Circulating miR-4739 and IGFBP-4 Levels in Postmenopausal Women with Osteoporosis and Osteoporotic Vertebral Fracture.

Objective: This study aimed to investigate the potential plasma miRNA-mRNA regulatory networks in postmenopausal women with osteoporosis (OP) and osteoporotic vertebral fracture (OVF). Methods: The study employed a cross-sectional design, and the microarray dataset GSE93883 was acquired from the Gene Expression Omnibus (GEO) to assess plasma miRNA profiles in postmenopausal women with osteoporosis (OP) and osteoporotic vertebral fracture (OVF). Subsequently, plasma microRNA-4739 (miR-4739) and Insulin-like Growth Factor Binding Protein-4 (IGFBP-4) levels were validated in a well-defined cohort comprising 210 postmenopausal women. This cohort consisted of three distinct groups: healthy controls (HC, n = 70), OP patients (n = 70), and OVF patients (n = 70). Results: Analysis of the GSE93883 dataset revealed a stepwise increase in four miRNAs (hsa-miR-4739, hsa-miR-4505, hsa-miR-4459, hsa-miR-665) in plasma samples from HC to OP patients to OVF patients. Conversely, plasma miR-4666a-3p showed a gradual decrease. We predicted six genes targeted by miR-4739 using six online databases. Plasma miR-4739 levels were significantly higher in OP and OVF patients compared to HC, especially in OVF patients. However, plasma IGFBP-4 exhibited an inverse pattern. Pearson analysis demonstrated a significant negative correlation between plasma miR-4739 and plasma IGFBP-4 in OP and OVF patients. Receiver operating characteristic (ROC) curve analysis of plasma miR-4739 yielded a sensitivity of 35.71% and specificity of 95.71% for predicting the presence of OP and a sensitivity of 71.43% and specificity of 95.71% for predicting OVF, with an AUC of 0.865. Moreover, the area under the curve (AUC) for IGFBP-4 was higher than that for plasma miR-4739 when differentiating OP patients from OVF patients. Conclusions: Circulating miR-4739 and IGFBP-4 demonstrated a negative correlation in OP and OVF patients, suggesting their potential as diagnostic biomarkers for OP and OVF in the future.

[Protective effects of rhizoma paridis total saponins on septic rats].

OBJECTIVE: To investigate the protective effect of rhizoma paridis total saponins and its mechanism on septic rats. METHODS: Septic model was reproduced by cecal ligation and puncture (CLP) in Wistar rats. Rhizoma paridis total saponins was administered to observe its protective effects on septic rats. Blood was collected to determine serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta(IL-1 beta)levels at 2, 6, 12, 24 and 48 hours after operation by means of enzyme-linked immunosorbent assay (ELISA). The pathological changes of lung tissue were observed with light microscope at 72 hours after operation. The peritoneal macrophages (PMPhi) in rats were isolated and the release of TNF-alpha and IL-1 beta in PMPhi after exposure to lipopolysaccharide (LPS, 100 microg/L) were measured by ELISA. RESULTS: Mortality in the rhizoma paridis total saponins group was significantly lower than the CLP group (50.0% vs. 85.0%, P < 0.05). The levels of TNF-alpha and IL-1 beta in serum were significantly lower than those of the CLP group at the same time (P < 0.05 or P < 0.01). The degree of inflammatory injury to the lung was much milder than that in the CLP group. In the in vitro experiment, it was shown that rhizoma paridis total saponins in concentrations of 5, 10, 20 and 40 mg/L could inhibit remarkably the release of TNF-alpha and IL-1 beta from LPS-stimulated PMPhi of rats (all P < 0.01). The differences in TNF-alpha levels among the groups showed no statistically significant difference(all P > 0.05). The level of IL-1 beta in 5 mg/L group was significantly higher than that of the 10 mg/L group (P < 0.05), but showed no difference with those of 20 mg/L and 40 mg/L groups (both P > 0.05). CONCLUSION: Rhizoma paridis total saponins can protect the CLP rats by inhibiting the activation of rat PMPhi to release cytokines and ameliorating acute lung injury.