Melatonin inhibits tongue squamous cell carcinoma: Interplay of ER stress-induced apoptosis and autophagy with cell migration.

Tongue squamous cell carcinoma (TSCC) occupies a high proportion of oral squamous cell carcinoma. TSCC features high lymph node metastasis rates and chemotherapy resistance with a poor prognosis. Therefore, an effective therapy strategy is needed to improve patient prognosis. Melatonin (MT) is a natural indole compound shown to have anti-tumor effects in several cancers. This study focused on the role and mechanism of MT in TSCC cells. The results of the study suggest that MT could inhibit cell proliferation in CRL-1623 cells. Western blot analysis showed the down-regulate of cyclin B1 and the up-regulate P21 protein by MT. MT was also shown to down-regulate the expression of Zeb1, Wnt5A/B, and ß-catenin protein and up-regulate E-cadherin to inhibit the migration of CRL-1623 cells. MT also promoted the expression of ATF4, ATF6, Bip, BAP31 and CHOP in CRL-1623 cells leading to endoplasmic reticulum stress, and induced autophagy and apoptosis in CRL-1623 cells. Western blots showed that MT could promote the expression of Bax, LC3, and Beclin1 proteins and inhibit the expression of p62. We screened differentially expressed long non-coding RNAs (lncRNAs) in MT-treated cells and found that the expression of MALAT1 and H19 decreased. Moreover, MT inhibited tumor growth in nude mice inoculated with CRL-1623 cells. These results suggest that MT could induce autophagy, promote apoptosis, and provide a potential natural compound for the treatment of TSCC.

Functional drug-delivery hydrogels for oral and maxillofacial wound healing.

The repair process for oral and maxillofacial injuries involves hemostasis, inflammation, proliferation, and remodeling. Injury repair involves a variety of cells, including platelets, immune cells, fibroblasts, and various cytokines. Rapid and adequate healing of oral and maxillofacial trauma is a major concern to patients. Functional drug-delivery hydrogels play an active role in promoting wound healing and have shown unique advantages in wound dressings. Functional hydrogels promote wound healing through their adhesive, anti-inflammatory, antioxidant, antibacterial, hemostatic, angiogenic, and re-epithelialization-promoting properties, effectively sealing wounds and reducing inflammation. In addition, functional hydrogels can respond to changes in temperature, light, magnetic fields, pH, and reactive oxygen species to release drugs, enabling precise treatment. Furthermore, hydrogels can deliver various cargos that promote healing, including nucleic acids, cytokines, small-molecule drugs, stem cells, exosomes, and nanomaterials. Therefore, functional drug-delivery hydrogels have a positive impact on the healing of oral and maxillofacial injuries. This review describes the oral mucosal structure and healing process and summarizes the currently available responsive hydrogels used to promote wound healing.

Regulation of epigenetic modifications in the head and neck tumour microenvironment.

Head and neck tumours are common malignancies that are associated with high mortality. The low rate of early diagnosis and the high rates of local recurrence and distant metastasis are the main reasons for treatment failure. Recent studies have established that the tumour microenvironment (TME) can affect the proliferation and metastasis of head and neck tumours via several mechanisms, including altered expressions of certain genes and cytokines. Increasing evidence has shown that epigenetic modifications, such as DNA methylation, histone modification, RNA modification, and non-coding RNAs, can regulate the head and neck TME and thereby influence tumour development. Epigenetic modifications can regulate the expression of different genes and subsequently alter the TME to affect the progression of head and neck tumours. In addition, the cell components in the TME are regulated by epigenetic modifications, which, in turn, affect the behaviour of head and neck tumour cells. In this review, we have discussed the functions of epigenetic modifications in the head and neck TME. We have further examined the roles of such modifications in the malignancy and metastasis of head and neck tumours.

Engineered stem cell exosomes for oral and maxillofacial wound healing.

Wound healing of the oral and maxillofacial area affects the quality of life and mental health of the patient; therefore, effective therapies are required to promote wound healing. However, traditional treatment methods have limited efficacy. Exosomes secreted by stem cells used for oral and maxillofacial wound healing have shown outstanding results. Stem cell-derived exosomes possess the regenerative and repair ability of stem cells. Moreover, they are nontumorigenic and have good biosafety. However, the application of natural stem cell exosomes is limited owing to their low yield, impurity, lack of targeting, and low drug delivery rate. Many modification methods have been developed to engineered stem cell exosomes with beneficial properties, such as modifying parent cells and directly processing stem cell exosomes. These methods include coincubation, genetic engineering, electroporation, ultrasound, and artificial synthesis of engineered stem cell exosomes. These engineered stem cell exosomes can cargo nucleic acids, proteins, and small molecules. This gives them anti-inflammatory and cell proliferation regulatory abilities and enables the targeted promotion of efficient soft tissue repair after trauma. Engineered stem cell exosomes can decrease inflammation, promote fibroblast proliferation, and angiogenesis, and decrease scar formation to promote oral and maxillofacial wound healing, including diabetic and burn wounds. Thus, engineered stem cell exosomes are an effective treatment that has the potential for oral and maxillofacial wound healing.