a b s t r a c tTetraspanin 1 (TSPAN1) has been reported to be upregulated in gastric cancer (GC). However, whilst TSPAN1 is positively correlated with clinical stage and negatively correlated with survival rates, its function in GC remains elusive. Here we show that expression of TSPAN1 is significantly higher in GC tissues compared to non-cancerous tissues. Furthermore, we demonstrate that RNAi-mediated down-regulation of TSPAN1 expression markedly blocks GC cell proliferation, cell cycle progression and invasive activity. We identified TSPAN1 as a novel target gene of miR-573. Overexpression of miR-573 suppressed proliferation and invasion of GC cells by down-regulation of TSPAN1 expression. Restoration of TSPAN1 rescued the effects of miR-573 overexpression. Therefore, our findings suggest that the miR-573/TSPAN1 axis is important in the control of gastric carcinogenesis.
Osteoarthritis is a degenerative disorder that can severely affect joints, and new treatment strategies are urgently needed. Administration of mesenchymal stem cell (MSC)‐derived exosomes is a promising therapeutic strategy in osteoarthritis treatment. However, the poor yield of exosomes is an obstacle to the use of this modality in the clinic. Herein, a promising strategy is developed to fabricate high‐yield exosome‐mimicking MSC‐derived nanovesicles (MSC‐NVs) with enhanced regenerative and anti‐inflammatory capabilities. MSC‐NVs are prepared using an extrusion approach and are found to increase chondrocyte and human bone marrow MSC differentiation, proliferation, and migration, in addition to inducing M2 macrophage polarization. Furthermore, gelatin methacryloyl (GelMA) hydrogels loaded with MSC‐NVs (GelMA‐NVs) are formulated, which exhibit sustained release of MSC‐NVs and are shown to be biocompatible with excellent mechanical properties. In a mouse osteoarthritis model constructed by surgical destabilization of the medial meniscus (DMM), GelMA‐NVs effectively ameliorate osteoarthritis severity, reduce the secretion of catabolic factors, and enhance matrix synthesis. Furthermore, GelMA‐NVs induce M2 macrophage polarization and inflammatory response inhibition in vivo. The findings demonstrate that GelMA‐NVs hold promise for osteoarthritis treatment through modulation of chondrogenesis and macrophage polarization.
Background: The status of lymph nodes in early gastric cancer is critical to make further clinical treatment decision, but the prediction of lymph node metastasis remains difficult before operation. This study aimed to develop a nomogram that contained preoperative factors to predict lymph node metastasis in early gastric cancer patients. Methods: This study analyzed the clinicopathologic features of 823 early gastric cancer patients who underwent gastrectomy retrospectively, among which 596 patients were recruited in the training cohort and 227 patients in the independent validation cohort. Significant risk factors in univariate analysis were further identified to be independent variables in multivariable logistic regression analysis, which were then incorporated in and presented with a nomogram. And internal and external validation curves were plotted to evaluate the discrimination of the nomogram. Results: Totally, six independent predictors, including the tumor size, macroscopic features, histology differentiation, P53, carbohydrate antigen 19-9, and computed tomography-reported lymph node status, were enrolled in the nomogram. Both the internal validation in the training cohort and the external validation in the validation cohort showed the nomogram had good discriminations, with a C-index of 0.82 (95%CI, 0.78 to 0.86) and 0.77 (95%CI, 0.60 to 0.94) respectively. Conclusions: Our study developed a new nomogram which contained the most common and significant preoperative risk factors for lymph node metastasis in patients with early gastric cancer. The nomogram can identify early gastric cancer patients with the high probability of lymph node metastasis and help clinicians make more appropriate decisions in clinical practice.
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