Oral cancer has a high mortality rate, making early diagnosis crucial for effective treatment and prognosis. Unlike other cancers, oral cancer develops in the oral cavity, enabling direct contact between saliva and cancer cells.Therefore, saliva is a more useful diagnostic tool than serum or tissue. When DNA, RNA, or proteins produced by cancer cells enter the saliva, they can be easily detected as tumor markers. Therefore, salivary biomarkers can serve as a noninvasive alternative to serum- or tissue-based biomarkers. Early diagnosis is essential for increasing the treatment success rate, improving prognosis, and enhancing post-treatment recovery, ultimately improving the quality of life. Proteins are essential molecules involved in key processes, such as the development, growth, death, and metastasis of oral cancer. Recent advancements in molecular biology and salivary proteomics have enabled the detection and analysis of numerous proteins in saliva. Many of these protein molecules are currently the focus of extensive research. This article aims to review the potential of saliva as a diagnostic tool, techniques for detecting protein biomarkers, and salivary protein biomarkers for oral cancer diagnosis.

The swallowing reflex is modulated by multiple sensory inputs, such as bolus volume, viscosity, and taste. The interactions among different types of sensory information have been extensively studied. However, the influence of oral temperature on bolus volume perception has not been investigated. The aim of this study was to assess the effect of temperature on volume perception sensitivity in healthy individuals. Five volumes (5, 10, 15, 20, and 25 mL) of distilled water were estimated at three different temperatures, 4℃ (cold), 21℃ (room temperature), and 45℃ (warm), using a visual analogue scale. There were no significant differences in the sensitivity of oral volume perception across temperatures. These findings suggest that the ability to perceive bolus volume remains stable under temperature variation.

Sympathetic innervation stimulates β-adrenergic receptors, triggering cyclic adenosine monophosphate (cAMP) production and enhancing protein secretion in salivary gland cells. While cAMP signaling, in conjunction with Ca 2+ signaling, is essential for salivary gland function, the identified cAMP-producing G-protein-coupled receptors (GPCRs) remains limited. Here, we report the presence of cAMP-producing adenosine receptors in salivary gland cells. By reanalyzing publicly available single-cell transcriptome datasets of human and mouse submandibular glands, we identified mRNA expression of adenosine A1, A2A, A2B, and A3 receptors. Additionally, we confirmed that 5’-N-ethylcarboxamidoadenosine (NECA), an adenosine A2B receptor agonist, increases cAMP levels in human salivary gland cells, suggesting a physiological role for adenosine A2B receptors. Our findings enhance understanding of adenosine’s regulatory function in salivary glands and highlight new avenues for research on cAMPproducing adenosine receptors.

Visfatin, an adipokine secreted by cells, is crucial for intracellular nicotinamide adenine dinucleotide + biosynthesis.Extracellularly, visfatin plays diverse roles in inflammatory conditions, including obesity, which is closely linked to osteoclastogenesis. We previously showed that visfatin enhances receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis in bone marrow-derived macrophages. However, its enzymatic activity during this process is poorly understood. Here, we investigated visfatin’s effects on RANKL-induced osteoclast differentiation. Our results demonstrate that visfatin promotes this differentiation, an effect inhibited by FK866, an inhibitor of visfatin’s enzymatic activity. Furthermore, FK866 also inhibited RANKL-induced osteoclast differentiation.These findings suggest that inhibiting visfatin’s enzymatic activity modulates osteoclast differentiation. Thus, visfatin plays an important role in osteoclastogenesis, both intracellularly and extracellularly, and FK866 has therapeutic potential for diseases characterized by imbalanced osteoclast formation, such as osteoporosis and periodontitis.

Periodontitis is a chronic inflammatory disease characterized by the progressive destruction of periodontal tissue and alveolar bone loss. To develop effective treatment strategies, a model that mimics this disease must be implemented. From this perspective, animal models can be used to investigate its mechanisms by reproducing disease progression and providing insights into host-microbe interactions, immune responses, and bone remodeling.In addition, periodontitis-associated bone loss fundamentally differs from systemic bone loss. Targeted treatments require distinguishing periodontitis-induced and systemic bone loss mechanisms. This review examines the rationale for using animal models in periodontal research and evaluates various experimental approaches, such as bacterial inoculation, ligature-induced periodontitis, and chemically induced inflammation. These models have advanced our understanding of periodontal disease but have limitations in replicating the chronic nature of periodontitis and human immune responses. However, current models cannot fully replicate chronic disease progression and human immune responses. Recent developments have focused on improving animal models to more accurately simulate disease progression and host responses, which has led to the elucidation of the immunomodulatory mechanisms of periodontitis and their relevance to the human dental environment. Moreover, new approaches, such as developing age-related periodontitis models and improving ligature techniques, could enhance experimental reproducibility and translational potential. Future studies are needed to reflect these improvements and enhance the clinical relevance of periodontitis models.

Extracellular traps (ETs), primarily composed of DNA and antibacterial peptides, are mainly secreted by neutrophils to inhibit pathogen spread and eliminate microorganisms. Recent reports suggest that microglia can also secrete ETs, and these microglial ETs are associated with various neurological conditions, including nerve injury, tumor microenvironment, and ischemic stroke. However, the components and functions of microglial ETs remain underexplored. Secretagogin (Scgn), a calcium-sensor protein, plays a crucial role in the release of peptide hormones, such as insulin, in endocrine cells; however, its function in immune cells, including microglia, is not well understood. Our study demonstrated that Scgn deficiency can lead to the formation of abnormal ETs. We hypothesized that this may involve the c-Jun N-terminal kinase-myeloperoxidase pathway and autophagy.

Ophiopogonin D (OPD) is a steroidal glycoside derived from Ophiopogon japonicus, a traditional Chinese medicine with diverse biological activities, including antithrombosis, anti-inflammation, and antitussive effects. To investigate the cellular effects and mechanisms of OPD on oral squamous cell carcinoma, cell viability was explored, and the effects of OPD on cell cycle regulators, apoptotic marker proteins, and key proteins involved in metastasis and signaling pathways were examined by MTT assay and Western blotting in YD38 cells. OPD strongly inhibited cell proliferation and induced caspase-dependent apoptosis of YD38 cells by suppressing the cell cycle and activating caspase-3 and poly ADP ribose polymerase. Additionally, OPD suppressed the expression of vital proteins regulating metastasis and proliferation within the integrin/matrix metalloproteinases/FAK and AKT/PI3K/mTor pathways. Thus, OPD can be a potential treatment candidate for gingival cancer.

This study explores the histological features and Bmp4 expression patterns in the replaced tooth germ of Xenopus laevis. Tooth germ formation starts from the dental placode through epithelial-mesenchymal interactions, involving various signaling pathways such as Fgf, Shh, Bmp, and Wnt. In mice, Bmp4 expression in the dental placode inhibits Pax9 expression in the dental mesenchyme. Although absent in the presumptive dental lamina of birds and toothless mammals, Bmp4 remains conserved in reptiles and fish owing to gene duplication. However, its expression in amphibian tooth germs is poorly understood. Three-month-old X. laevis were employed in this study. Initially, samples underwent paraffin embedding and were sectioned into 5 or 12 μm ribbons for H&E staining and in situ hybridization, respectively. Results revealed teeth appearing in two maxillary rows: the labial side, with prefunctional and functional teeth, and the lingual side, with replaced tooth germs behind functional teeth. Enameloid was observed between the inner dental epithelium and dental mesenchyme at the cap or early bell stages, whereas enamel and dentin formed during the late bell or mineralization stages from the replaced tooth germ. Bmp4 expression was evident in the inner dental epithelium (ameloblasts), dental papilla (odontoblasts), stellate reticulum, and Hertwig’s epithelial root sheath.Overall, these findings highlight the conservation of Bmp4 expression in X. laevis tooth development.

Diabetes, a chronic hyperglycemic condition, is caused by insufficient insulin secretion or functional impairment.Long-term inadequate regulation of blood glucose levels or hyperglycemia can lead to various complications, such as retinopathy, nephropathy, and cardiovascular disease. Recent studies have explored the molecular mechanisms linking diabetes to bone loss and an increased susceptibility to fractures. This study reviews the characteristics and molecular mechanisms of diabetes-induced bone disease. Depending on the type of diabetes, changes in bone tissue vary. The molecular mechanisms responsible for bone loss in diabetes include the accumulation of advanced glycation end products (AGEs), upregulation of inflammatory cytokines, induction of oxidative stress, and deficiencies in insulin/IGF-1. In diabetes, alveolar bone loss results from complex interactions involving oral bacterial infections, host responses, and hyperglycemic stress in periodontal tissues. Therapeutic strategies for diabetes-induced bone loss may include blocking the AGEs signaling pathway, decreasing inflammatory cytokine activity, inhibiting reactive oxygen species generation and activity, and controlling glucose levels; however, further research is warranted.

Oral bacterial infections substantially affect the development of various periodontal diseases and oral cancers.However, the molecular mechanisms underlying the association between Fusobacterium nucleatum (F. nucleatum), a major periodontitis (PT)-associated pathogen, and these diseases require extensive research. Previously, our RNAsequencing analysis identified a few hundred differentially expressed genes in patients with PT and peri-implantitis (PI) than in healthy controls. Thus, in the present study using oral squamous cell carcinoma (OSCC) cells, we aimed to evaluate the effect of F. nucleatum infection on genes that are differentially regulated in patients with PT and PI. Human oral squamous cell carcinoma cell lines OSC-2O, HSC-4, and HN22 were used. These cells were infected with F. nucleatum at a multiplicity of infection of 100 for 3 hours at 37℃ in 5% CO2 . Gene expression was then measured using reverse-transcription polymerase chain reaction. Among 18 genes tested, the expression of CSF3, an inflammation-related cytokine, was increased by F. nucleatum infection. Additionally, F. nucleatum infection increased the phosphorylation of AKT, p38 MAPK, and JNK in OSC-20 cells. Treatment with p38 MAPK (SB202190) and JNK (SP600125) inhibitors reduced the enhanced CSF3 expression induced by F. nucleatum infection. Overall, this study demonstrated that F. nucleatum promotes CSF3 expression in OSCC cells through p38 MAPK and JNK signaling pathways, suggesting that p38 MAPK and JNK inhibitors may help treat F. nucleatum-related periodontal diseases by suppressing CSF3 expression.