摘要: ObjectivesProgesterone (P4) has the potential therapeutic effects for traumatic brain injury (TBI) whose recovery depended on the enhanced angiogenesis. Endothelial progenitor cell (EPC) plays an essential role in vascular biology. We previously demonstrated that P4 administration improved circulating EPC level and neurological recovery of rat with TBI. Here, we hypothesized that P4 augmented angiogenic potential of EPC and the angiogenesis-related neurorestoration after TBI through classical progesterone receptor (PR). Materials and methodsEPC derived from rats were stimulated with graded concentrations (0, 10(-10), 10(-9), 5x10(-9), 10(-8), 10(-7)mol/L) of P4 or 10(-6)mol/L ulipristal acetate (UPA, a PR antagonist). Male rats were subjected to cortical impact injury and treated with (i) DMSO (dimethyl sulfoxide), (ii) P4 and (iii) P4 and UPA. ResultsIt showed that P4 improved the angiogenic potential of EPC, including tube formation, adhesion, migration and vascular endothelial growth factor secretion, in a dose-dependent fashion with the maximal effect achieved at 10(-9)mol/L P4. High concentration (10(-7)mol/L) of P4 impaired the angiogenic potential of EPC. Notably, 10(-6)mol/L UPA antagonized the stimulatory effects of 10(-9)mol/L P4. After administrating P4, a significant improvement of neurological function and the restoration of the leaked blood-brain barrier were observed as well as a reduction of the brain water content. Both vessel density and expression of occludin of vessels were increased. When UPA was administered with P4, the neural restoration and angiogenesis were all reversed. Western blot showed that 10(-9)mol/L P4 increased the content of PRA and PRB of EPC, while 10(-7)mol/L P4 reduced the content of both PR isoforms, but there was no change found in the TBI rats. ConclusionsIt may suggest that P4-mediated angiogenic activity of EPC and angiogenesis in TBI rats were antagonized by PR antagonist.

摘要: Objectives: Maternal gestational diabetes leads to an adverse in utero environment and increases the risk of malformations during embryo organogenesis. In the present study, we analysed the effects of maternal diabetes on tooth germ cell proliferation and apoptosis in offspring, and investigated their underlying mechanisms. Materials and methods: A rat model of maternal diabetes was induced by intraperitoneal injection of streptozotocin and the pregnant rats were divided into three groups: controls, the diabetic group and diabetic group with insulin treatment. Offspring of the three groups were collected and cell proliferation and apoptosis in tooth germs were analysed. Primary dental papilla cells and dental epithelial stem cells were isolated and treated with high glucose in vitro, in an attempt to simulate maternal diabetes-induced hyperglycaemia in vivo. Results: Maternal diabetes significantly affected cell proliferation and apoptosis in offspring tooth germs. The TLR4/NF-kappa B signalling pathway was activated in the tooth germs of offspring of diabetic dams. High glucose treatment activated the TLR4/NF-kappa B signalling pathway in primary dental papilla cells and dental epithelial stem cells in vitro, resulting in suppression of cell proliferation and enhancement of apoptosis. TLR4 knockdown significantly reduced adverse effects induced by high glucose treatment. Conclusions: Maternal gestational diabetes significantly impaired dental epithelial and mesenchymal cell proliferation and apoptosis in offspring, possibly by activation of the TLR4/NF-kappa B signalling pathway.

摘要: Objectives: The formation of vascular neointima is mainly related to impairment of the vascular endothelial barrier and abnormal proliferation and migration of smooth muscle cells. The objective of this study was to investigate whether miR-29a exerts any promoting effect on the vascular neointimal hyperplasia and if so, its mechanism. Materials and methods: RT-qPCR was performed to determine expression of miR-29a in vascular smooth muscle cells (VSMC) and vascular neointimal hyperplasia. To further understand its role, we restored its expression in VSMCs by transfection with miR-29a mimics or inhibitors. Effects of miR-29a on cell proliferation were also determined. Results: In this study, we used two kinds of model to observe the role of miR-29a in neointimal hyperplasia induced by carotid ligation or balloon injury. The major findings were that: (i) miR-29a overexpression promoted neointimal hyperplasia induced by carotid ligation; (ii) miR-29a increased proliferation of VSMCs, one aspect of which was by targeting expression of Ying and yang 1 protein (YY1), a negative regulator of Cyclin D1. A further aspect, was by increasing expression of Kruppel-like factor 5, a positive regulator of Cyclin D1, thereby allowing formation a synergistic effect. (iii) Tongxinluo (TXL), a traditional Chinese medicine reduced neointimal formation in ligated vessels by inhibiting VSMC proliferation and migration. Conclusions: These findings provide a new molecular mechanism of TXL in decreasing neointima hyperplasia.

摘要: Aberrant overexpression of the long non-coding RNA NEAT1 (nuclear paraspeckle assembly transcript 1) has been documented in different types of solid tumours, such as lung cancer, oesophageal cancer, colorectal cancer and hepatocellular carcinoma, in which its high levels are associated with poor prognosis. In contrast, NEAT1 is down-regulated in acute promyelocytic leukaemia where it promotes leucocyte differentiation. In this review, we provide an overview of current evidence concerning the oncogenic role and potential clinical utilities of NEAT1. Further investigations are warranted to elucidate the upstream and downstream mechanisms of NEAT1 overexpression.

摘要: Objectives: Primary retinal pigment epithelium (RPE) cells have a limited capacity to re-establish epithelial morphology and to maintain native RPE function in vitro, and all commercially available RPE cell lines have drawbacks of morphology or function; therefore, the establishment of new RPE cell lines with typical characteristics of RPE would be helpful in further understanding of their physiological and pathological mechanisms. Here, we firstly report a new spontaneously generated RPE line, fhRPE-13A, from a 13-week aborted foetus. We aimed to investigate its availability as a RPE model. Materials and methods: RNA-seq data were mapped to the human genome assembly hg19. Global transcriptional data were analysed by Weighted Gene Co-expression Network Analysis (WGCNA) and differentially expressed genes (DEGs). The morphology and molecular characteristics were examined by immunofluorescence, transmission electron micrographs, PCR and western blot. Photoreceptor outer segments (POS) phagocytosis assay and transepithelial resistance measurement (TER) were performed to assess phagocytic activity and barrier function, respectively. Results: The fhRPE-13A cells showed typical polygonal morphology and normal biological processes of RPE. Meanwhile they were capable of POS phagocytosis in vitro, and the expression level of TYR and TYRP1 were significantly higher than that in ARPE-19 cells. Conclusions: The foetal human RPE line fhRPE-13A is a valuable system for researching phagocytosis and morphogenesis of RPE in vitro.