[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.

[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.

[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.

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.

[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.

[Research Progress in Glucose Metabolism of Chondrocytes].

Chondrocytes have a limited supply of glucose and oxygen for metabolism since articular cartilages are relatively avascular. We herein reviewed the characteristics of chondrocyte glucose metabolism and the new research progress in chondrocyte glucose metabolism in the osteoarthritis process. Current research has shown that chondrocytes obtain glucose from synovial fluids and subchondral bones, take in glucose via specific glucose transporters, and metabolize glucose mainly through glycolysis and mitochondrial respiration to produce adenosine triphosphate (ATP). Glucose metabolism in chondrocytes is distinctive because it relies much more on glycolysis rather than mitochondrial respiration for ATP production, and shows Warburg effect and Crabtree effect. In osteoarthritic chondrocytes, the glucose metabolism disorder is presented as further suppression of mitochondrial respiration, over-active or impaired glycolysis, and decreased total production of ATP. However, the significance of the glucose supply for chondrocytes from synovial fluids and subchondral bones remains undefined. There are still disputes in the understanding of the changes in glycolytic pathways in osteoarthritic chondrocytes. Therefore, future research is needed to explore the characteristics of glucose metabolism in normal and osteoarthritic chondrocytes in order to develop new diagnostic and therapeutic strategies for osteoarthritis.

[Study on the Effect of Polystyrene-Polyvinylpyrrolidone Electrospun Fibre in Inhibiting the Adhesion of Porphyromonas gingivalis].

OBJECTIVE: To explore the effect of polystyrene (PS) and PS-polyvinylpyrrolidone (PVP) electrospun materials on the adhesion ability of Porphyromonas gingivalis( P. gingivalis), a common periodontal pathogen. METHODS: PS and PS-PVP electrospun materials were prepared with stainless steel needles in high-voltage electric field. The growth and adhesion of P. gingivalis on the surface of different materials were observed with scanning electron microscope (SEM). The changes in the amount of P. gingivalis biofilm formed on the surface of different materials were measured according to viable colony forming units (CFU). The effect of surface charge of the different materials on the adhesion ability of P. gingivalis was determined through changing the charge properties on the surface of the electrospun materials. RESULTS: SEM images showed that both PS and PS-PVP can be used to form electrospun fibers with a diameter of 0.2 µm. SEM images and CFU counts of the biofilm at 24 h and 48 h showed that there was a smaller amount of P. gingivalis biofilm on the surface of the two materials ( P<0.05). After treatment with tetrabutylammonium bromide (TBAB), the surface charge of the PS-PVP electrospun material changed from being negatively charged to being positively charged, and the amount of bacterial adhesion on the surface increased significantly in comparison to that of untreated PS and PS-PVP materials ( P<0.05). CONCLUSION: PS and PS-PVP electrospun materials can be used to reduce the adhesion ability of P. gingivalis on the surface of different materials, and this ability may be related to the surface charge properties of the materials.

[The Role of Virtual Reality Technology in Medical Education in the Context of Emerging Medical Discipline].

According to Healthy China, a national strategy of the Government of China, new requirements were put forward for high-quality medical education, high-level surgical research, and precise clinical diagnosis and treatment. In the context of Emerging Medical Discipline, a strategic blueprint of medical education in China, this paper reviews the concept and core value of virtual reality (VR) and its significant role in the medical industry. On that basis, we explore the role of VR technology in medical training against the background of Emerging Medicine Discipline. Furthermore, typical cases are presented to help analyze and illustrate in detail the important role of VR technology in the teaching and training of stomatological and clinical procedures, skills assessment, online self-directed training, and clinical thinking skills training. We herein summarize useful information from past experience so as to help build innovative models of medical education in the context of Emerging Medical Discipline.

[Effects of Artemisinin and Its Derivatives on Oral Microbes].

The oral environment provides suitable conditions for the colonization of various microorganisms. However, the oral microbials could be the initial factors of some kinds of oral infectious diseases, therefore the treatment against oral microbial pathogens has become an effective strategy. Artemisinin, a kind of sesquiterpene lactone extracted from Traditional Chinese Medicine Artemisia annua L., is the first-line therapy to treat tertian malaria, subtertian malaria and anti-chloroquine malaria for its high efficiency and low toxicity. In recent years, artemisinin and its derivatives have also been proven to be effective against bacteria, fungi, viruses, parasites, and tumors, some of which are closely related to oral diseases. In this review, we summarize the potential effects of artemisinin and its derivatives on oral microorganism by analyzing previous research and latest progress to provide the evidence for further improvement, and look forward to the new research directions. Further studies are needed to improve existing technologies and standards to clarify the effects of artemisinin and its derivatives on microorganisms with controversial effects, to expand the detection of microorganisms associated with oral infectious diseases, and to clarify the interaction with existing antifungal agents in the field of antifungal diseases. In addition, in the study of anti-oral infectious diseases, artemisinin and its derivatives' administration scheme, potential drug interactions, toxic and side effects and other aspects are necessary conditions for further research, which is also a new direction of research. With the maturity of the production process, the improvement of relevant research and the potential demand for the treatment of oral infectious diseases, artemisinin and its derivatives have a broad prospect in the field of oral microorganisms, and provide a new opportunity for the research and development of oral drugs.

[Research progress of Candida albicans on malignant transformation of oral mucosal diseases].

Oral cancer is the most common malignant tumor in the head and neck, and is one of the world's top ten malignancies. Microbial infection is an important risk factor of oral cancer. Candida albicans is the most popular opportunistic fungal pathogen. Epidemiological studies have shown that Candida albicans is closely tied to oral malignancy. Animal experimentation have also proven that infection of Candida albicans can promote the development of oral epithelial carcinogenesis. The current studies have revealed several mechanisms involved in this process, including destroying the epithelial barrier, producing carcinogenic substances (nitrosamines, acetaldehyde), inducing chronic inflammation, activating immune response, etc. However, current researches on mechanisms are still inadequate, and some hypotheses remain controversial. Here, we review the findings related to Candida albicans' effect on the malignant transformation of oral mucosa, hoping to provide reference for deep research and controlling oral cancer clinically.

Runt-related transcription factor 1 is required for murine osteoblast differentiation and bone formation.

Despite years of research investigating osteoblast differentiation, the mechanisms by which transcription factors regulate osteoblast maturation, bone formation, and bone homeostasis is still unclear. It has been reported that runt-related transcription factor 1 (Runx1) is expressed in osteoblast progenitors, pre-osteoblasts, and mature osteoblasts; yet, surprisingly, the exact function of RUNX1 in osteoblast maturation and bone formation remains unknown. Here, we generated and characterized a pre-osteoblast and differentiating chondrocyte-specific Runx1 conditional knockout mouse model to study RUNX1's function in bone formation. Runx1 ablation in osteoblast precursors and differentiating chondrocytes via osterix-Cre (Osx-Cre) resulted in an osteoporotic phenotype and decreased bone density in the long bones and skulls of Runx1f/fOsx-Cre mice compared with Runx1f/f and Osx-Cre mice. RUNX1 deficiency reduced the expression of SRY-box transcription factor 9 (SOX9), Indian hedgehog signaling molecule (IHH), Patched (PTC), and cyclin D1 in the growth plate, and also reduced the expression of osteocalcin (OCN), OSX, activating transcription factor 4 (ATF4), and RUNX2 in osteoblasts. ChIP assays and promoter activity mapping revealed that RUNX1 directly associates with the Runx2 gene promoter and up-regulates Runx2 expression. Furthermore, the ChIP data also showed that RUNX1 associates with the Ocn promoter. In conclusion, RUNX1 up-regulates the expression of Runx2 and multiple bone-specific genes, and plays an indispensable role in bone formation and homeostasis in both trabecular and cortical bone. We propose that stimulating Runx1 activity may be useful in therapeutic approaches for managing some bone diseases such as osteoporosis.

Efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy: a systematic appraisal and meta-analysis.

BACKGROUND: The clinical significance of stem cell therapy in the treatment of dilated cardiomyopathy remains unclear. This systemic appraisal and meta-analysis aimed to assess the efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy. After searching the PubMed, Embase, and Cochrane library databases until November 2017, we conducted a meta-analysis to evaluate the efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy. METHODS: The weighted mean difference (WMD), standard mean difference (SMD), relative risk (RR), and 95% confidence interval (CI) were summarized in this meta-analysis. Both fixed effects and random effects models were used to combine the data. Sensitivity analyses were conducted to evaluate the impact of an individual dataset on the pooled results. RESULTS: A total of eight randomized controlled trials, which involved 531 participants, met the inclusion criteria in this systematic appraisal and meta-analysis. Our meta-analysis showed that stem cell therapy improves left ventricular ejection fraction (SMD = 1.09, 95% CI 0.29 to 1.90, I2 = 92%) and reduces left ventricular end-systolic volume (SMD = - 0.36, 95% CI - 0.61 to - 0.10, I2 = 20.5%) and left ventricular end-diastolic chamber size (SMD = - 0.48, 95% CI - 0.89 to - 0.07, I2 = 64.8%) in patients with dilated cardiomyopathy. However, stem cell therapy has no effect on mortality (RR = 0.72, 95% CI 0.50 to 1.02, I2 = 30.2%) and 6-min-walk test (WMD = 51.52, 95% CI - 24.52 to 127.55, I2 = 94.8%). CONCLUSIONS: This meta-analysis suggests that stem cell therapy improves left ventricular ejection fraction and reduces left ventricular end-systolic volume and left ventricular end-diastolic chamber size in patients with dilated cardiomyopathy. However, future well-designed large studies might be necessary to clarify the effect of stem cell therapy in patients with dilated cardiomyopathy.

[Research progress on the relationship between periodontal disease and common malignancies].

Periodontal disease is a common oral disease that can cause irreversible damage of periodontal support tissue. Studies on the relationship between periodontal disease and malignancies have also increased. In this review, the relationship between periodontal disease and gastrointestinal malignancies (e.g., stomach cancer, colorectal cancer, and pancreatic cancer), lung cancer, and breast cancer are discussed. The related mechanisms are summarized in terms of four aspects, namely, immu-nity, inflammation, gene, and microbiota and its products, to provide novel methods for the prevention and early diagnosis of malignancies.

[A review of peri-implant microbiology].

Dental implants represent the majority of treatment strategies used to replace missing teeth. However, peri-implant diseases caused by disturbance in peri-implant microbiological balance are among the reasons for implant failure. Since the 1980s, peri-implant microorganisms have been a hot research topic in dental microbiology. The bacterial ecology between the disease and health largely differs, which directly or indirectly increases the risk of peri-implant diseases. Accordingly, the determination of the 'core microbiome' of peri-implantitis and peri-implant mucositis is a key point of recent research.

[Research progress on the relationship between oral microbes and digestive system diseases].

The human microbiome project promoted further understanding on human oral microbes. Besides oral diseases such as dental caries, periodontal disease, and oral cancer, oral microbes are closely associated with systematic diseases. They have a close connection with digestive system diseases and even contribute to the origination and progression of colorectal cancer. By reviewing recent studies involving oral microbe-related digestive systemic diseases, we aim to propose the considerable role of oral microbes in relation to digestive systemic diseases and the way of oral microbes to multiple organs of digestive system.

Anti-inflammatory activities of hepatocyte growth factor in post-ischemic heart failure.

Hepatocyte growth factor (HGF) alleviates acute and chronic inflammation in experimental inflammatory bowel disease, glomerulonephritis, and airway inflammation. However, the anti-inflammatory effects of HGF on myocardial infarction are not defined. The current study assessed the anti-inflammatory effects of HGF in post-ischemic heart failure. The left anterior descending coronary artery was ligated in rats, and adenovirus containing human HGF (Ad-HGF) or control virus (Ad-GFP) was administered intramyocardially. The quantity of proinflammatory cytokines secreted by cardiomyocytes, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß, was evaluated. Cardiac function and LV remodeling were assessed using echocardiography and collagen deposition, respectively. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) four weeks after injection were significantly increased in Ad-HGF-treated animals compared to the Ad-GFP group. HGF gene therapy improved ventricular geometry with a significantly decreased left ventricular end-diastolic diameter (LVEDD) and markedly reduced myocardial collagen deposition. Treatment with Ad-HGF significantly decreased the mRNA levels of TNF-α, IL-6, and IL-1ß in the non-infarcted region four weeks after injection. Changes of the TNF-α, IL-6, and IL-1ß levels in the non-infarcted region positively correlated with the LVEDD 4 weeks after infarction. Treatment of acute myocardial infarction (AMI) with Ad-HGF in the early stage of MI reduced the pro-inflammatory cytokine levels and preserved cardiac function. These findings indicated that Ad-HGF gene therapy alleviated ventricular remodeling after infarction by reducing inflammation.

Saliva in the diagnosis of diseases.

Saliva is secreted from the salivary glands and has multiple functions, including mouth cleaning and protection, antibacterial effects and digestion. With the rapid advancement in salivaomics, saliva is well recognized as a pool of biological markers. Saliva, as a non-invasive and safe source, could be a substitute for blood in the diagnosis and prognosis of diseases. This review summarizes the latest advancements in saliva-related studies and addresses the potential value of saliva in the early diagnosis of oral diseases, such as dental caries and periodontal disease, as well as cancer, diabetes and other systemic disorders. Saliva biomarkers range from changes in the biochemical indices of DNA, RNA and proteins to the diversification of microbiota structures. This study integrates data reported in the recent literature and discusses the clinical significance and prospects for the application of saliva in the early diagnosis of diseases, translational medicine and precision medicine.

A ratiometric fluorescent probe for in situ quantification of basal mitochondrial hypochlorite in cancer cells.

A ratiometric fluorescent probe () for ClO(-) based on the conjugate of coumarin-rhodamine was presented, which could sense ClO(-) with fast response (within 5 s), high sensitivity and excellent selectivity. More importantly, is the first mitochondria-targeted ratiometric fluorescent probe to image exogenous and endogenous ClO(-).

Diol glycidyl ether-bridged low molecular weight PEI as potential gene delivery vehicles.

A series of cationic polymers (P1-P5) were designed and synthesized using a ring-opening polymerization strategy based on low molecular weight polyethyleneimine (PEI) and using diglycidyl ethers as the bridging moiety. Although these polymers have reduced amino group density relative to 25 kDa PEI, their pH buffering capacity and deoxyribonucleic acid (DNA) binding ability were seldom affected. They were able to condense plasmid DNA (pDNA) well to form nanoparticles of suitable sizes (150-300 nm) and positive zeta potentials (+25-40 mV). Cell Counting Kit-8 (CCK-8) assays revealed that polyplexes formed from these polymers have lower cytotoxicity than those derived from PEI. Luciferase reporter gene delivery experiments indicated that these polymers have much better transfection efficiency than 25 kDa PEI, especially P2 and P5. Unlike PEI, serum has little negative effect on the transfection by these materials, and their transfection efficiencies were seldom reduced even with high concentrations of serum. Under optimized conditions, up to 400 times higher transfection efficiency than with PEI could be achieved. Several assays including gel electrophoresis, dynamic light scattering and transmission electron microscopy also confirmed the good serum tolerance of these polyplexes. The evenly distributed hydroxyl groups formed by the ring-opening polymerization are considered to contribute much to their high serum tolerance, and such polymerization might be a promising strategy for the design of efficient non-viral gene delivery vectors.

Wnt5a promotes inflammatory responses via nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways in human dental pulp cells.

Wnt5a has been found recently to be involved in inflammation regulation through a mechanism that remains unclear. Immunohistochemical staining of infected human dental pulp and tissue from experimental dental pulpitis in rats showed that Wnt5a levels were increased. In vitro, Wnt5a was increased 8-fold in human dental pulp cells (HDPCs) after TNF-α stimulation compared with control cells. We then investigated the role of Wnt5a in HDPCs. In the presence of TNF-α, Wnt5a further increased the production of cytokines/chemokines, whereas Wnt5a knockdown markedly reduced cytokine/ chemokine production induced by TNF-α. In addition, in HDPCs, Wnt5a efficiently induced cytokine/chemokine expression and, in particular, expression of IL-8 (14.5-fold) and CCL2 (25.5-fold), as assessed by a Luminex assay. The cytokine subsets regulated by Wnt5a overlap partially with those induced by TNF-α. However, no TNF-α and IL-1ß was detected after Wnt5a treatment. We then found that Wnt5a alone and the supernatants of Wnt5a-treated HDPCs significantly increased macrophage migration, which supports a role for Wnt5a in macrophage recruitment and as an inflammatory mediator in human dental pulp inflammation. Finally, Wnt5a participates in dental pulp inflammation in a MAPK-dependent (p38-, JNK-, and ERK-dependent) and NF-κB-dependent manner. Our data suggest that Wnt5a, as an inflammatory mediator that drives the integration of cytokines and chemokines, acts downstream of TNF-α.