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Rapid endothelialization of cardiovascular stents is critical to prevent major clinical complications such as restenosis. Reconstruction of the native endothelium on the stent surface can be achieved by the capture of endothelial progenitor cells (EPCs) or neighboring endothelial cells (ECs) in vivo. In this study, stainless steel cardiovascular stents were functionalized with recombinant scFv antibody fragments specific for vascular endothelial growth factor receptor‐2 (VEGFR2) that is expressed on EPCs and ECs. Anti‐VEGFR2 scFvs were expressed in glycosylated form in Escherichia coli and covalently attached to amine‐functionalized, titania‐coated steel disks and stents. ScFv‐coated surfaces exhibited no detectable cytotoxicity to human ECs or erythrocytes in vitro and bound 15 times more VEGFR2‐positive human umbilical vein ECs than controls after as little as 3 min. Porcine coronary arteries were successfully stented with scFv‐coated stents with no adverse clinical events after 30 days. Endovascular imaging and histology revealed coverage of the anti‐VEGFR2 scFv‐coated stent with a cell layer after 5 days and the presence of a neointima layer with a minimum thickness of 80 μm after 30 days. Biofunctionalization of cardiovascular stents with endothelial cell‐capturing antibody fragments in this manner offers promise in accelerating stent endothelialization in vivo. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:213–224, 2020. [ABSTRACT FROM AUTHOR]

Background: Recently, many new potent multidrug resistance (MDR) reversal agents have been discovered, among them lathyrane and jatrophane diterpenes isolated from various Euphorbia species. In the present study, the cytotoxicity, P-glycoprotein inhibition activity, and MDR reversal potency of six diterpenes and two coumarins from two Euphorbia species were studied in human colon carcinoma LoVo cells, and doxorubicin-resistant, LoVo/Dx cells., Materials and Methods: Cytotoxicity of the studied compounds (alone and in combination with doxorubicin) was investigated. Inhibition of P-glycoprotein transport activity was monitored by flow cytometry. Changes in intracellular doxorubicin accumulation were observed by means of fluorescence microscopy., Results: Latilagascene B was demonstrated to be an effective P-glycoprotein inhibitor, able to increase doxorubicin accumulation in resistant cells, however not able to restore doxorubicin cytotoxicity in LoVo/Dx cells., Conclusion: The structure of latilagascene B seems to be an interesting candidate for further synthesis of new derivatives of reduced cytotoxicity and high anti-MDR potency., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

The use of dendritic cells (DCs) loaded with tumour antigen is one of the most promising approaches to induce tumour-specific immune response. However, methods of the vaccine preparation have not yet been standardized. The purpose of the study was to analyse the anti-tumour efficacy of tumour antigen-loaded mouse bone marrow-derived dendritic cells (BM-DC/TAg) at different maturation stages. BM-DCs were loaded with MC38 colon carcinoma cell lysate (TAg) alone, to become partially differentiated, or were additionally stimulated with inflammatory cytokines such as TNF-alpha, IFN-gamma, or IL-12 to reach complete maturity. BM-DCs simultaneously stimulated with TAg and cytokines (especially IL-12 or IFN-gamma+IL-12) were in vitro more effective immune response activators than BM-DC/TAg cells. However, the highest anti-tumour effect in vivo was noted when mice were treated just with BM-DC/TAg. In a further study, the ability of IL-12 gene transduced BM-DCs (BM-DC/IL-12) to augment the immune response induced by BM-DC/TAg cells at different stages of maturation was examined. The highest anti-tumour effect was observed when partially differentiated BM-DC/TAg cells were injected simultaneously with BM-DC/IL-12 cells. The results suggest that partially differentiated BM-DC/TAg cells are more potent in evoking a strong anti-tumour response in vivo than mature BM-DCs. Moreover, the capacity of BM-DC/TAg cells for further differentiation and their sensitivity to factors secreted in vivo by the host or cells engineered to cytokine production seem to be of great importance.

Pregnancy-induced hypertension (PIH) is the major cause of maternal and perinatal morbidity. However, the mechanisms responsible for PIH pathogenesis have not yet been fully elucidated. The known risk factors of PIH development are: multiple pregnancy, masculine sex of fetus, very young age of women (below 18 years), advanced age (above 40 years), and obesity of the pregnant woman. In this article an attempt is made to summarize recent knowledge of the pathogenesis of PIH and, particularly, the postulated link between placental ischemia and microvascular dysfunction. The initiating event in PIH has been implicated to be reduced uteroplacental perfusion as a result of abnormal extravillous cytotrophoblast invasion. Focal ischemia and hypoxia, deportation of hypoxemic trophoblast cells, and abnormal expression of various placental biological molecules, particularly the cytokines, are thought to lead to widespread activation/dysfunction of the maternal vascular endothelium. The increased expression of adhesion molecules on activated endothelium intensifies the inflammation process and causes further endothelial injury. The quantitative importance of the various endothelial and humoral factors in mediating PIH symptoms is still unclear. Some of the factors that activate and damage endothelial cells may be of prognostic significance; however, more intensive research should be performed for a precise description of their predictive value.

Interleukin (IL)-7 is a pleiotropic, non-redundant cytokine necessary for the development of B and T lymphocytes, in particular gammadelta T cell receptor-positive cell differentiation. The cytokine can function as a cofactor during myelopoiesis and the generation of cytotoxic T cells and natural killer cells, can activate monocytes/macrophages, and support the survival of mature T cells. A role for IL-7 in promoting the formation of Peyer's patch anlage has also been demonstrated. IL-7 is constitutively expressed in the thymus, bone marrow stromal cells, epithelial and dendritic cells, keratinocytes, as well as in fetal and adult liver. IL-7 acts on various cells through its receptor (IL-7R), a heterodimer consisting of an alpha chain (CD127) that specifically binds IL-7 and a common gamma(c) chain (CD132) shared by other cytokine receptors. The receptor is expressed on bone marrow progenitor cells, lymphoid T and B precursors, and mature T cells. IL-7 activity towards murine endothelial cells has been recently described. The presence of IL-7R on human endothelial cells has also been demonstrated. Several therapeutic applications of recombinant IL-7 have been proposed. These have focused on the enhancement of lymphopoiesis, promotion of stem cell engraftment, and the anti-tumor activity of the cytokine.

Pregnancy induced hypertension (PIH) is accompanied by injury and further activation of placental endothelial cells. Activated endothelial cells produce several mediators, among them endothelin-1 (ET-1)--one of the most potent vasoconstrictors. The aim of the study was to examine the ET-1 level in serum of 18 women with PIH and compare it to the group of 16 normotensive pregnant women. ET-1 level, as evaluated by ELISA test, was significantly higher in PIH than in normotensive pregnancy, 33.00 +/- 12.07 vs. 25.00 +/- 5.69 pg/mL (p = 0.005), respectively. It might be concluded, that ET-1 level is a prognostic parameter, indicating the possibility of PIH development.