The effects of dexmedetomidine on postoperative cognitive dysfunction in rats with bone fractures undergoing open reduction.

OBJECTIVE: To investigate the effects of dexmedetomidine on the cognitive dysfunction of aged rats after open tibia fracture surgery and the expression of inflammatory cytokines in the hippocampus. METHODS: A total of 45 aged healthy male Sprague Dawley rats were divided into control group, sham group, and dexmedetomidine group. The open tibia fracture surgery rat model was established, and dexmedetomidine was intraperitoneally injected before operation. The cognitive function of aged rats was examined by Morris Water-Maze Test, open field experiment, and passive avoidance memory test. The expression levels of IL-6, IL-1ß, and TNF-α in the hippocampus were examined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The escape latency over 5 continuous days in the dexmedetomidine group was significantly shorter than that in the control group (all P<0.05). The number of swimming times and the percentage of swimming time in the dexmedetomidine group were significantly higher and longer than those in the control group (all P<0.05). Moreover, rats in the dexmedetomidine group exhibited shorter time of stay at the central square and higher number of standing times in comparison with the control group (all P<0.05). Compared with the control group, dexmedetomidine intraperitoneally injected before surgery significantly inhibited the expression levels of IL-6, IL-1ß, and TNF-α in the hippocampus (all P<0.05). CONCLUSION: Dexmedetomidine could significantly relieve the postoperative cognitive dysfunction in aged rats. The mechanism may be associated with the decreased inflammatory cytokines in the hippocampus.

Downregulation of miR-145 alleviates ox-LDL-induced inflammation by targeting QKI in macrophages.

OBJECTIVE: Atherosclerosis (AS) is a chronic inflammatory disease with high mortality. miRNAs perform a vital role in its development. This study aimed to discuss the effect of miR-145 in AS occurrence and development. METHODS: The effects of miR-145 mimics and inhibitors on IL-6, IL-1ß and TNF-α expressions were assessed by qRT-PCR and ELISA. CCK-8 was applied to examine the influence of miR-145 on macrophage proliferation. The influence of miR-145 on the QKI transcriptional activity was analyzed using luciferase reporter gene assy. RESULTS: Overexpression of miR-145 could enhance the expression of IL-6, IL-1ß, and TNF-α. Down-regulation of miR-145 could inhibit the proliferation of macrophages and the expression level of inflammatory cytokines. The effect of miR-145 inhibitor on the expression of inflammatory factors was partially reversed by interfering with the transcription of QKI with siRNA. CONCLUSION: miR-145 regulates the inflammatory response induced by macrophage activation through targeting QKI. It provides a means for AS targeted therapy.

Elevated Circulating LINC-P21 Serves as a Diagnostic Biomarker of Type 2 Diabetes Mellitus and Regulates Pancreatic ß-cell Function by Sponging miR-766-3p to Upregulate NR3C2.

OBJECTIVE: The purpose of this study was to evaluate the clinical value and biological function of long non-coding RNA (lncRNA) LINC-P21 in type 2 diabetes mellitus (T2DM), and explore the underlying mechanisms. METHODS: The expression of LINC-P21 was estimated using quantitative real-time PCR. The functional role of LINC-P21 was explored by gain- and loss-of-function experiments. INS-1 cell proliferation was analyzed using a cell counting kit-8 (CCK-8)assay, and the glucose-stimulated insulin secretion was measured using an ELISA kit. The miRNAs that might be sponged by LINC-P21 were analyzed, and the subsequent target genes were predicted and assessed in INS-1 cells. RESULTS: Serum expression of LINC-P21 was elevated in T2DM patients, which was correlated with fasting blood glucose levels and disease diagnosis. The glucose-stimulated insulin secretion and the proliferation of INS-1 cells were enhanced by LINC-P21 knockdown, but the overexpression of LINC-P21 led to opposite effects. miR-766-3p could be directly inhibited by LINC-P21 in INS-1 cells and reverse the effects of LINC-P21 on ß-cell function. Additionally, NR3C2 was determined as a target of miR-766-3p, which could be positively regulated by LINC-P21 and had same effects with LINC-P21 on INS-1 cell proliferation and insulin secretion. CONCLUSION: All the data demonstrated that serum elevated LINC-P21 and decreased miR-766-3p serve as candidate diagnostic biomarkers in T2DM patients. LINC-P21 acts as a potential regulator in insulin secretion and proliferation of pancreatic ß-cells through targeting miR-766-3p to upregulate NR3C2.