MicroRNAs (miRNAs) have been shown to be important regulators of TLR signaling pathway at the post-transcriptional level. In this study, the potential role of miR-149 was explored in murine alveolar macrophage RAW264.7 cells. Our results demonstrated a dynamic change of the expressions of miR-149 expression and MyD88 in macrophage RAW264.7 upon Mycobacterium bovis Bacillus Calmette-Guerlin (BCG) infection or lipopolysaccharide (LPS) stimulation. The presence of BCG or LPS dynamically reduced the miR-149 expression, along with a substantially striking increase of MyD88 expression in these cells. More importantly, overexpression of miR-149 in RAW264.7 cells was associated with a significant decrease of MyD88 protein expression, as well as a reduced production of inflammatory mediator NF-κB 1, TNF-α and IL-6 in response to BCG infection or LPS stimulation. Further studies using immunoblotting assay against anti-MyD88 antibody and microRNA targeting luciferase reporter assay revealed that miR-149 was able to directly target the 3'-UTR of MyD88 mRNA and post-transcriptionally regulated MyD88 protein expression. These data suggested that miR-149 might be a key player of immune modulator for TLR/MyD88 signaling pathway in macrophages, which may through a mechanism of negatively regulating MyD88-dependent Toll-like receptors signaling pathway.

1. The clinical use of doxorubicin, an effective anticancer drug, is severely hampered by its cardiotoxicity. Berberine, a botanical alkaloid, has been reported to possess cardioprotective and antitumor effects. In this study, we investigated the cardioprotective effect of berberine on doxorubicin-induced cardiotoxicity and the effect of berberine on the metabolism of doxorubicin. 2. Adult male Sprague-Dawley rats were administered doxorubicin in the presence or absence of berberine for 2 weeks. Administration of berberine effectively prevented doxorubicin-induced body weight reduction and mortality in rats. 3. Berberine reduced the activity of myocardial enzymes, including aspartate aminotransferase (AST), creatine kinase (CK), CK isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Echocardiographic examination further demonstrated that berberine effectively ameliorated cardiac dysfunction induced by doxorubicin. 4. Berberine inhibited the metabolism of doxorubicin in the cytoplasm of rat heart and reduced the accumulation of doxorubicinol (a secondary alcohol metabolite of doxorubicin) in heart. 5. These data showed that berberine alleviated the doxorubicin-induced cardiotoxicity in rats via inhibition of the metabolism of doxorubicin and reduced accumulation of doxorubicinol selectively in hearts.

Most diabetic patients develop diabetic peripheral neuropathy (DPN). DPN is related to the increase of inflammatory cells in peripheral nerves, abnormal cytokine expression, oxidative stress, ischemia ,and pro-inflammatory changes in bone marrow. We summarized the progress of immune-inflammatory mechanism and treatment of DPN in recent years. Immune inflammatory mechanisms include TNF-α, HSPs, PARP, other inflammatory factors, and the effect of immune cells on DPN. Treatment includes tricyclic antidepressants and other drug therapy, immune and molecular therapy, and non-drug therapy such as exercise therapy, electrotherapy, acupuncture, and moxibustion. The pathogenesis of DPN is complex. In addition to strictly controlling blood glucose, its treatment should also start from other ways, explore more effective and specific treatment schemes for various causes of DPN, and find new targets for treatment will be the direction of developing DPN therapeutic drugs in the future.

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