Plasma exosomal miR-122 regulates the efficacy of metformin via AMPK in type 2 diabetes and hepatocellular carcinoma.

Metformin is a drug that has been applied in clinical use for many years for the treatment of type 2 diabetes mellitus (T2DM). It achieves its function through multiple targets and modulation of multiple signaling pathways. To date, the mechanism of the action of metformin is still not fully understood. Along with glycemic control, metformin has shown good inhibitory effects on the development of many tumors. Here, we elucidated that plasma exosomal microRNA-122-5p (miR-122) is closely related to the mechanism of metformin. MiR-122 regulates glycogen-glucose metabolism in hepatocytes or hepatocellular carcinoma cells (HCC) by inhibiting the phosphorylation of AMPK. Since miR-122 and metformin regulate glucose metabolism homeostasis through similar mechanisms, miR-122 can antagonize the effects of metformin. MiR-122 expression increases the sensitivity of hepatocytes or HCC to metformin. Conversely, decreased expression of miR-122 results in hepatocyte insensitivity to metformin. Therefore, significantly elevated levels of miR-122 in plasma exosomes of hepatocellular carcinoma patients could enhance their sensitivity to metformin. The results of the present study revealed a key regulatory role of plasma exosomal miR-122 on the molecular mechanism of metformin. The regulation of key molecules of related signaling pathways by miR-122 may lead to similar glycemic lowering and tumor suppression therapeutic effects as metformin. This provides new ideas for the development of new therapeutic strategies for hepatocellular carcinoma based on the mechanism of miR-122 and metformin.

Long noncoding RNA XIST regulates osteogenic differentiation of human bone marrow mesenchymal stem cells by targeting miR-9-5p.

This study aimed to investigate whether X inactivate-specific transcript (XIST) regulated the expression of tissue non-specific alkaline phosphatase (ALPL) through miR-9-5p to promote osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). We elucidated the molecular regulation mechanisms of XIST underlying osteogenic differentiation of hBMSCs. In osteoporotic patients with hBMSCs, the expression of miR-9-5p was upregulated and the expression of XIST was downregulated. When hBMSCs were treated with osteogenic induction, the expression of XIST was increased and the expression of miR-9-5p was decreased. The osteogenic differentiation of hBMSCs was significantly decreased after knocking down XIST. Luciferase analysis revealed that XIST could directly bind to miR-9-5p and exert a negative regulatory effect on its expression. MiR-9-5p could bind directly to the 3'-UTR of ALPL and inhibit the expression of ALPL. Knockout of XIST reduced the expression of ALPL, while co-transfection of the miR-9-5p inhibitor could reverse the expression of the ALPL gene. In hBMSCs, overexpression of XIST upregulated the expression of ALPL, but the miR-9-5p mimic could reverse the expression of ALPL. Furthermore, silencing of ALPL could downregulate the expression of osteopontin(OPN) and osteocalcin(OCN) induced by miR-9-5p inhibitors. In conclusion, XIST regulated the expression of ALPL by targeting miR-9-5p. It could be used as a positive regulator of osteogenic differentiation of hBMSC.

Cervical anterior hybrid technique with bi-level Bryan artificial disc replacement and adjacent segment fusion for cervical myelopathy over three consecutive segments.

This study aimed to assess the preliminary clinical efficacy and feasibility of the hybrid technique for multilevel cervical myelopathy. Considering the many shortcomings of traditional treatment methods for multilevel cervical degenerative myelopathy, hybrid surgery (bi-level Bryan artificial disc [Medtronic Sofamor Danek, Memphis, TN, USA] replacement and anterior cervical discectomy and fusion) should be considered. Between March 2006 and November 2012, 108 patients (68 men and 40 women, average age 45years) underwent hybrid surgery. Based on the Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI), and Odom's criteria, the clinical symptoms and neurological function before and after surgery were evaluated. Mean surgery duration was 90minutes, with average blood loss of 30mL. Mean follow-up duration was 36months. At the final follow-up, the mean JOA (± standard deviation) scores were significantly higher compared with preoperative values (15.08±1.47 versus 9.18±1.22; P<0.01); meanwhile, NDI values were markedly decreased (12.32±1.03 versus 42.68±1.83; P<0.01). Using Odom's criteria, the clinical outcomes were rated as excellent (76 patients), good (22 patients), fair (six patients), and poor (four patients). These findings indicate that the hybrid method provides an effective treatment for cervical myelopathy over three consecutive segments, ensuring a good clinical outcome.