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关键词： 种植体周炎   基因多态性   遗传变异,炎症细胞因子   单核苷酸多态性   白细胞介素  

摘要： 背景:种植体周炎的发生不仅与外源性因素有关,遗传风险因素也可能会导致种植体疾病的发生,主要体现在各种细胞因子多态性引起的表达改变,因此,种植体周炎与各种相关细胞因子基因多态性的关联备受关注。目的:总结种植体周炎与多种常见相关基因多态性的相关性。方法:以“种植体周炎,种植体周围炎,种植体周围疾病,基因变异,多态性”等为中文检索词,以“peri-implantitis,genotype,SNP,Single nucleotide polymorphisms,polymorphism,variant,dental implant failures,dental implant loss”等为英文检索词,应用计算机检索中国知网、Web of Science、PubMed数据库收录的相关文献。通过阅读文题和摘要进行筛选,最终纳入65篇文献进行综述。结果与结论:白细胞介素家族(白细胞介素1、白细胞介素4、白细胞介素6、白细胞介素10、白细胞介素17)、肿瘤坏死因子α、细胞核因子κB受体活化因子/细胞核因子κB受体活化因子配体/骨保护素系统、Fcγ受体、CD14的基因多态性与种植体周炎发生的相关性尚存在争议。针对基质金属蛋白酶与种植体周炎的关系,早期研究与近年来的研究结果相反。中国人群表皮生长因子和CXC趋化因子受体2基因多态性与种植体周炎易感相关。相关性争议存在的原因主要在于样本量小、从特定地理人群收集数据的潜在局限性以及缺乏更多的具体实验证据。

关键词： 类风湿性关节炎   细胞因子-细胞因子受体相互作用通路   机器学习   无监督聚类分析  

摘要： 背景:类风湿性关节炎是一种自身免疫性疾病,受发病机制和患者个体体质差异影响,患者治疗效果存在显著不同,部分患者因对治疗药物不敏感,发展为难治性类风湿性关节炎。因此寻找类风湿性关节炎的特征基因、挖掘新的治疗靶点,已成为该领域亟待解决的关键问题。目的:运用生物信息学分析方法,探究细胞因子-细胞因子受体相互作用通路相关基因在类风湿性关节炎诊断、分型及功能解析中的作用。方法:从基因表达综合数据库(GEO,https://***/geo/,由美国国立生物技术信息中心创建并维护的基因表达数据库)下载4个包含类风湿性关节炎样本的数据集,各数据集均为公开发表的数据,符合伦理学要求。将GSE55235、GSE55457和GSE77298数据集合并作为训练集,GSE12021数据集作为验证集。研究流程:(1)分析细胞因子-细胞因子受体相互作用通路在类风湿性关节炎中的失调状态,筛选该通路相关的差异表达基因;(2)综合采用随机森林算法、最小绝对收缩和选择算子、支持向量机-递归特征消除法、Boruta全特征选择算法及加权基因共表达网络分析,进一步筛选类风湿性关节炎中与细胞因子-细胞因子受体相互作用通路相关的特征基因;(3)基于筛选出的差异基因,运用无监督聚类分析方法,将类风湿性关节炎划分为不同的分子亚型,并对比分析各亚型间信号通路活性及免疫细胞浸润水平的差异;(4)通过构建类风湿性关节炎细胞模型,对特征基因的表达水平进行实验验证。结果与结论:(1)经多方法整合分析,成功筛选出3个特征基因;(2)基于细胞因子-细胞因子受体相互作用通路可将类风湿性关节炎分为2种亚型:甲氨蝶呤敏感型和不敏感型,根据此分型可以指导类风湿性关节炎的临床治疗,避免盲目使用甲氨蝶呤,及时调整治疗策略,选择更有效的药物或治疗组合,从而提高治疗效果,改善患者的病情,提升类风湿性关节炎治疗的有效性和精准性。

关键词： 脑卒中   炎症细胞因子   孟德尔随机化   因果关系   药物预测   分子对接   逆方差加权法  

摘要： 背景:炎症是脑卒中病理生理过程的关键组成部分,然而脑卒中与炎症之间的因果关系仍不清楚。目的:采用孟德尔随机化及分子对接技术探索91种靶向炎症细胞因子的脑卒中治疗机制。方法:从开放全基因组关联研究数据库(IEU Open GWAS,https://***/,由英国布里斯托大学医学研究委员会综合流行病学单位主办)中获得炎症细胞因子及脑卒中的数据,使用逆方差加权法作为主要研究方法进行两样本孟德尔随机化分析,评估91种炎症细胞因子与脑卒中之间的因果关系。随后基于孟德尔随机化研究结果进行了基因本体分析和京都基因与基因组通路分析,并构建了蛋白质-蛋白质相互作用网络。使用美国西奈山伊坎医学院建立的Enrichr数据库(http://***/Enrichr)和美国科罗拉多大学丹佛分校建立的药物特征数据库(http://***/dsigdb)进行脑卒中治疗药物预测,并使用AutoDock软件进行分子对接,通过Discovery Studio2019对结果进行可视化。结果与结论:(1)发现11种炎症细胞因子与全因脑卒中风险之间存在显著的因果关联;9种炎症细胞因子与缺血性脑卒中风险呈强相关;6种细胞因子与大动脉脑卒中风险显著相关;7种炎症细胞因子与心源性栓塞性脑卒中风险呈显著因果关系;12种细胞因子与小血管脑卒中风险显著相关;3种炎症细胞因子与脑内出血风险具有显著的因果关联;(2)基因本体分析和京都基因与基因组通路分析揭示,炎症细胞因子在代谢、炎症及免疫反应等方面对脑卒中具有重要影响;(3)通过蛋白质-蛋白质相互作用网络分析,筛选出与脑卒中密切相关的10种炎症细胞因子;(4)药物预测和分子对接结果表明,阿托伐他汀和氟氢可的松与关键核心靶点白细胞介素18和CCL3的结合力较高;(5)此次研究的数据来源于国际数据库中的欧洲人群,所获得的结果可为中国脑卒中的遗传流行病学研究提供参考;(6)此次研究阐明了炎症细胞因子与脑卒中之间的因果关系,揭示了炎症细胞因子治疗脑卒中的机制,为脑卒中的治疗提供了新思路。

关键词： Hybrid nanoparticle   Lipid-PLGA delivery system   Interferon-γ adjuvant   TLR3/TLR7/8 agonists   Immunopharmacotherapy   Oxycodone vaccine  

摘要： The ongoing opioid epidemic continues to drive high rates of substance use disorders (SUD), fatal and non fatal overdoses, with oxycodone being one of the most widely misused prescription opioids. Immunopharmacological strategies such as vaccines that induce drug-specific antibodies offer a non-addictive, long-lasting approach to neutralize opioids in the bloodstream and prevent their entry into the central nervous system (CNS). In this study, we evaluated the immunogenicity and efficacy of novel oxycodone vaccine formulations incorporating interferon-γ (IFN-γ), either alone or in combination with toll-like receptor (TLR) agonists, delivered via either conventional hapten-carrier conjugates or lipid-PLGA hybrid nanoparticles (hNPs). All adjuvanted formulations elicited robust anti-oxycodone IgG responses, with IFN-γ + TLR agonist combinations particularly in the hNP platform producing the highest titers and enhanced antibody affinity. Subclass analysis, performed on the hNP-based vaccines, revealed IgG1-dominant responses, with modest IgG2a induction in the TLR-adjuvanted groups, suggesting partial Th1 skewing. Pharmacokinetic studies showed significantly elevated serum and reduced brain oxycodone levels in all vaccinated animals, with the hNP-based vaccine adjuvanted with IFN-γ and R848 providing the most potent CNS protection. In the hot plate assay, all formulations significantly attenuated oxycodone-induced antinociception, with the hNP-based vaccine formulated with IFN-γ and poly I:C producing the greatest reduction. These findings demonstrate that co-delivery of IFN-γ and a TLR agonist via a nanoparticle platform enhances both the magnitude and functional quality of the immune response, supporting further development of this strategy as a promising therapeutic approach for opioid use disorder.

关键词： Anisakidosis   Anisakis-specific IgE   Eosinophils   ILC2s   Immediate hypersensitivity   Infection model   Th2 cells  

摘要： Anisakis simplex, a parasitic nematode transmitted through the consumption of raw or undercooked seafood, is known to cause gastric anisakidosis, often accompanied by acute inflammatory and allergic responses. However, the underlying immunological mechanisms remain poorly understood. In this study, we established a murine model by orally infecting BALB/c mice with live Anisakis larvae to elucidate the host immune response. Repeated infection with live Anisakis larvae, but not with homogenates, induced severe gastric inflammation, accompanied by a marked elevation of total IgE, Anisakis-specific IgE, Ani s 1-specific IgE, and interleukin (IL)-5 in the serum. Active cutaneous anaphylaxis confirmed the presence of functional Anisakis-specific IgE capable of mediating immediate hypersensitivity. Flow cytometry of gastric lamina propria cells showed increased infiltration of IL-5 producing group 2 innate lymphoid cells (ILC2s), eosinophils, IL-4 producing T helper (Th) cells and B cells in mice with repeated infection. Furthermore, immunohistochemistry revealed widespread localization of IL-33-positive cells in the gastric mucosa, consistent with the observed increased levels of truncated IL-33 and total IL-33. These findings suggest that Anisakis infection induces a type 2 immune response through IL-33-driven activation of ILC2s followed by Th2 development, thereby promoting eosinophilia and antigen-specific IgE. This model enables new insights of Anisakis-associated allergic inflammation and may serve as future therapeutic studies.

关键词： Interleukin-23   Interleukin-17   Th17   Spondyloarthritis   Psoriatic arthritis  

摘要： Introduction The lack of efficacy of therapies targeting interleukin (IL)-23 in axial spondyloarthritis (axSpA), despite their proven benefit in psoriatic arthritis (PsA), initially elicited perplexity and questions, ultimately leading the scienti...

关键词： 骨骼肌   骨骼肌再生   卫星细胞   细胞因子   运动   修复   炎症   综述  

摘要： 背景:卫星细胞和骨骼肌再生密切相关,当骨骼肌受到损伤或刺激时,卫星细胞能够迅速被激活并参与骨骼肌的修复过程。卫星细胞受到细胞因子的调控,而且研究表明运动能够促进卫星细胞的增殖和分化,但目前尚不清楚运动是否能够与细胞因子共同作用于卫星细胞促进骨骼肌修复。目的:综述细胞因子和运动对卫星细胞的调控作用,为肌肉疾病的治疗和康复提供新的思路和潜在的干预目标。方法:第一作者和通讯作者于2023-12-01/2024-02-01检索Web of Science、PubMed、中国知网、万方、维普等数据库,检索文献时限为各数据库建库至2024年2月。英文检索词为“skeletal muscle regeneration,satellite cells,cytokines in muscle repair,exercise,muscle stem cells,inflammation and repair”,中文检索词为“骨骼肌,卫星细胞,细胞因子,运动,肌肉再生,肌肉干细胞,炎症和修复”。最终严格按照纳入和排除标准筛选,共纳入76篇文献。结果与结论:①细胞因子在卫星细胞激活中的作用:在骨骼肌损伤后迅速激活卫星细胞,白细胞介素6促进卫星细胞增殖和迁移,从而加速肌肉的修复。肿瘤坏死因子α通过调控细胞凋亡和增殖通路,参与卫星细胞的分化和功能调节。干扰素γ则在炎症反应中发挥重要作用,调控卫星细胞参与肌肉损伤修复的免疫反应。②运动对细胞因子表达的调控作用:耐力运动和抗阻训练能够显著增加血液循环中白细胞介素6和肿瘤坏死因子α水平,进而可能促进卫星细胞的活化,参与骨骼肌再生过程。此外,运动还能增加骨骼肌分泌肌肉特异性蛋白(如肌肉生长抑制素、鸢尾素和胰岛素样生长因子1),这些因子对卫星细胞的增殖和肌肉再生具有重要调控作用。③未来研究的方向与展望:尽管已有研究揭示了多种细胞因子在卫星细胞调控中的关键作用,但相关机制仍需进一步深入探索,未来的研究可以通过整合多组学和生物信息学方法,深入解析不同细胞因子在运动促进骨骼肌损伤修复中的交互作用网络,以优化运动介入策略并提高骨骼肌再生的效率和质量。

关键词： Prunella vulgaris L   Triterpenoid components   Extraction and purification process   UPLC-Q-exactive orbitrap-MS   Anti-Inflammatory activity  

摘要： Prunella vulgaris L. (PV), recorded in Shen Nong Ben Cao Jing, is bitter/pungent, cold, and enters the Liver-Gallbladder meridians. In TCM, it clears liver-fire upward flare (red eyes, headache, dizziness) and treats breast abscess, goiter, and mammary hyperplasia.

关键词： Slowly progressive insulin-dependent diabetes mellitus   Glutamic acid decarboxylase   Insulinoma-associated protein 2   Antigen-specific autoreactive T cells   FACS   Fluorescence-activated cell sorting   FT1D   Fulminant type 1 diabetes   GAD   Glutamic acid decarboxylase 65   HLA   human leukocyte antigen   IA-2   Insulinoma-associated protein 2   PBMCs   Peripheral blood mononuclear cells   SPIDDM   Slowly progressive insulin-dependent diabetes mellitus   TNF-α   Tumor necrosis factor-α   T1DM   Type 1 diabetes mellitus   T1AD   Type 1A diabetes   T1BD   Type 1B diabetes   T2D   Type 2 diabetes  

摘要： Pancreatic islet antigen-specific autoreactive T cells are involved in inflammation in slowly progressive insulin-dependent diabetes mellitus (SPIDDM). Pancreatic islet antigens, such as glutamic acid decarboxylase 65 (GAD), insulinoma-associated protein 2 (IA-2), and insulin, are associated with SPIDDM. However, the association between pancreatic islet antigen-specific T cells and SPIDDM incidence remains unclear.

关键词： Acute inflammation   TNF-α   Spongy-like hydrogel   Hydroxyapatite   3D bone model  

摘要： Inflammatory bone diseases like osteoporosis affect over 200 million people globally, yet the mechanisms by which acute inflammation progresses to chronic remain poorly understood. To address this, we developed an in vitro 3D cortical-sponge bone model of acute inflammation by introducing TNF-α. The model consists of GG-HAp spongy-like hydrogels with osteoblasts from human mesenchymal stem cells (HBM-MSCs) in an outer compartment, and human dermal microvascular endothelial cells plus supporting HBM-MSCs in an inner compartment, mimicking cortical and trabecular bone, respectively. Acute inflammation was induced by TNF-α supplementation (1, 10, or 100 ng/mL) over 7 days, and its impact on vascular assembly, osteogenesis, and inflammation was evaluated via RT-PCR, luminex and ELISA. TNF-α did not affect cell viability and minimally affected angiogenic factors release. However, 100 ng/mL of TNF-α significantly reduced type I collagen, specifically to 53 % at 3 days and to 82 % at 7 days. Pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α, MCP-1, and M-CSF) gene expression and protein release were upregulated in a dose-dependent manner. For instance, 100 ng/mL of TNF-α increased IL-6 gene expression by 2.96 ± 2.38-fold at 3 days and 5.69 ± 3.09-fold at 7 days. Interestingly, 100 ng/mL of TNF-α declined IL-1β, IL-6 and TNF-α protein release from 3 to 7 days, indicating a proper resolution of the acute inflammatory response, mimicking the healing phase in bone repair. Overall, this model replicates acute inflammatory events in bone tissue, providing a quantitative platform to study TNF-α-driven bone dynamics and to evaluate targeted interventions, including anti-TNF-α therapies for osteoporosis.