Senile osteoporosis is closely related to the loss of function of stem cells. In this study, we tried to investigate the potential of secretome from human umbilical cord-derived mesenchymal stem cells (hUCMSCs) in recovering stem cell ability from senescence and then delaying bone loss. We first harvested bone marrow-derived mesenchymal stem cells (BMSCs) from young and old rats and then compared their cellular characteristics such as cell growth, anti-senescence and differentiation. The results showed that these abilities were negatively affected by animal aging. Subsequently, aged BMSCs were exposed to secretome from hUCMSCs, and we found that this loss of cell potential can be modified by secretome treatment. Thereafter, the secretome was loaded into silk fibroin-based hydrogels and used for an in vivo animal study. The results showed that compared to the old untreated group, the bone formation capacity of aged rats was improved by local treatment of secretome-loaded silk fibroin hydrogels. In conclusion, these findings demonstrated that secretome from hUCMSCs has the capacity to recover stem cell potential and delay local bone loss in age-related osteoporosis, which could potentially be applied in osteoporosis therapy in the future.
Background Gastric cancer is the most common malignant neoplasm of digestive system. Herein, we aim to detect the expression of nuclear factor I C (NFIC) in gastric cancer cells, and to explore the effect and mechanism of its expression on the development of gastric cancer. Methods qPCR and Western blot assays were carried out to detect NFIC expression. Then, BGC-823 and SGC-7901 cell lines were selected to perform the following functional experiments. The function of NFIC on gastric cancer cells was analyzed by biological experiments. The associations between miR-9-5p and NFIC were searched on the bioinformatics website and identified by dual luciferase assay. The effects of miR-9-5p and NFIC on cells were verified by co-transfection experiments. The related genes expression was examined by Western blot. Results A marked augmentation of NFIC was observed in gastric cancer cells. Knockdown of NFIC significantly inhibited the viability, colony formation, invasion, and migration of gastric cancer cells. Overexpression of miR-9-5p obviously suppressed the viability, colony formation, invasion, and migration of gastric cancer cells, and this phenomenon was aggravated by si-NFIC. Additionally, the expression levels of PCNA, vimentin, and Snail were obviously decreased after miR-9-5p mimic or/and si-NFIC treatment. Conclusions These results suggested that NFIC was highly expressed in gastric cancer cells, and knockdown of NFIC suppressed the growth and mobility of gastric cancer cells; miR-9-5p was identified as an upstream regulator of NFIC and suppressed the malignant behaviors of gastric cancer cells by targeting NFIC through affecting PCNA, vimentin, and Snail expression.
Abstract:Objective: To explore potential functional biomarkers in diabetes mellitus (DM) by utilizing gene pathway cross-talk. Methods: Firstly, potential disrupted pathways that were enriched by differentially expressed genes (DEGs) were identified based on biological pathways downloaded from the Ingenuity Pathways Analysis (IPA) database. In addition, we quantified the pathway crosstalk for each pair of pathways based on Discriminating Score (DS). Random forest (RF) classification was then employed to find the top 10 pairs of pathways with a high area under the curve (AUC) value between DM samples versus normal samples based on 10-fold cross-validation. Finally, a Monte Carlo Cross-Validation was applied to demonstrate the identified pairs of pathways by a mutual information analysis. Results: A total of 247 DEGs in normal and disease samples were identified. Based on the F-test, 50 disrupted pathways were obtained with false discovery rate (FDR) < 0.01. Simultaneously, after calculating the DS, the top 10 pairs of pathways were selected based on a higher AUC value as measured by RF classification. From the Monte Carlo Cross-Validation, we considered the top 10 pairs of pathways with higher AUC values ranked for all 50 bootstraps as the most frequently detected ones. Conclusion: The pairs of pathways identified in our study might be key regulators in DM.
Increasing evidence demonstrates that circular RNA (circRNA) plays a pivotal role in the development of disease, especially in Cancer. A previous circRNA microarray study showed that circGAK (hsa_circ_0005830) was remarkably down-regulated in hepatocellular carcinoma (HCC) tissues. However, the role of circGAK in HCC remains largely unclear. The candidate circRNAs were screened via integrating the Gene Expression Omnibus (GEO) database (GSE164803) analysis with the online program GEO2R. Quantitative real-time PCR (qRT-PCR) was employed to measure the expression of circGAK miR-1323, and hedgehog-interacting protein (HHIP) in HCC tissues and cells. The biological function of circGAK in HCC was examined using colony formation assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, wound healing assay, transwell cell invasion assay, endothelial tubular formation assay, western blot assay, and xenograft mouse model. Bioinformatics analysis, RNA immunoprecipitation (RIP) assay, and dual-luciferase reporter assay were utilized to test the interaction between miR-1323, and circGAK or HHIP. The expression of circGAK was abnormally down-regulated in HCC tissues and was associated with the tumor-node-metastasis (TNM) stage. Overexpression of circGAK remarkably impeded HCC cell proliferation, migration, invasion, and endothelial tube formation in vitro, and tumor growth in vivo. Bioinformatics predicted that circGAK interacted with miR-1323, which targeted the HHIP mRNA 3'untranslated regions (UTR). Furthermore, upregulation of miR-1323 or shRNA-mediated HHIP suppression could recover circGAK-mediated malignant behaviors of HCC cells and tube formation of endothelial cells. Taken together, the circGAK/miR-1323/HHIP axis could suppress the progression of HCC and may provide potential new targets for the diagnosis and therapy of HCC.
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