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关键词： CCL22   IFN   immunosuppression   macrophage   STING  

摘要： Immunosuppressive elements within the tumor microenvironment include both regulatory T cells (Tregs) and M2 macrophages. A well-described mechanism of Treg recruitment occurs via the chemokine CCL22, and CCL22 has also recently been implicated in the polarization of tumor-associated macrophages to the M2a subtype. Our lab and others have shown that CCL22 is upregulated in cancer cells following activation of the stimulator of interferon genes (STING). STING triggers immune responses against pathogenic nucleic acids as well as self-DNA mislocalized to the cytoplasm, which can accumulate in cancer cells due to chromosomal instability, damaged mitochondria, and increased expression of LINE-1 retrotransposons. STING activation has been associated with both anti-tumor and pro-tumor immune responses, and a potential mechanism of STING-mediated immune evasion is through CCL22 upregulation. CCL22 was first characterized in macrophages, and here we investigate the effects of STING activation on CCL22 expression in macrophages and monocytes. We report that human macrophages and monocytes are resistant to CCL22 upregulation by STING, but that STING-activated macrophages and monocytes release unidentified paracrine factor(s) that dramatically increase CCL22 upregulation in cancer cells in a manner that remains STING-dependent, as evidenced by the inability of STING knockout cells to upregulate CCL22 in response to these factors. We further found that exogenous type I interferons, a major downstream product of STING activation, also upregulate CCL22 in cancer cells via a STING-dependent mechanism and that exogenous IFN-β can directly activate STING. © The Author(s) 2025. Published by Oxford University Press on behalf of The American Association of Immunologists.

关键词： 猪免疫球蛋白J链   原核表达   抗血清  

摘要： 旨在制备猪免疫球蛋白J链抗血清,为研究J链的免疫学功能提供材料。运用PCR扩增J链开放阅读框,并将其克隆至原核表达载体pET30a,选择测序成功的pET30a-J重组质粒转化到大肠杆菌BL21(DE3)感受态细胞中进行蛋白表达验证;将J链与弗氏完全佐剂混合后经背部皮下免疫新西兰大白兔制备抗血清;采用ELISA、Western blot和间接免疫荧光试验(IFA)对获得的抗血清进行功能验证。结果:猪免疫球蛋白J链在大肠杆菌中以包涵体形式表达,经变性复性后通过NI-NTA亲和层析的方法纯化出纯净的目的蛋白;ELISA检测结果显示,四免后兔血清中抗体效价可达1∶6400;Western blot结果显示,获得的抗血清能与原核表达的J链特异性结合;为进一步验证抗血清的反应性,构建了pcDNA3.1-J重组载体,将其转染293T细胞,IFA与Western blot检测结果显示,本研究制备的抗血清能与真核表达的猪免疫球蛋白J链特异性结合,通过ELISA和Western blot检测抗血清与猪乳中J链的反应性,结果显示能与猪乳中的J链反应。综上表明,本研究成功制备出猪免疫球蛋白J链抗血清。

关键词： 宫颈癌   巨噬细胞   肿瘤微环境   CCL17  

摘要： 目的:研究宫颈癌(CC)中高表达的趋化因子配体17(CCL17)是否通过M2巨噬细胞极化推动CC进展。方法:通过流式细胞术和酶联免疫吸附试验,检测CCL17对CC细胞株中IL-27表达的影响。分析CCL17和IL-27在U937细胞增殖分化过程中的作用。应用巨噬细胞与CC细胞共培养模型,检测CCL17对U937和CC细胞增殖的影响。结果:CC细胞中IL-27表达在CCL17刺激后显著升高。此外,IL-27没有显著上调U937细胞中白细胞介素27受体(IL-27R,由WSX-1和GP130组成)比例。源于CC细胞的IL-27能够促进U937细胞的增殖,诱导M2巨噬细胞的极化。在共培养体系中,CCL17刺激CC细胞中IL-27表达比例显著升高,CCL17和IL-27均促进了CC和U937细胞的增殖,且CCL17的作用被αIL-27部分逆转。结论:CCL17通过刺激CC细胞分泌IL-27,促进巨噬细胞的增殖,诱导M2极化,从而加强CC细胞与巨噬细胞之间的串扰,最终CCL17参与CC的恶性演化。

关键词： α-乳糖   弓形虫   免疫病理   淋巴细胞   TIGIT  

摘要： [目的]弓形虫(Toxoplasma gondii)是一种可以寄生于几乎所有温血动物有核细胞内的原生动物寄生虫,其感染可导致宿主脾脏和外周血T细胞耗竭关键分子T细胞免疫球蛋白粘蛋白-3(T cell immunoglobulin and mucin domain-containing protein 3,TIM-3)表达上调,进而抑制免疫应答。已有研究证实α-乳糖能特异性调节TIM-3与其配体半乳糖凝集素9(Galectin-9,Gal-9)的相互作用,进而减弱其抑制功能,增强机体抗感染能力。评估α-乳糖通过竞争性结合TIM-3配体Gal-9对感染弓形虫不同毒力株(RH株和ME49株)小鼠的免疫病理的干预效果,以期为弓形虫感染的免疫调节治疗提供新策略。[方法]利用弓形虫感染小鼠模型,皮下注射α-乳糖后,分析小鼠生存率、脾指数及肺脏、脾脏组织病理学变化,并通过流式细胞术检测小鼠外周血淋巴细胞亚群的比例及其表面免疫检查点分子含免疫球蛋白(Immunoglobulin,Ig)及ITIM结构域的T细胞免疫受体(T cell immunoreceptor with Ig and ITIM domains,TIGIT)的表达情况。[结果]α-乳糖处理虽延长弓形虫感染小鼠的存活时间,但对脾指数及肺、脾组织的病理损伤无改善作用。此外,感染弓形虫后,小鼠外周血中不同淋巴细胞亚群(包括CD8⁺T细胞、NK细胞等)的TIGIT表达均未因α-乳糖处理而出现显著升高。[结论]α-乳糖对感染弓形虫的小鼠无显著影响,这可能与虫株毒力及宿主免疫衰竭状态相关。

摘要： Gene-directed enzyme prodrug therapy (GDEPT) represents a promising antitumor strategy owing to its low systemic toxicity. However, clinical translation has been hindered by challenges in suicide gene delivery. Artificially engineered circular RNA (circRNA) demonstrates exceptional potential for gene delivery when combined with lipid nanoparticle (LNP) technology, exhibiting high stability, prolonged protein-coding capacity, and cost-effective production. We developed an in vitro synthesized circRNA encoding the cytosine deaminase-uracil phosphoribosyltransferase (circCDUPRT). Upon intratumoral administration, circCDUPRT achieved sustained intratumoral expression with minimal systemic toxicity. The combination of circCDUPRT and prodrug 5-fluorocytosine (5-FC) showed significant antitumor efficacy in both in vitro and in vivo tumor models. In advanced melanoma models, combining circCDUPRT/5-FC with IL-15-expressing circRNA (circIL) potently enhanced expansion and activation of CD8+ T and NK cells. Collectively, these findings establish the synthetic circRNA platform as a cost-effective, high-efficiency delivery system for GDEPT and immunotherapy applications.

关键词： 解毒愈溃汤   他克莫司   糜烂型口腔扁平苔藓   趋化素   白细胞介素-17  

摘要： 目的探讨解毒愈溃汤联合他克莫司治疗糜烂型口腔扁平苔藓(EOLP)的疗效及其对血清白细胞介素(IL)-17、趋化素水平的影响。方法选取2022年3月至2024年4月该院收治的86例EOLP患者作为研究对象,随机分为中西结合组和西药组,每组43例。2组均给予他克莫司软膏治疗,中西结合组联合解毒愈溃汤治疗。比较2组治疗后临床疗效和不良反应发生率。比较2组治疗前后中医证候积分、视觉模拟评分法(VAS)评分、体征评分;比较2组治疗前后血清肿瘤坏死因子α(TNF-α)、IL-17、IL-10、趋化素水平;比较2组治疗前后体液免疫指标[免疫球蛋白(Ig)G、IgA、IgM]水平;比较2组治疗前后外周血Th17、Treg细胞百分比及Th17/Treg比值。结果中西结合组总有效率明显高于西药组,差异有统计学意义(P<0.05);2组治疗期间不良反应总发生率比较,差异无统计学意义(P>0.05);2组治疗后中医证候积分、VAS评分、体征评分均低于治疗前,且中西结合组治疗后中医证候积分、VAS评分、体征评分均低于西药组,差异均有统计学意义(P<0.05);2组治疗后血清TNF-α、IL-17、趋化素水平均低于治疗前,血清IL-10水平高于治疗前,且中西结合组治疗后血清TNF-α、IL-17、趋化素水平均低于西药组,血清IL-10水平均高于西药组,差异均有统计学意义(P<0.05);2组治疗后体液免疫指标(IgG、IgA、IgM)水平均高于治疗前,且中西结合组治疗后体液免疫指标(IgG、IgA、IgM)水平均高于西药组,差异均有统计学意义(P<0.05);2组治疗后外周血Th17、Treg细胞百分比及Th17/Treg比值均低于治疗前,且中西结合组治疗后外周血Th17、Treg细胞百分比及Th17/Treg比值均低于西药组,差异均有统计学意义(P<0.05)。结论解毒愈溃汤联合他克莫司治疗EOLP可改善患者中医症状,缓解疼痛,减轻炎症反应,调节免疫状态,明显提高临床疗效。

关键词： Ionic liquids  

摘要： Harnessing the vast design space of ionic liquid (IL) systems requires efficient, high-throughput computer-aided molecular design (CAMD) strategies. We present a hybrid classification-regression machine learning framework for predicting viscosity and conductivity of IL-solvent systems over wide temperature and composition ranges. Gradient boosting regression (GBR) models were trained using COSMO-RS sigma profiles and group contribution (GC) features, with GC features showing superior predictive performance. Additionally, SHapley Additive exPlanations analysis was implemented to provide insight into feature importance. Preclassifying property data sets into narrower ranges (three for viscosity, two for conductivity) enhanced accuracy, motivating the development of a hybrid support vector classification SVC-GBR framework. This framework achieved AARD (%) values of 19.2% for viscosity and 25.4% for conductivity on IL-solvent systems previously unseen by the model, representing improvements of 34.0% and 21.4% over baseline GBR models.

关键词： 儿童   急性淋巴细胞白血病   ARID5B基因   单核苷酸多态性   微小残留病  

摘要： 目的:探讨ARID5B基因单核苷酸多态性与宁夏地区回、汉族儿童急性淋巴细胞白血病(ALL)风险及微小残留病(MRD)的相关性。方法:采用病例对照研究,使用荧光共振能量转移技术,对54例ALL患儿及年龄、性别、民族相匹配的对照人群的ARID5B基因多态性位点进行检测,分析不同基因型ALL的易感性及其与MRD的相关性。结果:两组患儿rs10994982、rs7089424、rs10740055、rs7073837、rs4245595、rs7090445位点基因型及等位基因频率比较差异均无统计学意义(P>0.05)。在rs10821936位点上,ALL组T/T基因型和T等位基因频率均显著高于对照组(均P<0.05),ARID5B基因rs10821936的C/C基因型是ALL患儿MRD早期阳性的危险因素(P<0.05)。结论:ARID5B基因rs10821936与儿童ALL发生及MRD有一定相关性。

关键词： anti-IL-5R   anti-IL4Ra   anti-IL5   anti-IgE   biological treatment   chronic rhinosinusitis with nasal polyps   network meta-analysis   sinus surgery  

关键词： 抗原Ⅰ/Ⅱ蛋白   口腔链球菌   口腔疾病  

摘要： 抗原Ⅰ/Ⅱ蛋白是由变异链球菌、格氏链球菌等人类口腔固有链球菌编码的一类表面蛋白。在变异链球菌中,抗原Ⅰ/Ⅱ蛋白以黏附素的形式介导菌体在口腔硬组织表面的定植或与其他微生物如假丝酵母结合,影响龋病的发生发展。格氏链球菌抗原Ⅰ/Ⅱ蛋白能够作为受体,促进其他致病微生物的定植,从而影响口腔健康。在格氏链球菌抗原Ⅰ/Ⅱ蛋白的介导下,牙龈卟啉单胞菌对牙周及牙髓组织的侵袭力明显增强。本文对抗原Ⅰ/Ⅱ蛋白晶体结构、表达影响因素以及其在口腔链球菌致病性方面的贡献进行综述,旨在为多种口腔疾病的防治研究提供参考。