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关键词： IL-6   exercise   bone metabolism   muscle   skeletal muscle-bone crosstalk  

摘要： Skeletal muscles and bones maintain musculoskeletal system function through their collaborative interaction, whereby muscles regulate bone metabolism via mechanical coupling. An increasing number of studies have shown that various cytokines secreted by skeletal muscles during exercise closely regulate the balance of bone homeostasis. Interleukin-6 (IL-6), one of the first muscle-secreted factors to be discovered, not only plays an important role in regulating the function of the muscle itself but also regulates bone metabolic processes in a bidirectional manner through multiple complex signal transduction pathways, thereby affecting the balance between bone formation and bone resorption. The exact mechanism by which IL-6 regulates bone metabolism is not fully understood, and there are few summaries on how exercise affects bone metabolism through IL-6 from skeletal muscles. Accordingly, this study will take skeletal muscle-derived IL-6 as an entry point to explore how the cross-organ regulatory activities of the muscles targeting bones during exercise affect bone metabolic processes. This study also aims to improve the mechanism of muscle-bone crosstalk under the effect of exercise and provide a theoretical basis and clinical diagnosis and treatment ideas from multiple perspectives for exercise to improve bone health.

关键词： IL-33   IL-38   prostate cancer   precision medicine   diagnosis  

摘要： Prostate cancer (PCa) is still as a major cause of morbidity and mortality in men at the global level, highlighting the necessity for improved diagnostic and therapeutic strategies beyond current PSA screening limitations. This mini-review focuses on the complex and often opposing roles of two key cytokines, IL-33 and IL-38, within the tumour microenvironment and their implications for host immunosurveillance in PCa. Intra-tumoral IL-33 expression is significantly reduced in PCa tissues and correlates with aggressive disease features such as higher Gleason scores and lymphatic metastasis, suggesting an inherent anti-tumour function. Such a protective role may be mediated via the ST2/NF-kappa B signalling pathway and the recruitment of lymphocytes into the tumour microenvironment. However, a paradoxical increase in circulating IL-33 levels in PCa patients hints at complex systemic compensatory mechanisms or differential compartmental regulation. In contrast, intra-tumoral IL-38 exhibits markedly elevated expression in PCa compared to benign prostatic hyperplasia and non-cancerous tissues. This increased IL-38 correlates with tumour severity, advanced TNM stages, and poorer overall survival, indicating a pro-tumoral role. Mechanistically, IL-38 appears to inhibit CD8+ cytotoxic T cell infiltration and potentially promotes immunosuppression through the upregulation of regulatory T cells (Tregs), thereby facilitating tumour progression. The contrasting expression patterns and clinicopathological associations of IL-33 and IL-38 highlight their potential as novel biomarkers for PCa diagnosis and prognosis. Further comprehensive investigation, including multi-centre studies across diverse populations, functional in vitro and in vivo analyses, and exploration of their therapeutic targetability, is crucial to translate these findings into effective precision medicine strategies for PCa patients.

关键词： atherosclerosis   IFN gamma signaling   STAT1   multi-omics integration   macrophages   single cell RNA-seq   diagnostic markers   gene signature  

摘要： Atherosclerosis is a chronic inflammatory disease of blood vessels, characterized by atherosclerotic lesions in large- and medium-sized arteries. IFN gamma is a crucial mediator of atherosclerosis through activation of signal transducer and activator of transcription (STAT)1. Macrophages (M & Oslash;), in different subtypes, play a central role in atherosclerosis, from early foam cell formation to advanced plaque development and potential rupture. Recent evidence in M & Oslash;supports a collaborative role of STAT1 with PU.1, in association with histone acetylation and methylation marks, in M & Oslash;-specific IFN gamma-activated transcriptional responses. This study investigated the role of M & Oslash;STAT1-mediated signaling in atherosclerosis progression through multi-omics integration of IFN gamma-induced M & Oslash;and expression analysis in human and mouse atherosclerotic lesions. First, by integrating ATAC-seq, ChIP-seq, and RNA-seq data from IFN gamma-treated and untreated bone marrow-derived M & Oslash;, we identified 1139 STAT1-dependent integrative genes. Active transcription of these genes was characterized by prominent promoter STAT1-PU.1 co-binding, increased histone methylation and acetylation and chromatin accessibility. Moreover, KEGG-analysis unraveled a strong connection to lipid metabolism and atherosclerosis-related pathways, whereas STARNET analysis identified high association with LDL cholesterol and diseased vessel traits. Using scRNA-seq data analysis of human carotid and coronary atherosclerotic lesions revealed dynamic changes of STAT1-dependent integrated genes in M & Oslash;subtypes, including foamy M & Oslash;, monocytes, inflammatory M & Oslash;, tissue resident M & Oslash;and conventional dendritic cells. Comparative M & Oslash;-dependent expression analysis in aortic lesions from LDLr-/- and ApoE-/- high fat diet mouse models substantiated overlap between human and mouse atherosclerosis and identified 24 M & Oslash;-specific commonl

关键词： 重症肺炎   动态中性粒细胞/淋巴细胞比值变化   DIC  

摘要： 目的 探讨中性粒细胞与淋巴细胞比值（NLR）动态变化与重症肺炎患者发生弥散性血管内凝血（DIC）的关系。 方法 回顾性分析2019年1月至2023年12月常州市第二人民医院住院的重症肺炎患者340例，其中男性264例，女性76例；年龄28~101岁，平均（73.56±13.65）岁。根据并发症分为非DIC组（n=271）和DIC组（n=69）。采用广义估计方程（GEE）分析两组患者NLR的时间单独效应和组间主效应，Logistic回归分析不同时间点NLR对DIC的影响，绘制受试者工作特征（ROC）曲线评估动态NLR对重症肺炎患者发生DIC的预测价值。 结果 （1）GEE结果显示，DIC患者和非DIC患者在进入急诊室时NLR差异无统计学意义，但是随着时间推移，DIC患者NLR逐渐增大，非DIC患者NLR逐渐减小（P<0.001）。（2）多因素Logistic回归分析显示，校正混杂因素后入院24 h、48 h及72 h后NLR均为重症肺炎并发DIC的风险因素（P<0.05）。（3）ROC曲线分析显示，入院72 h后NLR（AUC=0.75）较入院24 h后（AUC=0.60）和入院48 h后（AUC=0.63）预测价值高。 结论 持续的高炎症反应打击诱发重症肺炎患者发生DIC。NLR动态变化有助于早期识别重症肺炎发生DIC的风险。

关键词： IL-1 beta   Antigen-capture ELISA (acELISA)   Horse   Donkey  

摘要： In this study, we developed a highly sensitive enzyme-linked immunosorbent assay (ELISA) using newly produced monoclonal antibodies (mAbs) for detecting horse/donkey IL-1 beta in cell culture medium and serum samples. The mAbs were generated via the use of a KLH-conjugated peptide and purified equine IL-1 beta protein as separate immunogens. Notably, the generated mAbs (3G8 and 5G3) demonstrated no cross-reactivity with other major inflammatory mediators, including IL-1 alpha, IL-1Ra, TNF-alpha, and SAA. The IL-1 beta assay, which is based on the screened mAbs, exhibits a detection range of 200-10,000 pg/mL, meeting clinical detection requirements. The coefficients of variation for the repeatability and reproducibility of the assay were both less than 5%, indicating an acceptable level of variation. Subsequently, 84 equine and 24 asinine serum samples were collected, and the IL-1 beta concentration was measured with both our assay and a commercial kit in parallel. Our results revealed no significant difference between the in-house and commercial ELISA kits for the detection of IL-1 beta concentrations in horse sera. Moreover, our ELISA method demonstrated superior sensitivity for IL-1 beta detection in donkey samples compared to existing commercial assays. These findings suggest that the newly developed ELISA provides a reliable analytical method for detecting IL-1 beta in both equine and asinine samples.

关键词： 哮喘   白细胞介素-33   干扰素-γ   气道炎症   症状控制水平  

摘要： 目的：分析外周血单个核细胞白细胞介素-33(interleukin-33,IL-33)、干扰素-γ(interferon-gamma,IFN-γ)与儿童哮喘气道炎症、症状控制水平的相关性及意义。方法：选取2022年11月至2024年12月郑州大学附属儿童医院/河南省儿童医院郑州儿童医院收治的105例哮喘患儿（哮喘组），选取同期健康体检儿童105例作为对照组。将哮喘组患儿根据症状控制水平分为控制组、未控制组。统计2组外周血单个核细胞IL-33、IFN-γ、气道炎症[嗜酸性粒细胞百分比（eosinophil percentage,EOS%）、呼出气一氧化氮（fractional exhaled nitric oxide,FeNO）、免疫球蛋白E(immunoglobulin e,IgE)]，分析外周血单个核细胞IL-33、IFN-γ与气道炎症、症状控制水平的相关性，并分析外周血单个核细胞IL-33、IFN-γ对哮喘症状控制水平的效应，受试者工作特征（receiver operating characteristic,ROC）曲线分析外周血单个核细胞IL-33联合IFN-γ预测哮喘控制水平的作用的影响及预测价值。结果：哮喘组IL-33、EOS%、FeNO、IgE[(36.19±4.20) ng/L、（18.65±0.91）%、（45.90±2.63） ppb、（275.68±20.39） IU/mL]高于对照组[（7.55±2.43） ng/L、（0.89±0.28）%、（5.77±1.94） ppb、（54.92±17.45） IU/mL],IFN-γ(52.72±16.18)ng/L低于对照组（90.15±20.77） ng/L(t=25.607、30.758、32.181、35.986、9.770,P<0.05);Pearson相关性分析显示，IL-33与EOS%、FeNO、IgE呈正相关（r=0.720、0.749、0.722,P<0.05）,IFN-γ与EOS%、FeNO、IgE呈负相关（r=-0.739、-0.703、-0.767,P<0.05）；未控制组IL-33(48.93±15.87) ng/L高于控制组（20.47±6.56） ng/L,IFN-γ(41.66±12.40) ng/L低于控制组（66.37±18.25） ng/L(t=11.515、8.234,P<0.05);IL-33(OR=1.398,95%CI=1.166～1.675)、IFN-γ(OR=0.421,95%CI=0.243～0.728)是症状控制水平的独立相关影响因素（P<0.05）;IL-33、IFN-γ与哮喘症状控制水平呈线性关系，其中IL-33为负向线性关系，IFN-γ呈正向线性关系；ROC分析显示，IL-33、IFN-γ预测哮喘控制水平的AUC分别为0.745(95%CI=0.651～0.825)、0.766(95%CI=0.673～0.843)；以R00为参照，R01、R10、R11亚组患儿哮喘控制不良的风险值OR(95%CI)分别为1.293(95%CI=1.056～1.582)、1.406(95%CI=1.133～1.744)、7.472(95%CI=5.062～11.029)(P<0.05);IL-33高表达+IFN-γ低表达对哮喘控制水平具有正相加交互作用，二者交互作用所占的比例为77.26%;IL-33联合IFN-γ预测哮喘控制水平的AUC为0.883(95%CI=0.806～0.938)，敏感度为82.98%，特异度为81.03%(P<0.001)，大于IL-33、IFN-γ(Z=2.409、2.030,P=0.016、0.042)。结论：外周血单个核细胞IL-33、IFN-γ水平与哮喘气道炎症反应、症状控制水平密切相关，为临床早期预测症状控制水平、针对性制定相应干预方案提供参考依据。

关键词： Sanguisorba officinalis l   processed   colon cancer   TNF-alpha/NF-kappa B   COX-2   iNOS  

摘要： Background Sanguisorba officinalis L. (S.L.), a traditional Chinese medicine from the Rosaceae family, is recognized for its rich content of triterpenoids, which are known for their antioxidant, anti-inflammatory, and anti-tumor properties. Although its traditional uses and biological activities are well known, its role in preventing colon cancer and the underlying mechanisms remain unclear. This study aims to elucidate the preventive mechanisms of triterpenoids in both raw (TR) and processed (TP) forms of S.L. against colon *** The AOM/DSS-induced mouse model of colon cancer was employed to elucidate the mechanism underlying the preventive effects of Sanguisorba officinalis L. triterpenoids (ST) against colon cancer. A comprehensive suite of techniques, including hematoxylin-eosin staining (H&E), immunohistochemistry (IHC), TUNEL staining, Western blotting (WB), and DNA methylation analysis, was utilized to investigate the preventive effects of ST on colon cancer. The main active compounds were identified using UPLC-Q-TOF-MS, and potential active compounds were screened through network pharmacology and molecular docking. The stability of the protein-ligand complexes was further assessed using molecular dynamics *** In vivo experiments, treatment with ST significantly improved the clinical manifestations, Disease Activity Index (DAI) scores, and pathological lesions associated with colon cancer, with all drug administration groups outperforming the model group. Additionally, ST markedly enhanced gut barrier function by downregulating the levels of TNF-alpha, p65, COX-2, and iNOS. Furthermore, ST dramatically ameliorated the colonic immune-inflammatory state, which was associated with decreased expression of proliferative proteins and increased expression of apoptotic proteins. Among the identified triterpenoids, compound 27 May be the main active compound. Notably, compound 27 can form a stable complex with *** These resul

关键词： interleukin-15   chimeric antigen receptor   cancer therapy   cytokine release syndrome  

摘要： Interleukin (IL)-15 engineering in chimeric antigen receptor (CAR)-cell therapy has demonstrated promising antitumor efficacy against both hematological malignancies and solid tumors in recent clinical trials. However, increased cytokine release syndrome (CRS) toxicity is primarily observed in conventional CAR-T cells, underscoring the need to balance safety and efficacy in IL-15-enhanced CAR therapy for clinical application.

关键词： CIBER   executive dysfunction   biomarker   polydrug consumers   addiction  

摘要： Background/Objectives: Individuals diagnosed with substance use disorders (SUD) exhibit notable deficits in executive function (EFs). Notably, the pro-inflammatory cytokine interleukin-6 (IL-6) has been associated with cognitive impairments in individuals with substance use disorders. The specific neuropsychological parameters most affected by executive dysfunction remain poorly understood. Methods: In this study, sixteen patients diagnosed with SUD in the withdrawal phase were compared to twenty age-matched control subjects to ascertain which aspects of EFs were most adversely impacted. Plasma levels of IL-6 were quantified using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using the Confidence Interval-Based Estimation of Relevance (CIBER) model to determine the most sensitive executive performance indicators. Results: Findings from the CIBER analysis revealed that the Wisconsin Card Sorting Test yielded the most pronounced cognitive discrepancies between males with and without SUD diagnoses. Elevated levels of IL-6 and associated executive dysfunction were observed to persist in males with SUD throughout the withdrawal phase. Conclusions: Notably, cognitive flexibility emerged as the most sensitive parameter indicative of executive dysfunction, suggesting its potential utility in tailoring clinical interventions for SUD patients during this critical recovery period.

关键词： 肿瘤疫苗   新生抗原   多肽合成   多肽纯化   流程优化  

摘要： 肿瘤新生抗原多肽具有高度的免疫原性和肿瘤特异性，是肿瘤精准化治疗的理想策略之一. 然而，受其个性化的特征限制，目前临床研究肿瘤新生抗原多肽疫苗的生产中面临合成难度大、制备周期长和纯化复杂等挑战，限制了其广泛应用. 针对目前面临的问题，本研究提出了一种全新的利用片段肽树脂储存的方式，将合成周期由2个月缩短至1个月；并对合成方法进行优化，大幅提高粗肽纯度，降低纯化难度. 利用该方法，可以在23个工作日内高效生产12条38个氨基酸长度的肿瘤新生抗原多肽，以满足临床需求（纯度大于95%，质量大于20 mg，转成醋酸盐且三氟乙酸根残留小于1%，内毒素残留小于10 EU/mg）. 本研究在新生抗原多肽制备流程的设计与优化方面取得了显著进展，不仅提高了合成肿瘤新生抗原多肽的质量，还显著缩短了制备周期，为肿瘤新生抗原多肽临床应用奠定了坚实基础.