Candida albicans-myeloid cells-T lymphocytes axis in the tumor microenvironment of oral tumor-bearing mice.

Candida albicans (C. albicans) is associated with the development of oral cancer. Here, we report the altered tumor microenvironment in oral tumor-bearing mice caused by C. albicans infection. Single-cell RNA sequencing showed that C. albicans infection influenced the tumor microenvironment significantly. Specifically, C. albicans infection reduced the CD8+ T cells but increased the IL-17A+ CD4+ T cells and IL-17A+ γδ T cells in oral tumor. The neutralization of IL-17A or TCR γ/δ alleviated the tumor progression caused by C. albicans infection. Additionally, C. albicans infection promoted the infiltration of myeloid-derived suppressor cells (MDSCs) into tumor, especially polymorphonuclear (PMN)-MDSCs, which infiltration was reduced after the neutralization of CCL2. Thus, our findings reveal the myeloid cells-T lymphocytes axis in oral tumor microenvironment with C. albicans infection, which helps to understand the mechanisms for C. albicans promoting oral cancer from the perspective of immune microenvironment.

Single-cell atlas of dental pulp stem cells exposed to the oral bacteria Porphyromonas gingivalis and Enterococcus faecalis.

Introduction: Porphyromonas gingivalis and Enterococcus faecalis promote the development of pulpitis and periapical periodontitis. These bacteria are difficult to eliminate from the root canal systems, leading to persistent infection and poor treatment outcomes. We explored the response of human dental pulp stem cells (hDPSCs) to bacterial invasion and the mechanisms underlying the impact of residual bacteria on dental pulp regeneration. Methods: Single-cell sequencing was used to categorize the hDPSCs into clusters based on their response to P. gingivalis and E. faecalis. We depicted a single-cell transcriptome atlas of hDPSCs stimulated by P. gingivalis or E. faecalis. Results: The most differentially expressed genes in the Pg samples were THBS1, COL1A2, CRIM1, and STC1, which are related to matrix formation and mineralization, and HILPDA and PLIN2, which are related to the cellular response to hypoxia. A cell cluster characterized by high expression levels of THBS1 and PTGS2 was increased after P. gingivalis stimulation. Further signaling pathway analysis showed that hDPSCs prevented P. gingivalis infection by regulating the TGF-ß/SMAD, NF-κB, and MAPK/ERK signaling pathways. Differentiation potency and pseudotime trajectory analyses showed that hDPSCs infected by P. gingivalis undergo multidirectional differentiation, particularly to the mineralization-related cell lineage. Furthermore, P. gingivalis can create a hypoxia environment to effect cell differentiation. The Ef samples were characterized by the expression of CCL2, which is related to leukocyte chemotaxis, and ACTA2, which is related to actin. There was an increased proportion of a cell cluster that was similar to myofibroblasts and exhibited significant ACTA2 expression. The presence of E. faecalis promoted the differentiation of hDPSCs into fibroblast-like cells, which highlights the role of fibroblast-like cells and myofibroblasts in tissue repair. Discussion: hDPSCs do not maintain their stem cell status in the presence of P. gingivalis and E. faecalis. They differentiate into mineralization-related cells in the presence of P. gingivalis and into fibroblast-like cells in the presence of E. faecalis. We identified the mechanism underlying the infection of hDPSCs by P. gingivalis and E. faecalis. Our results will improve understanding of the pathogenesis of pulpitis and periapical periodontitis. Furthermore, the presence of residual bacteria can have adverse effects on the outcomes of regenerative endodontic treatment.

TGF-ß Signaling in Progression of Oral Cancer.

Oral cancer is a common malignancy worldwide, accounting for 1.9% to 3.5% of all malignant tumors. Transforming growth factor ß (TGF-ß), as one of the most important cytokines, is found to play complex and crucial roles in oral cancers. It may act in a pro-tumorigenic and tumor-suppressive manner; activities of the former include cell cycle progression inhibition, tumor microenvironment preparation, apoptosis promotion, stimulation of cancer cell invasion and metastasis, and suppression of immune surveillance. However, the triggering mechanisms of these distinct actions remain unclear. This review summarizes the molecular mechanisms of TGF-ß signal transduction, focusing on oral squamous cell and salivary adenoid systemic carcinomas as well as keratocystic odontogenic tumors. Both the supporting and contrary evidence of the roles of TGF-ß is discussed. Importantly, the TGF-ß pathway has been the target of new drugs developed in the past decade, some having demonstrated promising therapeutic effects in clinical trials. Therefore, the achievements of TGF-ß pathway-based therapeutics and their challenges are also assessed. The summarization and discussion of the updated knowledge of TGF-ß signaling pathways will provide insight into the design of new strategies for oral cancer treatment, leading to an improvement in oral cancer outcomes.

Midpalatal Suture: Single-Cell RNA-Seq Reveals Intramembrane Ossification and Piezo2 Chondrogenic Mesenchymal Cell Involvement.

The midpalatal suture is mainly responsible for the growth and development of the maxillary and resistance to rapid maxillary expansion (RME). It is essential for clinical researchers to explore the intramembrane ossification and to elucidate the underlying mechanism of the maturation and ossification process of the midpalatal suture to help identify the optimum time and force of RME. However, mechanistic studies associated with the midpalatal suture are rare. The aim of this present study is to create an intramembrane osteogenesis model for the midpalatal suture region of mice. Interestingly, we discovered a type of chondrogenic mesenchymal cell expressing Piezo2, which might be related to the detection of mechanical and external stimuli. This result provides a potential molecular and cellular mechanism that explains why the midpalatal suture is not closed until adulthood. We depict a landscape of mesenchymal cells that might play an important role in the intramembrane osteogenesis of the midpalatal suture and provide new perspectives on midpalate suture maturation and ossification, which might lead to further possibilities for clinical operations.

Impacts of Delivery Mode and Maternal Factors on Neonatal Oral Microbiota.

Objectives: Initial oral microbial colonization has complicatedly interacted with growth and development. The aim of our study was to discover links between oral microbiota community structure and mode of delivery, maternal factors, such as systemic diseases, abortion history, and pregnancy complications. Methods: A total of 177 pregnant women and their neonates were enrolled at Peking university people's hospital. We collected oral samples, medical history, and development phenotype and used a 16S rRNA gene sequence to analyze microbial diversity at all taxonomic levels, network structure, and metabolic characteristics. Results: Firmicutes, Proteobacteria, and Actinobacteriota were the most predominant bacteria of neonatal oral samples among these phyla. Alpha-diversity of pregnant women with gestational diabetes mellitus (GDM), abortion history, and without immune diseases was higher than in control groups, and no significant dissimilarity in beta-diversity was observed between different maternal factors. Obvious separation or trend failed to be seen in different development phenotype groups. Besides, Oscillospirales were significantly more abundant in a natural delivery group than in the cesarean section group. Conclusion: Our study indicated that maternal factors and mode of delivery influenced the oral microbial structure, but longitudinal studies were indispensable for capturing the long-term effects on neonatal development phenotype and oral microbiota.

Nitrate ameliorates dextran sodium sulfate-induced colitis by regulating the homeostasis of the intestinal microbiota.

Inflammatory bowel disease (IBD) involves chronic inflammation, loss of epithelial integrity, and gastrointestinal microbiota dysbiosis. Effective therapies for IBD have not been established. Accordingly, in this study, we evaluated the effects of inorganic nitrate, a potent nitric oxide (NO) donor and microbiota regulator, in a mouse model of dextran sodium sulfate (DSS)-induced colitis. Mice were pretreated with NaNO3 (2 mM) in their drinking water for 5 days, and NaCl was used as a control. Feces were collected for microbiota analyses. The results showed that oral administration of dietary nitrate could maintained colon consistency, improved colon length, maintained body weight, decreased apoptosis in colon epithelial cells, and ameliorated inflammatory cell infiltration in both the colon and peripheral blood. Microbiota profiling revealed that nitrate regulated dysbiosis. Analysis of the top bacteria at the genus level showed that Bacteroidales_S24-7_group_unidentified, Lactobacillus, Bacteroides, and Prevotellaceae_UCG-001 decreased in the DSS group compared with that in the normal group, whereas Lactobacillus, Ruminococcaceae_UCG-014, and Prevotellaceae_UCG-001 were increased in the DSS + NaNO3 group compared with that in the DSS group. The enriched bacteria in the nitrate group included Gordonibacter, Ureaplasama, and Lachnospiraceae_UCG-006. Moreover, microbiota analysis revealed that nitrate could partially decrease the enriched metabolic pathways (p53 signaling pathway and colorectal cancer pathway) compared with that in the DSS and DSS + NaCl groups. Overall, these findings indicated that nitrate could ameliorate DSS-induced colitis by decreasing inflammation, reducing apoptosis, and regulating the microbiota by activation of the NO3-/NO2-/NO pathway. Nitrate might be a potential treatment for colitis patients in the future clinical application.

Oral microbiomes: more and more importance in oral cavity and whole body.

Microbes appear in every corner of human life, and microbes affect every aspect of human life. The human oral cavity contains a number of different habitats. Synergy and interaction of variable oral microorganisms help human body against invasion of undesirable stimulation outside. However, imbalance of microbial flora contributes to oral diseases and systemic diseases. Oral microbiomes play an important role in the human microbial community and human health. The use of recently developed molecular methods has greatly expanded our knowledge of the composition and function of the oral microbiome in health and disease. Studies in oral microbiomes and their interactions with microbiomes in variable body sites and variable health condition are critical in our cognition of our body and how to make effect on human health improvement.