Role of Nampt overexpression in a rat model of Hashimoto's thyroiditis and its mechanism of action.

The present study was designed to investigate the role of nicotinamide phosphoribosyltransferase (Nampt) overexpression in a rat model of Hashimoto's thyroiditis (HT) and its mechanism of action. A rat model of HT was constructed, and the HT rats were injected with an adenoviral expression vector carrying the Nampt gene. The expression of Nampt and Toll-like receptor 4 (TLR4) in thyroid tissues was examined using immunohistochemistry (IHC), RT-qPCR and western blot analyses. Serum anti-thyroglobulin antibodies (TGAb) and anti-thyroid peroxidase antibodies (TPOAb) were measured using chemiluminescence method. Hematoxylin and eosin (H&E) and IHC staining of the rat thyroid tissues showed destroyed thyroid follicles and monocyte infiltration, as well as increased Nampt expression in the thyroid tissues of rats with HT. Furthermore, it was found that Nampt overexpression led to increased severity of inflammatory infiltration in thyroid tissues and increased levels of TPOAb in the serum of HT rats; however, the serum TGAb level was not affected by Nampt overexpression. In addition, Nampt overexpression promoted TLR4 expression in HT rats. In conclusion, it was demonstrated that Nampt was strongly expressed in the capillary region of HT rats thyroid tissues. The Nampt mRNA level was increased but the Nampt protein level was decreased in the thyroid tissues of rats with HT. Nampt overexpression has a promotive effect on HT progression, and this effect was related to TLR4. This study suggests that inhibition of Nampt activity may be valuable in the treatment of HT.

miR­124 regulates the osteogenic differentiation of bone marrow­derived mesenchymal stem cells by targeting Sp7.

MicroRNAs (miRNAs) are novel key regulators of cellular differentiation. miR­124 has been reported to regulate osteogenic differentiation of bone marrow­derived mesenchymal stem cells (BMSCs). However, the specific mechanisms involved have not yet been fully elucidated. The present study aimed to investigate the effect of miR­124 on osteogenic differentiation of BMSCs and its underlying mechanisms. In the present study, it was found that alkaline phosphatase (ALP) activity, osteocalcin (OC) secretion, and the protein levels of osterix (Sp7) and runt­related transcription factor 2 (Runx2) were significantly increased, whereas the expression of miR­124 was decreased in a time­dependent manner during osteogenic differentiation of BMSCs. Following overexpression of miR­124 via transfection of miR­124 mimics in BMSCs, Runx2 protein expression and ALP activity were significantly decreased. By contrast, inhibition of miR­124 expression led to an increase in ALP activity and Runx2 expression. Sp7 expression was suppressed in BMSCs transfected with miR­124 mimics while increased when miR­124 expression was inhibited, indicating that miR­124 regulates the expression of Sp7. Moreover, a luciferase reporter assay further verified that Sp7 is the direct target of miR­124. Finally, the effect of miR­124 inhibitor on promoting the differentiation of BMSCs was abolished following treatment with a small interfering RNA targeting Sp7. Taken together, the present study demonstrates that miR­124 inhibits the osteogenic differentiation of BMSCs by targeting Sp7.

[Effects of glimepiride and metformin on free fatty acid in patients with Type 2 diabetes mellitus].

OBJECTIVE: To investigate the effect of glimepiride and metformin on free fatty acid (FFA) in patients with Type 2 diabetes mellitus and to further study the relationship between free fatty acid and insulin resistance in patients with Type 2 diabetes mellitus. METHODS: A prospective and case-control study was conducted. Ninty-four patients with Type 2 diabetes mellitus (35-70 year-old) were divided into 3 groups: glimepiride treated group (n=33), metformin treated group (n=29) and glimepiride plus metformin treated group (n=32). These patients were followed up for 6 months. Free fatty acids were measured by using an enzymatic colorimetry. RESULTS: The concentration of FFA didn't significantly change in the glimepiride treated group at the end of treatment, but it obviously decreased in the metformin treated group and in the glimepiride plus metformin treated group (P < 0.05 and P < 0.001, respectively). The decrease of FFA in the glimepiride plus metformin treated group was more obvious than that in the glimepiride treated group (P < 0.05). The fasting serum FFA concentration is positively related to HOMA-IR( homeostasis model assessment-insulin resistance) and the choice of drugs by stepwise regression analysis. CONCLUSION: Metformin alone or metformin plus glimepiride can decrease FFA levels, body weight index, blood glucose and insulin resistance. FFA level can reflect the index of insulin resistance to some degree.