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Leukocyte cytokine expression is associated with severity of autism in children 白细胞细胞因子的表达与儿童自闭症的严重程度有关
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13911-lce
Yuliya Y. Filippova, A. S. Alekseeva, A. L. Burmistrova
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with unknown etiology, high clinical heterogeneity and marked aberrations of the immune system. Evidence for an association between immune dysfunction and behavioral traits highlights the need for a study of the immune cell functional activity in order to search for pathogenesis mechanisms and potential targets for therapy at ASD. The purpose: to determine the expression levels of IL-1, IL-2, IL-4, IL-6, IL-10, IL-18, IFN and TNF in peripheral blood leukocytes of children with mild and severe ASD. The study included 81 children with ASD (77.8% boys) and 45 children with typical neurodevelopment (TDC, 71.1% boys). According to the Childhood Autism Rating Scale, 51 children (63.0%) had mild autistic symptoms (CARS score 32.01,5) and 30 children had severe ASD symptoms (CARS score 39.03,4). Cytokines expression in leukocytes was determined by quantitative PCR with SYBRGreen. The data were transformed using BoxCox transformation. The differences between groups were assessed by one-way ANOVA and Dunns test for multiple comparisons. In leukocytes of children with ASD, regardless of the severity, the expression of IL-1, IL-18 and IL-2, was significantly reduced compared to TDC. Moreover, in children with mild ASD, low expression of TNF, compared with TDC was found. In children with severe ASD, the expression of the main cytokine of Th1 IFN, was significantly increased, without an increased expression of an important cytokine of Treg IL-10. Activation of the Th1 adaptive immune response without compensation by cytokines of Treg, the number of which is reduced in ASD, can lead to increased inflammation, even in the central nervous system, and correlates with the severity of ASD clinical symptoms. Despite extensive immunological evidence suggesting immune system dysregulation, further research is required to clarify the relationship between immune system cell function and ASD pathology.
自闭症谱系障碍(ASD)是一种病因不明、临床异质性高、免疫系统明显异常的复杂神经发育障碍。免疫功能障碍与行为特征之间存在关联的证据表明,需要对免疫细胞功能活性进行研究,以寻找ASD的发病机制和潜在治疗靶点。目的:测定轻、重度ASD患儿外周血白细胞中IL-1、IL-2、IL-4、IL-6、IL-10、IL-18、IFN、TNF的表达水平。该研究包括81名ASD儿童(77.8%的男孩)和45名典型神经发育儿童(71.1%的男孩)。根据儿童自闭症评定量表,51例患儿(63.0%)有轻度自闭症症状(CARS评分32.01,5),30例患儿有重度自闭症症状(CARS评分39.03,4)。SYBRGreen应用定量PCR检测白细胞细胞因子表达。使用BoxCox变换对数据进行变换。组间差异采用单因素方差分析和Dunns检验进行多重比较。在ASD患儿的白细胞中,无论严重程度如何,与TDC相比,IL-1、IL-18和IL-2的表达均显著降低。此外,在轻度ASD患儿中,与TDC相比,TNF表达较低。在重度ASD患儿中,主要细胞因子Th1 IFN的表达显著升高,而重要细胞因子Treg IL-10的表达未见升高。在ASD中,Treg细胞因子的数量减少,在没有补偿的情况下激活Th1适应性免疫反应,可导致炎症增加,甚至在中枢神经系统,并与ASD临床症状的严重程度相关。尽管大量的免疫学证据表明免疫系统失调,但需要进一步的研究来阐明免疫系统细胞功能与ASD病理之间的关系。
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引用次数: 0
Comparison of immune response to various SARS-CoV-2 vaccines within 6 months after starting vaccination and following revaccination 开始接种和重新接种后6个月内对各种SARS-CoV-2疫苗免疫反应的比较
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13943-coi
Irina V. Astrakhantseva
The pandemic of coronavirus infection (COVID-19) has stimulated the development, testing and widespread use of preventive vaccines based on various platforms. Our aim was to perform a direct comparison of immunogenicity of various vaccines within a single study in small groups within six months of SARS-CoV-2 vaccination and revaccination. The stdy group included subjects vaccinated with Sputnik V adenovirus vaccine, mRNA vaccines, and CoviVac whole-virion vaccine. Their immune status was assessed by enzyme immunoassay as specific antibody levels. Moreover, the neutralizing ability of detected antibodies was assessed using a cell test system based on pseudoviral technology. All of the mentioned vaccines were shown to elicit an immune response against SARS-CoV-2 RBD antigen, however, appropriate antibody titers and neutralizing capacities differed depending on the type of vaccine. The mRNA vaccines proved to be the most immunogenic, the effectiveness of the immune response to the Sputnik V adenovirus-based vaccine was lower. However, 6 months after vaccination, the effectiveness of virus neutralizing antibodies induced by these vaccines did not differ. The whole-virion CoviVac vaccine with proven efficiency by independent epidemiological studies, induced an antibody response against the RBD protein to a lesser extent. The seropositive participants of the study, both previously exposed to COVID-19 disease or vaccinated, exhibited high-titer production of antibodies already after the first dose of the Sputnik V vaccine, and a significantly higher antibody titer 6 months after the booster immunization as compared with initial level of antibodies, along with direct correlation between the antibody titers and their neutralizing activity.
冠状病毒感染(COVID-19)大流行刺激了基于各种平台的预防性疫苗的开发、测试和广泛使用。我们的目的是在接种SARS-CoV-2疫苗和重新接种疫苗六个月内的小群体中,在一项单一研究中对各种疫苗的免疫原性进行直接比较。研究组包括接种了Sputnik V腺病毒疫苗、mRNA疫苗和CoviVac全病毒粒子疫苗的受试者。采用酶免疫分析法测定其特异性抗体水平,评估其免疫状态。此外,使用基于伪病毒技术的细胞测试系统评估检测到的抗体的中和能力。 所有上述疫苗均显示出针对SARS-CoV-2 RBD抗原的免疫应答,然而,适当的抗体滴度和中和能力因疫苗类型而异。mRNA疫苗被证明是最具免疫原性的,而基于Sputnik V腺病毒的疫苗免疫应答的有效性较低。然而,接种疫苗6个月后,这些疫苗诱导的病毒中和抗体的有效性没有差异。经独立流行病学研究证实有效的全病毒粒子CoviVac疫苗在较小程度上诱导了针对RBD蛋白的抗体应答。该研究的血清阳性参与者,无论是先前暴露于COVID-19疾病还是接种过疫苗,在第一剂Sputnik V疫苗后已经表现出高滴度的抗体产生,并且在加强免疫后6个月的抗体滴度与初始抗体水平相比显着更高,并且抗体滴度与其中和活性之间存在直接相关性。
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 The stdy group included subjects vaccinated with Sputnik V adenovirus vaccine, mRNA vaccines, and CoviVac whole-virion vaccine. Their immune status was assessed by enzyme immunoassay as specific antibody levels. Moreover, the neutralizing ability of detected antibodies was assessed using a cell test system based on pseudoviral technology.
 All of the mentioned vaccines were shown to elicit an immune response against SARS-CoV-2 RBD antigen, however, appropriate antibody titers and neutralizing capacities differed depending on the type of vaccine. The mRNA vaccines proved to be the most immunogenic, the effectiveness of the immune response to the Sputnik V adenovirus-based vaccine was lower. However, 6 months after vaccination, the effectiveness of virus neutralizing antibodies induced by these vaccines did not differ. The whole-virion CoviVac vaccine with proven efficiency by independent epidemiological studies, induced an antibody response against the RBD protein to a lesser extent.
 The seropositive participants of the study, both previously exposed to COVID-19 disease or vaccinated, exhibited high-titer production of antibodies already after the first dose of the Sputnik V vaccine, and a significantly higher antibody titer 6 months after the booster immunization as compared with initial level of antibodies, along with direct correlation between the antibody titers and their neutralizing activity.","PeriodicalId":21507,"journal":{"name":"Russian journal of immunology : RJI : official journal of Russian Society of Immunology","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136059435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficiency of combined postoperative treatment including an immunomodulatory Hexapeptide in children with acute destructive pneumonia 急性破坏性肺炎患儿术后联合免疫调节六肽治疗的疗效观察
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13954-eoc
V. N. Chapurina, Irina V. Nesterova, G. A. Chudilova, S. V. Kovaleva, D. E. Lyagusha, Yu. V. Teterin, N. K. Barova, V. A. Tarakanov
Acute destructive pneumonia (ADP) is a severe purulent and septic infectious disorder of childhood, characterized by a high level of morbidity and associated with imbalance of the immune system (IS). Hence, there is an obvious need to study the immunopathogenesis of this disease in order to develop new therapeutic strategy aimed at eliminating the pathogen, detoxifying the body, relieving respiratory failure and correcting functional immune deficiency. Our aim was to perform a clinical and immunological study in order to evaluate efficiency of immunomodulatory therapy using a medical drug with hexapeptide as an active substance. This drug was included into the complex postoperative treatment of children with acute destructive pneumonia. Clinical and immunological examination of 15 children 2-5 years old with ADP was performed before (study group 1 SG1) and after (study group 1a SG1a) combined postsurgical treatment including immunomodulatory therapy with a Hexapeptide-based pharmaceutical (HP, Arginyl-alpha-Aspartyl-Lysyl-Valyl-Tyrosyl-Arginine). Comparison group (CG) included twenty healthy children. The contents of T and B lymphocytes, natural killer cells (NK) were measured by means of flow cytometry (CYTOMICS FC 500, USA). Serum levels of IgA, IgM, IgG (ELISA), phagocytic and microbicidal activity of neutrophil granulocytes (NG) were also evaluated. Prior to the treatment in SG1 patients, a decreased number of CD3+CD19-T lymphocytes, CD3+CD8+ TCTL lymphocytes was revealed along with significant decrease in the contents of CD3-CD16+CD56+ NK (p1-3 0.05). It was found that in children with ADP, the IgG level did not differ from indices of control group, with a decrease of IgM (p1, 2 0.05), and increased level of IgA (p 0.05). We have also found a deficiency of NG effector functions, i.e., insufficiency of active phagocytic NG with impaired capture and killing of bacterial antigen. Assays of NADPH-oxidase activity showed lacking response to both inflammation and additional induction by S. aureus. After complex treatment including immunomodulatory therapy in the SG1a group, we revealed a recovery in CD3+CD19-T lymphocyte contents, CD3+CD8+TCTL lymphocytes, CD3-CD16+CD56+ NK (p1-3 0.05). The trends towards normalization of IgA, IgM, improved NG effector functions (killing ability) were revealed due to activation of NADPH-oxidases. The restoration of immunological parameters in ADP was associated with earlier recovery from the purulent-destructive process in lungs, absence of postoperative complications including the prevention of septic process. The clinical and immunological effects of the immunomodulatory therapy program with HP-based pharmaceutical preparations suggest its potential usage during postoperative period in immunocompromised children with ADP.
急性破坏性肺炎(Acute destructive pneumonia, ADP)是一种严重的儿童期化脓性和败血性感染性疾病,其特点是发病率高,并与免疫系统失衡(immune system, is)相关。因此,有必要研究该病的免疫发病机制,以制定新的治疗策略,以消除病原体,排毒,缓解呼吸衰竭和纠正功能性免疫缺陷。我们的目的是进行临床和免疫学研究,以评估使用六肽作为活性物质的药物进行免疫调节治疗的效果。将该药纳入儿童急性破坏性肺炎术后复杂治疗。对15例2-5岁ADP患儿在手术前(研究组1 SG1)和手术后(研究组1a SG1a)进行临床和免疫学检查,包括使用六肽类药物(HP、精氨酸- α -天冬氨酸-赖氨酸-缬氨酸-酪氨酸-精氨酸)进行免疫调节治疗。对照组(CG)为健康儿童20例。采用流式细胞术(美国公司CYTOMICS FC 500)检测T淋巴细胞、B淋巴细胞和自然杀伤细胞(NK)的含量。同时测定血清IgA、IgM、IgG水平(ELISA)和中性粒细胞(NG)的吞噬和杀微生物活性。SG1患者治疗前CD3+CD19-T淋巴细胞、CD3+CD8+ TCTL淋巴细胞数量减少,CD3- cd16 +CD56+ NK细胞含量显著降低(p1-3 0.05)。结果发现,ADP患儿IgG水平与对照组各项指标差异无统计学意义,IgM水平降低(p < 0.05), IgA水平升高(p < 0.05)。我们还发现了NG效应功能的缺陷,即活性吞噬NG功能不足,导致细菌抗原的捕获和杀伤受损。nadph氧化酶活性测定显示对炎症和金黄色葡萄球菌的额外诱导缺乏反应。经过包括免疫调节治疗在内的SG1a组的综合治疗,我们发现CD3+CD19-T淋巴细胞、CD3+CD8+TCTL淋巴细胞、CD3- cd16 +CD56+ NK细胞的含量有所恢复(p1-3 0.05)。由于nadph氧化酶的激活,IgA、IgM趋于正常化,NG效应功能(杀伤能力)得到改善。ADP中免疫参数的恢复与肺部脓性破坏过程的早期恢复有关,没有术后并发症,包括预防脓毒性过程。基于hp的药物制剂的免疫调节治疗方案的临床和免疫学效果提示其在ADP免疫功能低下患儿术后的潜在应用。
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引用次数: 0
Expression of IL-7 receptor on Th1, Th17 lymphocytes in patients with psoriatic arthritis 银屑病关节炎患者Th1、Th17淋巴细胞IL-7受体的表达
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13982-eoi
Elena A. Blinova, O. A. Angelskaya, V. A. Kozlov
Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease of the joints, spine, and entheses that can occur in patients with psoriasis. The prevalence of psoriatic arthritis is high in Russia, in recent years there has been an increase in its incidence rates. The pathogenesis of PsA is based on the activation of Th1, Th17 cells. Pro-inflammatory cytokines produced by the cells are involved in the cascade of reactions leading to the joint deformity and bone destruction. For some autoimmune diseases associated with the Th1/Th17 response, IL-7 has been found to be involved in pathogenetic mechanisms. At the same time, IL-7 is assumed to support autoreactive T lymphocytes. Effect of the cytokine on cells is provided by the binding to a specific receptor thus causing a signal transmission into the cell and inducing the processes of differentiation, proliferation, and production of cytokines. In animal models of autoimmune diseases, usage of blocking antibodies to -chain of the IL-7 receptor (IL-7R) was shown to cause reduced inflammation in target tissues and decreased number of infiltrating T lymphocytes. Therefore, the aim of this work was to investigate the in vitro effects of IL-7 and blockade of the -chain of the IL-7 receptor on the contents of Th1, Th17 lymphocytes and expression of IL-7 receptor subunits on these cells in normal subjects and in psoriatic arthritis. The study included nine patients with PsA in the stage of exacerbation of the underlying disease (mean age 446.5 years) and 6 healthy individuals (mean age 452.7 years). The in vitro effects of IL-7 and specific blocking monoclonal antibodies (aCD127) was evaluated in cultures of mononuclear cells from peripheral blood. Flow cytometry was used to determine the expression of IL-7 receptor subunits (CD127, CD132) and to assess cell phenotypes in peripheral blood and cultured cells. We have shown for the first time that patients with PsA have an increased number of CD127+CD132- and CD127+CD132+ cells among Th17 lymphocytes, as well as CD127+CD132-, CD127+CD132+ and CD127-CD132+ cells among Th1 lymphocytes, which suggests participation of IL-7 in maintaining these cell populations. Upon the in vitro supplement of IL-7, an increase in the Th1 cell contents and a decreased number of Th17 cells were observed, both in donors and PsA patients, and the opposite effect was observed under the conditions of IL-7R of blockade. Under the influence of IL-7, as well as with blocking antibodies, there was a significant decrease in CD127 expression on Th1, Th17 lymphocytes. However, a decrease in the number of CD127-132+ among Th1, Th17 lymphocytes occurred only following blockade with antibodies. That is, despite redistribution of Th1 and Th17 lymphocytes in culture, the cells of these populations were not activated under the IL-7 receptor blockade. The obtained data may serve as a basis for choosing the IL-7 receptor as a target in the development of targeted drugs for the treatmen
银屑病关节炎(PsA)是一种慢性免疫介导的炎症性疾病,可发生在银屑病患者的关节、脊柱和关节。银屑病关节炎在俄罗斯的患病率很高,近年来发病率有所上升。PsA的发病机制是基于Th1、Th17细胞的活化。细胞产生的促炎细胞因子参与了导致关节畸形和骨破坏的级联反应。对于一些与Th1/Th17应答相关的自身免疫性疾病,已发现IL-7参与了发病机制。同时,IL-7被认为支持自身反应性T淋巴细胞。细胞因子对细胞的作用是通过与特定受体结合,从而引起信号传递到细胞内,并诱导细胞因子的分化、增殖和产生过程。在自身免疫性疾病的动物模型中,使用IL-7受体-链(IL-7R)阻断抗体可减少靶组织的炎症,减少浸润T淋巴细胞的数量。因此,本研究旨在探讨IL-7和IL-7受体-链阻断对正常人和银屑病关节炎患者Th1、Th17淋巴细胞含量及这些细胞上IL-7受体亚基表达的体外影响。该研究纳入了9例处于基础疾病加重期的PsA患者(平均年龄446.5岁)和6例健康个体(平均年龄452.7岁)。在外周血单核细胞培养中评价IL-7和特异性阻断单克隆抗体(aCD127)的体外作用。流式细胞术检测外周血和培养细胞中IL-7受体亚单位(CD127、CD132)的表达,并评估细胞表型。我们首次发现PsA患者Th17淋巴细胞中CD127+CD132-和CD127+CD132+细胞数量增加,Th1淋巴细胞中CD127+CD132-、CD127+CD132+和CD127-CD132+细胞数量增加,提示IL-7参与维持这些细胞群。在体外补充IL-7后,供体和PsA患者的Th1细胞含量均增加,Th17细胞数量减少,阻断IL-7R的情况下则相反。在IL-7及阻断抗体的作用下,Th1、Th17淋巴细胞上CD127的表达明显降低。然而,只有在抗体阻断后,Th1、Th17淋巴细胞中CD127-132+的数量才会减少。也就是说,尽管在培养中Th1和Th17淋巴细胞重新分布,但这些群体的细胞在IL-7受体阻断下没有被激活。所得数据可作为选择IL-7受体作为靶点,开发治疗PsA的靶向药物的依据。
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引用次数: 0
Mitochondrial dysfunction as a probable mechanism for triggering inflammatory joint diseases 线粒体功能障碍是引发炎性关节疾病的可能机制
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13991-mda
Andrey G. Goncharov, M. A. Tatarkina, V. V. Lobanova, I. I. Kozenkov, A. K. Dzhigkaev, K. V. Gunbin
The article concerns the contribution of mitochondrial dysfunction to the development of inflammatory joint diseases. Mitochondria are the main suppliers of adenosine triphosphate (ATP). Reactive oxygen species (ROS) are a by-product of this metabolic process. Mitochondria also have an effective antioxidant mechanism: there is a certain balance between the ROS formation and their inactivation. Accumulation with age of mutations (single nucleotide substitutions, e.g., transversions, transitions, and deletions) in mitochondrial DNA, may cause a disorder in selective destruction (utilization) of damaged and dysfunctional mitochondria (mitophagy) thus leading to imbalance between the ROS production and their neutralization. This process is triggered by both internal factors (ROS overproduction) and external factors, i.e., tissue damage / injury and infection. The failure of quality control mechanisms resulting from disruption of mitophagy leads to a significant increase in terminally damaged mitochondria, which become a threat to cell survival. High level of genetic mutations accumulating with age in mitochondrial genome causes an increased formation of ROS, which, in turn, are one of the leading activators of the cytosolic NLRP3 protein, the main component of inflammasome type of the same name. Increased inflammasome formation ultimately triggers caspase-1 dependent production of pro-inflammatory interleukins-1(IL-1) and 18 (IL-18). Inadequate removal of damaged mitochondria leads to hyperactivation of inflammatory signaling pathways and, subsequently, to chronic systemic inflammation and development of inflammatory diseases, including primary osteoarthritis (OA). To assess the level of mitochondrial dysfunction, we assessed the numbers of mitochondrial genome copies in post-mitotic muscle cells in 48 patients aged 45 to 95 years who were diagnosed with OA of the knee or hip joints. As a result of our study, we have discovered and confirmed some regularities of human mtDNA mutations corresponding to those in vertebrates, and, in particular, in mammals. Degenerate mutation spectra (without classification of mutations by mtDNA chains and the context of surrounding nucleotides) were constructed for mtDNA in general, and for each individual sample. It was demonstrated that, in one-third of muscle samples, the critical threshold of mtDNA heteroplasmy was exceeded, at which the aberrant biochemical phenotype, in terms of oxidative phosphorylation functioning, (OXPHOS) becomes dominant. Of note, the heteroplasmy rates are lower in older patients who have had significant physical activity during their lives (sports, moderate physical work, etc.). Moreover, the heteroplasmy showed an inverse correlation with high mtDNA copy number. The results obtained can be used to diagnose pathologies in elderly, and the process of healthy aging.
本文关注线粒体功能障碍对炎性关节疾病发展的贡献。线粒体是三磷酸腺苷(ATP)的主要供给者。活性氧(ROS)是这种代谢过程的副产物。线粒体也具有有效的抗氧化机制:ROS的形成与失活之间存在一定的平衡。随着线粒体DNA中突变(单核苷酸取代,例如,翻转,转变和缺失)的年龄积累,可能导致受损和功能失调线粒体(线粒体自噬)的选择性破坏(利用)紊乱,从而导致ROS产生与其中和之间的不平衡。这一过程是由内部因素(ROS过量产生)和外部因素(即组织损伤/损伤和感染)触发的。线粒体自噬破坏导致的质量控制机制失效,导致线粒体终末损伤显著增加,成为细胞生存的威胁。随着年龄的增长,线粒体基因组中积累的高水平基因突变导致ROS的形成增加,而ROS又是胞质NLRP3蛋白的主要激活因子之一,而NLRP3蛋白是同名炎症小体类型的主要成分。炎性小体形成的增加最终触发caspase-1依赖性的促炎白介素-1(IL-1)和IL-18 (IL-18)的产生。受损线粒体的清除不足导致炎症信号通路的过度激活,随后导致慢性全身性炎症和炎性疾病的发展,包括原发性骨关节炎(OA)。为了评估线粒体功能障碍的水平,我们评估了48名年龄在45岁至95岁之间被诊断为膝关节或髋关节OA的患者有丝分裂后肌肉细胞中线粒体基因组拷贝的数量。通过我们的研究,我们发现并证实了人类mtDNA突变与脊椎动物,特别是哺乳动物mtDNA突变的一些规律。退化突变谱(没有mtDNA链和周围核苷酸的突变分类)被构建为一般的mtDNA,并为每个单独的样本。研究表明,在三分之一的肌肉样本中,超过了mtDNA异质性的临界阈值,在此阈值下,就氧化磷酸化功能而言,异常生化表型(OXPHOS)成为主导。值得注意的是,在生活中有大量体力活动(运动、适度体力劳动等)的老年患者中,异质性率较低。此外,异质性与高mtDNA拷贝数呈负相关。所得结果可用于老年人的病理诊断,以及健康衰老的过程。
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引用次数: 0
Contents of matrix metalloproteinase type 2 (MMP-2) and complexes MMP-9/TIMP-1, MMP-2/TIMP-2, and total cholesterol in practically healthy people and patients with hypertension 实际健康人及高血压患者基质金属蛋白酶2 (MMP-2)及其复合物MMP-9/TIMP-1、MMP-2/TIMP-2和总胆固醇的含量
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13546-com
Natalya S. Chepurnova, S. V. Knysh, V. N. Yushchuk, E. V. Markelova, K. R. Sanatsky, A. N. Yushchenko, M. Z. Yermolitskaya
Arterial hypertension (AH) is the most common age-associated disease among the working population. Polyetiology of AH requires a more thorough definition and study of its predictors aiming for understanding the role of external influences, as well as detection of genetic polymorphisms at early stages, in order to limit their implementation. The scientific reviews discuss the important role of abnormal vascular remodeling in the pathogenesis of hypertension. The main factor of such alterations is the rearrangement of extracellular matrix due to matrix metalloproteinases (MMP), the zinc-dependent enzymes with a wide substrate specificity. In addition, in more than 70% of cases, AH is combined with lipid metabolism disorders, including an increase in cholesterol levels. These mechanisms should be taken into account when assessing risk factors for development of cardiovascular accidents. The role of MMP-2 and the complexes MMP- 9/ TIMP- 1, MMP-2/TIMP-2 in pathogenesis of vascular restructuring is insufficiently described in the review articles. The article presents our results of studying the system of proteolytic enzymes and the level of total cholesterol in 110 practically healthy people and 90 persons with AH aged 18 to 74 years old. The levels of MMP-2, MMP-9/ TIMP- 1, MMP-2/TIMP-2 complexes in blood serum were studied by the sandwich variant of ELISA technique. Statistical processing of the obtained data was carried out using the analytical software IBM SPSS Statistics, v. 22.0.1. It was found that in the groups of women, regardless of the presence, or absence of pathology, the level of total cholesterol is higher if compared with male subjects. MMP-2 values were low both in the general group of practically healthy people, regardless of gender, and in the group of men with hypertension. Proteolytic activity of MMP-2 shows a broader substrate activity in women with hypertension. In the group of practically healthy men and women, we have registered lower levels of the studied MMP complexes and their tissue inhibitors. An imbalance in the proteolysis/antiproteolysis system is observed both in the group of hypertensive women with more pronounced effects upon migration, proliferation and apoptosis of smooth muscle cells, endothelial and inflammatory cells, thus determining formation of intima and arterial remodeling, as well as in the group of men with hypertension with predominance of remodeling factors that affects the rigidity of vascular wall.
动脉高血压(AH)是工作人群中最常见的与年龄相关的疾病。AH的多聚学需要对其预测因子进行更彻底的定义和研究,以了解外部影响的作用,并在早期阶段检测遗传多态性,以限制其实施。文献综述讨论了血管重构异常在高血压发病中的重要作用。这种改变的主要因素是由于基质金属蛋白酶(MMP)引起的细胞外基质的重排,这是一种具有广泛底物特异性的锌依赖性酶。此外,在70%以上的病例中,AH合并脂质代谢紊乱,包括胆固醇水平升高。在评估心血管事故发生的危险因素时,应考虑到这些机制。MMP-2及其复合物MMP- 9/ TIMP- 1、MMP-2/TIMP-2在血管重构发病机制中的作用在综述文章中没有得到充分的描述。本文介绍了110例实际健康人及90例18 ~ 74岁AH患者的蛋白水解酶系统及总胆固醇水平的研究结果。采用夹心型ELISA技术检测血清中MMP-2、MMP-9/ TIMP- 1、MMP-2/TIMP-2复合物的水平。使用IBM SPSS Statistics, v. 22.0.1分析软件对所得数据进行统计处理。研究发现,在女性群体中,无论是否存在病理,总胆固醇水平都高于男性受试者。MMP-2值在一般健康人群(不分性别)和男性高血压患者组中均较低。在女性高血压患者中,MMP-2的蛋白水解活性显示出更广泛的底物活性。在实际健康的男性和女性组中,我们已经记录到较低水平的研究MMP复合物及其组织抑制剂。在高血压女性组和高血压男性组中均观察到蛋白水解/抗蛋白水解系统失衡,前者对平滑肌细胞、内皮细胞和炎症细胞的迁移、增殖和凋亡的影响更为明显,从而决定了内膜的形成和动脉重构,而前者则以影响血管壁刚性的重塑因子为主。
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引用次数: 0
sIgA-protease activity of microorganisms isolated from the prostate secretion 前列腺分泌物中分离的微生物siga蛋白酶活性
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13776-spa
Olga A. Pashinina, O. L. Kartashova, T. M. Pashkova, V. A. Gritsenko
Our aim was to characterize the ability of bacteria from prostate secretions of different taxonomic affiliations to inactivate secretory IgA (sIgA). Materials and methods: We performed experiments with 122 isolates of eight types of microorganisms isolated from prostate secretions of the patients with chronic bacterial prostatitis (CBP) and healthy males. The bacterial spectrum of microbiota was studied by bacteriological techniques, the species identification of microorganisms was carried out by mass spectrometry. The sIgA-protease activity of microorganisms was determined by the enzyme immunoassay using the IgA secretory ELISA-BEST kit. Results: A wide prevalence of sIgA-protease activity has been detected in the microorganisms of different types isolated from prostate secretions of patients with CBP and healthy males. E. faecalis was the most active producer of sIgA proteases. We revealed an intraspecific and interspecific variability of the levels of sIgA-protease activity among Staphylococci. The microorganisms isolated from CBP were shown to express a significantly more pronounced ability to inactivate sIgA compared to strains isolated from healthy men.
我们的目的是表征不同分类关系的前列腺分泌物细菌灭活分泌IgA (sIgA)的能力。材料与方法:从慢性细菌性前列腺炎(CBP)患者和健康男性前列腺分泌物中分离8种微生物122株进行实验。采用细菌学技术研究了微生物群的细菌谱,采用质谱法对微生物进行了种类鉴定。采用IgA分泌ELISA-BEST试剂盒,采用酶免疫法测定微生物的siga蛋白酶活性。结果:从CBP患者和健康男性前列腺分泌物中分离的不同类型微生物中均检测到广泛存在的siga蛋白酶活性。粪肠杆菌是sIgA蛋白酶最活跃的生产者。我们揭示了葡萄球菌中siga蛋白酶活性水平的种内和种间变异性。与从健康男性中分离的菌株相比,从CBP中分离的微生物表现出更明显的sIgA灭活能力。
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引用次数: 0
Concomitant infections in children with allergic pathology in the Kaliningrad region 加里宁格勒地区过敏性病理儿童的伴随感染
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13986-cii
Aishat Z. Markhaychuk, A. O. Pleshkova, A. C. Mun, A. G. Goncharov
The aim of our work was to study the structure and prevalence of the infectious syndrome in children from Kaliningrad Region with moderate-to-severe allergic pathology, with a complex manifestations of allergic reactions, both on skin and on the mucous membranes of the digestive and respiratory tract. Ninety children from 0 to 18 years old with various symptoms of allergic pathology were examined and included in the study group using standard clinical, objective and laboratory criteria. The severity of clinical course was associated with the severe and long-lasting symptoms, as well as with frequent bacterial and bacterial-fungal complications, with impaired quality of life and night sleep. The children were consulted by the specialists in otorhinolaryngology, hematology, pulmonology, surgery, ophthalmology, infectology, endocrinology, cardiology. Diagnoses according to nosological forms were made in accordance with the current clinical recommendations of Russian Ministry of Health. Our article presents data on concomitant infectious diseases and their impact on general condition and severity of hypersensitive responses. The average age of allergic manifestations in the group of children was 3.122.72 years. The average duration of the disease in the observed group was 7.50.88 years. The number of boys in our group prevailed (n = 56) by 1.6 times. Complicated heredity factors were reported by 15% of the patients parents. However, with careful collection of medical history taking, upon dynamic observation, the aggravated heredity on the mothers side was detected in 45.56% (n = 41), and on the fathers side, in 31.1% of cases (n = 28). In eight families, both parents suffered from allergic pathology, in siblings, 21.1% (n = 19) of the examined children had allergies. In the families, including grandparents, allergic pathology was reported in 56 cases (62.2%). Almost all patients had problems with nasal breathing, 77 (85.6%) children with adenoid hypertrophy had a habit of breathing through the mouth. Postnasal drip syndrome was found in 78 cases. Allergic rhinitis with adenoid hypertrophy is, generally, accompanied by postnasal leakage, which can provoke aspiration bronchitis and pneumonia, especially if pathogenic or opportunistic flora is transferred to the nasal cavity and/or to the pharynx. Conclusions: 1. Identification and rehabilitation of chronic foci of infection, bacterial, fungal, should be a necessary component of the personalized therapy of allergic pathology in children. 2. In cases of recurrent sowing or finding of pathogenic flora (iodophilic flora, fungi, coccal flora) in the coprogram, one should exclude not only transient lactase deficiency, but also congenital lactase deficiency, thus preventing development of enterocolitis in the future like as worsening of skin status and respiratory manifestations. 3. In case of severe respiratory viral infections in children during the period of adaptation for pre-school inst
我们的工作目的是研究加里宁格勒地区患有中度至重度过敏病理的儿童感染综合征的结构和流行情况,这些儿童的过敏反应表现复杂,包括皮肤和消化道和呼吸道的粘膜。采用标准的临床、客观和实验室标准,对90名0至18岁具有各种过敏病理症状的儿童进行检查,并将其纳入研究组。临床病程的严重程度与症状的严重程度和持续时间有关,也与频繁的细菌和细菌-真菌并发症有关,与生活质量和夜间睡眠受损有关。这些儿童由耳鼻喉科、血液科、肺科、外科、眼科、感染科、内分泌科、心脏病科的专家进行咨询。根据俄罗斯卫生部目前的临床建议,根据分类学表格进行诊断。我们的文章介绍了伴随性传染病及其对一般情况和过敏反应严重程度的影响的数据。患儿出现过敏症状的平均年龄为3.122.72岁。观察组平均病程为7.50.88年。本组男生人数占比(n = 56) 1.6倍。15%的患者父母报告有复杂的遗传因素。然而,通过仔细收集病史,动态观察发现,母亲侧遗传加重占45.56% (n = 41),父亲侧遗传加重占31.1% (n = 28)。在8个家庭中,父母双方都患有过敏病理,在兄弟姐妹中,21.1% (n = 19)的被检查儿童患有过敏。在包括祖父母在内的家庭中,过敏病理报告56例(62.2%)。 几乎所有患者都有鼻腔呼吸问题,77例(85.6%)腺样体肥大患儿有通过口呼吸的习惯。鼻后滴涕综合征78例。变应性鼻炎伴腺样体肥大,通常伴有鼻后漏,可引起吸入性支气管炎和肺炎,特别是当致病性或机会性菌群转移到鼻腔和/或咽部时。 结论:1。慢性感染病灶的识别和康复,细菌,真菌,应是儿童过敏病理个性化治疗的必要组成部分。2. 如果在共程序中反复播种或发现致病性菌群(嗜碘菌群,真菌,球菌菌群),则不仅应排除短暂性乳糖酶缺乏症,还应排除先天性乳糖酶缺乏症,从而防止将来发展为小肠结肠炎,如皮肤状况恶化和呼吸症状。3.儿童在适应学前机构期间发生严重呼吸道病毒感染时,应排除对室内尘螨和家畜表皮过敏原的过敏。4. 一种全面和个性化的方法来诊断过敏性疾病和合并症,使我们能够为稳定缓解创造条件,使进行过敏原特异性免疫治疗成为可能,这可能为我们的患者的高反应状态提供疾病修饰作用。
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引用次数: 0
Interaction between MSCS and blood mononuclear cells during <i>in vitro</i> co-cultivation in the presence of a three-dimensional artificial matrix mimicking regenerating bone tissue 体外培养过程中MSCS与血单个核细胞的相互作用在模拟再生骨组织的三维人工基质中共同培养
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13547-ibm
Kristina A. Yurova, I. K. Norkin, O. G. Khaziakhmatova, V. V. Malashchenko, O. B. Melashchenko, P. A. Ivanov, D. D. Ligatyuk, I. A. Khlusov, L. S. Litvinova
Bone tissue repair and regeneration is a complex process involving many cells and controlled by multiple factors. Immune cells and cytokines play a crucial role in regulating the balance of bone formation and resorption. However, the immunomodulatory mechanism of bone regeneration is still unclear. Nevertheless, the reciprocal regulatory influence of immunocompetent cells and mesenchymal stem cells (MSCs) is well known. MSCs and immunocompetent cells secrete various cytokines, growth factors, and extracellular matrix molecules that play important roles in regulating hematopoiesis, angiogenesis, immune and inflammatory responses. Several studies confirm that different molecules expressed by MSCs may induce lymphocyte proliferation. Therefore, the study of the mutual influence of MSCs and blood mononuclear cells during in vitro co-cultivation, even in the presence of an artificial matrix mimicking regenerating bone tissue, is relevant and expedient. In this experimental series, the studies were performed at the interface between living and non-living substrate phases thus mimicking the regenerating bone / hematopoietic microenvironment system. A series of separated in time experiments was performed on a plastic surface (2D culture model) and in the presence of three-dimensional artificial matrices mimicking regenerating bone tissue (3D culture model).
骨组织的修复和再生是一个涉及许多细胞、受多种因素控制的复杂过程。免疫细胞和细胞因子在调节骨形成和骨吸收平衡中起着至关重要的作用。然而,骨再生的免疫调节机制尚不清楚。然而,免疫活性细胞和间充质干细胞(MSCs)的相互调节作用是众所周知的。MSCs和免疫能力细胞分泌各种细胞因子、生长因子和细胞外基质分子,在调节造血、血管生成、免疫和炎症反应中发挥重要作用。多项研究证实,MSCs表达的不同分子可诱导淋巴细胞增殖。因此,在体外共培养过程中,即使在模拟再生骨组织的人工基质存在的情况下,研究间充质干细胞和血单核细胞的相互影响是相关的和有利的。在这个实验系列中,研究在活体和非活体基质阶段的界面上进行,从而模拟再生骨/造血微环境系统。在塑料表面(2D培养模型)和模拟再生骨组织的三维人工基质(3D培养模型)上进行了一系列分离的时间实验。
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引用次数: 0
Immune system dysfunction in purulent inflammatory diseases of the maxillofacial area in pediatric patients 小儿颌面部化脓性炎症性疾病的免疫系统功能障碍
Pub Date : 2023-09-22 DOI: 10.46235/1028-7221-13992-isd
Marina N. Mitropanova, T. A. Ponomarenko, G. A. Chudilova, Yu. V. Teterin, V. N. Chapurina
The issues of treatment of purulent inflammatory diseases of the maxillofacial region (PMMA) are quite urgent, due to increasing number of such patients. Their clinical course is getting worse, and the efficiency of antibiotic therapy is decreasing. Clinical outcomes of purulent maxillofacial pathology in children are complicated by potential severe local deformities at the growth areas of the jaw bones which are difficult to eliminate. The number of cases of prolonged and chronic inflammatory processes, development of local and general complications is increased. The reason for these complications may be an impaired susceptibility to infectious agents, which is determined by the state of the immune system. Therefore, our aim was to reveal some features of immune functions in children with purulent-inflammatory diseases of maxillofacial area. The study included a group of pediatric patients 8-17 years old with maxillofacial inflammatory diseases of the maxilla (the study group), and 13 conditionally healthy children (the comparison group). The contents of T cells (CD3+CD19-, CD3+CD4+, CD3+CD8+, CD3+CD4+/CD3+CD8+), and В cells (CD3-CD19+), NK (CD3-CD16+CD56+) was determined using Cytomics FC-500 (Beckman Coulter, USA);concentrations of serum IgA, IgM, IgG were determined by ELISA technique (Vector-Best, Russia). Phagocytic activity of neutrophilic granulocytes (NG) was evaluated as percentage of actively phagocytic NGs, capturing processes were assessed by appropriate phagocytic indices, and the digestive activity was evaluated against S. aureus (strain 209). Combined defects of immune response in children with maxillofacial hypertension were established: decrease of T lymphocytes contents along with decrease of T helpers and CTL ratio along with unchanged content of NK cells and B lymphocytes. Increase of IgA and IgG levels was also found. Defects of phagocytosis were revealed, primarily connected with the processes of completed phagocytosis and increased content of actively phagocytizing NG. Treatment of children suffering with purulent inflammatory diseases of maxillofacial region is still an urgent problem in dentistry. The revealed dysfunction of immune response to pathogens in the purulent maxillofacial disorders may explain a prolonged clinical course of inflammatory processes, thus determining a need for usage of immunotropic therapy in complex treatment schedules including operative aid as well as conventional drug and physiotherapeutic treatment aiming for increase of rehabilitation efficiency and prevention of postoperative complications in these patients.
颌面区化脓性炎症性疾病(PMMA)的治疗问题非常紧迫,因为这类患者的数量越来越多。他们的临床病程越来越差,抗生素治疗的效率也在下降。儿童颌面部化脓性病变的临床结果是复杂的潜在严重的局部畸形在颌骨的生长区域,难以消除。长期和慢性炎症过程的病例数,局部和一般并发症的发展增加。这些并发症的原因可能是对感染因子的易感性受损,这是由免疫系统的状态决定的。因此,我们的目的是揭示儿童颌面部化脓性炎症性疾病免疫功能的一些特征。研究包括一组8-17岁的上颌面炎症性疾病患儿(研究组)和13名有条件健康的儿童(对照组)。T细胞(CD3+CD19-、CD3+CD4+、CD3+CD8+、CD3+CD4+/CD3+CD8+)、В细胞(CD3-CD19+)、NK细胞(CD3- cd16 +CD56+)的含量采用美国Beckman Coulter公司的Cytomics FC-500检测;血清IgA、IgM、IgG浓度采用ELISA技术检测(Vector-Best,俄罗斯)。以吞噬活性中性粒细胞(NG)的百分比评价其吞噬活性,以适当的吞噬指标评价其捕获过程,并评价其对金黄色葡萄球菌(菌株209)的消化活性。建立了颌面部高血压患儿免疫反应的综合缺陷:T淋巴细胞含量降低,T辅助细胞和CTL比例降低,NK细胞和B淋巴细胞含量不变。同时发现IgA和IgG水平升高。吞噬缺陷显现,主要与吞噬完成过程和主动吞噬NG含量增加有关。 儿童颌面部化脓性炎症性疾病的治疗仍是牙科医学亟待解决的问题。化脓性颌面疾病中对病原体的免疫反应功能障碍可能解释了炎症过程的临床病程延长,从而确定了在复杂的治疗方案中需要使用免疫治疗,包括手术辅助以及常规药物和物理治疗,旨在提高这些患者的康复效率和预防术后并发症。
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引用次数: 0
期刊
Russian journal of immunology : RJI : official journal of Russian Society of Immunology
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