬细胞在 AAA 中的作用提供了独特的见解。进一步研究 AAA 相关巨噬细胞的精确代谢变化及其功能后果至关重要。
{"title":"Macrophage polarization and metabolic reprogramming in abdominal aortic aneurysm","authors":"Ningxin Hou,&nbsp;Hongmin Zhou,&nbsp;Jun Li,&nbsp;Xiaoxing Xiong,&nbsp;Hongping Deng,&nbsp;Sizheng Xiong","doi":"10.1002/iid3.1268","DOIUrl":"10.1002/iid3.1268","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Abdominal aortic aneurysm (AAA) is a macrovascular disease with high morbidity and mortality in the elderly. The limitation of the current management is that most patients can only be followed up until the AAA diameter increases to a threshold, and surgical intervention is recommended. The development of preventive and curative drugs for AAA is urgently needed. Macrophage-mediated immune inflammation is one of the key pathological links in the occurrence and development of AAA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This review article aims to evaluate the impact of immunometabolism on macrophage biology and its role in AAA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyze publications focusing on the polarization and metabolic reprogramming in macrophages as well as their potential impact on AAA, and summarize the potential interventions that are currently available to regulate these processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The phenotypic and functional changes in macrophages are accompanied by significant alterations in metabolic pathways. The interaction between macrophage polarization and metabolic pathways significantly influences the progression of AAA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Macrophage polarization is a manifestation of the gross dichotomy of macrophage function into pro-inflammatory killing and tissue repair, that is, classically activated M1 macrophages and alternatively activated M2 macrophages. Macrophage functions are closely linked to metabolic changes, and the emerging field of immunometabolism is providing unique insights into the role of macrophages in AAA. It is essential to further investigate the precise metabolic changes and their functional consequences in AAA-associated macrophages.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"12 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619361","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
Immunogenicity of two-dose sinopharm BBIB-CorV vaccine in Morocco: One-year follow-up and neutralizing activity against severe acute respiratory syndrome coronavirus 2 variants of concern 摩洛哥两剂国药集团 BBIB-CorV 疫苗的免疫原性:一年随访和针对严重急性呼吸系统综合征冠状病毒 2 变异株的中和活性。
IF 3.1 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-12 DOI: 10.1002/iid3.1359
Maha Ouarab, Elarbi Bouaiti, Zineb Rhazzar, Hicham El Annaz, Safae el kochri, Mouhssine Hemlali, Hamza Ghammaz, Omar Nyabi, Karim el Bakkouri, Nadia Touil, Mostafa Elouennass, Lamiae Belayachi, Jean Luc Gala, Khalid Ennibi, Elmostafa El Fahime

Background

This study aimed to evaluate the immunogenicity of a two-dose Sinopharm BBIB-CorV (Vero cells) vaccine against SARS-CoV-2, at 28 days, 6 months, and 1-year postvaccination. And assess the capacity of two-dose vaccine recipients to neutralize SARS-CoV-2 strains B.1 (Wuhan/D614G), B.1.1.7 (Alpha), AY.33 (Delta), or BA.5.2.2 (Omicron) variants of concern (VOCs).

Methods

A prospective matched case–control cohort study was conducted at the Military Hospital of Rabat, Morocco between February 2021 and 2022. Immunogenicity was evaluated by standard Microneutralization (MN) assay against four variants (Wuhan D614G, Alpha, Delta, and Omicron).

Results

The overall positive neutralizing rates for vaccine recipients against B.1 D614G were 72.09%, 74.82%, and 75.19% on 28-, 180-, 365- day respectively. The proportion of NAbs targeting the Wuhan D614G, and Alpha variants under the BBIBP-CorV vaccination was high on Day 28- and 6 months postvaccination.

Conclusion

The immunogenic response to the newly emerging SARS-CoV-2 variants of concern (VOCs), such as Delta and Omicron was comparatively reduced. As a result, it is recommended that additional boost vaccinations be considered.

研究背景本研究旨在评估国药集团 BBIB-CorV (Vero 细胞) 两剂疫苗在接种后 28 天、6 个月和 1 年对 SARS-CoV-2 的免疫原性。并评估两剂疫苗接种者中和 SARS-CoV-2 株 B.1(武汉/D614G)、B.1.1.7(阿尔法)、AY.33(德尔塔)或 BA.5.2.2(奥米克隆)变异株(VOCs)的能力:2021 年 2 月至 2022 年 2 月期间,摩洛哥拉巴特军事医院开展了一项前瞻性匹配病例对照队列研究。方法:2021 年 2 月至 2022 年 2 月期间,在摩洛哥拉巴特军事医院开展了一项前瞻性匹配病例对照队列研究,针对四种变异株(武汉 D614G、Alpha、Delta 和 Omicron)采用标准微中和(MN)检测法评估免疫原性:28 天、180 天和 365 天,疫苗接种者对 B.1 D614G 的总体阳性中和率分别为 72.09%、74.82% 和 75.19%。接种BBIBP-CorV疫苗后第28天和6个月,针对武汉D614G和Alpha变体的NAbs比例较高:结论:对新出现的 SARS-CoV-2 变异株(VOCs)(如 Delta 和 Omicron)的免疫原反应相对较低。因此,建议考虑进行额外的强化免疫接种。
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引用次数: 0
Identification of Vesicle-Mediated Transport-Related Genes for Predicting Prognosis, Immunotherapy Response, and Drug Screening in Cervical Cancer 鉴定用于预测宫颈癌预后、免疫疗法反应和药物筛选的囊泡介导转运相关基因
IF 3.1 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-08 DOI: 10.1002/iid3.70052
Shuai Lou, Hongqing Lv, Lin Zhang

Background

Cervical cancer is one of the most common malignancies among women. Vesicle-mediated transport mechanisms significantly influence tumor cell behavior through intercellular material exchange. However, prognostic significance in CC patients remains underexplored.

Research Design and Methods

We identified differentially expressed vesicle-mediated transport-related genes from TCGA and GeneCards datasets through differential expression analysis. We constructed a prognostic model using Cox regression and LASSO regression, categorized patients into high- and low-risk groups, and validated the model in the GEO data set. A nomogram integrating clinical features and risk scores demonstrated the model's independent prognostic capability. We analyzed tumor immune cell infiltration, immune checkpoints, and predicted immunotherapy responses in the high- and low-risk groups. Finally, we screened potential drugs for targeting CC and conducted drug-sensitivity analysis.

Results

We successfully established a 10-gene prognostic model based on VMTRGs. The low-risk group exhibited favorable prognosis, significant immune cell infiltration, and promising immunotherapy response, whereas the high-risk group showed higher sensitivity to chemotherapeutic agents such as Docetaxel and Paclitaxel. Potential drugs identified for targeting CC patients included Megestrol acetate, Lenvatinib, Adavosertib, and Barasertib.

Conclusions

The VMTRG-based prognostic model demonstrates reliable clinical prognostic value and enhances understanding of vesicle-mediated transport mechanisms in CC.

背景:宫颈癌是女性最常见的恶性肿瘤之一:宫颈癌是女性最常见的恶性肿瘤之一。囊泡介导的运输机制通过细胞间的物质交换对肿瘤细胞的行为产生重大影响。然而,宫颈癌患者的预后意义仍未得到充分探讨:我们通过差异表达分析从TCGA和GeneCards数据集中识别了差异表达的囊泡介导转运相关基因。我们利用 Cox 回归和 LASSO 回归构建了一个预后模型,将患者分为高风险组和低风险组,并在 GEO 数据集中验证了该模型。一个整合了临床特征和风险评分的提名图证明了该模型的独立预后能力。我们分析了肿瘤免疫细胞浸润、免疫检查点,并预测了高风险组和低风险组的免疫治疗反应。最后,我们筛选了针对CC的潜在药物,并进行了药物敏感性分析:结果:我们成功建立了基于VMTRGs的10基因预后模型。低危组预后良好,免疫细胞浸润明显,免疫治疗反应良好,而高危组对多西他赛和紫杉醇等化疗药物的敏感性较高。针对CC患者的潜在药物包括醋酸甲地孕酮、Lenvatinib、Adavosertib和Barasertib:基于VMTRG的预后模型具有可靠的临床预后价值,并加深了人们对CC中囊泡介导的转运机制的了解。
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引用次数: 0
The Effects of the oxLDL/β2GPI/anti-β2GPI Complex on Macrophage Autophagy and its Mechanism oxLDL/β2GPI/anti-β2GPI 复合物对巨噬细胞自噬的影响及其机制
IF 3.1 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-07 DOI: 10.1002/iid3.70058
Qianqian Wu, Guiting Zhang, Ting Wang, Hong Zhou

Background

Previous research has established that the oxidized low-density lipoprotein/β2-glycoprotein I/anti-β2-glycoprotein I antibody (oxLDL/β2GPI/anti-β2GPI) complex can stimulate macrophages to secrete molecules associated with atherosclerosis (AS), such as monocyte chemotactic protein 1 (MCP-1), tissue factor (TF), and tumor necrosis factor-α (TNF-α). This complex also enhances the uptake of oxLDL, thereby accelerating foam cell formation through the Toll-like receptor-4/nuclear factor kappa B (TLR4/NF-κB) pathway. Given the critical role of macrophage autophagy in the instability of vulnerable atherosclerotic plaques, it is imperative to investigate whether the oxLDL/β2GPI/anti-β2GPI complex influences macrophage autophagy in AS. This study aims to elucidate the effects and underlying mechanisms of the oxLDL/β2GPI/anti-β2GPI complex on macrophage autophagy in AS.

Methods

Experiments were conducted using murine macrophage RAW264.7 cells and the human monocytic cell line THP-1. Western blot analysis was employed to determine the expressions of autophagy-associated markers and signaling pathway proteins. Autophagosomes were detected through mRFP-GFP-LC3 adenoviral transfection and transmission electron microscopy (TEM).

Results

Treatment of macrophages with the oxLDL/β2GPI/anti-β2GPI complex resulted in decreased expressions of Beclin1 and LC3 proteins, alongside an upregulation of SQSTM1/P62 protein expression. Additionally, there was a reduction in the number of autophagosomes and autolysosomes. An increase in the phosphorylation levels of phosphoinositide-3-kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) was also observed. Notably, the expressions of autophagy-associated markers were partially restored when the TLR4/NF-κB and PI3K/AKT/mTOR pathways were inhibited by their respective inhibitors.

Conclusions

Our findings indicate that the oxLDL/β2GPI/anti-β2GPI complex inhibits macrophage autophagy in AS via the TLR4/NF-κB and PI3K/AKT/mTOR signaling pathways.

背景:先前的研究已经证实,氧化低密度脂蛋白/β2-糖蛋白I/抗-β2-糖蛋白I抗体(oxLDL/β2GPI/抗-β2GPI)复合物可刺激巨噬细胞分泌与动脉粥样硬化(AS)相关的分子,如单核细胞趋化蛋白1(MCP-1)、组织因子(TF)和肿瘤坏死因子-α(TNF-α)。这种复合物还能增强对氧化低密度脂蛋白的吸收,从而通过 Toll 样受体-4/核因子卡巴 B(TLR4/NF-κB)途径加速泡沫细胞的形成。鉴于巨噬细胞自噬在易损动脉粥样硬化斑块的不稳定性中起着关键作用,研究 oxLDL/β2GPI/anti-β2GPI 复合物是否会影响 AS 中巨噬细胞的自噬势在必行。本研究旨在阐明 oxLDL/β2GPI/anti-β2GPI 复合物对 AS 中巨噬细胞自噬的影响及其内在机制:使用鼠巨噬细胞 RAW264.7 和人单核细胞系 THP-1 进行实验。采用 Western 印迹分析法确定自噬相关标记物和信号通路蛋白的表达。通过 mRFP-GFP-LC3 腺病毒转染和透射电子显微镜(TEM)检测自噬体:结果:用 oxLDL/β2GPI/anti-β2GPI 复合物处理巨噬细胞后,Beclin1 和 LC3 蛋白表达量减少,同时 SQSTM1/P62 蛋白表达量上调。此外,自噬体和自溶酶体的数量也有所减少。还观察到磷酸肌醇-3-激酶(PI3K)、蛋白激酶 B(AKT)和哺乳动物雷帕霉素靶标(mTOR)的磷酸化水平增加。值得注意的是,当 TLR4/NF-κB 和 PI3K/AKT/mTOR 通路被各自的抑制剂抑制时,自噬相关标记物的表达得到了部分恢复:我们的研究结果表明,oxLDL/β2GPI/抗β2GPI复合物可通过TLR4/NF-κB和PI3K/AKT/mTOR信号通路抑制AS中巨噬细胞的自噬。
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引用次数: 0
Clinical Significance of Combined Detection of CCL22 and IL-1 as Potential New Bronchial Inflammatory Mediators in Children's Asthma 联合检测 CCL22 和 IL-1 作为儿童哮喘潜在新支气管炎性介质的临床意义
IF 3.1 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-07 DOI: 10.1002/iid3.70043
Lei Cui, Xiaozhen Song, Yanping Peng, Min Shi

Backgrounds

Severe asthma is a significant health burden because children with severe asthma are vulnerable to medication-related side effects, life-threatening deterioration, and impaired quality of life. However, there is a lack of data to elucidate the role of inflammatory variables in asthma. This study aimed to compare the levels of inflammatory factors in serum and sputum in children with acute and stable asthma to those in healthy children and the ability to predict clinical response to azithromycin therapy.

Methods

This study recruited 95 individuals aged 1−3 years old and collected data from January 2018 to 2020. We examined serum and sputum inflammatory factors and constructed the least absolute shrinkage and selection operator (LASSO) model. Predictive models were constructed through multifactor logistic regression and presented in the form of column-line plots. The performance of the column-line diagrams was measured by subject work characteristics (ROC) curves, calibration plots, and decision curve analysis (DCA). Then, filter-paper samples were collected from 45 children with acute asthma who were randomly assigned to receive either azithromycin (10 mg/kg, n = 22) or placebo (n = 23). Pretreatment levels of immune mediators were then analyzed and compared with clinical response to azithromycin therapy.

Results

Of the 95 eligible participants, 21 (22.11%) were healthy controls, 29 (30.53%) had stable asthma, and 45 (47.37%) had acute asthma. The levels of interferon-γ (IFN-γ), tumor necrosis factor-a (TNF-α), chemokine CCL22 (CCL22), interleukin 12 (IL-12), chemokine CCL4 (CCL4), chemokine CCL2 (CCL2), and chemokine CCL13 (CCL13)were significantly higher in the acute asthma group than in the stable asthma group. A logistic regression analysis was performed using CCL22 and IL-1 as independent variables. Additionally, IFN-γ, TNF-α, IL-1, IL-13, and CCL22 were identified in the LASSO model. Finally, we found that CCL22 and IL-1 were more responsive in predicting the response to azithromycin treatment.

Conclusion

Our results show that CCL22 and IL-1 are both representative markers during asthma symptom exacerbations and an immune mediator that can predict response to azithromycin therapy.

背景:严重哮喘是一种重大的健康负担,因为患有严重哮喘的儿童很容易出现与药物相关的副作用、危及生命的病情恶化和生活质量下降。然而,目前还缺乏数据来阐明炎症变量在哮喘中的作用。本研究旨在比较急性和稳定型哮喘儿童与健康儿童血清和痰中的炎症因子水平,以及预测阿奇霉素治疗临床反应的能力:本研究招募了95名1-3岁的个体,收集了2018年1月至2020年的数据。我们检测了血清和痰中的炎症因子,并构建了最小绝对收缩和选择算子(LASSO)模型。预测模型通过多因素逻辑回归构建,并以柱状线图的形式呈现。通过受试者工作特征(ROC)曲线、校准图和决策曲线分析(DCA)来衡量柱状线图的性能。然后,收集了 45 名急性哮喘患儿的滤纸样本,随机分配他们接受阿奇霉素(10 毫克/千克,n = 22)或安慰剂(n = 23)治疗。然后对治疗前的免疫介质水平进行分析,并与阿奇霉素治疗的临床反应进行比较:在 95 名符合条件的参与者中,21 人(22.11%)为健康对照组,29 人(30.53%)为稳定型哮喘患者,45 人(47.37%)为急性哮喘患者。急性哮喘组的干扰素-γ(IFN-γ)、肿瘤坏死因子-a(TNF-α)、趋化因子CCL22(CCL22)、白细胞介素12(IL-12)、趋化因子CCL4(CCL4)、趋化因子CCL2(CCL2)和趋化因子CCL13(CCL13)的水平明显高于稳定哮喘组。以 CCL22 和 IL-1 为自变量进行了逻辑回归分析。此外,在 LASSO 模型中还发现了 IFN-γ、TNF-α、IL-1、IL-13 和 CCL22。最后,我们发现CCL22和IL-1在预测阿奇霉素治疗反应方面反应更灵敏:结论:我们的研究结果表明,CCL22和IL-1既是哮喘症状加重时的代表性标志物,也是可以预测阿奇霉素治疗反应的免疫介质。
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引用次数: 0
期刊
Immunity, Inflammation and Disease
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