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In addition to their chemical composition various physical properties of synthetic bone substitute materials have been shown to influence their regenerative potential and to influence the expression of cytokines produced by monocytes, the key cell-type responsible for tissue reaction to biomaterials in vivo. In the present study both the regenerative potential and the inflammatory response to five bone substitute materials all based on β-tricalcium phosphate (β-TCP), but which differed in their physical characteristics (i.e., granule size, granule shape and porosity) were analyzed for their effects on monocyte cytokine expression. To determine the effects of the physical characteristics of the different materials, the proliferation of primary human osteoblasts growing on the materials was analyzed. To determine the immunogenic effects of the different materials on human peripheral blood monocytes, cells cultured on the materials were evaluated for the expression of 14 pro- and anti-inflammatory cytokines, i.e., IL-6, IL-10, IL-1β, VEGF, RANTES, IL-12p40, I-CAM, IL-4, V-CAM, TNF-α, GM-CSF, MIP-1α, Il-8 and MCP-1 using a Bio-Plex® Multiplex System. The granular shape of bone substitutes showed a significant influence on the osteoblast proliferation. Moreover, smaller pore sizes, round granular shape and larger granule size increased the expression of GM-CSF, RANTES, IL-10 and IL-12 by monocytes, while polygonal shape and the larger pore sizes increased the expression of V-CAM. The physical characteristics of a bone biomaterial can influence the proliferation rate of osteoblasts and has an influence on the cytokine gene expression of monocytes in vitro. These results indicate that the physical structure of a biomaterial has a significant effect of how cells interact with the material. Thus, specific characteristics of a material may strongly affect the regenerative potential in vivo.Five new compounds viz kaempferol 3-O-(4″-galloyl)-β-d-glucopyranosyl-(1‴→6″)-O-β-d-glucopyranoside (1), kaempferol 3-O-β-d-mannuronopyranoside (2), kaempferol 3-O-β-d-mannopyranoside (3), quercetin 3-O-β-d-mannuronopyranoside (4), 2, 3 (S)- hexahydroxydiphenoyl]-d-glucose (5) along with fifteen known compounds were isolated from 80% aqueous methanol extract (AME) of C. viminalis. AME and compounds exerted similar or better antioxidant activity to ascorbic acid using DPPH, O2-, and NO inhibition methods. In addition, compounds 16, 4, and 7 showed cytotoxic activity against MCF-7 cell lines while 3, 7 and 16 exhibited strong activity against HepG2. An in silico analysis using molecular docking for polyphenolic compounds 2, 3, 7, 16 and 17 against human stable 5-LOX was performed and compared to that of ascorbic acid and quercetin. The binding mode as well as the enzyme-inhibitor interactions were evaluated. All compounds occupied the 5-LOX active site and showed binding affinity greater than ascorbic acid or quercetin. The data herein suggest that AME, a source of polyphenols, could be used against oxidative-stress-related disorders.The blood-brain barrier (BBB) plays an important protective role in the central nervous system and maintains its homeostasis. It regulates transport into brain tissue and protects neurons against the toxic effects of substances circulating in the blood. However, in the case of neurological diseases or primary brain tumors, i.e., gliomas, the higher permeability of the blood-derived substances in the brain tissue is necessary. Currently applied methods of treatment for the primary brain neoplasms include surgical removal of the tumor, radiation therapy, and chemotherapy. Despite the abovementioned treatment methods, the prognosis of primary brain tumors remains bad. Moreover, chemotherapy options seem to be limited due to low drug penetration into the cancerous tissue. Modulation of the blood-brain barrier permeability may contribute to an increase in the concentration of the drug in the CNS and thus increase the effectiveness of therapy. Interestingly, endothelial cells in cerebral vessels are characterized by the presence of adenosine 2A receptors (A2AR). It has been shown that substances affecting these receptors regulate the permeability of the BBB. The mechanism of increasing the BBB permeability by A2AR agonists is the actin-cytoskeletal reorganization and acting on the tight junctions. In this case, the A2AR seems to be a promising therapy target. This article aims to assess the possibility of increasing the BBB permeability through A2AR agonists to increase the effectiveness of chemotherapy and to improve the results of cancer therapy.Despite its many clinical applications, indomethacin is seldom used in pregnancy, principally because of concerns regarding the potential for constriction of the arterial duct. The aim of this study was to document adverse antenatal effects and postnatal outcomes after in utero exposure to low-dose indomethacin. We studied a retrospective cohort of pregnancies between 2005 and 2016 at the John Radcliffe Hospital, Oxford, UK, in which mothers at extremely high risk of preterm birth were treated as prophylaxis with indomethacin 25 mg, 12 hourly, before 29 weeks. Antenatal effects on the arterial duct and postnatal outcomes were analysed. Overall, 198 fetuses had in utero follow-up, and 13 (6.6%) had ductal constriction, all within 9 days of starting treatment. click here No ductal constriction was seen in pregnancies when therapy was started before 20 weeks, and all effects were reversed after cessation of therapy. An analysis of postnatal complications was possible in 181 neonates. There were eight (4.4%) neonatal deaths, all but one associated with extreme preterm birth. Seven (5%) patent ductus arteriosus cases occurred in the 140 neonates delivered after 28 weeks who were alive at discharge. Postnatal complications were not more common in neonates in whom antenatal ductal constriction had been demonstrated. In conclusion, fetuses exposed to prolonged low dose indomethacin have a low incidence of in utero complications; these complications can be diagnosed with ultrasound and are reversible. Adverse postnatal events are related to gestation at birth and do not appear more common.

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