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Local cytokine levels as prognostic factors for early relapse of non-muscle-invasive bladder carcinoma 局部细胞因子水平作为非肌肉浸润性膀胱癌早期复发的预后因素
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-lcl-2723
E. Zlatnik, A. B. Sagakyants, O. G. Shulgina, A. N. Shevchenko, E. V. Filatova, L. I. Belyakova, A. A. Breus, A. Maslov, A. Maslov, L. Rozenko
The aim of our study is to assess the local cytokine levels as prognostic factors for early relapse in NMIBC patients. 75 patients with NMIBC were enrolled in the study: 51 with primary NMIBC and 24 with initially recurrent NMIBC, LG and HG tumors were diagnosed in each group. Patients with primary NMIBC were monitored during 9 months after treatment: TURB and chemotherapy (No. 6). During TURB samples of tumors were taken, supernatants were obtained and tissue cytokine levels were measured (IL-1β, IL-6, IL-10, IL-18, TNFα, IFNγ, IL-8) by ELISA test. The results showed that in patients with primary NMIBC early relapses were diagnosed in 15 (46.8%) of LG tumors and in 11 (45%) of HG tumors matching that there was no difference depending upon tumor grade. In initially recurrent tumors of both LG and HG NMIBC the amounts of cytokines were maximal: in LG tumors they exceeded the primary ones from 7.1 (IFNγ) to 300 (IL-6) while in HG - from 2.0 (IL-10) to 9.7 (IL-6). The amounts of IL-1β, IL-6, IL-10, IFNγ, IL-8 were higher in those LG primary tumors which relapsed in 6-9 months compared to the ones which didn't, though their levels were much lower than in initially manifested relapse (from 2.6 times for IFNy to 150 times for IL-6). A similar trend, though not for all the same cytokines, was observed in HG tumors: tissue levels of IL-6, IL-10, IL-18 and TNFα were higher in tumors which relapsed in 6-9 months after treatment. The increase of 2 cytokines' levels were common for both LG and HG tumors (IL-6 and IL-10). This finding might be considered as a new prognostic factor of the early relapse. We conclude that relapse of LG and HG NMIBC is related to some immune mechanisms, namely to local hyperproduction of cytokines, especially IL-6 and IL-10, though IL-1β, IL-8, IFNγ could have an impact on LG and IL-18, TNFα — on HG tumors. Taking into account common signaling pathways of IL-6 and IL-10 like JAK/STAT, these transcription factors might be potential targets for new effective approaches to treatment.
我们研究的目的是评估局部细胞因子水平作为NMIBC患者早期复发的预后因素。75例NMIBC患者入组研究:51例为原发性NMIBC, 24例为初始复发性NMIBC,每组诊断为LG和HG肿瘤。对原发性NMIBC患者进行TURB和化疗(第6期)后9个月的监测。TURB期间取肿瘤标本,取上清液,ELISA检测组织细胞因子(IL-1β、IL-6、IL-10、IL-18、TNFα、IFNγ、IL-8)水平。结果显示,原发性NMIBC早期复发患者中,LG肿瘤有15例(46.8%),HG肿瘤有11例(45%),与肿瘤分级无差异。在早期复发的LG和HG NMIBC肿瘤中,细胞因子的含量最高:LG肿瘤的细胞因子含量高于原发肿瘤,从7.1 (IFNγ)到300 (IL-6), HG -从2.0 (IL-10)到9.7 (IL-6)。IL-1β、IL-6、IL-10、IFNγ、IL-8的水平在6-9个月复发的LG原发肿瘤中高于未复发的肿瘤,但其水平远低于最初表现复发的肿瘤(IFNy为2.6倍,IL-6为150倍)。在HG肿瘤中观察到类似的趋势,尽管不是所有的细胞因子都相同:治疗后6-9个月复发的肿瘤组织中IL-6、IL-10、IL-18和TNFα水平较高。2种细胞因子(IL-6和IL-10)在LG和HG肿瘤中均有升高。这一发现可能被认为是早期复发的一个新的预后因素。我们得出结论,LG和HG NMIBC的复发与某些免疫机制有关,即局部细胞因子的过量产生,特别是IL-6和IL-10,尽管IL-1β, IL-8, IFNγ可能对HG肿瘤的LG和IL-18, TNFα -有影响。考虑到IL-6和IL-10的常见信号通路如JAK/STAT,这些转录因子可能是新的有效治疗方法的潜在靶点。
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引用次数: 0
Role of IL-6 in the immunopathogenesis of mild, moderate and severe TBI IL-6在轻、中、重度脑外伤免疫发病机制中的作用
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-roi-2805
A. O. Norka, S. Vorobyev, R. Kuznetsova, S. Lapin, Z. Korobova, D. N. Monashenko, A. Totolian
Traumatic brain injury (TBI) results in a significant inflammatory burden that increase the production of inflammatory mediators and biomarkers. The immune system plays a key role in the pathogenesis of traumatic brain injury. Neuroinflammatory mediators released from resident glia (activated microglia and astrocytes) inside the brain recruit immune cells where cytokines are small soluble proteins that confer instructions and mediate communication among immune and non-immune cells. Interleukin-6 (IL-6) is a proinflammatory cytokine known to be elevated after trauma, and a major contributor to the inflammatory response following TBI. Previous studies have investigated associations between IL-6 and outcome following TBI, but to date, studies have been inconsistent in their conclusions. The purpose of the current study was to assessment of cerebrospinal fluid (CSF) interleukin-6 (IL-6) and MBP levels in patients with TBI. Samples of cerebrospinal fluid of 85 patients with TBI were examined. Concentrations IL-6 were measured via xMAP multiplexing technology. The control was the course of CSF in patients with concussion. An increased content was found in all patients with traumatic brain injury: 19.59 pg/mL in the group with mild traumatic brain injury; 103.6 pg/mL in the group with moderate traumatic brain injury; and 2225 pg/mL in the group with severe traumatic brain injury load versus 2.58 pg/mL in the control group. A direct correlation was found with the presence of basic myelin proteins in the cerebrospinal fluid, which indicates the degree of damage and neurodegeneration processes. Identification of the features of IL-6 content in patients with brain injury may indicate its important role in the course of disease. It also requires additional more detailed study, including comparison with IL-6 content in peripheral blood.
创伤性脑损伤(TBI)导致显著的炎症负担,增加炎症介质和生物标志物的产生。免疫系统在创伤性脑损伤的发病机制中起关键作用。脑内驻留的胶质细胞(活化的小胶质细胞和星形胶质细胞)释放的神经炎症介质招募免疫细胞,其中细胞因子是小的可溶性蛋白,可传递指令并介导免疫细胞和非免疫细胞之间的通信。白细胞介素-6 (IL-6)是一种促炎细胞因子,已知在创伤后升高,是TBI后炎症反应的主要因素。先前的研究已经调查了IL-6与TBI后预后之间的关系,但迄今为止,研究的结论并不一致。本研究的目的是评估脑外伤患者脑脊液(CSF)白介素-6 (IL-6)和MBP水平。对85例脑外伤患者的脑脊液进行了检测。通过xMAP多路复用技术检测IL-6浓度。对照组为脑震荡患者的脑脊液病程。所有颅脑外伤患者均有升高,轻度颅脑外伤组为19.59 pg/mL;中度颅脑损伤组为103.6 pg/mL;重型颅脑损伤负荷组为2225 pg/mL,对照组为2.58 pg/mL。发现与脑脊液中碱性髓磷脂蛋白的存在直接相关,这表明损伤程度和神经变性过程。对脑损伤患者IL-6含量特征的识别可能提示其在病程中的重要作用。它还需要额外的更详细的研究,包括与外周血中IL-6含量的比较。
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引用次数: 0
Morphofunctional changes of microglia in adult and old Wistar rats 成年和老年Wistar大鼠小胶质细胞形态功能的变化
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-mco-2757
A. V. Sentyabreva, E. A. Melnikova, E. A. Miroshnichenko, I. S. Tsvetkov, A. M. Kosyreva
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases leading to dementia. There is no effective treatments for this disease so far, as well as a consensus concerning the mechanisms of its pathogenesis initiation. Obtaining data on them in vivo is possible only by modeling neurodegeneration in laboratory animals. Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases leading to dementia. There is no effective treatments for this disease so far, as well as a consensus concerning the mechanisms of its pathogenesis initiation. Obtaining data on them in vivo is possible only by modeling neurodegeneration in laboratory animals. Among the various theories of the initiation of neurodegeneration, the impact of microglia is vigorously studied recently, as well as inflammaging, which is a term for chronic age-related low-grade systemic inflammation. It manifests in the increasing number of senescent cells with senescence-associated secretory phenotype (SASP). Eventually, it leads to manifestation and progression of age-related diseases, such as AD. The aim of the study was to evaluate age-related changes in microglia, pro- and anti-inflammatory cytokines expression levels in the brain, as well as ones of microglial activation, and also subpopulations of lymphocytes in peripheral blood. We used male Wistar rats of two age groups, which were composed of old (age 24 months) and adult (age 3 months) rodents, without any additional exposure. In the hippocampus, morphological changes in microglia were assessed on preparations stained with antibodies to Iba1. In the prefrontal cortex, RT-qPCR was used to study the level of expression of pro-inflammatory IL-6 and TNFa, anti-inflammatory IL-10 and TGF-b cytokines, as well as microglial activation markers iNOS and MMP-9. In the peripheral blood, the relative numbers of the main subpopulations of lymphocytes and monocyte were measured by flow cytometry. It was shown that, compared with adult rats, old animals are characterized by significant changes in the morphology of microglia, an increase in the level of expression of pro-inflammatory and a decrease in anti-inflammatory cytokines, and an increase in microglia activation markers. With aging, a decrease in the percentage of monocytes and B cells in peripheral blood was observed. These data indicate the development of inflammaging, which displays itself in microglia activation, a shift in the balance of cytokine production towards pro-inflammatory ones, and, as a result, activation of the migration of monocytes and B lymphocytes from the blood into tissues. Thus, it is justified to study the role of inflammation in the development of AD in old animals whose physiological state corresponds to that in humans. Further research in this area will expand the understanding of the mechanisms of initiation and progression of neurodegeneration, which is necessary for the development of novel and effective therapeutic approa
阿尔茨海默病(AD)是导致痴呆的最常见的神经退行性疾病之一。目前尚无有效的治疗方法,对其发病机制也没有共识。只有通过模拟实验室动物的神经变性,才能在体内获得有关它们的数据。阿尔茨海默病(AD)是导致痴呆的最常见的神经退行性疾病之一。目前尚无有效的治疗方法,对其发病机制也没有共识。只有通过模拟实验室动物的神经变性,才能在体内获得有关它们的数据。在各种关于神经退行性变起始的理论中,最近对小胶质细胞的影响以及炎症的影响进行了大力研究,炎症是一种慢性年龄相关的低度全身性炎症。它表现为衰老相关分泌表型(SASP)的衰老细胞数量增加。最终,它会导致年龄相关疾病的表现和发展,如阿尔茨海默病。该研究的目的是评估大脑中小胶质细胞、促炎性和抗炎性细胞因子表达水平的年龄相关变化,以及小胶质细胞激活水平和外周血淋巴细胞亚群的变化。我们使用两个年龄组的雄性Wistar大鼠,包括老年(24月龄)和成年(3月龄)啮齿动物,没有任何额外的暴露。在海马中,用Iba1抗体染色的制剂评估小胶质细胞的形态学变化。在前额叶皮层,RT-qPCR研究促炎IL-6和TNFa、抗炎IL-10和TGF-b细胞因子以及小胶质细胞激活标志物iNOS和MMP-9的表达水平。在外周血中,用流式细胞术测定淋巴细胞和单核细胞主要亚群的相对数量。结果表明,与成年大鼠相比,老龄大鼠小胶质细胞形态发生明显变化,促炎因子表达水平升高,抗炎因子表达水平降低,小胶质细胞激活标志物升高。随着年龄的增长,外周血单核细胞和B细胞的比例下降。这些数据表明炎症的发展,表现为小胶质细胞的激活,细胞因子生产平衡向促炎因子的转变,结果是单核细胞和B淋巴细胞从血液迁移到组织的激活。因此,在与人类生理状态相对应的老年动物中,研究炎症在AD发生中的作用是有道理的。在这一领域的进一步研究将扩大对神经退行性变的发生和发展机制的理解,这对于开发新的有效的治疗阿尔茨海默病的治疗方法是必要的。
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引用次数: 0
Peculiarities of post-viral chronic fatigue syndrome associated with mild cognitive decline in patients with atypical chronic active herpesvirus infections 非典型慢性活动性疱疹病毒感染患者与轻度认知能力下降相关的病毒后慢性疲劳综合征的特点
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-pop-2826
E. Khalturina, I. Nesterova
According to modern ideas, changes in the functioning of the immune system affect the immune processes in the nervous system, contributing to the development of neuro-immuno-inflammation and thereby indirectly affect the rate of progression of neurodegenerative processes. The aim of our study was to investigate the prevalence of post-viral chronic fatigue syndrome and cognitive impairment (aMCI) among patients with atypical, chronic active herpesvirus infections (ACA-HVI).Under our supervision were 126 patients of both sexes aged 18 to 60 years with ACA-HVI.It was established that mono-EBV infection affects 27.7%; mixed EBV infection is observed in 72.3% of patients. When assessing cognitive functioning using CGI, MMSE scales, the incidence of aMCI was found to be 68.3%: with mixed HVI — 87.4%, with mono HVI — 38.8%. During the study, significant limitations were identified in the use of standard scales due to the impossibility of conducting a comprehensive assessment of clinical status parameters and cognitive dysfunctions, as well as correlation of these parameters and assessment of dynamics of the immunocorrection. To achieve this goal the Scale of assessment of the criterion clinical symptoms of patients with ACA-HVI with CFS was used. It was shown that in mixed-HVI, the severity of symptoms exceeded the severity of symptoms of patients with mono-HVI and was 52.7 (43.1-62.2) and 38.0 (31.9-42.8) points, respectively (p > 0.05). Thus, it was found that patients suffering from mixed HVI have more pronounced, severe manifestations of CFS and aMCI, which are 1.5 times higher than similar manifestations in patients with mono-HVI, significantly reducing the quality of life of these patients, worsening their social adaptation.Prolonged persistence of herpes viruses in immune-compromised people creates conditions for constant antigenic stimulation and immune imbalance with the onset of secondary immunodeficiency or clinical manifestation of existing primary disorders in the immune system, which creates the prerequisites for the development of neuro-immuno-inflammatory changes in nervous system, followed by the formation of clinical manifestations of ME/CFS with different cognitive impairments that may be classified as aMCI.
根据现代观点,免疫系统功能的变化影响神经系统的免疫过程,促进神经免疫炎症的发展,从而间接影响神经退行性过程的进展速度。本研究的目的是调查非典型慢性活动性疱疹病毒感染(ACA-HVI)患者的病毒性后慢性疲劳综合征和认知功能障碍(aMCI)的患病率。在我们的监督下,126名年龄在18至60岁的男女ACA-HVI患者。确定单ebv感染占27.7%;72.3%的患者存在混合性EBV感染。当使用CGI、MMSE量表评估认知功能时,发现aMCI的发生率为68.3%,混合HVI为87.4%,单一HVI为38.8%。在研究过程中,由于无法对临床状态参数和认知功能障碍进行全面评估,以及这些参数与免疫矫正动力学评估的相关性,在使用标准量表时发现了显著的局限性。为达到这一目的,采用了ACA-HVI合并CFS患者标准临床症状评估量表。结果表明,混合hvi患者的症状严重程度超过单一hvi患者的症状严重程度,分别为52.7(43.1-62.2)和38.0(31.9-42.8)分(p > 0.05)。因此,我们发现混合HVI患者的CFS和aMCI表现更为明显、严重,是单一HVI患者类似表现的1.5倍,显著降低了这些患者的生活质量,使其社会适应能力恶化。疱疹病毒在免疫功能低下人群中的长期存在,为持续的抗原刺激和免疫失衡创造了条件,伴随着继发性免疫缺陷的发生或免疫系统现有原发性疾病的临床表现,这为神经系统中神经免疫炎症变化的发展创造了先决条件。随后形成ME/CFS伴不同认知障碍的临床表现,可归类为aMCI。
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引用次数: 0
Experimental application results of mesenchymal stem cell microvesicles in the mouse model of acute renal failure 间充质干细胞微泡在急性肾功能衰竭小鼠模型中的实验应用结果
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-ear-2716
I. Ivanova, G. Seledtsova, V. Seledtsov, T. Khabalova, A. B. Dorzhieva
An important role in restoration of damaged organs and tissues is played by mesenchymal stem cells (MSCs) and microvesicular particles (MV) produced by them. They can be a source of cytokines, anti- apoptotic and growth stimulating factors. In addition, MVs carry out transport of mRNA, miRNA, and signal proteins into damaged tissues. This increases the ability of cells to regenerate and to inhibit apoptosis, promote to angiogenesis and stimulate cell proliferation. The aim of our research was to study the immunoregulatory and pro-regenerative properties of mesenchymal stem cell microvesicles (MSC-MV) in a model of glycerol- induced acute renal failure (ARF) in mice. The experiments were carried out on CBA mice aged 3-4 months. AKI was induced by a single intramuscular injection of 50% glycerol. MSCs were obtained from the bone marrow of healthy animals and cultivated under standard conditions. Microvesicles were obtained by centrifugation at 12000g of MSC supernatant after induction of their apoptosis by culturing under oxygen deprivation conditions and in serum-free medium. MSC-MV was injected intravenously into the retroorbital sinus one day after induction of ARF. The MV dose was calculated as equivalent to (derived from) 1 million MSCs, which was 100 mL per mouse. Animals were taken out of the experiment on days 4 and 11 after MSC-MV injection. Blood plasma was taken to determine the level of creatinine, urine – for albumin analysis, kidneys – for histological examination. It has been shown that MVs induced by MSCs dose-dependently stimulated splenocyte proliferation in both spontaneous and Con-A induced tests. The addition of MV caused a decrease in doxorubicin-induced apoptosis of splenic lymphocytes in mice. Probably, in this case, MV produced by MSCs had an immunostimulatory and antiapoptotic effect. Also, MVs had a positive impact on the restoration of structure and function kidneys in a model of ARF in mice. The use of MSC-MV in treatment of acute renal failure induced by a single injection of 50% glycerol contributed to decrease albumin level urine and restoration of creatinine level in blood serum of animals. Morphological studies have shown decrease in the height cell and collecting duct diameter in the medulla and a decrease in the largest transverse diameter of superficial glomeruli in the renal cortex of sick mice. Thus, the obtained results indicate significant therapeutic and pro-regenerative properties of MSC-MV, which require further study.
间充质干细胞(MSCs)及其产生的微泡颗粒(MV)在受损器官和组织的修复中起着重要作用。它们可以是细胞因子、抗凋亡因子和生长刺激因子的来源。此外,mv还将mRNA、miRNA和信号蛋白转运到受损组织中。增加细胞再生能力,抑制细胞凋亡,促进血管生成,刺激细胞增殖。我们的研究目的是研究间充质干细胞微泡(MSC-MV)在甘油诱导的小鼠急性肾功能衰竭(ARF)模型中的免疫调节和促再生特性。实验以3 ~ 4月龄CBA小鼠为实验对象。单次肌内注射50%甘油诱导AKI。从健康动物骨髓中获得MSCs,并在标准条件下培养。在缺氧条件下和无血清培养基中培养诱导细胞凋亡后,在12000g间充质干细胞上清液中离心获得微囊泡。在ARF诱导1天后,将MSC-MV静脉注入眶后窦。MV剂量计算相当于(源自)100万个MSCs,即每只小鼠100 mL。小鼠于注射MSC-MV后第4天和第11天退出实验。血浆测定肌酐水平,尿液测定白蛋白分析,肾脏测定组织学检查。在自发和Con-A诱导试验中,MSCs诱导的MVs均以剂量依赖性刺激脾细胞增殖。MV的加入使阿霉素诱导的小鼠脾淋巴细胞凋亡减少。在这种情况下,MSCs产生的MV可能具有免疫刺激和抗凋亡作用。此外,在ARF小鼠模型中,mv对肾脏的结构和功能的恢复有积极的影响。用MSC-MV治疗单次注射50%甘油致急性肾功能衰竭,可降低动物尿白蛋白水平,恢复血清肌酐水平。形态学研究显示,患病小鼠肾皮质的高度细胞和集束管直径减少,浅表肾小球最大横径减小。因此,所得结果表明MSC-MV具有显著的治疗和促再生特性,有待进一步研究。
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引用次数: 0
Association of single nucleotide polymorphisms of TLR2, TLR4 and TLR9 with atopic dermatitis TLR2、TLR4和TLR9单核苷酸多态性与特应性皮炎的关系
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-aos-2807
O. A. Svitich, O. Olisova, E. Meremianina, N. D. Rasskazova, V. A. Fomina, M. Potapova
Toll-like receptors (TLRs) are the most studied among all Pattern Recognition Receptors, the main function of which is to initiate innate immune response by recognizing pathogen-associated molecular patterns of various microorganisms on the skin surface. TLR-mediated recognition plays an important role in linking innate and adaptive immunity that ultimately leads to the production of key cytokines, chemokines and antimicrobial peptides. Today, there is growing interest in research on single nucleotide polymorphisms (SNPs) in TLR genes and its influence on susceptibility to inflammatory disease, including atopic dermatitis. The aim of the research was to study the association of the rs5743708 gene polymorphism in the TLR2 gene, the rs4986791 gene polymorphism in the TLR4 gene and the rs352140 gene polymorphism in the TLR9 gene with the risk of developing severe cases of AD. A total of 100 patients with AD were included in the study (38 male and 62 female). The age range was from 18 to 65 years old. All participants were divided into 2 groups according to the SCORAD index (SCORing Atopic Dermatitis). The control group included 72 volunteers over 18 years old. The results of our study showed a statistically significant difference between the moderate AD group and healthy controls in the rs352140 gene polymorphism in the TLR9 gene (Figure 1). The frequency of the GG genotype of SNP rs352140 in TLR9 was 0.169 in the AD group versus 0.329 in the control group (p < 0.05; OR = 0.42; 95% CI = 0.18-0.97).In conclusion, the results of our study showed that the TLR9 rs352140 gene polymorphism may be linked to an increased risk of atopic dermatitis. Moreover, it was found that the GG genotype of SNP rs352140 in TLR9 can be used as a predictor of the risk of developing moderate AD.
toll样受体(Toll-like receptor, TLRs)是所有模式识别受体中研究最多的一种,其主要功能是通过识别皮肤表面各种微生物病原体相关的分子模式来启动先天免疫反应。tlr介导的识别在连接先天免疫和适应性免疫中起着重要作用,最终导致关键细胞因子、趋化因子和抗菌肽的产生。如今,人们对TLR基因的单核苷酸多态性(snp)及其对炎症性疾病(包括特应性皮炎)易感性的影响的研究越来越感兴趣。本研究旨在研究TLR2基因中rss5743708基因多态性、TLR4基因中rs4986791基因多态性、TLR9基因中rs352140基因多态性与AD重症发病风险的关系。研究共纳入100例AD患者(男性38例,女性62例)。年龄范围从18岁到65岁。根据评分特应性皮炎(SCORAD)指数将所有参与者分为2组。对照组包括72名18岁以上的志愿者。我们的研究结果显示,中度AD组与健康对照组的TLR9基因rs352140基因多态性差异有统计学意义(图1)。中度AD组TLR9中SNP rs352140的GG基因型频率为0.169,对照组为0.329 (p < 0.05;Or = 0.42;95% ci = 0.18-0.97)。总之,我们的研究结果表明,TLR9 rs352140基因多态性可能与特应性皮炎风险增加有关。此外,我们发现TLR9中SNP rs352140的GG基因型可以作为中度AD发生风险的预测因子。
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引用次数: 0
Immunological indicators of complications of surgical bowel disease in children
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-iio-2859
D. A. Musakhodjayeva, R. K. Karimov, S. Rasulova
The article is devoted to the development of immunological indicators of intestinal inflammation in children, which is of great importance for health authorities when organizing specialized pediatric and surgical services. The proposed method contributes to the early diagnosis and prevention of complications of inflammatory surgical bowel diseases in children, which is of great practical importance. The purpose of the study: To develop immunological indicators of complications of surgical bowel diseases in children. A retrospective analysis of 867 case histories of children who received inpatient treatment at the Department of Pediatric Surgery of the Bukhara branch of the Republican Scientific Center of Emergency Medical Care from 2019 to 2022 for surgical diseases of the gastrointestinal tract was carried out. The authors conducted an immunological study of 91 pediatric patients. All children underwent immunological blood tests: cellular and humoral immunity, cytokines (TNFα, IFNα, IL-8, MCP-1 and vascular endothelial growth factor VEGF-A) were studied. For the prevention of postoperative complications of CKD in children, it is recommended to determine IFNα in the blood serum in the period before surgery to solve the indications for immunocorrection. A noticeable positive relationship was established between IFNα and CD8 – r = 0.34, between IFNα and CD23 – r = 0.38, between IFNα and IgA – r = 0.39, between IFNα and PCT – r = 0.36. At the same time, PCT has a noticeable negative relationship with CD16 – r = -0.31 and with CD8 – r = -0.31 against the background of a noticeable positive relationship with IgG – r = 0.32 and IFNα – r = 0.36. It was found that IFNα is a more informative indicator of the effectiveness of the immune response, and PCT is an indicator of the effectiveness of antibacterial therapy in surgical bowel diseases in children
本文致力于儿童肠道炎症的免疫学指标的发展,这对卫生当局在组织专门的儿科和外科服务时非常重要。该方法有助于早期诊断和预防儿童炎性外科肠病的并发症,具有重要的现实意义。研究目的:探讨儿童外科肠病并发症的免疫学指标。回顾性分析2019 - 2022年在共和急救科学中心布哈拉分院儿科外科住院治疗的867例胃肠道外科疾病患儿的病史。作者对91名儿科患者进行了免疫学研究。所有儿童都进行了免疫血液检查:研究细胞和体液免疫、细胞因子(TNFα、IFNα、IL-8、MCP-1和血管内皮生长因子VEGF-A)。为预防儿童CKD术后并发症,建议术前测定血清IFNα水平,解决免疫矫正指征。IFNα与CD8 - r = 0.34,与CD23 - r = 0.38,与IgA - r = 0.39,与PCT - r = 0.36呈显著正相关。PCT与CD16 - r = -0.31、CD8 - r = -0.31呈显著负相关,与IgG - r = 0.32、ifn - r = 0.36呈显著正相关。研究发现,IFNα是免疫反应有效性的一个更有信息量的指标,而PCT是儿童外科肠病抗菌治疗有效性的一个指标
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引用次数: 0
Content of CD4+T cell subpopulations in predicting the efficacy of biological therapy for psoriasis in children CD4+T细胞亚群的含量预测儿童银屑病生物治疗的疗效
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-coc-2704
D. Kuptsova, T. Radigina, O. Kurbatova, A. I. Materikin, R. Epishev, L. A. Opryatin, A. Khotko, N. Murashkin, S. Petrichuk
Psoriasis is a chronic inflammatory skin disease characterized by increased proliferation of epidermal cells, impaired keratinization and an inflammatory reaction in dermis caused by activation of T lymphocytes and synthesis of pro-inflammatory cytokines. The pathophysiology of psoriasis is also associated with a decrease in anti-inflammatory functions of immunosuppressive cells. Recently, there are more cases of development of resistance to ongoing therapy with biologics in children, requiring cancellation of drug or its replacement. The aim of the study was to evaluate the content of T helper subpopulations in prognosis of effectiveness of biologics in children with psoriasis. Immunophenotyping of T helper populations was performed in 110 children with psoriasis vulgaris before appointment of biologics, at 16 and 52 weeks. Age of children ranged from 6 to 18 years. Severity of psoriasis and effectiveness of therapy were assessed by index PASI, which varied 0-68. Content of Tregs, Thact and Th17 was determined by flow cytometry. In group with a sufficient effect of biologics, a decrease in PASI was obtained, both at week 16 of therapy (p = 0.000) and by year of treatment, p = 0.017. In children with psoriasis, regardless of duration and effectiveness of biologics, percentage of Thact was increased relative to normal values. In group 1 before prescription of biologics was increased percentage of Thact (p = 0.005) and Th17 (p = 0.001). Analysis of dynamics of content of small populations of T helper during 1 year of use of biologics in children with different efficacy of therapy showed that significant changes were found in content of Th17 and Treg, as well as their Th17/Treg. ROC analysis showed that when Th17 deviation was above 53%, Thact above 181% and Th17/Treg above 2.6 before biologics were prescribed, insufficient efficacy of therapy could be expected in 75% of cases by year. By the end of induction course, with a Th17 deviation above 102% and a Th17/Treg above 2.6, probability of ineffective treatment was already 82%. The study shows the informative value of assessment of Thact before appointment of biologics, dynamics of Th17 by the end of induction course and Treg after 16 weeks of therapy in prognosis of effectiveness of biologics in children with psoriasis.
银屑病是一种慢性炎症性皮肤病,其特征是表皮细胞增殖增加、角化受损以及由T淋巴细胞激活和促炎细胞因子合成引起的真皮炎症反应。牛皮癣的病理生理也与免疫抑制细胞的抗炎功能下降有关。最近,越来越多的儿童对正在进行的生物制剂治疗产生耐药性,需要取消药物或替代药物。本研究的目的是评估辅助性T细胞亚群的含量对银屑病儿童生物制剂疗效预后的影响。对110例寻常型银屑病患儿在16周和52周使用生物制剂前进行T辅助人群免疫分型。儿童的年龄从6岁到18岁不等。用PASI指数(0-68)评价银屑病的严重程度和治疗效果。流式细胞术检测Tregs、Thact和Th17的含量。在生物制剂效果充分的组中,PASI在治疗第16周(p = 0.000)和治疗后一年(p = 0.017)均有所下降。在患有牛皮癣的儿童中,无论生物制剂的持续时间和有效性如何,Thact的百分比相对于正常值都有所增加。1组患者在开生物制剂前Thact和Th17百分比均升高(p = 0.005), Th17百分比升高(p = 0.001)。通过对不同疗效儿童使用生物制剂1年期间小群体辅助性T细胞含量的动态分析,发现Th17和Treg含量及其Th17/Treg含量发生了显著变化。ROC分析显示,在使用生物制剂前,Th17偏差大于53%,Thact大于181%,Th17/Treg大于2.6,按年计算,75%的病例可预期治疗效果不足。诱导疗程结束时,Th17偏差大于102%,Th17/Treg大于2.6,治疗无效的概率已达82%。本研究显示,在预约生物制剂前评估Thact、诱导疗程结束时Th17的动态以及治疗16周后评估Treg对银屑病儿童生物制剂疗效预后的信息价值。
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引用次数: 0
Anthocyanins as a factor in the alimentary restoration of cellular immunity in diet induced obesity in rats 花青素在饮食性肥胖大鼠细胞免疫功能的消化道恢复中的作用
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-aaa-2719
E. Trushina, O. Mustafina, I. Aksenov, V. Tutelyan
The article presents the results of a study of the effect of anthocyanins on cellular immunity in rats on a model of alimentary obesity. The aim of the study was to study the effect of an anthocyanin- enriched diet on cellular immunity in diet induced obesity in rats. The study was carried out on male Wistar rats with an initial body weight of 108±2 g. The animals were randomized by body weight into 3 groups (8 pcs. in group). For 12 weeks, rats of the 1st (control) group received a complete modified diet of AIN93M; rats of the 2nd group consumed a high-calorie choline-deficient diet (HCChDD), the fat content of which was 45%, fructose – 20% of the energy value of the diet; rats of the 3rd group received HCChDD with the addition of standardized blueberry and blackcurrant extract (30% anthocyanins) at an average daily dose of 11 mg anthocyanins/kg body weight. The expression of differentiation markers of peripheral blood lymphocytes was carried out by flow cytofluorimetry. As a result of the study, it was found that in rats of the 2nd group with alimentary obesity, the relative content in the peripheral blood of T helpers (CD3+CD4+) was increased (p < 0.05) (75.75±1.11% versus 70.07±0 49% – group 1, 72.14±0.91% – group 3) and reduced (p < 0.05) content of T cytotoxic lymphocytes (CD3+CD8+) (22.54±1.14% versus 28.09±0.72% – 1st group, 26.07±0.87% – 3rd group). The CD3/CD4 ratio in rats of the 2nd group exceeded (p < 0.05) this index in rats of the 1st and 3rd groups (3.44±0.25 versus 2.47±0.09 – 1st group, 2.79±0.13 – 3rd group). Enrichment of the HCChDD with the blueberry and blackcurrant extract led to the normalization of these parameters of cellular immunity. The number of B lymphocytes (CD45R+), Т lymphocytes (CD3+) and NK cells (CD161+) in the rat peripheral blood of all experimental groups had no statistically significant differences. The results of the study of cellular immunity in rats with alimentary obesity indicate the presence of metainflammation. The received data indicate the prospect of using biologically active substances.
本文介绍了花青素对食源性肥胖大鼠细胞免疫影响的研究结果。本研究的目的是研究富含花青素的饮食对饮食性肥胖大鼠细胞免疫的影响。研究对象为初始体重为108±2 g的雄性Wistar大鼠。按体重随机分为3组,每组8只。在集团)。第1组(对照组)饲喂完全改良的AIN93M日粮,为期12周;第二组大鼠食用高热量胆碱缺乏饮食(HCChDD),其中脂肪含量为45%,果糖含量为饮食能量值的20%;第三组大鼠接受HCChDD,并添加标准蓝莓和黑加仑提取物(30%花青素),平均每日剂量为花青素11 mg /kg体重。流式细胞荧光法检测外周血淋巴细胞分化标志物的表达。结果发现,第二组食性肥胖大鼠外周血辅助T细胞(CD3+CD4+)相对含量升高(p < 0.05)(75.75±1.11%,第1组为70.07±0.49%,第3组为72.14±0.91%),T细胞毒性淋巴细胞(CD3+CD8+)含量降低(p < 0.05)(22.54±1.14%,第1组为28.09±0.72%,第3组为26.07±0.87%)。第2组大鼠CD3/CD4比值高于第1组和第3组大鼠(3.44±0.25 vs 2.47±0.09 - 1组,2.79±0.13 - 3组)(p < 0.05)。用蓝莓和黑加仑提取物富集HCChDD导致这些细胞免疫参数正常化。各实验组大鼠外周血B淋巴细胞(CD45R+)、Т淋巴细胞(CD3+)、NK细胞(CD161+)数量差异均无统计学意义。食源性肥胖大鼠的细胞免疫研究结果表明存在间炎症。收到的数据表明使用生物活性物质的前景。
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引用次数: 0
Immunological factor development of external genital endometriosis 外生殖器子宫内膜异位症的免疫因素发展
Q4 Medicine Pub Date : 2023-06-01 DOI: 10.15789/1563-0625-ifd-2796
M. Levkovich, N. V. Ermolova, I. Krukier, T. N. Pogorelova, L. Kravchenko
External genital endometriosis (EGE) is one of the common gynecological diseases of women of reproductive age with a relapsing, progressive course that worsens the quality of life of patients due to pain, emotional imbalance, fear of relapse and possible surgical intervention. Currently, endometriosis is recognized as one of the most common diseases associated with infertility. Thus, among fertile women with preserved childbearing function, the disease is generally diagnosed in approximately 6-7%, while among patients suffering from infertility, its frequency can reach 20-48%.However, the causes that determine reproductive dysfunction in patients with EGE are not well understood. Much attention is currently paid to the role of immunity in the formation of endometriosis. Patients with EGE show changes in both local immunity factors and immunological components of circulating blood.Purpose of the study: the study of factors of innate and adaptive immunity in patients of reproductive age with external genital endometriosis (EGE).The study included 71 patients with various stages of external genital endometriosis, the control group included 24 patients without endometriosis. Determination of the population composition of peripheral blood lymphocytes, the level of monocytes expressing TLR, activation markers, was carried out by laser flow cytometry — Immunotex (France), Caltag (USA), FITC (fluorescein isothiocynate) — labeled CD3, CD4, CD8, CD16, CD19, HLA-DR, CD282, CD284 and PE (phycoerythrin) - labeled with CD25, CD69, CD95, CD107a, CD14.External genital endometriosis is characterized by: at stages I-II of the disease - a violation of the early stages of the innate immune response (an increase in the number of monocytes expressing TLR-4, a violation of the activation and differentiation processes of immunocompetent cells, which is reflected in a decrease in the expression of CD16, CD8, CD16+HLA-DR+, CD16+CD107a+, CD8+CD107a+, at III-IV stages of the disease, there is a decrease in the level of CD16 and activation markers CD69, HLA-DR, CD107a on their surface, which is combined with a decrease in the expression of CD8, CD16, HLADR and CD107a on their surface. CD95+ and CD8+CD95+ were found at various stages of EGE.The results obtained allow us to understand the features of the functioning of innate and adaptive immunity at various stages of external genital endometriosis, and the studied immunological parameters can be used as diagnostic criteria for the formation of various stages of EGE. These data can serve as a theoretical basis for further identification of markers of EGE progression, as well as the mechanisms underlying immune inflammation.
外生殖器子宫内膜异位症(EGE)是育龄妇女常见的妇科疾病之一,具有反复进行性病程,因疼痛、情绪失衡、害怕复发及可能的手术干预而使患者的生活质量恶化。目前,子宫内膜异位症被认为是与不孕症相关的最常见疾病之一。因此,在保留生育功能的育龄妇女中,该病的诊断率通常约为6-7%,而在患有不孕症的患者中,其发病率可达20-48%。然而,决定EGE患者生殖功能障碍的原因尚不清楚。免疫在子宫内膜异位症形成中的作用是目前研究的重点。EGE患者表现出局部免疫因子和循环血液免疫成分的改变。研究目的:探讨育龄外生殖器子宫内膜异位症(EGE)患者先天免疫和适应性免疫的相关因素。本研究包括71例不同阶段的外生殖器子宫内膜异位症患者,对照组包括24例无子宫内膜异位症患者。采用激光流式细胞术测定外周血淋巴细胞的群体组成和表达TLR(活化标志物)的单核细胞水平——Immunotex(法国)、Caltag(美国)、FITC(异硫代酸荧光素)标记CD3、CD4、CD8、CD16、CD19、HLA-DR、CD282、CD284和PE(藻红蛋白)标记CD25、CD69、CD95、CD107a、CD14。外生殖器子宫内膜异位症的特点是:阶段i ii的疾病——违反了先天免疫反应的早期阶段(单核细胞表达地的数量的增加,违反了激活免疫活性的细胞和分化过程,这是反映在CD16的表达减少,CD8, CD16 + HLA-DR + CD16 + CD107a +、CD8 + CD107a +, iii iv阶段的疾病,有一个减少CD16和激活标记CD69水平,HLA-DR, CD107a表面,同时细胞表面CD8、CD16、HLADR和CD107a的表达减少。CD95+和CD8+CD95+在不同阶段均有表达。本研究结果使我们能够了解外生殖器子宫内膜异位症各阶段先天免疫和适应性免疫功能的特点,所研究的免疫学参数可作为各阶段EGE形成的诊断标准。这些数据可以作为进一步鉴定EGE进展标记物以及免疫炎症机制的理论基础。
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引用次数: 0
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Medical Immunology (Russia)
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