Orofacial pain represents one of the most common health problems that negatively affects the activities of daily living. However, the mechanisms underlying these conditions are still unclear, and their comprehensive management is often lacking. Moreover, even if pain is a common symptom in dentistry, differential diagnostic procedures are needed to exclude other pain origins. Misinterpretation of the pain origin, in fact, can lead to misdiagnosis and to subsequent mismanagement. Pain in the orofacial area is the most common reason for patients to visit the dentist, but this area is complex, and the pain could be associated with the hard and soft tissues of the head, face, oral cavity, or to a dysfunction of the nervous system. Considering that the origins of orofacial pain can be many and varied, a thorough assessment of the situation is necessary to enable the most appropriate diagnostic pathway to be followed to achieve optimal clinical and therapeutic management.

Glioblastoma (GB) is an extremely aggressive, highly invasive brain tumor of astrocytic or oligodendrocyte glial origin. This tumor often infiltrates adjacent healthy brain tissue and can migrate significant distances from the primary tumor site. Given the poor overall survival of GB patients and the limited efficacy of current local and systemic treatments, new therapeutic strategies are needed to improve outcomes, reduce side effects, and enhance patients’ quality of life. In recent years, the potential chemotherapeutic effects of natural molecules have been investigated, either as primary agents or in combination with established chemotherapies in various types of cancer. Melatonin (MLT, N-acetyl-5-methoxytryptamine) is an endogenous indolamine primarily secreted by the pineal gland. MLT appears to discriminate between normal and tumoral cellular contexts and to modulate appropriate actions, thereby acting as a “smart killer” against cancer cells; however, further studies are needed to clarify this apparently paradoxical behavior. This review aims to summarize recent findings on the potential regulatory role of MLT in the modulation of key intracellular pathways in GB, underlining its potential role as a complementary adjuvant to conventional therapies. The clinical advantage of MLT in GB patients has not been demonstrated in randomized controlled trials; therefore, multicenter studies with well-defined objectives, appropriate dosage schedules, and clear patient classification are needed.

Early identification of the risk of malignant transformation in oral potentially malignant disorders (OPMDs) is critical for improving outcomes in oral squamous cell carcinoma (OSCC). This comprehensive review examines immunological biomarkers obtained from minimally invasive oral cytobrush (OCB) specimens for the early detection of OSCC within a precision medicine framework. The objectives were to (1) identify and characterise key immunological biomarkers associated with early oral carcinogenesis; (2) evaluate the diagnostic utility of OCB sampling for detecting these biomarkers; and (3) explore the potential of OCB-based profiling to support personalised screening and patient management. The review highlights the potential advantages of OCB compared with conventional diagnostic methods, as reported in the literature, particularly its ability to capture early malignant changes through immunological analysis. Evidence is discussed for biomarker pathways related to cell-cycle and differentiation dysregulation (p53, Ki-67, CKs), inflammation-driven epithelial transformation (IL-1β, IL-6, IL-8, TNF-α), and immune suppression and checkpoint activation (PD-L1, B7-H6). OCB provides reliable and patient-friendly cyto-salivary samples that are suitable for immunological and molecular analyses. Aberrant biomarker expression detected in OCB specimens correlates with epithelial dysplasia and reflects early non-invasive neoplastic transformation, supporting the diagnostic value of integrated biomarker panels. Overall, OCB-based immunoanalysis represents a practical, non-invasive approach for the early detection of OSCC. Emerging technologies, including AI and multi-omics approaches, may further support the precision and predictive values of immunological analysis for OSCC. When combined with relevant biomarker pathways reflecting tumour biology and host immune responses, this strategy could offer a strong foundation for precision-medicine screening. It may also support personalised monitoring in patients with OPMDs.