No abstract

Background and Objective MicroRNA‐146a (miR‐146a) is a small noncoding RNA that plays a critical role in the negative regulation of the innate immune response, and the dysregulation of miR‐146a has been associated with several inflammatory disorders. In generalized aggressive periodontitis (GAgP) the degree of clinical inflammation appears to be similar to that of chronic periodontitis, and, in this situation, age of onset and family history are important additional criteria for diagnosis. This study was performed to evaluate the level of miR‐146a expressed in gingival tissues of patients with GAgP and its association with disease severity. Material and Methods Gingival samples from 18 patients with GAgP and 10 healthy subjects were collected and the level of miR‐146a and its targets, including necrosis factor‐alpha, interleukin‐1beta, and interleukin‐6, were assessed using real‐time PCR. Clinical parameters, including probing depth and clinical attachment loss, were measured and their correlations with the level of miR‐146a were determined. Results Our results demonstrated an elevation in the level of miR‐146a expressed in patients with GAgP compared with healthy controls (P < .001), which was directly associated with disease severity (P < .05). Overexpression of miR‐146a was accompanied by a reduction in the levels of pro‐inflammatory cytokines. Conclusions Our findings suggest that there is an association between miR‐146a and GAgP and imply that miR‐146a may serve as an indicator of periodontal disease severity. However, further studies and additional information are required to confirm this relationship and the precise role of miR‐146a in the development and/or progression of periodontitis.

No abstract

No abstract

Exosomes have been introduced as a new alternative delivery system for the transmission of small molecules. Tumor-derived exosomes (TEXs) not only contain tumor-associated antigens to stimulate antitumor immune responses but also act as natural carriers of microRNAs. The aim of the current study was to evaluate the efficacy of miR-124-3p-enriched TEX (TEXomiR) as cell-free vaccine in the induction of antitumor immune responses in a mouse model of colorectal cancer. Briefly, the exosomes were isolated from cultured CT-26 cell line, and modified calcium chloride method was used to deliver miR-124-3p mimic into the exosomes. We used a CT-26-induced BALB/c mouse model of colorectal cancer and analyzed the effect of TEXomiR on survival, tumor size, spleen and tumor-infiltrated lymphocytes, and splenocyte proliferation. Furthermore, intra-tumor regulatory T cells, cytotoxic activity of the splenocytes, and cytokine secretion was also evaluated to describe the anti-tumor immune response. When the tumor size reached 100 mm3, the mice were injected with TEXomiR, TEX, and/or phosphate-buffered saline (PBS) subcutaneously three times with 3-day interval, and then tumor size was monitored every 2 days. The in vitro results indicated that TEXs could efficiently deliver functional miR-124-3p mimic. The in vivo evaluation in tumor-bearing mice showed that treatment with TEXomiR can elicit a stronger anti-tumor immune response than unloaded TEX and PBS. Significant tumor growth inhibition and increased median survival time was achieved in tumor-bearing mice treated with TEXomiR. A significant decrease in CD4/CD8 and Treg/CD8 ratio in tumor tissue was demonstrated. Moreover, increased cytotoxicity and proliferation of splenocytes in the TEXomiR group compared to the TEX and PBS groups were identified. Taken together, our data demonstrated that tumor-derived exosomes efficiently deliver miR-124-3p mimic, and TEXomiR promotes anti-tumor immune responses.