IL-1ra

IL - 1ra
  • 文章类型: Journal Article
    类风湿性关节炎(RA)是一种自身免疫性疾病,可导致关节滑膜组织的慢性炎症,导致关节损伤和严重残疾。尽管正在进行研究,RA的确切病因尚不清楚,目前的治疗方法有局限性。这项研究探索了利用白细胞介素-1受体拮抗剂(IL-1RA)和在同种异体间充质干细胞(MSC)上清液附近极化的抗炎巨噬细胞作为RA新治疗方法的潜力。
    构建含有IL-1RA基因的表达盒并在大肠杆菌BL21中表达。将所得蛋白质纯化并稳定化以用于体内实验。分离骨髓MSC并用于从分离的外周血单核细胞产生抗炎M2巨噬细胞。然后将巨噬细胞用于治疗由II型胶原诱导的RA小鼠。
    IL-1RA和M2巨噬细胞的组合改善了该疾病的临床和组织病理学症状,炎症因子水平降低,并调节治疗小鼠组中的免疫系统。结果表明,这种联合疗法对RA治疗具有协同作用。
    同时使用IL-1RA和M2细胞可能是治疗RA的有希望的方法。这种联合疗法有可能改善RA患者的疾病并降低炎症的严重程度。
    UNASSIGNED: Rheumatoid arthritis (RA) is a type of autoimmune disease that results in chronic inflammation of the joint synovial tissue, leading to joint damage and significant disability. Despite ongoing research, the exact cause of RA remains unclear, and current treatments have limitations. This study explores the potential of utilizing interleukin-1 receptor antagonist (IL-1RA) and anti-inflammatory macrophages polarized in the vicinity of the supernatant from allogeneic mesenchymal stem cells (MSCs) as a novel therapeutic approach for RA.
    UNASSIGNED: An expression cassette containing the IL-1RA gene was constructed and expressed in E. coli BL21. The resulting protein was purified and stabilized for use in in vivo experiments. Bone marrow MSCs were isolated and used to produce anti-inflammatory M2 macrophages from the isolated peripheral blood monocytes. The macrophages were then used to treat mice with RA induced by collagen type II.
    UNASSIGNED: The combination of IL-1RA and M2 macrophages improved clinical and histopathological symptoms of the disease, reduced levels of inflammatory factors, and modulated the immune system in the treated mouse groups. The results showed that this combinatory therapy had a synergistic effect for RA treatment.
    UNASSIGNED: The simultaneous use of IL-1RA and M2 cells could be a promising approach for the treatment of RA. This combinatory therapy has the potential to improve the disease and decrease the severity of inflammation in patients with RA.
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  • 文章类型: Journal Article
    胰腺癌是一种非常侵袭性的疾病,预后不佳。肿瘤微环境通过分泌多种细胞因子发挥免疫抑制活性,包括白细胞介素(IL)-1。IL-1/IL-1受体(IL-1R)轴是肿瘤促进T辅助(Th)2-和Th17型炎症的关键调节因子。Th2细胞通过由IL-1激活的癌症相关成纤维细胞(CAF)分泌的胸腺基质淋巴细胞生成素(TSLP)被赋予Th2极化能力的树突状细胞分化。Thl7细胞在IL-1和其他IL-1调节的细胞因子存在下分化。在胰腺癌中,使用重组IL-1R拮抗剂(IL1RA,anakinra,ANK)在体外和体内模型中已显示出靶向IL-1/IL-1R途径的功效。在这项研究中,我们已经开发了负载ANK的鞘磷脂纳米系统(SNs)(ANK-SNs),以比较它们在体外抑制Th2-和Th17型炎症的能力与游离药物的能力。我们发现ANK-SNs以与ANK相似的水平抑制TSLP和CAF释放的其他促肿瘤细胞因子。重要的是,抑制Th17细胞分泌IL-17,但不是干扰素-γ,明显更高,在较低的浓度下,ANK-SNs与ANK相比。总的来说,使用ANK-SNs可能有利于减少药物的有效剂量及其毒性作用.
    Pancreatic cancer is a very aggressive disease with a dismal prognosis. The tumor microenvironment exerts immunosuppressive activities through the secretion of several cytokines, including interleukin (IL)-1. The IL-1/IL-1 receptor (IL-1R) axis is a key regulator in tumor-promoting T helper (Th)2- and Th17-type inflammation. Th2 cells are differentiated by dendritic cells endowed with Th2-polarizing capability by the thymic stromal lymphopoietin (TSLP) that is secreted by IL-1-activated cancer-associated fibroblasts (CAFs). Th17 cells are differentiated in the presence of IL-1 and other IL-1-regulated cytokines. In pancreatic cancer, the use of a recombinant IL-1R antagonist (IL1RA, anakinra, ANK) in in vitro and in vivo models has shown efficacy in targeting the IL-1/IL-1R pathway. In this study, we have developed sphingomyelin nanosystems (SNs) loaded with ANK (ANK-SNs) to compare their ability to inhibit Th2- and Th17-type inflammation with that of the free drug in vitro. We found that ANK-SNs inhibited TSLP and other pro-tumor cytokines released by CAFs at levels similar to ANK. Importantly, inhibition of IL-17 secretion by Th17 cells, but not of interferon-γ, was significantly higher, and at lower concentrations, with ANK-SNs compared to ANK. Collectively, the use of ANK-SNs might be beneficial in reducing the effective dose of the drug and its toxic effects.
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  • 文章类型: Journal Article
    由于其半衰期短,必须每天注射Anakinra,这导致患者依从性降低。因此,本研究的目的是制备具有白蛋白结合域(ABD)的白细胞介素-1受体拮抗剂(IL-1Ra)作为新型融合蛋白,并评估其与白蛋白的结合能力及其生物学效应.
    通过MODELLER软件预测IL-1Ra-ABD的三维结构,并通过HADDOCK服务器评估其与IL-1R的相互作用。IL-1Ra-ABD的表达在与可溶形式的pTWIN1的内含肽1融合的大肠杆菌中进行,然后纯化。IL-1Ra-ABD对人血清白蛋白(HSA)的亲和力在天然-PAGE上测定,并评估了其随时间的释放百分比。此外,用MTT法测定重组IL-1Ra-ABD对A375和HEK293细胞系中IL-1β的拮抗特性。
    IL-1Ra-ABD与IL-1R的稳定复合物确立了由于将ABD添加到IL-1Ra中而不存在空间位阻。在15°C下使用0.1mMIPTG诱导内含肽1-IL-1Ra-ABD的表达,其切割代表约50和23kDa的条带。此外,孵育2小时后,约78%的IL-1Ra-ABD附着于HSA,MTT分析显示IL-1Ra-ABD和天然IL-1Ra在细胞存活中的作用之间没有显著差异。
    成功地产生了可溶性IL-1Ra-ABD,而IL-1Ra拮抗作用没有显着差异。IL-1Ra-ABD显示与HSA的合适相互作用,并随时间释放。然而,IL-1Ra-ABD在体内的半衰期必须在随后的研究中确定。
    UNASSIGNED: Anakinra must be injected daily due to its short half-life and this leads to lower patient compliance. Therefore, the aim of this study was to produce an interleukin-1 receptor antagonist (IL-1Ra) with albumin binding domain (ABD) as a novel fusion protein and evaluate its binding ability to albumin and its biological effects.
    UNASSIGNED: The three-dimensional structure of IL-1Ra-ABD was predicted by MODELLER software and its interaction with IL-1R was evaluated by the HADDOCK server. The expression of IL-1Ra-ABD was performed in E. coli in fusion with intein 1 of pTWIN1 in soluble form and then purified. The affinity of IL-1Ra-ABD to human serum albumin (HSA) was determined on native-PAGE, and its release percent toward time was evaluated. Moreover, an MTT assay was used to determine the antagonizing properties of recombinant IL-1Ra-ABD against IL-1β in A375 and HEK293 cell lines.
    UNASSIGNED: The stable complex of IL-1Ra-ABD with IL-1R established the absence of steric hindrance due to the addition of ABD to IL-1Ra. The expression induction of intein 1-IL-1Ra-ABD using 0.1 mM IPTG at 15 °C, and its cleavage represented bands approximately in 50 and 23 kDa. Furthermore, about 78% of IL-1Ra-ABD was attached to the HSA after 2 h of incubation, and the MTT assay showed no significant differences between the effects of IL-1Ra-ABD and native IL-1Ra in cell survival.
    UNASSIGNED: The production of soluble IL-1Ra-ABD with no significant differences in IL-1Ra antagonizing effects was successfully performed. IL-1Ra-ABD showed suitable interaction with HSA and was released over time. However, the half-life of IL-1Ra-ABD in vivo must be determined in the subsequent investigations.
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  • 文章类型: Journal Article
    营养保健免疫支持为设计具有互补作用机制的混合物提供了潜力,以强大地支持先天免疫警觉性。我们记录了当牛初乳肽(BC-Pep)添加到含有酵母β-葡聚糖的免疫混合物(IB)中时增强的免疫激活,香菇,maitake,和植物性非β-葡聚糖多糖。人外周血单核细胞(PBMC)与IB培养,BC-Pep,和IB+BC-Pep持续20小时,然后在NK细胞上评估活化标记CD69的表达,NKT细胞,和T细胞。在培养上清液中测试细胞因子水平。将PBMC与K562靶细胞共培养以评估T细胞介导的细胞毒性。IB+BC-Pep引发IL-1β高度显著增加,IL-6和TNF-α,高于用匹配剂量的IB或BC-Pep处理的培养物。通过IB+BC-Pep增加NK细胞和T细胞活化,达到比单独BC-Pep或IB高几倍的CD69表达水平。IB+BC-Pep显著增加K562靶细胞的T细胞介导的细胞毒性杀伤。这种协同作用表明,由于BC-Pep对IB诱导的信号传导途径的调节,NK细胞和T细胞的信号转导的独特放大,并且对于针对病毒感染和转化的细胞的免疫防御活性的进一步临床前和临床试验是有意义的。
    Nutraceutical immune support offers potential for designing blends with complementary mechanisms of action for robust support of innate immune alertness. We documented enhanced immune activation when bovine colostrum peptides (BC-Pep) were added to an immune blend (IB) containing β-glucans from yeast, shiitake, maitake, and botanical non-β-glucan polysaccharides. Human peripheral blood mononuclear cells (PBMCs) were cultured with IB, BC-Pep, and IB + BC-Pep for 20 h, whereafter expression of the activation marker CD69 was evaluated on NK cells, NKT cells, and T cells. Cytokine levels were tested in culture supernatants. PBMCs were co-cultured with K562 target cells to evaluate T cell-mediated cytotoxicity. IB + BC-Pep triggered highly significant increases in IL-1β, IL-6, and TNF-α, above that of cultures treated with matching doses of either IB or BC-Pep. NK cell and T cell activation was increased by IB + BC-Pep, reaching levels of CD69 expression several fold higher than either BC-Pep or IB alone. IB + BC-Pep significantly increased T cell-mediated cytotoxic killing of K562 target cells. This synergistic effect suggests unique amplification of signal transduction of NK cells and T cells due to modulation of IB-induced signaling pathways by BC-Pep and is of interest for further pre-clinical and clinical testing of immune defense activity against virally infected and transformed cells.
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  • 文章类型: Journal Article
    (1)背景:Fuchs内皮角膜营养不良(FECD)患者可能合并白内障,因此,可能需要白内障手术,由于潜在的内皮细胞损伤,这带来了挑战。FECD是一种病因不明的退行性眼病,炎性细胞因子可能在其发生发展中起重要作用。本研究旨在研究患有白内障的FECD眼房水中的细胞因子谱。(2)方法:52例患者纳入研究,26以FECD+白内障和26以白内障为对照组。使用Bio-Plex200系统分析房水样品的促炎和抗炎细胞因子。(3)结果:与对照组/白内障组相比,FECD+白内障患者房水白细胞介素1受体拮抗剂(IL-1Ra)和白细胞介素IL-8水平明显增高。此外,与对照组相比,FECD+白内障组的抗炎IL-10水平呈较高趋势.相比之下,IL-1β无统计学差异,IL-6、IL-4、IL-10、IL-13、IL-17A、各组间肿瘤坏死因子TNF-α。(4)结论:本研究有助于更好地理解FECD的发病机制。IL-1Ra和IL-8水平的升高可能是患有FECD和共存白内障的人的防御机制。
    (1) Background: Patients with Fuchs\' endothelial corneal dystrophy (FECD) may have coexisting cataracts and, therefore, may require a cataract surgery, which poses challenges due to potential endothelial cell damage. FECD is a degenerative eye disease of unclear etiology, with inflammatory cytokines maybe playing an important role in its development and progression. The present study aimed to investigate the cytokine profile in the aqueous humor of FECD eyes with cataract. (2) Methods: Fifty-two patients were included in the study, 26 with FECD + cataract and 26 with cataract as a control group. Samples of the aqueous humor were analyzed for pro- and anti-inflammatory cytokines using a Bio-Plex 200 system. (3) Results: Interleukin 1 receptor antagonist (IL-1Ra) and interleukin IL-8 levels were significantly higher in the aqueous humor of FECD + cataract patients compared to the control/cataract group. Moreover, the levels of anti-inflammatory IL-10 showed a strong trend to be higher in the FECD + cataract group compared to the control group. In contrast, there were no statistically significant differences in IL-1β, IL-6, IL-4, IL-10, IL-13, IL-17A, and tumor necrosis factor TNF-α between the groups. (4) Conclusions: Presented research contributes to a better understanding of FECD pathogenesis. Elevated levels of IL-1Ra and IL-8 may serve as a defense mechanism in people with FECD and coexisting cataract.
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  • 文章类型: Journal Article
    炎性细胞因子(IC)在勃起功能障碍(ED)中起重要作用。以前的研究表明,大多数ED患者有高水平的肿瘤坏死因子-α(TNF-α),白细胞介素-6(IL-6)和白细胞介素-8(IL-8)。使用孟德尔随机化(MR)方法研究了41个IC和ED之间的因果关系。
    41个IC的单核苷酸多态性(SNP)暴露数据来自8293个受试者的全基因组关联研究(GWAS)。同时,FINNGENR9数据库提供了包含2205例ED患者和164104例对照的ED结局数据.MR-Egger(ME),方差逆加权(IVW),和加权中位数(WM)用于进行MR研究,以IVW为主要标准。
    从遗传的角度来看,干扰素诱导蛋白-10(IP-10)水平的升高显著增加ED的风险(P=0.043,比值比(OR)=1.269,95%置信区间(95CI):1.007-1.600),而白细胞介素-1受体拮抗剂(IL-1RA)的增加显着降低了ED的风险(P=0.037,OR=0.768,95CI:0.600-0.984)。同时,IP-10(p=0.099)和IL-1RA(p=0.135)在反向MR分析中未能证明因果关系。
    IC水平的变化将显著影响ED的风险,特别是IP-10作为ED的风险成分和IL-1RA作为ED的保护成分。在未来,通过对特定炎症因子的干预,可以实现对ED的针对性治疗和预防。
    UNASSIGNED: Inflammatory cytokines (ICs) play an important role in erectile dysfunction (ED). Previous studies have demonstrated that most ED patients have high levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8). The causality between 41 ICs and ED is investigated using the Mendelian randomization (MR) approach.
    UNASSIGNED: Single nucleotide polymorphisms (SNPs) exposure data of 41 ICs came from a genome-wide association study (GWAS) of 8293 subjects. At the same time, the FINNGEN R9 database provided the ED outcome data containing 2205 ED patients and 164104 controls. MR-Egger (ME), inverse variance weighting (IVW), and weighted median (WM) were applied to conduct the MR study and IVW was taken as the main criterion.
    UNASSIGNED: From a genetic perspective, the increase of interferon-inducible protein-10 (IP-10) level significantly increased the risk of ED (P=0.043, odds ratio (OR)=1.269, 95% confidence interval (95%CI): 1.007-1.600), while the increase of interleukin-1 receptor antagonist (IL-1RA) markedly decreased the risk of ED (P=0.037, OR=0.768, 95%CI: 0.600-0.984). Meanwhile, IP-10 (p=0.099) and IL-1RA (p=0.135) failed to demonstrate causality in reverse MR analysis.
    UNASSIGNED: Changes in ICs levels will significantly affect the risk of ED, especially IP-10 as a risk component for ED and IL-1RA as a protective component for ED. In the future, we can achieve targeted treatment and prevention of ED by intervening with specific inflammatory factors.
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  • 文章类型: Preprint
    免疫系统在神经退行性疾病中具有动态作用,嘌呤受体允许免疫细胞识别神经元信号,细胞损伤,或压力。嘌呤能受体7(P2RX7)可调节炎症级联反应,其在阿尔茨海默病(AD)脑组织中的表达上调。P2RX7表达富集在小胶质细胞中,在大脑中β淀粉样蛋白斑块周围的小胶质细胞中发现水平升高。虽然P2RX7被认为在神经退行性疾病中起作用,它如何调节病理和疾病进展还没有很好的理解。这里,我们利用人类单核细胞衍生的小胶质细胞样细胞(MDMi)模型来询问P2RX7活化和下游对小胶质细胞功能的影响.通过使用来自人类捐赠者的MDMi,我们可以研究人类供体变异如何影响小胶质细胞功能。我们评估了P2RX7驱动的IL1β和IL18的产生以及淀粉样β肽1-42(Aβ1-42)的摄取水平。我们的结果表明,ATP刺激MDMi引发IL1β和IL18表达上调。细胞因子基因表达的这种上调被A740003P2RX7拮抗剂阻断。我们发现,高细胞外ATP条件也降低了Aβ1-42摄取的MDMi能力,并且通过A740003抑制P2RX7来防止这种功能丧失。此外,用IL-1RA限制ATP驱动的IL1β和IL18基因表达上调预处理MDMi,表明P2RX7的ATP免疫调节是IL-1R依赖性的。与单独的ATP治疗相比,IL-1RA预处理的Aβ1-42摄取更高,提示P2RX7通过IL-1信号调节吞噬。总的来说,我们的结果表明,P2RX7是人类小胶质细胞样细胞中高细胞外ATP的关键反应蛋白,其功能可通过IL-1信号调节。这项工作为将来研究抗IL-1生物制剂以增加淀粉样β的清除打开了大门。
    The immune system has a dynamic role in neurodegenerative diseases, and purinergic receptors allow immune cells to recognize neuronal signaling, cell injury, or stress. Purinergic Receptor 7 (P2RX7) can modulate inflammatory cascades and its expression is upregulated in Alzheimer\'s disease (AD) brain tissue. P2RX7 expression is enriched in microglia, and elevated levels are found in microglia surrounding amyloid-beta plaques in the brain. While P2RX7 is thought to play a role in neurodegenerative diseases, how it modulates pathology and disease progression is not well understood. Here, we utilize a human monocyte-derived microglia-like cell (MDMi) model to interrogate P2RX7 activation and downstream consequences on microglia function. By using MDMi derived from human donors, we can examine how human donor variation impacts microglia function. We assessed P2RX7-driven IL1β and IL18 production and amyloid-beta peptide 1-42 (Aβ1-42) uptake levels. Our results show that ATP-stimulation of MDMi triggers upregulation of IL1β and IL18 expression. This upregulation of cytokine gene expression is blocked with the A740003 P2RX7 antagonist. We find that high extracellular ATP conditions also reduced MDMi capacity for Aβ1-42 uptake, and this loss of function is prevented through A740003 inhibition of P2RX7. In addition, pretreatment of MDMi with IL-1RA limited ATP-driven IL1β and IL18 gene expression upregulation, indicating that ATP immunomodulation of P2RX7 is IL-1R dependent. Aβ1-42 uptake was higher with IL-1RA pretreatment compared to ATP treatment alone, suggesting P2RX7 regulates phagocytic engulfment through IL-1 signaling. Overall, our results demonstrate that P2RX7 is a key response protein for high extracellular ATP in human microglia-like cells, and its function can be modulated by IL-1 signaling. This work opens the door to future studies examining anti-IL-1 biologics to increase the clearance of amyloid-beta.
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  • 文章类型: Journal Article
    背景:白细胞介素-1受体拮抗剂(DIRA)缺乏是一种罕见的危及生命的常染色体隐性遗传性自身炎症性疾病,其症状包括但不限于骨髓炎,骨膜炎,和全身性炎症。DIRA是从编码IL-1受体拮抗剂(IL-1RA)的IL1RN基因的功能丧失双等位基因突变发展而来的,导致不受控制的促炎信号和随后的全身性炎症。因此,作为重组IL-1RA的anakinra已成为治疗DIRA的主要药物。尽管anakinra对DIRA的完全缓解有效,它还显示出各种副作用。为了确认与DIRA治疗相关的疗效和安全性问题,我们进行了文献综述和二次数据分析,以增强我们对这一重要主题的理解。
    方法:通过全面的文献检索,我们已经确定了15篇论文,对25名患者进行了研究。人口统计,临床,提取遗传数据,随后进行统计分析,以支持anakinra治疗的生理机制。
    结果:通过文献回顾和数据分析,结果发现,88%的患者在持续接受anakinra治疗后,DIRA的临床完全缓解;患者的血红蛋白平均改善(+3.18g/dL),红细胞沉降率(-53.4mm/h),和C反应蛋白(-135.45mg/L)水平,提示改善造血功能和炎症反应是阿那党乐治疗的一种机制。还从患者数据中确定了导致IL-1RA功能丧失的各种遗传变异,提供真实的患者基因组数据来支持anakinra治疗。
    结论:考虑到临床研究受特定条件影响的不一致和某些差异,本综述与数据分析一起证实了阿纳金拉治疗DIRA的有效性和安全性.
    BACKGROUND: Deficiency of interleukin-1 receptor antagonist (DIRA) is a rare life-threatening autosomal recessive autoinflammatory disease with symptoms including but not limited to osteomyelitis, periostitis, and systemic inflammation. DIRA is developed from the loss-of-function biallelic mutations of the IL1RN gene that encodes IL-1 receptor antagonist (IL-1RA), leading to the unchecked pro-inflammatory signaling and subsequent systemic inflammation. Thus, anakinra as the recombinant IL-1RA has become the primary drug to treat DIRA. Although anakinra has been effective for the complete remission of DIRA, it has also shown various side effects. To confirm the efficacy and safety issues associated with DIRA treatment, we conducted a literature review and secondary data analysis to enhance our understanding on this important topic.
    METHODS: Through comprehensive literature search, we have identified 15 papers with 25 patients studied. The demographic, clinical, and genetic data were extracted, followed by statistical analysis to support the physiological mechanisms of anakinra treatment.
    RESULTS: Through the literature review and data analysis, it was found that 88% of patients had complete clinical remission of DIRA upon continual treatment with anakinra; patients had a mean improvement of Hemoglobin (+3.18 g/dL), Erythrocyte Sedimentation Rate (-53.4 mm/h), and C-reactive Protein (-135.45 mg/L) levels, suggesting that the improvement of hematopoietic function and inflammation is a mechanism for anakinra treatment. Various genetic variants were also identified from the patient data that cause the loss of function of IL-1RA, providing real patient genomic data to support the anakinra treatment.
    CONCLUSIONS: Considering the inconsistency and certain variations from clinical research influenced by specific conditions, this review along with the data analysis confirms the efficacy and safety of anakinra treatment for DIRA.
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  • 文章类型: Journal Article
    背景:迫切需要更有效,更方便的诊断方法来减轻结核病(TB)的负担。本研究探讨了基于QuantiFERON-TBGoldPlus(QFT-Plus)的多种细胞因子分泌,并筛选具有诊断潜力的最佳细胞因子以区分TB感染状态。
    方法:20名活动性肺结核(ATB)患者,15例潜伏性结核感染(LTBI)患者,纳入10例既往结核病患者和10例健康对照(HC).收集全血样品并用QFT-Plus的TB1和TB2抗原刺激。IFN-γ的水平,TNF-α,IL-2、IL-6、IL-5、IL-10、IP-10、IL-1Ra、通过基于Luminex珠的多重测定测量上清液中的CXCL-1和MCP-1。采用受试者工作特征曲线评价细胞因子对不同结核感染状态的诊断准确性。
    结果:用QFT-PlusTB1和TB2抗原刺激后,所有细胞因子的水平,除了TB2管中的IL-5,ATB组明显高于HC组。IL-1Ra的水平同时显示出同样最高的AUC,以区分TB感染和HC。其次是TB1管和TB2管中的IP-10水平。此外,IP-10水平显示出区别ATB患者和非ATB患者的最大AUC。同时,在区分ATB患者和LTBI患者的TB1管和TB2管中,IP-10的水平也显示出最大的AUC.
    结论:除常规检测IFN-γ外,基于QFT-Plus测量IP-10和IL-1Ra可能具有更巨大的潜力来区分不同的TB感染状态。
    BACKGROUND: More efficient and convenient diagnostic method is a desperate need to reduce the burden of tuberculosis (TB). This study explores the multiple cytokines secretion based on QuantiFERON-TB Gold Plus (QFT-Plus), and screens for optimal cytokines with diagnostic potential to differentiate TB infection status.
    METHODS: Twenty active tuberculosis (ATB) patients, fifteen patients with latent TB infection (LTBI), ten patients with previous TB and ten healthy controls (HC) were enrolled. Whole blood samples were collected and stimulated by QFT-Plus TB1 and TB2 antigens. The levels of IFN-γ, TNF-α, IL-2, IL-6, IL-5, IL-10, IP-10, IL-1Ra, CXCL-1 and MCP-1 in supernatant were measured by Luminex bead-based multiplex assays. The receiver operating characteristic curve was used to evaluate the diagnostic accuracy of cytokine for distinguishing different TB infection status.
    RESULTS: After stimulation with QFT-Plus TB1 and TB2 antigens, the levels of all cytokines, except IL-5 in TB2 tube, in ATB group were significantly higher than that in HC group. The levels of IL-1Ra concurrently showed the equally highest AUC for distinguishing TB infection from HC, followed by the levels of IP-10 in both TB1 tube and TB2 tube. Moreover, IP-10 levels displayed the largest AUC for distinguishing ATB patients from non-ATB patients. Meanwhile, the levels of IP-10 also demonstrated the largest AUC in both TB1 tube and TB2 tube for distinguishing ATB patients from LTBI.
    CONCLUSIONS: In addition to conventional detection of IFN-γ, measuring IP-10 and IL-1Ra based on QFT-Plus may have the more tremendous potential to discriminate different TB infection status.
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  • 文章类型: Journal Article
    背景技术富血小板血浆(PRP)是通过离心全血制备的自体产物。据报道,PRP具有高的组织修复潜力和抗炎性质。最近,PRP已成为骨关节炎的潜在治疗选择,有助于缓解疼痛和改善机车。然而,PRP的潜在治疗机制和关键生化因素尚不清楚.本研究旨在通过比较使用Luminex测定法从同一患者制备的血清和PRP来评估PRP治疗中涉及的组织修复的主要因素。方法从9名健康志愿者中收集血液样本,制备血清和PRP。PRP是使用DePuySynthesMitek运动医学(Raynham,马萨诸塞州,美国),这是一种市售的PRP制备试剂盒。白细胞计数,血红蛋白水平,在医院的临床实验室中,使用XE-5000™自动血液学系统(Sysmex,神户,日本)。然后使用Luminex测定对血清和PRP进行生物因素的比较分析。结果发现PRP的白细胞和血小板计数明显高于全血,血红蛋白水平较低。此外,PRP含有明显较高水平的各种因素,包括白细胞介素(IL)-1ra,IL-10,IL-13,C-C基序趋化因子配体(CCL)-2,CCL3,CCL4,CCL8,CCL13,CCL21,C-X-C基序趋化因子配体(CXCL)-10,基质金属蛋白酶(MMP)-3,MMP-9,分化簇(CD)40配体,血管内皮生长因子(VEGF),VEGF-C,血小板衍生生长因子(PDGF)-AB,PDGF-BB,和骨形态发生蛋白(BMP)-2。此外,PRP中IL-1ra和IL-4与白细胞计数呈显著相关,而VEGF与血小板计数有显著相关性。结论PRP含有多种因子的含量高于血清。具体来说,抗炎细胞因子IL-1ra的显着增加被认为是PRP的主要治疗机制。
    Background Platelet-rich plasma (PRP) is an autologous product prepared by centrifuging whole blood. PRP is reported to have high tissue repair potential and anti-inflammatory properties. Recently, PRP has become a potential treatment option for osteoarthritis, contributing to pain relief and locomotive improvement. However, the underlying therapeutic mechanisms and key biochemical factors in PRP remain unclear. This study aimed to estimate the major factors for tissue repair involved in PRP treatment by comparing between serum and PRP prepared from the same patients using the Luminex assay. Methodology Blood samples were collected from nine healthy volunteers, and serum and PRP were prepared. PRP was prepared using a PEAK©︎ PRP SYSTEM kit of DePuy Synthes Mitek Sports Medicine (Raynham, Massachusetts, USA), which is a commercially available PRP preparation kit. The white blood cell count, hemoglobin level, and platelet count were automatically measured for both whole blood and PRP in the hospital\'s clinical laboratory using the XE-5000™ Automated Hematology System (Sysmex, Kobe, Japan). Comparative analysis of biological factors was then performed using the Luminex assay on serum and PRP. Results PRP was found to have significantly higher white blood cell and platelet counts and lower hemoglobin levels than whole blood. Furthermore, PRP contained significantly higher levels of various factors, including interleukin (IL)-1ra, IL-10, IL-13, C-C motif chemokine ligand (CCL)-2, CCL3, CCL4, CCL8, CCL13, CCL21, C-X-C motif chemokine ligand (CXCL)-10, matrix metalloproteinase (MMP)-3, MMP-9, cluster of differentiation (CD) 40 ligand, vascular endothelial growth factor (VEGF), VEGF-C, platelet-derived growth factor (PDGF)-AB, PDGF-BB, and bone morphogenic protein (BMP)-2. Additionally, IL-1ra and IL-4 showed significant correlations with white blood cell counts in PRP, whereas VEGF had a significant correlation with platelet counts. Conclusions PRP contains various factors in higher quantities than serum. Specifically, the notable increase in the anti-inflammatory cytokine IL-1ra is suggested to play a key role as a major therapeutic mechanism of PRP.
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