Recently, the association of polymorphism rs1800562 (p.C282Y) in the hemochromatosis (HFE) gene with the increased risk of venous ulceration was shown. We hypothesized that HFE gene polymorphism might be involved not only in ulceration process, but also in susceptibility to primary varicose veins. We genotyped HFE p.C282Y (rs1800562) and p.H63D (rs1799945) variants in patients with primary varicose veins (n = 463) and in the control group (n = 754). In our study, p.282Y variant (rs1800562 A allele) was significantly associated with the risk of varicose veins (OR 1.79, 95 % CI = 1.11-2.89, P = 0.02). A borderline significant reverse association of p.63D variant (rs1799945 G allele) with venous leg ulcer development was revealed in Russians (OR 0.25, 95 % CI = 0.06-1.00, P = 0.05), but not in the meta-analysis (P = 0.56). We conclude that the HFE gene polymorphism can affect the risk of developing primary varicose veins.
Институт химической биологии и фундаментальной медицины Сибирского отделения Российской академии наук 1 , Федеральный исследовательский центр фундаментальной и трансляционной медицины Министерства науки и высшего образования РФ, Институт молекулярной патологии и патоморфологии 2 , АО Медицинский центр «Авиценна» 3 , г. Новосибирск, Российская Федерация Цель. Изучить результаты применения экстрацеллюлярных микровезикул мультипотентных мезенхимальных стромальных клеток костномозгового происхождения крысы (ЭМВ) для регенерации дефекта костной ткани кроликов, а также получить данные о сохранности ЭМВ в тканях после их введения. Материал и методы. В проксимальных мыщелках большеберцовой кости беспородных кроликов создавали дефект диаметром 2 мм и глубиной 4 мм. На левой конечности дефект заполняли физиологическим раствором, на правой конечности в дефект вводили 50 мкг ЭМВ. Результаты. К 12-м суткам в контроле у всех кроликов сохранялся дефект в костной ткани с формирующимися костными структурами и грубым толстым рубцом на границе с неповрежденными участками. После введения ЭМВ в большинстве случаев повреждение кости не было найдено, рубец был тонким, с упорядоченными структурами межклеточного матрикса. Спустя 12 суток после применения ЭМВ, меченных Vybrant ® CM-Dil, в надкостнице и рядом с ней, костном мозге, сосудах костной ткани были найдены единичные, очень мелкие, пылевидные объекты, флюоресцирующие красным цветом на фоне применения фильтра для родамина. Иногда был отмечен четкий красный оттенок включений в крупных клеточных элементах-макрофагах. К 21-му дню справа (опыт) в 4 случаях из 5 на месте дефекта костной ткани были найдены только структуры рубца, тогда как слева (контроль)-только в 2 наблюдениях из 5. Заключение. Предварительные результаты применения ЭМВ для регенерации дефекта костной ткани в эксперименте свидетельствуют о более быстром заживлении, увеличении частоты успешной регенерации поврежденной кости и формировании менее грубой костной мозоли. У кроликов ЭМВ присутствуют в тканях в месте применения не менее 12 суток. Часть введенных ЭМВ оказывается в макрофагах. Ключевые слова: костная ткань, регенерация костной ткани, экстрацеллюлярные микровезикулы, макрофаги, люминесцентная микроскопия Objective. To study the results of application extracellular microvesicles from rat multipotent mesenchymal stromal cells of the bone marrow origin (EMV) for the regeneration of rabbit bone defects, as well as to obtain data about the EMV preservation after their introduction into tissues. Methods. The bone defect (2 mm diameter and 4 mm depth) was created in the proximal condyles of the outbred rabbit tibia. On the left limb the bone defect was filled with saline, on the right-the 50 μ g EMV were introduced into defect. Results. By the 12 th day all control rabbits had retained a defect in the bone tissue with forming bone structures and hypertrophiс scar in the border with intact areas. In the most cases after the EMV introduction, no bone damage was found; the scar was thin with ordered structures of the interc...
A coherent model proposed incorporates the relevant signaling networks and will hopefully aid further studies on varicose vein pathogenesis.
When administered intravenously, extracellular vesicles derived from multipotent stromal cells (MSC EVs) immediately pass through the lungs along with the blood and regularly spread to all organs. When administered intraperitoneally, they are absorbed either into the blood or into the lymph and are quickly disseminated throughout the body. The possibility of generalized spread of MSC EVs to distant organs in case of local intratissular administration remains unexplored. However, it is impossible to exclude MSC EV influence on tissues distant from the injection site due to the active or passive migration of these injected nanoparticles through the vessels. The research is based on findings obtained when studying the samples of lungs, heart, spleen, and liver of outbred rabbits of both sexes weighing 3–4 kg at various times after the injection of EVs derived from MSCs of bone marrow origin and labeled by PKH26 into an artificially created defect of the proximal condyle of the tibia. MSC EVs were isolated by serial ultracentrifugation and characterized by transmission electron microscopy and flow cytometry. After the introduction of MSC EVs into the damaged proximal condyle of the tibia of rabbits, these MSC EVs can be found most frequently in the lungs, myocardium, liver, and spleen. MSC EVs enter all of these organs with the blood flow. The lungs contained the maximum number of labeled MSC EVs; moreover, they were often associated with detritus and were located in the lumen of the alveoli. In the capillary network of various organs except the myocardium, MSC EVs are adsorbed by paravasal phagocytes; in some cases, specifically labeled small dust-like objects can be detected throughout the entire experiment—up to ten days of observation. Therefore, we can conclude that the entire body, including distant organs, is effected both by antigenic detritus, which appeared in the bloodstream after extensive surgery, and MSC EVs introduced from the outside.
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