No abstract

The alteration of age‐related molecules in the bone marrow microenvironment is one of the driving forces in osteoporosis. These molecules inhibit bone formation and promote bone resorption by regulating osteoblastic and osteoclastic activity, contributing to age‐related bone loss. Here, we observed that the level of microRNA‐31a‐5p (miR‐31a‐5p) was significantly increased in bone marrow stromal cells (BMSCs) from aged rats, and these BMSCs demonstrated increased adipogenesis and aging phenotypes as well as decreased osteogenesis and stemness. We used the gain‐of‐function and knockdown approach to delineate the roles of miR‐31a‐5p in osteogenic differentiation by assessing the decrease of special AT‐rich sequence‐binding protein 2 (SATB2) levels and the aging of BMSCs by regulating the decline of E2F2 and recruiting senescence‐associated heterochromatin foci (SAHF). Notably, expression of miR‐31a‐5p, which promotes osteoclastogenesis and bone resorption, was markedly higher in BMSCs‐derived exosomes from aged rats compared to those from young rats, and suppression of exosomal miR‐31a‐5p inhibited the differentiation and function of osteoclasts, as shown by elevated RhoA activity. Moreover, using antagomiR‐31a‐5p, we observed that, in the bone marrow microenvironment, inhibition of miR‐31a‐5p prevented bone loss and decreased the osteoclastic activity of aged rats. Collectively, our results reveal that miR‐31a‐5p acts as a key modulator in the age‐related bone marrow microenvironment by influencing osteoblastic and osteoclastic differentiation and that it may be a potential therapeutic target for age‐related osteoporosis.

Osteosarcoma is the most common malignant bone tumor in children and adolescence. Multiple immune-related genes have been reported in different cancers. The aim is to identify an immune-related gene signature for the prospective evaluation of prognosis for osteosarcoma patients. In this study, we evaluated the infiltration of immune cells in 101 osteosarcoma patients downloaded from TARGET using the ssGSEA to the RNA-sequencing of these patients, thus, high immune cell infiltration cluster, middle immune cell infiltration cluster and low immune cell infiltration cluster were generated. On the foundation of high immune cell infiltration cluster vs. low immune cell infiltration cluster and normal vs. osteosarcoma, we found 108 common differentially expressed genes which were sequentially submitted to univariate Cox and LASSO regression analysis. Furthermore, GSEA indicated some pathways with notable enrichment in the high- and low-immune cell infiltration cluster that may be helpful in understanding the potential mechanisms. Finally, we identified seven immune-related genes as prognostic signature for osteosarcoma. Kaplan-Meier analysis, ROC curve, univariate and multivariate Cox regression further confirmed that the seven immune-related genes signature was an innovative and significant prognostic factor independent of clinical features. These results of this study offer a means to predict the prognosis and survival of osteosarcoma patients with uncovered seven-gene signature as potential biomarkers.

Multidrug resistance-associated protein 3 (MRP3, ABCC3) plays an important role in protecting hepatocytes and other tissues by excreting an array of toxic organic anion conjugates, including bile salts. MRP3/ABCC3 expression is increased in the liver of some cholestatic patients, but the molecular mechanism of this up-regulation remains elusive. In this report, we assessed liver MRP3/ABCC3 expression in patients (n=22) with obstructive cholestasis due to gallstones blockage of bile ducts and non-cholestatic patient controls (n=22). MRP3/ABCC3 mRNA and protein expression were significantly increased 3.4- and 4.6- fold, respectively in these cholestatic patients where elevated plasma TNFα (4.7-fold, P<0.01) and hepatic SP1 and LRH-1 expression (3.1- and 2.1-fold at mRNA level, 3.5- and 2.5-fold at protein level, respectively) were also observed. The induction of hepatic MRP3/ABCC3 mRNA expression is significantly positively correlated with the level of plasma TNFα in these patients. In HepG2 cells, TNFα treatment induced SP1 and MRP3/ABCC3 expression in a dose- and time-dependent manner, where increased phosphorylation of JNK/SAPK was also detected. These inductions were significantly reduced in the presence of the JNK inhibitor SP600125. TNFα treatment enhanced HepG2 cell nuclear extract binding activity to the MRP3/ABCC3 promoter, but was abolished by SP600125 as demonstrated by EMSA. An increase in nuclear protein binding activity to the MRP3/ABCC3 promoter consisting primarily of SP1 was also seen in liver samples from cholestatic patients as assessed by supershift EMSA assays. Conclusions Our findings indicate that up-regulation of hepatic MRP3/ABCC3 expression in human obstructive cholestasis is likely triggered by TNFα, mediated by activations of JNK/SAPK and SP1.

No abstract

In this study, graphene oxide (GO) is incorporated into poly(vinyl alcohol) (PVA) for the purpose of improving the mechanical properties. Nanocomposite scaffolds with an interconnected porous structure are fabricated by selective laser sintering (SLS). The results indicate that the highest improvements in the mechanical properties are obtained, that is, a 60%, 152% and 69% improvement of compressive strength, Young's modulus and tensile strength is achieved at the GO loading of 2.5 wt%, respectively. The reason can be attributed to the enhanced load transfer due to the homogeneous dispersion of GO sheets and the strong hydrogen bonding interactions between GO and the PVA matrix. The agglomerates and restacking of GO sheets occur on further increasing the GO loading, which leads to the decrease in the mechanical properties. In addition, osteoblast-like cells attach and grow well on the surface of scaffolds, and proliferate with increasing time of culture. The GO/PVA nanocomposite scaffolds are potential candidates for bone tissue engineering.

The Depression Anxiety Stress Scale-21 (DASS-21) is an instrument in the assessment of mental health status. The current study recruited 1,532 Chinese hospital workers [74.4% female; mean age = 31.97 (SD = 9.70) years] to examine the reliability, latent structure, and measurement invariance of the DASS-21 between genders. The Cronbach's α values were greater than 0.90 for total score. This study examined four possible models of the DASS-21 using the confirmatory factor analysis (CFA) in Chinese hospital workers. The results from CFA revealed that the latent structure of the DASS-21 in medical staffs is best represented by a one-factor model. Then we used the one-factor model to examine measurement invariance across genders by using a multiple-group categorical CFA. All values of root mean square error approximation (RMSEA) were less than 0.08, all Comparative Fix Index (CFI) and Tucker-Lewis Index values were greater than 0.90, all CFI (changes in CFI) values were less than 0.010, and RMSEA (the changes in RMSEA) were less than 0.015. These findings supported the gender invariance of the DASS-21 among Chinese hospital workers.

Matrix metalloproteinase 9 (MMP-9) plays an important role in the progression of several types of cancer by increasing tumor growth, migration, invasion, and metastasis and is associated with poor disease prognosis. The possible prognostic value of MMP-9 in osteosarcoma has also been examined, but due to inconsistent results between studies, it has not been possible to draw firm conclusions. To clarify this issue, we conducted a meta-analysis of published studies to provide a comprehensive evaluation of the effect of high MMP-9 expression on the survival outcomes of osteosarcoma patients. Seven studies with a total of 339 patients with osteosarcoma were examined. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated to evaluate the effect of MMP-9 expression on overall survival. Meta-analysis showed that patients with high MMP-9 expression were significantly associated with lower overall survival when compared to their counterparts with low or undetectable MMP-9 expression (OR=6.13, 95 % CI 3.45-10.89, P<0.001). Sensitivity analysis suggested the pooled OR was stable and not significantly changed when a single study was removed. The results from the systematic review and meta-analysis show that MMP-9 is an effective biomarker for predicting survival of patients with osteosarcoma.