Immunity, Inflammation and Disease最新文献_第6页

The Joint Effect of Renal Function Status and Coagulation Biomarkers on In-Hospital Outcomes in Acute Ischemic Stroke Patients With Intravenous Thrombolysis 肾功能状况和凝血生物标志物对急性缺血性脑卒中静脉溶栓患者住院预后的共同影响

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-11 DOI: 10.1002/iid3.70099

Manli Lu, Junwen Xue, Yi Wang, Dongqin Chen, Yongjun Cao, Chongke Zhong, Xia Zhang

Objective

To demonstrate whether combining renal function status [estimating glomerular filtration rate (eGFR)] with coagulation biomarkers [fibrinogen (Fg) and d-dimer] is more beneficial in predicting in-hospital outcomes following intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients.

Methods

We studied 417 AIS patients with IVT. According to the cut-offs of coagulation biomarkers (Fg and d-dimer) and eGFR determined by receiver operating characteristic (ROC) curves, the patients were divided into four groups: LFLG (low Fg and low eGFR), LFHG (low Fg and high eGFR), HFLG (high Fg and low eGFR), and HFHG (high Fg and high eGFR); or LDLG (low d-dimer and low eGFR), LDHG (low d-dimer and high eGFR), HDLG (high d-dimer and low eGFR), and HDHG (high d-dimer and high eGFR). Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for poor outcomes at discharge and post-stroke pneumonia across the four groups.

Results

The patients in the HFLG and HDLG groups had the poorest prognosis at discharge and the highest risk of in-hospital pneumonia. They experienced 3.00 or 4.59 times higher risk of in-hospital pneumonia than those in the LFHG and LDHG groups (95%CI: 1.07–8.44, p < 0.05; 95%CI: 1.58–13.32, p = 0.005). Similarly, the risk of adverse outcome at discharge was 3.02 and 1.52 times higher in HFLG and HDLG groups (95%CI: 1.63–9.91, p < 0.005; 95%CI: 1.11–5.74, p < 0.05) compared to that in LFHG and LDHG groups. Adding eGFR and Fg or d-dimer to the risk model improved the risk reclassification for in-hospital pneumonia and functional outcomes at discharge.

Conclusion

Combining renal function status and coagulation biomarkers within 4.5 h after onset could better predict in-hospital outcomes of AIS patients with IVT.

目的：探讨结合肾功能状态[估计肾小球滤过率（eGFR）]和凝血生物标志物[纤维蛋白原（Fg）和d-二聚体]是否更有利于预测急性缺血性卒中（AIS）患者静脉溶栓（IVT）后的住院预后。方法：对417例AIS患者进行IVT治疗。根据受试者工作特征（ROC）曲线测定的凝血生物标志物（Fg、d-二聚体）和eGFR的截止值，将患者分为LFLG（低Fg、低eGFR）、LFHG（低Fg、高eGFR）、HFLG（高Fg、低eGFR）、HFHG（高Fg、高eGFR） 4组；或LDLG（低d二聚体和低eGFR）、LDHG（低d二聚体和高eGFR）、HDLG（高d二聚体和低eGFR）和HDHG（高d二聚体和高eGFR）。使用Logistic回归模型计算四组出院时不良结局和卒中后肺炎的比值比（ORs）和95%置信区间（ci）。结果：HFLG组和HDLG组患者出院时预后最差，院内肺炎发生风险最高。与LFHG组和LDHG组相比，他们发生院内肺炎的风险分别高出3.00和4.59倍（95%CI: 1.07-8.44, p）。结论：结合起病后4.5 h内的肾功能状况和凝血生物标志物可以更好地预测AIS合并IVT患者的院内结局。

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引用次数: 0

IL-17A Mediates Depressive-Like Symptoms by Inducing Microglia Activation in Psoriasiform Dermatitis Mice IL-17A通过诱导银屑病样皮炎小鼠小胶质细胞活化介导抑郁样症状

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-11 DOI: 10.1002/iid3.70092

Yue Dou, Jingjing You, Jing Wang, Xinxin Li, Yawen Lin, Bin Liu, Lei Ma

Background

Psoriasis is recognized as a systemic disease for its accompanying comorbidities, among which psychological disorders present a high incidence rate and affect patients’ life quality. Interleukin (IL)-17A is the central pathological factor in the pathogenesis and development of psoriasis.

Objective

To clarify if psoriasis-induced systemic IL-17A increase can mediate the neuronal inflammation and result in depressive-like symptoms.

Methods

Psoriasiform dermatitis model was established by imiquimod (IMQ) application on male BALB/c mice and IL-17A intervention was performed by lateral ventricular catheterization. Skin structural, histopathological characteristics, and behavioral tests were assessed. Serum IL-17A levels were detected by Enzyme-linked immunosorbent assay. mRNA expression of pro-inflammatory factors IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) as well as anti-inflammatory factors IL-4 and IL-10 in the hippocampus and cortex were measured by RT-qPCR. The number of microglia and hippocampal neurons was quantified by immunofluorescent assay.

Results

IMQ treatment resulted in significant skin structural and histopathological characters of psoriasiform dermatitis with elevated serum IL-17A levels, obvious depressive-like behaviors, microglia activation with increased IL-1β, IL-6, and TNF-α expression levels in the hippocampus and cortex, and notable inhibition of hippocampal neurogenesis. While, IL-17A neutralization by intracerebroventricular injection of anti-IL-17A antibody can remarkably inhibit microglia activation and decrease the abnormally increased expression levels of IL-1β, IL-6, and TNF-α in the hippocampus and cortex of psoriasiform dermatitis mice, promote hippocampal neurogenesis, thus alleviate the depressive-like behaviors.

Conclusion

In the pathological condition of psoriasis, systemic IL-17A elevation can trigger microglia activation, provoke pro-inflammation mediators to release, evoke neuroinflammation, subsequently inhibit hippocampal neurogenesis, and result in depression. IL-17A, as an important pathogenic factor in psoriasis, contributes to its critical role in mediating systemic inflammation and depression comorbidity.

背景：银屑病因其伴随的合并症而被认为是一种全身性疾病，其中心理障碍的发病率较高，影响患者的生活质量。白细胞介素(IL)-17A是银屑病发病发展的中心病理因子。目的：阐明银屑病诱导的全身IL-17A升高是否介导神经元炎症并导致抑郁样症状。方法：应用咪喹莫特（IMQ）建立雄性BALB/c小鼠银屑病样皮炎模型，采用侧脑室置管法干预IL-17A。评估皮肤结构、组织病理学特征和行为测试。采用酶联免疫吸附法检测血清IL-17A水平。采用RT-qPCR方法检测海马和皮质组织中促炎因子IL-1β、IL-6、肿瘤坏死因子-α (TNF-α)及抗炎因子IL-4、IL-10的mRNA表达。免疫荧光法定量测定小胶质细胞和海马神经元的数量。结果：IMQ治疗导致银屑病样皮炎的皮肤结构和组织病理学特征显著，血清IL-17A水平升高，抑郁样行为明显，海马和皮质小胶质细胞活化，IL-1β、IL-6和TNF-α表达水平升高，海马神经发生明显抑制。而脑室内注射抗IL-17A抗体中和IL-17A，可显著抑制银屑病样皮炎小鼠海马和皮质中异常升高的IL-1β、IL-6、TNF-α表达水平，促进海马神经发生，从而减轻抑郁样行为。结论：银屑病病理状态下，全身IL-17A升高可触发小胶质细胞活化，刺激促炎介质释放，引起神经炎症，抑制海马神经发生，导致抑郁。IL-17A是银屑病的重要致病因子，在介导全身性炎症和抑郁共病中起关键作用。

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引用次数: 0

Monocyte-Derived Macrophages Induce Alveolar Macrophages Death via TNF-α in Acute Lung Injury 单核细胞源性巨噬细胞通过TNF-α诱导急性肺损伤肺泡巨噬细胞死亡。

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-11 DOI: 10.1002/iid3.70081

Junjie Xiao, Fei Hou, Huan Wang, Ruixuan Wang, Ying Liu, Xiayan Wu, Lixin Xie

Introduction

Acute lung injury (ALI) and its subsequent progression to acute respiratory distress syndrome (ARDS) are severe respiratory conditions. They are marked by rapid lung function deterioration and extensive pulmonary inflammation, often resulting in critical patient outcomes. Alveolar macrophages (AMs) and monocyte-derived macrophages (MDMs) are two distinct subsets of lung macrophages present in the alveoli during ALI. Both are critical mediators of pulmonary inflammation. Our study examined the interplay between AMs and MDMs in the inflammatory environment of ALI/ARDS.

Methods

Mice were treated with lipopolysaccharide (LPS) to establish ALI models. The lung tissues of mice were subjected to hematoxylin-eosin staining to observe the degree of tissue damage. In vivo, CCR2-deficient mice or depleting peripheral blood mononuclear cells by clodronate liposomes were used to reduce MDMs recruitment. The bronchoalveolar lavage fluid (BALF) supernatants were used for cytokine and total protein analyses. AMs and MDMs in the BALF were analyzed by flow cytometry. The levels of AMs death were determined through propidium iodide staining and measured by flow cytometry. In vitro, primary AMs were exposed to MDM-conditioned medium or TNF-α, and their death levels were assessed under a fluorescence microscope with propidium iodide staining.

Results

AMs significantly decrease in number and undergo extensive cell death during ALI. The reduced MDMs recruitment can increase the number of AMs, reduce AMs death, and alleviate lung injury. In vitro, MDM-conditioned medium can induce AMs death and TNF-α is one of the major secretions. It indicates that TNF-α stimulation in vitro promotes AMs death. In vivo, MDMs are identified as the primary cells secreting TNF-α. Additionally, the treatment with TNF-α antagonists can reduce AMs death and the severity of lung injury.

Conclusion

Our study demonstrates that MDMs contribute to AMs death during ALI through TNF-α. Targeting TNF-α may offer a therapeutic strategy to mitigate AMs death and lung injury in ALI/ARDS.

急性肺损伤（ALI）及其随后发展为急性呼吸窘迫综合征（ARDS）是严重的呼吸系统疾病。它们的特点是肺功能迅速恶化和广泛的肺部炎症，往往导致严重的患者预后。肺泡巨噬细胞（AMs）和单核细胞源性巨噬细胞（MDMs）是ALI期间肺泡中存在的两个不同的肺巨噬细胞亚群。两者都是肺部炎症的重要介质。本研究探讨了急性呼吸窘迫综合征（ALI/ARDS）炎症环境中AMs和MDMs之间的相互作用。方法：采用脂多糖（LPS）处理小鼠，建立ALI模型。采用苏木精-伊红染色法观察小鼠肺组织损伤程度。在体内，用氯膦酸脂质体消耗ccr2缺陷小鼠或外周血单个核细胞来减少MDMs的募集。支气管肺泡灌洗液（BALF）上清液用于细胞因子和总蛋白分析。流式细胞术分析BALF中的AMs和MDMs。采用碘化丙啶染色和流式细胞术检测AMs死亡水平。在体外，将原代am暴露于mdm条件培养基或TNF-α中，在碘化丙啶染色的荧光显微镜下评估其死亡水平。结果：急性脑损伤时，am细胞数量明显减少，细胞大量死亡。MDMs募集减少可增加am数量，降低am死亡率，减轻肺损伤。在体外，mdm条件培养基可诱导AMs死亡，TNF-α是其主要分泌物之一。提示体外刺激TNF-α可促进AMs死亡。在体内，MDMs被鉴定为分泌TNF-α的原代细胞。此外，TNF-α拮抗剂治疗可降低AMs死亡率和肺损伤的严重程度。结论：我们的研究表明，MDMs通过TNF-α参与ALI期间AMs的死亡。靶向TNF-α可能为减轻急性呼吸窘迫综合征（ALI/ARDS）患者的AMs死亡和肺损伤提供治疗策略。

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引用次数: 0

N6-Methyladenosine Modification on the Function of Female Reproductive Development and Related Diseases n6 -甲基腺苷修饰对女性生殖发育功能及相关疾病的影响。

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-11 DOI: 10.1002/iid3.70089

Xiangrong Cui, Huihui Li, Xia Huang, Tingting Xue, Shu Wang, Xinyu Zhu, Xuan Jing

Background

N6-methyladenosine (m6A) modification is a widespread and reversible epigenetic alteration in eukaryotic mRNA, playing a pivotal role in various biological functions. Its significance in female reproductive development and associated diseases has recently become a focal point of research.

Objective

This review aims to consolidate current knowledge of the role of m6A modification in female reproductive tissues, emphasizing its regulatory dynamics, functional significance, and implications in reproductive health and disease.

Methods

A comprehensive analysis of recent studies focusing on m6A modification in ovarian development, oocyte maturation, embryo development, and the pathogenesis of reproductive diseases.

Results

m6A modification exhibits dynamic regulation in female reproductive tissues, influencing key developmental stages and processes. It plays critical roles in ovarian development, oocyte maturation, and embryo development, underpinning essential aspects of reproductive health. m6A modification is intricately involved in the pathogenesis of several reproductive diseases, including polycystic ovary syndrome (PCOS), premature ovarian failure (POF), and endometriosis, offering insights into potential molecular mechanisms and therapeutic targets.

Conclusion

The review highlights the crucial role of m6A modification in female reproductive development and related diseases. It underscores the need for further research to explore innovative diagnostic and therapeutic strategies for reproductive disorders, leveraging the insights gained from understanding m6A modification's impact on reproductive health.

背景：n6 -甲基腺苷（m6A）修饰是真核生物mRNA中广泛存在且可逆的表观遗传改变，在多种生物学功能中起着关键作用。其在女性生殖发育及相关疾病中的意义已成为近年来研究的焦点。目的：综述m6A修饰在女性生殖组织中的作用，强调其调控动态、功能意义及其在生殖健康和疾病中的意义。方法：综合分析近年来有关m6A修饰在卵巢发育、卵母细胞成熟、胚胎发育及生殖疾病发病机制中的研究进展。结果：m6A基因的修饰在雌性生殖组织中具有动态调控作用，影响关键发育阶段和过程。它在卵巢发育、卵母细胞成熟和胚胎发育中起着至关重要的作用，是生殖健康的重要方面。m6A修饰复杂地参与多种生殖疾病的发病机制，包括多囊卵巢综合征（PCOS）、卵巢早衰（POF）和子宫内膜异位症，为潜在的分子机制和治疗靶点提供了新的见解。结论：本文综述了m6A基因修饰在女性生殖发育及相关疾病中的重要作用。它强调需要进一步研究，探索生殖疾病的创新诊断和治疗战略，利用从了解m6A修饰对生殖健康的影响中获得的见解。

{"title":"N6-Methyladenosine Modification on the Function of Female Reproductive Development and Related Diseases","authors":"Xiangrong Cui, Huihui Li, Xia Huang, Tingting Xue, Shu Wang, Xinyu Zhu, Xuan Jing","doi":"10.1002/iid3.70089","DOIUrl":"10.1002/iid3.70089","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>N6-methyladenosine (m6A) modification is a widespread and reversible epigenetic alteration in eukaryotic mRNA, playing a pivotal role in various biological functions. Its significance in female reproductive development and associated diseases has recently become a focal point of research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This review aims to consolidate current knowledge of the role of m6A modification in female reproductive tissues, emphasizing its regulatory dynamics, functional significance, and implications in reproductive health and disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive analysis of recent studies focusing on m6A modification in ovarian development, oocyte maturation, embryo development, and the pathogenesis of reproductive diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>m6A modification exhibits dynamic regulation in female reproductive tissues, influencing key developmental stages and processes. It plays critical roles in ovarian development, oocyte maturation, and embryo development, underpinning essential aspects of reproductive health. m6A modification is intricately involved in the pathogenesis of several reproductive diseases, including polycystic ovary syndrome (PCOS), premature ovarian failure (POF), and endometriosis, offering insights into potential molecular mechanisms and therapeutic targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The review highlights the crucial role of m6A modification in female reproductive development and related diseases. It underscores the need for further research to explore innovative diagnostic and therapeutic strategies for reproductive disorders, leveraging the insights gained from understanding m6A modification's impact on reproductive health.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"12 12","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806158","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

Post-COVID immunity in patients with solid tumor or hematological malignancies treated with SARS-CoV-2 monoclonal antibodies 使用SARS-CoV-2单克隆抗体治疗实体瘤或血液系统恶性肿瘤患者的covid后免疫

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-10 DOI: 10.1002/iid3.70039

Gilberto Sabino-Santos, Cathryn E. Leggio, Sean M. Litwin, Najia Waheed, Shuangyi Bai, Sinem Ulusan, Anoli Karunathilake, Debra H. Elliott, Ashley R. Smira, Sruti Chandra, Lin Li, Bo Ning, Tony Hu, John S. Schieffelin, Bronwyn M. Gunn, James E. Robinson, Jyotsna Fuloria, Elizabeth B. Norton

<div> <section> <h3> Purpose</h3> <p>SARS-CoV-2 monoclonal antibody (mAB) therapy has effectively treated severe COVID-19, although how this contributes to protective antiviral immunity in settings of malignancy is poorly defined.</p> </section> <section> <h3> Patients and Methods</h3> <p>We evaluated the development of post-infection immunity in five patients with malignancies who received mAB therapy targeting spike protein for their PCR-confirmed SARS-CoV-2 infection in 2021, compared with non-mAB controls. Patients were identified from a larger study on oncology with a history or documented current infection with SARS-CoV-2. Subjects include two patients with lymphoma and CD20-depletion therapy, one with myeloma and two with solid tumor (stage IIA rectal adenocarcinoma and metastatic breast cancer). Cancer therapies and COVID vaccination history varied by patient. Blood samples (1–4 per patient) were collected 71–635 days post-mAB therapy. We employed clinical histories with comprehensive immunoprofiling analysis, including systems serology antibody isotyping and effector function, T-cell immunophenotyping for subset and memory cells, and sensitive blood viral RNA detection up to 2 years post-mAB therapy.</p> </section> <section> <h3> Results</h3> <p>B-cell deficiency was confirmed in 3/5 patients. All patients had detectable anti-spike and nucleoprotein antibody isotypes, effector functions, and neutralizing antibodies (which increased over time by subject) at similar levels to the control group. Virus-specific T-cell activation and phenotypes varied by time and patient. Spike-specific effector and memory CD8 + T-cells were significantly elevated in mAB subjects compared to the control group. SARS-CoV-2 viral RNA detection was also higher in mAB-treated patients. One patient on bortezomib therapy had unique alterations in these populations.</p> </section> <section> <h3> Conclusion</h3> <p>All mAB-treated patients with malignancies developed polyfunctional immunity humoral and T-cell immunity to SARS-CoV-2 even in the setting of B-cell deficiency. The evolution of this immunity, including new variant-specific antibodies, without secondary illnesses suggests that patients were protected from symptomatic re-infection, and mAB therapy did not blunt the development of host immunity. Future studies are warranted to better characterize immunologic memory over time with exposures to new viral variants, evaluate prolonged viral shedding and the continued use of appropriate mAB for infection in high-risk patients.</p> </section>

目的：SARS-CoV-2单克隆抗体（mAB）疗法已有效治疗重症COVID-19，尽管目前尚不清楚这如何在恶性肿瘤环境中促进保护性抗病毒免疫。患者和方法：我们评估了5例恶性肿瘤患者感染后免疫的发展，这些患者在2021年接受了针对刺突蛋白的单抗治疗，以治疗pcr确诊的SARS-CoV-2感染，与非单抗对照组相比。患者是从一项更大的肿瘤学研究中确定的，他们有SARS-CoV-2感染史或有记录的当前感染。研究对象包括2例淋巴瘤和cd20消耗治疗患者，1例骨髓瘤患者和2例实体瘤患者（IIA期直肠腺癌和转移性乳腺癌）。癌症治疗和COVID疫苗接种史因患者而异。单抗治疗后71-635天采集血样（每位患者1-4份）。我们利用临床病史进行全面的免疫谱分析，包括系统血清学抗体等型和效应功能，亚群和记忆细胞的t细胞免疫表型，以及单抗治疗后2年的敏感血液病毒RNA检测。结果：3/5患者确认b细胞缺乏。所有患者检测到的抗刺突和核蛋白抗体同型、效应功能和中和抗体（随受试者时间增加）水平与对照组相似。病毒特异性t细胞活化和表型随时间和患者而变化。与对照组相比，mAB患者的spike特异性效应细胞和记忆CD8 + t细胞显著升高。在单克隆抗体治疗的患者中，SARS-CoV-2病毒RNA检测也更高。一名接受硼替佐米治疗的患者在这些人群中有独特的改变。结论：即使在b细胞缺乏的情况下，所有接受单克隆抗体治疗的恶性肿瘤患者也对SARS-CoV-2产生了多功能免疫、体液免疫和t细胞免疫。这种免疫的进化，包括新的变异特异性抗体，没有继发性疾病，表明患者免受有症状的再感染，单克隆抗体治疗并没有削弱宿主免疫的发展。未来的研究有必要更好地描述暴露于新病毒变体的免疫记忆，评估长期的病毒脱落和继续使用适当的单克隆抗体治疗高危患者感染。

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引用次数: 0

Serum Level of RIPK1/3 Correlated With the Prognosis in ICU Patients With Acute Ischemic Stroke 急性缺血性脑卒中ICU患者血清RIPK1/3水平与预后的关系

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-10 DOI: 10.1002/iid3.70085

Jianhong Dong, Xinli Xiong

Background

Acute ischemic stroke (AIS) is a common cerebrovascular disease with high mortality. AIS patients in the intensive care unit (ICU) often have severe conditions that require close monitoring and timely treatment. Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 play important roles in cell apoptosis and inflammation. However, the relevance of serum RIPK1/3 to AIS patients in the ICU has not been clarified.

Objective

To explore the correlation of serum RIPK1 and RIPK3 with the prognosis of AIS patients in the ICU.

Methods

One hundred and twenty AIS patients were selected as the research subjects for the retrospective analysis. The subjects were grouped based on the volume of cerebral infarction and the score of the National Institute of Health Stroke Scale (NIHSS) and mRS. The correlation was explored using Pearson analysis. The predictive value was valued using the ROC curve.

Results

The content of serum RIPK1 and RIPK3 was gradually elevated with increased cerebral infarction volume and the severity of the disease (p < 0.05). Patients with poor prognosis had a higher content of serum RIPK1 and RIPK3 than those with good prognosis (p < 0.05). Serum RIPK1 and RIPK3 levels were positively correlated with infarct volume, NHISS, and mRS scores (p < 0.001). The area under the curve (AUC) of RIPK1 and RIPK3 for predicting the severity of AIS was 0.703, 0.883, and 0.912, respectively. The AUC for predicting poor prognosis of AIS was 0.797, 0.721, and 0.893, respectively. The cooperative detection of RIPK1 and RIPK3 had higher clinical value.

Conclusion

AIS patients in the ICU had abnormally elevated content of serum RIPK1 and RIPK3, which was closely related to the volume of cerebral infarction, severity, and prognosis. Combined detection of RIPK1 and RIPK3 might help to early identify the severity and evaluate the prognosis, providing a reference basis for clinical doctors to develop treatment strategies.

背景：急性缺血性脑卒中（Acute ischemic stroke， AIS）是一种常见的高致死率的脑血管疾病。重症监护病房（ICU）的AIS患者往往病情严重，需要密切监测和及时治疗。受体相互作用蛋白激酶1 （RIPK1）和RIPK3在细胞凋亡和炎症中起重要作用。然而，血清RIPK1/3与ICU AIS患者的相关性尚不明确。目的：探讨血清RIPK1、RIPK3与ICU AIS患者预后的相关性。方法：选取120例AIS患者作为研究对象，进行回顾性分析。根据脑梗死体积、美国国立卫生研究院卒中量表（NIHSS）评分和mrs评分进行分组，采用Pearson分析探讨相关性。采用ROC曲线对预测值进行评估。结果：血清RIPK1、RIPK3含量随脑梗死体积和病情严重程度的增加而逐渐升高(p)。结论：ICU AIS患者血清RIPK1、RIPK3含量异常升高，与脑梗死体积、病情严重程度及预后密切相关。联合检测RIPK1和RIPK3可能有助于早期识别严重程度和评估预后，为临床医生制定治疗策略提供参考依据。

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引用次数: 0

Blocking of Tim-3 Ameliorates Spinal Cord Ischemia-Reperfusion Injury Through Inhibiting Neuroinflammation and Promoting M1-to-M2 Phenotypic Polarization of Microglia 阻断Tim-3通过抑制神经炎症和促进小胶质细胞M1-to-M2表型极化改善脊髓缺血再灌注损伤

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-06 DOI: 10.1002/iid3.70084

Zhenxing Li, Binbin Zhou, Guanghui Chen, Xiangyu Yang, Han Su, Bolin Li

Background

Blocking of Tim-3 exerts therapeutic effects in a series of ischemia-reperfusion injury (IRI).

Methods

In this work, a cross-clamped aortic arch was conducted to establish SCIRI rat model. Besides, rat spinal microglia was subjected to OGD/R to mimic I/R-like conditions in vitro. The in vivo and in vitro therapeutic effects of Tim-3 antibody in SCIRI were investigated from these aspects: neuronal apoptosis, neuroinflammation, microglia activation, and polarization.

Results

It was verified that Tim-3 was highly expressed in spinal cord tissues of SCIRI rats and blocking of Tim-3 attenuated SCIRI-induced pathological injury, neuronal apoptosis, neuroinflammation, and microglia activation (M1 polarization). In addition, it was verified that Tim-3 was highly expressed in OGD/R-treated rat spinal microglia and blocking of Tim-3 attenuated OGD/R-induced inflammation and spinal microglia activation (M1 polarization).

Conclusions

Tim-3 antibody can exert therapeutic effects in SCIRI through inhibiting neuroinflammation and promoting microglia polarization from M1 to M2 phenotype.

背景：阻断Tim-3在一系列缺血再灌注损伤（IRI）中发挥治疗作用。方法：采用交叉夹紧主动脉弓建立SCIRI大鼠模型。此外，在体外对大鼠脊髓小胶质细胞进行OGD/R模拟I/R样条件。从神经元凋亡、神经炎症、小胶质细胞活化、极化等方面研究Tim-3抗体对SCIRI的体内外治疗作用。结果：证实Tim-3在scii大鼠脊髓组织中高表达，阻断Tim-3可减轻scii诱导的病理性损伤、神经元凋亡、神经炎症和小胶质细胞激活（M1极化）。此外，证实Tim-3在OGD/ r处理大鼠脊髓小胶质细胞中高表达，阻断Tim-3可减轻OGD/ r诱导的炎症和脊髓小胶质细胞激活（M1极化）。结论：Tim-3抗体可通过抑制神经炎症和促进小胶质细胞从M1向M2表型极化来发挥治疗scii的作用。

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引用次数: 0

The Diagnosis and Prognosis Value of Circulating Exosomal lncRNA MALAT1 and LNC_000226 in Patients With Acute Myocardial Infarction: An Observational Study 循环外泌体lncRNA MALAT1和lncr_000226在急性心肌梗死患者中的诊断和预后价值：一项观察性研究

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-06 DOI: 10.1002/iid3.70088

Xiaodong Gu, Jingyuan Hou, Ruiqiang Weng, Jiawei Rao, Sudong Liu

Background

Acute myocardial infarction (AMI) stands as a leading cause of global morbidity and mortality. This study aims to explore the potential roles of circulating exosomal lncRNA MALAT1 and LNC_000226 in AMI diagnosis and prognosis.

Methods

This retrospective observational study included 90 patients with AMI and 88 patients with normal coronary artery (NCA). Plasma exosomes were isolated via ultracentrifugation, and the levels of exosomal lncRNA MALAT1 and LNC_000226 were examined using qRT-PCR. Major adverse cardiovascular events (MACEs) that occurred during 1-year follow-up post-stent implantation were collected. The diagnostic value of exosomal MALAT1 and LNC_000226 was determined by receiver operating characteristic (ROC) analysis. The association between exosomal LNC_000226 and MACEs was assessed by Kaplan–Meier and Cox regression analysis.

Results

Both lncRNA MALAT1 and LNC_000226 levels in plasma exosomes were elevated in AMI patients compared to NCA controls. Moreover, LNC_000226 (AUC: 0.889, sensitivity: 82%, specificity: 72%) exhibited superior diagnostic performance compared to MALAT1 (AUC: 0.707, sensitivity: 71%, specificity: 57%). During 1-year follow-up period, the incidence of MACEs was significantly higher among patients with high exosomal LNC_000226 levels compared to those with low exosomal LNC_000226 levels [64% (29/45) vs. 40% (18/45), p < 0.05]. Multivariable Cox regression analysis revealed a positive association between exosomal LNC_000226 level and the risk of MACEs in AMI patients (HR: 1.959, 95% CI: 1.040–3.689).

Conclusion

Circulating exosomal lncRNA MALAT1 and LNC_000226 are promising biomarkers for diagnosing AMI, with LNC_000226 potentially indicating a prognosis.

背景：急性心肌梗死（AMI）是全球发病率和死亡率的主要原因。本研究旨在探讨循环外泌体lncRNA MALAT1和LNC_000226在AMI诊断和预后中的潜在作用。方法：回顾性观察研究纳入90例AMI患者和88例正常冠状动脉（NCA）患者。通过超离心分离血浆外泌体，采用qRT-PCR检测外泌体lncRNA MALAT1和lncr_000226的水平。收集支架植入术后1年随访期间发生的主要不良心血管事件（mace）。采用受试者工作特征（ROC）分析确定外泌体MALAT1和LNC_000226的诊断价值。采用Kaplan-Meier和Cox回归分析评估外泌体LNC_000226与mace的相关性。结果：与NCA对照组相比，AMI患者血浆外泌体中的lncRNA MALAT1和lncr_000226水平均升高。此外，LNC_000226 （AUC: 0.889，敏感性：82%，特异性：72%）的诊断性能优于MALAT1 （AUC: 0.707，敏感性：71%，特异性：57%）。在1年的随访期间，外显体LNC_000226高水平患者的mace发生率明显高于外显体LNC_000226低水平患者[64% (29/45)vs. 40%(18/45)]。p结论：循环外显体lncRNA MALAT1和LNC_000226是诊断AMI的有希望的生物标志物，LNC_000226可能指示预后。

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引用次数: 0

Association of the Inflammatory Burden Index With Increased Mortality Among Cancer Patients: Insights From the NHANES Study 癌症患者炎症负担指数与死亡率增加的关系：来自NHANES研究的见解

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-06 DOI: 10.1002/iid3.70067

Xiuxiu Qiu, Yiyi Zhang, Yingjie Zhu, Ming Yang, Li Tao

Background

The systemic inflammatory response significantly influences the progression and prognosis of various cancers. The novel Inflammatory Burden Index (IBI) was recently introduced as a biomarker to gauge systemic inflammation and evaluate cancer patient prognosis. However, studies investigating the relationship between IBI and mortality rates in cancer patients remain limited.

Methods

This study analyzed data from 2748 cancer patients enrolled in the National Health and Nutrition Examination Surveys between 1999 and 2018. We used weighted Cox regression analysis and restricted cubic spline models to examine the relationship between the IBI and mortality due to all causes, cardiovascular disease (CVD), and cancer. Furthermore, we employed Kaplan-Meier survival curves, subgroup analyses, and receiver operating characteristic curves to elaborate on these associations.

Results

Over a median follow-up period of 112 months, the cohort experienced 1067 deaths, including 320 from cancer, 239 attributable to heart disease, and 508 from various other causes. The Kaplan-Meier curve indicated that individuals in the higher quartiles of the IBI faced significantly increased mortality risks compared to those in lower quartiles. Analyses using weighted Cox proportional hazards models demonstrated that subjects in the top IBI quartile were at a substantially higher risk for all-cause mortality (Hazard Ratio [HR] 2.09, 95% Confidence Interval [CI] 1.67–2.62, p < 0.001), CVD mortality (HR = 1.95, 95% CI= 1.18–3.23, p = 0.010), and cancer mortality (HR = 2.06, 95% CI = 1.31–3.26, p = 0.002). Furthermore, stratification and interaction analyses affirmed the uniformity of these initial findings. The areas under the curve for the 3-, 5-, and 10-year survival predictions for all-cause mortality were 0.62, 0.62, and 0.67, respectively; for cardiovascular mortality, they were 0.64, 0.64, and 0.70; and for cancer mortality, they were 0.62, 0.77, and 0.70.

Conclusion

In cancer patients, higher IBI levels significantly correlate with increased mortality from all causes, CVD, and cancer-specific deaths. This index could possess considerable diagnostic and prognostic importance, possibly acting as a new biomarker for evaluating outcomes in cancer patients.

背景：全身炎症反应显著影响各种癌症的进展和预后。新的炎症负担指数（IBI）最近被引入作为衡量全身炎症和评估癌症患者预后的生物标志物。然而，调查IBI与癌症患者死亡率之间关系的研究仍然有限。方法：本研究分析了1999年至2018年参加全国健康与营养检查调查的2748名癌症患者的数据。我们使用加权Cox回归分析和限制三次样条模型来检验IBI与全因死亡率、心血管疾病（CVD）和癌症之间的关系。此外，我们采用Kaplan-Meier生存曲线、亚组分析和受试者工作特征曲线来详细说明这些关联。结果：在112个月的中位随访期间，该队列经历了1067例死亡，其中320例死于癌症，239例死于心脏病，508例死于各种其他原因。Kaplan-Meier曲线表明，IBI高四分位数的个体与低四分位数的个体相比，面临着显著增加的死亡风险。使用加权Cox比例风险模型进行的分析显示，IBI最高四分位数的受试者全因死亡率的风险明显更高（风险比[HR] 2.09, 95%置信区间[CI] 1.67-2.62, p）。结论：在癌症患者中，较高的IBI水平与全因死亡率、心血管疾病和癌症特异性死亡的增加显著相关。该指标具有相当大的诊断和预后重要性，可能作为评估癌症患者预后的新生物标志物。

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引用次数: 0

Serotype 3 Streptococcus pneumoniae Escapes the Immune Responses Induced by PCV13 in Mice With High Susceptibility to Infection 血清3型肺炎链球菌逃避PCV13诱导的高易感小鼠免疫应答

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease

Pub Date : 2024-12-06 DOI: 10.1002/iid3.70062

Giuliana S. Oliveira, Johanna Rivera, Tasson C. Rodrigues, Giovanna B. Carneiro, Orlando G. Ribeiro, Eliane N. Miyaji, Liise-anne Pirofski, Maria Leonor S. Oliveira

Background

Streptococcus pneumoniae (pneumococcus) is a common cause of respiratory and invasive infections in humans. PCV13, a pneumococcal conjugate vaccine used globally, is highly effective against diseases caused by pneumococcal serotypes included in its formulation. However, one of them, the serotype 3 (ST3) is still being relatively commonly isolated from patients, suggesting an escape from vaccine-induced immunity. The thick capsule produced by ST3 facilitates bacterial evasion from the immune system. Additionally, host immune responses may influence the outcome of ST3 infection. Here we evaluated the influence of inflammation in the adaptive immune responses and protection induced by PCV13 against ST3, using two outbred mice lines that were phenotypically selected for high (AIRmax) and low (AIRmin) inflammatory responses.

Methods

AIRmin and AIRmax mice were immunized with PCV13. Inbred BALB/c mice were used as reference for vaccine efficacy. Induction of IgG against polysaccharides (PS) from pneumococcal serotype 1 (ST1) and ST3 were evaluated by ELISA. Protection was tested against invasive infections with ST1 and ST3 pneumococcal strains. Sera were compared by IgG binding to pneumococcal surface, induction of pneumococcal agglutination and opsonophagocytosis. The phagocytic capacity of mice-derived neutrophils was also evaluated.

Results

Immunization of AIRmin, AIRmax and BALB/c mice with PCV13 induced IgG against PS from ST1 and ST3 pneumococci. Despite vaccination, AIRmin mice were not protected against fatal infection with ST3. Sera from AIRmin mice immunized with PCV13 presented lower levels of anti-PS3 IgG, with reduced capacity to bind to pneumococcal surface. Reduced capacity to induce opsonophagocytosis of ST3 pneumococci in vitro was also observed. Conversely, PCV13 protected AIRmin mice against fatal infection with ST1 and this correlated with the capacity of the sera to induce ST1 opsonophagocytosis.

Conclusions

Our results show that both host and bacterial features can influence the outcome of protection induced by PCV13 against ST3 pneumococcal infection.

背景：肺炎链球菌（肺炎球菌）是人类呼吸道和侵袭性感染的常见原因。PCV13是一种全球使用的肺炎球菌结合疫苗，对其配方中包括的肺炎球菌血清型引起的疾病非常有效。然而，其中一种，血清型3 （ST3）仍然相对普遍地从患者中分离出来，这表明从疫苗诱导的免疫中逃脱。ST3产生的厚胶囊有助于细菌逃避免疫系统。此外，宿主免疫反应可能影响ST3感染的结果。在这里，我们评估了炎症对适应性免疫反应的影响以及PCV13诱导的对ST3的保护作用，使用两种远交种小鼠系，表型上选择高（AIRmax）和低（AIRmin）炎症反应。方法：用PCV13免疫AIRmin和AIRmax小鼠。以近交系BALB/c小鼠为对照，观察疫苗的效力。采用ELISA法观察IgG对1型和3型肺炎球菌多糖（PS）的诱导作用。测试了对ST1和ST3肺炎球菌菌株侵袭性感染的保护作用。比较血清中IgG与肺炎球菌表面的结合、诱导肺炎球菌凝集和调理吞噬作用。小鼠源性中性粒细胞的吞噬能力也被评估。结果：用PCV13免疫AIRmin、AIRmax和BALB/c小鼠可诱导IgG抗ST1和ST3型肺炎球菌的PS。尽管接种了疫苗，但AIRmin小鼠对ST3致命感染没有保护。用PCV13免疫的AIRmin小鼠血清中抗ps3 IgG水平降低，与肺炎球菌表面的结合能力降低。体外还观察到ST3肺炎球菌诱导调理吞噬的能力降低。相反，PCV13保护AIRmin小鼠免受ST1致命感染，这与血清诱导ST1调性噬噬作用的能力相关。结论：我们的研究结果表明，宿主和细菌特征都可以影响PCV13对ST3肺炎球菌感染的保护效果。

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引用次数: 0