[Latest Findings on Salivary Tumor Biomarkers].

Saliva, a complex mixed biological fluid secreted by the salivary glands in the oral cavity, contains a wide variety of substances and information. With the development of saliva omics, studies have shown that saliva not only serves as a huge reservoir of biomarker, but saliva diagnostics has also become a new diagnostic technology with the advantages of non-invasiveness, easy access, and low cost. However, finding "true" saliva biomarkers is still a challenge due to the complex and changeable nature of the oral environment and the high susceptibility of biomarker content to influences. Herein, mainly focusing on potential salivary biomarkers of common tumors, including DNA, RNA, proteins, metabolites and microorganisms, we gave a systematic overview of the biomarkers that had been identified so far or the associated biomarkers. We suggested that the future development direction should be the establishment of a multidisciplinary system for developing saliva diagnosis technology, the gradual construction of a saliva diagnosis platform, and the search for more precise pre-warning tumor biomarkers.

[Explorations in and Practice of Integrating Ideological and Political Theories Education in Stomatology Textbooks].

Stomatology textbooks are an important carrier of integrated ideological and political education. The preparation of textbooks for the stomatology specialty in the new era is an important issue of concern for administrators and teachers of higher education institutions. Integrating ideological and political education in the instruction and practice composnents of academic courses on stomatology is an important issue to be resolved. Herein, we introduced the significance of ideological and political education and elaborated on the method of integrating ideological and political education in stomatology courses and textbooks from the perspectives of curriculum design, textbook compilation, teacher training, teaching evaluation, etc. We analyzed the different ways of integrating ideological and political education in stomatology courses and textbooks from the perspectives of classroom instruction, clinical practice, campus culture, social activities, and some other aspects.

[Mechanisms and Management of COVID-19-Associated Taste Disorders].

The taste buds in the human tongue contain specialized cells that generate taste signals when they are stimulated. These signals are then transmitted to the central nervous system, allowing the human body to distinguish nutritious substances from toxic or harmful ones. This process is critical to the survival of humans and other mammals. A number of studies have shown that dysgeusia, or taste disorder, is a common complication of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which can severely affect patients' nutritional intake and quality of life. Based on the physiological process of taste perception, the direct causes of dysgeusia include dysfunction of taste receptors and damage to the taste nervous system, while indirect causes include genetic factors, aging-related changes, bacterial and viral infections, and cancer treatments such as radiotherapy and chemotherapy. The pathogenic factors of dysgeusia are complicated, further research is needed to fully understand the underlying mechanisms, and some of the reported findings and conclusions still need further validation. All these form a great challenge for clinical diagnosis of the cause and targeted treatment of dysgeusia. Herein, we reviewed published research on the physiological process of taste perception, the potential mechanisms of taste disorders related to SARS-CoV-2 infection, and strategies for prevention and treatment, providing theoretical support for establishing and improving the comprehensive management of COVID-19 complicated by taste disorders.

[Research Progress in Niacinamide in the Prevention and Treatment of Mouth and Systemic Diseases].

Nicotinamide (NAM) is the amide form of niacin and one of the precursors of nicotinamide adenine dinucleotide (NAD +). NAM can be used as a dietary supplement or clinical therapeutic drug to replenish NAD + levels in the human body and participate in key bodily functions such as cellular metabolism and DNA repair. NAM has the advantage of low cost, wide availability, and sound biosafety. It also has multiple biological functions, including antibacterial effect, anti-inflammatory effect, and modulation of cellular immunity, producing significant ameliorative effects on skin and neurodegenerative diseases. However, most studies on NAM are still at the laboratory stage. Herein we reviewed the role and mechanism of NAM in the prevention and treatment of oral and systemic diseases, explored its potential as clinical therapeutic medication, provided some basis and references for the clinical application of nicotinamide in the prevention and treatment of various diseases, and discussed its prospects for future research and application.

[Developments in Research on Salivary Biomarkers in the Diagnosis of Systemic Diseases].

Saliva, an important biological fluid secreted by oral glands, serves multiple functions. It performs cleaning and protective functions for oral tissues, safeguarding against biological, mechanical and chemical stimuli, while allowing for the sensory perception of taste and temperature. It is also responsible for the preliminary digestion of food. These functions and properties of saliva are attributed to the presence of electrolytes, buffers, proteins, glycoproteins, and lipids in saliva. Recent studies have found that saliva contains biomarkers that are closely connected with the pathophysiological status of the human body, suggesting that saliva makes an ideal biological fluid for drug monitoring and biomarker screening. Therefore, salivary biomarkers can be used as an instrument for physical monitoring and localization of the occurrence of diseases, thereby accomplishing early diagnosis of diseases and assessment of the overall health status of patients. However, the actual application of salivary biomarkers in the diagnosis and treatment of systemic diseases is still not widely available, and the establishment of evaluation criteria and the exploration of its mechanism are not sufficiently investigated. Herein, we reviewed the latest research findings on applying the salivary biomarkers in the diagnosis of systemic diseases.

[New Developments in Research on the Relationship Between Osteoarthritis and Oral-Gut Microbes].

Osteoarthritis (OA) is the most common type of arthritis. The prevalence and the incidence of OA have been continuously growing along with increased life expectancy and the emerging problem of an aging population around the global. Reported findings have confirmed that osteoarthritis is a chronic inflammatory disease and its major risk factors included genetic susceptibility, aging, and environmental factors. However, the pathogenic mechanisms of osteoarthritis remain unclear. Recent studies have shown that oral-gut microbes are associated with the onset and development of osteoarthritis and may provide new targets for osteoarthritis treatment. Herein, we reviewed the latest developments in research on the relationship between oral-gut microbes and the onset and development of osteoarthritis, with a view to creating new perspectives for further elucidation of the pathogenesis of osteoarthritis and exploration of effective treatments in the future.

[Research Progress in the Correlation Between Oral Microbiota and Chronic Kidney Disease].

Chronic kidney disease (CKD), one of the common clinical urological diseases, is increasingly more prevalent in recent years and has emerged as a major concern of public health around the globe. The continuous recurrence of CKD caused by renal function impairment leads eventually to irreversible renal failure and severe systemic complications, which causes severe negative impact on the quality of life of the patient. As an essential component of human microbiome, oral microbiota plays a major role in maintaining health, and there has been research suggesting close association between oral dysbiosis and CKD. It is therefore of great clinical significance to understand the correlation between CKD and oral microbiota. Herein, we reviewed the characteristics of oral microbiota of CKD patients, the possible mechanisms of oral microbiota's involvement in the pathogenesis and development of CKD, and the latest research findings on oral dysbiosis and CKD, with a view to finding new approaches to early prevention and control of CKD through oral microbial targets.

[Developments in Research on the Relationship Between Matrix Metalloproteinases and Osteoarthritis].

Matrix metalloproteinases (MMPs) acquired their names because they depend on metal ions such as Ca 2+ and Zn 2+ as their cofactors. Members of this family of proteins share a similar structure consisting of five functionally distinct structural domains. MMPs, including MMP-1, MMP-3, MMP-9, and MMP-13, are key substances that promote cartilage matrix degradation and play an important role in the occurrence and progression of osteoarthritis (OA). MMPs boost the development of OA through the degradation of extracellular matrix proteins of chondrocytes, the promotion of inflammation, and other mechanisms, and are hence attracting extensive and increasing attention from the medical community. OA is a common degenerative disease that occurs in the joints and is associated with aging, metabolism, infections, genetics, exercise, and other predisposing factors. The pathological changes it causes can lead to a series of clinical symptoms such as joint pain, morning stiffness, and restricted joint movement, severely affecting patients' quality of life. The pathogenic mechanism of this highly prevalent disease is still unclear. At present, there is no effective treatment available for disease improvement. In the future, selective inhibition of MMPs, the key enzymes, may become an effective therapeutic approach. Focusing on the pathogenic effects of MMPs in OA, we herein reviewed the latest findings on the role of MMPs in the occurrence and progression of OA.

[Advances in Research on the Role of Bacterial c-di-AMP in Host Immunity].

Cyclic dimeric adenosine 3',5'-monophosphate (c-di-AMP) is a newly-discovered second messenger in bacteria and archaea. By directly binding to or affecting the expression of target proteins, c-di-AMP regulates the physiological functions of bacteria, including maintaining osmotic pressure, balancing central metabolism, monitoring DNA damage, and controlling biofilm and spore formation. As a new pathogen-associated molecular pattern (PAMP), it binds to the host pattern recognition receptor (PRR), induces cyclic GMP-AMP synthase (cGAS)-STING signal axis to produce type Ⅰ interferon by activating the stimulator of interferon genes (STING), and promotes the secretion of inflammatory factors through nuclear factor κB (NF-κB) signaling pathway, thereby playing an important role in host immunity to bacterial infection and tumorigenesis. Due to its immunogenicity, c-di-AMP could be used as an immune adjuvant to provide new targets for the development of vaccines. However, the specific mechanism of action of c-di-AMP in host immunity awaits further exploration. Herein, we presented the structure and biological characteristics of c-di-AMP, and summarized the possible mechanism of c-di-AMP's regulation of host immune response. In addition, we also reported the latest findings on using c-di-AMP as an immune adjuvant in clinical treatment. Research on the function of c-di-AMP and its mechanism of action on host immune response provides new ideas for finding clinical solutions to bacterial resistance, infection control, tumor prevention, and vaccine development in the future.

[Latest Research Findings on Health Management Based on Saliva Testing].

Being one of the most important exocrine fluids of the human body, saliva can reflect the health status of the body. Soliva collection has various advantages--it is simple, painless, fast, and safe, and soliva can be collected multiple times a day. Therefore, it has been gradually applied in the exploration for biomarkers for disease detection, providing a basis for the monitoring of the course of diseases, medication monitoring, and efficacy evaluation. We should implement health management based on saliva testing, collect the medical data of the healthy and diseased individuals and monitor their whole life cycle health, perform clinical cohort study, aggregate the data on platforms for big data on health and medicine, manage and provide guidance for the health status of populations, pinpoint the high-risk factors for pathogenesis, and provide effective intervention, early warning, and assessment of the vital signs of individuals, thereby reinforcing health management of the whole life cycle and safeguarding people's health in an all-round way. In addition, it drives the development of the health industry and bears strategic significance for the promotion of national economic development. It is becoming a hot research topic promising great potential and impressive applicational prospects. Herein, we reviewed new techniques for clinical saliva testing and health management based on saliva testing.

[Salivary Metabolic Profiling in Patients with Periodontitis].

Objective: To analyze the salivary metabolic profile of patients with periodontitis through metabolomic techniques and to explore the metabolic patterns associated with periodontal diseases. Methods: Liquid chromatography/mass spectrometry (LC/MS) technique in conjunction with principal component analysis (PCA) analysis and orthogonal partial least squares identification (OPLS-DA) method was used to study the metabolomics of saliva samples from gingivitis patients, periodontitis patients, and healthy controls, with 10 samples for each group. We examined the correlation between migration in metabolic profile and the progression of periodontal diseases. Results: Saliva metabolite profiles of gingivitis and periodontitis patients was significantly different from those of the healthy controls. Significant differences were identified between the different groups for eight salivary metabolites, including arachidonic acid, tyramine, L-arginine, thymine, N-acetylgalactosamine sulfate, prostaglandin E2, L-phenylalanine, and 5-aminoimidazole-4-carboxamide-riboside (AICAR). In comparison with those of the health controls, the concentration of AICAR in patients with gingivitis and periodontitis was lower and the metabolic trend was down-regulated, while the other metabolites were up-regulated. Conclusion: Salivary metabolic profile changes along with the progression of periodontal diseases. Abnormal metabolism of the periodontal tissue and of pathogenic microorganisms related to periodontal diseases is one of the mechanisms involved in the pathogenesis, development and prognosis of periodontal diseases.

High-Quality Development of Stomatology under the National Strategy.

The 19th National Congress of the Communist Party of China has proposed a national strategy for a healthy China, which includes the formulation of a new plan to promote high-quality development. Oral diseases have been included in the national "Medium- and Long-term Plan for the Prevention and Treatment of Chronic Diseases". China's national oral health strategy provides great opportunities for advancements in stomatology and for the improvement of the people's oral health. This article discusses these opportunities for advancement in the field of stomatology in China from six aspects: societal needs of oral health; advances in science and technology; changed diagnosis and treatment modes; application of big data; multidisciplinary integration; and talent training.

[Latest Research Findings on the Mechanism of Periodontal Pathogens in Cardiovascular Disease].

Cardiovascular disease (CVD) is a major cause of death worldwide. Research findings indicate that periodontal infection is an independent risk factor for CVD. Periodontal pathogens can cause cardiovascular diseases through various pathways, including direct invasion, induction of platelet activation and agglutination, immune inflammatory response, bacteremia, and oxidative stress. Moreover, CVD symptoms are relieved after the patients undergo periodontal interventional treatment. There have been substantial findings indicating that there may be a close connection between periodontal disease and CVD. However, periodontal disease is a chronic disease. The treatment of periodontal diseases and the improvement of periodontal health require long-term efforts. Long-term effective reduction of the incidence of CVD in clinical practice through prevention of periodontal disease remains a challenging area of study. Here we summarized and reported the latest findings on the mechanism of action of periodontal pathogens in cardiovascular diseases, intending to contribute to the better understanding of the pathogenesis of CVD and to provide potential targets and new ideas for its prevention and treatment.

The FnBPA from methicillin-resistant Staphylococcus aureus promoted development of oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is the most common tumor in the oral cavity. Methicillin-resistant Staphylococcus aureus (MRSA) were highly detected in OSCC patients; however, the interactions and mechanisms between drug-resistant bacteria (MRSA) and OSCC are not clear. Aim: The aim of this study was to investigate the promotion of MRSA on the development of OSCC. Methods: MRSA and MSSA (methicillin-susceptible) strains were employed to investigate the effect on the proliferation of OSCC in vitro and vivo. Results: All of the MRSA strains significantly increased the proliferation of OSCC cells and MRSA arrested the cell cycles of OSCC cells in the S phase. MRSA activated the expression of TLR-4, NF-κB and c-fos in OSCC cells. MRSA also promoted the development of squamous cell carcinoma in vivo. The virulence factor fnbpA gene was significantly upregulated in all MRSA strains. By neutralizing FnBPA, the promotions of MRSA on OSCC cell proliferation and development of squamous cell carcinoma were significantly decreased. Meanwhile, the activation of c-fos and NF-κB by MRSA was also significantly decreased by FnBPA antibody. Conclusion: MRSA promoted development of OSCC, and the FnBPA protein was the critical virulence factor. Targeting virulence factors is a new method to block the interaction between a drug-resistant pathogen and development of tumors.

[Latest Research Findings on the Regulation of Bone Homeostasis by ALK3].

Bone remodeling, which is well orchestrated by osteogenesis of osteoblasts and osteoclastogenesis of osteoclasts, maintains the homeostasis of osteal development and metabolism under physiological conditions. Bone morphogenetic protein receptor type 1A, also known as activin receptor-like kinase 3 (ALK3), which exists on cytomembrane, is one of the key receptors of BMP factors, and is an important "gateway" that regulates the entrance of BMP signaling into cells in order to perform biological functions. The roles of BMP signaling in bone remodeling have been extensively studied. Many new discoveries have been reported in recent years through research based on transgenic mice models and focused on ALK3 as targets, shedding new light on the regulations of bone remodeling, cartilage and joint development, and the occurrence and treatment of bone-related diseases. Established understanding has been expanded, but new challenges on existing clinical application of BMPs also appeared. Hence, we reviewed recent studies on ALK3's involvement in bone formation and bone resorption, analyzed its mechanism of action in bone regulation, summarized the roles of ALK3 in the development of cartilage and temporomandibular joint, and reported the latest progress in treatment in preclinical studies, intending to provide references for subsequent studies and clinical applications in the future.

[Research Progress of CD47-Related Signaling Pathway and the Role of CD47 in Pathogenic Infection].

CD47, a transmembrane glycoprotein widely expressed on the cell surface, is one of the important checkpoints through which cells escape innate immune surveillance. The important role of CD47-related signaling pathway and changes in expression level in immune regulation, pathogen infection and anti-tumor immunity has gradually come to be recognized. We reviewed herein the structure and biological characteristics of CD47, the interaction and the downstream signaling of CD47 with integrin, thrombospondin 1, and signal regulatory protein, and the upregulated expression of CD47 induced by the infection of different pathogens and the role of CD47 in different types of immune response to infection. Discussions were made regarding the prospective application of CD47 targeted immunotherapy in pathogenic infection-related cancers, intending to provide guidance for future research.

[Omicron Variant of SARS-CoV-2 and Its Potential Impact on Dental Practice].

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been raging across the world for over two years, but the daily reported numbers of new infections and deaths are still increasing. The newly identified Omicron variant has significant changes in its transmissibility and pathogenicity due to the multiple mutations in the spike protein, posing new challenges to the global public health. World Health Organization has categorized Omicron as a variant of concern (VOC). The spread of SARS-CoV-2 and its variants has caused disruptions to the dental practice worldwide. During the course of diagnosis and treatment of dental care, face-to-face communication at close quarters, droplets, aerosols, and exposure to saliva and blood increase the risks of SARS-CoV-2 transmission. The emergence of new variants, especially the Omicron variant, has formed new challenges to dental healthcare provision. In addition, oral tissues, including the tongue and oral mucosa, can overexpress the angiotensin converting enzyme 2 (ACE2), which is also the binding receptors of SARS-CoV-2. As a result, the oral cavity is one of the target sites of SARS-CoV-2 infection. SARS-CoV-2 infection in oral cavity may cause different oral complications, such as loss of taste. However, there are few reports about Omicron and the other variants of SARS-CoV-2 and their impacts on dental healthcare provision. Herein we made an overview of the Omicron variant and its characteristics, including its pathogenicity and immune evasion, and its potential impact on dental practice. We also proposed some control measures with the aim of reducing the possible transmission of SARS-CoV-2 and its variants during dental care.

[Research Updates: Relationship between Gingival Epithelial Intercellular Junctions and Periodontal Pathogenic Bacteria].

Gingival epithelial barrier is the first line of defense of periodontal tissues against the invasion of pathogenic bacteria. The destruction of gingival epithelial barrier is closely related to the development of periodontal disease. Studies have shown that periodontal pathogenic bacteria and their inflammatory microenvironment can inhibit the expression of gingival epithelial junctional proteins via molecular mechanisms such as the downregulation of the expression of grainyhead-like protein family and the upregulation of the methylation level of gene promoter of epithelial connexin, and thus cause damage to the gingival epithelial barrier and the development of periodontitis. We herein reviewed the effects of bacteria and inflammatory factors induced by bacterial infection on gingival epithelial intercellular junctions and related mechanisms, and summarized the research progress on the relationship between gingival epithelial intercellular junctions and periodontal pathogenic bacteria in recent years. Most recent studies were focused on i n vitro cytological experiments and animal models of infections caused by a single kind of bacterium. We have suggested that building gingival epithelial organoid model and combining multi-omics approaches with high resolution three-dimensional electron microscopy are expected to help pinpoint the key microorganisms and their most important virulence factors that trigger periodontal microecologcal imbalance and cause functional damage to the gingival epithelial barrier, to reveal the key molecular mechanisms involved in the maintenance and destruction of gingival epithelial barrier function, and to provide new perspectives on the pathogenesis and the clinical prevention and treatment of periodontitis.

[Development and Influencing Factors of Oral Microbiota in Early Life].

Oral cavity, an important component of and the gateway to the digestive system, is also the colonization site and the microecological environment of trillions of microorganisms. The establishment and succession of oral microbiota are of great importance for the development of human immune system, and function as a major determinant of oral and systemic health. Within a few hours after birth, early colonizers such as Streptococcus and Lactobacillus can be detected in an infant's mouth. The oral microbiota communities mature gradually along with the growth of the host, expanding in their species abundance and diversity. In addition to genetic factors, a number of cross-sectional studies have revealed that the development of oral microecosystems in early life is influenced and tuned by multiple external factors, including maternal health status, mode of delivery, feeding habits, antibiotics use, etc. The dysbiosis of oral microecology in early life is closely related to the pathogenesis and progression of oral and systemic diseases. Therefore, good oral hygiene habits are of vital importance to the early management of oral microbial diseases and their effective prevention and control. Herein, we summarized the colonization and succession of oral microbiota in early life and further discussed the key external factors that affect early life oral microecosystem, as well as the impact of early life oral microbiota on the host's health at a later stage, intending to help providing new insights into and new strategies for the management of the whole lifecycle oral and systemic health.

[frtR Gene Affects Acid Production and Demineralization Ability of Streptococcus mutans].

Objective: To study the effect of the frtR gene of TetR family on the acid production ability of Streptococcus mutans( S. mutans) and the bacteria's ability to induce tooth demineralization . Methods: The growth of two strains of S. mutans UA159, Δ frtR, the frtR gene in-frame deletion strain, and Δ frtR/pDL278- frtR, the complement strain, was examined. The structure of biofilm was observed by laser scanning confocal microscopy (LSCM). The quantitative determination of water-insoluble extracellular polysaccharide (EPS) in the bacterial biofilms was done by anthrone-sulfuric acid method. The acid production capacity of S. mutans was measured by glycolytic pH drop. The demineralization-inducing ability of the strains on bovine teeth was determined by transverse microradiography (TMR). Results: The growth curves of the strains showed that frtR did not affect the growth of S. mutans. According to the findings of LSCM observation, frtR did not affect the biofilm formation. According to the findings of the anthrone-sulfuric acid method, frtR did not have any significant impact on the EPS synthesis of S. mutans. The results of the glycolytic pH drop assay showed that the deletion of frtR delayed the rate of acid production by S. mutans when sucrose was the only carbon source. In addition, according to the TMR results, knocking out frtR reduced the depth and amount of demineralization induced by S. mutans on the surface of bovine teeth. Conclusion: The deletion of frtR can weaken the acid production ability and the demineralization ability of S. mutans.