Cancer stem cells (CSCs) represent a subpopulation of cancer cells that are believed to initiate and drive cancer progression. In animal models, xenotransplanted CSCs have demonstrated the ability to produce tumors. Since their initial isolation in blood cancers, CSCs have been identified in various solid human cancers, including oral squamous cell carcinoma (OSCC). In addition to their tumorigenic properties, dysregulated stem-cell-related signaling pathways—Wnt family member (Wnt), neurogenic locus notch homolog protein (Notch), and hedgehog—have been shown to endow CSCs with characteristics like self-renewal, phenotypic plasticity, and chemoresistance, contributing to recurrence and treatment failure. Consequently, CSCs have become targets for new therapeutic agents, with some currently in different phases of clinical trials. Notably, small molecule inhibitors of the hedgehog signaling pathway, such as vismodegib and glasdegib, have been approved for the treatment of basal cell carcinoma and acute myeloid leukemia, respectively. Other strategies for eradicating CSCs include natural compounds, nano-drug delivery systems, targeting mitochondria and the CSC microenvironment, autophagy, hyperthermia, and immunotherapy. Despite the extensive documentation of CSCs in OSCC since its first demonstration in head and neck (HN) SCC in 2007, none of these novel pharmacological approaches have yet entered clinical trials for OSCC patients. This narrative review summarizes the in vivo and in vitro evidence of CSCs and CSC-related signaling pathways in OSCC, highlighting their role in promoting chemoresistance and immunotherapy resistance. Additionally, it addresses methodological challenges and discusses future research directions to improve experimental systems and advance CSC studies.

Objectives: This study aims to investigate whether apoptosis repressor with caspase recruitment domain (ARC) could promote survival and enhance osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Materials and methods: The lentivirus transfection method was used to establish ARC-overexpressing BMSCs. The CCK-8 method was used to detect cell proliferation. The BD Pharmingen™ APC Annexin V Apoptosis Detection kit was used to detect cell apoptosis. The osteogenic capacity was investigated by OCN immunofluorescence staining, ALP analysis, ARS assays, and RT-PCR analysis. Cells were seeded into calcium phosphate cement (CPC) scaffolds and then inserted subcutaneously into nude mice and the defect area of the rat calvarium. Histological analysis was conducted to evaluate the in vivo cell apoptosis and new bone formation of the ARC-overexpressing BMSCs. RNA-seq was used to detect the possible mechanism of the effect of ARC on BMSCs. Results: ARC promoted BMSC proliferation and inhibited cell apoptosis. ARC enhanced BMSC osteogenic differentiation in vitro. An in vivo study revealed that ARC can inhibit BMSC apoptosis and increase new bone formation. ARC regulates BMSCs mainly by activating the Fgf-2/PI3K/Akt pathway. Conclusions: The present study suggests that ARC is a powerful agent for promoting bone regeneration of BMSCs and provides a promising method for bone tissue engineering.

This study aimed to assess the reliability and validity of Graded Chronic Pain Scale 2.0 (GCPS 2.0) and Jaw Functional Limitation Scale-20 (JFLS-20) of the Malaysian English version of Diagnostic Criteria for Temporomandibular Disorders (M-English DC/TMD). GCPS 2.0 and JFLS-20 underwent psychometric analysis involving content, face, criterion, and construct (exploratory factor analysis (EFA), convergent, discriminant, known group) validity including internal and test-retest reliability on 208 samples. The construct validity was assessed against 14 hypotheses and non-parametric statistics were used to assess the data. The GCPS 2.0 and JFLS-20 had high internal consistencies (α = 0.85 and 0.96) with an intraclass correlation coefficient value of 0.95 and 0.97, respectively. The content validity index for GCPS 2.0 and JFLS-20 were 0.87 and 0.95, respectively. The EFA of GCPS 2.0 identified one factor whereas three factors were identified for JFLS-20. Both instruments had moderate to strong positive correlation with other instruments when assessing for concurrent (r = 0.75–0.80, p < 0.01) and convergent (r = 0.58–0.70, p < 0.01) validity, while moderate to high negative correlation (r = −0.86–−0.68, p < 0.01) against the global self-rating oral health items. Based on the study, GCPS 2.0 and JFLS-20 of the M-English DC/TMD proven to be reliable and valid for use in the Malaysian population with TMD.