Cytokine最新文献_第2页

Interleukin 17 producing T cell responses in human chronic trichinellosis-insight from a case study 人类慢性旋毛虫病中产生白细胞介素 17 的 T 细胞反应--一项病例研究的启示。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-11-03 DOI: 10.1016/j.cyto.2024.156795

Chiara Della Bella , Chiara Medici , Sofia D’Elios , Marisa Benagiano , Alessandra Ludovisi , Maria Angeles Gomez-Morales , Mario M. D’Elios , Fabrizio Bruschi

Introduction

We studied the cellular immune response in a patient infected since 10 months (along with other 51 people) during a trichinellosis outbreak caused by Trichinella spp.

Methods

A 46 years old female resulted serologically positive for trichinellosis. We isolated peripheral blood mononuclear cells (PBMCs) and incubated them with excretory/secretory antigens (ESA) of Trichinella spiralis (T1) or Trichinella pseudospiralis (T4) to produce antigen specific T cell lines and clones, analysed for the phenotype (T helper or cytotoxic cells), for their T4 or T1 antigens specificity and for their cytokine profile (IFNγ, IL-17A, IL-4) by flow cytometry, thymidine incorporation assay and ELISpot.

Results

The test performed using ESA from T1 or T4 has identified the species responsible for infection as T. pseudospiralis since the proliferative responses (evaluated by CFSE, Carboxyfluorescein succinimidyl ester, FACS analysis) was higher for T4 (72,8%) than T1 (23.6 %) antigen. The cell lines produced significant levels of IFNγ, IL-4 and IL-17A after stimulation. From the T cell line obtained in response to T1 ESA, as regards CD4 + cells, 12 % Th2, 22.8 % Th1, 6.6 % Th17, 6 % Th0, 2.2 % Th1/Th17 and 0.7 % Th2/Th17, were obtained. From the T1-specific TCL we generated 15 clones. From the TCL specific for T4 ESA, as regards CD4+, 15.2 % Th2, 27.1 % Th1, 3 % Th17, 10.3 %Th0, 1.9 % Th1/Th17 and 1 % Th2/ Th17 were obtained. From such TCL 4 clones were isolated, 1Th2, 1 Th1, 1 Th17, 1 Th1/Th17 and no Th0 nor Th2/Th17.

Conclusions

By cellular immunology techniques the species responsible of the infection resulted T. pseudospiralis, confirming the results previously obtained by serology. For the first time it was revealed in a human chronic infection the presence of Th17 cells.

简介：我们研究了一名在由旋毛虫引起的旋毛虫病暴发中感染了 10 个月（以及其他 51 人）的患者的细胞免疫反应：我们研究了一名在由旋毛虫引起的旋毛虫病爆发期间感染了 10 个月的患者（以及其他 51 人）的细胞免疫反应：一名 46 岁女性的毛霉菌病血清学检测结果呈阳性。我们分离了外周血单核细胞（PBMCs），并将其与螺旋毛癣菌（T1）或假螺旋毛癣菌（T4）的排泄/分泌抗原（ESA）培养，以产生抗原特异性 T 细胞系和克隆、通过流式细胞术、胸腺嘧啶掺入试验和 ELISpot 分析表型（T 辅助细胞或细胞毒性细胞）、T4 或 T1 抗原特异性及其细胞因子谱（IFNγ、IL-17A、IL-4）。结果：使用 T1 或 T4 的 ESA 进行的检测确定了造成感染的物种为假丝酵母菌，因为 T4（72.8%）的增殖反应（通过 CFSE、羧基荧光素琥珀酰亚胺酯和 FACS 分析评估）高于 T1（23.6%）抗原。细胞系在受到刺激后会产生大量的 IFNγ、IL-4 和 IL-17A。从对 T1 ESA 有反应的 T 细胞系中获得的 CD4 + 细胞中，Th2 细胞占 12%，Th1 细胞占 22.8%，Th17 细胞占 6.6%，Th0 细胞占 6%，Th1/Th17 细胞占 2.2%，Th2/Th17 细胞占 0.7%。我们从 T1 特异性 TCL 中产生了 15 个克隆。从 T4 ESA 特异性 TCL 中获得了 15.2 % Th2、27.1 % Th1、3 % Th17、10.3 %Th0、1.9 % Th1/Th17 和 1 % Th2/Th17。从这些 TCL 中分离出 4 个克隆，1 个 Th2、1 个 Th1、1 个 Th17、1 个 Th1/Th17，没有 Th0 或 Th2/Th17：通过细胞免疫学技术，导致感染的物种是伪螺旋体，这证实了之前通过血清学获得的结果。在人类慢性感染中首次发现了 Th17 细胞的存在。

{"title":"Interleukin 17 producing T cell responses in human chronic trichinellosis-insight from a case study","authors":"Chiara Della Bella , Chiara Medici , Sofia D’Elios , Marisa Benagiano , Alessandra Ludovisi , Maria Angeles Gomez-Morales , Mario M. D’Elios , Fabrizio Bruschi","doi":"10.1016/j.cyto.2024.156795","DOIUrl":"10.1016/j.cyto.2024.156795","url":null,"abstract":"<div><h3>Introduction</h3><div>We studied the cellular immune response in a patient infected since 10 months (along with other 51 people) during a trichinellosis outbreak caused by <em>Trichinella</em> spp.</div></div><div><h3>Methods</h3><div>A 46 years old female resulted serologically positive for trichinellosis. We isolated peripheral blood mononuclear cells (PBMCs) and incubated them with excretory/secretory antigens (ESA) of <em>Trichinella spiralis</em> (T1) or <em>Trichinella pseudospiralis</em> (T4) to produce antigen specific T cell lines and clones, analysed for the phenotype (T helper or cytotoxic cells), for their T4 or T1 antigens specificity and for their cytokine profile (IFNγ, IL-17A, IL-4) by flow cytometry, thymidine incorporation assay and ELISpot.</div></div><div><h3>Results</h3><div>The test performed using ESA from T1 or T4 has identified the species responsible for infection as <em>T. pseudospiralis</em> since the proliferative responses (evaluated by CFSE, Carboxyfluorescein succinimidyl ester, FACS analysis) was higher for T4 (72,8%) than T1 (23.6 %) antigen. The cell lines produced significant levels of IFNγ, IL-4 and IL-17A after stimulation. From the T cell line obtained in response to T1 ESA, as regards CD4 + cells, 12 % Th2, 22.8 % Th1, 6.6 % Th17, 6 % Th0, 2.2 % Th1/Th17 and 0.7 % Th2/Th17, were obtained. From the T1-specific TCL we generated 15 clones. From the TCL specific for T4 ESA, as regards CD4+, 15.2 % Th2, 27.1 % Th1, 3 % Th17, 10.3 %Th0, 1.9 % Th1/Th17 and 1 % Th2/ Th17 were obtained. From such TCL 4 clones were isolated, 1Th2, 1 Th1, 1 Th17, 1 Th1/Th17 and no Th0 nor Th2/Th17.</div></div><div><h3>Conclusions</h3><div>By cellular immunology techniques the species responsible of the infection resulted <em>T. pseudospiralis</em>, confirming the results previously obtained by serology. For the first time it was revealed in a human chronic infection the presence of Th17 cells.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156795"},"PeriodicalIF":3.7,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Diphencyprone reduces the CD8+ lymphocytes and IL-4 and enhences IgG2a/IgG1 ratio in pathogenicity of acute leishmania major infection in BALB/c mice 在 BALB/c 小鼠急性利什曼原虫感染的致病性过程中，地芬诺酯可减少 CD8+ 淋巴细胞和 IL-4，并提高 IgG2a/IgG1 比率。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-11-02 DOI: 10.1016/j.cyto.2024.156792

Pourandokht Mousavian , Vahid Mashayekhi Goyonlo , Mohammad Javanbakht , Mahmoud Reza Jafari , Hamidreza Moosavian , Monovar Afzal Aghaei , Mohammadreza Malekzadeh

Background

The exact role of different immune cells and cytokines in control or promotion of intracellular growth of leishmania has still remained a controversial topic. The aim of the present study was to study effects of cellular changes and relevant cytokines in cell mediated immunity by diphencyprone (DCP) in pathogenicity of acute L.major infection in BALB/c mice.

Methods

45 healthy female BALB/c mice were injected with L. major promastigotes under the base of tail. The mice were randomly divided to three groups of 15 mice: (1) control group without any treatment. (2) acetone group: Acetone was applied topically on the cutaneous lesions weekly and (3) DCP group: DCP was applied topically on the cutaneous lesions with increasing concentrations to induce local allergy. The mice were followed by the end of eighth week, and then macroscopic changes, histopathology, immunology studies, and organ parasite burden were determined.

Results

In DCP group, in comparison to other groups the ulcer size and parasite burden in ulcer site and spleen increased, significantly. There was a deep lymphohistiocytic infiltration in the ulcer site. Total IgG, IgG1, and IgG2a levels as well as IgG2a/IgG1 ratio and intracellular IFN-gamma in CD8⁺ lymphocytes were significantly higher. IL4 and T CD8⁺ lymphocytes were significantly lower in DCP group. The IgG2a/IgG1 ratio was more than 1 in all groups.

Conclusion

Our findings demonstrated that DCP reduced the CD8⁺ lymphocytes and IL-4 production. In spite of increased IgG2a/IgG1 ratio, the parasite burden and inflammation severity increased in infected mice. The results can show the pivotal role of CD8⁺ lymphocytes in conjunction with Th1 lymphocytes in the control of acute leishmania infection in mice.

背景：不同的免疫细胞和细胞因子在控制或促进利什曼原虫细胞内生长中的确切作用仍是一个有争议的话题。本研究的目的是研究二苯基丙酮（DCP）对 BALB/c 小鼠急性利什曼原虫感染致病性的细胞变化和细胞介导免疫中相关细胞因子的影响。将小鼠随机分为三组，每组 15 只：（1）对照组，不做任何处理。(2）丙酮组：每周将丙酮局部涂抹在皮肤病变处；(3) DCP 组：在小鼠皮损处局部涂抹二氯丙醇，浓度不断增加，以诱发局部过敏。第八周结束时对小鼠进行随访，然后测定小鼠的宏观变化、组织病理学、免疫学研究和器官寄生虫负荷：结果：与其他组相比，DCP 组的溃疡面积和溃疡部位及脾脏的寄生虫量明显增加。溃疡部位有深层淋巴组织细胞浸润。总 IgG、IgG1 和 IgG2a 水平以及 IgG2a/IgG1 比率和 CD8+ 淋巴细胞内的 IFN-gamma 均明显升高。DCP组的IL4和T CD8+淋巴细胞明显降低。所有组的 IgG2a/IgG1 比值均大于 1：我们的研究结果表明，DCP 减少了 CD8+ 淋巴细胞和 IL-4 的产生。结论：我们的研究结果表明，DCP 减少了 CD8+ 淋巴细胞和 IL-4 的产生，尽管 IgG2a/IgG1 比率增加，但感染小鼠的寄生虫负荷和炎症严重程度却增加了。这些结果表明，CD8+淋巴细胞与 Th1 淋巴细胞一起在控制小鼠急性利什曼病感染中发挥着关键作用。

{"title":"Diphencyprone reduces the CD8+ lymphocytes and IL-4 and enhences IgG2a/IgG1 ratio in pathogenicity of acute leishmania major infection in BALB/c mice","authors":"Pourandokht Mousavian , Vahid Mashayekhi Goyonlo , Mohammad Javanbakht , Mahmoud Reza Jafari , Hamidreza Moosavian , Monovar Afzal Aghaei , Mohammadreza Malekzadeh","doi":"10.1016/j.cyto.2024.156792","DOIUrl":"10.1016/j.cyto.2024.156792","url":null,"abstract":"<div><h3>Background</h3><div>The exact role of different immune cells and cytokines in control or promotion of intracellular growth of <em>leishmania</em> has still remained a controversial topic. The aim of the present study was to study effects of cellular changes and relevant cytokines in cell mediated immunity by diphencyprone (DCP) in pathogenicity of acute <em>L.</em>major infection in BALB/c mice.</div></div><div><h3>Methods</h3><div>45 healthy female BALB/c mice were injected with <em>L. major</em> promastigotes under the base of tail. The mice were randomly divided to three groups of 15 mice: (1) control group without any treatment. (2) acetone group: Acetone was applied topically on the cutaneous lesions weekly and (3) DCP group: DCP was applied topically on the cutaneous lesions with increasing concentrations to induce local allergy. The mice were followed by the end of eighth week, and then macroscopic changes, histopathology, immunology studies, and organ parasite burden were determined.</div></div><div><h3>Results</h3><div>In DCP group, in comparison to other groups the ulcer size and parasite burden in ulcer site and spleen increased, significantly. There was a deep lymphohistiocytic infiltration in the ulcer site. Total IgG, IgG1, and IgG2a levels as well as IgG2a/IgG1 ratio and intracellular IFN-gamma in CD8<sup>+</sup> lymphocytes were significantly higher. IL4 and T CD8<sup>+</sup> lymphocytes were significantly lower in DCP group. The IgG2a/IgG1 ratio was more than 1 in all groups.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrated that DCP reduced the CD8<sup>+</sup> lymphocytes and IL-4 production. In spite of increased IgG2a/IgG1 ratio, the parasite burden and inflammation severity increased in infected mice. The results can show the pivotal role of CD8<sup>+</sup> lymphocytes in conjunction with Th1 lymphocytes in the control of acute <em>leishmania</em> infection in mice.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156792"},"PeriodicalIF":3.7,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the role of sTLR2: A novel biomarker for predicting septic-associated AKI 揭示 sTLR2 的作用：预测脓毒症相关性 AKI 的新型生物标记物。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-11-01 DOI: 10.1016/j.cyto.2024.156798

Li Yuan , Yongshuang Zhou , Ruiyu Wang , Xin Huang , Ruilin Tang , Fang Yan

Background

Acute kidney injury (AKI) is common in septic patients and strongly associated with adverse outcomes. The pathophysiology of AKI in septic patients remains elusive, and detection of patients at risk of AKI or at risk of progression to severe and persistent AKI is critical for timely and adequate support measures, including mitigating further renal damage. Therefore, identification of biomarkers associated with septic-associated AKI that contribute to improve septic AKI is an area of intensive research.

Methods

A total of 116 consecutive patients with sepsis were categorized into two groups (AKI and non-AKI) based on the occurrence of AKI within 24 h of admission to the intensive care unit (ICU). Serum levels of soluble TLR2 (sTLR2), as well as biomarkers such as interleukin(IL)-6, IL-22, IL-10, creatinine, urea, procalcitonin, hypersensitive C-reactive protein (hs-CRP), and D-Dimer (D2), were measured within 24 h after ICU admission. Demographic and clinical characteristics including sequential organ failure assessment (SOFA) scores and acute physiology and chronic health evaluation II (APACHE II) scores were recorded. Logistic regression analysis was conducted to identify potential predictive biomarkers. Receiver operating characteristic (ROC) curve analysis was employed to determine the optimal model for predicting septic-associated AKI.

Results

Patients in the AKI group exhibited significantly higher serum concentrations of IL-6, IL-10, sTLR2, creatinine, urea, hs-CRP, procalcitonin, D2 and lower serum albumin concentrations as well as higher APACHE II scores compared to those in the non-AKI group. Logistic regression analysis revealed that APACHE II scores, log10-transformed sTLR2 concentration, creatinine and D2 concentration were valuable predictors of AKI among septic patients. ROC curves demonstrated that log10-transformed sTLR2 concentration exhibited comparable predictive value to creatinine in determining the incidence of sepsis-associated AKI. The model with variables of APACHE II score, Log10-transformed serum TLR2 concentration, creatinine and D2 concentration yielded the greatest area under the curve of 0.863.

Conclusion

Elevated levels of sTLR2 in early-stage of septic patients may serve as a promising novel biomarker for predicting sepsis-associated AKI.

背景：急性肾损伤（AKI）是脓毒症患者的常见病，与不良预后密切相关。脓毒症患者急性肾损伤的病理生理学仍然难以捉摸，而检测有急性肾损伤风险或有进展为严重和持续性急性肾损伤风险的患者对于及时采取适当的支持措施（包括减轻进一步的肾损伤）至关重要。因此，鉴定与脓毒症相关性 AKI 有关的生物标志物以改善脓毒症 AKI 是一个需要深入研究的领域：方法：根据脓毒症患者入住重症监护室（ICU）后 24 小时内发生 AKI 的情况，将 116 名脓毒症患者分为两组（AKI 组和非 AKI 组）。研究人员在患者入住重症监护室 24 小时内测量了血清中可溶性 TLR2（sTLR2）的水平，以及白细胞介素（IL）-6、IL-22、IL-10、肌酐、尿素、降钙素原、超敏 C 反应蛋白（hs-CRP）和 D-二聚体（D2）等生物标志物。记录了人口统计学和临床特征，包括序贯器官衰竭评估（SOFA）评分和急性生理学和慢性健康评估 II（APACHE II）评分。进行逻辑回归分析以确定潜在的预测性生物标记物。采用接收者操作特征（ROC）曲线分析来确定预测脓毒症相关性 AKI 的最佳模型：结果：与非 AKI 组患者相比，AKI 组患者血清中 IL-6、IL-10、sTLR2、肌酐、尿素、hs-CRP、降钙素原、D2 的浓度明显升高，血清白蛋白浓度降低，APACHE II 评分升高。逻辑回归分析显示，APACHE II 评分、经 log10 变形的 sTLR2 浓度、肌酐和 D2 浓度是脓毒症患者发生 AKI 的重要预测指标。ROC 曲线显示，在确定脓毒症相关性 AKI 的发生率方面，对数 10 变形的 sTLR2 浓度与肌酐具有相当的预测价值。包含 APACHE II 评分、血清 TLR2 浓度对数 10 变形值、肌酐和 D2 浓度等变量的模型得出的曲线下面积最大，为 0.863：脓毒症患者早期的 sTLR2 水平升高可作为预测脓毒症相关性 AKI 的新型生物标记物。

{"title":"Unveiling the role of sTLR2: A novel biomarker for predicting septic-associated AKI","authors":"Li Yuan , Yongshuang Zhou , Ruiyu Wang , Xin Huang , Ruilin Tang , Fang Yan","doi":"10.1016/j.cyto.2024.156798","DOIUrl":"10.1016/j.cyto.2024.156798","url":null,"abstract":"<div><h3>Background</h3><div>Acute kidney injury (AKI) is common in septic patients and strongly associated with adverse outcomes. The pathophysiology of AKI in septic patients remains elusive, and detection of patients at risk of AKI or at risk of progression to severe and persistent AKI is critical for timely and adequate support measures, including mitigating further renal damage. Therefore, identification of biomarkers associated with septic-associated AKI that contribute to improve septic AKI is an area of intensive research.</div></div><div><h3>Methods</h3><div>A total of 116 consecutive patients with sepsis were categorized into two groups (AKI and non-AKI) based on the occurrence of AKI within 24 h of admission to the intensive care unit (ICU). Serum levels of soluble TLR2 (sTLR2), as well as biomarkers such as interleukin(IL)-6, IL-22, IL-10, creatinine, urea, procalcitonin, hypersensitive C-reactive protein (hs-CRP), and D-Dimer (D2), were measured within 24 h after ICU admission. Demographic and clinical characteristics including sequential organ failure assessment (SOFA) scores and acute physiology and chronic health evaluation II (APACHE II) scores were recorded. Logistic regression analysis was conducted to identify potential predictive biomarkers. Receiver operating characteristic (ROC) curve analysis was employed to determine the optimal model for predicting septic-associated AKI.</div></div><div><h3>Results</h3><div>Patients in the AKI group exhibited significantly higher serum concentrations of IL-6, IL-10, sTLR2, creatinine, urea, hs-CRP, procalcitonin, D2 and lower serum albumin concentrations as well as higher APACHE II scores compared to those in the non-AKI group. Logistic regression analysis revealed that APACHE II scores, log10-transformed sTLR2 concentration, creatinine and D2 concentration were valuable predictors of AKI among septic patients. ROC curves demonstrated that log10-transformed sTLR2 concentration exhibited comparable predictive value to creatinine in determining the incidence of sepsis-associated AKI. The model with variables of APACHE II score, Log10-transformed serum TLR2 concentration, creatinine and D2 concentration yielded the greatest area under the curve of 0.863.</div></div><div><h3>Conclusion</h3><div>Elevated levels of sTLR2 in early-stage of septic patients may serve as a promising novel biomarker for predicting sepsis-associated AKI.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156798"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Serum endocan (ESM-1) as diagnostic and prognostic biomarker in Multisystem inflammatory syndrome in children (MIS-C) 血清内切酶（ESM-1）作为儿童多系统炎症综合征（MIS-C）的诊断和预后生物标志物。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-11-01 DOI: 10.1016/j.cyto.2024.156797

Alessandro Cannavo , Monica Gelzo , Caterina Vinciguerra , Graziamaria Corbi , Marco Maglione , Vincenzo Tipo , Antonietta Giannattasio , Giuseppe Castaldo

Endothelial-cell-specific molecule-1 (ESM-1) also called endocan is a well-known biomarker for detecting inflammation, endothelial dysfunction (ED), and cardiovascular (CV) risk in COVID-19 patients. Upon SARS-CoV-2 infection, a small percentage of children develop Multisystem Inflammatory Syndrome in children (MIS-C). Whether endocan can be used as a biomarker of MIS-C is unknown. In this study, we assessed ESM-1 levels in MIS-C (n = 19) and healthy controls (HC; n = 17). We observed a significant increase in serum ESM-1 levels in MIS-C vs HC (p = 0.0074). In addition, ROC curve analysis demonstrated that this factor has a reasonable discriminatory power between MIS-C patients and HC (AUC of 0.7585). Notably, after one week of hospitalization and care, ESM-1 levels decreased, and this reduction was observed also for other inflammatory and pro-thrombotic markers like C-reactive protein, procalcitonin, fibrinogen, D-dimer, and ferritin, suggesting a general recovery trend in MIS-C patients. In fact, we observed that serum ESM-1 levels positively correlated with procalcitonin (PCT) (r = 0.468; p = 0.043). Finally, logistic regression analysis demonstrated an association between endocan levels and cardiac complications like myocarditis. Therefore, this study suggests that ESM-1 is a valuable diagnostic and prognostic biomarker in patients with MIS-C that may help identify those MIS-C patients at higher risk for cardiovascular complications and guide treatment strategies.

内皮细胞特异性分子-1（ESM-1）又称内皮素，是检测 COVID-19 患者炎症、内皮功能障碍（ED）和心血管（CV）风险的著名生物标志物。感染 SARS-CoV-2 后，一小部分儿童会出现儿童多系统炎症综合征（MIS-C）。内切酶能否作为儿童多系统炎症综合征（MIS-C）的生物标志物尚不清楚。在这项研究中，我们评估了 MIS-C（19 人）和健康对照组（17 人）的 ESM-1 水平。我们观察到，与健康对照组相比，MIS-C 患者血清中的 ESM-1 水平明显升高（p = 0.0074）。此外，ROC 曲线分析表明，该因子在 MIS-C 患者和 HC 之间具有合理的区分能力（AUC 为 0.7585）。值得注意的是，经过一周的住院和护理后，ESM-1 水平有所下降，而且其他炎症和促血栓形成标志物，如 C 反应蛋白、降钙素原、纤维蛋白原、D-二聚体和铁蛋白的水平也有所下降，这表明 MIS-C 患者的血清 ESM-1 水平呈总体恢复趋势。事实上，我们观察到血清 ESM-1 水平与降钙素原 (PCT) 呈正相关（r = 0.468; p = 0.043）。最后，逻辑回归分析表明，内切酶水平与心肌炎等心脏并发症存在关联。因此，这项研究表明，ESM-1 是 MIS-C 患者的一种有价值的诊断和预后生物标志物，可帮助识别心血管并发症风险较高的 MIS-C 患者并指导治疗策略。

{"title":"Serum endocan (ESM-1) as diagnostic and prognostic biomarker in Multisystem inflammatory syndrome in children (MIS-C)","authors":"Alessandro Cannavo , Monica Gelzo , Caterina Vinciguerra , Graziamaria Corbi , Marco Maglione , Vincenzo Tipo , Antonietta Giannattasio , Giuseppe Castaldo","doi":"10.1016/j.cyto.2024.156797","DOIUrl":"10.1016/j.cyto.2024.156797","url":null,"abstract":"<div><div>Endothelial-cell-specific molecule-1 (ESM-1) also called endocan is a well-known biomarker for detecting inflammation, endothelial dysfunction (ED), and cardiovascular (CV) risk in COVID-19 patients. Upon SARS-CoV-2 infection, a small percentage of children develop Multisystem Inflammatory Syndrome in children (MIS-C). Whether endocan can be used as a biomarker of MIS-C is unknown. In this study, we assessed ESM-1 levels in MIS-C (n = 19) and healthy controls (HC; n = 17). We observed a significant increase in serum ESM-1 levels in MIS-C vs HC (p = 0.0074). In addition, ROC curve analysis demonstrated that this factor has a reasonable discriminatory power between MIS-C patients and HC (AUC of 0.7585). Notably, after one week of hospitalization and care, ESM-1 levels decreased, and this reduction was observed also for other inflammatory and pro-thrombotic markers like C-reactive protein, procalcitonin, fibrinogen, D-dimer, and ferritin, suggesting a general recovery trend in MIS-C patients. In fact, we observed that serum ESM-1 levels positively correlated with procalcitonin (PCT) (r = 0.468; p = 0.043). Finally, logistic regression analysis demonstrated an association between endocan levels and cardiac complications like myocarditis. Therefore, this study suggests that ESM-1 is a valuable diagnostic and prognostic biomarker in patients with MIS-C that may help identify those MIS-C patients at higher risk for cardiovascular complications and guide treatment strategies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156797"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

FOXA2 inhibits the TLR4/NF-κB signaling pathway and alleviates inflammatory activation of macrophages in rheumatoid arthritis by repressing LY96 transcription FOXA2 可抑制 TLR4/NF-κB 信号通路，并通过抑制 LY96 转录缓解类风湿性关节炎巨噬细胞的炎症激活

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-10-31 DOI: 10.1016/j.cyto.2024.156796

Jin Cao , Zhaowen Yang

Background

Rheumatoid arthritis (RA) remains a devastating autoimmune disease characterized by joint damage, inflammation, and disability. This study investigates the function of lymphocyte antigen 96 (LY96) in the inflammatory response in RA and explores its regulatory mechanism.

Methods

A mouse model of RA was developed using type II collagen, and the LY96 expression in the ankle joint tissue was determined. Upstream regulators targeting LY96 were investigated using bioinformatics, followed by chromatin immunoprecipitation and luciferase reporter assays for validation. Gain- or loss-of-functions of LY96 and forkhead box A2 (FOXA2) were performed to analyze their roles in arthritis score, pathological changes, and inflammatory responses in mice. The effects of FOXA2 and LY96 on pro-inflammatory activation of macrophages were additionally investigated in vitro using a mouse RAW264.7 macrophage model with lipopolysaccharide treatment.

Results

LY96 mRNA and protein (MD-2) levels were increased in the RA mice. Knockdown of LY96 alleviated arthritis severity, joint deformities, inflammation, and cartilage destruction in mice. In vitro, the LY96 knockdown reduced the pro-inflammatory activation of RAW264.7 macrophages by inhibiting the TLR4/NF-κB inflammatory signaling transduction. FOXA2 was identified as a transcriptional repressor of LP96 poorly expressed in RA. Overexpression of FOXA2 similarly alleviated inflammation and reduced M1-type macrophages in vivo and in vitro. However, these changes were reversed by the additional LY96 upregulation.

Conclusion

This study suggests that FOXA2 represses LY96 transcription to inhibit the TLR4/NF-κB signaling transduction, thus reducing pro-inflammatory activation of macrophages in the context of RA.

背景类风湿性关节炎（RA）仍然是一种以关节损伤、炎症和残疾为特征的破坏性自身免疫性疾病。本研究调查了淋巴细胞抗原 96（LY96）在 RA 炎症反应中的功能，并探讨了其调控机制。方法利用 II 型胶原蛋白建立了 RA 小鼠模型，并测定了 LY96 在踝关节组织中的表达。采用生物信息学方法研究了以 LY96 为靶标的上游调控因子，并通过染色质免疫沉淀和荧光素酶报告实验进行了验证。对 LY96 和叉头框 A2（FOXA2）的功能增益或缺失进行了研究，以分析它们在小鼠关节炎评分、病理变化和炎症反应中的作用。此外，研究人员还利用小鼠 RAW264.7 巨噬细胞模型和脂多糖处理，在体外研究了 FOXA2 和 LY96 对巨噬细胞促炎激活的影响。敲除 LY96 可减轻小鼠关节炎的严重程度、关节畸形、炎症和软骨破坏。在体外，LY96基因敲除通过抑制TLR4/NF-κB炎症信号转导，减少了RAW264.7巨噬细胞的促炎激活。FOXA2被鉴定为LP96的转录抑制因子，在RA中表达较差。FOXA2 的过表达同样减轻了炎症，并减少了体内和体外的 M1 型巨噬细胞。结论这项研究表明，FOXA2抑制LY96转录以抑制TLR4/NF-κB信号转导，从而减少RA情况下巨噬细胞的促炎激活。

{"title":"FOXA2 inhibits the TLR4/NF-κB signaling pathway and alleviates inflammatory activation of macrophages in rheumatoid arthritis by repressing LY96 transcription","authors":"Jin Cao , Zhaowen Yang","doi":"10.1016/j.cyto.2024.156796","DOIUrl":"10.1016/j.cyto.2024.156796","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) remains a devastating autoimmune disease characterized by joint damage, inflammation, and disability. This study investigates the function of lymphocyte antigen 96 (LY96) in the inflammatory response in RA and explores its regulatory mechanism.</div></div><div><h3>Methods</h3><div>A mouse model of RA was developed using type II collagen, and the LY96 expression in the ankle joint tissue was determined. Upstream regulators targeting LY96 were investigated using bioinformatics, followed by chromatin immunoprecipitation and luciferase reporter assays for validation. Gain- or loss-of-functions of LY96 and forkhead box A2 (FOXA2) were performed to analyze their roles in arthritis score, pathological changes, and inflammatory responses in mice. The effects of FOXA2 and LY96 on pro-inflammatory activation of macrophages were additionally investigated <em>in vitro</em> using a mouse RAW264.7 macrophage model with lipopolysaccharide treatment.</div></div><div><h3>Results</h3><div>LY96 mRNA and protein (MD-2) levels were increased in the RA mice. Knockdown of LY96 alleviated arthritis severity, joint deformities, inflammation, and cartilage destruction in mice. <em>In vitro</em>, the LY96 knockdown reduced the pro-inflammatory activation of RAW264.7 macrophages by inhibiting the TLR4/NF-κB inflammatory signaling transduction. FOXA2 was identified as a transcriptional repressor of LP96 poorly expressed in RA. Overexpression of FOXA2 similarly alleviated inflammation and reduced M1-type macrophages <em>in vivo</em> and <em>in vitro</em>. However, these changes were reversed by the additional LY96 upregulation.</div></div><div><h3>Conclusion</h3><div>This study suggests that FOXA2 represses LY96 transcription to inhibit the TLR4/NF-κB signaling transduction, thus reducing pro-inflammatory activation of macrophages in the context of RA.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156796"},"PeriodicalIF":3.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Cytokines in chest tube drainage after pediatric cardiac surgery – Is chylothorax the only phenotype? 小儿心脏手术后胸管引流中的细胞因子--乳糜胸是唯一的表型吗？

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-10-29 DOI: 10.1016/j.cyto.2024.156786

Stephanie A. Goldstein , Melissa Winder , Camille Carter , J. Bair Diamond , Eric Bowles , Thomas B. Martins , Harry R. Hill , David K. Bailly

Background

Chylothorax after pediatric cardiac surgery is associated with increased morbidity and mortality. Poor understanding exists regarding inflammation within the pleural fluid. Our aim was to determine the relationship between proinflammatory markers and chylothorax.

Methods

This is a single-center prospective observational cohort study. Pediatric patients after cardiac surgery with >20 mL/kg/day of chest tube output were included from January 2022 through January 2023. The pleural fluid was tested for 13 cytokine concentrations using a multiplexed immunoassay and for albumin and C-Reactive Protein (CRP) levels. Bivariable comparisons and Spearman’s rank correlations were made.

Results

Out of 63 patients, chylothorax occurred in 20 (32 %), of which 10 (50 %) were neonates. Cytokine concentrations, CRP, and albumin levels were not different between chylothorax and non-chylothorax patients. Higher levels of four proinflammatory cytokines (IL-1β, IL-5, IL-8, IL-13) correlated with longer chest tube drainage (r = 0.29, 0.43, 0.28, 0.39 respectively). There were higher concentrations of IL-1β, IL-5, IL-8 and IL-13 in each progressively longer quartile of days to resolution. The longest quartile of days to resolution (12–50 days) showed the highest median cytokine levels.

Conclusions

The 13 cytokines tested were not associated with the diagnosis of chylothorax. However, higher IL-1β, IL-5, IL-8, and IL-13 concentrations were correlated with longer days to resolution. These findings demonstrate an inflammatory component to effusion resolution and may indicate an inflammatory phenotype that is distinct from chylothorax.

背景小儿心脏手术后出现的乳糜胸会增加发病率和死亡率。人们对胸腔积液中的炎症缺乏了解。我们的目的是确定促炎标记物与乳糜胸之间的关系。研究纳入了 2022 年 1 月至 2023 年 1 月期间胸腔插管输出量为 20 毫升/千克/天的心脏手术后小儿患者。使用多重免疫测定法检测胸腔积液中 13 种细胞因子的浓度以及白蛋白和 C 反应蛋白 (CRP) 的水平。结果在 63 例患者中，20 例（32%）发生了乳糜胸，其中 10 例（50%）为新生儿。乳糜胸患者和非乳糜胸患者的细胞因子浓度、CRP 和白蛋白水平没有差异。四种促炎细胞因子（IL-1β、IL-5、IL-8、IL-13）水平较高与胸管引流时间较长相关（r = 0.29、0.43、0.28、0.39）。在缓解天数逐渐延长的每个四分位数中，IL-1β、IL-5、IL-8 和 IL-13 的浓度都较高。结论测试的 13 种细胞因子与乳糜胸的诊断无关。然而，较高的IL-1β、IL-5、IL-8和IL-13浓度与较长的缓解天数相关。这些研究结果表明，渗出物的消退有炎症因素的影响，这可能表明炎症表型与乳糜胸不同。

{"title":"Cytokines in chest tube drainage after pediatric cardiac surgery – Is chylothorax the only phenotype?","authors":"Stephanie A. Goldstein , Melissa Winder , Camille Carter , J. Bair Diamond , Eric Bowles , Thomas B. Martins , Harry R. Hill , David K. Bailly","doi":"10.1016/j.cyto.2024.156786","DOIUrl":"10.1016/j.cyto.2024.156786","url":null,"abstract":"<div><h3>Background</h3><div>Chylothorax after pediatric cardiac surgery is associated with increased morbidity and mortality. Poor understanding exists regarding inflammation within the pleural fluid. Our aim was to determine the relationship between proinflammatory markers and chylothorax.</div></div><div><h3>Methods</h3><div>This is a single-center prospective observational cohort study. Pediatric patients after cardiac surgery with >20 mL/kg/day of chest tube output were included from January 2022 through January 2023. The pleural fluid was tested for 13 cytokine concentrations using a multiplexed immunoassay and for albumin and C-Reactive Protein (CRP) levels. Bivariable comparisons and Spearman’s rank correlations were made.</div></div><div><h3>Results</h3><div>Out of 63 patients, chylothorax occurred in 20 (32 %), of which 10 (50 %) were neonates. Cytokine concentrations, CRP, and albumin levels were not different between chylothorax and non-chylothorax patients. Higher levels of four proinflammatory cytokines (IL-1β, IL-5, IL-8, IL-13) correlated with longer chest tube drainage (<em>r</em> = 0.29, 0.43, 0.28, 0.39 respectively). There were higher concentrations of IL-1β, IL-5, IL-8 and IL-13 in each progressively longer quartile of days to resolution. The longest quartile of days to resolution (12–50 days) showed the highest median cytokine levels.</div></div><div><h3>Conclusions</h3><div>The 13 cytokines tested were not associated with the diagnosis of chylothorax. However, higher IL-1β, IL-5, IL-8, and IL-13 concentrations were correlated with longer days to resolution. These findings demonstrate an inflammatory component to effusion resolution and may indicate an inflammatory phenotype that is distinct from chylothorax.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156786"},"PeriodicalIF":3.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142537873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Strategies for the enhancement of IL-21 mediated antitumor activity in solid tumors 增强 IL-21 介导的实体瘤抗肿瘤活性的策略。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-10-29 DOI: 10.1016/j.cyto.2024.156787

You Wu , Jing Jiao , Shaoxian Wu , Jingting Jiang

Solid tumors significantly impact global health, necessitating enhanced prevention, early diagnosis, and treatment approaches. Tumor immunotherapy, notably through programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1), offers new hope to patients with advanced tumors, although many still do not benefit. Interleukin-21 (IL-21), a cytokine produced by certain immune cells, performs various biological functions by activating the JAK/STAT signaling pathway. Currently, recombinant IL-21 demonstrates promising antitumor activity and acceptable toxicity in several clinical trials. However, challenges such as side effects, off-target reactions, and a short half-life limit the effectiveness of cytokine-based immunotherapies. Therefore, researching enhanced IL-21 treatment strategies in solid tumors is crucial. Integrating IL-21 with various treatment modalities, including immune checkpoint inhibitors, additional cytokines, vaccines, or radiotherapy, is essential for improving response rates and prolonging patient survival. This review explores the specific mechanisms of IL-21 in prevalent high-incidence tumors, examines improved strategies for IL-21 in solid tumors, and aims to provide a theoretical basis for developing targeted treatment strategies.

实体瘤严重影响全球健康，需要加强预防、早期诊断和治疗方法。肿瘤免疫疗法，尤其是通过程序性细胞死亡蛋白 1（PD-1）和程序性细胞死亡配体 1（PD-L1）进行的免疫疗法，为晚期肿瘤患者带来了新的希望，尽管许多患者仍无法从中获益。白细胞介素-21（IL-21）是由某些免疫细胞产生的一种细胞因子，通过激活 JAK/STAT 信号通路发挥各种生物功能。目前，重组 IL-21 在多项临床试验中显示出良好的抗肿瘤活性和可接受的毒性。然而，副作用、脱靶反应和半衰期短等挑战限制了基于细胞因子的免疫疗法的有效性。因此，研究IL-21在实体瘤中的强化治疗策略至关重要。将IL-21与免疫检查点抑制剂、其他细胞因子、疫苗或放疗等各种治疗方式相结合，对于提高应答率和延长患者生存期至关重要。本综述探讨了IL-21在流行性高发肿瘤中的具体机制，研究了IL-21在实体瘤中的改进策略，旨在为制定靶向治疗策略提供理论依据。

{"title":"Strategies for the enhancement of IL-21 mediated antitumor activity in solid tumors","authors":"You Wu , Jing Jiao , Shaoxian Wu , Jingting Jiang","doi":"10.1016/j.cyto.2024.156787","DOIUrl":"10.1016/j.cyto.2024.156787","url":null,"abstract":"<div><div>Solid tumors significantly impact global health, necessitating enhanced prevention, early diagnosis, and treatment approaches. Tumor immunotherapy, notably through programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1), offers new hope to patients with advanced tumors, although many still do not benefit. Interleukin-21 (IL-21), a cytokine produced by certain immune cells, performs various biological functions by activating the JAK/STAT signaling pathway. Currently, recombinant IL-21 demonstrates promising antitumor activity and acceptable toxicity in several clinical trials. However, challenges such as side effects, off-target reactions, and a short half-life limit the effectiveness of cytokine-based immunotherapies. Therefore, researching enhanced IL-21 treatment strategies in solid tumors is crucial. Integrating IL-21 with various treatment modalities, including immune checkpoint inhibitors, additional cytokines, vaccines, or radiotherapy, is essential for improving response rates and prolonging patient survival. This review explores the specific mechanisms of IL-21 in prevalent high-incidence tumors, examines improved strategies for IL-21 in solid tumors, and aims to provide a theoretical basis for developing targeted treatment strategies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156787"},"PeriodicalIF":3.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cold water immersion regulates NLRP3 inflammasome pathway in the rat skeletal muscle after eccentric exercise by regulating the ubiquitin proteasome related proteins 冷水浸泡通过调节泛素蛋白酶体相关蛋白，调节大鼠骨骼肌在偏心运动后的 NLRP3 炎症小体通路。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-10-29 DOI: 10.1016/j.cyto.2024.156793

Farzaneh Abolfathi , Rouhollah Ranjbar , Mohammad Reza Tabandeh , Abdolhamid Habibi

Background

Eccentric exercise (ECC) can induce NLRP3-related inflammation in skeletal muscle tissue. Limited available data have shown that Cold water immersion (CWI) after ECC can suppress skeletal muscle inflammation. This study aims to investigate the effect of CWI after ECC on the NLRP3 inflammasome pathway, and the expression of ubiquitin–proteasome-related proteins (UPPs) in the skeletal muscle of rats.

Methods

Twenty-five male Wistar rats were randomly divided into control, ECC, ECC + CWI, ECC + NWI (normal water immersion), and ECC + AR (active recovery) groups. The Eccentric exercise consisted of 90 min of downhill running on a treadmill with a speed of 16 m/min and −16° incline. Animals in the NWI and CWI groups were immersed in water at 25 °C and 10 °C after ECC. Eventually, The soleus muscle was isolated and the expression of NLRP3, caspase-1, FBXL2, TRIM31, and PARKIN was evaluated by western blot. Tissue levels of IL-1β and IL-18 were measured by ELISA assay.

Results

ECC significantly increased the expression of NLRP3, caspase-1, and the tissue levels of IL-1β and IL-18 compared to the control group. After ECC, FBXL2, and PARKIN were downregulated, whereas TRIM31 was up-regulated (P < 0.05). CWI after ECC suppressed the NLRP3 inflammasome components and increased the protein levels of FBXL2 and TRIM31 at higher levels than other recovery methods (P < 0.05). CWI and AR had the same increase in PARKIN expression and the same decrease in CK level compared to the ECC group (P < 0.05).

Conclusion

Our results indicated that CWI increased the expression of NLRP3-related UPPs in concomitant with suppression of NLRP3 in the soleus muscle of rats after ECC. As a result the beneficial effects of CWI on the attenuation of skeletal muscle inflammation may contribute to an alteration of UPPs expression.

背景：偏心运动（ECC）可诱发骨骼肌组织中与 NLRP3 相关的炎症。有限的现有数据显示，ECC后冷水浸泡（CWI）可抑制骨骼肌炎症。本研究旨在探讨 ECC 后冷水浸泡对大鼠骨骼肌中 NLRP3 炎症小体通路和泛素蛋白酶体相关蛋白（UPPs）表达的影响：将 25 只雄性 Wistar 大鼠随机分为对照组、ECC 组、ECC + CWI 组、ECC + NWI 组（正常水浸泡）和 ECC + AR 组（积极恢复）。偏心运动包括在速度为 16 米/分钟、坡度为 -16° 的跑步机上进行 90 分钟的下坡跑步。偏心运动后，NWI 组和 CWI 组的动物分别浸泡在 25°C 和 10°C 的水中。最后，分离比目鱼肌，并用Western印迹法评估NLRP3、caspase-1、FBXL2、TRIM31和PARKIN的表达。用 ELISA 法检测组织中 IL-1β 和 IL-18 的水平：结果：与对照组相比，ECC明显增加了NLRP3、caspase-1的表达以及组织中IL-1β和IL-18的水平。ECC后，FBXL2和PARKIN被下调，而TRIM31被上调（P 结论：CWI增加了NLRP3、Caspase-1和IL-18的表达：我们的研究结果表明，CWI 增加了 NLRP3 相关 UPPs 的表达，同时抑制了 ECC 后大鼠比目鱼肌中 NLRP3 的表达。因此，CWI 对减轻骨骼肌炎症的有益作用可能是由于 UPPs 表达的改变。

{"title":"Cold water immersion regulates NLRP3 inflammasome pathway in the rat skeletal muscle after eccentric exercise by regulating the ubiquitin proteasome related proteins","authors":"Farzaneh Abolfathi , Rouhollah Ranjbar , Mohammad Reza Tabandeh , Abdolhamid Habibi","doi":"10.1016/j.cyto.2024.156793","DOIUrl":"10.1016/j.cyto.2024.156793","url":null,"abstract":"<div><h3>Background</h3><div>Eccentric exercise (ECC) can induce NLRP3-related inflammation in skeletal muscle tissue. Limited available data have shown that Cold water immersion (CWI) after ECC can suppress skeletal muscle inflammation. This study aims to investigate the effect of CWI after ECC on the NLRP3 inflammasome pathway, and the expression of ubiquitin–proteasome-related proteins (UPPs) in the skeletal muscle of rats.</div></div><div><h3>Methods</h3><div>Twenty-five male Wistar rats were randomly divided into control, ECC, ECC + CWI, ECC + NWI (normal water immersion), and ECC + AR (active recovery) groups. The Eccentric exercise consisted of 90 min of downhill running on a treadmill with a speed of 16 m/min and −16° incline. Animals in the NWI and CWI groups were immersed in water at 25 °C and 10 °C after ECC. Eventually, The soleus muscle was isolated and the expression of NLRP3, caspase-1, FBXL2, TRIM31, and PARKIN was evaluated by western blot. Tissue levels of IL-1β and IL-18 were measured by ELISA assay.</div></div><div><h3>Results</h3><div>ECC significantly increased the expression of NLRP3, caspase-1, and the tissue levels of IL-1β and IL-18 compared to the control group. After ECC, FBXL2, and PARKIN were downregulated, whereas TRIM31 was up-regulated (P < 0.05). CWI after ECC suppressed the NLRP3 inflammasome components and increased the protein levels of FBXL2 and TRIM31 at higher levels than other recovery methods (P < 0.05). CWI and AR had the same increase in PARKIN expression and the same decrease in CK level compared to the ECC group (P < 0.05).</div></div><div><h3>Conclusion</h3><div>Our results indicated that CWI increased the expression of NLRP3-related UPPs in concomitant with suppression of NLRP3 in the soleus muscle of rats after ECC. As a result the beneficial effects of CWI on the attenuation of skeletal muscle inflammation may contribute to an alteration of UPPs expression.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156793"},"PeriodicalIF":3.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluating the association between immunological proteins and common intestinal diseases using a bidirectional two-sample Mendelian randomization study 利用双向双样本孟德尔随机研究评估免疫蛋白与常见肠道疾病之间的关联。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-10-29 DOI: 10.1016/j.cyto.2024.156788

Ziwei Wang , Qiuai Shu , Jian Wu , Yutong Cheng , Xiru Liang , Xindi Huang , Yixin Liu , Zhiwei Tao , Jinhai Wang , Feihu Bai , Na Liu , Ning Xie

Dysregulation of intestinal homeostasis, characterized by imbalanced immunological proteins, contributes to the pathogenesis of common intestinal diseases, e.g., irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and colorectal cancer (CRC). However, the potential causal relationships between specific immunological proteins and these diseases remain to be fully elucidated. In this study, we employed the bidirectional two-sample Mendelian randomization analysis to infer potential causal relationships between representative immunological proteins and these intestinal diseases. Genome-wide association study (GWAS) summary statistics of IBS, IBD, and CRC were obtained from public databases and utilized in MR analysis. Multiple sensitivity analyses were performed to evaluate the robustness, with p-values adjusted using the Benjamini-Hochberg method for multiple comparisons. Our findings revealed a significant association between IL-1β (OR = 0.783, 95 % CI: 0.676 to 0.908, adjusted P = 0.048) and a decreased risk of IBS. Furthermore, genetic predisposition to IBS was related to the reduced levels of IL-25 (β = − 0.233, 95 % CI: −0.372 to −0.094, adjusted P = 0.047). Additionally, genetic predisposition to IBD was correlated with elevated levels of IL-6 (β = 0.046, 95 % CI: 0.022–0.069, adjusted P = 0.010). The levels of TNF-α (OR = 1.252, 95 % CI: 1.102 to 1.423, adjusted P = 0.047) were associated with an increased risk of CRC. Our study suggests associations between specific immunological proteins and intestinal diseases, which would provide valuable insights for developing targeted immunomodulation therapies for these conditions. Further investigation into underlying mechanisms remains a research priority in the future.

以免疫蛋白失衡为特征的肠道平衡失调是肠易激综合征（IBS）、炎症性肠病（IBD）和结直肠癌（CRC）等常见肠道疾病的发病机理之一。然而，特定免疫蛋白与这些疾病之间的潜在因果关系仍有待全面阐明。在本研究中，我们采用了双向双样本孟德尔随机分析法来推断代表性免疫蛋白与这些肠道疾病之间的潜在因果关系。我们从公共数据库中获得了 IBS、IBD 和 CRC 的全基因组关联研究（GWAS）摘要统计，并将其用于 MR 分析。为了评估稳健性，我们进行了多重敏感性分析，并使用 Benjamini-Hochberg 方法调整了多重比较的 p 值。我们的研究结果表明，IL-1β（OR = 0.783，95 % CI：0.676 至 0.908，调整后 P = 0.048）与肠易激综合征的发病风险降低之间存在显著关联。此外，肠易激综合征的遗传易感性与 IL-25 水平的降低有关（β = - 0.233，95 % CI：-0.372 至 -0.094，调整后 P = 0.047）。此外，IBD 遗传易感性与 IL-6 水平升高相关（β = 0.046，95 % CI：0.022-0.069，调整后 P = 0.010）。TNF-α 的水平（OR = 1.252，95 % CI：1.102 至 1.423，调整后 P = 0.047）与 CRC 风险的增加有关。我们的研究表明了特定免疫蛋白与肠道疾病之间的关联，这将为开发针对这些疾病的免疫调节疗法提供宝贵的见解。进一步研究其潜在机制仍是未来研究的重点。

{"title":"Evaluating the association between immunological proteins and common intestinal diseases using a bidirectional two-sample Mendelian randomization study","authors":"Ziwei Wang , Qiuai Shu , Jian Wu , Yutong Cheng , Xiru Liang , Xindi Huang , Yixin Liu , Zhiwei Tao , Jinhai Wang , Feihu Bai , Na Liu , Ning Xie","doi":"10.1016/j.cyto.2024.156788","DOIUrl":"10.1016/j.cyto.2024.156788","url":null,"abstract":"<div><div>Dysregulation of intestinal homeostasis, characterized by imbalanced immunological proteins, contributes to the pathogenesis of common intestinal diseases, <em>e.g.,</em> irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and colorectal cancer (CRC). However, the potential causal relationships between specific immunological proteins and these diseases remain to be fully elucidated. In this study, we employed the bidirectional two-sample Mendelian randomization analysis to infer potential causal relationships between representative immunological proteins and these intestinal diseases. Genome-wide association study (GWAS) summary statistics of IBS, IBD, and CRC were obtained from public databases and utilized in MR analysis. Multiple sensitivity analyses were performed to evaluate the robustness, with <em>p</em>-values adjusted using the Benjamini-Hochberg method for multiple comparisons. Our findings revealed a significant association between IL-1β (OR = 0.783, 95 % CI: 0.676 to 0.908, adjusted <em>P</em> = 0.048) and a decreased risk of IBS. Furthermore, genetic predisposition to IBS was related to the reduced levels of IL-25 (β = − 0.233, 95 % CI: −0.372 to −0.094, adjusted <em>P</em> = 0.047). Additionally, genetic predisposition to IBD was correlated with elevated levels of IL-6 (β = 0.046, 95 % CI: 0.022–0.069, adjusted <em>P</em> = 0.010). The levels of TNF-α (OR = 1.252, 95 % CI: 1.102 to 1.423, adjusted <em>P</em> = 0.047) were associated with an increased risk of CRC. Our study suggests associations between specific immunological proteins and intestinal diseases, which would provide valuable insights for developing targeted immunomodulation therapies for these conditions. Further investigation into underlying mechanisms remains a research priority in the future.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156788"},"PeriodicalIF":3.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dexamethasone in COVID-19 treatment: Analyzing monotherapy and combination therapy approaches 地塞米松在 COVID-19 治疗中的应用：分析单一疗法和联合疗法

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-10-29 DOI: 10.1016/j.cyto.2024.156794

Seyed Mohammadmahdi Meybodi , Venus Shahabi Rabori , Darya Salkhorde , Negar Jafari , Mahsa Zeinaly , Elham Mojodi , Prashant Kesharwani , Mohammadreza Saberiyan , Amirhossein Sahebkar

The COVID-19 pandemic has prompted the exploration of effective treatment options, with dexamethasone emerging as a key corticosteroid for severe cases. This review evaluates the efficacy and safety of dexamethasone, highlighting its ability to reduce mortality rates, alleviate acute respiratory distress syndrome (ARDS), and mitigate hyperinflammation. While dexamethasone shows therapeutic promise, potential adverse effects—including cardiovascular issues, neuropsychiatric complications, lung infections, and liver damage—necessitate careful monitoring and individualized treatment strategies. The review also addresses the debate over using dexamethasone alone versus in combination with other therapies targeting SARS-CoV-2, examining potential synergistic effects and drug resistance. In summary, dexamethasone is a valuable treatment option for COVID-19 but its risks highlight the need for tailored surveillance approaches. Further research is essential to establish clear guidelines for optimizing treatment and improving patient outcomes.

COVID-19 大流行促使人们探索有效的治疗方案，地塞米松成为治疗重症病例的主要皮质类固醇。本综述对地塞米松的疗效和安全性进行了评估，强调了其降低死亡率、缓解急性呼吸窘迫综合征（ARDS）和减轻高炎症反应的能力。虽然地塞米松显示出治疗前景，但其潜在的不良反应--包括心血管问题、神经精神并发症、肺部感染和肝脏损伤--需要仔细监测和个体化的治疗策略。综述还讨论了单独使用地塞米松还是与其他针对 SARS-CoV-2 的疗法联合使用的问题，研究了潜在的协同效应和耐药性。总之，地塞米松是治疗 COVID-19 的一个重要选择，但其风险突出表明需要有针对性的监测方法。进一步的研究对于制定优化治疗和改善患者预后的明确指南至关重要。

{"title":"Dexamethasone in COVID-19 treatment: Analyzing monotherapy and combination therapy approaches","authors":"Seyed Mohammadmahdi Meybodi , Venus Shahabi Rabori , Darya Salkhorde , Negar Jafari , Mahsa Zeinaly , Elham Mojodi , Prashant Kesharwani , Mohammadreza Saberiyan , Amirhossein Sahebkar","doi":"10.1016/j.cyto.2024.156794","DOIUrl":"10.1016/j.cyto.2024.156794","url":null,"abstract":"<div><div>The COVID-19 pandemic has prompted the exploration of effective treatment options, with dexamethasone emerging as a key corticosteroid for severe cases. This review evaluates the efficacy and safety of dexamethasone, highlighting its ability to reduce mortality rates, alleviate acute respiratory distress syndrome (ARDS), and mitigate hyperinflammation. While dexamethasone shows therapeutic promise, potential adverse effects—including cardiovascular issues, neuropsychiatric complications, lung infections, and liver damage—necessitate careful monitoring and individualized treatment strategies. The review also addresses the debate over using dexamethasone alone versus in combination with other therapies targeting SARS-CoV-2, examining potential synergistic effects and drug resistance. In summary, dexamethasone is a valuable treatment option for COVID-19 but its risks highlight the need for tailored surveillance approaches. Further research is essential to establish clear guidelines for optimizing treatment and improving patient outcomes.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"184 ","pages":"Article 156794"},"PeriodicalIF":3.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142537872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0