Exosomes miR-92a-3p from human exfoliated deciduous teeth inhibits periodontitis progression via the KLF4/PI3K/AKT pathway.

BACKGROUND: Periodontitis is a chronic inflammatory disease mediated by dysbiosis of the oral microflora, resulting in the destruction of periodontal tissue. Increasing evidence suggested that mesenchymal stem cell (MSCs) and exosomes derived from MSCs play a critical role in periodontal tissue regeneration. However, whether stem cells from exfoliated deciduous teeth (SHED)-secreted exosomes can improve the therapeutic potential of periodontitis is largely unknown. OBJECTIVE: Here, we aim to evaluate the effect of SHED-exosomes on inflammation, apoptosis and osteogenic differentiation in periodontitis. METHODS: The periodontitis cell model was constructed by stimulating periodontal ligament stem cells (PDLSCs) with lipopolysaccharide (LPS), and the periodontitis rats were established by ligation. RESULTS: First, we isolated exosomes from the SHED, and we figured out that exosomes secreted by SHED were enriched in miR-92a-3p and the exosomes enhanced proliferation and osteogenic differentiation and reduced apoptosis and inflammatory responses in PDLSCs. In addition, we found that SHED-exosomes alleviated inflammatory effect and elevated the expression of osteogenic-related genes in periodontitis rat model. Moreover, miR-92a-3p targeted downstream Krüppel-Like Transcription Factor 4 (KLF4) and regulated the PI3K/AKT pathway. Finally, our data indicated that upregulation of KLF4 or activation of PI3K/AKT by 740Y-P counteracted the inhibitory effect of SHED-exosomes on periodontitis progression. CONCLUSION: Taken together, our finding revealed that exosomal miR-92a-3p derived from SHED contributed to the alleviation of periodontitis development and progression through inactivating the KLF4/PI3K/AKT signaling pathway, which may provide a potential target for the treatment of periodontitis.

Ablation of FAM20C caused short root defects via suppressing the BMP signaling pathway in mice.

Short root defects are prone to cause various periodontal diseases and lead to tooth loss in some serious cases. Studies about the mechanisms governing the development of the root are needed for a better understanding of the pathogenesis of short root defects. The protein family with sequence similarity 20 group C (FAM20C) is a Golgi casein kinase that has been well studied in the development of tooth crown formation. However, whether FAM20C plays a role in the development of tooth root is still unknown. Thus, we generated Sox2-Cre;Fam20cfl/fl (cKO) mice, in which Fam20c was ablated in both the dental epithelium and dental mesenchyme, and found that the cKO mice showed severe short root defects mainly by inhibiting the development of dental mesenchyme in the root region. In this investigation, we found morphological changes and differentiation defects, with reduced expression of dentin sialophosphoprotein (DSPP) in odontoblasts of the root region in cKO mice. Furthermore, the proliferation rate of apical papillary cells was reduced in the root of cKO mice. In addition, the levels of bone morphogenetic protein 4 (BMP4) and phospho-Smad1/5/8, and that of Osterix and Krüppel-like factor 4 (KLF4), two downstream target molecules of the BMP signaling pathway, were significantly reduced in the root of cKO mice. These results indicate that FAM20C plays an essential role in the development of the root by regulating the BMP signaling pathway.

Placental-Cadherin, a biomarker for local immune status and poor prognosis among patients with tongue squamous cell carcinoma.

BACKGROUND: The prognostic and clinicopathological value of placental-Cadherin (CDH3) in multiple cancers is controversial. The diagnostic significance and functional mechanism of CDH3 in tongue squamous cell carcinoma (TSCC) have not been thoroughly investigated. This study aims to clarify the potential of CDH3 as biomarker for TSCC. METHODS: Here, meta-analysis, bioinformatics, along wet-lab techniques were employed to evaluate the diagnostic, as well as the prognostic value of CDH3 in diverse types of cancers, especially TSCC. Meta-analysis was used to determine the influence of CDH3 on prognostic and clinicopathological features in numerous cancers. Molecular biology function was used to investigate the role of CDH3 in TSCC cells. The relationship of CDH3 with tumor-infiltrating immune cells (TIICs) in TSCC was assessed using CIBERSORT. Moreover, gene set enrichment analysis (GSEA) was done based on TCGA. Besides, the hub genes and associated cascades were uncovered based on gene co-expression with CDH3. RESULTS: CDH3 upregulation correlated with worse overall survival and disease-free survival in various cancers. CDH3 was validated as an independent risk factor for HNSC and was linked to the onset of tumors, tumor stage, and infiltration depth. CDH3 silencing inhibited cell growth and induced apoptosis of the CAL-27 cell line. CDH3 expression level correlated with infiltration by macrophages, T cells, T cell regulatory cells (Tregs), and plasma cells in TSCC. GSEA revealed that CDH3 influences multiple cancer-associated cascades. Besides, CBX3, CCHCR1, along NFYC were identified as the core hub genes for CDH3. CONCLUSION: We identified CDH3 as a pan-cancer gene with potential prognostic and diagnostic significance in various cancers, particularly in TSCC, where it is tumorigenic.

Catechol-Coordinated Framework Film-based Micro-Supercapacitors with AC Line Filtering Performance.

Coordination polymer frameworks (CPFs) have broad applications due to their excellent features, including stable structure, intrinsic porosity, and others. However, preparation of thin-film CPFs for energy storage and conversion remains a challenge because of poor compatibility between conductive substrates and CPFs and crucial conditions for thin-film preparation. In this work, a CPF film was prepared by the coordination of the anisotropic four-armed ligand and CuII at the liquid-liquid interface. Such film-based micro-supercapacitors (MSCs) are fabricated through high-energy scribing and electrolytes soaking. As-fabricated MSCs displayed high volumetric specific capacitance of 121.45 F cm-3 . Besides, the volumetric energy density of MSCs reached 52.6 mWh cm-3 , which exceeds the electrochemical performance of most reported CPF-based MSCs. Especially, the device exhibited alternating current (AC) line filtering performance (-84.2° at 120 Hz) and a short resistance capacitance (RC) constant of 0.08 ms. This work not only provides a new CPF for MSCs with AC line filtering performance but also paves the way for thin-film CPFs preparation with versatile applications.

Molecular mechanisms linking peri-implantitis and type 2 diabetes mellitus revealed by transcriptomic analysis.

AIMS: To explore molecular mechanisms that link peri-implantitis and type 2 diabetes mellitus (T2DM) by bioinformatic analysis of publicly available experimental transcriptomic data. MATERIALS AND METHODS: Gene expression data from peri-implantitis were downloaded from the Gene Expression Omnibus database, integrated and differentially expressed genes (DEGs) in peri-implantitis were identified. Next, experimentally validated and computationally predicted genes related to T2DM were downloaded from the DisGeNET database. Protein-protein interaction network (PPI) pairs of DEGs related to peri-implantitis and T2DM related genes were constructed, "hub" genes and overlapping DEG were determined. Functional enrichment analysis was used to identify significant shared biological processes and signaling pathways. The PPI networks were subjected to cluster and specific class analysis for identifying "leader" genes. Module network analysis of the merged PPI network identified common or cross-talk genes connecting the two networks. RESULTS: A total of 92 DEGs overlapped between peri-implantitis and T2DM datasets. Three hub genes (IL-6, NFKB1, and PIK3CG) had the highest degree in PPI networks of both peri-implantitis and T2DM. Three leader genes (PSMD10, SOS1, WASF3), eight cross-talk genes (PSMD10, PSMD6, EIF2S1, GSTP1, DNAJC3, SEC61A1, MAPT, and NME1), and one signaling pathway (IL-17 signaling) emerged as peri-implantitis and T2DM linkage mechanisms. CONCLUSIONS: Exploration of available transcriptomic datasets revealed IL-6, NFKB1, and PIK3CG expression along with the IL-17 signaling pathway as top candidate molecular linkage mechanisms between peri-implantitis and T2DM.

Oridonin inhibits LPS-induced inflammation in human gingival fibroblasts by activating PPARγ.

Oridonin, the major terpene isolated from Rabdosia rubescens, has been used as dietary supplement. Recently, it has been known to exhibit anti-inflammatory effect. This study we employed an in vitro model of LPS-stimulated human gingival fibroblasts to investigate the anti-inflammatory effects and mechanism of oridonin. Oridonin (10-30 µg/mL) was administrated 1 h before LPS treatment. The results showed that oridonin significantly inhibited inflammatory mediators PGE2, NO, IL-6, and IL-8 production. Immunoblotting experiments revealed that oridonin reduced the expression of phosphorylation levels of NF-κB p65 and IκBα. Furthermore, the expression of PPARγ was up-regulated by the treatment of oridonin. Further studies showed that PPARγ inhibitor GW9662 could reverse the inhibition of oridonin on PGE2, NO, IL-6, and IL-8 production. In conclusion, oridonin inhibited LPS-induced microglia activation through activating PPARγ.