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关键词： Diabetic nephropathy   IL-6   Polymorphisms  

摘要： Introduction: The pathogenesis of diabetes mellitus (DM) and its complications has been previously linked to elevated levels of interleukin-6 (IL-6);IL-6 triggers intracellular pathways through interaction with the IL-6 receptor (IL-6R). This study aimed to determine the association of single nucleotide polymorphisms (SNPs) IL-6 -597G/A (rs1800797), -572G/C (rs1800796), -174G/C (rs1800795), its receptor (IL-6R) Asp358Ala (+48892A/C, rs2228145) and DM or its complications in the Czech population. Materials and Methods: In total, 669 subjects participated in this case-control study, including 167 controls, 119 patients with type 1 DM (T1DM), and 383 patients with type 2 DM (T2DM). The subjects were monitored for glycemia, glycated hemoglobin, lipid profile, glomerular filtration rate (GFR), and common complications, such as diabetic nephropathy (DN), retinopathy (DR), (poly)neuropathy (DPN), and periodontitis (P). Results: Frequencies of the IL-6 and IL-6R alleles or genotypes, and IL-6 haplotypes were similar between the controls and the patients with T1DM or T2DM (P > 0.05). However, lower values of GFR were observed in diabetic patients with IL-6 -174CC homozygotes compared to other (CG and GG) genotypes (P <= 0.05). In addition, the IL-6R Asp358Ala variant was associated with DN (P = 0.031, OR = 1.74, 95% CI: 1.05-2.89). After subclassification according to the type of DM, the significant association of the IL-6R polymorphism with DN was only found in T1DM (P = 0.013, OR = 2.90, 95% CI: 1.25-6.71). Conclusions: This study implies a significant relationship between the IL-6R Asp358Ala polymorphism and DN in Czech T1DM patients.

关键词： 降钙素原   hs—CRP   白介素-6   血清淀粉样蛋白A   细菌感染  

摘要： 研究PCT、hs—CRP、IL-6及SAA在细菌感染诊断中的作用。方法 选取重症监护室住院患者采用随机法,从已经确诊的感染患者中抽取63例为观察组,从发热未细菌感染患者中抽取50例为对照组,入院后予以降钙素原、hs—CRP、白介素-6及血清淀粉样蛋白A检验,分析最终检验指标。结果 观察组检出PCT、hs—CRP的阳性率高于对照组(P<0.05);观察组检出的PCT、hs—CRP、IL-6及SAA水平均高于对照组(P<0.05);观察组PCT、hs—CRP的占比明显高于对照组(P<0.05)。结论 针对出现发热但不确定是否细菌感染患者,予以降钙素原、hs—CRP、白介素-6及血清淀粉样蛋白A等指标检测,通过获取准确数据有助于判断患者是否存在细菌感染,制定合理治疗方案对细菌进行抑制,提高疾病治疗效果。

摘要： BackgroundInterleukin (IL)-23p19 and IL-17 inhibitors have demonstrated high efficacy for psoriasis in randomized controlled trials, though real-world data, particularly for risankizumab (IL-23p19 inhibitor) and brodalumab (IL-17 receptor (IL-17R) inhibitor), is *** assess drug survival of IL-23p19 and IL-17 inhibitors compared to other biologics for *** conducted a cohort study using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from November 2007 to June 2023. Multivariable flexible parametric models assessed drug survival, with discontinuation due to ineffectiveness and adverse effects reported separately. The primary outcome measure was the absolute difference in restricted mean survival time at 2 years, referred to as adjusted survival time, between all *** 19,034 treatment courses (median follow-up: 2.3 years), treatments included adalimumab (tumour necrosis factor-alpha (TNF-a) inhibitor, n = 6,815), ustekinumab (IL-12/23p40 inhibitor, n = 5,639), secukinumab (IL-17A inhibitor, n = 3,051), ixekizumab (IL-17A inhibitor, n = 1,072), brodalumab (n = 367), guselkumab (IL-23p19 inhibitor, n = 1,258) and risankizumab (n = 832). Guselkumab and risankizumab had the highest adjusted survival times (years [interquartile ranges]) for effectiveness (1.93 [1.91-1.95] and 1.93 [1.90-1.96], respectively). Risankizumab had the highest survival for safety (1.94 [1.92-1.96]) followed by guselkumab (1.92 [1.90-1.94]) and ustekinumab (1.92 [1.91-1.93]). Brodalumab showed lower adjusted survival time for effectiveness (1.75 [1.69-1.81]) than most biologics except secukinumab and adalimumab;and similar survival for safety (1.85 [1.81-1.90]) compared to IL-17A inhibitors and adalimumab. In patients with psoriatic arthritis, ustekinumab showed reduced drug survival. Prior biologic exposure was associated with a dose-response reduction in survival which was significantly large

摘要： In this issue of Blood, Gibson et al1 have identified the impact of HLA alloimmunization in autologous gene-modified hematopoietic cell transplantation (GM-HCT) for transfusion-dependent thalassemia (TDT). Nickel et al have previously reported increased need for platelet and red cell transfusions after MSD HCT due to preexisting HLA and red cell antibodies in patients with sickle cell disease (SCD). © 2025 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

关键词： Ii   MHC   binding interaction   duck   localization  

摘要： Objective:To investigate the intracellular localization and binding of duck invariant chain (Ii) to major histocompatibility complex (MHC) class Iα or MHC class IIβ molecules. Methods:First, the genes of duck Ii, MHC Iα, and MHC IIβ were amplified by PCR, cloned into expression plasmids, and then sequenced to compare homology between ducks and selected agricultural species. Second, Rosetta or 293T cells were transfected with plasmids encoding Ii, MHC Iα, and MHC IIβ either alone or in combination to interrogate binding following expression. The fluorescent reporter molecules used to tag/image transfected cells and expressed protein were identified by western blot. Additionally, the binding interaction of the expressed products was observed by affinity purification using pull-down assay and coimmunoprecipitation. Finally, intracellular colocalization was observed by laser confocal microscopy. Results:The results of western blots demonstrated that all constructed plasmids successfully expressed proteins. Pull down and coimmunoprecipitation revealed that Ii could bind Iα or IIβ, forming Ii-Iα or Ii-IIβ complexes, and they dissociated into single molecules after SDS treatment. In 293T cells, Ii interacts with MHC Iα or MHC IIβ chains and colocalizes intracellularly. Confocal fluorescence microscopy assay indicated that MHC Iα and IIβ were located in the endoplasmic reticulum and endosome. Conclusions:Both MHC and Ii proteins exhibit direct interactions and can colocalize in the endoplasmic reticulum and endosomes. Clinical Relevance:This study investigates the relationship between duck Ii and MHC proteins, offering a theoretical foundation for exploring the role of Ii in immune responses and advancing the development of Ii-vectored avian vaccines.

关键词： 胃癌   术后复发   淋巴细胞亚群   IL-6   PCT   预测价值  

摘要： 目的 探讨外周血淋巴细胞亚群及白细胞介素-6（IL-6）、降钙素原（PCT）的表达对胃癌患者术后复发的预测价值。方法 选取2021年4月至2023年5月于黄石市中心医院行根治性手术治疗的206例胃癌患者作为研究对象,根据是否复发将其分为复发组（58例）和未复发组（148例）。抽取复发组和未复发组静脉血,应用流式细胞术（FCM）对外周血T细胞亚群、NK细胞、B细胞进行测定,应用循环增强荧光免疫发光法对外周血IL-6、PCT进行检测,比较两组人群中各指标的表达情况,绘制受试者工作特征（ROC）曲线评估外周血淋巴细胞亚群及IL-6、PCT的表达水平对胃癌术后复发的预测价值。结果复发组和未复发组中CD3+、CD3+CD8+、CD3+CD4+、CD4+/CD8+均无明显差异（P均>0.05）;复发组CD3-CD19+、CD3-CD56+、IL-6、PCT水平均高于未复发组（P均<0.05）;CD3-CD19+、CD3-CD56+、IL-6、PCT预测胃癌术后复发的曲线下面积（AUC）分别为0.656、 0.682、0.888、0.868,四者联合预测术后复发的AUC为0.919,优于各指标单独预测（P<0.05）。结论 外周血淋巴细胞亚群及IL-6、PCT的表达水平与胃癌患者术后复发有着紧密联系,联合检测可能为胃癌术后复发患者提供更优质的诊断效能和预测价值。

摘要： Unresolved tissue damage is a common feature of Inflammatory Bowel Disease (IBD) that facilitates disease progression. Here, we showed that high animal fat diets (HFD), an environmental risk factor associated with IBD pathogenesis, suppress intestinal macrophage production of critical tissue repair responses after damage. This includes reduced IL-23 production, which drives downstream production of the IL-22, which is needed for barrier repair. Indicating that dietary lipids interfere with responses to microbial molecules needed to induce barrier protective functions, we found oleic acid could directly suppress macrophage induction after lipopolysaccharide (LPS) treatment. Deleting the lipid transporter CD36 on macrophages restored the and response, reducing intestinal damage in HFD-fed DSS-treated mice. We found that CD36-mediated intracellular lipid accumulation, mainly oleic acid, in macrophages leads to peroxisome proliferator-activated receptor delta (PPARd)release of the transcriptional repressor protein B-cell lymphoma 6 (BCL6). BCL6 suppresses transcription in microbe-exposed macrophages. The studies suggest dietary lipid modulation of the macrophage PPARd/BCL6 transcriptional repressor complex is a key mechanism of fat-associated defects in intestinal damage repair and immune dysregulation. Overall, our findings provide new insights into dietary lipid contribution to intestinal disease progression and identify new potential therapeutic targets to decrease diet-associated risk for IBD.

关键词： HLA haplotype frequencies   immunogenetics   population genetics   next-generation sequencing (NGS)  

摘要： Human Leukocyte Antigen (HLA) genes are remarkable for their structural complexity and polymorphism. Located on chromosome 6 within the Major Histocompatibility Complex (MHC), these genes exhibit significant frequency variations across human populations and play a crucial role in immune responses, disease susceptibility, and transplant compatibility. This study aimed to assess the genetic profiles and HLA-A/HLA-B/HLA-C/HLA-DRB1 haplotype frequencies in a Romanian cohort. Whole venous blood samples were collected from 405 healthy, unrelated Romanian volunteers. Using next-generation sequencing (NGS), the study population was genotyped for HLA class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DRB1) loci. Haplotype frequencies were estimated using the expectation-maximization algorithm, addressing phase and allelic ambiguity. The Romanian cohort was compared with multiple populations sourced from the Allele Frequencies Net Database. The study identified 635 different HLA-A/HLA-B/HLA-C/HLA-DRB1 haplotypes. Among them, two haplotypes had frequencies close to 3%: HLA-A*01:01:01/HLA-B*08:01:01/HLA-C*07:01:01/HLA-DRB1*03:01:01, with a frequency of 3.33%, and HLA-A*02:01:01/HLA-B*18:01:01/HLA-C*17:01:01/HLA-DRB1*11:04:01, with a frequency of 2.84%. All other 633 haplotypes (approximately 99.7% of the total) had frequencies below 1%. The results of the current study underscore the extremely high diversity of HLA haplotypes in this population and the fact that even the most frequent haplotypes are relatively low in prevalence (each under 5% in this cohort). These findings and the great haplotypical diversity detected highlight the importance of NGS and high-resolution HLA typing in hematopoietic stem cell and solid organ transplantation, while also contributing to the better understanding of the area-specific population genetics resulting from historical regional dynamics. Further research with larger cohorts is necessary to validate these findings and expand upon their clin

关键词： Mesenchymal stem cells   Inflammation   Phagocytosis   Microglia   Exosome   CD44  

摘要： Identifying the specific bioactive molecules produced by mesenchymal stem cells (MSCs) and the signaling pathways and cell types upon which they act is critical to developing MSC-based therapeutics for inflammatory diseases with high unmet needs. Our study aimed to investigate the impact of extracellular vesicle (EV)-derived TNF-Stimulated Gene-6 (TSG-6, from adipose tissue-derived mesenchymal stem cell concentrated conditioned medium, ASC-CCM or TSG-6 overexpression in ASC using ORF expression-ready clone) on microglia and its potential anti-inflammatory effects. EV but not non-vesicular secretome prepared by ultracentrifugation confirmed the expression of TSG-6 exclusively in the small EV (sEV) fraction. sEV ranged from 50-150 nm as determined by Zetasizer, demonstrated bilipid membrane evidenced by transmission electron microscopy, expressed positive exosomal (e.g. CD63) markers, and were endocytosed by BV2 cells confirmed by DiI fluorescently labeled exosomes. BV2 microglia cultured under serum-free conditions stimulated with TLR4 agonists (LPS and IFN gamma) for 12 h in the presence of p-ASC-EV (sEV derived from ASC after cytokine stimulation) and TSG-6-ORF-EV significantly reduced nitrite release (p < 0.001), phagocytic activity (p < 0.001) and reduced CD44 expression (p < 0.05). CD44 knockdown in BV2 cells ablated TSG-6-ORF-EV mediated nitrite release, IL1 beta downregulation, and phagocytosis with TLR4 agonists. Our results revealed that under cytokine stimulation, the EV portion of ASC-CCM becomes enriched with TSG-6. Overexpressing TSG-6 in ASC leads to an increased concentration of TSG-6 in sEVs. This enriched EV fraction, containing TSG-6, regulates microglial dynamics through a feedback loop with CD44. EV-associated TSG-6 can influence immune cell behavior and signaling, mitigating excessive inflammation or immune dysfunction.