Cytokine最新文献_第2页

Integrated experimental and computational approaches to analyze TNF superfamily ligand–receptor interactions 综合实验和计算方法分析TNF超家族配体-受体相互作用

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2026-01-03 DOI: 10.1016/j.cyto.2025.157100

Anne-Laure Favier , Cyril Salama , Chloé Cervera , Diane Riccobono , Krisztina Nikovics

The TNF superfamily, composed of cytokines and their receptors, plays a central role in regulating immune responses, apoptosis, inflammation, and tissue regeneration. TNF itself is a key orchestrator of the cytokine cascade in many diseases and is often described as a “master regulator.” It engages in complex ligand-receptor interactions, making the study of these dynamics essential for the development of new therapeutic strategies.

This review summarizes the current experimental and computational tools used to study ligand–receptor interactions within the TNF superfamily, highlighting both their strengths and limitations. Particular attention is given to methods for analyzing protein–protein interactions, which are fundamental to deciphering the regulatory functions of this family. While traditional in vitro, in vivo, and in situ approaches have confirmed numerous authentic ligand–receptor pairs, in silico analyses reveal a much broader landscape of predicted interactions. These computational predictions do not represent experimentally validated binding events; rather, they indicate possible ligand–receptor compatibilities based on structural homology, interface similarity, and docking-derived binding energies. Such predictions suggest that the TNF interaction network may be more extensive than previously recognized, underscoring the need for systematic experimental validation to uncover additional biologically relevant interactions.

TNF超家族由细胞因子及其受体组成，在调节免疫应答、细胞凋亡、炎症和组织再生中起核心作用。TNF本身是许多疾病中细胞因子级联的关键协调者，通常被描述为“主调节器”。它参与复杂的配体-受体相互作用，使得这些动力学的研究对于开发新的治疗策略至关重要。这篇综述总结了目前用于研究TNF超家族中配体-受体相互作用的实验和计算工具，强调了它们的优势和局限性。特别关注分析蛋白质-蛋白质相互作用的方法，这是破译该家族调控功能的基础。虽然传统的体外、体内和原位方法已经证实了许多真实的配体-受体对，但计算机分析揭示了预测相互作用的更广泛的前景。这些计算预测并不代表实验验证的结合事件；相反，它们表明了基于结构同源性、界面相似性和对接衍生的结合能的可能的配体-受体相容性。这些预测表明，TNF相互作用网络可能比以前认识到的更广泛，强调需要系统的实验验证来发现其他生物学相关的相互作用。

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引用次数: 0

Shared inflammation in takotsubo syndrome and sepsis: Lipocalin-2 mediates neutrophil infiltration and cardiac damage takotsubo综合征和败血症的共同炎症：脂钙素-2介导中性粒细胞浸润和心脏损伤。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-12-30 DOI: 10.1016/j.cyto.2025.157102

Yuxi Huang , Piaorong Zeng , Tianmin Liu , Mei Xu , Wenyi Tang , Fangyuan Cheng , Zhijuan Zhou , Bairong Chen , Kan Liu , TouKun Chong , Jian Chen

Background

Takotsubo syndrome (TTS) and sepsis often co-occur with poor outcomes, yet their underlying molecular mechanisms remain to be elucidated. Transcriptomic analysis is employed to detect diagnostic biomarkers and reveal shared pathophysiological mechanisms in sepsis-associated TTS.

Methods

Myocardial gene expression data (TTS, sepsis, and controls) from GEO were analyzed to identify shared differentially expressed genes. WGCNA and PPI networks were used for candidate gene selection. Key genes were further refined using random forest and LASSO algorithms. Immune cell infiltration was assessed using CIBERSORT. Myocardial injury and gene expression in rat models were evaluated using HE staining, TUNEL assay, immunohistochemistry, qPCR, and Western blotting. Clinical validation was conducted using plasma samples from the China TTS Registry. t-tests and ANOVA were conducted via GraphPad Prism 8 software. A P-value < 0.05 was considered statistically significant.

Results

Lipocalin-2 (LCN2) was recognized as an important biomarker through WGCNA, PPI network analysis, and machine learning algorithms, showing strong predictive performance. Its expression was significantly associated with neutrophil infiltration and myocardial injury in TTS. Consistent with the bioinformatics findings, the TTS-sepsis comorbidity model showed elevated mRNA and protein levels of LCN2 in myocardial tissue, accompanied by increased neutrophil infiltration and severe cardiac injury. Clinical validation confirmed elevated plasma LCN2 levels in patients with sepsis-associated TTS, correlating with neutrophil counts, NT-proBNP, and cTnI levels.

Conclusion

LCN2 is identified as a key inflammatory mediator linking neutrophil-driven inflammation to myocardial injury in sepsis-associated TTS, with dual potential as a diagnostic biomarker and therapeutic target.

背景：Takotsubo综合征（TTS）和脓毒症通常同时发生，预后不良，但其潜在的分子机制仍有待阐明。转录组学分析用于检测诊断性生物标志物，揭示败血症相关TTS的共同病理生理机制。方法：分析GEO心肌基因表达数据（TTS、败血症和对照组），以确定共享的差异表达基因。利用WGCNA和PPI网络进行候选基因选择。使用随机森林和LASSO算法进一步细化关键基因。采用CIBERSORT评估免疫细胞浸润情况。采用HE染色、TUNEL法、免疫组化、qPCR、Western blotting等方法评价模型大鼠心肌损伤及基因表达。使用中国TTS注册中心的血浆样本进行临床验证。采用GraphPad Prism 8软件进行t检验和方差分析。结果：通过WGCNA、PPI网络分析和机器学习算法，Lipocalin-2 （LCN2）被认为是一种重要的生物标志物，具有较强的预测能力。其表达与TTS中性粒细胞浸润及心肌损伤有显著相关性。与生物信息学研究结果一致，tts -脓毒症共病模型显示心肌组织中LCN2 mRNA和蛋白水平升高，伴有中性粒细胞浸润增加和严重的心脏损伤。临床验证证实败血症相关TTS患者血浆LCN2水平升高，与中性粒细胞计数、NT-proBNP和cTnI水平相关。结论：LCN2被认为是脓毒症相关TTS中连接中性粒细胞驱动的炎症和心肌损伤的关键炎症介质，具有作为诊断生物标志物和治疗靶点的双重潜力。

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引用次数: 0

IL-8-, IL-12-, and VEGF-producing peripheral blood mononuclear cells enable differentiation between vertebral osteomyelitis and degenerative spinal diseases 白细胞介素-8-、白细胞介素-12-和产生vegf的外周血单个核细胞能够区分椎体骨髓炎和退行性脊柱疾病。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-12-30 DOI: 10.1016/j.cyto.2025.157104

Julia Schenk , Martin Thelen , Hans Anton Schlößer , Esther Mahabir

Vertebral osteomyelitis (VO) is a rare but serious spinal infection that presents significant challenges in early diagnosis and treatment. Diagnostic delays can result in severe complications, including neurological deficits, sepsis, organ failure, and death. In this study, we investigated the immune cell source of candidate cytokines – IL-6, IL-8, IL-12, and VEGF – with the aim of distinguishing VO from degenerative spinal diseases. Peripheral blood samples were collected pre-operatively and 40 to 56 days post-operatively. Cytokine production by major immune cell subsets within peripheral blood mononuclear cells (PBMCs) was analyzed using intracellular flow cytometry. Our findings indicate that pre-operative differentiation between VO and degenerative spinal diseases is feasible, particularly based on IL-8-positive CD8⁺ T-cells, IL-12-positive CD45⁺ lymphocytes, and VEGF-positive cells (including CD45⁺ cells, B-cells, T-cells, and CD8⁺ T-cells).

椎体骨髓炎（VO）是一种罕见但严重的脊柱感染，在早期诊断和治疗方面提出了重大挑战。诊断延误可导致严重的并发症，包括神经功能缺损、败血症、器官衰竭和死亡。在这项研究中，我们研究了候选细胞因子IL-6、IL-8、IL-12和VEGF的免疫细胞来源，目的是区分VO和退行性脊柱疾病。术前及术后40 ~ 56 d采集外周血标本。采用细胞内流式细胞术分析外周血单核细胞（PBMCs）内主要免疫细胞亚群产生的细胞因子。我们的研究结果表明术前区分VO和退行性脊柱疾病是可行的，特别是基于il -8阳性CD8+ t细胞、il -12阳性CD45+淋巴细胞和vegf阳性细胞（包括CD45+细胞、b细胞、t细胞和CD8+ t细胞）。

引用次数: 0

BPI modulates IL-1β-driven inflammation in periodontitis: A case-control study in gingival crevicular fluid BPI调节牙周炎中il -1β驱动的炎症：牙龈沟液的病例对照研究。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-12-29 DOI: 10.1016/j.cyto.2025.157093

Kazım Korkmaz, Nezahat Arzu Kayar, Kemal Üstün

Bactericidal/permeability-increasing protein (BPI) is a neutrophil-derived antimicrobial protein with high affinity for lipopolysaccharide (LPS) of gram-negative bacteria. This study aimed to compare BPI and interleukin-1 beta (IL-1β) levels in gingival crevicular fluid (GCF) between healthy and diseased individuals and to investigate their correlation with clinical parameters. We collected GCF from 50 consecutive ≥18 to <65 years old individuals with generalized periodontitis (P group) and 50 consecutive healthy individuals (H group). Clinical periodontal parameters were documented. IL-1β and BPI levels from GCF were analyzed via ELISA. Receiver operating characteristic (ROC) analysis was performed to evaluate diagnostic performance. GCF levels of BPI and IL-1β were significantly higher in the periodontitis group compared to healthy controls (p < 0.001). Both biomarkers demonstrated strong positive correlations with clinical parameters (p < 0.01). Strong positive correlations were found between GCF BPI levels and GCF IL-1β levels in the P group (P ˂ 0.01). ROC analysis revealed that BPI had a sensitivity of 100 % and an area under the curve (AUC) of 0.76 for detecting periodontitis but low specificity (50 %, AUC = 0.76), while IL-1β had a specificity of 86 % and sensitivity of 72 %. Elevated GCF levels of BPI and its correlation with IL-1β and clinical periodontal measures suggest that BPI might play a dual role in host response by contributing to microbial elimination and regulating inflammation.

杀菌/通透性增加蛋白（BPI）是一种中性粒细胞衍生的抗菌蛋白，对革兰氏阴性菌的脂多糖（LPS）具有高亲和力。本研究旨在比较健康和患病人群龈沟液（GCF）中BPI和白细胞介素-1β (IL-1β)水平，并探讨其与临床参数的相关性。我们收集了50例连续≥18 ~

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引用次数: 0

IL-7 promotes naïve T cell motility to enable T cell scanning of dendritic cells in the LN IL-7促进naïve T细胞运动，使T细胞扫描LN中的树突状细胞。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-12-29 DOI: 10.1016/j.cyto.2025.157105

Janie R. Byrum , Kimberly A. Morrissey , David J. Torres , Sreenivasa Rao Oruganti , Judy L. Cannon

IL-7 is a key regulator of naïve T cell homeostasis including T cell development, survival, and proliferation. IL-7 is highly expressed in lymph nodes (LNs), and we investigated the potential for IL-7 to drive naïve T cell movement in LNs. We show that IL-7 can mediate high speed T cell movement in vitro and in LNs. Downstream of IL-7R, T cell motility requires JAK1/3 and STAT5 activation, but mTOR signaling is not required. Using computational modeling and imaging of T cell motion in lymph nodes through two photon microscopy, we find that IL-7R-mediated motility accounts for T cell localization near DCs in the LN, suggesting that IL-7 can regulate naive T cell contacts with DCs. These data demonstrate a novel role for the IL-7/IL-7R pathway in controlling rapid T cell motility, showing that IL-7/IL-7R mediated T cell motion can facilitate efficient T cell-DC interactions in the LN.

IL-7是naïve T细胞稳态的关键调节因子，包括T细胞的发育、存活和增殖。IL-7在淋巴结（LNs）中高度表达，我们研究了IL-7在LNs中驱动naïve T细胞运动的潜力。我们发现IL-7可以在体外和LNs中介导T细胞的高速运动。在IL-7R的下游，T细胞的运动需要JAK1/3和STAT5的激活，但不需要mTOR信号。通过双光子显微镜对淋巴结中的T细胞运动进行计算建模和成像，我们发现il - 7r介导的运动解释了LN中dc附近T细胞的定位，这表明IL-7可以调节初始T细胞与dc的接触。这些数据证明了IL-7/IL-7R通路在控制T细胞快速运动中的新作用，表明IL-7/IL-7R介导的T细胞运动可以促进LN中T细胞- dc的有效相互作用。

引用次数: 0

Group 2 innate lymphoid cells (ILC2s) in childhood allergic diseases: A review of the mechanisms and therapeutic advances 2组先天淋巴样细胞（ILC2s）在儿童变应性疾病中的作用机制及治疗进展

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-12-27 DOI: 10.1016/j.cyto.2025.157101

Yun Zhang , Yaling Wu , Yingying Wang , Haoquan Zhou

Recent advances in pediatric immunology have clarified the pivotal role of group 2 innate lymphoid cells (ILC2s) in the pathophysiology of childhood allergic diseases. As key components of the innate immune system, ILC2s mediate the initiation and progression of these disorders. Their activation is triggered primarily by epithelial-derived cytokines, whose expression is highly elevated in children with allergies. Upon activation, ILC2s rapidly secrete type 2 cytokines, driving disease-specific pathogenesis. In allergic asthma, airway ILC2 expansion exacerbates eosinophilic inflammation, airway hyperresponsiveness, and remodeling; in allergic rhinitis, nasal mucosal ILC2 activation induces typical symptoms; and in food allergies, intestinal mucosal ILC2s cause epithelial damage and increased permeability, promoting allergic progression. These mechanistic insights have underpinned the development of innovative therapies. Clinical trials have confirmed the efficacy of treatments targeting ILC2-derived cytokines or their receptors: anti-IL-5 monoclonal antibodies (targeting the IL-5 ligand), anti-IL-13 monoclonal antibodies (targeting the IL-13 ligand), and anti-IL-4Rα monoclonal antibodies (targeting IL-4 receptor α and blocking IL-4/IL-13 signaling) are promising treatments for specific childhood allergic diseases. Emerging strategies targeting ILC2 activation pathways and modulating the microbiome to regulate ILC2 activity are under active investigation. Collectively, the past five years of research have improved the understanding of the mechanisms underlying childhood allergic diseases and established new treatment paradigms, with great potential to optimize clinical management and improve the outcomes of pediatric patients with allergies.

儿童免疫学的最新进展明确了2组先天淋巴样细胞（ILC2s）在儿童变应性疾病病理生理中的关键作用。作为先天免疫系统的关键组成部分，ILC2s介导这些疾病的发生和发展。它们的激活主要由上皮源性细胞因子触发，其表达在过敏儿童中高度升高。激活后，ILC2s迅速分泌2型细胞因子，驱动疾病特异性发病机制。在过敏性哮喘中，气道ILC2扩张加剧嗜酸性粒细胞炎症、气道高反应性和重塑；变应性鼻炎中，鼻黏膜ILC2激活可诱发典型症状；在食物过敏中，肠黏膜ILC2s引起上皮损伤和通透性增加，促进过敏进展。这些机制的洞见为创新疗法的发展奠定了基础。临床试验已经证实了针对ilc2来源的细胞因子或其受体的治疗的有效性：抗IL-5单克隆抗体（靶向IL-5配体）、抗IL-13单克隆抗体（靶向IL-13配体）和抗il - 4r α单克隆抗体（靶向IL-4受体α并阻断IL-4/IL-13信号传导）是治疗特定儿童过敏性疾病的有希望的治疗方法。针对ILC2激活途径和调节微生物组来调节ILC2活性的新兴策略正在积极研究中。总的来说，过去五年的研究提高了对儿童过敏疾病机制的理解，建立了新的治疗范式，具有优化临床管理和改善儿科过敏患者预后的巨大潜力。

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引用次数: 0

Dynamics of the immune cell signature associated with the development of immune-related adverse event: Results from longitudinal immune profiling 与免疫相关不良事件发展相关的免疫细胞特征动力学：来自纵向免疫分析的结果

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-12-26 DOI: 10.1016/j.cyto.2025.157103

Jiana Chen , Xiaoyan Si , Jiaqi Xu , Ziyue Zhou , Dan Yang , Mengyuan Wang , Li Zhang , Naixin Liang , Yunyun Fei , Xu Jiang , Huaxia Yang

Background

The dynamics of peripheral immune cells during the development of immune-related adverse events (irAEs) remain incompletely characterized, underscoring the need to elucidate their temporal patterns to uncover immune disturbances and identify biomarkers.

Methods

In this prospective study, patients with lung cancer receiving immune checkpoint inhibitors (ICIs) were enrolled at Peking Union Medical College Hospital and were consecutively followed up for the development of irAEs. Comprehensive immune profiling by multicolor flow cytometry of peripheral blood samples collected at baseline (T0), early (T1, 1-3 weeks) and late (T2, 3-6 months) treatment, and at the onset of irAE (Tae) was performed. We utilized Mfuzz clustering analysis to characterize immune cell trajectories and calculated the change in cell frequencies (ΔT) from T0 to subsequent time points (ΔTae, ΔT1, and ΔT2) to identify time-dependent immune signatures predictive of irAE occurrence, severity, and specific organ involvement.

Results

Among the 60 lung cancer patients who received ICIs, 26 (43.3 %) developed irAEs. Mfuzz clustering highlighted the distinct dynamics of CD8^mid T cells and CD14⁺CD16⁻HLA-DR^hi monocytes during ICIs therapy. During early treatment, the irAE group showed a greater increase in CD8⁺CTLA-4⁺ T cells and greater reductions in both total CD8⁺ T cells and double-negative B (DNB) cells. At ΔT2, the irAE group exhibited significantly greater alterations in CD4⁺CD25⁺ T cells, CD4⁺HLA-DR⁺ T cells, CD14⁺CD16⁻HLA-DR^hi monocytes, and CD8^mid T cells. At ΔTae, patients with irAEs exhibited a significant expansion of non-switched memory (NSM) B cells and a reduction in CD3⁺ T cells, whereas non-irAE patients showed opposite trends. Stratified analysis confirmed that the ΔT of NSM B cells, CD8⁺CTLA-4⁺ T cells, DNB cells, CD4⁺CD25⁺ T cells, and CD14⁺CD16⁻HLA-DR^hi monocytes aligned with both clinical severity and specific organ involvement of irAEs.

Conclusion

The distinct dynamics of cellular signatures during irAEs development provide potential biomarkers associated with the development of irAEs and shed novel insights into immune disturbance.

背景：在免疫相关不良事件（irAEs）发生过程中，外周免疫细胞的动态特征仍然不完全，这强调了阐明其时间模式以发现免疫紊乱和识别生物标志物的必要性。方法本前瞻性研究纳入北京协和医院接受免疫检查点抑制剂（ICIs）治疗的肺癌患者，对其irae的发展情况进行连续随访。采用多色流式细胞术对基线（T0）、早期（T1, 1-3周）和晚期（T2, 3-6个月）以及irAE发病（Tae）时收集的外周血样本进行综合免疫谱分析。我们利用Mfuzz聚类分析来表征免疫细胞轨迹，并计算细胞频率（ΔT）从T0到随后的时间点（ΔTae， ΔT1和ΔT2）的变化，以确定预测irAE发生，严重程度和特定器官累及的时间依赖性免疫特征。结果60例接受ICIs的肺癌患者中，26例（43.3%）发生了irae。Mfuzz聚类强调了在ICIs治疗期间CD8mid T细胞和CD14+CD16−HLA-DRhi单核细胞的不同动态。在早期治疗期间，irAE组显示CD8+CTLA-4+ T细胞增加较多，总CD8+ T细胞和双阴性B （DNB）细胞减少较多。在ΔT2， irAE组在CD4+CD25+ T细胞、CD4+HLA-DR+ T细胞、CD14+CD16−HLA-DRhi单核细胞和CD8mid T细胞中表现出更大的变化。在ΔTae，患有irae的患者表现出非开关记忆（NSM） B细胞的显著扩增和CD3+ T细胞的减少，而非irae患者则表现出相反的趋势。分层分析证实，NSM B细胞、CD8+CTLA-4+ T细胞、DNB细胞、CD4+CD25+ T细胞和CD14+CD16−HLA-DRhi单核细胞的ΔT与irAEs的临床严重程度和特异性器官累及程度一致。结论irAEs发展过程中细胞特征的不同动态提供了与irAEs发展相关的潜在生物标志物，并为免疫紊乱提供了新的见解。

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引用次数: 0

The role of HMGB1 in central nervous system (CNS) diseases: mechanisms and therapeutic perspectives HMGB1在中枢神经系统（CNS）疾病中的作用：机制和治疗前景

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-12-26 DOI: 10.1016/j.cyto.2025.157099

Ou Du, Yi-Jin Wu, Meng-Yang Li, Jun-Rong Du

Central nervous system (CNS) diseases represent a major global health burden and are among the leading causes of disability and mortality worldwide. The pathological mechanisms underlying CNS disorders are complex and multifactorial, involving processes such as neuroinflammation, oxidative stress, neuronal damage, and synaptic dysfunction. High-mobility group box 1 (HMGB1), a member of the high-mobility group box (HMGB) protein family, is predominantly localized in the nucleus under physiological conditions, where it contributes to DNA repair, transcriptional regulation, and other cellular functions. However, in various CNS pathologies—including stroke, traumatic brain injury (TBI), Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), glioblastoma (GBM), epilepsy, depression, multiple sclerosis (MS), and schizophrenia—HMGB1 is released or secreted into the extracellular space. There, it plays a key role in regulating neuroinflammation, cell death, cell migration, and tissue damage and repair, thereby contributing to disease pathogenesis and progression. HMGB1 not only functions as a critical regulator in the progression of CNS diseases but also serves as a biomarker for predicting poor clinical outcomes. Moreover, a growing body of evidence indicates that therapeutic strategies targeting HMGB1 can significantly alleviate pathological damage in various CNS disorders, highlighting its potential as a promising therapeutic target. This review comprehensively summarizes the structure, post-translational modifications, release mechanisms, and receptor systems of HMGB1, along with its roles and mechanisms in CNS diseases. It also discusses the potential of HMGB1 as a biomarker and examines emerging HMGB1-targeted therapeutic strategies, aiming to provide a theoretical foundation for the treatment and drug development of CNS disorders.

中枢神经系统（CNS）疾病是全球主要的健康负担，也是全球致残和死亡的主要原因之一。中枢神经系统疾病的病理机制是复杂和多因素的，涉及神经炎症、氧化应激、神经元损伤和突触功能障碍等过程。高迁移率组盒1 （HMGB1）是高迁移率组盒（HMGB）蛋白家族的一员，在生理条件下主要定位于细胞核，参与DNA修复、转录调控等细胞功能。然而，在各种中枢神经系统病理中——包括中风、创伤性脑损伤（TBI）、阿尔茨海默病（AD）、帕金森病（PD）、肌萎缩性侧索硬化症（ALS）、胶质母细胞瘤（GBM）、癫痫、抑郁症、多发性硬化症（MS）和精神分裂症——hmgb1被释放或分泌到细胞外空间。在那里，它在调节神经炎症、细胞死亡、细胞迁移和组织损伤和修复中起关键作用，从而促进疾病的发病和进展。HMGB1不仅在中枢神经系统疾病的进展中起着关键的调节作用，而且还可以作为预测不良临床结果的生物标志物。此外，越来越多的证据表明，靶向HMGB1的治疗策略可以显著减轻各种中枢神经系统疾病的病理损伤，突出了其作为有前景的治疗靶点的潜力。本文综述了HMGB1的结构、翻译后修饰、释放机制、受体系统及其在中枢神经系统疾病中的作用和机制。本文还讨论了HMGB1作为生物标志物的潜力，并探讨了新兴的HMGB1靶向治疗策略，旨在为中枢神经系统疾病的治疗和药物开发提供理论基础。

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引用次数: 0

Clinical observation of anti-PD-1/PD-L1 immunotherapy plus concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma 抗pd -1/PD-L1免疫联合同步放化疗治疗局部晚期食管鳞状细胞癌的临床观察

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-12-24 DOI: 10.1016/j.cyto.2025.157096

Xudong Sun , Dongmei Wu , Guangcheng Ding , Xueying Zhang , Changli Shi , Yulong Tian

Objective

This study analyzed the efficacy of the PD-1 inhibitor Sintilimab combined with concurrent chemoradiotherapy (CCRT) in patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC).

Methods

A retrospective study involved 177 individuals with unresectable advanced ESCC, treated with anti-PD-1/PD-L1 immunotherapy combined with CCRT. Patients were categorized into three groups: combined positive score (CPS) ≥ 50, 1 < CPS < 50, and CPS < 1. Clinical data and laboratory markers (carcinoembryonic antigen [CEA] and squamous cell carcinoma antigen [SCC-Ag]) were collected at baseline, 6, 12, and 24 months. PET/CT and CT scans assessed tumor response, ORR, and DCR. Kaplan-Meier curves analyzed the impact of CPS scores on progression-free survival (PFS) and overall survival (OS). Baseline data were matched at a 1:1 ratio by propensity score matching, followed by Cox regression analyses.

Results

No noticeable differences were present among the groups regarding gender, tumor location, prior chemotherapy, prior radiotherapy, or laboratory markers. After treatment, CEA and SCC-Ag levels significantly decreased, with the lowest levels observed at 24 months post-treatment. Higher CPS scores were associated with reduced CEA and SCC-Ag levels. PD-L1-positive groups (CPS > 1) had higher ORR and DCR than the PD-L1-negative group. As CPS scores increased, PFS and OS were significantly prolonged. Serum fibrinogen, CEA and SCC-Ag were identified as independent risk factors for OS; Serum CEA and SCC-Ag were independent risk factors affecting PFS.

Conclusion

Higher CPS scores are associated with improved PFS and OS in patients with locally advanced ESCC receiving anti-PD-1/PD-L1 immunotherapy combined with CCRT.

目的：分析PD-1抑制剂辛替单抗联合同步放化疗（CCRT）治疗无法切除的局部晚期食管鳞状细胞癌（ESCC）的疗效。方法：回顾性研究纳入177例不可切除的晚期ESCC患者，接受抗pd -1/PD-L1免疫治疗联合CCRT治疗。将患者分为三组：联合阳性评分(CPS)≥50,1。结果：各组在性别、肿瘤部位、既往化疗、放疗或实验室标志物方面无显著差异。治疗后，CEA和SCC-Ag水平显著降低，治疗后24个月最低。较高的CPS评分与较低的CEA和SCC-Ag水平相关。pd - l1阳性组（CPS >1）的ORR和DCR均高于pd - l1阴性组。随着CPS评分的增加，PFS和OS明显延长。血清纤维蛋白原、CEA和SCC-Ag被确定为OS的独立危险因素；血清CEA和SCC-Ag是影响PFS的独立危险因素。结论：接受抗pd -1/PD-L1免疫治疗联合CCRT治疗的局部晚期ESCC患者，CPS评分较高与PFS和OS改善相关。

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引用次数: 0

Relationship between IL-17_A and pneumococcal carriage in children aged under two years: data from a randomised controlled trial in Vietnam IL-17_A与两岁以下儿童肺炎球菌携带的关系：来自越南一项随机对照试验的数据

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-12-23 DOI: 10.1016/j.cyto.2025.157094

Zheng Quan Toh , Yi Ying Ma , Beth Temple , Jeremy Anderson , Hani Hosseini Far , Thanh V. Phan , Vo Thi Trang Dai , Tran Ngoc Huu , Nguyen Trong Toan , Kathryn Bright , Monica Larissa Nation , Belinda D. Ortika , Cattram Nguyen , Heidi Smith-Vaughan , Catherine Satzke , Kim Mulholland , Paul V. Licciardi

Objective

Pneumococcal carriage is a prerequisite for invasive pneumococcal disease (IPD). Interleukin (IL)-17 A and IL-17 A-producing cells are involved in the clearance of pneumococcal carriage in adults, but their role in children is unclear. This study aims to examine the relationship between IL-17 A, IL-17 A-related cytokines (IL-22, IL-23, IFNγ) and IL-17 A-producing cells and pneumococcal carriage in children aged under two years.

Methods

Blood samples (n = 143) collected from unvaccinated children at 18 months (m) of age and nasopharyngeal swabs collected from unvaccinated children at 2, 6, 9, 12, 18, 24 m in the Vietnam Pneumococcal Project (ClinicalTrials.gov, NCT01953510) were included in this analysis. Pneumococcal carriage was previously determined. Plasma cytokine concentrations were measured by multiplex bead array or ELISA. Flow cytometry was used to measure IL-17 A/IFNγ-producing cells in peripheral blood mononuclear cells.

Results

IL-17 A, IL-22, IL-23 and IFNγ plasma cytokine concentrations were 1.7 to 2.6-fold higher among pneumococcal carriers at 18 m of age compared with non-carriers. Two-to four-fold higher IL-17 A, IL-22, IL-23 concentrations were observed in children carrying two or more pneumococcal serotypes at 18 m compared with children who only carried one pneumococcal serotype or non-carriers. Pneumococcal carriers at 18 m of age had 1.6 to 2-fold higher IL-17 A, IL-22, IL-23 compared with carriers at earlier timepoints (≤12 m). No differences in the frequencies of IL-17 A-producing cells were observed between carriers and non-carriers at 18 m of age. IL-17 A and related cytokines at 18 m of age did not appear to influence clearance of pneumococcus at 24 m of age.

Conclusion

Pneumococcal carriage is associated with higher plasma IL-17 A, IL-22 and IL-23 concentrations in children aged under two years.

目的：肺炎球菌携带是侵袭性肺炎球菌病（IPD）的先决条件。白细胞介素(IL)- 17a和产生IL- 17a的细胞参与成人肺炎球菌携带的清除，但它们在儿童中的作用尚不清楚。本研究旨在探讨2岁以下儿童IL-17 A、IL-17 A相关细胞因子（IL-22、IL-23、IFNγ）和IL-17 A产生细胞与肺炎球菌携带的关系。方法：本分析纳入越南肺炎球菌项目（ClinicalTrials.gov, NCT01953510）中18个月(m)时未接种疫苗儿童的血液样本（n = 143）和2、6、9、12、18、24 m时未接种疫苗儿童的鼻咽拭子。先前已确定肺炎球菌携带。血浆细胞因子浓度测定采用多重头阵列法或ELISA法。流式细胞术检测外周血单核细胞中IL-17 A/ ifn γ生成细胞。结果：18 m龄肺炎球菌携带者血浆细胞因子IL-17 A、IL-22、IL-23和IFNγ浓度比非携带者高1.7 ~ 2.6倍。在18米时，携带两种或两种以上肺炎球菌血清型的儿童的IL-17 A、IL-22、IL-23浓度比仅携带一种肺炎球菌血清型或非携带者的儿童高2至4倍。18 m年龄肺炎球菌携带者的IL-17 A、IL-22、IL-23水平较早年龄（≤12 m）携带者高1.6 ~ 2倍。在18岁时，携带者和非携带者之间IL-17 a产生细胞的频率没有差异。il - 17a和相关细胞因子在18岁时似乎不影响24岁时肺炎球菌的清除。结论：肺炎球菌携带与2岁以下儿童较高的血浆IL-17 A、IL-22和IL-23浓度相关。

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