Oral submucous fibrosis (OSF), characterized by excessive deposition of extracellular matrix (ECM) that causes oral mucosal tissue sclerosis, and even cancer transformation, is a chronic, progressive fibrosis disease. However, despite some advancements in recent years, no targeted antifibrotic strategies for OSF have been approved; likely because the complicated mechanisms that initiate and drive fibrosis remain to be determined. In this review, we briefly introduce the epidemiology and etiology of OSF. Then, we highlight how cell-intrinsic changes in significant structural cells can drive fibrotic response by regulating biological behaviors, secretion function, and activation of ECM-producing myofibroblasts. In addition, we also discuss the role of innate and adaptive immune cells and how they contribute to the pathogenesis of OSF. Finally, we summarize strategies to interrupt key mechanisms that cause OSF, including modulation of the ECM, inhibition of inflammation, improvement of vascular disturbance. This review will provide potential routes for developing novel anti-OSF therapeutics.

Oral squamous cell carcinoma (OSCC) is a type of malignancy with high mortality, leading to poor prognosis worldwide. However, the molecular mechanisms underlying OSCC carcinogenesis have not been fully understood. Recently, the discovery and characterization of long non-coding RNAs (lncRNAs) have revealed their regulatory importance in OSCC. Abnormal expression of lncRNAs has been broadly implicated in the initiation and progress of tumors. In this review, we summarize the functions and molecular mechanisms regarding these lncRNAs in OSCC. In addition, we highlight the crosstalk between lncRNA and tumor microenvironment (TME), and discuss the potential applications of lncRNAs as diagnostic and prognostic tools and therapeutic targets in OSCC. Notably, we also discuss lncRNA-targeted therapeutic techniques including CRISPR-Cas9 as well as immune checkpoint therapies to target lncRNA and the PD-1/PD-L1 axis. Therefore, this review presents the future perspectives of lncRNAs in OSCC therapy, but more research is needed to allow the applications of these findings to the clinic.

Introduction: 5-methyltetrahydrofolate (5-MTHF), the biologically active form of folate, possesses well-characterized anti-inflammatory and antioxidant properties that are closely implicated in the regulation of cellular senescence. Accordingly, this study aimed to investigate whether 5-MTHF attenuates periodontitis by mitigating cellular senescence. Methods: We performed a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 to evaluate the association between serum 5-MTHF levels and periodontitis. Weighted multivariable regression models were applied, and exploratory mediation analysis assessed the contribution of biological aging. In vitro experiments examined the anti-senescence effect of 5-MTHF on lipopolysaccharide (LPS)-induced human gingival fibroblasts (HGFs). An in vivo mouse model of experimental periodontitis was used to evaluate alveolar bone loss. Results: Among 6,245 adults, higher serum 5-MTHF levels were significantly associated with lower odds of periodontitis, reduced clinical attachment loss, and shallower probing depth. Biological aging mediated 5.5%–17.3% of these associations. Mechanistically, 5-MTHF treatment attenuated LPS-induced cellular senescence in HGFs, as shown by decreased SA-β-gal activity, downregulation of p16, p21, and senescence-associated secretory phenotype genes. Correspondingly, local administration of 5-MTHF significantly alleviated alveolar bone resorption in mice with periodontitis. Discussion: 5-MTHF is associated with improved periodontal health, partly through attenuating cellular senescence. Our findings suggest that targeting senescence with 5-MTHF may represent a novel mechanism-based strategy for preventing and treating periodontitis.