Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats

Induced neural stem cells (iNSCs) can be directly transdifferentiated from somatic cells. One potential clinical application of the iNSCs is for nerve regeneration. However, it is unknown whether iNSCs function in disease models. We produced transdifferentiated iNSCs by conditional overexpressing Oct4, Sox2, Klf4, c-Mycin mouse embryonic fibroblasts. They expanded readily in vitro and expressed NSC mRNA profile and protein markers. These iNSCs differentiated into mature astrocytes, neurons and oligodendrocytes in vitro. Importantly, they reduced lesion size, promoted the recovery of motor and sensory function as well as metabolism status in middle cerebral artery stroke rats. These iNSCs secreted nerve growth factors, which was associated with observed protection of neurons from apoptosis. Furthermore, iNSCs migrated to and passed through the lesion in the cerebral cortex, where Tuj1+ neurons were detected. These findings have revealed the function of transdifferentiated iNSCs in vivo, and thus provide experimental evidence to support the development of personalized regenerative therapy for CNS diseases by using genetically engineered autologous somatic cells.     

Developmental changes in the ovarian follicular basal lamina detected by immunofluorescence and electron microscopy

Alterations in the basal lamina (BL) of developing follicles were studied by immunofluorescent microscopy using antibodies against type IV collagen, laminin, and fibronectin, and by electron microscopy. Ovarian development was induced in immature rats by sequential administration of estradiol, follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG). A continuous BL was observed in healthy follicles treated with estradiol and FSH. As determined by immunofluorescence, laminin, type IV collagen, and fibronectin were restricted to the BL and the theca but not to the granulosa. When follicles were allowed to undergo atresia or induced to ovulate with hCG, the BL became fragmented. This was confirmed by electron microscopy of healthy, atretic, and luteinizing follicles which showed that in healthy follicles the BL was continuous, whereas in both atretic and luteinizing follicles, it was fragmented. Atresia was also associated with the penetration of thecal cells into the follicles. These observations indicate that the intact BL present in healthy follicles undergo extensive changes during atresia and ovulation.     

Alpha-methylene-gamma-lactone fused to steroidal ring D as potential antitumor agent

Steroidal alpha-methylene-gamma-lactone la has been synthesised from 3 beta-hydroxy-5-androsten-17-one 2 and showed to be active against HeLa cells.     

Synthesis of pregnenoic acid derivatives possessing structural elements of prostaglandins

Pregneoic acid derivative V in which the character of functional groups and distances between them (expressed in terms of C-C bonds) resemble those occurring in prostaglandins has been synthetised. 3beta-Hydroxyandrost-5-en-17-one acetate VII was converted to ethyl 3beta-acetoxypregn-5-en-21-oate XIIa via a Reformatsky reaction followed by dehydration of adduct VIIIa and selective hydrogenation of the diene X. Compound XIIa was then transformed into trienone XIII by oxidation of the 3beta-hydroxy-5-ene XIIc with DDQ. The trienone XIII was subsequently epoxidised with alkaline hydrogen peroxide and m-chloroperbenzoic acid to give diepoxide XV which was reduced with aluminum amalgam to the final product V.