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Evaluation of the long-term memory T cell in mice after immunization with a live tularemia vaccine 兔热病活疫苗免疫后小鼠长期记忆T细胞的评价
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-eot-2746
A. S. Kartseva, M. V. Silkina, G. Titareva, T. I. Kombarova, R. Mironova, V. V. Firstova
The vaccine strain F. tularensis 15 NIIEG induces long-lived cell-mediated immunity but exhibits a certain reactogenicity and genetic instability. Progress in development of a vaccine against tularemia has been limited by a lack of information regarding the mechanisms required to protect against this disease. The BALB/c mouse is the most commonly used animal to study tularemia due to its relatively low cost, well-characterized genetics, available immunological tools and mouse infection with virulent F. tularensis recapitulates human disease.CD4+ and CD8+T cells are known to be critical for the formation of protective immunity but the relative roles of memory T cell subpopulations in long lived protection against virulent strains of F. tularensis are not well established. We hypothesized that this immunity depends on central (TCM) and effector memory (TEM) T cells and their functional activity. In this study we have dissected the T cell immune response in BALB/c mice 30, 60 and 90 days after subcutaneous vaccination with 15 NIIEG.Multiparametric flow cytometry were used to characterize in vitro recall responses of splenocytes to F. tularensis antigen. TEM cells were identified as CD3+CD4+CD44+CD62L- and CD3+CD8+CD44+CD62L-, TCM cells as CD3+CD4+CD44+CD62L+ and CD3+CD8+CD44+CD62L+, respectively. The functional activity of memory T cells was assessed by the following parameters: the level of expression of the activation marker CD69 and cytokine-producing activity by staining with the intracellular cytokines IFNg and TNFa.Thus, development of a long-lived vaccine directed against F. tularensis is dependent on identifying not only the correlates of immunity present early after vaccination, but also those that persist in the host after the effector phase has ended. The maintenance of long-term protective immunity initiated by vaccination with F. tularensis strain 15 NIIEG has been shown to require the presence of antigen-specific CD4+ and CD8+ memory T cells producing IFNg and TNFa and expressing the activation marker CD69. A decrease in count and functional activity of CD8+TCM and CD8+TEM was detected in the long term after vaccination. The detected parameters of functional activity of memory T cells can be used as criteria for evaluation of protective immunity against virulent strains of F. tularensis.
土拉菌15 NIIEG疫苗株诱导细胞介导的长寿命免疫,但表现出一定的反应原性和遗传不稳定性。由于缺乏预防这种疾病所需机制的信息,兔热病疫苗的研制进展受到限制。BALB/c小鼠是研究土拉菌病最常用的动物,因为其成本相对较低,遗传学特征明确,可用的免疫工具,并且小鼠感染毒力强的土拉菌病重现人类疾病。众所周知,CD4+和CD8+T细胞对保护性免疫的形成至关重要,但记忆T细胞亚群在抵抗土拉菌毒力菌株的长期保护中的相对作用尚未得到很好的确定。我们假设这种免疫依赖于中枢(TCM)和效应记忆(TEM) T细胞及其功能活性。在这项研究中,我们解剖了皮下接种15 NIIEG后30,60和90天BALB/c小鼠的T细胞免疫反应。采用多参数流式细胞术检测兔拉菌抗原对脾细胞的体外召回反应。TEM细胞鉴定为CD3+CD4+CD44+CD62L-和CD3+CD8+CD44+CD62L-,中医细胞鉴定为CD3+CD4+CD44+CD62L+和CD3+CD8+CD44+CD62L+。通过以下参数评估记忆T细胞的功能活性:激活标志物CD69的表达水平和细胞内细胞因子IFNg和TNFa染色的细胞因子产生活性。因此,针对土拉菌病的长效疫苗的开发不仅取决于确定疫苗接种后早期存在的免疫相关因素,还取决于确定效应期结束后在宿主体内持续存在的相关因素。通过接种土拉菌菌株15 NIIEG疫苗来维持长期保护性免疫已被证明需要抗原特异性CD4+和CD8+记忆T细胞的存在,这些T细胞产生IFNg和TNFa并表达激活标记CD69。长期接种后,CD8+TCM和CD8+TEM的计数和功能活性均下降。记忆T细胞功能活性的检测参数可作为评价对土拉菌毒力菌株保护性免疫的标准。
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引用次数: 0
Immunomodulatory properties of caffeine and caffeine-treated immune cells in depression-like state 咖啡因和咖啡因处理的免疫细胞在抑郁状态下的免疫调节特性
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-ipo-2666
E. V. Markova, M. Knyazheva
Depression is one of the leading global health problems worldwide. A significant increase in prevalence among the working-age population, as well as high comorbidity, partial or complete drug resistance in a third of patients determines the need to develop new approaches to the treatment of depression. Violation of mutual regulation of the main homeostatic systems plays an important role in the pathogenesis of depression. Psycho- and immunopathology are closely interrelated: pathological changes in the functioning of both systems occur simultaneously and are interdependent. This determines the prospects for the treatment of depression based on immunological approaches. Caffeine, a drug known for its psychoneuromodulatory properties, is an adenosine receptor antagonist with a pronounced dose-dependent effect. Adenosine receptors are expressed by both CNS cells and cells of the immune system, which determines its immunomodulatory properties. The similarity of both phenotypes and functions of the cellular elements of the immune and nervous systems, as well as the unidirectional effect of most psychoactive drugs on the central nervous system and the immune system, determines the interest in studying the immunomodulatory properties of caffeine for a targeted effect on the functional activity of immune cells, with a view to their subsequent use as model objects for the normalization of neuroimmune regulatory connections disturbed in a depressive state. Previously, we first demonstrated the possibility of editing depression-like behavior by immune cells precultivated with caffeine and showed the central mechanisms of this effect aimed at stimulating neuroplasticity processes and reducing neuroinflammation. The aim of this study was to evaluate the functional phenotype of immune cells in depressive-like animals after in vitro treatment of cells with caffeine, as well as the effects of transplantation of caffeine-precultured immune cells on the parameters of the functional activity of the immune system of syngeneic depressive-like recipients. As a result of the study, it was shown that low concentrations of caffeine increase the spontaneous and mitogen-induced proliferative activity of splenocytes of depression-like male mice (CBA x C57BL/6)F1 in vitro; this changes the spontaneous and mitogen-stimulated production of cytokines TNFa IL-1b, IFNg, IL-2, and IL-10 by these cells. After intravenous administration of the precultured with caffeine depression-like donor’s splenocytes to syngeneic depression-like recipients, stimulation of the humoral immune response was observed in the latter, assessed by an increase in both the relative and absolute number of antibody-forming spleen cells. Stimulation of spontaneous proliferative activity of lymphocytes in splenocyte culture was also registered. The data obtained indicate a positive effect of caffeine in vitro on the immune cell’s functional activity, as well as a positive immunomodulatory effect of the immune
抑郁症是世界范围内主要的全球性健康问题之一。工作年龄人口中患病率的显著增加,以及高合并症,三分之一的患者部分或完全耐药,决定了需要开发治疗抑郁症的新方法。主要体内平衡系统相互调节的破坏在抑郁症的发病机制中起着重要作用。心理和免疫病理是密切相关的:两个系统功能的病理变化同时发生并且相互依赖。这决定了基于免疫学方法治疗抑郁症的前景。咖啡因,一种以其精神神经调节特性而闻名的药物,是一种腺苷受体拮抗剂,具有明显的剂量依赖效应。腺苷受体在中枢神经系统细胞和免疫系统细胞中均有表达,这决定了其免疫调节特性。免疫系统和神经系统细胞成分的表型和功能的相似性,以及大多数精神活性药物对中枢神经系统和免疫系统的单向作用,决定了研究咖啡因对免疫细胞功能活性的靶向作用的免疫调节特性的兴趣。目的是为了将其作为抑郁状态下神经免疫调节连接正常化的模型对象。在此之前,我们首先展示了用咖啡因预培养的免疫细胞编辑抑郁样行为的可能性,并展示了这种作用的中心机制,旨在刺激神经可塑性过程和减少神经炎症。本研究旨在评价咖啡因体外处理抑郁样动物免疫细胞的功能表型,以及咖啡因预培养免疫细胞移植对同基因抑郁样受体免疫系统功能活性参数的影响。研究结果表明,低浓度咖啡因增加体外抑郁样雄性小鼠(CBA x C57BL/6)F1脾细胞自发和丝裂原诱导的增殖活性;这改变了这些细胞自发的和受丝裂原刺激的细胞因子TNFa、IL-1b、IFNg、IL-2和IL-10的产生。将预先培养的含有咖啡因的抑郁样供体脾细胞静脉注射给同基因抑郁样受体后,后者的体液免疫反应受到刺激,通过产生抗体的脾细胞的相对数量和绝对数量的增加来评估。脾细胞培养中淋巴细胞的自发增殖活性也得到了刺激。结果表明,咖啡因在体外对免疫细胞的功能活性有积极的影响,在体内用咖啡因预培养的免疫细胞处于抑郁状态,也有积极的免疫调节作用。
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引用次数: 0
Phenotype characteristic of colonic intraepithelial lymphocytes in patients with Crohn's disease 克罗恩病患者结肠上皮内淋巴细胞的表型特征
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-pco-2839
D. Nizheharodava, A. Shuleika, A. Starastsin, M. I. Vanslau, G. Ivanchyk, A. V. Vialichka, M. Zafranskaya
Intraepithelial lymphocytes (IEL) play a critical role in maintaining the immune balance of the gut and provide the first line of mucosal defense against luminal antigens as well as rapidly respond to epithelial injury. Recently, IEL have received a lot of attention as key mediators of aberrant immune response resulted in persistent immune activation, inflammation and altered intestinal barrier function, seen in Crohn's disease (CD). This study describes for the first time subsets of colonic IEL in CD patients as compared to healthy controls aimed at characterization of altered IEL contribution to the pathogenesis of Crohn's disease.The peripheral venous blood and colon tissues were obtained from 10 CD patients and 6 donors. IEL were isolated from the mucosa by incubation the tissue in a predigesting solution. Lymphoid cells phenotype was investigated using monoclonal antibodies and flow cytometry.The majority of colonic IEL was identified as СD3+T lymphocytes and no significant differences were found in their numbers in investigated groups. However, changes in T cell subsets composition have been shown: the ratio of СD3+СD4+IEL and СD3+СD8+IEL was 1:1 in colon of CD patients and correlated with T cells in peripheral blood (R = 0.7; p < 0.05) while donor tissues were characterized by expected СD3+СD8+T killers prevalence and the ratio reached 1:2 (p < 0.05). The increase of unconventional γδIEL (mainly due to V81+T cells) and СD161+T cells in association with TNK cells decrease were revealed in colon (p < 0.01) as well as in peripheral blood (p < 0.05) of CD patients as compared to donors. Moreover, the number of colonic γδIEL was correlated with disease location (R = -0.6; p < 0.05), and disease behavior (R = 0.7; p < 0.01) according to Montreal classification.The observed data indicates changes in colonic IEL composition in CD patients that may provide valuable insight into the contribution of T helpers, γδT cells and mucosa-associated СD161+T cells in autoimmune intestinal inflammation but need further possible mechanisms discussion.
上皮内淋巴细胞(IEL)在维持肠道免疫平衡中起着至关重要的作用,为黏膜防御腔内抗原提供了第一道防线,并对上皮损伤做出快速反应。最近,IEL作为异常免疫反应的关键介质,引起了克罗恩病(CD)中持续的免疫激活、炎症和肠道屏障功能改变,受到了广泛的关注。本研究首次描述了与健康对照相比,CD患者结肠IEL亚群,旨在表征改变的IEL对克罗恩病发病机制的贡献。取10例CD患者和6例供体外周静脉血和结肠组织。IEL通过在预消化液中培养组织从粘膜中分离出来。采用单克隆抗体和流式细胞术检测淋巴样细胞表型。大多数结肠IEL被鉴定为СD3+T淋巴细胞,在调查组中其数量无显著差异。然而,T细胞亚群组成的变化已经被证实:在CD患者的结肠中СD3+СD4+IEL和СD3+СD8+IEL的比例为1:1,并且与外周血中的T细胞相关(R = 0.7;p < 0.05),而供体组织中预期的СD3+СD8+T杀手患病率达到1:2 (p < 0.05)。CD患者结肠和外周血中非常规γδIEL(主要由V81+T细胞引起)和СD161+T细胞升高,与TNK细胞减少相关(p < 0.01)。结肠γδIEL数目与病变部位相关(R = -0.6;p < 0.05)、疾病行为(R = 0.7;p < 0.01)。观察到的数据表明,CD患者结肠IEL组成的变化可能为T辅助细胞、γδT细胞和粘膜相关СD161+T细胞在自身免疫性肠道炎症中的作用提供有价值的见解,但需要进一步探讨可能的机制。
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引用次数: 0
Cucurbituril-based Supramolecular complexes with platinum compounds influence on expression of CTLA-4 on Regulatory T cells 瓜脲基超分子复合物与铂类化合物对调节性T细胞CTLA-4表达的影响
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-cbs-2752
A. Aktanova, M. V. Bykova, O. Boeva, E. Pashkina, L. Grishina, V. Kozlov
Tumors are a leading pathology in the population. Chemotherapy cannot provide adequately and effectively to cure patients. Some medicine, such as cytostatic, are characterized by a wide range of side effects and resistance of solid tumors to chemotherapy by these medicines. In recent research, the mechanisms of action of cytotoxic agents have been described, and the most appropriate causes of resistance have been suggested. Drug delivery system based on Cucurbit[7]uril (CB[7]) was used to minimize side effects and overcome resistance. CB[7] has ability to form host-guest supramolecular complexes with oxaliplatin and carboplatin.It is important to consider the immune system maintain to a great role, and platinum compounds are able to have an immunomodulatory effect on immunocompetent cells. There is convincing evidence about the cytotoxic response against tumor cells is also associated with immunomodulating properties. A specific immune microenvironment with high frequency of suppressor cells is made by tumors. FoxP3+ regulatory T cells are recruited by the tumor, an increased number of these cells and expression levels of CTLA-4 and PD-1 on them contribute to the progression of the tumor process. These markers correlate with recurrence and poor survival of the patients. Therefore, it is necessary that antitumor therapy agents have an effect on a subpopulation of regulatory T cells and their functional activity. This study evaluated the effects of cucurbit[7] uril, platinum compounds, and supramolecular complexes on FoxP3+ regulatory T cells and the expression of immune checkpoint molecules.In this study peripheral blood cells from volunteers (n = 8, average 29.0±2.4) were used. Mononuclear cells obtained in the standard protocol were incubated for 72 h at concentrations of 0.3 and 0.1 mM for carboplatin and oxaliplatin, respectively, as well as complexes and CB[7] in equivalent dosages. Next, the samples were labeled with monoclonal antibodies to determine the phenotype and expression of immune checkpoint molecules by flow cytometry.We obtained the following results: The CB[7]-carboplatin complex in stimulated and non-stimulated cultures significantly reduced the number of FoxP3+ regulatory T cells compared to the control. At the same time, carboplatin and the CB[7]-carboplatin complex reduced the expression of CTLA-4 in an non-stimulated culture compared to CB[7].Complexes of Cucurbit[7]urils with platinum compounds are a perspective antitumor agent with immunomodulatory properties.
肿瘤是人群中的主要病理。化疗不能充分有效地治愈患者。一些药物,如细胞抑制剂,具有广泛的副作用和实体肿瘤对这些药物化疗的耐药性。在最近的研究中,已经描述了细胞毒性药物的作用机制,并提出了最合适的耐药原因。采用以Cucurbit[7]uril (CB[7])为基础的给药系统,最大限度地减少副作用,克服耐药性。CB[7]能够与奥沙利铂和卡铂形成主客体超分子复合物。重要的是考虑到免疫系统维持的巨大作用,铂类化合物能够对免疫能力细胞产生免疫调节作用。有令人信服的证据表明,针对肿瘤细胞的细胞毒性反应也与免疫调节特性有关。肿瘤形成了具有高频率抑制细胞的特异性免疫微环境。FoxP3+调节性T细胞被肿瘤募集,这些细胞数量的增加及其上CTLA-4和PD-1的表达水平有助于肿瘤过程的进展。这些标志物与复发和患者的不良生存率相关。因此,抗肿瘤药物有必要对调节性T细胞亚群及其功能活性产生影响。本研究评估了葫芦[7]、铂类化合物和超分子复合物对FoxP3+调节性T细胞和免疫检查点分子表达的影响。本研究使用志愿者外周血细胞(n = 8,平均29.0±2.4)。在标准方案中获得的单核细胞分别在0.3和0.1 mM浓度的卡铂和奥沙利铂,以及相同剂量的配合物和CB[7]中孵育72小时。接下来,用单克隆抗体标记样品,通过流式细胞术检测免疫检查点分子的表型和表达。我们得到了以下结果:与对照组相比,刺激和非刺激培养中的CB[7]-卡铂复合物显著减少了FoxP3+调节性T细胞的数量。同时,与CB相比,卡铂和CB[7]-卡铂复合物在非刺激培养中降低了CTLA-4的表达[7]。葫芦[7]与铂类化合物的配合物是一种很有前景的具有免疫调节作用的抗肿瘤药物。
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引用次数: 0
Content of mediators of innate immunity in the tears of patients with vascular and neurodegenerative manifestations of diabetic retinopathy 糖尿病视网膜病变血管和神经退行性表现患者泪液中先天免疫介质的含量
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-com-2671
M. P. Ruchkin, E. Markelova, G. A. Fedyashev
According to the results of recent studies, diabetic retinopathy can be considered not only as a vascular disease, but also as a neurodegenerative process. Study of the composition of the tear fluid is used to assess the state of local immunity in the development of eye diseases. However, studies examining the effect of tear composition in diabetic retinopathy are few. The aim of the study is to determine the levels of IL-1β, IL-10, TGF-β3, MMP-7, TIMP-2, protein S100b, BDNF and NGF in the tear fluid ofpatients with vascular and neurodegenerative manifestations of diabetic retinopathy. The study included 80 patients diagnosed with type 2 diabetes which were divided into 2 groups: the 1st group included 40 patients who had no clinical signs of diabetic retinopathy on the fundus; the 2nd group included 40 patients with initial signs of non-proliferative diabetic retinopathy. All those included in the study were examined on an optical coherent tomograph RTVue-100 (USA); the volume of focal losses of retinal ganglion cells (FLV) was determined. An increase in FLV above the normative base of the device was regarded as an OCT-sign of retinal neurodegeneration. According to the results of OCT, the participants of the first and second groups were additionally divided into 4 subgroups: 1A — patients without vascular changes in the fundus and without OCT signs of retinal neurodegeneration (n = 12); 1B — patients without vascular changes in the fundus and with the presence of OCT signs of retinal neurodegeneration (n = 28); 2A — patients with initial non-proliferative DR and without OCT signs of retinal neurodegeneration (n = 10); and 2B — patients with initial non-proliferative DR and with OCT signs of retinal neurodegeneration (n = 30). The levels of IL-1β, IL-10, TGF-β3, MMP-7, TIMP-2, protein S100 b, BDNF, and NGF in tear fluid were determined by enzyme-linked immunosorbent assay. Levels of IL-1β and IL-10 in tear fluid in all subgroups were comparable to controls throughout the study. TGF-β3 content in the tear fluid of patients in the group with initial signs of non-proliferative DR (group 2) was significantly (p = 0.001) lower compared with control and group 2. However, there was no significant difference (p > 0.05) between subgroups A and B within groups. The concentration of MMP-7 in the tear fluid in all subgroups was significantly lower than in the control (p < 0.05). However, in the subgroups with OCT signs of retinal neurodegeneration (1B and 2B), the deficiency of this metalloproteinase was more pronounced (p = 0.0001). The levels of the neuropeptides under study NGF, BDNF and S100 B in tear fluid did not differ from controls in all subgroups.
根据最近的研究结果,糖尿病视网膜病变不仅可以被认为是一种血管疾病,而且可以被认为是一种神经退行性过程。泪液成分的研究可用于评估眼部疾病发展过程中的局部免疫状态。然而,关于泪液成分在糖尿病视网膜病变中的作用的研究很少。本研究的目的是测定糖尿病视网膜病变血管和神经退行性表现患者泪液中IL-1β、IL-10、TGF-β3、MMP-7、TIMP-2、蛋白S100b、BDNF和NGF的水平。本研究纳入80例诊断为2型糖尿病的患者,将其分为两组:第一组40例无糖尿病眼底视网膜病变临床体征的患者;第二组包括40例初始症状为非增殖性糖尿病视网膜病变的患者。所有纳入研究的患者均在RTVue-100(美国)光学相干层析成像仪上进行检查;测定视网膜神经节细胞(FLV)的局灶性损失体积。FLV高于设备的标准基线被认为是视网膜神经变性的oct征象。根据OCT结果,将第一组和第二组的参与者再分为4个亚组:1A -眼底无血管改变且无OCT视网膜神经退行性变征象的患者(n = 12);1B -眼底无血管改变且存在视网膜神经退行性变OCT征象的患者(n = 28);2A -初始非增殖性DR且无OCT视网膜神经变性征象的患者(n = 10);2B -首发非增殖性DR且有OCT视网膜神经退行性变征象的患者(n = 30)。采用酶联免疫吸附法检测泪液中IL-1β、IL-10、TGF-β3、MMP-7、TIMP-2、蛋白s100b、BDNF、NGF水平。在整个研究过程中,所有亚组泪液中IL-1β和IL-10的水平与对照组相当。非增殖性DR初始症状组(2组)患者泪液中TGF-β3含量显著低于对照组和2组(p = 0.001)。但组内A、B亚组间差异无统计学意义(p > 0.05)。各亚组泪液中MMP-7浓度均显著低于对照组(p < 0.05)。然而,在有视网膜神经退行性变OCT体征的亚组(1B和2B)中,这种金属蛋白酶的缺乏更为明显(p = 0.0001)。在所有亚组中,泪液中所研究的神经肽NGF、BDNF和s100b的水平与对照组没有差异。
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引用次数: 0
Laboratory biomarker galectin-3 in the diagnostics of myocardial inflammatory changes in patients with atrial fibrillation 实验室生物标志物半凝集素-3在房颤患者心肌炎症变化诊断中的价值
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-lbg-2743
A. Gusakova, Y. Rogovskaya, E. A. Archakov
Atrial fibrillation (AF) is one of the most common cardiac arrhythmias. Numerous data indicate a significant contribution of myocardial inflammatory changes in the development and progression of AF. The search for new laboratory biomarkers to assess the activity of myocardial inflammatory processes, and the study of their diagnostic significance for noninvasive diagnosis in patients with AF is relevant. Therefore, the aim was to study the features of the serum level of the biomarker Gal-3 and to identify its relationship with inflammatory changes in the myocardium in patients with AF. Depending on the results of histological studies, the patients were divided into 2 groups: group 1 – with morphologically verified active lymphocytic myocarditis (ALM), group 2 – with lymphocytic infiltration (LI). Analysis of the frequency of detection and severity of the inflammatory process in the myocardium showed that activity of 4-5 scores was detected only in group 1. In 2nd group, activity of the inflammatory process in most patients was 1 score. All patients with LI mild interstitial inflammation were showed. In the ALM group moderate and severe interstitial inflammation was detected. A high number of CD3+ and CD45+ cells were found in 1st group compared to group 2 (p < 0.001).There were no significant intergroup differences in the serum level of Gal-3. At the same time, in 1st group showed a significant decrease in Gal-3 in 6 months after treatment (p = 0.028). Positive correlations of Gal-3 with the severity of the inflammatory process and endocardial involvement were revealed in patients with ALM. The association of serum Gal-3 levels with CD68+ levels in 1st group was detected (R = 0.48, p = 0.030). In 2nd group, a correlation between the level of Gal-3 in 6 months after ablation with infiltration of CD45+ cells was found (R = 0.69, p = 0.003). Thus, in patients with AF and active lymphocytic myocarditis, significant associations were established between biomarkers of Gal-3 and inflammatory changes in the myocardium. This confirms the important role of Gal-3 as a participant in the inflammatory process.
心房颤动(AF)是最常见的心律失常之一。大量数据表明,心肌炎症变化在房颤的发生和发展中起着重要作用。寻找新的实验室生物标志物来评估心肌炎症过程的活性,并研究它们对房颤患者无创诊断的诊断意义是相关的。因此,我们的目的是研究生物标志物Gal-3的血清水平特征,并确定其与AF患者心肌炎症变化的关系。根据组织学研究结果,将患者分为2组:1组-形态学证实的活动性淋巴细胞性心肌炎(ALM), 2组-淋巴细胞浸润(LI)。分析心肌炎症过程的检测频率和严重程度,发现只有1组检测到4-5分的活性。第二组多数患者炎症过程活动性为1分。所有LI患者均出现轻度间质性炎症。ALM组有中重度间质性炎症。1组CD3+和CD45+细胞数量明显高于2组(p < 0.001)。血清Gal-3水平组间差异无统计学意义。同时,第1组患者治疗后6个月Gal-3明显降低(p = 0.028)。在ALM患者中,Gal-3与炎症过程的严重程度和心内膜受累呈正相关。第1组血清Gal-3水平与CD68+水平的相关性(R = 0.48, p = 0.030)。第二组消融后6个月Gal-3水平与CD45+细胞浸润相关(R = 0.69, p = 0.003)。因此,在房颤和活动性淋巴细胞性心肌炎患者中,Gal-3的生物标志物与心肌炎症变化之间存在显著关联。这证实了Gal-3在炎症过程中的重要作用。
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引用次数: 0
Identification of the relationship between biomarkers of autophagy, apoptosis and inflammation in the acute period of atherothrombotic ischemic stroke 动脉粥样硬化性血栓性缺血性脑卒中急性期自噬、细胞凋亡与炎症生物标志物关系的研究
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-iot-2832
A. Lugovaya, N. Kalinina, A. M. Ivanov, Y. Nikitin, I. A. Sukhina, V. F. Mitreikin, E. Semenova
The postischemic inflammatory response plays a significant role in the pathogenesis of acute ischemic stroke (IS). It has been established that acute IS is accompanied by aseptic inflammation, which induces the activation of costimulatory molecules in the process of innate immunity response to brain tissue damage. The constantly progressive destruction of neuronal antigens contributes to an increase in the volume of the ischemic lesion. Evidence continues to accumulate indicating an important role of NLRP3-mediated inflammation in the pathogenesis of IS. It has been shown that autophagy is involved in the inflammatory cascade in acute IS. Many of the anti-inflammatory mechanisms mediated by autophagy in acute IS involve the key autophagic proteins Beclin-1, LC3, and p62. Experimental studies have shown that autophagy suppresses the activation of NLRP3 inflammation. Data on cross interactions between apoptosis and autophagy in the pathogenesis of IS are still controversial. The aim of the study was to evaluate the relationship between biomarkers of autophagy, inflammation, and apoptosis in the dynamics of the acute period of atherothrombotic IS. The article presents the results of a dynamic study of the serum concentration of the key autophagy biomarkers Beclin-1, LC3 and p62, apoptosis indicators Bcl-2 and p53, pro-inflammatory cytokines IL-1β, TNFα, IL-8, IL-18 which are involved in postischemic neuroinflammation. A statistically significant increase in the studied parameters was established in comparison with the control group. The maximum increase in the studied biomarkers is noted on the 1st day after the development of ischemia in patients with a severe course of the disease. The relationship between autophagy activity, apoptosis biomarkers, and some indicators of the systemic inflammatory response in patients with moderate and severe atherothrombotic stroke was revealed. The results obtained confirm the literature data on the involvement of autophagy in the regulation of the postischemic inflammatory response.
缺血后炎症反应在急性缺血性脑卒中(IS)的发病机制中起着重要作用。已证实急性IS伴无菌性炎症,无菌性炎症在脑组织损伤的先天免疫应答过程中诱导共刺激分子的激活。不断进行性破坏神经元抗原有助于增加体积的缺血性病变。越来越多的证据表明nlrp3介导的炎症在IS的发病机制中起着重要作用。研究表明,自噬参与了急性is的炎症级联反应。急性IS自噬介导的许多抗炎机制涉及关键的自噬蛋白Beclin-1、LC3和p62。实验研究表明,自噬抑制NLRP3炎症的激活。关于细胞凋亡和自噬在IS发病机制中的交叉相互作用的数据仍然存在争议。该研究的目的是评估自噬、炎症和凋亡的生物标志物在动脉粥样硬化性IS急性期动力学中的关系。本文介绍了参与缺血后神经炎症的关键自噬生物标志物Beclin-1、LC3和p62、凋亡指标Bcl-2和p53、促炎因子IL-1β、TNFα、IL-8、IL-18的血清浓度动态研究结果。与对照组相比,研究参数有统计学意义的增加。在病程严重的患者出现缺血后第1天,所研究的生物标志物的最大增加。揭示了中重度动脉粥样硬化性卒中患者自噬活性、细胞凋亡生物标志物与一些全身炎症反应指标之间的关系。本研究结果证实了自噬参与缺血后炎症反应调控的文献数据。
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引用次数: 0
Association of myeloid-derived suppressor cells with hematopoietic recovery after high-dose chemotherapy in multiple myeloma 髓源性抑制细胞与多发性骨髓瘤大剂量化疗后造血恢复的关系
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-aom-2700
V. S. Anmut, T. Tyrinova, E. Batorov, T. Aristova, S. Sizikova, G. Ushakova, V. Denisova, E. Chernykh
Myeloid-derived suppressor cells (MDSCs) play an important role in the immune response regulation in many pathologies, primarily in malignant tumors, but their role in the hematopoietic stem cell engraftment and the hematopoietic recovery after high-dose chemotherapy and autologous stem cell transplantation remains practically unexplored. This study is aimed at studying the correlation between the number of MDSC subpopulations and blood parameters at the stage of hematopoietic recovery after high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with multiple myeloma (MM). Circulating MDSCs were assessed at the stage of leukopenia recovery (absolute leukocyte count in peripheral blood (PB) > 1 x 109/L) by flow cytometry. The number of transplanted CD34+CD45+ hematopoietic stem cells was 4.38 x 106/kg (IQR (3.1—5.6) x 106/kg). The duration of recovery from leukopenia varied from 8 to 18 days (Me 12 days). The number of MDSCs at the engraftment was not associated with the number of CD34+ cells/kg in the graft. The relative number of monocytic MDSCs (M-MDSCs, CD14+HLA-DRlow/-) directly correlated with the number of monocytes at the stage of recovery from leukopenia (R = 0.417, p = 0.002). Granulocytic MDSCs (PMN-MDSCs, Lin-HLA-DR-CD33+CD66b+) were characterized by an inverse correlation with the number of monocytes (R = -0.493, p = 0.0003) while the association with the absolute number of neutrophils was weak (R = 0.273, p = 0.048). The number of lymphocytes at the stage of recovery from leukopenia had an inverse correlation with PMN-MDSCs (R = -0.347, p = 0.014) and did not correlate with M-MDSCs. When analyzing the duration of leukopenia, an inverse correlation with this indicator was revealed for the percentage and absolute number of M-MDSCs (R = -0.347, p = 0.018 and R = -0.469, p = 0.0008, respectively). Multiple regression analysis showed dependence of the lymphopenia duration on the proportion of circulating M-MDSCs (p = 0.014) and the number of transplanted CD34+ cells/kg (p = 0.032). According to the data of multivariate analysis of variance, the number of transplanted CD34+ cells/kg and the number of M-MDSCs were significant factors for the duration of leukopenia. At the same time, such clinical parameters as the depth of response and minimal residual disease status before high-dose chemotherapy and hematopoietic stem cell transplantation, as well as the MM stage, did not affect the duration of hematopoietic recovery. Thus, the obtained results indicate the association of a higher number of M-MDSCs with a shorter duration of leukopenia after high-dose chemotherapy with autologous stem cell transplantation and indicate a positive role of M-MDSCs in hematopoietic recovery in the early post-transplant period in patients with MM.
髓源性抑制细胞(Myeloid-derived suppressor cells, MDSCs)在多种病理(主要是恶性肿瘤)的免疫应答调节中发挥重要作用,但其在造血干细胞植入以及大剂量化疗和自体干细胞移植后的造血恢复中的作用实际上尚未被探索。本研究旨在研究多发性骨髓瘤(multiple myeloma, MM)患者在大剂量化疗和自体造血干细胞移植后造血恢复阶段MDSC亚群数量与血液参数的相关性。流式细胞术评估循环MDSCs在白细胞减少恢复阶段(外周血白细胞绝对计数(PB) > 1 × 109/L)。移植CD34+CD45+造血干细胞数量为4.38 × 106/kg (IQR (3.1-5.6) × 106/kg)。白细胞减少的恢复时间从8天到18天不等(Me 12天)。移植物中MDSCs的数量与移植物中CD34+细胞/kg的数量无关。单核细胞MDSCs (M-MDSCs、CD14+HLA-DRlow/-)的相对数量与白细胞减少恢复期单核细胞数量直接相关(R = 0.417, p = 0.002)。粒细胞MDSCs (PMN-MDSCs, Lin-HLA-DR-CD33+CD66b+)与单核细胞数量呈负相关(R = -0.493, p = 0.0003),与中性粒细胞绝对数量的相关性较弱(R = 0.273, p = 0.048)。白细胞减少恢复期淋巴细胞数量与PMN-MDSCs呈负相关(R = -0.347, p = 0.014),与M-MDSCs无相关性。在分析白细胞减少持续时间时,M-MDSCs的百分比和绝对数量与该指标呈负相关(R = -0.347, p = 0.018和R = -0.469, p = 0.0008)。多元回归分析显示,淋巴细胞减少持续时间与循环M-MDSCs比例(p = 0.014)和移植CD34+细胞/kg数量(p = 0.032)有关。多变量方差分析数据显示,移植CD34+细胞/kg数量和M-MDSCs数量是影响白细胞减少持续时间的显著因素。同时,大剂量化疗及造血干细胞移植前的应答深度、最小残留病状态等临床参数及MM分期对造血恢复时间无影响。因此,所获得的结果表明,自体干细胞移植高剂量化疗后,M-MDSCs数量的增加与白细胞减少持续时间的缩短有关,并表明M-MDSCs在移植后早期MM患者的造血功能恢复中具有积极作用。
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引用次数: 0
Eotaxin and cardio-ankle vascular index in patients with high and very high cardiovascular risk Eotaxin与心踝血管指数的关系
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-eac-2768
E. Kravchenko, T. Suslova, I. Kologrivova, O. Koshelskaya
Eotaxin is a chemokine, which is a chemoattractant mainly to eosinophils, as well as basophils and Th2 lymphocytes. According to studies, overexpression of eotaxin is found in endothelial and smooth muscle cells of blood vessels in the area of atherosclerotic plaque. In clinical medicine, cardio-ankle vascular index (CAVI) is widely used as an indicator of arteriosclerosis and a predictor of cardiovascular events. Few studies have shown the relationship of eotaxin with coronary atherosclerosis; in other studies, the relationship of eotaxin with atherosclerosis, myocardial infarction and pulse wave velocity was not revealed. The aim of the present study was to assess blood level of eotaxin and cardio-ankle vascular index and their association with major cardiovascular risk factors in patients with high and very high cardiovascular risk. We examined 65 patients with high and very high cardiovascular risk, due to documented coronary artery disease, type 2 diabetes mellitus, or combination of cardiovascular risk factors and who were undergoing generally accepted cardioactive, hypoglycemic therapy and lipid-lowering therapy. All patients were examined for the elastic properties of the vascular wall by volumetric sphygmography with assessment of CAVI. In the blood, the concentrations of eotaxin, high-sensitivity C-reactive protein, glycosylated hemoglobin and lipid spectrum indicators were determined. All examined were divided into two groups: with a normal value of CAVI (less than 8) and elevated. Patients with elevated CAVI had higher concentrations of eotaxin (p = 0.013), total cholesterol (p = 0.009), low-density lipoprotein cholesterol (p = 0.016), were older (p < 0.0001) and less likely to take statins (p = 0.002). In all those examined, correlations were found between serum eotaxin concentration and CAVI (rs = 0.34; p = 0.005), as well as age (rs = 0.32; p = 0.006). The age of the patients correlated with CAVI (rs = 0.35; p = 0.007). Thus, in our study, we for the first time showed the relationship between higher concentrations of eotaxin and an increased cardio-ankle vascular index in patients with high and very high cardiovascular risk. Cardio-ankle vascular index was associated with age, lipid metabolism and lipid-lowering therapy. The obtained results allow us to consider eotaxin as a factor associated with atherogenesis and arterial stiffness.
Eotaxin是一种趋化因子,主要对嗜酸性细胞、嗜碱性细胞和Th2淋巴细胞具有趋化作用。研究表明,在动脉粥样硬化斑块区域的血管内皮细胞和平滑肌细胞中发现了eotaxin的过度表达。在临床医学中,心踝血管指数(CAVI)作为动脉硬化的指标和心血管事件的预测指标被广泛应用。很少有研究表明eotaxin与冠状动脉粥样硬化的关系;其他研究未发现eotaxin与动脉粥样硬化、心肌梗死、脉波速度的关系。本研究的目的是评估eotaxin血药浓度和心踝血管指数,以及它们与心血管高危和极高危患者主要心血管危险因素的关系。我们检查了65例心血管疾病高风险和极高风险的患者,这些患者由于记录在案的冠状动脉疾病、2型糖尿病或心血管危险因素的组合,并且正在接受普遍接受的心脏活性、降糖和降脂治疗。所有患者均通过容量血压计检查血管壁的弹性特性并评估CAVI。测定血中eotaxin、高敏c反应蛋白、糖化血红蛋白、脂质谱指标的浓度。将所有患者分为正常(小于8)和升高两组。CAVI升高的患者eotaxin (p = 0.013)、总胆固醇(p = 0.009)、低密度脂蛋白胆固醇(p = 0.016)浓度较高,年龄较大(p < 0.0001),服用他汀类药物的可能性较小(p = 0.002)。在所有检查中,血清eotaxin浓度与CAVI之间存在相关性(rs = 0.34;P = 0.005)、年龄(rs = 0.32;P = 0.006)。患者年龄与CAVI相关(rs = 0.35;P = 0.007)。因此,在我们的研究中,我们首次证明了在心血管风险高和极高的患者中,较高浓度的eotaxin与心踝血管指数升高之间的关系。心踝血管指数与年龄、脂质代谢和降脂治疗有关。获得的结果使我们能够考虑eotaxin是与动脉粥样硬化和动脉硬化相关的因素。
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引用次数: 0
Cytokine diagnostics in the prognosis of critical conditions in newborns born to mothers infected with COVID-19 细胞因子诊断在COVID-19感染母亲所生新生儿危重病情预后中的作用
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-cdi-2762
S. I. Navruzova, др Medical, Meditsinskaya, Baratov Navruzova Sh.I.
The article is devoted to the development of a cytokine diagnostic method for predicting the development of critical conditions in newborns born to mothers with COVID-19, which is of great importance for health authorities when organizing specialized neonatology and pediatric services. Objective: to develop a method of noninvasive cytokine diagnostics for predicting the development of critical conditions in newborns born from a mother with COVID-19. The proposed method allows early diagnosis and prevention of the development of critical conditions in newborns, which is of great practical importance. The control of urine cytokines in dynamics determines the prognosis of the development of critical conditions, both in the early and late period of adaptation of newborns. As a marker of the inflammatory process and a key cytokine of bone resorption, IL-17A plays a complex role in the adaptation process of newborns born from a mother with COVID-19. Newborns born from a mother with COVID-19 have an increase in IFNγ and IFNα in the blood on the first day of life against the background of an increase in IL-17A by 1.48 times, which shows the risk of developing both infection and osteogenesis disorders. Activation of interferon status by the 7th day of life in newborns was established against the background of an increase in the key cytokine of bone resorption (IL-17A). A decrease in the urine of molecular markers of vascular endothelial damage – MSR-1 by 4.25 times was found in newborn children born from a mother infected with COVID-19. A decrease in VEGF in the urine of newborns was found, both with COVID-19 infection in the mother and in its absence. Non-invasive urine cytokine diagnostics allows achieving economic efficiency by reducing hospital beds, as well as medical efficiency due to minimal traumatization of newborns.
本文致力于开发一种细胞因子诊断方法,用于预测COVID-19母亲所生新生儿的危重病情发展,这对卫生当局在组织新生儿和儿科专业服务时具有重要意义。目的:建立一种无创细胞因子诊断方法,用于预测COVID-19母亲所生新生儿危重病情的发展。提出的方法可以早期诊断和预防新生儿危重病情的发展,这是非常重要的实际意义。尿细胞因子的动态控制决定了新生儿适应早期和晚期危重病情发展的预后。IL-17A作为炎症过程的标志物和骨吸收的关键细胞因子,在COVID-19母亲所生新生儿的适应过程中发挥着复杂的作用。患有COVID-19的母亲所生的新生儿在出生第一天血液中IFNγ和IFNα增加,背景是IL-17A增加1.48倍,这表明发生感染和成骨障碍的风险。新生儿出生第7天干扰素激活的背景是骨吸收关键细胞因子(IL-17A)的增加。在感染COVID-19的母亲所生的新生儿中,尿中血管内皮损伤分子标志物- MSR-1减少了4.25倍。在母亲感染COVID-19和未感染COVID-19的情况下,新生儿尿液中VEGF均下降。非侵入性尿液细胞因子诊断可以通过减少医院床位来实现经济效益,以及由于新生儿创伤最小而提高医疗效率。
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Medical Immunology (Russia)
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