Prognostic significance of SOX2 for chemotherapeutic patients with oral squamous cell carcinoma

Oral squamous cell carcinoma(OSCC)is the most common oral cancers worldwide,accounting for over 90%of all oral malignancies[1].Despite encouraging improvements in therapeutic approaches,including surgical resection,chemotherapy,and radiotherapy,the five-year overall survival rate of OSCC has not been improved significantly over the past decades,mainly due to the high ratio of tumor recurrence and metastasis.

The role and applications of extracellular vesicles in osteoporosis

Osteoporosis is a widely observed condition characterized by the systemic deterioration of bone mass and microarchitecture,which increases patient susceptibility to fragile fractures.The intricate mechanisms governing bone homeostasis are substantially impacted by extracellular vesicles(EVs),which play crucial roles in both pathological and physiological contexts.EVs derived from various sources exert distinct effects on osteoporosis.Specifically,EVs released by osteoblasts,endothelial cells,myocytes,and mesenchymal stem cells contribute to bone formation due to their unique cargo of proteins,miRNAs,and cytokines.Conversely,EVs secreted by osteoclasts and immune cells promote bone resorption and inhibit bone formation.Furthermore,the use of EVs as therapeutic modalities or biomaterials for diagnosing and managing osteoporosis is promising.Here,we review the current understanding of the impact of EVs on bone homeostasis,including the classification and biogenesis of EVs and the intricate regulatory mechanisms of EVs in osteoporosis.Furthermore,we present an overview of the latest research progress on diagnosing and treating osteoporosis by using EVs.Finally,we discuss the challenges and prospects of translational research on the use of EVs in osteoporosis.

Oral health status in Sichuan Province: findings from the oral health survey of Sichuan, 2015–2016

To investigate oral health status in the residents of Sichuan Province, southwest China, a cross-sectional study was performed using the latest Oral Health Survey Basic Methods recommended by the World Health Organization. A multistage stratified random cluster-sampling method was used to enroll participants from the following three groups： children aged 3-5 years, adolescents aged 12 years, and people aged 65-74 years. In these three groups, the mean numbers of teeth that were affected by caries were 3.28, 0.86 and 5.13, respectively, resulting in a prevalence of 63.47%, 37.20% and 83.20%, respectively. Relative to the high rate of decayed teeth, the prevalence of fillings was very low in all age groups （0.97%, 7.24% and 5.43%, respectively）, In the 12-year-old adolescent group, only 3.61% had good pit and fissure sealing. In addition, the rate of dental fluorosis was 24.80%, and the Community Fluorosis Index value was 0.39. In the elder group, the community periodontal index was 2.92. The prevalence in the elderly of having lost at least one tooth was 75.54%. Additionally, 4.44% of these participants were edentulous. The incidence of dental prosthesis was 51.75%, the proportion with a removable partial denture, a fixed denture, full dentures, dental implants and an informal fixed bridge was 21.59%, 11.45%, 4.64%, 0 and 16.67%, respectively. In this study, 8.2% of the elderly participants were affected by different types of oral mucosal lesions. Among such lesions, recurrent aphthous ulcers were most prevalent （2.69%） and oral lichen planuses were second （1.6%）. The conclusion presented in this survey is that oral diseases, especially dental caries and periodontal disease, are frequent and common in Sichuan province, China. Moreover, the treatment rate is very low, and primary prevention and treatment options are therefore urgently needed in this population.

Photodynamic therapy guidelines for the management of oral leucoplakia

With recent developments in photosensitizers and light delivery systems,topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) has become the fourth alternative therapeutic approach in the management of oral leucoplakia (OLK) due to its minimally invasive nature,efficacy,and low risk of systemic side effects and disfigurement.This report presents step-by-step guidelines for applying topical ALA-PDT in the management of OLK based on both the clinical experience of the authors and a systematic review of the current literature.Studies using protocols with standardized parameters and randomized clinical trials at multiple centres with adequate sample sizes and both interim and long-term follow-ups are needed before universally applicable guidelines can be produced in this field.

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.

The mucosal immune system in the oral cavity——an orchestra of T cell diversity

The mucosal immune system defends against a vast array of pathogens, yet it exhibits limited responses to commensal microorganisms under healthy conditions. The oral-pharyngeal cavity, the gateway for both the gastrointestinal and respiratory tracts, is composed of complex anatomical structures and is constantly challenged by antigens from air and food. The mucosal immune system of the oral-pharyngeal cavity must prevent pathogen entry while maintaining immune homeostasis, which is achieved via a range of mechanisms that are similar or different to those utilized by the gastrointestinal immune system. In this review, we summarize the features of the mucosal immune system,focusing on T cell subsets and their functions. We also discuss our current understanding of the oral-pharyngeal mucosal immune system.

Influences of trans-trans farnesol,a membrane-targeting sesquiterpenoid,on Streptococcus mutans physiology and survival within mixed-species oral biofilms

Trans-trans farnesol （tt-farnesol） is a bioactive sesquiterpene alcohol commonly found in propolis （a beehive product） and citrus fruits, which disrupts the ability of Streptococcus mutans （S. mutans） to form virulent biofilms. In this study, we investigated whether tt-farnesol affects cell-membrane function, acid production and/or acid tolerance by planktonic cells and biofilms of S. mutans UA159. Furthermore, the influence of the agent on S. mutans gene expression and ability to form biofilms in the presence of other oral bacteria （Streptococcus oralis （S. oralis） 35037 and Actinomyces naeslundii （.4. naeslundil） 12104） was also examined. In general, tt-farnesol （1 mmol-L-1） significantly increased the membrane proton permeability and reduced glycolytie activity of S. mutans in the planktonic state and in biofilms （P〈0.05）. Moreover, topical applications of 1 mmol-L＂l tt-farnesol twice daily （1 min exposure/treatment） reduced biomass accumulation and prevented ecological shifts towards S. mutans dominance within mixed-species biofilms after introduction of 1% sucrose. S. oralis （a non-cariogenie organism） became the major species after treatments with tt-farnesol, whereas vehicle-treated biofilms contained mostly S. mutans （〉90% of total bacterial population）. However, the agent did not affect significantly the expression of S. mutans genes involved in acidogenicity, acid tolerance or polysaccharide synthesis in the treated biofilms. Our data indicate that tt-farnesoi may affect the competi- tiveness of S. mutans in a mixed-species environment by primarily disrupting the membrane function and physiology of this bacterium. This naturally occurring terpenoid could be a potentially useful adjunctive agent to the current anti-biofilm/anti-caries chemotherapeutic strategies.

Honokiol:a promising small molecular weight natural agent for the growth inhibition of oral squamous cell carcinoma cells

Honokiol （HNK） is a small organic molecule purified from magnolia species and has demonstrated anticancer activities in a variety of cancer cell lines; however, its effect on oral squamous cell carcinoma （OSCC） cells is unknown. We investigated the antitumor activities of HNK on OSCC ceils in vitro for the first time. The inhibitory effects of HNK on the growth and proliferation of OSCC cells were demonstrated via in vitro 3-（4,5-dimethyl thiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） and propidium iodide （PI） assays, and the apoptotic cells were investigated by the observation of morphological changes and detection of DNA fragmentation via PI, TdT-mediated dUTP-biotin nick end labeling （TUNEL）, and DNA ladder assays, as well as flow cytometry assay. The results showed that HNK inhibited the growth and proliferation of OSCC cells in vitro in a time and dose-dependent manner. The inhibitory effect was associated with the cell apoptosis induced by HNK, evidenced by the morphological features of apoptotic cells, TUNEL-positive cells and a degradation of chromosomal DNA into small internucleosomal fragments. The study also demonstrated here that the inhibition or apoptosis mediated by 15 μg.mL-1 or 20 μg.mL-1 of HNK were more stronger compared with those of 20 μg-mL-1 5-fluorouracil （5-Fu, the control） applied to OSCC cells, when the ratio of OSCC cell numbers were measured between the treatment of different concentrations of HNK to the 5-Fu treatment for 48 h. HNK is a promising compound that can be potentially used as a novel treatment agent for human OSCC.

Salivary protease spectrum biomarkers of oral cancer

Proteases are important molecules that are involved in many physiological and pathological processes of the human body,such as growth,apoptosis and metastasis cancer cells.They are potential targets in cancer diagnosis and biotherapy.In this study,we analyzed the salivary protease spectrum of patients with oral squamous cell carcinoma (OSCC),oral benign masses and chronic periodontitis,as well as that of health,using human protease array kits,enzyme-linked immunosorbent assay,western blot and immunofluorescence.The salivary protease spectrum was found to be associated with oral diseases.For example,the saliva of patients with OSCC contained increased numbers of proteases than those of other oral diseases and health.The levels of matrix metalloproteinase (MMP)-1,MMP-2,MMP-10,MMP-12,A disintegrin and metalloprotease (ADAM)9,A disintegrin and metalloprotease with thrombospondin type 13 motifs (ADAMST13),cathepsin V and kallikrein 5 in the saliva of patients with OSCC were significantly increased compared with those of other groups.Taking MMP-1,cathepsin V,kallikrein 5 and ADAM9 as biomarkers of OSCC,cutoff values were199,11.34,9.29 and 202.55 pg·mL?1,respectively.From the area under the curve,sensitivity and specificity,the combination of cathepsin V/kallikrein5/ADAM9 was an optimal biomarker for diagnosing OSCC.Thus,analysis of the salivary protease spectrum may be an innovative and cost-efficient approach to evaluating the health status of the oral cavity.Specifically,increases in cathepsin V,kallikrein 5 and ADAM9 may be useful biomarkers in the screening and diagnosis of OSCC.

The Prevalence of Hepatitis C Virus Infection in Oral Lichen Planus in an Ethnic Chinese Cohort of 232 Patients

Aim Oral lichen planush （OLP） is a chronic inflammatory disease, and has been reported to have a correlation with hepatitis Cvirus （HCV） infection in some regional investigations. In this study, we investigated the prevalence of HCV in patients with oral lichen planus in an ethnic Chinese cohort. Methodology The antibody of HCV infection was detected by using enzymelinked immunosorbent assay. Moreover, the clinical characteristics of whole the cohort have also been studied, such as the gender, age, clinical type, habits and social factors. Results Of all 232 patients, the antibody of HCV infection was detected positive in 4 patients （1.72%） using enzyme-linked immunosorbent assay. It was lower than that in control group of 2.5%, but not significant （P=0.309）. The positive rate of HCV antibody in the erosive type ones （4.2%） was higher than that in the reticular type ones （1.0%）, but this difference was proved to be not significant （P=0.389）. The clinical characteristics of whole cohort, such as the gender, age, clinical type, habits and social factors, showed the outcome obtained in the present study were similar to thao of our previous study. Conclusion HCV may play no etiological role in oral lichen planus in ethnic Chinese OLP patients.

A preliminary study on the key factors contributing to the attractive lips of Chinese children

Objective:To explore the aesthetic characteristics of the Chinese children lips.Methods: Frontal and profile photographs of 653 healthy children were categorized as the attractive and the unattractive by three laypersons and objectively measured for comparison.Results: The attractive group tended to be smaller in the upper paramedian red lip height,the lower paramedian red lip height,the midline upper red lip height,the central bow angle,and the lip angle,while greater in the Cupid’s bow width.Conclusions:Thinner lips seemed to be more attractive than full ones among Chinese children.

Analysis of interspecies adherence of oral bacteria using a membrane binding assay coupled with polymerase chain reaction-denaturing gradient gel electrophoresis profiling

Information on co-adherence of different oral bacterial species is important for understanding interspecies interactions within oral microbial community. Current knowledge on this topic is heavily based on pariwise coaggregation of known, cultivable species. In this study, we employed a membrane binding assay coupled with polymerase chain reaction-denaturing gradient gel electrophoresis （PCR-DGGE） to systematically analyze the co-adherence profiles of oral bacterial species, and achieved a more profound knowledge beyond pairwise coaggregation. Two oral bacterial species were selected to serve as ＂bait＂： Fusobacterium nucleatum （F. nucleatum） whose ability to adhere to a multitude of oral bacterial species has been extensively studied for pairwise interactions and Streptococcus mutans （S. mutans） whose interacting partners are largely unknown. To enable screening of interacting partner species within bacterial mixtures, cells of the ＂bait＂ oral bacterium were immobilized on nitrocellulose membranes which were washed and blocked to prevent unspecific binding. The ＂prey＂ bacterial mixtures （including known species or natural saliva samples） were added, unbound ceils were washed off after the incubation period and the remaining cells were eluted using 0.2 mol.L1 glycine. Genomic DNA was extraeted, subjeeted to 16S rRNA PCR amplification and separation of the resulting PCR produets by DGGE. Selected bands were recovered from the gel, sequenced and identified via Nucleotide BLAST searches against different databases. While few bacterial species bound to S. mutans, consistent with previous findings F.. nucleatum adhered to a variety of bacterial species including uncultivable and uneharacterized onesl This new approach can more effectively analyze the co-adherence profiles of oral bacteria, and could facilitate the systematic study of interbacterial binding of oral microbial species.

Expression of p53, p21^(CIP1/WAF1) and eIF4E in the adjacent tissues of oral squamous cell carcinoma:establishing the molecular boundary and a cancer progression model

The present study evaluated the expression of key molecules and the status of DNA in both oral squamous cell carcinoma（OSCC） and adjacent tissues to establish a molecular surgical boundary and provide a cancer progression model. Biopsy samples from 50 OSCC patients were divided into T（cancer）, P1（0–0.5 cm）, P2（0.5–1 cm）, P3（1–1.5 cm） and P4（1.5–2 cm） groups based on the distances from the visible boundary of the primary focus. Twenty samples of normal mucosa were used as controls. We used immunohistochemical staining and flow cytometry to evaluate p53, p21CIP1/WAF1, e IF4 E and Ki-67 expression and to determine DNA status, respectively. Sub-mucosal invasion was present in the P1 and P2 groups as determined by haematoxylin and eosin staining.Mutant p53 expression decreased gradually from cancerous to normal mucosae, whereas p21CIP1/WAF1 expression displayed an opposite trend. e IF4 E expression decreased from cancerous to normal mucosae. Ki-67 expression, the heteroploidy ratio, S-phase fraction and proliferative index decreased gradually with the distance from the tumour centre. Based on these results, we suggest that the resection boundary in OSCC surgery should be beyond 2 cm from the tumour. Additionally, the adjacent tissues of the primary focus could be used as a model for assessing cancer progression.

Effect of Srt A on Interspecies Adherence of Oral Bacteria

This study aimed to study whether the Sortase A（srt A） gene helps mediate coaggregation and co-adherence between Streptococcus mutans（S.mutans） and other salivary bacteria.S.mutans UA159 and srt A-deficient mutant served as ＂bait＂ in classical co-aggregation assays and membrane-based co-adherence assays were used to examine interactions of S.mutans with Fusobacterium nucleatum（F.nucleatum）,Streptococcus mitis（S.mitis）,Streptococcus gordonii（S.gordonii）,Streptococcus sanguis（S.sanguis）,Actinomyces naeslundii（A.naeslundii） and Lactobacillus.Co-adherence assays were also performed using unfractionated saliva from healthy individuals.Co-adhering partners of S.mutans were sensitively detected using polymerase chain reaction-denaturing gradient gel electrophoresis（PCR-DGGE）.Both UA159 and its srt A-deficient mutant bound to F.nucleatum but not to any of the other five salivary bacteria.The srt A-deficient mutant showed lower co-adherence with F.nucleatum.The two S.mutans strains also showed similar co-adherence profiles against unfractionated salivary bacteria,except that UA159 S.mutans but not the srt A-deficient bound to a Neisseria sp.under the same conditions.Deleting srt A reduces the ability of S.mutans to bind to F.nucleatum,but it does not appear to significantly affect the binding profile of S.mutans to bulk salivary bacteria.Key words

The role of TGF-beta3 in cartilage development and osteoarthritis

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-βsuperfamily,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.

Dental-craniofacial manifestation and treatment of rare diseases

Rare diseases are usually genetic, chronic and incurable disorders with a relatively low incidence. Developments in the diagnosis and management of rare diseases have been relatively slow due to a lack of sufficient profit motivation and market to attract research by companies. However, due to the attention of government and society as well as economic development, rare diseases have been gradually become an increasing concern. As several dental-craniofacial manifestations are associated with rare diseases,we summarize them in this study to help dentists and oral maxillofacial surgeons provide an early diagnosis and subsequent management for patients with these rare diseases.

Meeting report: a close look at oral biofilms and microbiomes

The "Biofilms, Microbiomes and Oral Diseases: Challenges and Future Perspectives" symposium jointly organized by Penn Dental Medicine and West China School of Stomatology was held on 30 September 2017 at Penn Wharton China Center(PWCC) in Beijing,China. The topics included the pathogenicity of oral biofilms, novel strategies for the control of biofilm-related diseases, oral microbiome and single-cell approaches, and the link between oral diseases and overall health. Researchers from a number of disciplines, representing institutions from China and Penn Dental Medicine, gathered to discuss advances in our understanding of biofilms, as well as future directions for the control of biofilm-related oral and systemic diseases.

Glucocorticoid reduces the efficacy of afatinib on the head and neck squamous cell carcinoma

Glucocorticoids(GC)are widely used to counter the adverse events during cancer therapy;nonetheless,previous studies pointed out that GC may reduce the efficacy of chemotherapy on cancer cells,especially in epidermal growth factor receptor(EGFR)-targeted therapy of head and neck squamous cell carcinoma(HNSCC)remaining to be elucidated.The primary aim of the present study was to probe into the GC-induced resistance of EGFR-targeted drug afatinib and the underlying mechanism.HNSCC cell lines(HSC-3,SCC-25,SCC-9,and H-400)and the human oral keratinocyte(HOK)cell lines were assessed for GC receptor(GR)expression.The promoting tumor growth effect of GC was evaluated by the CCK-8 assay and flow cytometry.Levels of signaling pathways participants GR,mTOR,and EGFR were determined by quantitative polymerase chain reaction and western blotting.GC increased the proliferation of HNSCC cells in a GR-dependent manner and promoted AKT/mTOR signaling.But GC failed in counteracting the inhibition of rapamycin in the mTOR signaling pathway.Besides,GC also induced resistance to EGFR-targeted drug afatinib through AKT/mTOR instead of the EGFR/ERK signaling pathway.Thus,GCs reduce the efficacy of afatinib on HNSCC,implicating a cautious use of glucocorticoids in clinical practice.

3D bioprinting of collagen-based materials for oral medicine

Oral diseases have emerged as one of the leading public health challenges globally.Although the existing clinical modalities for restoration of dental tissue loss and craniomaxillofacial injuries can achieve satisfactory therapeutic results,they cannot fully restore the original complex anatomical structure and physiological function of the tissue.3D printing of biological tissues has gained growing interest in the field of oral medicine with the ability to control the bioink component and printing structure for spatially heterogeneous repairing constructs,holding enormous promise for the precise treatment of oral disease.Particularly,collagen-based materials have been recognized as promising biogenic bioinks for the regeneration of several tissues with high cell-activating and biocompatible properties.In this review,we summarize 3D printing methods for collagen-based biomaterials and their mechanisms.Additionally,we highlight the animal sources of collagen and their characteristics,as well as the methods of collagen extraction.Furthermore,this review provides an overview of the 3D bioprinting technology for the regeneration of the pulpal nerve and blood vessels,cartilage,and periodontal tissue.We envision that this technique opens up immense opportunities over the conventional ones,with high replicability and customized function,which can ultimately promote effective oral tissue regeneration.

Dysbiosis of oral and gut microbiota and its association with metabolites in patients with different degrees of coronary artery stenosis

To the Editor:Coronary atherosclerotic heart disease(CAD)arises from coronary atherosclerosis(CAS)plaque buildup,resulting in coronary stenosis(CS)and occlusion,ultimately causing myocardial ischemia,hypoxia,or necrosis.Studies showed that the high-grade CS may be an important predictor of ST segment elevation myocardial infarction in subsequent months.