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Association of single nucleotide polymorphisms of TLR2, TLR4 and TLR9 with atopic dermatitis TLR2、TLR4和TLR9单核苷酸多态性与特应性皮炎的关系
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-aos-2807
O. A. Svitich, O. Olisova, E. Meremianina, N. D. Rasskazova, V. A. Fomina, M. Potapova
Toll-like receptors (TLRs) are the most studied among all Pattern Recognition Receptors, the main function of which is to initiate innate immune response by recognizing pathogen-associated molecular patterns of various microorganisms on the skin surface. TLR-mediated recognition plays an important role in linking innate and adaptive immunity that ultimately leads to the production of key cytokines, chemokines and antimicrobial peptides. Today, there is growing interest in research on single nucleotide polymorphisms (SNPs) in TLR genes and its influence on susceptibility to inflammatory disease, including atopic dermatitis. The aim of the research was to study the association of the rs5743708 gene polymorphism in the TLR2 gene, the rs4986791 gene polymorphism in the TLR4 gene and the rs352140 gene polymorphism in the TLR9 gene with the risk of developing severe cases of AD. A total of 100 patients with AD were included in the study (38 male and 62 female). The age range was from 18 to 65 years old. All participants were divided into 2 groups according to the SCORAD index (SCORing Atopic Dermatitis). The control group included 72 volunteers over 18 years old. The results of our study showed a statistically significant difference between the moderate AD group and healthy controls in the rs352140 gene polymorphism in the TLR9 gene (Figure 1). The frequency of the GG genotype of SNP rs352140 in TLR9 was 0.169 in the AD group versus 0.329 in the control group (p < 0.05; OR = 0.42; 95% CI = 0.18-0.97).In conclusion, the results of our study showed that the TLR9 rs352140 gene polymorphism may be linked to an increased risk of atopic dermatitis. Moreover, it was found that the GG genotype of SNP rs352140 in TLR9 can be used as a predictor of the risk of developing moderate AD.
toll样受体(Toll-like receptor, TLRs)是所有模式识别受体中研究最多的一种,其主要功能是通过识别皮肤表面各种微生物病原体相关的分子模式来启动先天免疫反应。tlr介导的识别在连接先天免疫和适应性免疫中起着重要作用,最终导致关键细胞因子、趋化因子和抗菌肽的产生。如今,人们对TLR基因的单核苷酸多态性(snp)及其对炎症性疾病(包括特应性皮炎)易感性的影响的研究越来越感兴趣。本研究旨在研究TLR2基因中rss5743708基因多态性、TLR4基因中rs4986791基因多态性、TLR9基因中rs352140基因多态性与AD重症发病风险的关系。研究共纳入100例AD患者(男性38例,女性62例)。年龄范围从18岁到65岁。根据评分特应性皮炎(SCORAD)指数将所有参与者分为2组。对照组包括72名18岁以上的志愿者。我们的研究结果显示,中度AD组与健康对照组的TLR9基因rs352140基因多态性差异有统计学意义(图1)。中度AD组TLR9中SNP rs352140的GG基因型频率为0.169,对照组为0.329 (p < 0.05;Or = 0.42;95% ci = 0.18-0.97)。总之,我们的研究结果表明,TLR9 rs352140基因多态性可能与特应性皮炎风险增加有关。此外,我们发现TLR9中SNP rs352140的GG基因型可以作为中度AD发生风险的预测因子。
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引用次数: 0
Experimental application results of mesenchymal stem cell microvesicles in the mouse model of acute renal failure 间充质干细胞微泡在急性肾功能衰竭小鼠模型中的实验应用结果
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-ear-2716
I. Ivanova, G. Seledtsova, V. Seledtsov, T. Khabalova, A. B. Dorzhieva
An important role in restoration of damaged organs and tissues is played by mesenchymal stem cells (MSCs) and microvesicular particles (MV) produced by them. They can be a source of cytokines, anti- apoptotic and growth stimulating factors. In addition, MVs carry out transport of mRNA, miRNA, and signal proteins into damaged tissues. This increases the ability of cells to regenerate and to inhibit apoptosis, promote to angiogenesis and stimulate cell proliferation. The aim of our research was to study the immunoregulatory and pro-regenerative properties of mesenchymal stem cell microvesicles (MSC-MV) in a model of glycerol- induced acute renal failure (ARF) in mice. The experiments were carried out on CBA mice aged 3-4 months. AKI was induced by a single intramuscular injection of 50% glycerol. MSCs were obtained from the bone marrow of healthy animals and cultivated under standard conditions. Microvesicles were obtained by centrifugation at 12000g of MSC supernatant after induction of their apoptosis by culturing under oxygen deprivation conditions and in serum-free medium. MSC-MV was injected intravenously into the retroorbital sinus one day after induction of ARF. The MV dose was calculated as equivalent to (derived from) 1 million MSCs, which was 100 mL per mouse. Animals were taken out of the experiment on days 4 and 11 after MSC-MV injection. Blood plasma was taken to determine the level of creatinine, urine – for albumin analysis, kidneys – for histological examination. It has been shown that MVs induced by MSCs dose-dependently stimulated splenocyte proliferation in both spontaneous and Con-A induced tests. The addition of MV caused a decrease in doxorubicin-induced apoptosis of splenic lymphocytes in mice. Probably, in this case, MV produced by MSCs had an immunostimulatory and antiapoptotic effect. Also, MVs had a positive impact on the restoration of structure and function kidneys in a model of ARF in mice. The use of MSC-MV in treatment of acute renal failure induced by a single injection of 50% glycerol contributed to decrease albumin level urine and restoration of creatinine level in blood serum of animals. Morphological studies have shown decrease in the height cell and collecting duct diameter in the medulla and a decrease in the largest transverse diameter of superficial glomeruli in the renal cortex of sick mice. Thus, the obtained results indicate significant therapeutic and pro-regenerative properties of MSC-MV, which require further study.
间充质干细胞(MSCs)及其产生的微泡颗粒(MV)在受损器官和组织的修复中起着重要作用。它们可以是细胞因子、抗凋亡因子和生长刺激因子的来源。此外,mv还将mRNA、miRNA和信号蛋白转运到受损组织中。增加细胞再生能力,抑制细胞凋亡,促进血管生成,刺激细胞增殖。我们的研究目的是研究间充质干细胞微泡(MSC-MV)在甘油诱导的小鼠急性肾功能衰竭(ARF)模型中的免疫调节和促再生特性。实验以3 ~ 4月龄CBA小鼠为实验对象。单次肌内注射50%甘油诱导AKI。从健康动物骨髓中获得MSCs,并在标准条件下培养。在缺氧条件下和无血清培养基中培养诱导细胞凋亡后,在12000g间充质干细胞上清液中离心获得微囊泡。在ARF诱导1天后,将MSC-MV静脉注入眶后窦。MV剂量计算相当于(源自)100万个MSCs,即每只小鼠100 mL。小鼠于注射MSC-MV后第4天和第11天退出实验。血浆测定肌酐水平,尿液测定白蛋白分析,肾脏测定组织学检查。在自发和Con-A诱导试验中,MSCs诱导的MVs均以剂量依赖性刺激脾细胞增殖。MV的加入使阿霉素诱导的小鼠脾淋巴细胞凋亡减少。在这种情况下,MSCs产生的MV可能具有免疫刺激和抗凋亡作用。此外,在ARF小鼠模型中,mv对肾脏的结构和功能的恢复有积极的影响。用MSC-MV治疗单次注射50%甘油致急性肾功能衰竭,可降低动物尿白蛋白水平,恢复血清肌酐水平。形态学研究显示,患病小鼠肾皮质的高度细胞和集束管直径减少,浅表肾小球最大横径减小。因此,所得结果表明MSC-MV具有显著的治疗和促再生特性,有待进一步研究。
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引用次数: 0
Peculiarities of post-viral chronic fatigue syndrome associated with mild cognitive decline in patients with atypical chronic active herpesvirus infections 非典型慢性活动性疱疹病毒感染患者与轻度认知能力下降相关的病毒后慢性疲劳综合征的特点
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-pop-2826
E. Khalturina, I. Nesterova
According to modern ideas, changes in the functioning of the immune system affect the immune processes in the nervous system, contributing to the development of neuro-immuno-inflammation and thereby indirectly affect the rate of progression of neurodegenerative processes. The aim of our study was to investigate the prevalence of post-viral chronic fatigue syndrome and cognitive impairment (aMCI) among patients with atypical, chronic active herpesvirus infections (ACA-HVI).Under our supervision were 126 patients of both sexes aged 18 to 60 years with ACA-HVI.It was established that mono-EBV infection affects 27.7%; mixed EBV infection is observed in 72.3% of patients. When assessing cognitive functioning using CGI, MMSE scales, the incidence of aMCI was found to be 68.3%: with mixed HVI — 87.4%, with mono HVI — 38.8%. During the study, significant limitations were identified in the use of standard scales due to the impossibility of conducting a comprehensive assessment of clinical status parameters and cognitive dysfunctions, as well as correlation of these parameters and assessment of dynamics of the immunocorrection. To achieve this goal the Scale of assessment of the criterion clinical symptoms of patients with ACA-HVI with CFS was used. It was shown that in mixed-HVI, the severity of symptoms exceeded the severity of symptoms of patients with mono-HVI and was 52.7 (43.1-62.2) and 38.0 (31.9-42.8) points, respectively (p > 0.05). Thus, it was found that patients suffering from mixed HVI have more pronounced, severe manifestations of CFS and aMCI, which are 1.5 times higher than similar manifestations in patients with mono-HVI, significantly reducing the quality of life of these patients, worsening their social adaptation.Prolonged persistence of herpes viruses in immune-compromised people creates conditions for constant antigenic stimulation and immune imbalance with the onset of secondary immunodeficiency or clinical manifestation of existing primary disorders in the immune system, which creates the prerequisites for the development of neuro-immuno-inflammatory changes in nervous system, followed by the formation of clinical manifestations of ME/CFS with different cognitive impairments that may be classified as aMCI.
根据现代观点,免疫系统功能的变化影响神经系统的免疫过程,促进神经免疫炎症的发展,从而间接影响神经退行性过程的进展速度。本研究的目的是调查非典型慢性活动性疱疹病毒感染(ACA-HVI)患者的病毒性后慢性疲劳综合征和认知功能障碍(aMCI)的患病率。在我们的监督下,126名年龄在18至60岁的男女ACA-HVI患者。确定单ebv感染占27.7%;72.3%的患者存在混合性EBV感染。当使用CGI、MMSE量表评估认知功能时,发现aMCI的发生率为68.3%,混合HVI为87.4%,单一HVI为38.8%。在研究过程中,由于无法对临床状态参数和认知功能障碍进行全面评估,以及这些参数与免疫矫正动力学评估的相关性,在使用标准量表时发现了显著的局限性。为达到这一目的,采用了ACA-HVI合并CFS患者标准临床症状评估量表。结果表明,混合hvi患者的症状严重程度超过单一hvi患者的症状严重程度,分别为52.7(43.1-62.2)和38.0(31.9-42.8)分(p > 0.05)。因此,我们发现混合HVI患者的CFS和aMCI表现更为明显、严重,是单一HVI患者类似表现的1.5倍,显著降低了这些患者的生活质量,使其社会适应能力恶化。疱疹病毒在免疫功能低下人群中的长期存在,为持续的抗原刺激和免疫失衡创造了条件,伴随着继发性免疫缺陷的发生或免疫系统现有原发性疾病的临床表现,这为神经系统中神经免疫炎症变化的发展创造了先决条件。随后形成ME/CFS伴不同认知障碍的临床表现,可归类为aMCI。
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引用次数: 0
Application of stem cells in guided bone regeneration 干细胞在引导骨再生中的应用
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-aos-2724
N. S. Chumakov, K. A. Khlystova, N. G. Sarkisyan, F. A. Fadeev, M. M. Mamedov
Modern medicine allows us to study and develop materials and methods of restorative treatment that would be based on the immunological mechanisms of bone repair. One of the promising directions in guided bone regeneration is the use of mesenchymal stem cells. Interest in MSCs is associated with their ability to regulate the inflammatory process, and directly participate in the formation of new bone structures, thereby providing a physiological repair process. The effector impact of MSCs on the inflammatory process due to their ability to form a specific microenvironment. Low expression of MHC-II and CD80/CD86, the production of PGE2 and NO determines their low immunoconflict, and the production of TGF-b1, IDO and IL-10 has an immunomodulating effect. The ability of MSCs to differentiate into an osteogenic phenotype is accompanied with the synthesis of ALP, BSP and, subsequently, Gla-protein and OPN determine the synthesis of the extracellular matrix and its subsequent mineralization. This process is provided by the action of Runx2, which activates the differentiation of MSCs along the osteogenic pathway. These effects of MSCs were taken as the basis for the development of a new method for the treatment of bone atrophy. To accomplish the task set, a model of bone tissue atrophy and a drug containing MSCs was developed, and an experimental study was conducted to evaluate the effectiveness of the developed methodology. As the main criteria, data from clinical and laboratory studies were taken. Visual changes in the studied area were taken into account, compared with a similar area in the developed model of atrophy, the parameters of the complete blood count (CBC) were evaluated. The performed study allows us to determine the developed treatment method as capable of fully recreating the conditions of bone repair processes, taking into account the optimization of the body’s immune reactions and repair processes, without additional external influence, to obtain predictable and controllable results.
现代医学使我们能够研究和开发基于骨修复免疫机制的恢复性治疗材料和方法。间充质干细胞的应用是引导骨再生的一个很有前途的方向。对MSCs的兴趣与它们调节炎症过程的能力有关,并直接参与新骨结构的形成,从而提供生理修复过程。由于MSCs能够形成特定的微环境,MSCs对炎症过程的影响。MHC-II和CD80/CD86的低表达,PGE2和NO的产生决定了它们的低免疫冲突,TGF-b1、IDO和IL-10的产生具有免疫调节作用。MSCs向成骨表型分化的能力伴随着ALP、BSP的合成,随后,gla蛋白和OPN决定了细胞外基质的合成及其随后的矿化。这一过程是由Runx2的作用提供的,它激活MSCs沿成骨途径的分化。MSCs的这些作用为开发治疗骨萎缩的新方法奠定了基础。为了完成任务集,我们建立了骨组织萎缩模型和含有MSCs的药物,并进行了实验研究来评估所开发方法的有效性。以临床和实验室研究数据为主要标准。考虑到研究区域的视觉变化,并与开发的萎缩模型中的类似区域进行比较,评估全血细胞计数(CBC)参数。所进行的研究使我们能够确定所开发的治疗方法能够完全重现骨修复过程的条件,考虑到人体免疫反应和修复过程的优化,没有额外的外部影响,以获得可预测和可控的结果。
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引用次数: 0
Expression of arginase 1 and tyrosine kinase Mer by blood monocytes in the dynamics of physiological pregnancy 精氨酸酶1和酪氨酸激酶Mer在生理性妊娠过程中单核细胞的表达
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-eoa-2728
E. Shevela, N. G. Bukhtueva, M. Tikhonova, L. Sakhno, N. Pasman, E. Chernykh
During pregnancy, the maternal immune system must maintain tolerance to paternal antigens, at the same time being able to eliminate pathogens, which is achieved by the weakening of adoptive immunity and the activation of innate immunity, in particular, monocytes. However, the question about the functional phenotype of monocytes, having not only pro-inflammatory, but also anti-inflammatory activity, remains open. In the given work, we have investigated the expression of M2-associated suppressive markers Arg1 and MerTK in monocyte subpopulations during uncomplicated pregnancy. Fifty-three pregnant women with uncomplicated gestation were recruited, including 14 pregnant in the 1st trimester, 20 – in the 2nd and 19 – in the third pregnancy trimester. The comparison group consisted of 15 fertile unpregnant women without aggravated somatic anamnesis, with a history of at least one childbirth. The findings showed that in the unpregnant group circulating Mo express Arg1 and MerTK, and the most relative number of Arg1+ and MerTK+ cells is concentrated in intermediate and nonclassic monocytes. During pregnancy the expression of researched molecules in monocytes reliably increases. An increase in MerTK expression is manifested by a simultaneous increase in the number of MerTK+ cells and the mean fluorescence intensity of this marker; it is observed in the 1st and 2nd trimesters and registered in all three monocyte subpopulations. At the same time, an increase in Arg1 expression is manifested either by an enhancement of Arg1+ cells, or an increase in receptor density; it is registered throughout pregnancy, including the 3rd trimester, and is maximally expressed in classic monocytes. There is a direct correlation between the number of Arg1+ and MerTK+ cells in intermediate Mo, which increases with the progression of pregnancy, and in the 3rd trimester is also detected in classical and non-classical Mo. In general, the revealed increase in the expression of Arg1 and MerTK by monocytes indicates an increase in the anti-inflammatory potential of monocytes during pregnancy, and the involvement of monocytes in the regulation of the inflammatory process at the system level. Moreover, the features of Arg1 and MerTK expression in various monocyte subpopulations during pregnancy suggest that monocytes expressing Arg1 and MerTK can mediate different mechanisms of immune adaptation during pregnancy.
在怀孕期间,母体免疫系统必须保持对父本抗原的耐受性,同时能够消除病原体,这是通过削弱过继免疫和激活先天免疫,特别是单核细胞来实现的。然而,关于单核细胞功能表型的问题,不仅具有促炎活性,而且具有抗炎活性,仍然是开放的。在本研究中,我们研究了m2相关抑制标记Arg1和MerTK在单核细胞亚群中的表达。研究招募了53名妊娠无并发症的孕妇,包括14名妊娠早期的孕妇,20名妊娠晚期的孕妇和19名妊娠晚期的孕妇。对照组包括15名没有加重躯体性记忆的有生育能力的未怀孕妇女,至少有一次分娩史。结果显示,在未妊娠组循环Mo中,Arg1和MerTK均有表达,且Arg1+和MerTK+细胞的相对数量主要集中在中间和非经典单核细胞中。在怀孕期间,研究分子在单核细胞中的表达确实增加。MerTK表达增加表现为MerTK+细胞数量和该标记物的平均荧光强度同时增加;它在妊娠的第一和第二阶段被观察到,并且在所有三个单核细胞亚群中都有记录。同时,Arg1表达的增加表现为Arg1+细胞的增强或受体密度的增加;它在整个妊娠期间都有记录,包括妊娠晚期,并在经典单核细胞中最大程度地表达。中间胎Mo中Arg1+和MerTK+细胞的数量直接相关,随着妊娠的进展而增加,在妊娠晚期经典胎Mo和非经典胎Mo中也检测到Arg1和MerTK的表达增加。总的来说,单核细胞表达Arg1和MerTK的增加表明妊娠期间单核细胞的抗炎潜能增加,单核细胞在系统水平上参与了炎症过程的调节。此外,Arg1和MerTK在妊娠期不同单核细胞亚群中的表达特点表明,表达Arg1和MerTK的单核细胞可以介导妊娠期不同的免疫适应机制。
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引用次数: 0
Proinflammatory cytokines VEGFA, IL-6, IL-8 as markers of hepatotoxicity after COVID-19 促炎因子VEGFA、IL-6、IL-8作为COVID-19后肝毒性的标志物
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-pcv-2843
M. A. Urevskii, L. V. Ilmukhina, Ya.E. Saranskaya, A. A. Lapshin, R. R. Gafurova
The mechanism of hepatocellular liver damage after COVID-19 is a multifactorial process. The most widely discussed causes are cytolytic liver damage due to the inflammatory response after COVID-19, drug-induced hepatotoxicity and direct cytotoxic effect of the virus. There are observations that SARSCoV-2 infection causes hepatitis B virus reactivation, but little has been described about the interaction between hepatitis C virus and SARS-CoV-2. The course of coronavirus infection is associated with marked expression of proinflammatory cytokines, participants in the multisystem inflammatory response, IL-1β, IL-6, IL-8, IL-18, MCP-1, TNFα, which contribute significantly to the observed early and late liver function impairment. The aim of the study was to evaluate the role of proinflammatory cytokines (VEGFA, IL-8, IL-6, MCP-1, TNFα, IL-18) as additional markers of hepatotoxicity after COVID-19. The study was performed between March and August 2022. Patients were divided into 2 groups: Group 1 – with increased aminotransferases against the background of treatment from COVID-19 and/or in the following 3-6 months after the disease without viral liver damage (n = 42), Group 2 – patients with co-infection (chronic viral hepatitis C (HCV) and COVID-19 (n = 26). The levels of cytokines – VEGF-A, IL-6, IL-8, MCP-1, IL-18, TNFα in blood serum were estimated by enzyme immunoassay method. Statistical analysis was performed using StatTech v. 3.1.4. The results of the study revealed a comparable increase in the level of transaminases and C-reactive protein in both groups, significantly different from the reference values. Direct correlations of moderate strength (linear Spearman correlation) were found between the following cytokines: TNFα-MCP-1 (R = 0.559; p = 0.001), TNFα-VEGFA (R = 0.400; p = 0.002), TNFα-IL-6 (R = 0.503; p = 0.001). We diagnosed a significant increase in serum VEGFA levels in group 1 patients (hepatotoxicity after COVID-19) (Me (Q0.25-Q0.75): 522 (250 to 1002), p = 0.001) and in group 2 patients (HCV + COVID-19) (Me 1196, Q0.25-Q0.75: (73 to 432). Similar trend with the level of IL-6, IL-8, exceeding the values of cytokines in healthy donors and significantly higher than in group 2 patients. Identified correlations between inflammatory cytokines prove unidirectional changes in the functioning of the regulatory network controlling immune virus-induced reactions.
新冠肺炎后肝细胞性肝损伤的机制是一个多因素的过程。最广泛讨论的原因是COVID-19后炎症反应引起的细胞溶解性肝损伤、药物诱导的肝毒性和病毒的直接细胞毒性作用。有观察表明,SARS-CoV-2感染可引起乙型肝炎病毒再激活,但关于丙型肝炎病毒与SARS-CoV-2之间相互作用的描述很少。冠状病毒感染过程中,促炎因子、多系统炎症反应参与者、IL-1β、IL-6、IL-8、IL-18、MCP-1、TNFα的显著表达与早期和晚期肝功能损害相关。本研究的目的是评估促炎细胞因子(VEGFA、IL-8、IL-6、MCP-1、TNFα、IL-18)作为COVID-19后肝毒性的附加标志物的作用。该研究于2022年3月至8月进行。患者分为2组:1组-在COVID-19治疗背景下转氨酶升高和/或在疾病后3-6个月内无病毒性肝损害(n = 42), 2组-合并感染(慢性病毒性丙型肝炎(HCV)和COVID-19患者(n = 26)。采用酶免疫分析法测定血清中VEGF-A、IL-6、IL-8、MCP-1、IL-18、tnf - α等细胞因子水平。使用StatTech v. 3.1.4进行统计分析。研究结果显示,两组患者的转氨酶和c反应蛋白水平均有相当程度的升高,与参考值有显著差异。以下细胞因子与TNFα-MCP-1呈中等强度的直接相关(线性Spearman相关):TNFα-MCP-1 (R = 0.559;p = 0.001), tnf - α- vegfa (R = 0.400;p = 0.002), TNFα-IL-6 (R = 0.503;P = 0.001)。我们诊断出第1组患者(COVID-19后肝毒性)(Me (Q0.25-Q0.75): 522(250至1002),p = 0.001)和第2组患者(HCV + COVID-19) (Me 1196, Q0.25-Q0.75: 73至432)血清VEGFA水平显著升高。IL-6、IL-8水平与健康供者相似,均超过细胞因子水平,且明显高于2组。已确定的炎症细胞因子之间的相关性证明了控制免疫病毒诱导反应的调节网络功能的单向变化。
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引用次数: 0
Assessment of the humoral immune response in children after immunization with different types of inactivated influenza vaccines in the 2019-2020 season 2019-2020季节接种不同类型流感灭活疫苗后儿童体液免疫应答的评价
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-aot-2737
Z. Buzitskaya, A. Popov, E. Romanovskaya-Romanko, M. Sergeeva, E. Varyushina, M. K. Erofeeva, M. Stukova, D. Lioznov
Causing millions of cases worldwide every year, influenza is one of the most common respiratory infections. The effectiveness of influenza vaccination and the nature of the resulting immune response may vary depending on the vaccine composition and age group. Since children are at the highest risk of disease and act as the main carriers of influenza, the assessment of the immunological efficacy of vaccines in this group is crucial for controlling the epidemic. Therefore, this study aimed to evaluate the characteristics of the humoral immune response in children after immunization with various types of inactivated influenza vaccines. An observational study was conducted in the 2019-2020 season and involved 230 children (< 18 years old) and a comparison group of 87 adults aged 18 to 60 years. The subjects, who provided informed consent to participate, were vaccinated with one of three vaccines (Grippol Plus, Sovigripp, or Ultrix) in an open-label fashion. The humoral immune response was assessed by measuring the hemagglutination inhibition (HI) titer in the paired sera taken before and three weeks after vaccination. The immunogenicity of the vaccines in the age group under 18, met the CPMP criteria for the assessment of inactivated influenza vaccines in terms of the fold increase in antibody titers and the proportion of individuals with seroconversion to all three components (A/H1N1pdm09, A/H3N2, and B/Victoria). Although 6 to 18-year-old participants showed a more robust immune response to the B/Victoria component compared to the adult participants (aged 18 to 60), it was insufficient to ensure that 70% of the participants have a protective antibody titer. A comparative analysis of the vaccines’ immunogenicity was carried out for a subgroup of children aged 6-18 who had initially low antibody levels at the time of vaccination. The analysis showed that the split vaccine Ultrix outperformed the adjuvanted vaccine Grippol Plus in generating an antibody response to the component B/Victoria; however, the antibody responses to the A/H1N1pdm09 and A/H3N2 components did not differ between the two vaccines. The children under 6 years of age demonstrated a less pronounced humoral immune response to vaccination compared with the other age groups, which may be due to the age-related characteristics of the immune system in children of preschool age.
流感是最常见的呼吸道感染之一,每年在全球造成数百万例病例。流感疫苗接种的有效性和由此产生的免疫反应的性质可能因疫苗成分和年龄组而异。由于儿童患病风险最高,并且是流感的主要携带者,因此评估疫苗在这一群体中的免疫功效对于控制流感流行至关重要。因此,本研究旨在评价儿童接种不同类型流感灭活疫苗后体液免疫反应的特点。在2019-2020赛季进行了一项观察性研究,涉及230名儿童(18岁以下)和87名18至60岁的成年人。提供知情同意参与的受试者以开放标签方式接种三种疫苗(Grippol Plus、Sovigripp或Ultrix)中的一种。体液免疫反应是通过测量疫苗接种前和接种后三周的配对血清中的血凝抑制(HI)滴度来评估的。在18岁以下年龄组中,疫苗的免疫原性符合CPMP对灭活流感疫苗的评估标准,抗体滴度增加了两倍,血清转化为所有三种成分(A/H1N1pdm09、A/H3N2和B/Victoria)的个体比例也达到了这一标准。虽然6至18岁的参与者对B/Victoria组分的免疫反应比成年参与者(18至60岁)更强,但这不足以确保70%的参与者具有保护性抗体滴度。对接种疫苗时抗体水平较低的6-18岁儿童亚组进行了疫苗免疫原性的比较分析。分析表明,分离疫苗Ultrix在产生对B/Victoria组分的抗体应答方面优于佐剂疫苗Grippol Plus;然而,对A/H1N1pdm09和A/H3N2组分的抗体反应在两种疫苗之间没有差异。与其他年龄组相比,6岁以下儿童对疫苗接种表现出较不明显的体液免疫反应,这可能是由于学龄前儿童免疫系统的年龄相关特征。
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引用次数: 0
Influence of microbial polyamines on the IL-10 production by peripheral blood leukocytes of healthy donors 微生物多胺对健康献血者外周血白细胞产生IL-10的影响
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-iom-2842
А. Р. Godovalov, I. A. Morozov
As is known, bacterial polyamines, which include cadaverine and putrescine, are capable of influencing the activity of immunocompetent cells in many ways. In particular, this situation is observed in long-term inflammatory diseases, especially with intensive reproduction of microorganisms capable of producing polyamines. It is of interest to study the production of one of the main anti-inflammatory cytokines, IL-10, under the influence of bacterial polyamines. For research, a population of mononuclear leukocytes was isolated from the peripheral blood of healthy donors by gradient centrifugation. The cell suspension was placed in a round-bottomed plates with preliminarily added polyamines at concentrations of 5, 25, 50, 75, and 100 mmol/L. Wells not containing polyamines were used as a control. After incubation for 72 h at 37 °C and 5% CO2, the supernatants were harvested and used to determine the concentration of IL-10. We used a kit for determining the concentration of IL-10 using the enzyme immunoassay method (Russia). Statistical analysis was performed using the Statistica 6.0 software package. In the case of a distribution close to normal, Student’s t-test was used; in the rest, the Mann–Whitney test was used to assess the significance of differences. Studies have shown that leukocytes in the presence of concanavalin A produce IL-10 at a concentration of 17.13±6.08 pg/mL. It has been established that under the influence of polyamines of bacterial origin, the production of IL-10 is enhanced only if putrescine and cadaverine are at concentrations of 50 mmol/L and higher. At low concentrations of polyamines, no significant increase in IL-10 production was detected. Since IL-10 is an anti- inflammatory cytokine, for which the analgesic effect is also known, it should be expected that with an increase in its concentration in the focus of invasion of opportunistic bacteria, the inflammatory process will develop latently, when the symptoms are mild. In general, it can be expected that polyamine-producing bacteria will contribute to the maintenance of few symptomatic inflammation.
众所周知,细菌多胺,包括尸胺和腐胺,能够以多种方式影响免疫能力细胞的活性。特别是在长期炎症性疾病中,特别是在能够产生多胺的微生物大量繁殖的情况下,可以观察到这种情况。在细菌多胺的影响下,研究主要抗炎细胞因子之一IL-10的产生具有重要意义。为了进行研究,用梯度离心法从健康献血者的外周血中分离出一群单核白细胞。将细胞悬液置于圆形底板中,初步加入浓度为5、25、50、75和100 mmol/L的多胺。不含多胺的井作为对照。37℃和5% CO2孵育72 h后,收集上清液,用于测定IL-10的浓度。我们使用酶免疫分析法测定IL-10浓度的试剂盒(俄罗斯)。采用Statistica 6.0软件包进行统计分析。在接近正态分布的情况下,使用学生t检验;在其余的研究中,采用曼-惠特尼检验来评估差异的显著性。研究表明,白细胞在刀豆蛋白A存在下产生的IL-10浓度为17.13±6.08 pg/mL。已经确定,在细菌源多胺的影响下,只有腐胺和尸胺浓度在50 mmol/L及以上时,IL-10的产生才会增加。在低浓度的多胺下,IL-10的产生没有显著增加。由于IL-10是一种抗炎细胞因子,其镇痛作用也是已知的,因此可以预期,随着IL-10在机会性细菌侵袭的病灶浓度的增加,炎症过程会潜伏发展,此时症状较轻。一般来说,可以预期产生多胺的细菌将有助于维持少数症状性炎症。
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引用次数: 0
Peculiarities of immunological manifestations in patients with rheumatoid arthritis in the presence of chronic infection with Helicobacter pylori variant encoding cytotoxin-associated gene A 编码细胞毒素相关基因A的幽门螺杆菌变异体慢性感染的类风湿关节炎患者免疫学表现的特殊性
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-poi-2702
A. Aleksandrov, L. Shilova, V. Aleksandrov, M. Levkina, O. Paramonova, N. Aleksandrova, I. Zborovskaya
The study aimed to evaluate the association between cyclic citrullinated peptide antibody seropositivity and chronic Helicobacter pylori (H. pylori) infection in patients with rheumatoid arthritis (RA). We examined 92 women with moderate RA activity. Serum antibodies to cyclic citrullinated peptide (antiCCP), antibodies to H. pylori (anti-H. pylori-IgG), and total antibodies to H. pylori CagA antigen (antiCagA) were determined by enzyme immunoassay; the presence of anti-CagA-IgG positivity was confirmed by immunoblot. 68.5% of RA patients were positive for anti-H. pylori-IgG, and 44.4% of patients in this group were positive for anti-CagA-IgG. All the study participants were divided into three groups: I – H. pylori seronegative (H. pylori- ); II – H. pylori positive, CagA negative (H. pylori+/CagA- ); III – H. pylori positive and CagA positive (CagA+). The anti-CCP values in RA patients with CagA+ (group III) were significantly higher not only in comparison with patients seronegative for H. pylori (p < 0.001), but also in comparison with patients from group II (H. pylori+/CagA- ) (p = 0.041). A study of the influence of the RA activity, the presence of RF and H. pylori on anti-CCP content demonstrated a small proportion of anti-CCP variability (R2 = 0.09), with a high contribution of H. pylori (beta = 0.25). The addition of the CagA(+) index (beta = 0.503) to the presented model allowed us to describe the variability of anti-CCP in almost 30% of cases (R2 = 0.29). In the group of RA patients with anti-CCP values exceeding the established threshold value of 20 U/mL (normal index), there was an increase in the proportion of patients infected with H. pylori (p < 0.001), but not the proportion of CagA-positive patients (p = 0.06). When the threshold level was increased to 60 U/mL (three times the upper limit of normal) in patients with significantly high anti-CCP, the association with positivity for CagA became significant (p = 0.005). CagA is highly immunogenic and is capable of inducing an inflammatory response in the host that goes beyond the effect of H. pylori itself. Additional experimental studies are needed to investigate possible clinical and laboratory associations that may influence the treatment tactics of CagA+ patients with RA who are seropositive for anti-citrullinated antibodies, as well as to evaluate the possible effects of therapeutic intervention aimed at the eradication of H. pylori in this group.
本研究旨在评估类风湿性关节炎(RA)患者环瓜氨酸肽抗体血清阳性与慢性幽门螺杆菌(H. pylori)感染之间的关系。我们检查了92名中度RA活动的女性。血清抗环瓜氨酸肽抗体(anticp),抗幽门螺杆菌抗体(anti-H。酶免疫法检测幽门螺杆菌CagA抗原(antiaga)总抗体;免疫印迹法证实抗caga - igg阳性。68.5% RA患者抗- h阳性。本组患者抗caga - igg阳性率为44.4%。所有的研究参与者被分为三组:I -幽门螺杆菌血清阴性(H. pylori-);II -幽门螺杆菌阳性,CagA阴性(幽门螺杆菌+/CagA-);III -幽门螺杆菌阳性,CagA阳性(CagA+)。CagA+组(III组)RA患者的抗ccp值不仅显著高于幽门螺杆菌血清阴性患者(p < 0.001),也显著高于II组(H. pylori+/CagA-)患者(p = 0.041)。一项关于RA活性、RF和幽门螺杆菌存在对抗ccp含量影响的研究表明,抗ccp变异的比例很小(R2 = 0.09),而幽门螺杆菌的贡献很大(beta = 0.25)。将CagA(+)指数(beta = 0.503)添加到所提出的模型中,使我们能够描述近30%病例中抗ccp的变异性(R2 = 0.29)。在抗ccp值超过既定阈值20 U/mL(正常指数)的RA患者组中,幽门螺杆菌感染患者比例增加(p < 0.001),但caga阳性患者比例未增加(p = 0.06)。当抗ccp显著增高的患者阈值水平提高到60 U/mL(正常上限的3倍)时,与CagA阳性的相关性变得显著(p = 0.005)。CagA具有高度的免疫原性,能够在宿主体内诱导炎症反应,这种反应超出了幽门螺杆菌本身的影响。需要进一步的实验研究来调查可能影响抗瓜氨酸化抗体血清阳性的CagA+ RA患者治疗策略的临床和实验室关联,以及评估旨在根除这组幽门螺杆菌的治疗干预的可能效果。
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引用次数: 0
Analysis of factors associated with sterile inflammation in women with pe receiving different antihypertensive treatment strategies 接受不同降压治疗策略的pe患者无菌性炎症相关因素分析
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-aof-2809
K. T. Muminova, Z. Khodzhaeva, E. Yarotskaya, M. M. Ziganshina
Systemic inflammation alongside endothelial dysfunction is considered to play a crucial role in PE pathogenesis. Endothelial dysfunction can be assessed by endothelial glycocalyx (eGC) damage. eGC is a superficial layer of cells associated with endothelial membrane that provides all endothelial cells functions. Its damage can be evaluated by the levels of its circulating components in blood. Patients with PE generally receive methyldopa (Dopegyt) solely or in combination with nifedipine (Cordaflex), and there is no understanding of their effect on proinflammatory state of blood vessels. Our study aimed to assess levels of IL-6, IL-18, TNFα, galektin-3 and homocysteine as well as levels of syndecan-1, eCG structural component, representing system inflammatory response and endothelial dysfunction development in blood of women with early- and late-onset PE receiving different antihypertensive treatment strategies. Eighty-two patients were enrolled into this interventional longitudinal pilot study. The comparison group included 15 patients before 34 gestational weeks and 15 patients after 34 weeks. Study subgroup 1 included 12 patients with early- onset PE receiving Dopegyt solely and 16 patients with early-onset PE receiving Dopegyt together with Cordaflex. Study subgroup 2 included 12 patients with late-onset PE receiving Dopegyt solely and 12 patients with late-onset PE receiving combined therapy. As for early-onset PE, only IL-6 demonstrated statistically significant differences in patients receiving both treatment strategies compared to control. Proinflammatory state was more profound in late-onset PE. IL-6 levels were significantly increased in late-onset PE treated with Dopegyt. IL-6 and TNFa levels were significantly higher in late-onset PE patients treated with Dopegyt + Cordaflex compared to control. Syndecan-1 levels were statistically significantly higher in patients with early-onset PE treated with Dopegyt solely. There were no statistically significant differences between the groups despite elevated mean values of syndecan-1 in late-onset PE. Galectin-3 and homocysteine levels did not differ significantly between the groups, representing lack of pronounced inflammatory response and endothelial dysfunction.
全身性炎症和内皮功能障碍被认为在PE发病中起关键作用。内皮功能障碍可以通过内皮糖萼(eGC)损伤来评估。eGC是与内皮膜相关的一层细胞,提供所有内皮细胞的功能。它的损害可以通过血液中循环成分的水平来评估。PE患者一般单用甲基多巴(Dopegyt)或联用硝苯地平(Cordaflex),其对血管促炎状态的影响尚不清楚。我们的研究旨在评估IL-6、IL-18、TNFα、galektin-3和同型半胱氨酸水平,以及syndecan-1水平,心电图结构成分,代表系统炎症反应和内皮功能障碍发展在接受不同降压治疗策略的早发性和晚发性PE妇女的血液中。82名患者参加了这项介入性纵向先导研究。对照组为孕34周前15例,孕34周后15例。研究亚组1包括12例单独接受Dopegyt治疗的早发性PE患者和16例接受Dopegyt联合Cordaflex治疗的早发性PE患者。研究亚组2包括12例单独接受Dopegyt治疗的晚发型PE患者和12例接受联合治疗的晚发型PE患者。对于早发性PE,只有IL-6在接受两种治疗策略的患者中与对照组相比有统计学差异。晚发性PE的促炎状态更为深刻。IL-6水平在Dopegyt治疗的晚发性PE中显著升高。与对照组相比,接受Dopegyt + Cordaflex治疗的晚发性PE患者IL-6和TNFa水平显著升高。单纯使用Dopegyt治疗的早发性PE患者Syndecan-1水平显著升高。尽管晚发性PE中syndecan-1的平均值升高,但两组间差异无统计学意义。半乳糖凝集素-3和同型半胱氨酸水平在两组之间没有显著差异,表明缺乏明显的炎症反应和内皮功能障碍。
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引用次数: 1
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Medical Immunology (Russia)
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