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Human umbilical cord-derived mesenchymal stem cells and nitric oxide modulators attenuate the proinflammatory cytokine pattern in experimental antiphospholipid syndrome in mice 人脐源性间充质干细胞和一氧化氮调节剂可减轻小鼠实验性抗磷脂综合征的促炎细胞因子模式
Q4 Medicine Pub Date : 2024-05-01 DOI: 10.22494/cot.v12i1.163
N. Mekhno, A. Dovgalyuk, M. Korda, O. Yaremchuk
Antiphospholipid syndrome is an autoimmune disease characterized by vascular thrombosis and/or obstetric pathology and the presence of antibodies against membrane phospholipids or certain phospholipid-related proteins. Objective. The aim of the research is to study the effect of mesenchymal stem cells, nitric oxide modulators (L-arginine and aminoguanidine) on the level of cytokines in bronchoalveolar lavage in experimental antiphospholipid syndrome in mice. Material and methods. Antiphospholipid syndrome was modeled on female BALB/c mice by intramuscular injections of cardiolipin 1.2 mg/kg 4 times with a 14-day interval. Cryopreserved human umbilical cord-derived mesenchymal stem cells (5×106 cells/kg) were injected once intraperitoneally, L-arginine (25 mg/kg) and aminoguanidine (10 mg/kg) were administered intraperitoneally 1 time per day during 10 days after APS had developed. The cytokines concentration in bronchoalveolar lavage from the lungs was assessed by means of ELISA in 10 days after APS development. Results. In the bronchoalveolar lavage of the BALB/c mice with experimental APS, an increased level of pro-inflammatory cytokines IL-1β, IL-6, TNF-α and decreased level of anti-inflammatory IL-4 and IL-10 were found. It was established that in cases of APS and administration of stem cells the concentration of proinflammatory cytokines decreased: IL-1β by 32.4 %, IL-6 by 30.6 % and TNF-α by 36.1 %, respectively, compare to the APS animals. At the same time the level of IL-4 increased by 50.5 % and IL-10 – by 57.5 % in the group of animals administered with stem cells compare to those with APS. Conclusion. In cases of correction of modeled antiphospholipid syndrome in mice using mesenchymal stem cells and combined application of mesenchymal stem cells and nitric oxide modulators (L-arginine and aminoguanidine), a decrease in the level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α ) and an increase in the level of anti-inflammatory cytokines (IL-4 and IL-10) in bronchoalveolar lavage has been established.
抗磷脂综合征(Antiphospholipid Syndrome)是一种自身免疫性疾病,其特征是血管血栓形成和/或产科病变以及存在针对膜磷脂或某些磷脂相关蛋白的抗体。研究目的研究目的是研究间充质干细胞、一氧化氮调节剂(L-精氨酸和氨基胍)对实验性抗磷脂综合征小鼠支气管肺泡灌洗液中细胞因子水平的影响。材料和方法给雌性 BALB/c 小鼠肌肉注射心磷脂 1.2 毫克/千克,4 次,每次间隔 14 天。冷冻保存的人脐带间充质干细胞(5×106个细胞/千克)腹腔注射1次,L-精氨酸(25毫克/千克)和氨基胍(10毫克/千克)腹腔注射1次,每天1次。APS发生10天后,用ELISA方法评估肺部支气管肺泡灌洗液中细胞因子的浓度。结果显示在实验性 APS 的 BALB/c 小鼠的支气管肺泡灌洗液中,发现促炎细胞因子 IL-1β、IL-6、TNF-α 水平升高,而抗炎细胞因子 IL-4 和 IL-10 水平降低。研究证实,在APS和干细胞给药的情况下,促炎细胞因子的浓度下降:与APS动物相比,IL-1β减少32.4%,IL-6减少30.6%,TNF-α减少36.1%。同时,与APS动物相比,干细胞给药组的IL-4水平提高了50.5%,IL-10水平提高了57.5%。结论在使用间充质干细胞以及间充质干细胞与一氧化氮调节剂(L-精氨酸和氨基胍)联合应用纠正小鼠模型化抗磷脂综合征的病例中,证实支气管肺泡灌洗液中促炎性细胞因子(IL-1β、IL-6、TNF-α)水平下降,抗炎性细胞因子(IL-4和IL-10)水平上升。
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引用次数: 0
Foreign experience of legal regulation of criminal liability for violation of the procedure for transplantation of human anatomical materials established by law 国外对违反法律规定的人体解剖材料移植程序的刑事责任进行法律规范的经验
Q4 Medicine Pub Date : 2024-05-01 DOI: 10.22494/cot.v12i1.162
Yu. O. Tkach
The article examines the experience of individual countries in matters of legal regulation of criminal liability for violation of the procedure for transplantation of human anatomical materials in order to determine important legal assets of foreign legislation, which could be discussed for the purpose of further implementation in Ukrainian legislation. Within the framework of the article, we will analyze national and international legislation, namely, we will compare the content of Articles 143 and 144 of the Criminal Code of Ukraine with the content of the corresponding articles and provisions in the legislation of several countries from the perspective of the used terminology, interpretation of concepts, descriptions of crimes, measures of criminal liability, etc. The Constitution of Ukraine guarantees every person the right to life. However, experts increasingly raise questions about various violations of this right from the perspective of transplantation of human anatomical materials. Today, criminal offenses in relation to both donors and recipients become difficult to detect due to high self-interest and profitability, disguised nature, network systematicity, extensive illegal infrastructure and fast mechanisms for its recovery, group organization and strong connections with other criminal groups, use of deception, coercion, intimidation and other methods of forced donation, corruption in the field of donation, large-scale latent level of crimes related to transplantation. Detection of illegal transplantation is also burdened by their contradictory geography, when potential donors are recruited in the so-called "depressed" countries around the world, and anatomical materials are seized in countries that are highly developed in the field of transplantology, having loyal legislation to carry out such operations. In Ukraine, the detection of such crimes is also aggravated by the fact that people who are ready to illegally donate their organs for payment, travel to remove the organ outside the country and carry out their plans in other countries ("transplant tourism"). Due to the low level of information and enlightenment of the society in matters of transplantation, the detection of crimes in this area is also complicated by the so-called "victimhood" of people (both donors and recipients) – a set of personal traits that cause a high probability of becoming the object of a criminal attack (a tendency to become a victim of crime). These grounds contribute to a dynamic increase in the number of violations of the law-enforced procedure for the transplantation of human anatomical materials, which constitutes a high public danger. At the same time, the legal regulation of criminal liability for such violations still has certain differences. Therefore, the study of foreign experience in matters of transplantation, the comparison of the norms of articles in the Criminal Codes of different countries, and the analysis of concepts used in normative leg
本文研究了各个国家在对违反人体解剖材料移植程序的刑事责任进行法律调节方面的经验,以确定外国立法的重要法律资产,并对其进行讨论,以便在乌克兰立法中进一步实施。在本文框架内,我们将对国内和国际立法进行分析,即从使用的术语、概念解释、犯罪描述、刑事责任措施等角度,将《乌克兰刑法典》第 143 条和第 144 条的内容与一些国家立法中相应条款和规定的内容进行比较。乌克兰宪法》保障每个人的生命权。然而,专家们越来越多地从人体解剖材料移植的角度对各种侵犯这一权利的行为提出质疑。如今,与捐献者和受捐者有关的刑事犯罪变得难以发现,原因在于高自身利益和高利润、伪装性、网络系统性、广泛的非法基础设施和快速恢复机制、集团组织和与其他犯罪集团的紧密联系、使用欺骗、胁迫、恐吓和其他强迫捐献方法、捐献领域的腐败、与移植有关的大规模犯罪潜伏。非法移植的侦查工作还因其相互矛盾的地理位置而受到影响,因为潜在的捐献者是在世界范围内所谓的 "不景气 "国家招募的,而解剖材料则是在移植学领域高度发达的国家缴获的,这些国家拥有开展此类行动的忠实立法。在乌克兰,由于准备非法捐献器官以换取报酬的人前往国外摘取器官,并在其他国家实施其计划("移植旅游"),也加剧了此类犯罪的侦破。由于社会对移植问题的了解和认识水平较低,人们(包括捐献者和接受者)所谓的 "受害 性"--一系列导致极有可能成为犯罪攻击对象的个人特征(成为犯罪受害者的倾向)--也使该 领域犯罪的侦查工作变得更加复杂。这些原因导致违反人体解剖材料移植法律执行程序的数量不断增加,对公众造成了极大的危害。与此同时,关于此类违法行为刑事责任的法律规定仍存在一定差异。因此,研究外国在移植问题上的经验,比较不同国家《刑法典》的条款规范,分析规范性法律文件中使用的概念及其解释,有助于发现乌克兰立法中的漏洞,澄清措辞,扩大犯罪范围,促进对其构成进行定性,根据欧洲标准对乌克兰法律制度进行调整。
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引用次数: 0
Levels of melatonin and some indicators of angiogenesis, antioxidant system and lipid peroxidation in blood plasma in women with uterine leiomyoma 子宫肌瘤妇女血浆中褪黑激素的水平以及血管生成、抗氧化系统和脂质过氧化的一些指标
Q4 Medicine Pub Date : 2024-05-01 DOI: 10.22494/cot.v12i1.161
B. Sokolov, A. Berbets, Shashi Kant, O. Yuzko
Uterine leiomyoma is one of the most common gynaecological diseases, which often leads to loss of fertility. It is known that in this pathology, damage to the tissues of the uterus is accompanied by oxidative stress, and the mechanisms of its compensation play a decisive role in the process of myometrial regeneration, especially when performing organ-preserving operations. The aim of the study was to determine the levels of melatonin, reproductive hormones and state of angiogenesis, antioxidant system and lipid peroxidation in women of reproductive age who were diagnosed with uterine leiomyoma. Material and methods. 60 women of reproductive age with uterine leiomyoma (study group) were examined. The control group consisted of 20 healthy women of the same age group. Melatonin levels in women's blood were determined once, on an empty stomach, at 8 a.m.; the concentrations of estradiol and progesterone in the follicular phase of the menstrual cycle were also measured. The state of the angiogenesis system was studied by examining the levels of vascular endothelial growth factor (VEGF) and the content of the final metabolites of nitric oxide NO in blood plasma. The activity of the antioxidant system was assessed by blood plasma concentrations of reduced glutathione, glutathione peroxidase, and glutathione transferase. Indicators of lipid peroxidation were investigated by the content of malondialdehyde (MDA) in blood plasma and erythrocytes. Results. It was found that in the patients of the study group with leiomyoma, there was a significantly lower level of melatonin in blood plasma (111.1 ± 18.5 ng/mL) compared to the control group (153.5 ± 8.5 ng/mL), while the concentration of estradiol was almost three times higher (107.4 ± 25.3 pg/mL) compared to the control group (36.2 ± 3.2 pg/mL), and the concentration of progesterone was 1.9 times higher (2.1 ± 0.4 ng/mL compared to 1.1 ± 0.5 ng/mL in the control group). The level of VEGF in blood plasma in women with uterine leiomyoma was also higher (90.4 ± 23.6 pg/mL) compared to the control group (35.1 ± 8.3 pg/mL), as well as the concentration of final metabolites of nitric oxide, which reached 25.3 ± 5.9 pg/mL compared to 9.9 ± 3.9 pg/mL in the control group. The reduced glutathione level in the blood plasma of women with uterine leiomyoma was significantly lower (0.77 ± 0.13 µmol/L) compared to healthy women (1.02 ± 0.14 µmol/L) in the control group, while the concentrations of glutathione-S-transferase and glutathione peroxidase enzymes were higher (161.3 ± 22.3 ng/mL and 235.7 ± 35.9 ng/mL, respectively), whereas in the control group these indicators were 118.9 ± 18.0 ng/mL and 105.3 ± 41.2 ng/mL, respectively. The MDA content in women of the study group was higher, measuring 5.2 ± 0.8 nmol/L in plasma and 10.8 ± 1.1 nmol/L in erythrocytes compared to 2.3 ± 0.8 nmol/L and 5.3 ± 0.8 nmol/L in the control group, respectively. Conclusions. The levels of melatonin and reduced glutathione in the blood pla
子宫肌瘤是最常见的妇科疾病之一,通常会导致丧失生育能力。众所周知,在这种病理情况下,子宫组织的损伤伴随着氧化应激,而氧化应激的补偿机制在子宫肌瘤的再生过程中起着决定性作用,尤其是在进行器官保留手术时。本研究的目的是测定被诊断患有子宫肌瘤的育龄妇女体内褪黑激素、生殖激素的水平以及血管生成、抗氧化系统和脂质过氧化的状态。材料和方法研究对象为 60 名患有子宫肌瘤的育龄妇女(研究组)。对照组由 20 名同年龄组的健康妇女组成。早上 8 点空腹测定一次妇女血液中的褪黑激素水平;还测定了月经周期卵泡期的雌二醇和孕酮浓度。通过检测血浆中血管内皮生长因子(VEGF)的水平和一氧化氮最终代谢物 NO 的含量,研究了血管生成系统的状态。抗氧化系统的活性通过血浆中还原型谷胱甘肽、谷胱甘肽过氧化物酶和谷胱甘肽转移酶的浓度进行评估。血浆和红细胞中丙二醛(MDA)的含量是脂质过氧化的指标。结果发现研究发现,与对照组(153.5 ± 8.5 ng/mL),而雌二醇浓度(107.4 ± 25.3 pg/mL)几乎是对照组(36.2 ± 3.2 pg/mL)的三倍,孕酮浓度是对照组(2.1 ± 0.4 ng/mL,对照组为 1.1 ± 0.5 ng/mL)的 1.9 倍。子宫肌瘤妇女血浆中血管内皮生长因子的水平(90.4 ± 23.6 pg/mL)也高于对照组(35.1 ± 8.3 pg/mL),一氧化氮最终代谢物的浓度也较高,达到 25.3 ± 5.9 pg/mL,而对照组为 9.9 ± 3.9 pg/mL。与健康妇女(1.02 ± 0.14 µmol/L)相比,子宫纵膈肌瘤妇女血浆中的还原型谷胱甘肽水平明显较低(0.77 ± 0.13 µmol/L)。14 µmol/L),而谷胱甘肽-S-转移酶和谷胱甘肽过氧化物酶的浓度较高(分别为 161.3 ± 22.3 ng/mL 和 235.7 ± 35.9 ng/mL),而对照组中这些指标分别为 118.9 ± 18.0 ng/mL 和 105.3 ± 41.2 ng/mL。研究组妇女的 MDA 含量较高,血浆中为 5.2 ± 0.8 nmol/L,红细胞中为 10.8 ± 1.1 nmol/L,而对照组分别为 2.3 ± 0.8 nmol/L 和 5.3 ± 0.8 nmol/L。结论与健康妇女相比,子宫纵膈肌瘤妇女血浆中褪黑激素和还原型谷胱甘肽的水平明显较低,而雌二醇、孕酮、谷胱甘肽-S-转移酶、谷胱甘肽过氧化物酶、血管内皮生长因子、一氧化氮的最终代谢产物以及血浆和红细胞中平均 MDA 含量的浓度则明显较高。在研究组中,血浆中孕酮水平与红细胞中丙二醛含量之间的关系用线性回归方程来描述,正如我们所认为的,这表明孕酮对子宫肌层氧化应激机制有激活作用。我们认为,子宫肌瘤中的氧化应激是由于抗氧化系统(褪黑激素是其中不可或缺的一部分)的活性不足导致的,在雌激素诱导子宫肌瘤增殖的背景下,褪黑激素导致血管生成增强。
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引用次数: 0
Ultrasound-guided accesses for regenerative injection therapy of hip and knee 超声引导下的髋关节和膝关节再生注射治疗通道
Q4 Medicine Pub Date : 2024-05-01 DOI: 10.22494/cot.v12i1.164
S. Strafun, O. Haiko, Y. Holiuk, L. Klymchuk, T. Maslova
Interventional diagnostic and therapeutic technologies have gained considerable popularity in many surgical specialties – cardiology, vascular surgery, neurosurgery, oncology, and in orthopedics and traumatology. But unlike other specialties, ultrasound became the driving force behind the development and implementation of interventional technologies in the treatment of diseases of the musculoskeletal system. In recent years, ultrasound-guided injections have gained significant popularity, as they have given an advantage in accuracy compared to injections without such navigation. The purpose of our study was the development of ultrasound navigation accesses to the hip and knee joints for the interventional application of regenerative technologies in their pathology. The material for the study was the results of ultrasound examination of the hip and knee joints of 486 patients with diseases and injuries of the hip and knee, who were treated in the scientific and practical department of tissue and cell therapy of the State Institute of Traumatology and Orthopedics of the National Academy of Medical Sciences of Ukraine in the period from 2016 to 2023. The results. The following accesses to the knee joint under ultrasound navigation have been developed: suprapatellar longitudinal access for injections into the quadriceps tendon and patellofemoral joint, suprapatellar longitudinal access with knee bending for injections into the upper turn of the knee joint, infrapatellar longitudinal access for injections into the patellar ligament and deep infrapatellar bursa, infrapatellar transverse access for injections into Hoffa’s fat pad, lateral longitudinal access with knee bending for injections into the lateral meniscus, medial longitudinal access with bending in the knee for injections in the medial meniscus, medial transverse access for injections in the medial part of the joint space, lateral transverse access with bending in the knee joint for injections in the lateral part of the joint space, lateral longitudinal access for performing injections in the collateral fibular ligament, medial longitudinal access for performing injections in the collateral tibial ligament, infrapatellar diagonal access for performing injections in the “crow’s foot” area of the knee joint, infrapatellar medial longitudinal access for performing other injection into the medial meniscus and joint capsule, lateral longitudinal access for injections into the tendons of the biceps femoris and hamstrings. The following accesses have been developed for the hip joint: anterior longitudinal access for performing injections in the subcapsular-cervical space, anterior diagonal access for performing injections in the acetabular labrum, capsule-ligament apparatus of the hip and tendon of the rectus femoris muscle, lateral longitudinal access for performing injections in the paratrochanteric region. Conclusions. 13 ultrasonic navigation accesses have been developed for the administration o
介入诊断和治疗技术在心脏科、血管外科、神经外科、肿瘤科、骨科和创伤科等许多外科专科中都得到了广泛应用。但与其他专科不同的是,在治疗肌肉骨骼系统疾病方面,超声波已成为开发和实施介入技术的推动力。近年来,超声波引导下的注射技术越来越受欢迎,因为与没有超声波引导的注射技术相比,超声波引导下的注射技术在准确性方面更具优势。我们研究的目的是开发髋关节和膝关节的超声导航通道,以便在病理中介入应用再生技术。研究材料是 486 名髋关节和膝关节疾病和损伤患者的髋关节和膝关节超声检查结果,这些患者于 2016 年至 2023 年期间在乌克兰国家医学科学院国家创伤和矫形研究所组织和细胞治疗科学与实践部接受治疗。结果如何?在超声波导航下,已开发出以下膝关节入路:髌骨上纵向入路,用于股四头肌腱和髌股关节的注射;髌骨上纵向入路,膝关节弯曲,用于膝关节上翻的注射;髌骨下纵向入路,用于髌韧带和髌下深滑囊的注射、髌下横向入路,用于注射到 Hoffa 脂肪垫;外侧纵向入路,屈膝后用于注射到外侧半月板;内侧纵向入路,屈膝后用于注射到内侧半月板;内侧横向入路,用于注射到关节间隙的内侧部分、弯曲膝关节的外侧横向通道,用于在关节间隙的外侧部分进行注射;外侧纵向通道,用于在腓骨副韧带进行注射;内侧纵向通道,用于在胫骨副韧带进行注射、用于膝关节 "乌鸦嘴 "区域注射的髌下对角入路;用于内侧半月板和关节囊注射的髌下内侧纵向入路;用于股二头肌和腘绳肌肌腱注射的外侧纵向入路。为髋关节开发了以下入路:前纵向入路,用于在髋关节囊下-颈椎间隙进行注射;前对角线入路,用于在髋臼唇、髋关节囊-韧带装置和股直肌腱进行注射;外侧纵向入路,用于在转子旁区域进行注射。结论目前已开发出13条超声波导航通道,用于在膝关节内注射生物技术产品,3条用于在髋关节内注射生物技术产品,这些通道不仅可以检测膝关节和髋关节的关节内和关节旁受损结构,还可以将矫形生物技术产品直接注射到这些结构中,以达到最大的再生效果。
{"title":"Ultrasound-guided accesses for regenerative injection therapy of hip and knee","authors":"S. Strafun, O. Haiko, Y. Holiuk, L. Klymchuk, T. Maslova","doi":"10.22494/cot.v12i1.164","DOIUrl":"https://doi.org/10.22494/cot.v12i1.164","url":null,"abstract":"Interventional diagnostic and therapeutic technologies have gained considerable popularity in many surgical specialties – cardiology, vascular surgery, neurosurgery, oncology, and in orthopedics and traumatology. But unlike other specialties, ultrasound became the driving force behind the development and implementation of interventional technologies in the treatment of diseases of the musculoskeletal system. In recent years, ultrasound-guided injections have gained significant popularity, as they have given an advantage in accuracy compared to injections without such navigation. The purpose of our study was the development of ultrasound navigation accesses to the hip and knee joints for the interventional application of regenerative technologies in their pathology. The material for the study was the results of ultrasound examination of the hip and knee joints of 486 patients with diseases and injuries of the hip and knee, who were treated in the scientific and practical department of tissue and cell therapy of the State Institute of Traumatology and Orthopedics of the National Academy of Medical Sciences of Ukraine in the period from 2016 to 2023. The results. The following accesses to the knee joint under ultrasound navigation have been developed: suprapatellar longitudinal access for injections into the quadriceps tendon and patellofemoral joint, suprapatellar longitudinal access with knee bending for injections into the upper turn of the knee joint, infrapatellar longitudinal access for injections into the patellar ligament and deep infrapatellar bursa, infrapatellar transverse access for injections into Hoffa’s fat pad, lateral longitudinal access with knee bending for injections into the lateral meniscus, medial longitudinal access with bending in the knee for injections in the medial meniscus, medial transverse access for injections in the medial part of the joint space, lateral transverse access with bending in the knee joint for injections in the lateral part of the joint space, lateral longitudinal access for performing injections in the collateral fibular ligament, medial longitudinal access for performing injections in the collateral tibial ligament, infrapatellar diagonal access for performing injections in the “crow’s foot” area of the knee joint, infrapatellar medial longitudinal access for performing other injection into the medial meniscus and joint capsule, lateral longitudinal access for injections into the tendons of the biceps femoris and hamstrings. The following accesses have been developed for the hip joint: anterior longitudinal access for performing injections in the subcapsular-cervical space, anterior diagonal access for performing injections in the acetabular labrum, capsule-ligament apparatus of the hip and tendon of the rectus femoris muscle, lateral longitudinal access for performing injections in the paratrochanteric region. Conclusions. 13 ultrasonic navigation accesses have been developed for the administration o","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"76 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141032447","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
Mesenchymal stem cell therapy modulates macrophage dynamics in ARDS-associated liver injury in rats 间充质干细胞疗法可调节大鼠 ARDS 相关肝损伤中巨噬细胞的动态变化
Q4 Medicine Pub Date : 2023-11-30 DOI: 10.22494/cot.v11i2.157
Olesya Redko, A. Dovgalyuk, Solomiia Kramar, N. Ohinska, Zoia Nebesna, Mykhaylo Korda
Acute Respiratory Distress Syndrome (ARDS) is a life-threatening pulmonary condition characterized by severe hypoxemia and respiratory failure. Beyond its devastating impact on the lungs, ARDS often triggers systemic responses affecting vital organs throughout the body. One such organ commonly affected is the liver, which experiences various degrees of injury during the course of ARDS. Pathophysiological changes in liver during ARDS, particularly polarization of Kupffer cells during the disease and its treatment, have drawn increasing attention. Purpose. To explore the macrophage transformation in liver injury associated with ARDS and investigate the potential of mesenchymal stem cell (MSC) therapy as a means to modulate macrophage responses and mitigate liver injury. Materials and methods. 72 mature male Wistar rats were randomly allocated to nine experimental groups as follows: the control group, groups assessed at 3 days, 7 days, and 28 days following intranasal LPS administration, groups that received 24 hours of LPS followed by 2 days of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), groups exposed to 4 days of LPS and 3 days of hUC-MSCs, groups subjected to 14 days of LPS and 14 days of hUC-MSCs, groups treated with LPS 21 days and 7 days with hUC-MSCs injection, and a control group assessed 3 days after hUC-MSCs injection. For the administration of hUC-MSCs, intraperitoneal injections were performed at a dose of 1∙106 cells/kg body weight. Immunohistochemistry was employed to analyze macrophage subpopulations in liver tissues. Animal experiments adhered to ethical guidelines. Results. Early ARDS stages showed increased M1 macrophages, indicating pro-inflammatory responses, while later stages showed M2 macrophage activation, suggestive of anti-inflammatory and tissue repair roles. MSC administration facilitated the transition from M1 to M2 macrophages, promoting an anti-inflammatory milieu. Conclusions. MSCs demonstrate the potential to modulate macrophage polarization into M2 anti-inflammatory phenotype. Such findings reflect one of the mechanisms of MSC action which holds practical significance for future ARDS therapies, aiming to mitigate excessive inflammation and enhance tissue repair.
急性呼吸窘迫综合征(ARDS)是一种以严重低氧血症和呼吸衰竭为特征的危及生命的肺部疾病。除了对肺部造成破坏性影响外,ARDS 还经常引发全身反应,影响全身的重要器官。其中一个常受影响的器官是肝脏,它在 ARDS 过程中会受到不同程度的损伤。ARDS 期间肝脏的病理生理学变化,特别是疾病期间 Kupffer 细胞的极化及其治疗,已引起越来越多的关注。研究目的探索巨噬细胞在与 ARDS 相关的肝损伤中的转化,并研究间充质干细胞(MSC)疗法作为调节巨噬细胞反应和减轻肝损伤的一种手段的潜力。材料与方法将 72 只成熟雄性 Wistar 大鼠随机分配到以下 9 个实验组:对照组;在鼻内注射 LPS 后 3 天、7 天和 28 天进行评估的各组;接受 24 小时 LPS 后再注射 2 天人脐带间充质干细胞(hUC-MSCs)的各组、暴露于 4 天 LPS 和 3 天人脐带间充质干细胞的组,暴露于 14 天 LPS 和 14 天人脐带间充质干细胞的组,接受 LPS 治疗 21 天和注射人脐带间充质干细胞 7 天的组,以及在注射人脐带间充质干细胞 3 天后进行评估的对照组。腹腔注射 hUC-MSCs 的剂量为 1∙106 cells/kg 体重。免疫组化技术用于分析肝脏组织中的巨噬细胞亚群。动物实验符合伦理准则。结果ARDS早期阶段显示M1巨噬细胞增加,表明有促炎反应,而后期阶段显示M2巨噬细胞活化,表明有抗炎和组织修复作用。间充质干细胞的施用促进了巨噬细胞从M1向M2的转变,促进了抗炎环境的形成。结论间充质干细胞具有调节巨噬细胞极化为 M2 抗炎表型的潜力。这些发现反映了间充质干细胞的作用机制之一,对未来的ARDS疗法具有实际意义,旨在缓解过度炎症并促进组织修复。
{"title":"Mesenchymal stem cell therapy modulates macrophage dynamics in ARDS-associated liver injury in rats","authors":"Olesya Redko, A. Dovgalyuk, Solomiia Kramar, N. Ohinska, Zoia Nebesna, Mykhaylo Korda","doi":"10.22494/cot.v11i2.157","DOIUrl":"https://doi.org/10.22494/cot.v11i2.157","url":null,"abstract":"Acute Respiratory Distress Syndrome (ARDS) is a life-threatening pulmonary condition characterized by severe hypoxemia and respiratory failure. Beyond its devastating impact on the lungs, ARDS often triggers systemic responses affecting vital organs throughout the body. One such organ commonly affected is the liver, which experiences various degrees of injury during the course of ARDS. Pathophysiological changes in liver during ARDS, particularly polarization of Kupffer cells during the disease and its treatment, have drawn increasing attention. Purpose. To explore the macrophage transformation in liver injury associated with ARDS and investigate the potential of mesenchymal stem cell (MSC) therapy as a means to modulate macrophage responses and mitigate liver injury. Materials and methods. 72 mature male Wistar rats were randomly allocated to nine experimental groups as follows: the control group, groups assessed at 3 days, 7 days, and 28 days following intranasal LPS administration, groups that received 24 hours of LPS followed by 2 days of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), groups exposed to 4 days of LPS and 3 days of hUC-MSCs, groups subjected to 14 days of LPS and 14 days of hUC-MSCs, groups treated with LPS 21 days and 7 days with hUC-MSCs injection, and a control group assessed 3 days after hUC-MSCs injection. For the administration of hUC-MSCs, intraperitoneal injections were performed at a dose of 1∙106 cells/kg body weight. Immunohistochemistry was employed to analyze macrophage subpopulations in liver tissues. Animal experiments adhered to ethical guidelines. Results. Early ARDS stages showed increased M1 macrophages, indicating pro-inflammatory responses, while later stages showed M2 macrophage activation, suggestive of anti-inflammatory and tissue repair roles. MSC administration facilitated the transition from M1 to M2 macrophages, promoting an anti-inflammatory milieu. Conclusions. MSCs demonstrate the potential to modulate macrophage polarization into M2 anti-inflammatory phenotype. Such findings reflect one of the mechanisms of MSC action which holds practical significance for future ARDS therapies, aiming to mitigate excessive inflammation and enhance tissue repair.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"145 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139196959","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
The effects of human umbilical cord-derived multipotent mesenchymal stromal cells transplantation in mice of different strains with an experimental model of parkinsonism 人脐带源性多能间充质间质细胞移植对不同品系小鼠帕金森病模型的影响
Q4 Medicine Pub Date : 2023-11-30 DOI: 10.22494/cot.v11i2.155
Iryna Labunets, Tetyana Panteleymonova, Vitalii Kyryk, Olena Toporova, Zoya Litoschenko
One of the promising directions in cell therapy for Parkinson's disease or parkinsonism is the transplantation of multipotent mesenchymal stromal cells from various sources, including human umbilical cord (hUC-MMSCs), the effectiveness of which may depend on the recipient's genotype. Objective. To compare the impact of transplanted MMSC-P on behavior, T-lymphocytes, and macrophages in the brain and lymphoid organs of mice from different lines with a toxic model of parkinsonism. Materials and methods. Adult (6-7 months old) male mice of FVB/N (genotype H-2q) and 129/Sv (genotype H-2b) strains were administered the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dose of 30 mg/kg (control group), and after 7 days, hUC-MMSCs (500,000 cells) were transplanted into the tail vein. Behavioral reactions were assessed in open field, rigidity, and rotarod tests. The relative content of T-lymphocytes and activated macrophages in the brain was measured by flow cytometry, and the mass of lymphoid organs was determined. Results. Under the influence of MPTP, the number of rearings, "sniffs into the nest," body length, and step length decreased, the number of boluses increased in FVB/N and 129/Sv mice, and the number of squares crossed in the open field test decreased in 129/Sv mice. In the brain of mice from both lines, the content of activated macrophages increased, and in FVB/N mice, the number of T-lymphocytes also increased. The thymus mass decreased in mice from both lines, while the spleen mass decreased only in 129/Sv mice. The transplantation of hUC-MMSCs improved predominantly motor activity in FVB/N mice, while in 129/Sv mice, emotional activity improved, and manifestations of rigidity decreased in mice from both lines. The content of T-lymphocytes and activated macrophages in the brain of mice from both lines, as well as the thymus mass, corresponded to the values of intact animals. MMSC transplantation promoted the survival of FVB/N and 129/Sv mice with the MPTP-induced parkinsonism model. Conclusions. The manifestations of behavioral disorders, changes in the content of T-lymphocytes and activated macrophages in the brain, and the mass of lymphoid organs in mice with the MPTP-induced parkinsonism model, as well as the positive effects of transplanted hUC-MMSCs in these animals, largely depend on their genotype according to the H-2 system (analogous to the HLA system in humans). The results may provide a basis for developing personalized cell therapy for this pathology using multipotent mesenchymal stromal cells.
帕金森氏病或帕金森病的细胞治疗有希望的方向之一是移植各种来源的多能间充质间质细胞,包括人脐带(hUC-MMSCs),其有效性可能取决于受体的基因型。目标。比较移植骨髓间充质干细胞- p对不同系帕金森中毒模型小鼠行为、脑和淋巴器官中t淋巴细胞和巨噬细胞的影响。材料和方法。将FVB/N(基因型H-2q)和129/Sv(基因型H-2b)的成年雄性小鼠(6-7月龄)按30 mg/kg的剂量给药(对照组)1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP), 7 d后将hucc - mmscs(500,000个细胞)移植到尾静脉。行为反应通过开阔场地、刚性和旋转杆试验进行评估。流式细胞术测定大鼠脑内t淋巴细胞和活化巨噬细胞的相对含量,测定淋巴器官的质量。结果。在MPTP的影响下,FVB/N和129/Sv小鼠的产仔次数、“入巢次数”、体长和步长减少,丸数增加,129/Sv小鼠的空地试验中交叉方块数减少。两系小鼠脑内活化巨噬细胞含量均增加,FVB/N小鼠t淋巴细胞数量也增加。两系小鼠胸腺肿块均减少,而脾脏肿块仅在129/Sv小鼠中减少。hUC-MMSCs移植在FVB/N小鼠中主要改善了运动活动,而在129/Sv小鼠中,两系小鼠的情绪活动得到改善,僵硬症状减少。两系小鼠脑及胸腺肿块中t淋巴细胞和活化巨噬细胞的含量与完整动物的值一致。MMSC移植可促进mptp诱导的帕金森模型FVB/N和129/Sv小鼠的存活。结论。mptp诱导的帕金森模型小鼠的行为障碍的表现、脑内t淋巴细胞和活化巨噬细胞含量的变化、淋巴器官的质量,以及移植hUC-MMSCs的积极作用,在很大程度上取决于它们根据H-2系统(类似于人类的HLA系统)的基因型。结果可能为利用多能间充质间质细胞开发针对这种病理的个性化细胞治疗提供基础。
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引用次数: 0
Sleep disorders and changes in melatonin concentrations in pregnant women with preeclampsia 子痫前期孕妇的睡眠障碍和褪黑激素浓度的变化
Q4 Medicine Pub Date : 2023-11-30 DOI: 10.22494/cot.v11i2.158
Ruslan Savka, Andrii Berbets
Melatonin plays a significant role in the development of normal pregnancy, in particular, it contributes to the successful implantation of the fertilized egg, affects the act of childbirth, is actively produced by the trophoblast and placenta, reduces oxidative stress, in particular, with preeclampsia. In addition, melatonin is one of the essential hormones in the protection of the endothelium and stem cells from the oxidant stress. Objective – to study the mechanisms of development, terms of manifestation, and types of sleep disorders, as well as changes in the concentrations of melatonin in the blood of pregnant women with preeclampsia. Material and methods. 50 pregnant women at a mean age of 29.1±3.4 years who had preeclampsia in the 3rd pregnancy trimester were examined (experimental group). All women in the research group had a gestation term of 30-32 weeks of pregnancy. The control group consisted of 33 women with a mean age of 31.2±6.6 years who had an uncomplicated pregnancy. The presence of sleep disorders was established using a questionnaire: pregnant women were asked about the term of pregnancy in which complaints of sleep disorders appeared, the nature of sleep disorders, the frequency of episodes of sleep disorders (how many times a week such a condition was noted), etc. The concentration of melatonin in the venous blood of the examined pregnant women was also determined, for which IBL melatonin ELISA diagnostic kits manufactured by IBL, Germany were used. Blood was taken at 9:00 a.m., on an empty stomach, and all patients were analyzed at the same time of a day. Results and their discussion. The study showed that sleep disorders in pregnant women with pre-eclampsia, which complicates the pregnancy in the 3rd trimester, occurred earlier, compared to women with an uncomplicated course of pregnancy: pregnant women with pre-eclampsia were more likely to notice worsening of sleep, starting from 22-30 weeks of pregnancy (in 26.0 % of cases), while in pregnant women with a physiological course of gestation, similar complaints appeared mainly after 30 weeks. In the third trimester of pregnancy women with preeclampsia were more likely to wake up 2 or more times per night (in 68.0 % of cases) compared to controls (in 23.3 % of cases, p < 0.001) and 3 or more times per night per week (in 54.0 % of cases, in controls – in 16.7 % of cases, p < 0.001), which may be a consequence of a disorder of the function of the pineal gland. Women with preeclampsia were more likely (56.0 % vs. 13.3 % in the control group, p < 0.01) to use gadgets (electronic devices, mainly smartphones) for more than 2 hours after 9:00 p.m., which also negatively affects the function of the pineal gland. In pregnant women whose pregnancy was complicated by preeclampsia in the 3rd trimester, a significant (1.78-fold) decrease in the level of melatonin in venous blood taken at 9 a.m. was observed, compared to women with an uncomplicated pregnancy (p = 0.029). Conclusions. Slee
褪黑素在正常妊娠的发展中起着重要的作用,特别是,它有助于受精卵的成功着床,影响分娩的行为,由滋养细胞和胎盘积极产生,减少氧化应激,特别是与先兆子痫。此外,褪黑激素是保护内皮细胞和干细胞免受氧化应激的重要激素之一。目的:研究子痫前期孕妇睡眠障碍的发展机制、表现形式、类型以及血液中褪黑激素浓度的变化。材料和方法。选取平均年龄29.1±3.4岁的妊娠晚期先兆子痫孕妇50例(实验组)。研究小组中所有女性的妊娠期均为30-32周。对照组包括33名平均年龄(31.2±6.6岁)无并发症妊娠的妇女。睡眠障碍的存在是通过一份调查问卷来确定的:孕妇被问及出现睡眠障碍的孕期、睡眠障碍的性质、睡眠障碍发作的频率(每周有多少次出现这种情况),等等。检测孕妇静脉血中褪黑素的浓度,使用德国IBL公司生产的IBL褪黑素ELISA诊断试剂盒。上午9点空腹抽血,并在一天的同一时间对所有患者进行分析。结果和讨论。研究表明,与妊娠无并发症的孕妇相比,患有子痫前期的孕妇的睡眠障碍发生得更早,子痫前期的孕妇在妊娠22-30周(占26.0%)更容易注意到睡眠恶化,而在生理妊娠期的孕妇中,类似的症状主要出现在30周之后。子痫前期会使妊娠晚期的妊娠复杂化。在妊娠晚期,与对照组(23.3%)相比,患有先兆子痫的妇女每晚更有可能醒来2次或2次以上(占68.0%)。0.001),每周每晚3次或3次以上(54.0%的病例,对照组- 16.7%的病例,p <0.001),这可能是松果体功能紊乱的结果。有先兆子痫的女性更有可能(56.0% vs. 13.3%, p <在晚上9点以后使用电子设备(以智能手机为主)超过2小时,也会对松果体的功能产生负面影响。在妊娠晚期合并先兆子痫的孕妇中,与未合并妊娠的妇女相比,在上午9点测得的静脉血中褪黑素水平显著下降(1.78倍)(p = 0.029)。结论。与妊娠过程无并发症的孕妇相比,患有先兆子痫的孕妇睡眠障碍发生得更早,也更容易表达。在我们看来,在妊娠中期出现失眠的抱怨,可以被认为是子痫前期松果体功能障碍的诊断标志。在松果体每日活动最少(上午9点)的背景下,孕妇子痫前期褪黑素水平下降,表明胎盘褪黑素产生功能下降,这可能对胎儿和胎盘干细胞的状况产生影响。
{"title":"Sleep disorders and changes in melatonin concentrations in pregnant women with preeclampsia","authors":"Ruslan Savka, Andrii Berbets","doi":"10.22494/cot.v11i2.158","DOIUrl":"https://doi.org/10.22494/cot.v11i2.158","url":null,"abstract":"Melatonin plays a significant role in the development of normal pregnancy, in particular, it contributes to the successful implantation of the fertilized egg, affects the act of childbirth, is actively produced by the trophoblast and placenta, reduces oxidative stress, in particular, with preeclampsia. In addition, melatonin is one of the essential hormones in the protection of the endothelium and stem cells from the oxidant stress. Objective – to study the mechanisms of development, terms of manifestation, and types of sleep disorders, as well as changes in the concentrations of melatonin in the blood of pregnant women with preeclampsia. Material and methods. 50 pregnant women at a mean age of 29.1±3.4 years who had preeclampsia in the 3rd pregnancy trimester were examined (experimental group). All women in the research group had a gestation term of 30-32 weeks of pregnancy. The control group consisted of 33 women with a mean age of 31.2±6.6 years who had an uncomplicated pregnancy. The presence of sleep disorders was established using a questionnaire: pregnant women were asked about the term of pregnancy in which complaints of sleep disorders appeared, the nature of sleep disorders, the frequency of episodes of sleep disorders (how many times a week such a condition was noted), etc. The concentration of melatonin in the venous blood of the examined pregnant women was also determined, for which IBL melatonin ELISA diagnostic kits manufactured by IBL, Germany were used. Blood was taken at 9:00 a.m., on an empty stomach, and all patients were analyzed at the same time of a day. Results and their discussion. The study showed that sleep disorders in pregnant women with pre-eclampsia, which complicates the pregnancy in the 3rd trimester, occurred earlier, compared to women with an uncomplicated course of pregnancy: pregnant women with pre-eclampsia were more likely to notice worsening of sleep, starting from 22-30 weeks of pregnancy (in 26.0 % of cases), while in pregnant women with a physiological course of gestation, similar complaints appeared mainly after 30 weeks. In the third trimester of pregnancy women with preeclampsia were more likely to wake up 2 or more times per night (in 68.0 % of cases) compared to controls (in 23.3 % of cases, p < 0.001) and 3 or more times per night per week (in 54.0 % of cases, in controls – in 16.7 % of cases, p < 0.001), which may be a consequence of a disorder of the function of the pineal gland. Women with preeclampsia were more likely (56.0 % vs. 13.3 % in the control group, p < 0.01) to use gadgets (electronic devices, mainly smartphones) for more than 2 hours after 9:00 p.m., which also negatively affects the function of the pineal gland. In pregnant women whose pregnancy was complicated by preeclampsia in the 3rd trimester, a significant (1.78-fold) decrease in the level of melatonin in venous blood taken at 9 a.m. was observed, compared to women with an uncomplicated pregnancy (p = 0.029). Conclusions. Slee","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"51 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136227830","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
The efficacy of two models – MEAF and pMELD, as indicators of lethal outcome in early postoperative period after liver transplantation in children MEAF和pMELD两种模型作为儿童肝移植术后早期致死结局指标的疗效观察
Q4 Medicine Pub Date : 2023-11-30 DOI: 10.22494/cot.v11i2.153
Andrey Goncharov, Yordanka Uzunova
The current study is aiming to prove the effectiveness and compare “Model for Early Allograft Function” (MEAF) and “postoperative Model for End-stage Liver Disease” (pMELD) in the early posttransplant setting in children. Methods. We did a retrospective study on 43 liver transplant patients for a 17-year period between the ages 0 – 18 years. MEAF and pMELD were calculated on the third and fifth postoperative day, respectively, and a Cox regression analysis was performed to find the correlation between them and mortality in the early postoperative period (EPOP). Results. Both scores proved to be statistically significant and applicable in EPOP. MEAF had P value of 0.0003 and a hazard ratio of 10.99, while pMELD demonstrated P value of 0.003 and a hazard ratio of 1.24. Conclusions. Both MEAF and pMELD can be used for the diagnostics of early allograft dysfunction and predicting the outcome of the transplantation, with MEAF having the upper hand.
本研究旨在证明“早期同种异体移植功能模型”(MEAF)和“终末期肝病术后模型”(pMELD)在儿童移植后早期环境中的有效性并进行比较。方法。我们对43例肝移植患者进行了回顾性研究,时间跨度为17年,年龄在0 - 18岁之间。分别于术后第3天和第5天计算MEAF和pMELD,并进行Cox回归分析,寻找其与术后早期死亡率(EPOP)的相关性。结果。两项评分均具有统计学意义,适用于EPOP。MEAF的P值为0.0003,风险比为10.99,pMELD的P值为0.003,风险比为1.24。结论。MEAF和pMELD均可用于异体移植早期功能障碍的诊断和移植预后的预测,其中MEAF具有优势。
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引用次数: 0
The improvement of endothelial function by inhibition of platelet activity using acetylsalicylic acid in patients with arterial hypertension 乙酰水杨酸抑制血小板活性对高血压患者内皮功能的改善
Q4 Medicine Pub Date : 2023-11-30 DOI: 10.22494/cot.v11i2.154
Tatyana Talaieva, Larysa Mishchenko, Iryna Tretyak, Olena Matova, Natalia Vasilinchuk, Larysa Vavilova
In accordance with modern ideas about the pathogenesis of thrombotic complications of cardiovascular diseases (myocardial infarction, stroke), it should be noted that platelets and platelet humoral factors play a key role in the development of thrombosis. Activated platelets are able to activate both endotheliocytes and pro-inflammatory cells - monocytes/macrophages, which take a direct part in the formation and progression of atherosclerotic plaque. The purpose of the study is to investigate the potential improvement of endothelial function through the inhibition of platelet activity using acetylsalicylic acid in patients with arterial hypertension and established atherosclerotic cardiovascular diseases. Materials and methods. We enrolled 41 patients with arterial hypertension and established atherosclerotic cardiovascular diseases in our study. The participants were divided into two groups. Group 1 comprised 20 patients who were already taking acetylsalicylic acid (ASA) before the study, while Group 2 consisted of 21 patients who had not received ASA before participating. During the 6-month study period, patients from both groups received ASA (75 mg once a day) as part of their basic therapy, which included antihypertensive and statin therapy. Platelet activity was assessed in all patients before the study and at the final stage by determining the expression of glycoproteins GPIIb-IIIa and P-selectin on their surface. Additionally, the content of endothelial progenitor cells (phenotype CD45-CD31+CD133+) and desquamated endothelial cells (phenotype CD45-CD31+CD133-) in the blood was analyzed using flow cytometry. ELISA was employed to measure the content of C-reactive protein, cytokines TNF-α and IL-10, as well as asymmetric dimethylarginine (ADMA) in the blood. Finally, all patients underwent a test with flow-dependent vasodilation of the brachial artery. Results. In patients who did not receive ASA before the study, there was a higher level of platelet activity in peripheral blood flow, along with signs of more pronounced endothelial dysfunction compared to those who received it. After 6 months of taking ASA alongside standard antihypertensive therapy, the activation level of circulating blood platelets decreased in both groups. Specifically, in patients of group 1, the expression level of CD41 (GPIIb) decreased by 31.8 % (p < 0.01), and CD61 (GPIIIa) decreased by 15.2 % (p < 0.01). In group 2 patients, the suppression of platelet activity was even more pronounced, with the expression level of CD41 (GPIIb) decreasing by 55.2 % (p < 0.001), and CD61 (GPIIIa) decreasing by 27.5 % (p < 0.05). Furthermore, in patients of group 1, the percentage of platelets carrying P-selectin on the surface decreased by 78.1 % (p < 0.01). In group 2, the number of such platelets also significantly decreased by 42.5 % (p < 0.05). The number of progenitor cells of endothelial cells in the circulating blood increased significantly in both groups, showing a 3-fold in
根据现代关于心血管疾病(心肌梗死、卒中)血栓性并发症发病机制的观点,应该注意到血小板和血小板体液因子在血栓形成的发展中起着关键作用。活化的血小板能够激活内皮细胞和促炎细胞-单核细胞/巨噬细胞,它们直接参与动脉粥样硬化斑块的形成和进展。本研究的目的是探讨乙酰水杨酸对高血压和动脉粥样硬化性心血管疾病患者血小板活性的抑制对内皮功能的潜在改善。材料和方法。在我们的研究中,我们招募了41名患有动脉高血压和动脉粥样硬化性心血管疾病的患者。参与者被分成两组。第1组包括20例在研究前已服用乙酰水杨酸(ASA)的患者,第2组包括21例参与研究前未服用ASA的患者。在6个月的研究期间,两组患者均接受ASA (75 mg,每天1次)作为基础治疗的一部分,其中包括抗高血压和他汀类药物治疗。在研究前和最后阶段,通过测定血小板表面糖蛋白GPIIb-IIIa和p -选择素的表达来评估所有患者的血小板活性。此外,用流式细胞术分析血液中内皮祖细胞(表型为CD45-CD31+CD133+)和脱皮内皮细胞(表型为CD45-CD31+CD133-)的含量。ELISA法测定大鼠血液中c反应蛋白、细胞因子TNF-α、IL-10及不对称二甲基精氨酸(ADMA)的含量。最后,所有患者都进行了肱动脉血流依赖性血管舒张试验。结果。在研究之前未接受ASA治疗的患者,与接受ASA治疗的患者相比,外周血中血小板活性水平更高,内皮功能障碍的迹象更明显。在标准降压治疗的同时服用ASA 6个月后,两组循环血小板活化水平均下降。具体来说,在1组患者中,CD41 (GPIIb)的表达水平下降了31.8% (p <0.01), CD61 (GPIIIa)降低15.2% (p <0.01)。在2组患者中,血小板活性的抑制更为明显,CD41 (GPIIb)表达水平下降55.2% (p <0.001), CD61 (GPIIIa)下降27.5% (p <0.05)。此外,在第1组患者中,表面携带p -选择素的血小板百分比下降了78.1% (p <0.01)。在第2组,这种血小板的数量也显著减少了42.5% (p <0.05)。两组患者循环血液中内皮细胞祖细胞数量均显著增加,其中1组患者增加3倍(p <0.001),第2组患者增加2.3倍(p<0.001)。在两组患者中,观察到内皮依赖性血管舒张指数显著增加2倍(p <0.01)。研究结束时,1组和2组患者血液中CRP水平分别下降了12.2%和18.8%,促炎细胞因子TNF-α分别下降了50%和57% (p <0.001)。结论。ASA引起的高血压和动脉粥样硬化性心血管疾病患者血小板活性降低与全身炎症强度的显著改变和内皮功能的恢复有关。这些发现表明ASA在调节血小板功能和内皮健康方面具有潜在的治疗作用。
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引用次数: 0
Regenerative potential and clinical application of mesenchymal stem cell-derived exosomes (review) 间充质干细胞来源外泌体的再生潜力及临床应用(综述)
Q4 Medicine Pub Date : 2023-11-30 DOI: 10.22494/cot.v11i2.152
Inna Gordiienko, Maryna Shamshur, Svitlana Novikova, Igor Zlatskiy, Alona Zlatska
For more than 50 years, mesenchymal stem cells have been extensively studied as a therapeutic agent in the treatment of various diseases. It became clear that MSC-derived secretome including the growth factors, cytokines, microvesicles and exosomes are the major drivers in the realization of beneficial effect of MSC-based therapy. Exosomes play an important role in the organism homeostasis and diseases development working as a vehicle for the transfer of the signaling and regulatory molecules between cells. Exosomes size, stability, cargo content that reflect the physiological state of parent cells make them an attractive new tool for regenerative medicine. Cell-free therapy or cell therapy 2.0 are being developed. Here, we review the molecular profile of exosomes derived from different MSC sources and their biological properties, the results of clinical application of MSC-derived exosomes in the of treatment COVID-19, alopecia, skin aging and osteoarthritis, discuss what issues exist in the development and application of a new biomedical product. The purpose of this study was to analyze the literature data on the regenerative potential and clinical application of exosomes derived from mesenchymal stem cells. Materials and methods. An analytical review of literature data was conducted using the information analysis of Medline (PubMed), Web of Science and Scopus databases, Google Scholar and the Cochrane Central Register of Controlled Trials (CENTRAL) and other sources until 2022 inclusive using the keywords: «exosomes», «mesenchymal stem cells», «cell-free therapy», «secretome», «miRNA» Results. In this review, we consider the molecular profile of exosomes derived from different MSC sources and their biological properties, the results of clinical application of MSC-derived exosomes in the treatment of COVID-19, alopecia, skin aging and osteoarthritis, discuss what issues exist in the development and application of a new biomedical product. Conclusion. The study, research and development of biotechnological products based on exosomes from different stem cell types are new stages in the development of regenerative medicine. Understanding the unique biological properties of MSCs derived from various tissue sources is one of the keys to develop effective exosomes-based biotechnological products to address specific medical goals.
50多年来,间充质干细胞作为一种治疗多种疾病的药物被广泛研究。显然,包括生长因子、细胞因子、微囊泡和外泌体在内的骨髓间质干细胞衍生的分泌组是实现骨髓间质干细胞治疗有益效果的主要驱动因素。外泌体作为信号和调控分子在细胞间传递的载体,在生物稳态和疾病发展中起着重要作用。外泌体的大小、稳定性和载货量反映了亲本细胞的生理状态,使其成为有吸引力的再生医学新工具。无细胞疗法或细胞疗法2.0正在开发中。本文综述了不同来源间质干细胞外泌体的分子特征及其生物学特性,以及间质干细胞外泌体在治疗新冠肺炎、脱发、皮肤老化和骨关节炎等方面的临床应用结果,并探讨了新型生物医学产品的开发和应用中存在的问题。本研究的目的是分析间充质干细胞外泌体的再生潜力和临床应用的文献资料。材料和方法。使用Medline (PubMed)、Web of Science和Scopus数据库、Google Scholar和Cochrane Central Register of Controlled Trials (Central)和其他来源的信息分析,对文献数据进行分析性回顾,直到2022年,使用关键词:“外泌体”、“间充质干细胞”、“无细胞治疗”、“分泌组”、“miRNA”结果。本文综述了不同来源间质干细胞外泌体的分子特征及其生物学特性,以及间质干细胞外泌体在治疗新冠肺炎、脱发、皮肤老化和骨关节炎等方面的临床应用结果,并讨论了新型生物医学产品的开发和应用中存在的问题。结论。基于不同干细胞类型外泌体的生物技术产品的研究和开发是再生医学发展的新阶段。了解来自不同组织来源的间充质干细胞的独特生物学特性是开发有效的基于外泌体的生物技术产品以解决特定医疗目标的关键之一。
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Cell and Organ Transplantology
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