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关键词： cisplatin   MSC   immunomodulation   tumor microenvironment   IL-6   IDO1  

摘要： Mesenchymal stromal cells (MSCs) influence tumor biology and immunology by releasing cytokines, chemokines and growth factors. Currently, cisplatin is an integral part of drug-based tumor therapy, for example, in head and neck squamous cell carcinoma (HNSCC). Cisplatin treatment induces apoptosis as a primary mechanism of action;however, additional immunomodulatory effects of cisplatin are gaining interest. The aim of this study is to evaluate the possible immunomodulatory effects of cisplatin in human MSCs (hMSCs). The MSCs, obtained from human bone marrow, were characterized by analyzing plastic adherence, typical surface features, and ability to differentiate. Toxicity analysis of cisplatin's effects on primary MSCs, including the determination of a subtoxic concentration, was performed using the MTT assay. Enzyme-linked immunosorbent assays (ELISA) and a quantitative real-time polymerase chain reaction (qRT-PCR) were used to identify potentially immunomodulatory factors. Additionally, a scratch assay was performed to evaluate cell migration. First, subtoxic cisplatin concentrations were determined. A significantly reduced protein expression of indoleamine 2,3-dioxygenase 1 (IDO1) in MSCs under the influence of subtoxic cisplatin concentrations was demonstrated. Similarly, IL-6 protein expression was qualitatively reduced at subtoxic concentrations, although without statistical significance. At the mRNA level, qRT-PCR showed a non-significant, cisplatin concentration-dependent reduction in the expression of both IL-6 and IDO1. The scratch assay showed no statistically significant influence on migration after cisplatin treatment. In MSCs, there is tendency to a decrease in IL-6 and IDO1 at both protein and mRNA level after cisplatin exposure. These effects are congruent with each other and dose-dependent. This indicates that cisplatin not only acts via the known cytotoxic effect, but may induce a reduction in tumor-supporting proteins, like IL-6 and IDO1, by MSCs

关键词： pluripotent   phagocytosis   sphingosine-1-phosphate   HLA   immunotolerance   clinical trials  

摘要： Muse cells are endogenous reparative stem cells with dual characteristics: pluripotent-like and macrophage-like. They can be identified by the pluripotent surface marker stage-specific embryonic antigen-3-positive (SSEA-3 (+)) cells in the bone marrow, peripheral blood, and various organs, including the umbilical cord and amnion. Muse cells can differentiate into ectodermal, endodermal, and mesodermal lineage cells, self-renew, and selectively migrate to damaged sites by sensing one of the universal tissue damage signals, sphingosine-1-phosphate (S1P). At these sites, they phagocytose damaged/apoptotic cells and differentiate into the same cell type as the phagocytosed cells. In this manner, Muse cells replace damaged/apoptotic cells with healthy, functioning cells, thereby repairing tissues. Due to their specific immunosuppressive and immunotolerant mechanism, clinical trials have been conducted for acute myocardial infarction (AMI), subacute ischemic stroke, epidermolysis bullosa, amyotrophic lateral sclerosis (ALS), cervical spinal cord injury, neonatal hypoxic-ischemic encephalopathy (HIE), and COVID-19 acute respiratory distress syndrome. These trials involved the intravenous injection of similar to 1.5 x 107 donor Muse cells without human leukocyte antigen (HLA) matching or immunosuppressant treatment, and they demonstrated safety and therapeutic efficacy. Thus, donor Muse cell treatment does not require gene manipulation, differentiation induction, or surgical intervention. These unique characteristics distinguish Muse cells from other somatic stem cells, such as mesenchymal stem cells, VSEL stem cells, and marrow-isolated adult multi-lineage inducible (MIAMI) cells.

关键词： Peronema canescens Jack.   kaempferol   IL-6   molecular docking   molecular dynamics   RAW 264.7  

摘要： Sungkai leaves were selected due to their herbal medicine prevalence and documented biological activities. This study explores the immunomodulatory potential of kaempferol isolated from Sungkai (Peronema canescens Jack.) through a combination of in silico and in vitro methods. P. canescens leaves were extracted with ethanol using maceration, followed by fractionation with n-hexane, ethyl acetate, and water using a separatory funnel. Among all the fractions, the ethyl acetate fraction demonstrated the strongest inhibitory effect on IL-6 (Interleukin 6) expression, leading to further separation for the enhanced analysis of its activity. The resulting sub-fractions were purified by vacuum liquid chromatography with n-hexane and ethyl acetate gradient. Sub-fraction E was isolated through preparative thin-layer chromatography to obtain a pure compound identified as kaempferol using UV, FTIR, MS, and NMR analyses. The isolated kaempferol was then evaluated by molecular docking and molecular dynamics simulations, employing MM-PBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) for binding affinity calculations. Kaempferol showed a binding affinity (Delta G) of -5.98 kcal/mol, slightly stronger than TLA (tartaric acid) (-5.90 kcal/mol). Key interactions with amino acid residues, such as Gln175, Arg182, and Arg179, were observed. Additionally, molecular dynamics simulation demonstrated that kaempferol exhibited better stability than TLA between 15 ns and 100 ns. The MM-PBSA analysis showed that kaempferol has strong van der Waals (-17.02 kcal/mol) and electrostatic interactions (-293.16 kcal/mol), with binding free energy (-17.85 kcal/mol) significantly stronger than TLA (-1.00 kcal/mol). This stability, combined with its ability to reduce IL-6 expression in vitro, highlights kaempferol's immunomodulatory potential.

关键词： interleukin 23   inflammation   pain   inflammatory disease   immune system  

摘要： Interleukin-23 is crucial in the initiation and progression of certain inflammatory disorders. As a key cytokine, IL-23 is involved in the differentiation and activation of Th17 cells, which play a role in a broad spectrum of inflammatory diseases. This review examines the molecular mechanisms through which IL-23 contributes to the pathogenesis of conditions including psoriasis, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. By elucidating the significant role of IL-23 in inflammation, this review underscores its importance as a therapeutic target for managing inflammatory conditions, with particular emphasis on current and emerging biologic treatments.

关键词： EBV   感染   免疫应答   免疫逃避   B细胞   T细胞   细胞因子  

摘要： EB病毒（Epstein-Barr virus,EBV）作为一种广泛存在于人类社会并传播的疱疹病毒，其感染对机体免疫应答系统产生深远影响。本文将从EBV感染的免疫学基础、感染机制、宿主免疫应答反应、免疫逃避、细胞因子的分泌及其功能等方面进行详细综述，这对深入了解机体感染EBV后的宿主免疫应答特点，为后续EBV疫苗研发、相关疾病的预防和诊治具有重要的促进意义。

关键词： inflammation   senescence   nucleus pulposus cell   intervertebral disc degeneration   homoplantaginin  

摘要： The incidence of intervertebral disc degeneration (IDD) is increasing year by year, while the age of onset of IDD is decreasing year by year. For the individuals affected by IDD, an alternative treatment to surgery is required. IDD is thought to be related to nucleus pulposus (NP) cell senescence and inflammation. Therefore, inhibition of NP cell inflammation and senescence may counteract IDD. We screened 20 small-molecule drugs to compare their anti-inflammatory effects, and finally selected homoplantaginin (HPG) as a treatment regimen. HPG is an extract of Salvia miltiorrhiza with anti-inflammatory properties. The objective of this research was to investigate if HPG could have a therapeutic effect on IDD through its anti-inflammatory or anti-aging effects. We identified the appropriate concentration of HPG in primary NP cell cultures and demonstrated that it inhibited inflammatory pathway activation and reduced the senescence phenotype of NP cells in vitro. And in vivo, the therapeutic effect of HPG on caudal disc degeneration was confirmed consistently. In conclusion, our findings suggest that HPG can alleviate the degeneration in the pathogenesis of IDD and that it has a potential effect in the treatment of IDD.

关键词： 支气管哮喘   呼出气一氧化氮   肿瘤坏死因子α   白细胞介素8   嗜酸性粒细胞  

摘要： 目的 探讨支气管哮喘患者呼出气一氧化氮（fractional exhaled nitric oxide，FeNO）与气道炎症因子肿瘤坏死因子α（tumor necrosis factor alpha，TNF-α）、白细胞介素8（interleukin-8，IL-8）及血嗜酸性粒细胞（eosinophils，EOS）的相关性。方法 选取2022年6月—2023年12月在无锡市第二中医医院就诊的50例支气管哮喘急性发作期患者，评估所有患者的病情严重程度，根据结果分为轻度组、中度组及重度组，测定三组患者的FeNO、TNF-α、IL-8及血EOS水平并比较，分析支气管哮喘患者FeNO、TNF-α、IL-8及血EOS水平与病情严重程度的关系，及FeNO与TNF-α、IL-8及血EOS水平的关系。结果 50例支气管哮喘患者中，轻度15例，中度18例，重度17例；重度组的FeNO、TNF-α、IL-8及血EOS水平依次高于中度组、轻度组（P<0.05）；经多项Logistic回归分析结果显示，FeNO、TNF-α、IL-8及血EOS水平的过表达为中重度支气管哮喘的危险因子（OR>1，P<0.05）；采用双变量Pearson直线相关性分析结果显示，支气管哮喘患者FeNO与TNF-α、IL-8及血EOS水平呈正相关（r>0，P<0.05）。结论 随着支气管哮喘患者的病情严重程度提高，FeNO、TNF-α、IL-8及血EOS水平升高，且FeNO与TNF-α、IL-8及血EOS水平呈正相关。

摘要： Background:Canine and human malignant melanoma are naturally occurring cancers with many similarities, making the dog an important parallel patient population to study both diseases. However, development of canine anti-human antibodies (CAHA) needs to be considered when evaluating humanized biotherapeutics in dogs. Objectives:Characterize CAHA in sera from dogs with spontaneous melanoma receiving radiotherapy and intratumoral immunocytokine (IT-IC) with humanized 14.18-IL2. Methods:Serum samples were obtained pre-treatment and at several post-treatment times from 12 dogs with locally advanced or metastatic melanoma treated with radiotherapy to the primary site and regional lymph nodes (when clinically involved) followed by IT-IC of humanized 14.18-IL2. Two CAHA assays were developed. A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to detect antibodies against the humanized IgG component of hu14.18-IL2. A flow cytometry assay was developed to determine the ability of CAHA to inhibit binding of a mouse anti-GD2 monoclonal antibody to its target. Results:Post-treatment sera from 7 of 12 dogs developed CAHA levels over pre-treatment that were identified by ELISA as significant increases at Day 30 and/or Day 60. Day 10, Day 30, and Day 60 post-treatment sera from 10 of 12 dogs significantly inhibited the binding of anti-GD2 monoclonal antibody to its target compared to pre-treatment. Significant binding inhibition was also detected in 2 of 12 dogs after local RT but before IT-IC (Day 1). Normal canine sera did not mediate binding inhibition. Conclusions:This study advances CAHA detection strategies and reports the kinetics of CAHA following IT-IC in dogs with spontaneous melanoma.

摘要： 德国时代周报网站刊发《肌肉如何治愈我们的身体》,文章称,肌肉具有治愈的能力.锻炼肌肉可降低患糖尿病、高血压或癌症的风险,改善记忆力并延长寿命.这背后的原因是什么?几十年来,科学家们通过研究一步步接近答案:起决定性作用的可能是名为"肌细胞因子"的小分子.它们数量庞大,能帮助身体保持年轻.

关键词： 布鲁菌   脂多糖   单克隆抗体   阻断ELISA  

摘要： 旨在使用布鲁菌脂多糖（LPS)和HRP标记的单克隆抗体（HRP-mAb）建立阻断ELISA抗体检测方法，并评价其检测性能以及初步应用。结果显示，当布鲁菌LPS的包被量为400 ng/孔，10 g/L 阿拉伯树胶溶液封闭2 h，血清稀释4倍后37℃孵育20 min，稀释度为1︰6000的HRP-mAb 37℃孵育20 min，显色10 min时为最佳反应条件，该方法的临界值为PI = 46.7%。该方法的最低检测水平为3.125 IU/mL，与常见的细菌病阳性血清无交叉反应，批内和批间变异系数均小于10%，具有良好的敏感性、特异性和重复性。该方法可检测牛、羊、鹿、犬等宿主的布鲁菌阳性血清。使用建立的阻断ELISA方法检测284份临床血清，与虎红凝集试验、竞争ELISA和间接ELISA试剂盒的符合率分别达到97.18%（276/284）、98.59%（280/284）和96.13%（273/284）。结果表明，建立了敏感性高、特异性好、重复性好的布鲁菌抗体阻断ELISA检测方法，全部反应过程不超过1 h，并且可检测多物种布鲁菌阳性血清。该方法弥补了我国布鲁菌抗体阻断ELISA检测技术的空白，为布鲁菌病的快速诊断以及免疫水平监测提供了技术支持。