Репозиторий Университета

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. We studied the expression of Hif-1α, Nf-κb, and Vegf genes in the liver and serum levels of HIF-1α, erythropoietin, VEGF, TGF-β, 8-isoprostane, and corticosterone in Wistar rats with different resistance to hypoxia in 5 and 90 min after acute exposure to hypobaric hypoxia. In 5 min after hypoxic exposure, Hif-1α expression in the liver and serum levels of erythropoietin, VEGF, and TGF-β in high-resistant rats were higher than in low-resistant animals. In highresistant rats, the increment in expression of Nf-κb gene responsible for the control over the inflammatory processes was more pronounced than in low-resistant animals. In 90 min after hypoxic exposure, the serum levels of HIF-1α, erythropoietin, VEGF, and TGF-β returned to normal in high-resistant rats, while in low-resistant animals, an increase in 8-isoprostane and TGF-β concentrations was observed. The rats with different resistance to hypoxia were characterized by different changes in biomolecular parameters determining predilection to inflammatory diseases.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Colostrum is produced in the first days postpartum. It is a known source of immune mediators for a newborn within the first week of life. Although it is still unclear if colostrum composition varies between populations, recent data suggest differences. Hepatocyte growth factor (HGF); transforming growth factor-β (TGF-β) 1, 2, and 3; and immunoglobulin A (IgA) are key immunological components of colostrum that stimulate neonatal gastrointestinal and immune system development. We aimed to investigate the differences in the concentration between immune markers in the colostrum of mothers living in Burundi and Italy, and to identify the factors associated with differences. In this cross-sectional birth cohort study, a total of 99 colostrum samples from Burundian (n = 23) and Italian (n = 76) women were collected at 0 to 6 days postpartum. A clinical chemistry analyser was used for IgA quantification and electro-chemiluminescence, for HGF and TGFβ1-3 assessment. A univariate analysis and multivariate linear regression model were used for statistical testing. The concentrations of TGF-β2 (p = 0.01) and IgA (p < 0.01) were significantly higher in the colostrum from the women residing in Burundi than in Italy, both in a univariate analysis and upon the adjustment for confounding factors. A similar trend is seen for HGF, reaching statistical significance upon a multivariate analysis. We found a moderate to strong positive correlation between the TGF-β isoforms and IgA concentration in both countries (p < 0.01), with stronger concentration in the colostrum from Burundi. The results of this study are in support of previous data, suggesting that concentration of the immune active molecules is higher in the human milk of women residing in developing countries. However, with a small sample size, caution must be applied, as the findings require further confirmation. Future work should also be focused on other factors (e.g., lipid and microbial composition), as well as the investigation into colostrum and between populations comparison, adjusting for potential confounders.

© 2018  Extensive scar tissue formation often occurs after severe burn injury, trauma, or as one of complications after surgical intervention. Despite significant therapeutic advances, it is still a significant challenge to manage massive scar tissue formation while also promoting normal wound healing. The goal of this study was to investigate the therapeutic effect of bone mesenchymal stem cells (BMSCs) that were genetically modified to overexpress transforming growth factor-beta 3 (TGF-β 3 ), an inhibitor of myofibroblast proliferation and collagen type I deposition, on full-thickness cutaneous wound healing in a rabbit model. Twenty-four rabbits with surgically-induced full-thickness cutaneous wounds created on the external ear (1.5 × 1.5 cm, two wounds/ear) were randomized into four groups: (G1), wounds with no special treatment but common serum-free culture medium as negative controls; (G2), topically-applied recombinant adenovirus, expressing TGF-β 3 /GFP; (G3), topically-applied BMSCs alone; (G4), topically-applied BMSCs transfected with Ad-TGF-β 3 /GFP (BMSCs TGF-β3 ); and (G5), an additional normal control (n = 2) with neither wound nor treatment on the external ear skin. The sizes of wounds on the ear tissues were grossly examined, and the scar depth and density of wounds were histologically evaluated 21, 45, and 90 days after surgical wound creation. Our results demonstrated that G4 significantly reduced the wound scar depth and density, compared to G1~3. Numbers of cells expressing GFP significantly increased in G4, compared to G2. The protein expression of TGF-β 3 and type III collagen in G4 significantly increased, while the ratio of type I to type III collagen was also significantly reduced, which is similar to the tissue architecture found in G5, as compared the other treatment groups. In conclusion, transplantation of BMSCs TGF-β3 remarkably improves wound healing and reduces skin scar tissue formation in an animal model, which may potentially provide an alternative in the treatment of extensive scar tissue formation after soft tissue injury.

© Bionika Media Ltd. Different factors caused by both equipment and the course of surgery (conditions under which the operation is performed, the location of incision, the characteristics of suture material, the type of surgical suture, and the amount of blood loss), by the course of the postoperative period, and the peculiarities of repair of damaged tissues influence wound healing of the uterus during cesarean section. Objective. To establish the value of premature amniorrhea and uterine inertia as predictors of impaired myometrial repair after cesarean section, by using clinical and morphological analyses. Subjects and methods. The investigation enrolled 129 patients who had given birth via cesarean section. Of them, 44 patients had delivery before birth activity, 85 during the first stage of labor. 49 and 80 women delivered before and after amniorrhea, respectively. During cesarean section, uterine tissue was taken from the upper edge of the wound after uterine incision. The myometrial biopsy specimens obtained during cesarean section were morphologically and immunohistochemically examined. The patients were divided into 4 groups according to the level of birth activity and the preservation of amniotic fluid at the time of cesarean section. Group 1 included patients with regular labor activity and amniorrhea at the time of caesarean section; Group 2 consisted of those with labor activity in the presence of whole amniotic fluid; Group 3 comprised those without birth activity in the presence of whole amniotic fluid; Group 4 included patients with premature amniorrhea without uterine contractions. 36 cases (9 in each group) were selected by random sampling for morphological and immunohistochemical examinations. The biopsy specimens were fixed in 10% neutral formalin and embedded in paraffin. The serial paraffin-embedded sections underwent histological examination and immunohistochemical tests for the following markers: TGF-β, VEGF, MMP2, TIMP1, types I and III collagen, TNF, and PDGF. Results. The morphological and immunohistochemical analyses revealed the most pronounced signs of myometrial damage during cesarean section in Group 4 patients having premature amniorrhea without uterine contractions. There were decreased VEGF, PDGF, MMP2, and TIMP levels and simultaneously increased TNF-α expression in leiomyocytes, vascular endothelium, and myometrial stromal cells. The findings may indicate the relatively lower reparative potential of the myometrium and the increased readiness for an inflammatory response in the group of women undergoing cesarean section in the presence of premature amniorrhea without uterine contractions. Conclusion. Clinical, morphological, and immunohistochemical analyses have revealed differences in the myometrial status in relation to typical clinical factors, such as amniorrhea and birth activity. Wound healing occurs under the influence of growth factors and the ratio of expression levels for growth factors can vary in different pathological conditions. The reduced expression of VEGF, MMP2, TIMP, and PDGF and the increased expression of TNF in the group having amniorrhea without uterine contractions (P-B+) suggest that there are pronounced inflammatory processes and impaired myometrial repair with the longer latency period in the absence of labor activity, which may refer these women to a group at risk for incompetent scar formation.

Обширное образование рубцовой ткани часто происходит после тяжелой ожоговой травмы, травмы или как одно из осложнений после хирургического вмешательства. Несмотря на значительные терапевтические успехи, все еще остается серьезной проблемой управлять формированием массивной рубцовой ткани, одновременно способствуя нормальному заживлению ран. Целью данного исследования было изучение терапевтического эффекта костных мезенхимальных стволовых клеток (BMSCs), которые были генетически модифицированы для сверхэкспрессии трансформирующего фактора роста-бета 3 (TGF-β 3).), ингибитор пролиферации миофибробластов и отложения коллагена I типа, на заживление кожных ран полной толщины на модели кролика. Двадцать четыре кролика с хирургически индуцированными кожными ранами полной толщины, созданными на внешнем ухе (1,5 × 1,5 см, две раны / ухо), были рандомизированы на четыре группы: (G1), раны без специальной обработки, но с обычной бессывороточной культурой средний как отрицательный контроль; (G2) местно применяемый рекомбинантный аденовирус, экспрессирующий TGF-β 3 / GFP; (G3), только для местного применения BMSC; (G4), местно применяемые BMSC, трансфицированные Ad-TGF-β 3 / GFP (BMSCs TGF-β3); и (G5), дополнительный нормальный контроль (n = 2) без раны или обработки кожи наружного уха. Размеры ран на тканях уха были тщательно исследованы, а глубина рубца и плотность ран были оценены гистологически через 21, 45 и 90 дней после создания хирургической раны. Наши результаты показали, что G4 значительно уменьшил глубину и плотность рубцов на ране по сравнению с G1 ~ 3. Количество клеток, экспрессирующих GFP, значительно увеличилось в G4 по сравнению с G2. Экспрессия белка TGF-β 3 и коллагена типа III в G4 значительно увеличилась, в то время как отношение типа I к коллагену типа III также значительно уменьшилось, что аналогично структуре ткани, обнаруженной в G5, по сравнению с другими группами лечения. В заключение трансплантация BMSCs TGF-β3 значительно улучшает заживление ран и уменьшает образование рубцовой ткани кожи на животной модели, что потенциально может предоставить альтернативу в лечении обширного образования рубцовой ткани после повреждения мягких тканей.

Обширное образование рубцовой ткани часто происходит после тяжелой ожоговой травмы, травмы или как одно из осложнений после хирургического вмешательства. Несмотря на значительные терапевтические успехи, все еще остается серьезной проблемой управлять формированием массивной рубцовой ткани, одновременно способствуя нормальному заживлению ран. Целью данного исследования было изучение терапевтического эффекта костных мезенхимальных стволовых клеток (BMSCs), которые были генетически модифицированы для сверхэкспрессии трансформирующего фактора роста-бета 3 (TGF-β 3).), ингибитор пролиферации миофибробластов и отложения коллагена I типа, на заживление кожных ран полной толщины на модели кролика. Двадцать четыре кролика с хирургически индуцированными кожными ранами полной толщины, созданными на внешнем ухе (1,5 × 1,5 см, две раны / ухо), были рандомизированы на четыре группы: (G1), раны без специальной обработки, но с обычной бессывороточной культурой средний как отрицательный контроль; (G2) местно применяемый рекомбинантный аденовирус, экспрессирующий TGF-β 3 / GFP; (G3), только для местного применения BMSC; (G4), местно применяемые BMSC, трансфицированные Ad-TGF-β 3 / GFP (BMSCs TGF-β3); и (G5), дополнительный нормальный контроль (n = 2) без раны или обработки кожи наружного уха. Размеры ран на тканях уха были тщательно исследованы, а глубина рубца и плотность ран были оценены гистологически через 21, 45 и 90 дней после создания хирургической раны. Наши результаты показали, что G4 значительно уменьшил глубину и плотность рубцов на ране по сравнению с G1 ~ 3. Количество клеток, экспрессирующих GFP, значительно увеличилось в G4 по сравнению с G2. Экспрессия белка TGF-β 3 и коллагена типа III в G4 значительно увеличилась, в то время как отношение типа I к коллагену типа III также значительно уменьшилось, что аналогично структуре ткани, обнаруженной в G5, по сравнению с другими группами лечения. В заключение трансплантация BMSCs TGF-β3 значительно улучшает заживление ран и уменьшает образование рубцовой ткани кожи на животной модели, что потенциально может предоставить альтернативу в лечении обширного образования рубцовой ткани после повреждения мягких тканей.