Channels formed by the transient receptor potential (TRP) family of proteins have a variety of physiological functions. Here we report that two members of the TRP cation channel (TRPC) subfamily, TRPC3 and 6, protected cerebellar granule neurons (CGNs) against serum deprivation-induced cell death in cultures and promoted CGN survival in rat brain. In CGN cultures, blocking TRPC channels or downregulating TRPC3 or 6 suppressed brain-derived neurotrophic factor (BDNF)-mediated protection, BDNF-triggered intracellular Ca2+ elevation and BDNF-induced CREB activation. By contrast, overexpressing TRPC3 or 6 increased CREB-dependent reporter gene transcription and prevented apoptosis in the neurons deprived of serum, and this protection was blocked by the dominant negative form of CREB. Furthermore, downregulating TRPC3 or 6 induced CGN apoptosis in neonatal rat cerebellum, and this effect was rescued by overexpressing either TRPC3 or 6. Thus, our findings provide in vitro and in vivo evidence that TRPC channels are important in promoting neuronal survival.

The transient receptor potential canonical (TRPC) channels are Ca2+-permeable, nonselective cation channels with different biological functions, but their roles in brain are largely unknown. Here we report that TRPC6 was localized to excitatory synapses and promoted their formation via a CaMKIV-CREB-dependent pathway. TRPC6 transgenic mice showed enhancement in spine formation, and spatial learning and memory in Morris water maze. These results reveal a previously unknown role of TRPC6 in synaptic and behavioral plasticity.

NCT02442414;Pre-results.

The periodontal ligament (PDL) and alveolar bone are two critical tissues for understanding orthodontic tooth movement. The current literature is replete with descriptive studies of multiple cell types and their matrices in the PDL and alveolar bone, but is deficient with how stem/progenitor cells differentiate into PDL and alveolar bone cells. Can one type of orthodontic force with a specific magnitude and frequency preferably activate osteoblasts, whereas another force type activates osteoclasts? This chapter will discuss the biology of not only mature cells and their matrices in the periodontal ligament and alveolar bone, but also stem/progenitor cells that differentiate into fibroblasts, osteoblasts and osteoclasts. Key advances in tooth movement rely on further understanding of osteoblast and fibroblast differentiation from mesenchymal stem/progenitor cells, and osteoclastogenesis from the hematopoietic/monocyte lineage.

BackgroundCircular RNAs(circRNAs) have been reported as a diverse class of endogenous RNA that regulate gene expression in eukaryotes. Recent evidence suggested that many circular RNAs can act as oncogenes or tumor suppressors through sponging microRNAs. However, the function of circular RNAs in gastric cancer remains largely unknown.Materials and methodsThe circRNA levels in gastric carcinoma tissues and plasmas were detected by real-time quantitative reverse transcription-polymerase chain reaction. The correlation between the expression of circRNA and clinic pathological features was analyzed. Rate of inhibiting of proliferation was measured using a CCK-8 cell proliferation assay. Clone formation ability was assessed with a clone formation inhibition test. We used the bioinformatics software to predict circRNA-miRNA and miRNA-mRNA interactions. Relative gene expression was assessed using quantitative real-time polymerase chain reaction and relative protein expression levels were determined with western blotting. CircRNA and miRNA interaction was confirmed by dual-luciferase reporter assays.ResultsWe characterized that one circRNA named circ-SFMBT2 showed an increased expression level in gastric cancer tissues compared to adjacent non-cancerous tissues and was associated with higher tumor stages of gastric cancer. Silencing of circ-SFMBT2 inhibited the proliferation of gastric cancer cells significantly. Importantly, we demonstrated that circ-SFMBT2 could act as a sponge of miR-182-5p to regulate the expression of CREB1 mRNA, named as cAMP response element binding protein 1, and further promote the proliferation of gastric cancer cells.ConclusionOur study reveals that circ-SFMBT2 participates in progression of gastric cancer by competitively sharing miR-182-5p with CREB1, providing a novel target to improve the treatment of gastric cancer. mutation-analysis-of-beta-thalassemia-in-east-western-indian-populatio-peer-reviewed-article-TACG for an example.