Emerging evidence indicates that mesenchymal stem cells (MSCs) serve an indispensable role in the tumor microenvironment. However, whether MSCs participate in the development of oral carcinogenesis remains unclear. The present study isolated MSCs from clinical tissues and investigated the differences of MSCs derived from normal oral mucosa (N-MSC), oral leukoplakia with dysplasia (LK-MSC) and oral carcinoma (Ca-MSC). The results revealed that the LK-MSCs exhibited reduced proliferation and migration, compared with the N-MSCs and Ca-MSCs. Furthermore, it was demonstrated that the exosomes secreted by LK-MSCs have significant roles in promoting proliferation, migration and invasion in vitro , which was similar to the Ca-MSC-derived exosomes. The promoting effect was also demonstrated in a 3D coculture model. When the secretion of exosomes was blocked, the promoting effect of LK-MSCs was reversed. Based on a microarray analysis of MSC-derived exosomes, microRNA-8485 (miR-8485) was identified to be ectopically expressed. The exosomal miR-8485 was capable of promoting the proliferation, migration and invasion of tumor cells. Therefore, the present study highlights the significance of MSC-derived exosomes and exosomal miR-8485 in premalignant lesions and carcinogenesis. Intervention with the secretion of MSC-derived-exosomes may be an innovative strategy to retard the carcinogenesis.

The capability to analyze small RNAs responsible for post-transcriptional regulation of genes expression is essential for characterizing cellular phenotypes. Here, we describe an intracellular biopsy technique (inCell-Biopsy) for fast, multiplexed, and highly sensitive profiling of microRNAs (miRNAs). The technique uses an array of diamond nanoneedles that are functionalized with size-dependent RNA binding proteins, working as “fishing rods” to directly pull miRNAs out of cytoplasm while keeping the cells alive, thus enabling quasi-single-cell miRNA analysis. Each nanoneedle works as a reaction chamber for parallel in situ amplification, visualization, and quantification of miRNAs as low as femtomolar, which is sufficient to detect miRNAs of a single-copy intracellular abundance with specificity to single-nucleotide variation. Using inCell-Biopsy, we analyze the temporal miRNA transcriptome over the differentiation of embryonic stem cells (ESCs). The combinatorial miRNA expression patterns derived by inCell-Biopsy identify emerging cell subpopulations differentiated from ESCs and reveal the dynamic evolution of cellular heterogeneity.

Introduction: There has been a lack of treatments available to lower the frequency of recurrent aphthous ulcers (RAUs) until now. Total glucosides of paeony (TGP) is a botanical drug extracted from the dried roots of Paeonia lactiflora Pall. [Ranunculaceae; Paeoniae Radix Alba]. This study aims to evaluate the efficacy and safety of TGP in the treatment of RAU.Methods: This study was registered with the Chinese Clinical Trial Registry (ChiCTR1900025623). Patients were randomly assigned to the TGP or placebo group and treated with 1.8 g/day for 24 weeks. Participants were observed for a total of 36 weeks and were asked to record ulcer severity, medication, and adverse reactions in the form of diaries or apps every day. The primary outcome was the monthly ulcer-free interval.Results: A total of 79 individuals were enrolled, with 40 assigned to the TGP group and 39 to the placebo group. The dropout rate was 18.18%. In the TGP group, the monthly ulcer-free interval was significantly longer than baseline (median, 9.6 days) since weeks 13–24 (median, 18.5 days) (p < 0.05), and after discontinuation, it was further prolonged (median, 24.7 days) than in weeks 13–24 (p < 0.05). In addition, the monthly ulcer-free interval was longer in the TGP group than in the placebo group (median, 15.9 days) at weeks 25—36 (p < 0.001). There were better improvements in the monthly number of ulcers and monthly area of ulcers, and visual analog scoring in the TGP group at weeks 25—36 (p < 0.001).Conclusion: TGP had a good long-term therapeutic effect on RAU with frequent occurrence.Systematic Review Registration:www.chictr.org.cn, identifier ChiCTR1900025623.

RNA biology is orchestrated by the dynamic interactions of RNAs and RNA‐binding proteins (RBPs). In the present study, we describe a new method of proximity‐dependent protein labeling to detect RNA–protein interactions [RNA‐bound protein proximity labeling (RBPL)]. We selected the well‐studied RNA‐binding protein PUF to examine the current proximity labeling enzymes birA* and APEX2. A new version of birA*, BASU, was used to validate that the PUF protein binds its RNA motif. We further optimized the RBPL labeling system using an inducible expression system. The RBPL (λN‐BASU) labeling experiments exhibited high signal‐to‐noise ratios. We subsequently determined that RBPL (λN‐BASU) is more suitable than RBPL (λN‐APEX2) for the detection of RNA–protein interactions in live cells. Interestingly, our results also reveal that proximity labeling is probably capable of biotinylating proximate nascent peptide.

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