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Changes in accommodation disorders in children with anisometropic amblyopia and hypermetropia 各向异性弱视和远视儿童调节障碍的变化
Pub Date : 2024-03-26 DOI: 10.29413/abs.2024-9.1.13
I. L. Kulikova, K. A. Aleksandrova
Background. Accommodation disorders in  children with  hypermetropia is  one of  the  main factors in  emmetropization disorders and  maintenance of  image defocusing. The most severe changes in accommodation are observed in children with anisometropia and hyperopia.The  aim of  the work. To  evaluate the  changes in  the  accommodative function of the eye in children with hyperopia, amblyopia, who underwent refractive laser surgery (RLS), as  well  as in  children with  spectacle and  contact lens correction in combination with pleoptic treatment.Methods and materials. Group 1 consisted of 30 children after RLS; group 2 consisted of 29 children who had spectacle correction; group 3 consisted of 26 children who had soft contact lens correction; all children received pleoptic treatment. Clinical examination included the analysis of objective reserves of relative accommodation (RRA) and objective accommodative response (OAR) with an open field autorefractometer, and the results of accommodation measurement.Results. In 1.5 years, statistically significant changes were observed in the coefficient of accommodation response (CAR) of the amblyopic eye between the groups 1 and 2 – 0.12 ± 0.02 and 0.00 ± 0.1 relative units, respectively (p = 0.01). Similar statistically significant changes were obtained in OAR and objective RRA of the amblyopic eye. OAR in the group 1 was –2.1 ± 0.67 dpt, in the group 2 – –1.38 ± 0.19 dpt (p = 0.01). At the end of the observation, the OAR in the group 1 was –2.1 ± 0.67 dpt, the objective RRA – –2.1 ± 0.67 dpt; in the group 2 the OAR was –1.38 ± 0.19 dpt (p = 0.01), the objective RRA – –1.38 ± 0.19 dpt (p = 0.01). There were no statistically significant changes in these parameters of the amblyopic eye between the groups 1 and 3.Conclusion. There was an  improvement of  accommodation disorders in  children with anisometropia, hyperopia and  amblyopia after refractive laser surgery and in children with contact lens correction. Due to a decrease in the refractive indices of the amblyopic eye, the values of CAR, OAR and objective RRA after refractive laser surgery tended to be closer to the normal values.
背景。儿童远视患者的适应障碍是造成散光障碍和维持图像散焦的主要因素之一。在患有异性斜视和远视的儿童中,适应性的变化最为严重。评估接受屈光激光手术(RLS)的远视和弱视儿童,以及接受眼镜和隐形眼镜矫正并结合散光治疗的儿童的眼球调节功能变化。第 1 组包括 30 名接受过屈光激光手术的儿童;第 2 组包括 29 名接受过眼镜矫正的儿童;第 3 组包括 26 名接受过软性隐形眼镜矫正的儿童;所有儿童都接受了褶视治疗。临床检查包括用视野自动折射仪分析客观相对容积储备(RRA)和客观容积反应(OAR),以及容积测量结果。在 1.5 年的时间里,第 1 组和第 2 组弱视眼的调节反应系数(CAR)分别为 0.12 ± 0.02 和 0.00 ± 0.1 个相对单位(P = 0.01),有显著的统计学变化。弱视眼的OAR和客观RRA也发生了类似的显著统计学变化。第 1 组的 OAR 为 -2.1 ± 0.67 dpt,第 2 组为 - -1.38 ± 0.19 dpt(p = 0.01)。观察结束时,第1组的OAR为-2.1 ± 0.67 dpt,客观RRA为-2.1 ± 0.67 dpt;第2组的OAR为-1.38 ± 0.19 dpt (p = 0.01),客观RRA为-1.38 ± 0.19 dpt (p = 0.01)。第 1 组和第 3 组弱视眼的这些参数在统计学上没有明显变化。屈光激光手术后,患有异视、远视和弱视的儿童以及佩戴隐形眼镜矫正的儿童的调节障碍都有所改善。由于弱视眼的屈光指数下降,屈光激光手术后的CAR、OAR和客观RRA值更接近正常值。
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引用次数: 0
Studies of the effect of indole and its derivative 1-benzylindole on the functional state of the heart and blood values of laboratory rats 吲哚及其衍生物 1-苄基吲哚对实验鼠心脏功能状态和血值影响的研究
Pub Date : 2024-03-26 DOI: 10.29413/abs.2024-9.1.7
L. G. Gorokhova, N. Mikhailova, A. G. Zhukova, A. S. Kazitskaya
Background. Indole and its derivatives are widely used in all areas of pharmaceutical production. The toxicometry of indole compounds has been sufficiently studied. At the same time, there is still no information on the toxic effect on individual organs and systems during long-term intake of most compounds.The aim. To carry out an experimental study of the toxic effect of indole and its derivative 1-benzylindole on the functional state of the heart and blood values.Materials and  methods. The  work was  carried  out on  46  white rats, divided into groups: control group (n = 22); animals receiving indole once a day for 1 month (n = 12); animals receiving 1-benzylindole once a day for 1 month (n = 12). The substances were administered intragastrically 5 days a week. The condition of the animals was assessed by integral parameters, peripheral blood parameters and biochemical serum tests, and morphological data.Results. Administration of indole and 1-benzylindole caused an increase in the electrical activity of the atria, a decrease in the duration of the QRS complex, and a statistically significant decrease in  blood pressure and  body temperature compared to the control group. The intake of indole and 1-benzylindole decreased the number of red blood cells and hemoglobin, increased the activity of aspartate aminotransferase and alanine aminotransferase, and increased the concentrations of urea, total cholesterol and triglycerides in the blood. Against the background of long-term exposure to indole and 1-benzylindole, dystrophic disorders, hypertrophic and atrophic changes in individual fibers with a pronounced congestion of the microcirculatory vessels were revealed in the heart of rats.Conclusion. Indole and 1-benzylindole in case of long-term intake lead to functional disorders of the cardiovascular system, which cause the development of arterial hypertension, coronary heart disease, and atherosclerotic vascular lesions. Preventive measures in industries with possible contact with indole and its derivatives should include regular medical examinations of workers with mandatory monitoring of electrocardiography and advanced indicators of general and biochemical blood tests.
背景。吲哚及其衍生物被广泛应用于医药生产的各个领域。人们已经对吲哚化合物的毒性进行了充分的研究。与此同时,关于长期摄入大多数化合物对各个器官和系统的毒性影响,目前仍没有相关资料。对吲哚及其衍生物 1-苄基吲哚对心脏功能状态和血值的毒性作用进行实验研究。实验对象为 46 只白鼠,分为以下几组:对照组(n = 22);每天接受一次吲哚治疗,为期 1 个月(n = 12);每天接受一次 1-苄基吲哚治疗,为期 1 个月(n = 12)。每周 5 天胃肠内给药。通过整体参数、外周血参数和生化血清检测以及形态学数据对动物的状况进行评估。与对照组相比,给药吲哚和 1-苄基吲哚可使心房电活动增加,QRS 波群持续时间缩短,血压和体温下降,差异有统计学意义。摄入吲哚和 1-苄基吲哚会减少红细胞和血红蛋白的数量,增加天门冬氨酸氨基转移酶和丙氨酸氨基转移酶的活性,增加血液中尿素、总胆固醇和甘油三酯的浓度。在长期接触吲哚和 1-苄基吲哚的背景下,大鼠心脏出现了萎缩性病变、单个纤维肥大和萎缩性变化,微循环血管明显充血。结论:长期摄入吲哚和 1-苄基吲哚会导致心血管系统功能紊乱,引起动脉高血压、冠心病和动脉粥样硬化血管病变。在可能接触吲哚及其衍生物的行业中采取的预防措施应包括对工人进行定期体检,强制监测心电图和先进的一般和生化血液检测指标。
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引用次数: 0
Lysophosphatidic acid and itsreceptors: Role in bronchial asthma pathogenesis 溶血磷脂酸及其受体:在支气管哮喘发病机制中的作用
Pub Date : 2024-03-25 DOI: 10.29413/abs.2024-9.1.2
O. Kytikova, T. Novgorodtseva, Y. K. Denisenko
Lysophosphatidic acid (LPA) is a biologically active lipid mediator that regulates a number ofsignaling pathways involved in the pathogenesis of bronchial asthma. Attention to studying the relationship of LPA with LPA receptors (LPARs) and ion channels with transient receptor potential (TRP) is caused by their role in the initiation and development of bronchial obstruction, which suggests the development of new effective strategies for the treatment of bronchial asthma through blocking LPA synthesis and/or regulation of the activity of the ligand-receptor relationship.The aim of the review. To summarize ideas on the role of lysophosphatidic acid and its receptors in the pathogenesis of bronchial asthma based on the analysis of articles published in English in 2020–2023 from the PubMed database.Conclusion. The review summarizes recent literature data on the chemical structure, biosynthetic pathways and LPA receptors. It presents the information on the role of LPA, LPARs andTRP channels inthepathogenesis of bronchial asthma; summarizes the bronchial asthma therapeutic strategies targeting LPA, LPARs, andTRP channels. The review highlights not only a new perspective on understanding the mechanisms of initiation of asthmatic reactions, but also possible ways to manage them at the stage of correction of their development.
溶血磷脂酸(LPA)是一种具有生物活性的脂质介质,可调节涉及支气管哮喘发病机制的多种信号通路。研究 LPA 与 LPA 受体(LPARs)和具有瞬时受体电位(TRP)的离子通道之间的关系,是因为它们在支气管阻塞的起始和发展中的作用,这表明通过阻断 LPA 的合成和/或调节配体-受体关系的活性,可以开发出治疗支气管哮喘的新的有效策略。通过分析PubMed数据库中2020-2023年发表的英文文章,总结溶血磷脂酸及其受体在支气管哮喘发病机制中的作用。这篇综述总结了近期有关LPA受体的化学结构、生物合成途径和LPA受体的文献数据。综述介绍了LPA、LPARs和TRP通道在支气管哮喘发病机制中的作用;总结了针对LPA、LPARs和TRP通道的支气管哮喘治疗策略。该综述不仅为了解哮喘反应的启动机制提供了一个新的视角,而且为在哮喘反应发展的纠正阶段对其进行管理提供了可能的方法。
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引用次数: 0
The role of L-arginine in the pathogenesis of essential arterial hypertension 左旋精氨酸在本质动脉高血压发病机制中的作用
Pub Date : 2024-03-25 DOI: 10.29413/abs.2024-9.1.4
V. A. Shcherbak, A. S. Medvedeva, T. Aksenova, N. M. Shcherbak, K. O. Aksenov
The role of arginine in the development of primary arterial hypertension continues to be clarified up to the present moment. During natural metabolic processes in cells, methylated forms of arginine are produced – symmetric (SDMA) and asymmetric (ADMA) dimethylarginine. ADMA is a nitric oxide synthase inhibitor and is now considered a well-established marker for endothelial dysfunction. SDMA is not a nitric oxide synthase inhibitor, but may indirectly reduce nitric oxide production through competitive interaction with cellular L-arginine.Currently, arginine preparations are practically not used for the treatment of primary arterial hypertension. This was the rationale for the given scientific review. The article summarizes the information available in the literature (2018–2022) on the pathogenetic mechanisms of  the  relationship between arginine and  the  development of impaired vascular tone. We used PubMed and RSCI databases for our review. Using keywords, 1784 publications were found over the past 5 years. The final selection criteria were time frame and matching keywords. The review provides data on the increased ADMA concentrations in experimental hypertensive animals and individuals with essential hypertension. The role of arginine metabolites in the genesis of endothelial dysfunction and arterial hypertension and the prospects for the therapeutic use of this compound are discussed.
直到现在,精氨酸在原发性动脉高血压发病过程中的作用仍有待进一步阐明。在细胞的自然代谢过程中,会产生精氨酸的甲基化形式--对称(SDMA)和不对称(ADMA)二甲基精氨酸。ADMA 是一氧化氮合酶抑制剂,目前被认为是内皮功能障碍的公认标志物。SDMA 不是一氧化氮合酶抑制剂,但可能会通过与细胞中的 L- 精氨酸竞争性相互作用而间接减少一氧化氮的产生。目前,精氨酸制剂实际上并未用于治疗原发性动脉高血压。文章总结了现有文献(2018-2022 年)中关于精氨酸与血管张力受损发展之间关系的致病机制的信息。我们使用 PubMed 和 RSCI 数据库进行综述。通过关键词,我们找到了过去 5 年中的 1784 篇出版物。最终的选择标准是时间范围和匹配的关键词。综述提供了实验性高血压动物和原发性高血压患者体内 ADMA 浓度增加的数据。文中讨论了精氨酸代谢物在内皮功能障碍和动脉高血压形成过程中的作用,以及该化合物的治疗应用前景。
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引用次数: 0
Association of FoxP3+ T regulatory lymphocytes with epicardial adipose tissue thickness in patients with coronary heart disease 冠心病患者体内 FoxP3+ T 调节性淋巴细胞与心外膜脂肪组织厚度的关系
Pub Date : 2024-03-25 DOI: 10.29413/abs.2024-9.1.5
I. Kologrivova, O. Kharitonova, A. Dmitriukov, E. Kravchenko, O. Koshelskaya, T. Suslova
Background. Increase ofthe epicardial adipose tissue (EAT) thickness isassociated with development of inflammation and cardiovascular complications, however, there is no data on the relationship between EAT thickening and the number of immunosuppressive regulatory T lymphocytes.The aim. To study the number of circulating T regulatory lymphocytes and nuclear translocation ofthe FoxP3 transcription factor in patients with stable coronary heart disease (CHD) depending on the epicardial adipose tissue thickness.Materials and methods. We examined 30 patients with chronic stable CHD. The EAT thickness was measured by echocardiography. Patients were divided into groups depending on the presence and absence of EAT thickening above 5 mm (groups 1 and 2, respectively). Imaging flow cytometry was used to determine the number of T regulatory lymphocytes and the level of FoxP3 nuclear translocation. The concentration of cytokines and high sensitivity C-reactive protein (hsCRP) was determined using enzyme-linked immunosorbent assay in blood serum.Results. Anthropometric indicators of obesity and the severity of atherosclerosis were comparable between groups. In group 2, there was an increase in low-density lipoprotein cholesterol concentration (p = 0.043), ratio of low-density lipoprotein cholesterol tohigh-density lipoprotein cholesterol (p = 0.017) and the concentration ofhsCRP (p = 0.044) andIL-1β (p = 0.005), adecrease in the number and relative count of Tregulatory lymphocytes (p = 0.020 andp = 0.026, respectively), aswellas thenumber of cells withFoxP3 nuclear translocation (p = 0.018) compared togroup1. According tomultiple logistic regression, the concentration ofhsCRP, IL-1β and T regulatory lymphocytes relative count in total were the predictors of EAT thickening (accuracy 80 %; sensitivity 75 %; specificity 84,6 %; AUC = 0.89).Conclusions. Thickening of epicardial adipose tissue inpatients withcoronary heart disease is associated with a decrease in the number of T regulatory lymphocytes andFoxP3 nuclear translocation inthem in presence of comparable anthropometric parameters of obesity and the severity of coronary atherosclerosis.
背景。心外膜脂肪组织(EAT)厚度的增加与炎症和心血管并发症的发生有关,但目前还没有关于心外膜脂肪组织增厚与免疫抑制调节性T淋巴细胞数量之间关系的数据。研究稳定型冠心病(CHD)患者循环 T 调节性淋巴细胞的数量和 FoxP3 转录因子的核转位与心外膜脂肪组织厚度的关系。我们对 30 名慢性稳定型冠心病患者进行了研究。超声心动图测量了心外膜脂肪组织的厚度。根据心外膜脂肪组织增厚是否超过 5 毫米将患者分为几组(分别为第 1 组和第 2 组)。使用成像流式细胞术测定 T 调节淋巴细胞的数量和 FoxP3 核易位水平。用酶联免疫吸附法测定血清中细胞因子和高敏 C 反应蛋白(hsCRP)的浓度。各组肥胖的人体测量指标和动脉粥样硬化的严重程度相当。第 2 组的低密度脂蛋白胆固醇浓度(p = 0.043)、低密度脂蛋白胆固醇与高密度脂蛋白胆固醇的比值(p = 0.017)和 hsCRP 浓度(p = 0.044) 和 IL-1β (p = 0.005),与第一组相比,T 调节淋巴细胞的数量和相对数量增加(分别为 p = 0.020 和 p = 0.026),以及出现 FoxP3 核易位的细胞数量增加(p = 0.018)。根据多重逻辑回归,hsCRP 浓度、IL-1β 和 T 调节淋巴细胞相对总数是 EAT 增厚的预测因子(准确率 80%;灵敏度 75%;特异性 84.6%;AUC = 0.89)。结论:冠心病患者心外膜脂肪组织的增厚与 T 调节淋巴细胞数量的减少和其中的 FoxP3 核易位有关,而肥胖的人体测量参数和冠状动脉粥样硬化的严重程度具有可比性。
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引用次数: 0
Deputy editor-in-chief’s preface to Issue 1, 2024 2024 年第 1 期副主编序言
Pub Date : 2024-03-25 DOI: 10.29413/abs.2024-9.1.1
L. Rychkova
.
.
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引用次数: 0
Social factors in the formation of eating disorders: Experience of sociological research 饮食失调症形成的社会因素:社会学研究经验
Pub Date : 2024-03-25 DOI: 10.29413/abs.2024-9.1.3
N. L. Antonova, D. V. Nagnoenko
Background. The increasingly complex structure of modern society and systemic changes associated with the processes of digitalization and mediatization are raising the issue of preserving the health of the younger generation, which is the most receptive and vulnerable group to external impact.The aim of the study. Based on survey data, to carry out an analysis of social factors influencing the development of eating disorders in girls.Materials and methods. The method of collecting information was an online survey of girls aged 18 to 25 years old, conducted in Yekaterinburg in the spring of 2023 (n  =  205). Using in-depth interviews, 8  girls were interviewed to  clarify the  social factors in the formation of eating disorders.Results. In girls’ assessments, distorted body image, fear of weight gain, and orthorexia are the signs of eating disorders. Social factors influencing the formation of  an  ideal body image and  eating disorders are  social media, circle of  contacts, as well as the external environment, which causes psychological and physical stress. Despite the negative perception of the content of communities promoting anorexic bodies, girls are well aware of the published materials. The main tool for achieving the standard model of a girl’s physicality is dietary practices, food restrictions and calorie counting, despite the recognition of the negative consequences of their use.Conclusion. Eating behavior for girls is one of the leading tools for achieving an ideal body, ideas about which are formed today by social media, as well as the immediate social environment, including the  opposite sex. Communities on  social networks can serve as  a  source for  development of  deviant eating attitudes, on  the  one hand, and a real driving force in providing assistance and support to young people with signs of eating disorders, on the other hand. We believe that online consultations with specialists and the development of a parental culture of health protection can have a significant impact on the development of harmonious, health-protecting eating habits.
背景。现代社会结构日趋复杂,与数字化和媒体化进程相关的系统性变化提出了保护年轻一代健康的问题,而年轻一代是最容易受到外界影响的群体。以调查数据为基础,对影响女孩饮食失调的社会因素进行分析。收集信息的方法是 2023 年春季在叶卡捷琳堡对 18 至 25 岁的女孩进行的在线调查(n = 205)。通过深度访谈,对 8 名女孩进行了访谈,以明确饮食失调形成的社会因素。在女孩的评估中,扭曲的身体形象、对体重增加的恐惧和厌食症是饮食失调的表现。影响理想身体形象和饮食失调形成的社会因素包括社交媒体、交往圈以及造成心理和生理压力的外部环境。尽管人们对宣传厌食身体的社区内容有负面看法,但女孩们对出版的材料还是很了解的。实现女孩身体标准模式的主要工具是饮食习惯、食物限制和卡路里计算,尽管人们认识到使用这些工具的负面影响。女孩的饮食行为是实现理想体型的主要工具之一,而关于理想体型的观念是由当今的社交媒体以及包括异性在内的直接社会环境形成的。一方面,社交网络上的社区可以成为培养偏差饮食态度的源泉,另一方面,也可以成为向有饮食失调迹象的年轻人提供援助和支持的真正动力。我们相信,在线咨询专家和培养家长保护健康的文化,可以对培养和谐、保护健康的饮食习惯产生重大影响。
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引用次数: 0
Biological properties and genetic structure of clinic isolates of Klebsiella pneumoniae species 肺炎克雷伯氏菌临床分离物的生物学特性和遗传结构
Pub Date : 2024-03-25 DOI: 10.29413/abs.2024-9.1.6
N. Belkova, E. Klimenko, U. Nemchenko, E. Grigorova, K. O. Sitnikova, R. E. Zugeeva, N. E. Smurova, N. Chemezova, E. Savilov
Klebsiella pneumoniae (Kp) species complex is a genetically and ecologically diverse group of bacteria that causes a wide range of infections in humans and animals.The aim. To carry out biological characterization and genotyping based on the study of different loci of Klebsiella pneumoniae clinical isolates.Materials and  methods. The  object of  the study was  three Klebsiella pneumoniae clinical isolates from different biotopes of patients from a regional children’s multidisciplinary hospital. We used a complex of bacteriological, molecular genetic and bioinformatic methods. Genotyping of the isolates was carried out using the Pasteur Institute service for strains of the K. pneumoniae species complex.Results. All strains were sensitive to antimicrobial drugs from carbapenem (imipenem, meropenem) and  tetracycline groups (tigecycline), and  demonstrated high sensitivity to the Klebsiella polyvalent bacteriophage. The antibiotic resistance of the Kp ODKB-16 and ODKB-81 isolates to seven and eight antimicrobial drugs, respectively, was registeredBased on  the results of  multi-locus sequence typing, all  strains were assigned to  Kp1  phylogroup, K2  type and  differed in  sequence type, scgMLST629  profile and KL type. Kp ODKB-16 strain was identified as ST-65, scgST-11107, KL2; ODKB-07 strain – as ST-219, scgST-6401, KL125KL114; ODKB-81 strain – as ST-86, scgST-2800, KL2KL30. The virulence gene clusters AbST, CbST, YbST, SmST, and RmST have been characterized only in the genome of the Kp ODKB-16 isolate, allowing it to be characterized as highly virulent with multidrug resistance (MDR). Additionally, genes responsible for the synthesis of types 1 and 3 fimbrial adhesins were registered in all strains, and ter operon loci were identified only in Kp ODKB-16. Resistome analysis showed that all strains had 2b genotype. Plasmids were found in the genomes of Kp ODKB-81 (IncI2) and ODKB-16 (IncFIA + IncFIB + IncHI1B).Conclusion. We used a comprehensive framework for genomic taxonomy of clinical isolates, which can contribute to the unification of global and regional peculiarities of the developing and microevolution of bacterial pathogens.
肺炎克雷伯菌(Kp)菌群是一种基因和生态多样化的细菌,可引起人类和动物的多种感染。在对肺炎克雷伯氏菌临床分离株的不同基因位点进行研究的基础上,对其进行生物学特性鉴定和基因分型。研究对象是来自一家地区性多学科儿童医院不同生物群患者的三种肺炎克雷伯氏菌临床分离株。我们使用了细菌学、分子遗传学和生物信息学的综合方法。利用巴斯德研究所的肺炎克雷伯菌种群服务对分离菌株进行了基因分型。所有菌株都对碳青霉烯类(亚胺培南、美罗培南)和四环素类(替加环素)抗菌药物敏感,并对克雷伯氏菌多价噬菌体表现出高度敏感性。Kp ODKB-16 和 ODKB-81 菌株分别对 7 种和 8 种抗菌药物具有耐药性。根据多焦点序列分型结果,所有菌株均被归入 Kp1 系统群、K2 类型,并在序列类型、scgMLST629 特征和 KL 类型上存在差异。Kp ODKB-16 菌株被鉴定为 ST-65,scgST-11107,KL2;ODKB-07 菌株--为 ST-219,scgST-6401,KL125KL114;ODKB-81 菌株--为 ST-86,scgST-2800,KL2KL30。仅在 Kp ODKB-16 株系的基因组中鉴定出了 AbST、CbST、YbST、SmST 和 RmST 毒力基因簇,因此该株系被鉴定为具有多重耐药性(MDR)的高毒力株系。此外,在所有菌株中都发现了负责合成 1 型和 3 型边缘粘附素的基因,而且只在 Kp ODKB-16 中发现了 ter 操作子基因座。抗性组分析表明,所有菌株都有 2b 基因型。在Kp ODKB-81(IncI2)和ODKB-16(IncFIA + IncFIB + IncHI1B)的基因组中发现了质粒。我们使用了一个全面的临床分离株基因组分类框架,它有助于统一全球和地区细菌病原体发展和微进化的特殊性。
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引用次数: 0
Cytotoxic effect of the VVGMCSF-Lact oncolytic virus against 3D cultures of human glioblastoma cells U-87 MG VVGMCSF-Lact 溶瘤病毒对三维培养的人类胶质母细胞瘤细胞 U-87 MG 的细胞毒作用
Pub Date : 2024-01-15 DOI: 10.29413/abs.2023-8.6.15
M. Dymova, T. A. Shnaider, S. A. Chechetkina, G. O. Petrov, D. O. Malysheva, D. V. Drokov, A. B. Ageenko, N. Vasileva, V. A. Richter, E. Kuligina
Background. One of the promising methods of treating tumors is virotherapy, which is based on direct lysis of cancer cells by a virus and a virus-mediated antitumor immune response of the body. For the recombinant vaccinia virus strain VVGMCSF-Lact, producing human GMCSF and the oncotoxic protein lactaptin, cytotoxic and antitumor effects were shown in experiments in vitro and in vivo, respectively, when using adhesive cultures of U-87 MG human glioblastoma cells. 3D cultures are a more relevant tumor model than adhesive models, as they more fully reflect the realistic scenario of cancer development, as well as the response of the tumor to anticancer therapy.The aim. To evaluate the cytotoxic effect of the oncolytic virus VV-GMCSF-Lact against 3D cultures of human glioblastoma U-87 MG.Materials and methods. The following methods were used in the work: cultivation of 3D cell cultures, cytofluorometry, microscopic analysis, virus titration, statistical analysis.Results. U-87 MG cells were transduced with a lentiviral vector carrying the GFP reporter gene. The cytotoxicity of the VV-GMCSF-Lact virus (IC50) against the studied cells was 0.024 PFU/cell. U-87 MG cells were cultured under conditions for the formation of 3D structures. Microscopic analysis showed the oncolytic effect of the virus on the cells of 3D cultures as early as 24 hours after the start of incubation. Flow cytometry showed an increase in the granularity of glioblastoma cells under the action of the virus, which indicates active replication of the virus in the cells. The virus titer was 0.44 PFU/cell.Conclusions. The recombinant VV-GMCSF-Lact virus has a cytotoxic effect on 3D human glioblastoma U-87 MG cell cultures and actively replicates in them. In the future, to test the oncolytic effect of VV-GMCSF-Lact, it is planned to use not only 3D human glioblastoma cultures, but also cerebral organelles obtained in the process of cocultivation of glioblastoma cells and induced human pluripotent cells.
背景。病毒疗法是治疗肿瘤的有前途的方法之一,它是基于病毒直接裂解癌细胞和病毒介导的机体抗肿瘤免疫反应。重组疫苗病毒株 VVGMCSF-Lact 能产生人类 GMCSF 和肿瘤毒性蛋白 lactaptin,利用 U-87 MG 人类胶质母细胞瘤细胞的粘附培养物进行的体外和体内实验分别显示了其细胞毒性和抗肿瘤效果。三维培养物是一种比粘附模型更贴切的肿瘤模型,因为它们能更全面地反映癌症发展的真实情况以及肿瘤对抗癌治疗的反应。评估溶瘤病毒 VV-GMCSF-Lact 对人胶质母细胞瘤 U-87 MG 三维培养物的细胞毒作用。工作中使用了以下方法:三维细胞培养、细胞荧光测定、显微镜分析、病毒滴定、统计分析。用携带 GFP 报告基因的慢病毒载体转导 U-87 MG 细胞。VV-GMCSF-Lact 病毒对研究细胞的细胞毒性(IC50)为 0.024 PFU/细胞。U-87 MG 细胞是在可形成三维结构的条件下培养的。显微镜分析表明,早在培养开始 24 小时后,病毒就对三维培养物的细胞产生了溶解作用。流式细胞仪显示,在病毒的作用下,胶质母细胞瘤细胞的颗粒度增加,这表明病毒在细胞中的复制活跃。病毒滴度为 0.44 PFU/细胞。重组 VV-GMCSF-Lact 病毒对三维人胶质母细胞瘤 U-87 MG 细胞培养物具有细胞毒性作用,并能在细胞内活跃复制。未来,为了测试 VV-GMCSF-Lact 的溶瘤效果,不仅计划使用三维人类胶质母细胞瘤培养物,还计划使用胶质母细胞瘤细胞和诱导人类多能细胞共培养过程中获得的脑细胞器。
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引用次数: 0
Pharmacological blockade of cannabinoid type II receptors and mesenchymal stem cell transplantation in a model of peripheral neuropathic pain 药理阻断大麻素 II 型受体和间充质干细胞移植在外周神经病理性疼痛模型中的应用
Pub Date : 2024-01-15 DOI: 10.29413/abs.2023-8.6.13
A.-M. V. Yerofeyeva, S. Pinchuk, S. Rjabceva, A. Molchanova
Objective. To evaluate the anti-nociceptive and reparative effects of adipose-derived mesenchymal stem cells (ADMSCs) under the pharmacological blockade of cannabinoid CB2 receptors in a model of peripheral neuropathic pain.Material and methods. In 40 male Wistar rats, modeling of peripheral neuropathy (NP) was performed by excising a sciatic nerve. On day 7 of the study, ADMSCs (1 × 106 cells/kg) were transplanted into the area of sciatic nerve injury without additional influences or after administration of the CB2 receptor antagonist AM630, as well as after incubation with AM630. Within 90  days, nociceptive sensitivity was studied, as well as a detailed analysis of gait using CatWalk XT (Noldus, Netherlands). On day 21 and day 90, histostructure of the distal segment of the sciatic nerve was assessed.Results. Pharmacological blockade of CB2 receptors both on the ADMSCs and in the soft tissues surrounding the site of sciatic nerve injury led to a decrease in withdrawal threshold and withdrawal latency from day 28 of the study compared with the group of rats with NP and transplantation of ADMSCs only. Local injection of AM630 before transplantation of ADMSCs contributed to the development of  NP-induced gait disturbances and increase of the number of damaged nerve fibers in the distal segment of sciatic nerve. Transplantation of ADMSCs pretreated with  AM630 did not significantly affect the rate of recovery of gait parameters, and decreased the number of damaged nerve fibers by day 90 of study.Conclusion. Blockade of CB2 receptors, both on the membranes of MSCs and in the area of damage to the peripheral nerve, has a negative effect on the development of the anti-nociceptive and reparative effects of MSCs.
目的评估脂肪间充质干细胞(ADMSCs)在周围神经病理性疼痛模型中,在大麻素 CB2 受体药理阻断作用下的抗痛觉和修复作用。在40只雄性Wistar大鼠中,通过切除坐骨神经建立周围神经病变(NP)模型。在研究的第 7 天,将 ADMSCs(1 × 106 cells/kg)移植到坐骨神经损伤区域,不施加额外影响,或在施用 CB2 受体拮抗剂 AM630 后,以及在与 AM630 一起孵育后移植。在 90 天内,对痛觉敏感性进行了研究,并使用 CatWalk XT(荷兰 Noldus 公司)对步态进行了详细分析。第 21 天和第 90 天,对坐骨神经远端组织结构进行了评估。与仅移植 ADMSCs 的 NP 组大鼠相比,药物阻断 ADMSCs 上和坐骨神经损伤部位周围软组织中的 CB2 受体可降低戒断阈值和戒断潜伏期。移植ADMSCs前局部注射AM630有助于NP引起的步态障碍的发展和坐骨神经远段受损神经纤维数量的增加。用AM630预处理的ADMSCs移植并没有明显影响步态参数的恢复速度,到研究的第90天,受损神经纤维的数量也有所减少。间充质干细胞膜上和周围神经损伤区域的 CB2 受体阻断对间充质干细胞抗痛觉和修复作用的发展有负面影响。
{"title":"Pharmacological blockade of cannabinoid type II receptors and mesenchymal stem cell transplantation in a model of peripheral neuropathic pain","authors":"A.-M. V. Yerofeyeva, S. Pinchuk, S. Rjabceva, A. Molchanova","doi":"10.29413/abs.2023-8.6.13","DOIUrl":"https://doi.org/10.29413/abs.2023-8.6.13","url":null,"abstract":"Objective. To evaluate the anti-nociceptive and reparative effects of adipose-derived mesenchymal stem cells (ADMSCs) under the pharmacological blockade of cannabinoid CB2 receptors in a model of peripheral neuropathic pain.Material and methods. In 40 male Wistar rats, modeling of peripheral neuropathy (NP) was performed by excising a sciatic nerve. On day 7 of the study, ADMSCs (1 × 106 cells/kg) were transplanted into the area of sciatic nerve injury without additional influences or after administration of the CB2 receptor antagonist AM630, as well as after incubation with AM630. Within 90  days, nociceptive sensitivity was studied, as well as a detailed analysis of gait using CatWalk XT (Noldus, Netherlands). On day 21 and day 90, histostructure of the distal segment of the sciatic nerve was assessed.Results. Pharmacological blockade of CB2 receptors both on the ADMSCs and in the soft tissues surrounding the site of sciatic nerve injury led to a decrease in withdrawal threshold and withdrawal latency from day 28 of the study compared with the group of rats with NP and transplantation of ADMSCs only. Local injection of AM630 before transplantation of ADMSCs contributed to the development of  NP-induced gait disturbances and increase of the number of damaged nerve fibers in the distal segment of sciatic nerve. Transplantation of ADMSCs pretreated with  AM630 did not significantly affect the rate of recovery of gait parameters, and decreased the number of damaged nerve fibers by day 90 of study.Conclusion. Blockade of CB2 receptors, both on the membranes of MSCs and in the area of damage to the peripheral nerve, has a negative effect on the development of the anti-nociceptive and reparative effects of MSCs.","PeriodicalId":505136,"journal":{"name":"Acta Biomedica Scientifica","volume":" 45","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139621788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Acta Biomedica Scientifica
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