Promoting the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts is an effective strategy against osteoporosis. Long non-coding RNAs are closely implicated in BMSC osteogenic differentiation. The present study explored the expression pattern and biological role of taurine upregulated gene 1 (TUG1) in osteogenic differentiation. The expressions of TUG1 and osteogenic markers following the osteogenic induction of BMSCs were detected. The functional relevance of TUG1 was evaluated by performing gain-and loss-of-function tests. Inhibitors of AMP-activated protein kinase (AMPK) autophagy were applied to ascertain the effects of TUG1 on the osteogenic differentiation of BMSCs. TUG1 expression increased during the osteogenic differentiation of BMSCs. The overexpression of TUG1 was promoted, whereas the knockdown of TUG1 was suppressed, by BMSC osteogenic differentiation. Mechanically, TUG1 promoted the osteogenesis of BMSCs via the AMPK-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Blocking AMPK and autophagy could abrogate the osteogenic role of TUG1 in BMSCs. These results demonstrated that TUG1 promoted the osteogenic differentiation of BMSCs by regulating the AMPK/mTOR/autophagy axis, suggesting that targeting TUG1 may be a potential therapy for osteoporosis.
Osteoarthritis (OA) is a degenerative disease characterized by articular cartilage and/or chondrocyte destruction, and although it has long been considered as a primary disease, the importance of meniscus endothelial cell modulation in the subchondral microenvironment has recently drawn attention. Previous studies have shown that apelin could potentially inhibit cellular apoptosis; however, it remains unclear whether apelin could play a protective role in protecting the endothelium in the OA meniscus. In this study, with the advantages of single-cell RNA sequencing (scRNA-seq) data, in combination with flow cytometry, we identified two endothelial subclusters in the meniscus, featured by high expression of Homeobox A13 (HOXA13) and Ras Protein-Specific Guanine Nucleotide Releasing Factor 2 (RASGRF2), respectively. Compared with control patients, both subclusters decreased in absolute cell numbers and exhibited downregulated APJ endogenous ligand (APLN, coding for apelin) and upregulated apelin receptor (APLNR, coding apelin receptor). Furthermore, we confirmed that in OA, decreased endothelial cell numbers, including both subclusters, were related to intrinsic apoptosis factors: one more relevant to caspase 3 (CASP3) and the other to BH3-Interacting Domain Death agonist (BID). In vitro culturing of meniscal endothelial cells purified from patients proved that apelin could significantly inhibit apoptosis by downregulating these two factors in endothelial cell subclusters, suggesting that apelin could potentially serve as a therapeutic target for patients with OA.
Stroke is a cerebrovascular disease that results in decreased blood flow. Although Panax notoginseng (PN), a Chinese herbal medicine, has been proven to promote stroke recovery, its molecular mechanism remains unclear. In this study, middle cerebral artery occlusion (MCAO) was induced in rats with thrombi generated by thread and subsequently treated with PN. After that, staining with 2,3,5-triphenyltetrazolium chloride was employed to evaluate the infarcted area, and electron microscopy was used to assess ultrastructural changes of the neurovascular unit. RNA-Seq was performed to determine the differential expressed genes (DEGs) which were then verified by qPCR. In total, 817 DEGs were identified to be related to the therapeutic effect of PN on stroke recovery. Further analysis by Gene Oncology analysis and Kyoto Encyclopedia of Genes and Genomes revealed that most of these genes were involved in the biological function of nerves and blood vessels through the regulation of neuroactive live receptor interactions of PI3K-Akt, Rap1, cAMP, and cGMP-PKG signaling, which included in the 18 pathways identified in our research, of which, 9 were reported firstly that related to PN’s neuroprotective effect. This research sheds light on the potential molecular mechanisms underlying the effects of PN on stroke recovery.
Through the reform of the current postgraduate training mode and the way of mentoring and teaching, such as increasing the proportion of scientific research-related courses, raising the threshold for graduation, establishing a team of tutors to provide effective guidance to students, etc. The idea of forming a postgraduate scientific research team is proposed, and students of different majors and degree types are encouraged to participate in scientific research activities as a team, so as to improve the scientific research atmosphere and scientific research enthusiasm of professional master of clinical medicine (hereinafter referred to as "professional master"), in order to achieve the goal of improving the scientific research and innovation ability of "professional master", put forward solutions for the problems encountered in the context of the "Double Tracks in One" policy and the large-scale expansion of postgraduate enrollment, and provide theoretical and theoretical ideas for the cultivation of innovation ability of "professional master". Practical basis.
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