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Association of the cytokine profile and metabolic syndrome components in young patients 细胞因子谱与年轻患者代谢综合征成分的关系
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1164-aot
V. Sumerkina, L. Telesheva, E. Golovneva
The components of metabolic syndrome (MS) are independent factors of cardiometabolic risk and are associated with impaired humoral immunity. However, the literature data on the cytokine profile features in MS are ambiguous. Therefore, associations between cytokine levels and MS components were determined in a group of MS patients of both sexes, as well as indices of visceral adipose tissue function were studied. The work included 149 patients aged 18-45 years. The patients were divided into 2 groups: group 1 (n = 71) included patients without abdominal obesity and MS components (comparison group); group 2 (n = 78), patients with MS. The concentrations of glucose, glycosylated hemoglobin, insulin, total cholesterol, HDL-C, LDL-C, triglycerides, leptin, adiponectin were determined. The indexes of insulin resistance HOMA-IR, Tg/HDL and TyG, as well as marker of visceral adipose tissue dysfunction VAI were calculated. ELISA technique was used to determine the concentration of IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IFN, IFN, МСР-1 и TNF. Results: In the patients with MS, we have found increased levels of IL-6, IL-10, MCP-1, and decrease of IL-2, IL-4, IFN levels. Correlation analysis established a relationship between glucose levels and MCP-1; glycosylated hemoglobin and IL-6, TNF. Among the indices of lipid metabolism, we have revealed some associations between LDL-C and IFN; HDL-C and IL-2, IL-4, IFN. The levels of triglycerides correlated with MCP-1. A negative relationship between the presence of arterial hypertension and the IL-4 contents was established. A negative correlation of leptin levels with IL-4 and IFN concentrations was also determined. Markers of insulin resistance (Tg/HDL and TyG) were associated with MCP-1 chemokine, thus supporting chronic inflammatory process. The VAI index, which reflects the dysfunction of visceral adipose tissue, showed a correlation with MCP-1. Thus, the results of investigation suggest an involvement of the cytokine system in the disorders of visceral adipose tissue and development of the metabolic syndrome.
代谢综合征(MS)的组成部分是心脏代谢风险的独立因素,并与体液免疫受损有关。然而,关于MS中细胞因子谱特征的文献数据是模糊的。因此,我们在一组男女多发性硬化症患者中确定了细胞因子水平与多发性硬化症成分之间的关系,并研究了内脏脂肪组织功能指标。这项研究包括149名年龄在18-45岁之间的患者。将患者分为两组:第一组(n = 71)为无腹部肥胖、无MS成分的患者(对照组);第二组(78例),ms患者,测定血糖、糖化血红蛋白、胰岛素、总胆固醇、HDL-C、LDL-C、甘油三酯、瘦素、脂联素的浓度。计算胰岛素抵抗指标HOMA-IR、Tg/HDL、TyG及内脏脂肪组织功能障碍标志物VAI。采用ELISA技术检测IL-1、IL-2、IL-4、IL-6、IL-8、IL-10、IFN、IFN、МСР-1 TNF的浓度。结果:MS患者IL-6、IL-10、MCP-1水平升高,IL-2、IL-4、IFN水平降低。相关分析建立了血糖水平与MCP-1之间的关系;糖化血红蛋白和IL-6, TNF。在脂质代谢指标中,我们揭示了LDL-C与IFN之间的一些关联;HDL-C和IL-2, IL-4, IFN。甘油三酯水平与MCP-1相关。动脉高血压的存在与IL-4含量呈负相关。瘦素水平与IL-4和IFN浓度呈负相关。胰岛素抵抗标志物(Tg/HDL和TyG)与MCP-1趋化因子相关,从而支持慢性炎症过程。反映内脏脂肪组织功能障碍的VAI指数与MCP-1存在相关性。因此,研究结果表明细胞因子系统参与内脏脂肪组织紊乱和代谢综合征的发展。
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引用次数: 0
Dynamics of cell-free DNA levels in the in vivo LPS-induced inflammation model lps诱导炎症模型中游离DNA水平的动态变化
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1179-doc
E. N. Demchenko, E. D. Gavrilova, E. Goiman, N. Volskiy, V. Kozlov
An increased concentration of extracellular cell free DNA (cfDNA) is a distinctive characteristic of pathologies that mainly occur in acute inflammation (myocardial infarction, sepsis, stroke, trauma). The increase of cfDNA in chronic inflammatory processes, oncological, autoimmune diseases is less significant and is mainly due to aberrant cell death processes. One of such diseases is systemic lupus erythematosus (SLE). It has recently been shown that, in addition to increased cfDNA concentration, the degree of inflammation can reflect the N/L index (neutrophil to lymphocyte ratio), being a simple and informative marker of disease activity in patients with SLE. The aim of the study was to study the dynamics of the level of cfDNA and the N/L index in the model of LPS-induced inflammatory response as observed in intact mice, and their relation to the phenotypic heterogeneity of model SLE. We used female hybrid mice (C57Bl/6xDBA/2) F1 and female DBA/2 mice at the age of 6-8 weeks. LPS of E. coli strain 111: B4 (Sigma) was injected intraperitoneally once at doses of 10 ng, 1 g and 100 g per mouse in PBS. The control group was injected with the appropriate volume of buffer. The TNF-binding domain of the variola virus CRMB protein was used as an inhibitor of TNF, which was administered 30 min before the introduction of LPS. The dynamics of the response to LPS was assessed after 4, 8, 11, 24 hours by the N/L index and the level of cfDNA; at the zero point, the parameters were determined before the introduction of LPS. A day after a single injection of LPS at a dose of 1 g/mouse, a SLE model was induced on the same hybrid mice (double intravenous administration with an interval of 6 days of spleen cells of the DBA/2 line, 60-70 106 cells each). Three months later, with proteinuria of 3 mg/ mL or more, mice were assigned to the SLEnephritis+ group, with a protein of less than 3 mg/mL, to the SLEnephritis- group. Statistical processing of the results was carried out by nonparametric statistics using the MannWhitney test. Differences were considered statistically significant at p 0.05. It was found that the change in the N/L index, as well as the change in the level of cfDNA, depends on the dose of LPS administered. It was shown that the level of cfDNA reaches its maximum after 8 and 11 hours after the introduction of LPS is reliably reduced when using the inhibitor TNF. A retrospective analysis indicates that there is a definite relationship between the response of intact mice to LPS before induction of cGVHD, and their subsequent division into variants of SLEnephritis + and SLEnephritis - in the course of disease development.
细胞外游离DNA (cfDNA)浓度升高是主要发生在急性炎症(心肌梗死、败血症、中风、创伤)的病理的显著特征。慢性炎症过程、肿瘤、自身免疫性疾病中cfDNA的增加不太显著,主要是由于异常的细胞死亡过程。其中一种疾病是系统性红斑狼疮(SLE)。最近有研究表明,除了cfDNA浓度升高外,炎症程度还可以反映N/L指数(中性粒细胞与淋巴细胞比值),这是SLE患者疾病活动性的一个简单且信息丰富的标志物。本研究旨在研究完整小鼠lps诱导炎症反应模型中cfDNA水平和N/L指数的动态变化及其与模型SLE表型异质性的关系。我们选用6-8周龄的雌性杂交小鼠(C57Bl/6xDBA/2) F1和雌性DBA/2小鼠。将大肠杆菌111:B4 (Sigma)的LPS以每只小鼠10 ng、1 g和100 g的剂量在PBS中腹腔注射一次。对照组注射适量的缓冲液。天花病毒CRMB蛋白的TNF结合域被用作TNF的抑制剂,在引入LPS前30分钟给药。在4、8、11、24 h后,通过N/L指数和cfDNA水平评估LPS的反应动态;在零点处,参数是在LPS引入前确定的。单次注射LPS 1 g/只1 d后,在同一杂交小鼠上诱导SLE模型(DBA/2系脾细胞两次静脉注射,间隔6天,每次注射60-70 106个细胞)。3个月后,蛋白尿达到或超过3mg /mL的小鼠被分配到睡眠肾炎+组,蛋白质低于3mg /mL的小鼠被分配到睡眠肾炎-组。采用曼惠特尼检验对结果进行非参数统计处理。p 0.05认为差异有统计学意义。结果发现,N/L指数的变化以及cfDNA水平的变化与LPS剂量有关。研究表明,cfDNA水平在LPS引入后8和11小时达到最大值,使用抑制剂TNF可靠地降低。回顾性分析表明,在cGVHD诱导前,完整小鼠对LPS的反应与随后在疾病发展过程中分化为SLEnephritis +和SLEnephritis -变体之间存在一定的关系。
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引用次数: 0
Role of innate errors of immunity in the group of children with fatal outcomes during the first year of life 先天性免疫错误在出生第一年致命性结局儿童群体中的作用
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1185-roi
D. A. Cheremokhin, I. Tuzankina, V. Chereshnev, M. A. Bolkov, Kh. Shinvari
In the modern world, inborn errors of immunity (IEIs), or primary immunodeficiencies (PIDs), are among of the main causes of childhood disability and mortality, determining the demographic state of mankind not only at present, but also in the future. In the Sverdlovsk Region over the past 5 years, there were about 30% of children who died from severe combined primary immunodeficiency. This retrospective study is devoted to the study of the nosological profile of mortality in the children with immune-dependent disorders in the Sverdlovsk Region, as well as to assess information significance of extrachromosomal circular DNA molecules (TREC and KREC) analysis. Some anamnestic data on the course of prenatal period in the current and previous pregnancies were considered the signs of suggested diagnosis of primary immunodeficiencies, i.e., threats of pregnancy loss at the early terms, documented cases of early childhood death, persistent viral and bacterial infections in the mother, complicated course of pregnancy in the mother, as well as some clinical manifestations, including fungal-bacterial sepsis, generalized viral infection, repair disorders, reduced physiological tolerance accompanied by autoimmune organ damage and uncontrolled systemic inflammation. The study demonstrated a wide range of nosological entities of innate errors of immunity in the structure of early childhood mortality, including both classical forms of primary immunodeficiencies and the disorders not directly related to innate errors of immunity, but those showing phenotypically pronounced immunodeficiency and their immediate role in statistical deviations. Among the main criteria that may presume possible presence of an immune-dependent pathology in the early neonatal period we considered the molecular markers of naive T and B cells (TREC and KREC, respectively) revealed in 70% of the cases studied, with, at least, one of these indexes found to be reduced. It is important to understand that primary immunodeficiencies are not as rare as previously thought. Therefore, it is necessary to carry out timely and high-quality diagnostics, in order to avoid unavoidable deaths.
在现代世界,先天免疫缺陷(IEIs)或原发性免疫缺陷(PIDs)是儿童残疾和死亡的主要原因之一,不仅决定了人类目前的人口状况,而且决定了未来的人口状况。在过去5年中,斯维尔德洛夫斯克州约有30%的儿童死于严重的联合原发性免疫缺陷。本回顾性研究致力于研究斯维尔德洛夫斯克地区免疫依赖性疾病儿童死亡率的病毒学特征,以及评估染色体外环状DNA分子(TREC和KREC)分析的信息意义。关于当前和以前怀孕期间的产前过程的一些记忆资料被认为是原发性免疫缺陷诊断的迹象,即早期妊娠流产的威胁、记录的幼儿死亡病例、母亲持续的病毒和细菌感染、母亲的复杂妊娠过程,以及一些临床表现,包括真菌-细菌败血症、全身性病毒感染、修复障碍、生理耐受性降低,伴有自身免疫器官损伤和不受控制的全身炎症。该研究证明了儿童早期死亡率结构中先天免疫缺陷的广泛的病源学实体,包括经典形式的原发性免疫缺陷和与先天免疫缺陷不直接相关的疾病,但那些表现出显着的免疫缺陷及其在统计偏差中的直接作用。在新生儿早期可能存在免疫依赖性病理的主要标准中,我们考虑了在70%的研究病例中发现的幼稚T细胞和B细胞的分子标记(分别为TREC和KREC),其中至少有一项指标被发现降低。了解原发性免疫缺陷并不像以前认为的那样罕见是很重要的。因此,有必要进行及时和高质量的诊断,以避免不可避免的死亡。
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引用次数: 0
Studying expression of IL-1β gene under the action of siRNA complexes with anti-influenza effect 研究抗流感siRNA复合物作用下IL-1β基因的表达
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1202-seo
E. Pashkov, A. V. Pak, N. Abramova, I. V. Yakovleva, N. Vartanova, E. Bogdanova, E. P. Pashkov, O. Svitich, V. Zverev
Influenza is one of the most urgent global health problems today. The influenza virus has immunosuppressive properties, which can lead to the development of secondary immunodeficiencies, interfering with the functioning of the interferon system activation, thus leading to impaired production of pro-inflammatory cytokines. IL-1 is the most important player in development of antiviral immunity. This cytokine plays an important role in boosting the expression of the MCP-1 and MCP-3 genes and maturation of macrophages and dendritic cells. Induction of IL-1 production occurs due to interaction of the ligand with Toll-like receptors. Currently, there is a lot of drugs aimed at the prevention and treatment of influenza infection. However, their use in some cases is difficult due to high mutational variability of the influenza virus, thus making it resistant to these drugs. Therefore, the issue of developing and creating effective methods to combat such infections is of particular importance. A promising approach to the treatment and prevention of viral respiratory infections may be connected with RNA interference. This process consists of degradation of foreign mRNA by small interfering RNA (siRNA) molecules. The aim of the present study was to evaluate expression of the IL-1 gene upon transfection of miRNA complexes directed to the cellular FLT4, Nup98, Nup205 genes. Evaluation of changed viral reproduction was carried out using titration by CPE virus-containing fluid. Expression level of the IL-1 gene was determined by means of real-time RT-PCR. Assessment of the changes in viral reproduction allowed us to reveal that the use of all the miRNA complexes directed to the cellular genes lead to a significant decrease in viral reproduction on the 1st day after infection. Usage of Nup205 + FLT4 and FLT4 + Nup205 + Nup98 complexes proved to cause a decrease in viral reproduction on the second day as well (p 0.05), as compared with nonspecific and viral controls. When analyzing expression profile of the IL-1 gene, an increase in its expression was observed on the 1st day for all miRNA complexes and on the 2nd and 3rd days for the Nup98 + FLT4 and Nup205 + Nup98 complexes. In the course of the study, it was found that suppression of the cellular genes FLT4, Nup98 and Nup205 activities, which are necessary for viral reproduction, led to a significant decrease in viral activity and an increase in IL-1 expression.
流感是当今最紧迫的全球卫生问题之一。流感病毒具有免疫抑制特性,可导致继发性免疫缺陷的发展,干扰干扰素系统激活的功能,从而导致促炎细胞因子的产生受损。IL-1在抗病毒免疫的发展中起着至关重要的作用。该细胞因子在促进巨噬细胞和树突状细胞MCP-1和MCP-3基因的表达和成熟中起重要作用。诱导IL-1的产生是由于配体与toll样受体的相互作用。目前,有很多药物旨在预防和治疗流感感染。然而,由于流感病毒的高度突变变异性,在某些情况下很难使用这些药物,从而使其对这些药物产生耐药性。因此,发展和创造有效的方法来对抗这种感染的问题是特别重要的。一种治疗和预防病毒性呼吸道感染的有希望的方法可能与RNA干扰有关。该过程由小干扰RNA (siRNA)分子降解外源mRNA组成。本研究的目的是评估转染指向细胞FLT4、Nup98、Nup205基因的miRNA复合物后IL-1基因的表达。用CPE含病毒液滴定法评价变异病毒的繁殖情况。real-time RT-PCR检测IL-1基因表达水平。对病毒繁殖变化的评估使我们发现,使用所有指向细胞基因的miRNA复合物导致感染后第1天病毒繁殖显著减少。与非特异性和病毒对照相比,Nup205 + FLT4和FLT4 + Nup205 + Nup98复合物的使用在第2天也导致病毒繁殖减少(p 0.05)。在分析IL-1基因的表达谱时,在所有miRNA复合物的第1天,以及Nup98 + FLT4和Nup205 + Nup98复合物的第2天和第3天,IL-1基因的表达均有所增加。在研究过程中发现,抑制病毒繁殖所必需的细胞基因FLT4、Nup98和Nup205的活性,导致病毒活性显著降低,IL-1表达增加。
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引用次数: 0
Innate immune response in the patients with heart disease and acute kidney injury after coronary artery bypass grafting, depending on the duration of extracorporeal circulation 冠心病合并急性肾损伤患者冠状动脉搭桥术后的先天免疫反应,取决于体外循环时间
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1189-iir
O. Fomina, E. Chagina, L. Fedyanina, V. E. Krasnikov
Incidence of chronic diseases is increased in the 21st century due to prolonged life expectancy. Cardiovascular disease is the most common disorder worldwide, complicated with high morbidity and mortality. Upon increased prevalence of this disease, cardiac surgery has become an essential strategy for patients that do not respond to medications and other therapeutic procedures. Some potential complications in cardiac surgery affect kidneys, lung, brain over the postoperative period. Acute kidney injury (AKI) is considered a serious complication of cardiac surgery characterized by rapid loss of kidney function leading to acute increase in the serum creatinine concentration. AKI occurs in up to 30% of patients after cardiac surgery and is observed in 2% of the cases with isolated coronary artery bypass grafting (CABG). There are literature data concerning the patients with coronary artery disease after CABG in the presence of evolving atherosclerosis. Development of inflammation and dysadaptation of innate immunity was established in this work. An imbalance in the cytokine system contributes to the progression of endothelial dysfunction and may promote development of renal injury after CABG. Hypercytokinemia in AKI patients suggests involvement of innate immunity factors in the development of acute inflammatory response. The purpose of this article was to assess the innate immune response in the patients subjected to CABG with different duration of extracorporeal circulation. In the present study, 100 patients underwent CABG, all of whom were in the on-pump group. General clinical, functional, biochemical, instrumental, immunological and statistical methods were used in the work. After analyzing the data on the content of pro- and anti-inflammatory cytokines in blood serum of the patients with stage 1 and 2 AKI (KDIGO), depending on the duration of cardiopulmonary bypass surgery, we found that their dynamics corresponded to the standard pattern of changes after CABG groups and hyperproduction of pro- and anti-inflammatory cytokines in the groups with higher duration of cardiopulmonary bypass. The pathogenetic role of pro- and anti-inflammatory mediators remains unclear. We support the view that the clinical prognosis after cardiopulmonary bypass depends on the balance of pro- and anti-inflammatory cytokines.
21世纪,由于预期寿命延长,慢性病的发病率有所增加。心血管疾病是世界上最常见的疾病,发病率和死亡率都很高。随着这种疾病的患病率增加,心脏手术已成为对药物和其他治疗方法无效的患者的基本策略。心脏手术的一些潜在并发症在术后影响肾脏、肺和脑。急性肾损伤(AKI)被认为是心脏手术的严重并发症,其特点是肾功能迅速丧失,导致血清肌酐浓度急性升高。心脏手术后AKI发生率高达30%,孤立冠状动脉旁路移植术(CABG)患者AKI发生率为2%。有文献资料显示,冠状动脉搭桥术后并发冠状动脉粥样硬化的患者。在这项工作中,炎症和先天免疫失调的发展得到了证实。细胞因子系统失衡有助于内皮功能障碍的进展,并可能促进CABG后肾损伤的发展。AKI患者的高细胞素血症提示先天免疫因子参与急性炎症反应的发展。本文旨在探讨不同体外循环时间冠脉搭桥患者的先天免疫反应。在本研究中,100例患者接受了冠脉搭桥,所有患者均为非泵组。在工作中使用了一般的临床、功能、生化、仪器、免疫学和统计学方法。通过分析1期和2期AKI (KDIGO)患者血清中促炎因子和抗炎因子含量随体外循环手术时间的变化,我们发现其动态符合CABG组后的标准变化模式,以及体外循环时间较长的组促炎因子和抗炎因子的过量产生。促炎和抗炎介质的发病作用尚不清楚。我们支持体外循环术后临床预后取决于促炎性和抗炎性细胞因子平衡的观点。
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引用次数: 0
Modulating effects of hexapeptide on the altered phenotype of neutrophil granulocyte CD16+CD62L+CD11b+CD63- and CD16+CD62L+CD11b+CD63+ subsets in children with acute osteomyelitis in the in vitro system 六肽对体外系统急性骨髓炎患儿中性粒细胞CD16+CD62L+CD11b+CD63-和CD16+CD62L+CD11b+CD63+亚群表型改变的调节作用
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1206-meo
G. Chudilova, Yu. V. Teterin, V. N. Chapurina, E. A. Chicherev, V. Tarakanov, I. Nesterova
The problem of acute osteomyelitis in children is of special importance among the inflammatory diseases of musculoskeletal system, due to infectious conditions arising in the body and spreading to the bone tissue caused by impaired immune regulation, first of all, concerning neutrophilic granulocytes. Of interest is studying the subsets of neutrophilic granulocytes arising when the cells are involved into the inflammatory process in acute pediatric osteomyelitis, and determining the opportinity to influence the level of receptor expression aiming for correction of their functions. The purpose of our study was to evaluate the effect of hexapeptide arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine on the altered phenotype of neutrophilic granulocytes in children with acute osteomyelitis using an in vitro experimental model. We examined the peripheral blood samples from children with acute hematogenous or post-traumatic osteomyelitis at the age of 10 to 17 years (n = 12) upon their admission to the hospital, and from healthy children (n = 7). Blood samples from children with acute osteomyelitis were incubated with hexapeptide (10-6 g/L) for 60 min, at 37 C. The content of neutrophilic granulocyte subsets (CD16+CD62L+CD11b+CD63- and CD16+CD62L+CD11b+CD63+), expression density of appropriate membrane receptors were assessed by flow cytometric technique (FC 500 Beckman Coulter, USA). Phagocytic function was studied by assessing the degree of completed phagocytosis of S. aureus. It was found that, in acute osteomyelitis, a 8.5-fold increased proportion of activated CD16+CD62L+CD11b+CD63+NG subset with the CD16brightCD62LbrightCD11bbrightCD63dimNG phenotype was revealed, along with a decrease in the CD16+CD62L+CD11b+CD63-NG subset and changes in the CD16dimCD62LbrightCD11bmidCD63- NG phenotype as compared with reference indexes of healthy children. At the same time, an increased number of actively phagocytic cells was noted, however, with decreased indexes characterizing capture and digestion of the bacterial antigen. In the in vitro experiments, the tested hexapeptide was shown to modulate the phenotypes of both studied subsets (CD16brightCD62LmidCD11bmidCD63- and CD16midCD62LmidCD11bmidCD63dimNG), thus promoting restoration of the receptor expression levels to the reference group values, as well as phagocytic activity, in terms of uptake and digestive capacity of microbial cells. Thus, the dominance of a diagnostically significant activated CD16+CD62L+CD11b+CD63+ neutrophil subset with the CD16brightCD62LbrightCD11bbrightCD63dimNG phenotype was found in acute osteomyelitis in children. The results of in vitro studies have shown that the hexapeptide caused phenotypic modulation of the CD16+CD62L+CD11b+CD63- neutrophils, and CD16+CD62L+CD11b+CD63+NG subsets, along with recovery of their phagocytic activity. In the future, our results may provide a basis for the development of new effective therapeutic regimens.
儿童急性骨髓炎问题在肌肉骨骼系统炎症性疾病中具有特别重要的意义,这是由于免疫调节受损引起的感染性疾病在体内产生并扩散到骨组织,首先是与中性粒细胞有关。我们感兴趣的是研究急性小儿骨髓炎炎症过程中产生的中性粒细胞亚群,并确定影响受体表达水平以纠正其功能的机会。我们的研究目的是通过体外实验模型来评估精氨酸- α -天冬氨酸-赖氨酸-缬氨酸-酪氨酸-精氨酸对急性骨髓炎儿童中性粒细胞表型改变的影响。我们检测了入院时10- 17岁急性血液性或创伤后骨髓炎患儿(n = 12)和健康儿童(n = 7)的外周血样本。急性骨髓炎患儿的血液样本用六肽(10-6 g/L)在37℃下孵育60分钟。流式细胞术检测合适膜受体的表达密度(FC 500 Beckman Coulter, USA)。通过评估金黄色葡萄球菌的吞噬完成程度来研究其吞噬功能。结果发现,在急性骨髓炎中,活化的CD16+CD62L+CD11b+CD63+NG亚群与cd16brightcd62lbrightcd11bbrightcd63diming表型的比例增加了8.5倍,同时CD16+CD62L+CD11b+CD63-NG亚群减少,CD16dimCD62LbrightCD11bmidCD63- NG表型与健康儿童的参考指标相比发生了变化。与此同时,活跃吞噬细胞数量增加,但表征捕获和消化细菌抗原的指标下降。在体外实验中,所测试的六肽被证明可以调节所研究的两个亚群(CD16brightCD62LmidCD11bmidCD63-和cd16midcd62lmidcd11bmidcd63diming)的表型,从而促进受体表达水平恢复到参照组值,以及在微生物细胞的摄取和消化能力方面的吞噬活性。因此,在儿童急性骨髓炎中发现具有诊断意义的活化CD16+CD62L+CD11b+CD63+中性粒细胞亚群与cd16brightcd62lbrightcd11bbrightcd63dimding表型的优势。体外研究结果表明,六肽引起CD16+CD62L+CD11b+CD63-中性粒细胞和CD16+CD62L+CD11b+CD63+NG亚群的表型调节,并恢复其吞噬活性。在未来,我们的结果可能为开发新的有效治疗方案提供基础。
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引用次数: 0
Gastrointestinal manifestations of allergy in the presence of Helicobacter pylori infection 幽门螺杆菌感染后胃肠道过敏的表现
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1201-gmo
A. A. Barilo, S. V. Smirnova, Albina A. Feizer
Association of Helicobacter pylori infection with gastrointestinal tract disorders is one of the most common problems in the modern medicine. There are conflicting data in the literature on the role of H. pylori infection in development of allergic diseases and its effect on the course of gastrointestinal disorders in allergic conditions. There is currently no conclusive evidence about the role of H. pylori in etiology and pathogenesis of allergic states. Hence, the studies of gastrointestinal disorders in allergic conditions in the presence of H. pylori infection are of sufficient relevance. Our aim was to study the features of sensitization spectrum and clinical course of gastrointestinal manifestations in allergic disorders in the children infected with H. pylori. We have carried out a retrospective analysis of medical histories of the children with gastrointestinal manifestations of allergies (n = 29) aged from 1 to 18 years (middle age, 110.7 years), living in Eastern Siberia. The presence of H. pylori infection was determined with enzyme immunoassay technique, by measuring concentrations of total antibodies to the CagA H. pylori antigen. Depending on the carriage of H. pylori infection, 2 groups were discerned: HP-infected (n = 8), and HP-non-infected patients (n = 21). The spectrum of sensitization was determined by evaluating skin-prick tests for the non-infectious allergens. Gastrointestinal tract evaluation was based on the results of anamnesis, complaints, objective examination and data of esophagogastroduodenoscopy. It was found that, in most cases, gastrointestinal manifestations of allergy were combined with dermatorespiratory syndrome (41.3% of total group). The incidence of H. pylori infection in the patients with gastrointestinal manifestations of allergies was 27.5% of the group. Among the gastrointestinal manifestations of allergies, inflammatory diseases of the esophagus, stomach, and intestines, e.g., gastroesophageal reflux, gastritis, and duodenitis were most common. In the group of HP-infected children the incompetence of cardia was more often, being statistically significant. In the group of HP-noninfected children, esophagitis, bulbitis, erosive lesions of the stomach and duodenum were more common, however, the difference did not reach statistical significance. The spectrum of sensitization in the patients with gastrointestinal manifestations of allergies showed some features depending on the presence of HP infection. E.g., sensitization to birch and meadow grass mixture was found to be significantly more often in the group of HP-infected children, Among the HP-noninfected children, sensitization to house dust mite, cat wool, and dog wool was more often detected. Hence, when examining children with gastrointestinal manifestations of allergies it is necessary to exclude the presence of H. pylori infection, which can modify the course of a genuine allergic pathology.
幽门螺杆菌感染与胃肠道疾病的关联是现代医学中最常见的问题之一。关于幽门螺杆菌感染在过敏性疾病发展中的作用及其对过敏性疾病胃肠道疾病进程的影响,文献中存在相互矛盾的数据。目前还没有确凿的证据表明幽门螺杆菌在过敏状态的病因和发病机制中的作用。因此,在幽门螺杆菌感染存在的过敏性条件下胃肠道疾病的研究具有足够的相关性。我们的目的是研究儿童幽门螺杆菌感染过敏性疾病的致敏谱特征和胃肠道表现的临床过程。我们对生活在东西伯利亚的1 - 18岁(中年,110.7岁)有胃肠道过敏表现的儿童(n = 29)的病史进行了回顾性分析。采用酶免疫分析技术,通过测量CagA幽门螺杆菌抗原的总抗体浓度来确定幽门螺杆菌感染的存在。根据幽门螺杆菌感染的携带情况,分为两组:hp感染(n = 8)和hp未感染(n = 21)。致敏谱是通过评估非感染性过敏原的皮肤点刺试验来确定的。胃肠道评估基于记忆、主诉、客观检查结果和食管胃十二指肠镜检查资料。结果发现,胃肠道过敏表现多合并皮肤呼吸综合征(占总病例的41.3%)。有胃肠道过敏表现的患者幽门螺杆菌感染发生率为27.5%。在过敏的胃肠道表现中,以食管、胃、肠的炎症性疾病最为常见,如胃食管反流、胃炎、十二指肠炎等。hp感染组患儿心脏功能不全发生率较高,差异有统计学意义。在未感染hp的患儿中,食管炎、十二指肠炎、胃糜烂病变更为常见,但差异无统计学意义。胃肠道过敏表现的患者的致敏谱根据HP感染的存在表现出一些特征。例如,在hp感染的儿童中,桦树和草甸草混合物的致敏率明显更高,在hp未感染的儿童中,对室内尘螨、猫毛和狗毛的致敏率更高。因此,当检查有胃肠道过敏表现的儿童时,有必要排除幽门螺杆菌感染的存在,这可以改变真正的过敏病理过程。
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引用次数: 0
Changes of blood serum cytokine profile in the patients with papillomavirus infection before and after therapeutic pregravid preparation 乳头瘤病毒感染患者妊娠前治疗前后血清细胞因子谱的变化
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1161-cob
M. Chernikova, E. Markelova, T. Nevezhkina, L. S. Matyshkina, M. S. Tulupova, S. Knysh, K. Shevchenko
Human papillomavirus is one of the most common sexually transmitted viruses. The state of the immune system is fundamental to the outcome of infectious processes of viral and bacterial genesis, thus determining the quality of pre-gravidar preparation. The purpose of present study was to perform a comprehensive analysis of pro- and anti-inflammatory cytokines in papillomavirus infection and to provide immunological assessment of therapeutic efficiency in women. Materials and methods: 137 patients with papillomavirus infection were observed, at the average age of 312.5 years old. The study consisted of 2 stages: stage 1 included analysis of humoral innate immunity in women of the main group, distributed according to etiological factor, i.e., G-I was with papillomavirus infection (PVI); G-II presented with papillomavirus and herpetic infection (PVI + HVI 1/2 type); G-III included the patients with papillomavirus and Chlamydia infection (PVI + Trash.). At Stage 2, we performed immunological analysis of the therapeutic efficiency for PVI: in G-IA group with papillomavirus infection (PVI) we used Inosine pranobex (n = 11); in the IB group, Solanum tuberosum was applied (n = 10); in G-II A group with papillomavirus and herpes infection (PVI+HVI 1/2 type), we used Valacyclovir + Inosine pranobex (n = 24); in G-IIB patients Valacyclovir + Solanum tuberosum were administered (n = 23); for G-IIIA group with papillomavirus and chlamydia infection (PVI + Trash.) Doxycycline + Inosine pranobex were used (n = 20); the patients from IIIB group were treated with Doxycycline + Solanum tuberosum (n = 19). Determination of levels of IL-17A, IL-12 p70, IL-12 p40, IL- 13 in blood serum was carried out using specific reagents from RD Diagnostics Inc. (USA). Results: Before therapy, an increase in IL-17 and IL-13 (p 0.05), and a pronounced deficiency of IL-12 p40 and IL-12 p70 (p 0.001) were observed in blood serum of the patients. After the course of therapy, a decrease in IL-13 and an increase in IL-12 p40 and IL-12 p 70 were found. The IL-17 level remained without dynamic changes. The applied therapeutic approaches had a positive effect in all studied groups of patients, regardless of the drug administered.
人乳头瘤病毒是最常见的性传播病毒之一。免疫系统的状态对病毒和细菌发生的感染过程的结果至关重要,因此决定了孕前准备的质量。本研究的目的是对乳头瘤病毒感染中的促炎性和抗炎性细胞因子进行综合分析,并对妇女的治疗效果进行免疫学评估。材料与方法:观察137例乳头瘤病毒感染患者,平均年龄312.5岁。研究分为2个阶段:第一阶段为主要组女性体液先天免疫分析,根据病因分布,即G-I合并乳头瘤病毒感染(PVI);G-II表现为乳头瘤病毒和疱疹感染(PVI + HVI 1/2型);G-III组包括乳头瘤病毒和衣原体感染患者(PVI + Trash)。在第2阶段,我们对PVI的治疗效果进行了免疫学分析:在G-IA组合并乳头瘤病毒感染(PVI)中,我们使用肌苷pranobex (n = 11);IB组应用龙葵(n = 10);合并乳头瘤病毒和疱疹感染的G-II - A组(PVI+HVI 1/2型),我们使用伐昔洛韦+肌苷pranobex (n = 24);G-IIB患者给予Valacyclovir +龙葵(n = 23);G-IIIA组乳头瘤病毒和衣原体感染(PVI + Trash)。多西环素+肌苷pranobx (n = 20);IIIB组患者给予强力霉素+龙葵治疗(n = 19)。血清中IL- 17a、IL- 12p70、IL- 12p40、IL- 13的检测采用美国RD诊断公司的特异性试剂。结果:治疗前患者血清IL-17、IL-13水平升高(p < 0.05), il - 12p40、il - 12p70水平明显降低(p < 0.001)。治疗结束后,发现IL-13降低,il - 12p40和il - 12p70升高。IL-17水平无动态变化。无论使用何种药物,应用治疗方法对所有研究组的患者都有积极作用。
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引用次数: 0
Increase of blood neuregulin 4 is associated with type 2 diabetes mellitus and hypertension in obese patients 肥胖患者血神经调节蛋白4升高与2型糖尿病和高血压有关
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1207-iob
M. Vulf, L. A. Safiullina, N. Gazatova, G. L. Kuznetsov, A. Komar, E. Kirienkova, L. Litvinova
Obesity and type 2 diabetes mellitus (T2DM) are global epidemics at the present time, being a serious public health issue. An increased prevalence in the number of obese people promotes a risk for developing cardiovascular diseases (CVD) and some types of cancer. The ErbB signaling pathway plays a significant role in development of the disorders associated with metabolic dysfunction (e.g., T2DM, obesity, arterial hypertension). Neuregulin 4 (NRG4) is a new adipokine with similar effects to adiponectin. Interaction between the ErbB3, ErbB4 receptors and their ligand, NRG4, launches the processes required to maintain the energy balance in the cells. There are controversial literature data on NRG4 levels in blood circulation. In particular, the existing data concerning functions / mechanism of NRG4 action has been obtained in experimental animals and cell lines, which is not always reproducible in humans. According to some works, liver may be the key target organ for NRG4. The present article is devoted to assessment of relationships between the NRG4 level in blood, and the parameters of carbohydrate and lipid metabolism, as well as presence of diseases associated with obesity. The study included obese patients with and without type 2 diabetes. The content of NRG4, indices of carbohydrate and lipid metabolism in the blood was assessed by means of enzyme immunoassay and biochemical techniques, respectively. It was found that the level of NRG4 was increased in obese patients with T2DM compared with healthy donors, and obese patients without T2DM. Statistical evaluation by correlation and regression analysis revealed numerous relationships between NRG4 and the parameters of lipid and carbohydrate metabolism, as well as some correlations between the NRG4 levels and clinical disorders associated with obesity (type 2 diabetes and arterial hypertension). Thus, NRG4 may be involved into the development of dyslipidemia in obese patients. We consider an increase of blood NRG4 levels in obese patients with type 2 diabetes as a compensatory response to the increased insulin-mediated lipogenesis. The data obtained are important in search for new points of influence upon pathogenesis of diseases associated with metabolic disorders. Neuroregulin 4 and its receptors may be promising targets for the treatment of socially significant clinical disorders.
肥胖和2型糖尿病(T2DM)是目前全球流行病,是一个严重的公共卫生问题。肥胖人数的增加增加了患心血管疾病(CVD)和某些类型癌症的风险。ErbB信号通路在与代谢功能障碍相关的疾病(如T2DM、肥胖、动脉高血压)的发展中起着重要作用。神经调节蛋白4 (neuroregulin 4, NRG4)是一种与脂联素作用相似的新型脂肪因子。ErbB3、ErbB4受体及其配体NRG4之间的相互作用启动了维持细胞内能量平衡所需的过程。关于NRG4在血液循环中的水平,文献数据存在争议。特别是,NRG4作用的功能/机制的现有数据已经在实验动物和细胞系中获得,在人类中并不总是可重复的。根据一些研究,肝脏可能是NRG4的主要靶器官。本文致力于评估血液中NRG4水平与碳水化合物和脂质代谢参数之间的关系,以及肥胖相关疾病的存在。该研究包括患有和不患有2型糖尿病的肥胖患者。采用酶免疫法和生化法分别测定大鼠血液中NRG4含量、碳水化合物和脂质代谢指标。研究发现,与健康供体和非T2DM肥胖患者相比,肥胖T2DM患者NRG4水平升高。通过相关分析和回归分析进行统计评价,发现NRG4与脂质和碳水化合物代谢参数存在诸多关系,NRG4水平与肥胖相关的临床疾病(2型糖尿病和动脉高血压)存在一定的相关性。因此,NRG4可能参与了肥胖患者血脂异常的发生。我们认为肥胖2型糖尿病患者血液中NRG4水平的升高是对胰岛素介导的脂肪生成增加的代偿反应。所获得的数据对于寻找与代谢紊乱相关的疾病发病机制的新影响点具有重要意义。神经调节蛋白4及其受体可能是治疗具有社会意义的临床疾病的有希望的靶点。
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引用次数: 0
Features of humoral immunity in patients with mild traumatic brain injury 轻度外伤性脑损伤患者体液免疫的特点
Pub Date : 2022-10-07 DOI: 10.46235/1028-7221-1182-foh
A. O. Norka, S. Vorobyev, R. Kuznetsova, M. Serebriakova, I. Kudryavtsev, S. N. Kovalenko, D. N. Monashenko, Z. Korobova
Traumatic brain injury (TBI) is an important problem of the healthcare system. A lPeading role in pathogenesis belongs to the action of shock wave upon skull and brain integuments, extending from the impacted site, as well as displacement and rotation of the cerebral hemispheres relative to the fixed brain stem. As a result, a cascade of metabolic, biochemical and inflammatory changes is initiated, leading to secondary damage. TBI, depending on its mechanism, severity and type, causes various primary structural and functional brain lesions at molecular, cellular, tissue and organ levels with dysregulation of all systems in the body, dependent on its degree and extent. In most cases, the brain injury increases the risk of developing epilepsy and neurodegenerative diseases such as Alzheimers disease, arkinsons disease and chronic traumatic encephalopathy (CTE), with mental health disorders. TBI is a long-term symptomatic process in patients with functional and structural damage. In response to a traumatic event, the damage-associated molecular patterns (DAMPs) encountered upon tissue damage are expressed, which cause activation of the resident brain tissue cells, and secretion of multiple chemokine and cytokine by distinct cell populations. Neutrophils migrate to focal lesions, which remove damaged cells and debris. Migration of T and B cells is observed 3-7 days after the trauma. Hence, following primary injury, due to a cascade of immune reactions, a more extensive lesion, the so-called secondary trauma, is developed. The aim of our study was to evaluate the role of immune response in pathogenesis of mild traumatic brain injury. An increased number of Bm2 cells, IgDdimCD27low naive B cells and B cells with the IgDlowCD27hi (plasmablasts) phenotype was found in patients with mild brain contusion, compared to comparison group. Moreover, the number of naive mature B cells with the CD27lowCD38dim phenotype was significantly decreased compared with the controls.
创伤性脑损伤(TBI)是医疗卫生系统的一个重要问题。在发病机制中起主导作用的是冲击波对颅骨和脑膜的作用,冲击波从撞击部位向外延伸,以及大脑半球相对于固定脑干的移位和旋转。因此,一系列代谢、生化和炎症变化被启动,导致继发性损伤。TBI根据其机制、严重程度和类型,在分子、细胞、组织和器官水平上引起各种原发性结构和功能性脑损伤,并根据其程度和程度导致体内所有系统失调。在大多数情况下,脑损伤会增加患癫痫和神经退行性疾病的风险,如阿尔茨海默病、阿金森氏病和慢性创伤性脑病(CTE),并伴有精神健康障碍。TBI是功能和结构损伤患者的一个长期症状过程。在对创伤事件的反应中,组织损伤时遇到的损伤相关分子模式(DAMPs)被表达,这导致常驻脑组织细胞的激活,并由不同的细胞群分泌多种趋化因子和细胞因子。中性粒细胞迁移到局灶性病变,清除受损细胞和碎片。外伤后3-7天观察T细胞和B细胞的迁移。因此,在原发性损伤之后,由于免疫反应的级联反应,更广泛的病变,即所谓的继发性创伤,被发展。本研究旨在探讨免疫反应在轻度外伤性脑损伤发病机制中的作用。与对照组相比,轻度脑挫伤患者的Bm2细胞、IgDdimCD27low初始B细胞和IgDlowCD27hi(浆母细胞)表型的B细胞数量增加。此外,与对照组相比,CD27lowCD38dim表型的幼稚成熟B细胞数量显著减少。
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Russian Journal of Immunology
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