Curcumin is a natural medicine with a wide range of sources and low toxicity. It has antibacterial, antifungal, anti-inflammatory and other pharmacological effects. In recent years, curcumin has attracted much attention in the field of prevention and treatment of oral infectious diseases. Single curcumin is easily degraded during application and has poor water solubility and low bioavailability, but it can be used as a natural photosensitizer to mediate photodynamic treatment of oral infections. Photodynamic therapy has high antibacterial efficiency and can better protect the appearance and function of the affected area. This article reviews the research on curcumin-mediated photodynamic therapy for oral infectious diseases. As a natural photosensitizer, curcumin mediates photodynamic therapy and has shown good therapeutic effects against dental caries, endodontics, periodontitis, oral candidiasis and other oral infectious diseases by enhancing antibacterial ability, increasing the production of reactive oxygen species, and inhibiting the formation of biofilms. In-depth exploration of the mechanism of action of curcumin-mediated photodynamic therapy in different oral infectious diseases can provide new strategies for the prevention and treatment of oral infectious diseases.

Dental and craniofacial bone development is a highly coordinated process that is tightly controlled by genetics and influenced by complex environments. The abnormal regulation of many development-related signaling molecules may lead to abnormal tooth development, severe craniofacial bone formation disorders, and developmental deformities. Transforming growth factor-β (TGF-β) is widely expressed in vivo and participates in many cellular biological processes, showing complex regulatory roles in mammalian craniofacial bone growth and tooth development. In tooth development, abnormal TGF-β signaling can lead to the failure of tooth germ formation, and its deletion mutation can directly affect odontoblast differentiation and enamel formation defects. However, the current research on TGF-β mainly focuses on the early stage of tooth development, and a comprehensive and systematic study of TGF-β-related tooth development is lacking. TGF-β signal transduction mainly controls the development of teeth and craniofacial bone by regulating the expression of development-related molecules via the classical Smad-dependent signaling pathway. In addition, the nonclassical mitogen-activated protein kinase (MAPK) pathway also participates in this process. Abnormal TGF-β signaling may cause jaw development disorders, temporomandibular joint dysplasia and inflammation, and cleft palate. Because the specific regulatory mechanism of TGF-β in craniofacial bone development has not been fully elucidated, its specific application in the treatment of related diseases is also greatly limited. This paper describes the new research progress of TGF-β in the development of teeth, jaws, temporomandibular joints and palate as well as related diseases.

Fibroblast growth factor 8 (FGF8) is a kind of secretory polypeptide that has crucial roles in the development of various tissues and organs. Current studies have found that FGF8 can regulate the differentiation of cranial neural crest cells by activating the mitogen-activated protein kinase (MAPK) signaling pathway and affect the establishment of mandibular arch polarity and the development of craniofacial symmetry by regulating the expression of target genes. Cleft lip with or without cleft palate, ciliopathies, macrostomia and agnathia are four developmental malformations involving the craniofacial region that seriously affect the quality of life of patients. The abnormal FGF8 signal caused by gene mutation, abnormal protein conformation or expression is closely related to the occurrence of craniofacial malformations, but the molecular mechanism and signaling pathway underlying these malformations have not been fully elucidated. Craniofacial development is a complex process mediated by a variety of signaling molecules. In the future, the role of various signaling molecules in craniofacial development and malformations need to be explored to provide a new perspective and vision for the prevention and treatment of these craniofacial malformations.

Mitochondria, ubiquitous energy-producing organelles in eukaryotic cells, can have their normal functions disrupted by bacterial infections, leading to mitochondrial dysfunction. This dysfunction is closely associated with inflammatory diseases. Periodontitis, a chronic inflammatory disorder of periodontal tissues caused by pathogenic microorganisms, has been increasingly linked to mitochondrial dysfunction in its pathogenesis and progression. Compared to healthy periodontal tissues, inflammatory lesions exhibit more pronounced mitochondrial dysfunction—a pathological process that is strongly correlated with periodontal pathogen infection. Studies reveal that these pathogens disrupt mitochondrial homeostasis in host cells (e.g., gingival epithelial cells and fibroblasts) through multiple mechanisms, including disrupting mitochondrial biogenesis, altering mitochondrial dynamics (promoting excessive fission), inhibiting mitophagy, impairing mitochondrial dysfunction-associated apoptosis, and inducing endogenous oxidative stress, which upregulates pro-inflammatory cytokines. Collectively, these processes drive the establishment and persistence of an inflammatory microenvironment. This review explores how periodontal pathogens affect mitochondrial function and their mechanistic contributions to periodontitis progression, with the goal of providing novel insights for developing mitochondria-targeted therapeutic strategies.

Caries is a chronic infectious disease that occurs in the hard tissues of teeth. The interaction of oral microorganisms, host, food and time leads to the occurrence and progression of caries. Free sugar is an important food factor in the occurrence of dental caries. This paper reviews the research progress on the relationship between free sugar and caries in recent years, providing a reference for further clarifying the mechanism of the occurrence and progression of caries caused by free sugar and exploring the methods of caries prevention. The cariogenic mechanism of free sugar is multifaceted. Free sugar can not only be used by oral microorganisms in dental plaque biofilms to produce acid and synthesize intracellular and extracellular polysaccharides but also cause an imbalance in oral microecology and enhance gene expression related to the cariogenic toxicity of oral microorganisms. Based on the correlation between free sugar and caries, it is important to limit the intake amount and frequency of free sugar to prevent caries. This can be achieved mainly by formulating public health policies for reducing sugar, creating a low-sugar family environment with good eating habits, using sugar substitutes and using fluoride. There are few studies on the relationship between free sugar and oral microecology. More research is needed to better understand the effect of free sugar on oral microecology and its mechanism and to validate the caries-preventing effect of various sugar reduction measures. We believe such studies would open up new avenues for the effective prevention of caries.

Alzheimer’s disease (AD), a common neurodegenerative disease, has been linked to periodontitis, especially Porphyromonas gingivalis (P.gingivalis) infection. This review summarizes the potential mechanisms and pathways through which P.gingivalis and its virulence factors are involved in AD pathogenesis, aiming to provide the scientific basis for the development of novel prevention and treatment strategies for AD. P.gingivalis can promote AD by exacerbating neuroinflammation, facilitating amyloid beta and Tau deposition, and disrupting the blood-brain barrier. Gingipains, secreted by P.gingivalis, serve as core effector molecules by increasing the blood-brain barrier permeability. The association between P.gingivalis and its effectors and AD pathology has been validated by metagenomic analysis and sample detection, indicating that P.gingivalis may be an environmental susceptibility factor or modifiable risk factor for AD. However, the precise mechanisms by which P.gingivalis influences AD, and its interactions with other potential AD-related factors, remain unclear. Moreover, further research needs to be conducted on the therapeutic potential of P.gingvalis intervention in improving AD.

Oral health is an integral component of overall well-being, with the oral cavity serving as a channel for external communication and expression of emotions such as stress and pessimism. Oral diseases can intensify feelings of depression, whereas depression can worsen oral health conditions. As a crucial part of the human microbiome, an imbalance in oral microbiota can release oral pathogenic microbes, which, through pathways including the circulation, nervous, and immune systems, can reach the brain and significantly affect the central nervous system. This can lead to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, further intensifying the development of depression. Similarly, an imbalance in oral microbiota in individuals with depression can intensify the occurrence of oral diseases. The relationship between depression and oral diseases is not isolated but rather a complex interplay in which they mutually influence and act as causative factors. To elucidate the causal relationship between oral diseases and depression and devise strategies for the prevention and treatment of both conditions, we explore the interaction mechanisms between oral diseases and depression from the perspective of oral microbiota. The occurrence of dental caries, periapical periodontitis, and periodontal diseases is closely associated with the excessive proliferation of specific bacteria in the oral cavity, such as Streptococcus mutans, Porphyromonas gingivalis, and Fusobacterium nucleatum. These bacteria can directly invade the brain through the compromised blood-brain barrier, activating pro-inflammatory cytokines and worsening depressive symptoms. Inflammatory conditions and ulcers in the oral mucosa are caused by various factors, including infection and immune abnormalities. Because of compromised immune function in individuals with depression, these inflammatory responses are often more severe and difficult to control. Malocclusion, trigeminal neuralgia, and temporomandibular joint disorders increase the risk of depression because of psychological stress and changes in the immune system. We also outline the diagnostic and therapeutic considerations for oral diseases in patients with depression, emphasizing the importance of early intervention for disease management. Future research will explore the therapeutic potential of oral microbiota in individuals with depression, with the aim to improve symptoms and treatment outcomes by adjusting oral microbiota, thus providing novel avenues for the prevention and treatment of depression.

Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.

Articular cartilage serves as a low-friction, load-bearing tissue without the support with blood vessels, lymphatics and nerves, making its repair a big challenge. Transforming growth factor-beta 3 (TGF-β3), a vital member of the highly conserved TGF-β superfamily, plays a versatile role in cartilage physiology and pathology. TGF-β3 influences the whole life cycle of chondrocytes and mediates a series of cellular responses, including cell survival, proliferation, migration, and differentiation. Since TGF-β3 is involved in maintaining the balance between chondrogenic differentiation and chondrocyte hypertrophy, its regulatory role is especially important to cartilage development. Increased TGF-β3 plays a dual role: in healthy tissues, it can facilitate chondrocyte viability, but in osteoarthritic chondrocytes, it can accelerate the progression of disease. Recently, TGF-β3 has been recognized as a potential therapeutic target for osteoarthritis (OA) owing to its protective effect, which it confers by enhancing the recruitment of autologous mesenchymal stem cells (MSCs) to damaged cartilage. However, the biological mechanism of TGF-β3 action in cartilage development and OA is not well understood. In this review, we systematically summarize recent progress in the research on TGF-β3 in cartilage physiology and pathology, providing up-to-date strategies for cartilage repair and preventive treatment.