<strong>Context:</strong> Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) has been identified in December 2019. Since then, it has been spreading around the world and has caused a pandemic. St...<strong>Context:</strong> Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) has been identified in December 2019. Since then, it has been spreading around the world and has caused a pandemic. Strict safety protocols should be followed to resume dental treatments. <strong>Evidence Acquisition: </strong>A comprehensive search was conducted on PubMed, Scopus, Medline and google scholar databases using the MeSH words of COVID-19, SARS-COV-2, Dentistry, and Child from December 2019 until July 2020. <strong>Results:</strong> Among COVID-19 patients, asymptomatic patients still are considered to be serious carriers of the COVID-19 which can play a key role in transmission of the virus. Children are reported to be less than 2 percent of the infected population and are considered as serious potential carriers. Telemedicine can take a key part in educating parents regarding this matter. Chronic and rare diseases such as Kawasaki Disease (KD) might show acute and more frequent symptoms amongst COVID-19 patients. Salivary testing can be a convenient chairside way for COVID-19 and it has been shown to be effective in identifying critically ill patients. Dry mouth and amblygeustia have been reported to be the oral symptoms of the COVID-19. <strong>Conclusions:</strong> Dentists must make tough decisions in prioritizing patient’s needs in the period of pandemic. They should frequently get updated as the situation is fluid and the protocols might change.展开更多
Dental stem cells(DSCs)have attracted significant interest as autologous stem cells since they are easily accessible and give a minimal immune response.These properties and their ability to both maintain self-renewal ...Dental stem cells(DSCs)have attracted significant interest as autologous stem cells since they are easily accessible and give a minimal immune response.These properties and their ability to both maintain self-renewal and undergo multi-lineage differentiation establish them as key players in regenerative medicine.While many regulatory factors determine the differentiation trajectory of DSCs,prior research has predominantly been based on genetic,epigenetic,and molecular aspects.Recent evidence suggests that DSC differentiation can also be influenced by autophagy,a highly conserved cellular process responsible for maintaining cellular and tissue homeostasis under various stress conditions.This comprehensive review endeavors to elucidate the intricate regulatory mechanism and relationship between autophagy and DSC differentiation.To achieve this goal,we dissect the intricacies of autophagy and its mechanisms.Subsequently,we elucidate its pivotal roles in impacting DSC differentiation,including osteo/odontogenic,neurogenic,and angiogenic trajectories.Furthermore,we reveal the regulatory factors that govern autophagy in DSC lineage commitment,including scaffold materials,pharmaceutical cues,and the extrinsic milieu.The implications of this review are far-reaching,underpinning the potential to wield autophagy as a regulatory tool to expedite DSC-directed differentiation and thereby promote the application of DSCs within the realm of regenerative medicine.展开更多
BACKGROUND In recent years,the association between oral health and the risk of gastric cancer(GC)has gradually attracted increased interest.However,in terms of GC incidence,the association between oral health and GC i...BACKGROUND In recent years,the association between oral health and the risk of gastric cancer(GC)has gradually attracted increased interest.However,in terms of GC incidence,the association between oral health and GC incidence remains contro-versial.Periodontitis is reported to increase the risk of GC.However,some studies have shown that periodontitis has no effect on the risk of GC.Therefore,the present study aimed to assess whether there is a relationship between oral health and the risk of GC.AIM To assess whether there was a relationship between oral health and the risk of GC.METHODS Five databases were searched to find eligible studies from inception to April 10,2023.Newcastle-Ottawa Scale score was used to assess the quality of included studies.The quality of cohort studies and case-control studies were evaluated separately in this study.Incidence of GC were described by odds ratio(OR)and 95%confidence interval(CI).Funnel plot was used to represent the publication bias of included studies.We performed the data analysis by StataSE 16.RESULTS A total of 1431677 patients from twelve included studies were enrolled for data analysis in this study.According to our analysis,we found that the poor oral health was associated with higher risk of GC(OR=1.15,95%CI:1.02-1.29;I2=59.47%,P=0.00<0.01).Moreover,after subgroup analysis,the outcomes showed that whether tooth loss(OR=1.12,95%CI:0.94-1.29;I2=6.01%,P>0.01),gingivitis(OR=1.19,95%CI:0.71-1.67;I2=0.00%,P>0.01),dentures(OR=1.27,95%CI:0.63-1.19;I2=68.79%,P>0.01),or tooth brushing(OR=1.25,95%CI:0.78-1.71;I2=88.87%,P>0.01)had no influence on the risk of GC.However,patients with periodontitis(OR=1.13,95%CI:1.04-1.23;I2=0.00%,P<0.01)had a higher risk of GC.CONCLUSION Patients with poor oral health,especially periodontitis,had a higher risk of GC.Patients should be concerned about their oral health.Improving oral health might reduce the risk of GC.展开更多
Autophagy is a widespread biological process that controls cellular growth,survival,development,and death.Circadian rhythm is a recurring reaction of living organisms and behaviors to variations in surrounding brightn...Autophagy is a widespread biological process that controls cellular growth,survival,development,and death.Circadian rhythm is a recurring reaction of living organisms and behaviors to variations in surrounding brightness and obscurity.Most of the fundamental physiological processes in mammals,such as the sleep-wake pattern and the rhythm of nutrition and energy metabolism,are governed by circadian rhythms.Research has indicated that autophagy exhibits a specific circadian pattern in both normal and abnormal conditions.Autophagy can modulate circadian rhythms by breaking down proteins that regulate the circadian clock.The potential regulatory connection between the two has been a popular subject of clinical and fundamental research.Understanding the interaction between circadian rhythm and autophagy could potentially lead to the development of novel approaches for disease treatment in the future.The present analysis presented a summary of the molecular processes implicated in the interplay between autophagy and circadian rhythm,as well as the pathological importance of the disrupted regulatory association between these two phenomena.展开更多
Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient's digestive functions, pronunciation, and esth...Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient's digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients' prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine.展开更多
Antibiotic drugs are a very important drug group considering their frequent use, safety profile and their impact on bacterial resistance induction. Aim: To investigate the utilization of antibiotic drugs at the Univer...Antibiotic drugs are a very important drug group considering their frequent use, safety profile and their impact on bacterial resistance induction. Aim: To investigate the utilization of antibiotic drugs at the University Dentistry Clinical Center of Kosovo (UDCCK). Methodology: Retrospective and descriptive study. Patient records were used as a data source collected for a period of 3 months. The total number of registered outpatients in the UDCCK was 1117 patients. The data analysis was performed using the WHO methodology and results were expressed in DDD per 1000 inhabitants per day. Results: The total prescription of antibiotics at UDCCK was 7.18 DDD/ 1000 inhabitants/day. Antibiotics were prescribed for 86 or 7.70% of patients. The most commonly prescribed antibiotic was Amoxicillin with clavulonic acid 3.12 (43.45%) DDD, followed by Metronidazole 2.31 DDD and Amoxicillin 1.25 DDD. Erythromycin and Cefalexin were prescribed evidently less compared to other antibiotics (0.38 and 0.12 DDD/1000 inhabitant/day, respectively). Conclusions: The quantitative analysis showed no rationality of prescription of antibiotics in UDCCK. Generally, the use of antibiotics in both departments of UDCCK is higher compared to other countries. We recommend the implementation of restrictive prescription standards for antibiotics.展开更多
Bacteremia induced by periodontal infection is an important factor for periodontitis to threaten general health. P. gingivalis DNA/virulence factors have been found in the brain tissues from patients with Alzheimer’s...Bacteremia induced by periodontal infection is an important factor for periodontitis to threaten general health. P. gingivalis DNA/virulence factors have been found in the brain tissues from patients with Alzheimer’s disease(AD). The blood-brain barrier(BBB) is essential for keeping toxic substances from entering brain tissues. However, the effect of P. gingivalis bacteremia on BBB permeability and its underlying mechanism remains unclear. In the present study, rats were injected by tail vein with P. gingivalis three times a week for eight weeks to induce bacteremia. An in vitro BBB model infected with P. gingivalis was also established. We found that the infiltration of Evans blue dye and Albumin protein deposition in the rat brain tissues were increased in the rat brain tissues with P. gingivalis bacteremia and P. gingivalis could pass through the in vitro BBB model. Caveolae were detected after P. gingivalis infection in BMECs both in vivo and in vitro. Caveolin-1(Cav-1) expression was enhanced after P. gingivalis infection.Downregulation of Cav-1 rescued P. gingivalis-enhanced BMECs permeability. We further found P. gingivalis-gingipain could be colocalized with Cav-1 and the strong hydrogen bonding between Cav-1 and arg-specific-gingipain(RgpA) were detected.Moreover, P. gingivalis significantly inhibited the major facilitator superfamily domain containing 2a(Mfsd2a) expression. Mfsd2a overexpression reversed P. gingivalis-increased BMECs permeability and Cav-1 expression. These results revealed that Mfsd2a/Cav-1 mediated transcytosis is a key pathway governing BBB BMECs permeability induced by P. gingivalis, which may contribute to P. gingivalis/virulence factors entrance and the subsequent neurological impairments.展开更多
Xenogenic organ transplantation has been considered the most promising strategy in providing possible substitutes with the physiological function of the failing organs as well as solving the problem of insufficient do...Xenogenic organ transplantation has been considered the most promising strategy in providing possible substitutes with the physiological function of the failing organs as well as solving the problem of insufficient donor sources.However,the xenograft,suffered from immune rejection and ischemia-reperfusion injury(IRI),causes massive reactive oxygen species(ROS)expression and the subsequent cell apoptosis,leading to the xenograft failure.Our previous study found a positive role of PPAR-γ in antiinflammation through its immunomodulation effects,which inspires us to apply PPAR-γ agonist rosiglitazone(RSG)to address survival issue of xenograft with the potential to eliminate the excessive ROS.In this study,xenogenic bioroot was constructed by wrapping the dental follicle cells(DFC)with porcine extracellular matrix(p ECM).The hydrogen peroxide(H_(2)O_(2))-induced DFC was pretreated with RSG to observe its protection on the damaged biological function.Immunoflourescence staining and transmission electron microscope were used to detect the intracellular ROS level.SD rat orthotopic transplantation model and superoxide dismutase 1(SOD1)knockout mice subcutaneous transplantation model were applied to explore the regenerative outcome of the xenograft.It showed that RSG pretreatment significantly reduced the adverse effects of H2O2on DFC with decreased intracellular ROS expression and alleviated mitochondrial damage.In vivo results confirmed RSG administration substantially enhanced the host’s antioxidant capacity with reduced osteoclasts formation and increased periodontal ligament-like tissue regeneration efficiency,maximumly maintaining the xenograft function.We considered that RSG preconditioning could preserve the biological properties of the transplanted stem cells under oxidative stress(OS)microenvironment and promote organ regeneration by attenuating the inflammatory reaction and OS injury.展开更多
Oral potentially malignant disorders(OPMDs)are precursors of oral squamous cell carcinoma(OSCC).Deregulated cellular energy metabolism is a critical hallmark of cancer cells.Peroxisome proliferator-activated receptor-...Oral potentially malignant disorders(OPMDs)are precursors of oral squamous cell carcinoma(OSCC).Deregulated cellular energy metabolism is a critical hallmark of cancer cells.Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha(PGC1α)plays vital role in mitochondrial energy metabolism.However,the molecular mechanism of PGC1αon OPMDs progression is less unclear.Therefore,we investigated the effects of knockdown PGC1αon human dysplastic oral keratinocytes(DOKs)comprehensively,including cell proliferation,cell cycle,apoptosis,xenograft tumor,mitochondrial DNA(mtDNA),mitochondrial electron transport chain complexes(ETC),reactive oxygen species(ROS),oxygen consumption rate(OCR),extracellular acidification rate(ECAR),and glucose uptake.We found that knockdown PGC1αsignificantly inhibited the proliferation of DOKs in vitro and tumor growth in vivo,induced S-phase arrest,and suppressed PI3K/Akt signaling pathway without affecting cell apoptosis.Mechanistically,downregulated of PGC1αdecreased mtDNA,ETC,and OCR,while enhancing ROS,glucose uptake,ECAR,and glycolysis by regulating lactate dehydrogenase A(LDHA).Moreover,SR18292(an inhibitor of PGC1α)induced oxidative phosphorylation dysfunction of DOKs and declined DOK xenograft tumor progression.Thus,our work suggests that PGC1αplays a crucial role in cell proliferation by reprograming energy metabolism and interfering with energy metabolism,acting as a potential therapeutic target for OPMDs.展开更多
Tooth root development involves intricate spatiotemporal cellular dynamics and molecular regulation.The initiation of Hertwig’s epithelial root sheath(HERS)induces odontoblast differentiation and the subsequent radic...Tooth root development involves intricate spatiotemporal cellular dynamics and molecular regulation.The initiation of Hertwig’s epithelial root sheath(HERS)induces odontoblast differentiation and the subsequent radicular dentin deposition.Precisely controlled signaling pathways modulate the behaviors of HERS and the fates of dental mesenchymal stem cells(DMSCs).Disruptions in these pathways lead to defects in root development,such as shortened roots and furcation abnormalities.Advances in dental stem cells,biomaterials,and bioprinting show immense promise for bioengineered tooth root regeneration.However,replicating the developmental intricacies of odontogenesis has not been resolved in clinical treatment and remains a major challenge in this field.Ongoing research focusing on the mechanisms of root development,advanced biomaterials,and manufacturing techniques will enable next-generation biological root regeneration that restores the physiological structure and function of the tooth root.This review summarizes recent discoveries in the underlying mechanisms governing root ontogeny and discusses some recent key findings in developing of new biologically based dental therapies.展开更多
Introduction: Oral health management is often difficult in patients after surgical tumor resection and/or radiotherapy due to defects, bulky flaps, limitation of tongue movement, and trismus. In addition, patients who...Introduction: Oral health management is often difficult in patients after surgical tumor resection and/or radiotherapy due to defects, bulky flaps, limitation of tongue movement, and trismus. In addition, patients who have undergone radiotherapy have serious disabilities such as oral mucositis, mucosal weakening, soft tissue fibrosis, salivary gland disorder, and osteoradionecrosis. Dental hygienists must understand the characteristics of patients after surgical tumor resection and/or radiotherapy. In this report, the oral health management of three patients after maxillectomy, mandibulectomy, and radiotherapy was shown. Case Description: Case 1: A 53-year-old male patient visited our clinic after chemotherapy, radiotherapy, and partial maxillectomy for cancer of the right maxillary gingiva. Case 2: A 65-year-old male patient visited our clinic after radiotherapy for a right-sided tongue cancer, partial mandibulectomy of the right tongue to the oropharynx, a right-sided segmental mandibulectomy and a speech aid and a mandibular prosthesis were provided. Case 3: A 36-year-old female visited our clinic for radiotherapy for left-sided tongue cancer. Dental hygienists provided oral health management to the patients. In oral health management, it was suggested that intervention before cancer treatment, oral hygiene instructions tailored to patients’ symptoms, and frequent professional care are important. Conclusion: Oral health management by dental hygienists is extremely important for patients undergoing maxillofacial cancer treatment to maintain their quality of life in the long term.展开更多
Sialolithiasis is the most common condition of the salivary glands and it is characterized by the development of a calcified structure within a salivary duct. This condition can lead to inflammation, bacterial infecti...Sialolithiasis is the most common condition of the salivary glands and it is characterized by the development of a calcified structure within a salivary duct. This condition can lead to inflammation, bacterial infection, and abscess. The different forms of management range from the direct massage of the duct to the complete removal of the gland. This report describes an unusual case of submandibular sialolithiasis in a four-year-old girl. The main complaints were pain when eating and swelling in the floor of the mouth. The diagnosis was sialolithiasis in the duct of the submandibular gland. Since the salivary stone was palpable and located in the anterior portion of the duct, a minimally invasive procedure was planned. An excisional biopsy was performed and a unilateral salivary stone was removed. The histopathological analysis confirmed the diagnosis. Although rare in children, understanding the diagnostic process and the different treatment modalities leads to a favorable prognosis.展开更多
Early childhood caries (ECC) is a term used to describe dental caries in children aged 6 years or younger. Oral streptococci, such as Streptococcus mutans and Streptococcus sorbrinus, are considered to be the main e...Early childhood caries (ECC) is a term used to describe dental caries in children aged 6 years or younger. Oral streptococci, such as Streptococcus mutans and Streptococcus sorbrinus, are considered to be the main etiological agents of tooth decay in children. Other bacteria, such as Prevotella spp. and Lactobacillus spp., and fungus, that is, Candida albicans, are related to the development and progression of ECC. Biomolecules in saliva, mainly proteins, affect the survival of oral microorganisms by multiple innate defensive mechanisms, thus modulating the oral microflora. Therefore, the protein composition of saliva can be a sensitive indicator for dental health. Resistance or susceptibility to caries may be significantly correlated with alterations in salivary protein components. Some oral microorganisms and saliva proteins may serve as useful biomarkers in predicting the risk and prognosis of caries. Current research has generated abundant information that contributes to a better understanding of the roles of microorganisms and salivary proteins in ECC occurrence and prevention. This review summarizes the microorganisms that cause caries and tooth-protective salivary proteins with their potential as functional biomarkers for ECC risk assessment. The identification of biomarkers for children at high risk of ECC is not only critical for early diagnosis but also important for preventing and treating the disease.展开更多
TGF-β 1–3 are unique multi-functional growth factors that are only expressed in mammals, and mainly secreted and stored as a latent complex in the extracellular matrix(ECM). The biological functions of TGF-β in adu...TGF-β 1–3 are unique multi-functional growth factors that are only expressed in mammals, and mainly secreted and stored as a latent complex in the extracellular matrix(ECM). The biological functions of TGF-β in adults can only be delivered after ligand activation, mostly in response to environmental perturbations. Although involved in multiple biological and pathological processes of the human body, the exact roles of TGF-β in maintaining stem cells and tissue homeostasis have not been well-documented until recent advances, which delineate their functions in a given context. Our recent findings, along with data reported by others, have clearly shown that temporal and spatial activation of TGF-β is involved in the recruitment of stem/progenitor cell participation in tissue regeneration/remodeling process, whereas sustained abnormalities in TGF-β ligand activation, regardless of genetic or environmental origin, will inevitably disrupt the normal physiology and lead to pathobiology of major diseases. Modulation of TGF-β signaling with different approaches has proven effective pre-clinically in the treatment of multiple pathologies such as sclerosis/fibrosis, tumor metastasis, osteoarthritis, and immune disorders. Thus, further elucidation of the mechanisms by which TGF-β is activated in different tissues/organs and how targeted cells respond in a context-dependent way can likely be translated with clinical benefits in the management of a broad range of diseases with the involvement of TGF-β.展开更多
The purpose of our study was to evaluate the effect of photodynamic therapy (PDT), using erythrosine as a photosensitizing agent and a dental halogen curing unit as a light source, on Streptococcus mutans in a biofi...The purpose of our study was to evaluate the effect of photodynamic therapy (PDT), using erythrosine as a photosensitizing agent and a dental halogen curing unit as a light source, on Streptococcus mutans in a biofilm phase. The S. mutans biofilms were formed in a 24-well cell culture cluster. Test groups consisted of biofilms divided into four groups: group 1: no photosensitizer or light irradiation treatment (control group); group 2: photosensitizer treatment alone; group 3: light irradiation alone; group 4: photosensitizer treatment and light irradiation. After treatments, the numbers of colony-forming unit (CFU) were counted and samples were examined by confocal laser scanning fluorescence microscopy (CLSM). Only group 4 (combined treatment) resulted in significant increases in cell death, with rates of 75% and 55% after 8 h of incubation, and 74% and 42% at 12 h, for biofilms formed in brain-heart infusion (BHI) broth supplemented with 0% or O. 1% sucrose, respectively. Therefore, PDT of S. mutans biofilms using a combination of erythrosine and a dental halogen curing unit, both widely used in dental clinics, resulted in a significant increase in cell death. The PDT effects are decreased in biofilms that form in the presence of sucrose.展开更多
Regenerative endodontics(RE)therapy means physiologically replacing damaged pulp tissue and regaining functional dentin–pulp complex.Current clinical RE procedures recruit endogenous stem cells from the apical papill...Regenerative endodontics(RE)therapy means physiologically replacing damaged pulp tissue and regaining functional dentin–pulp complex.Current clinical RE procedures recruit endogenous stem cells from the apical papilla,periodontal tissue,bone marrow and peripheral blood,with or without application of scaffolds and growth factors in the root canal space,resulting in cementum-like and bone-like tissue formation.Without the involvement of dental pulp stem cells(DPSCs),it is unlikely that functional pulp regeneration can be achieved,even though acceptable repair can be acquired.DPSCs,due to their specific odontogenic potential,high proliferation,neurovascular property,and easy accessibility,are considered as the most eligible cell source for dentin–pulp regeneration.The regenerative potential of DPSCs has been demonstrated by recent clinical progress.DPSC transplantation following pulpectomy has successfully reconstructed neurovascularized pulp that simulates the physiological structure of natural pulp.The self-renewal,proliferation,and odontogenic differentiation of DPSCs are under the control of a cascade of transcription factors.Over recent decades,epigenetic modulations implicating histone modifications,DNA methylation,and noncoding(nc)RNAs have manifested as a new layer of gene regulation.These modulations exhibit a profound effect on the cellular activities of DPSCs.In this review,we offer an overview about epigenetic regulation of the fate of DPSCs;in particular,on the proliferation,odontogenic differentiation,angiogenesis,and neurogenesis.We emphasize recent discoveries of epigenetic molecules that can alter DPSC status and promote pulp regeneration through manipulation over epigenetic profiles.展开更多
To investigate how the biofilm three-dimensional(3D) architecture influences in situ pH distribution patterns on the enamel surface. Biofilms were formed on human tooth enamel in the presence of 1% sucrose or 0.5% glu...To investigate how the biofilm three-dimensional(3D) architecture influences in situ pH distribution patterns on the enamel surface. Biofilms were formed on human tooth enamel in the presence of 1% sucrose or 0.5% glucose plus 0.5% fructose. At specific time points, biofilms were exposed to a neutral pH buffer to mimic the buffering of saliva and subsequently pulsed with 1% glucose to induce re-acidification. Simultaneous 3D pH mapping and architecture of intact biofilms was performed using two-photon confocal microscopy. The enamel surface and mineral content characteristics were examined successively via optical profilometry and microradiography analyses. Sucrose-mediated biofilm formation created spatial heterogeneities manifested by complex networks of bacterial clusters(microcolonies). Acidic regions(pH<5.5) were found only in the interior of microcolonies,which impedes rapid neutralization(taking more than 120 min for neutralization). Glucose exposure rapidly re-created the acidic niches, indicating formation of diffusion barriers associated with microcolonies structure. Enamel demineralization(white spots),rougher surface, deeper lesion and more mineral loss appeared to be associated with the localization of these bacterial clusters at the biofilm-enamel interface. Similar 3D architecture was observed in plaque-biofilms formed in vivo in the presence of sucrose. The formation of complex 3D architectures creates spatially heterogeneous acidic microenvironments in close proximity of enamel surface, which might correlate with the localized pattern of the onset of carious lesions(white spot like) on teeth.展开更多
Early childhood caries(ECC)is a significant chronic disease of childhood and a rising public health burden worldwide.ECC may cause a higher risk of new caries lesions in both primary and permanent dentition,affecting ...Early childhood caries(ECC)is a significant chronic disease of childhood and a rising public health burden worldwide.ECC may cause a higher risk of new caries lesions in both primary and permanent dentition,affecting lifelong oral health.The occurrence of ECC has been closely related to the core microbiome change in the oral cavity,which may be influenced by diet habits,oral health management,fluoride use,and dental manipulations.So,it is essential to improve parental oral health and awareness of health care,to establish a dental home at the early stage of childhood,and make an individualized caries management plan.Dental interventions according to the minimally invasive concept should be carried out to treat dental caries.This expert consensus mainly discusses the etiology of ECC,caries-risk assessment of children,prevention and treatment plan of ECC,aiming to achieve lifelong oral health.展开更多
Glucosyltransferases(Gtfs)play critical roles in the etiology and pathogenesis of Streptococcus mutans(S.mutans)-mediated dental caries including early childhood caries.Gtfs enhance the biofilm formation and promotes ...Glucosyltransferases(Gtfs)play critical roles in the etiology and pathogenesis of Streptococcus mutans(S.mutans)-mediated dental caries including early childhood caries.Gtfs enhance the biofilm formation and promotes colonization of cariogenic bacteria by generating biofilm extracellular polysaccharides(EPSs),the key virulence property in the cariogenic process.Therefore,Gtfs have become an appealing target for effective therapeutic interventions that inhibit cariogenic biofilms.Importantly,targeting Gtfs selectively impairs the S.mutans virulence without affecting S.mutans existence or the existence of other species in the oral cavity.Over the past decade,numerous Gtfs inhibitory molecules have been identified,mainly including natural and synthetic compounds and their derivatives,antibodies,and metal ions.These therapeutic agents exert their inhibitory role in inhibiting the expression gtf genes and the activities and secretion of Gtfs enzymes with a wide range of sensitivity and effectiveness.Understanding molecular mechanisms of inhibiting Gtfs will contribute to instructing drug combination strategies,which is more effective for inhibiting Gtfs than one drug or class of drugs.This review highlights our current understanding of Gtfs activities and their potential utility,and discusses challenges and opportunities for future exploration of Gtfs as a therapeutic target.展开更多
Runt-related transcription factor-1(Runxl)is required for chondrocyte-to-osteoblast lineage commitment by enhancing both chondrogenesis and osteogenesis during vertebrate development.However,the potential role of Runx...Runt-related transcription factor-1(Runxl)is required for chondrocyte-to-osteoblast lineage commitment by enhancing both chondrogenesis and osteogenesis during vertebrate development.However,the potential role of Runxl in joint diseases is not well known.In the current study,we aimed to explore the role of Runxl in osteoarthritis induced by anterior cruciate ligament transaction(ACLT)surgery.We showed that chondrocyte-specific Runxl knockout(Runx1f/fCol2a1-Cre)aggravated cartilage destruction by accelerating the loss of proteoglycan and collagen II in early osteoarthritis.Moreover,we observed thinning and ossification of the growth plate,a decrease in chondrocyte proliferative capacity and the loss of bone matrix around the growth plate in late osteoarthritis.We overexpressed Runxl by adeno-associated virus(AAV)in articular cartilage and identified its protective effect by slowing the destruction of osteoarthritis in cartilage in early osteoarthritis and alleviating the pathological progression of growth plate cartilage in late osteoarthritis.ChIP-seq analysis identified new targets that interacted with Runxl in cartilage pathology,and we confirmed the direct interactions of these factors with Runxl by ChIP-qPCR.This study helps us to understand the function of Runxl in osteoarthritis and provides new clues for targeted osteoarthritis therapy.展开更多
文摘<strong>Context:</strong> Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) has been identified in December 2019. Since then, it has been spreading around the world and has caused a pandemic. Strict safety protocols should be followed to resume dental treatments. <strong>Evidence Acquisition: </strong>A comprehensive search was conducted on PubMed, Scopus, Medline and google scholar databases using the MeSH words of COVID-19, SARS-COV-2, Dentistry, and Child from December 2019 until July 2020. <strong>Results:</strong> Among COVID-19 patients, asymptomatic patients still are considered to be serious carriers of the COVID-19 which can play a key role in transmission of the virus. Children are reported to be less than 2 percent of the infected population and are considered as serious potential carriers. Telemedicine can take a key part in educating parents regarding this matter. Chronic and rare diseases such as Kawasaki Disease (KD) might show acute and more frequent symptoms amongst COVID-19 patients. Salivary testing can be a convenient chairside way for COVID-19 and it has been shown to be effective in identifying critically ill patients. Dry mouth and amblygeustia have been reported to be the oral symptoms of the COVID-19. <strong>Conclusions:</strong> Dentists must make tough decisions in prioritizing patient’s needs in the period of pandemic. They should frequently get updated as the situation is fluid and the protocols might change.
基金funded by grants from the National Natural Science Foundation of China(Nos.81771095,82071235)Key R&D Program of Shaanxi Province(2017SF-103,2021KWZ-26,2023-JC-ZD-56)State Key Laboratory of Military Stomatology(2020ZA01).
文摘Dental stem cells(DSCs)have attracted significant interest as autologous stem cells since they are easily accessible and give a minimal immune response.These properties and their ability to both maintain self-renewal and undergo multi-lineage differentiation establish them as key players in regenerative medicine.While many regulatory factors determine the differentiation trajectory of DSCs,prior research has predominantly been based on genetic,epigenetic,and molecular aspects.Recent evidence suggests that DSC differentiation can also be influenced by autophagy,a highly conserved cellular process responsible for maintaining cellular and tissue homeostasis under various stress conditions.This comprehensive review endeavors to elucidate the intricate regulatory mechanism and relationship between autophagy and DSC differentiation.To achieve this goal,we dissect the intricacies of autophagy and its mechanisms.Subsequently,we elucidate its pivotal roles in impacting DSC differentiation,including osteo/odontogenic,neurogenic,and angiogenic trajectories.Furthermore,we reveal the regulatory factors that govern autophagy in DSC lineage commitment,including scaffold materials,pharmaceutical cues,and the extrinsic milieu.The implications of this review are far-reaching,underpinning the potential to wield autophagy as a regulatory tool to expedite DSC-directed differentiation and thereby promote the application of DSCs within the realm of regenerative medicine.
文摘BACKGROUND In recent years,the association between oral health and the risk of gastric cancer(GC)has gradually attracted increased interest.However,in terms of GC incidence,the association between oral health and GC incidence remains contro-versial.Periodontitis is reported to increase the risk of GC.However,some studies have shown that periodontitis has no effect on the risk of GC.Therefore,the present study aimed to assess whether there is a relationship between oral health and the risk of GC.AIM To assess whether there was a relationship between oral health and the risk of GC.METHODS Five databases were searched to find eligible studies from inception to April 10,2023.Newcastle-Ottawa Scale score was used to assess the quality of included studies.The quality of cohort studies and case-control studies were evaluated separately in this study.Incidence of GC were described by odds ratio(OR)and 95%confidence interval(CI).Funnel plot was used to represent the publication bias of included studies.We performed the data analysis by StataSE 16.RESULTS A total of 1431677 patients from twelve included studies were enrolled for data analysis in this study.According to our analysis,we found that the poor oral health was associated with higher risk of GC(OR=1.15,95%CI:1.02-1.29;I2=59.47%,P=0.00<0.01).Moreover,after subgroup analysis,the outcomes showed that whether tooth loss(OR=1.12,95%CI:0.94-1.29;I2=6.01%,P>0.01),gingivitis(OR=1.19,95%CI:0.71-1.67;I2=0.00%,P>0.01),dentures(OR=1.27,95%CI:0.63-1.19;I2=68.79%,P>0.01),or tooth brushing(OR=1.25,95%CI:0.78-1.71;I2=88.87%,P>0.01)had no influence on the risk of GC.However,patients with periodontitis(OR=1.13,95%CI:1.04-1.23;I2=0.00%,P<0.01)had a higher risk of GC.CONCLUSION Patients with poor oral health,especially periodontitis,had a higher risk of GC.Patients should be concerned about their oral health.Improving oral health might reduce the risk of GC.
基金funded by the National Natural Science Foundation of China(Code No.82100954/81800924)Natural Science Foundation of Inner Mongolia Autonomous Region(Code No.2023QN08026)+3 种基金Key Research and Development Projects of Shaanxi Province(Code No.2022KW-12)The Basic and Natural Science Research Program of Shaanxi Province(Code No.2022JQ-915)Key Research and Development Program of Tibet Autonomous Region(XZ202001ZY0059G)New Technology and New Business Project of the Third Affiliated Hospital of Air Force Military Medical University(Code No.LX2021-416).
文摘Autophagy is a widespread biological process that controls cellular growth,survival,development,and death.Circadian rhythm is a recurring reaction of living organisms and behaviors to variations in surrounding brightness and obscurity.Most of the fundamental physiological processes in mammals,such as the sleep-wake pattern and the rhythm of nutrition and energy metabolism,are governed by circadian rhythms.Research has indicated that autophagy exhibits a specific circadian pattern in both normal and abnormal conditions.Autophagy can modulate circadian rhythms by breaking down proteins that regulate the circadian clock.The potential regulatory connection between the two has been a popular subject of clinical and fundamental research.Understanding the interaction between circadian rhythm and autophagy could potentially lead to the development of novel approaches for disease treatment in the future.The present analysis presented a summary of the molecular processes implicated in the interplay between autophagy and circadian rhythm,as well as the pathological importance of the disrupted regulatory association between these two phenomena.
基金supported by the National Natural Science Foundation of China Grants(82370945, 82171001, 82222015 and 82370915)Research Funding from West China School/Hospital of Stomatology Sichuan University(RCDWJS2023-1)。
文摘Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient's digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients' prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine.
文摘Antibiotic drugs are a very important drug group considering their frequent use, safety profile and their impact on bacterial resistance induction. Aim: To investigate the utilization of antibiotic drugs at the University Dentistry Clinical Center of Kosovo (UDCCK). Methodology: Retrospective and descriptive study. Patient records were used as a data source collected for a period of 3 months. The total number of registered outpatients in the UDCCK was 1117 patients. The data analysis was performed using the WHO methodology and results were expressed in DDD per 1000 inhabitants per day. Results: The total prescription of antibiotics at UDCCK was 7.18 DDD/ 1000 inhabitants/day. Antibiotics were prescribed for 86 or 7.70% of patients. The most commonly prescribed antibiotic was Amoxicillin with clavulonic acid 3.12 (43.45%) DDD, followed by Metronidazole 2.31 DDD and Amoxicillin 1.25 DDD. Erythromycin and Cefalexin were prescribed evidently less compared to other antibiotics (0.38 and 0.12 DDD/1000 inhabitant/day, respectively). Conclusions: The quantitative analysis showed no rationality of prescription of antibiotics in UDCCK. Generally, the use of antibiotics in both departments of UDCCK is higher compared to other countries. We recommend the implementation of restrictive prescription standards for antibiotics.
基金supported by Scientific Research Funding Project of Education Department of Liaoning Province [grant number LJKZ0782]National Natural Science Foundation of China [grant numbers 81670999]。
文摘Bacteremia induced by periodontal infection is an important factor for periodontitis to threaten general health. P. gingivalis DNA/virulence factors have been found in the brain tissues from patients with Alzheimer’s disease(AD). The blood-brain barrier(BBB) is essential for keeping toxic substances from entering brain tissues. However, the effect of P. gingivalis bacteremia on BBB permeability and its underlying mechanism remains unclear. In the present study, rats were injected by tail vein with P. gingivalis three times a week for eight weeks to induce bacteremia. An in vitro BBB model infected with P. gingivalis was also established. We found that the infiltration of Evans blue dye and Albumin protein deposition in the rat brain tissues were increased in the rat brain tissues with P. gingivalis bacteremia and P. gingivalis could pass through the in vitro BBB model. Caveolae were detected after P. gingivalis infection in BMECs both in vivo and in vitro. Caveolin-1(Cav-1) expression was enhanced after P. gingivalis infection.Downregulation of Cav-1 rescued P. gingivalis-enhanced BMECs permeability. We further found P. gingivalis-gingipain could be colocalized with Cav-1 and the strong hydrogen bonding between Cav-1 and arg-specific-gingipain(RgpA) were detected.Moreover, P. gingivalis significantly inhibited the major facilitator superfamily domain containing 2a(Mfsd2a) expression. Mfsd2a overexpression reversed P. gingivalis-increased BMECs permeability and Cav-1 expression. These results revealed that Mfsd2a/Cav-1 mediated transcytosis is a key pathway governing BBB BMECs permeability induced by P. gingivalis, which may contribute to P. gingivalis/virulence factors entrance and the subsequent neurological impairments.
基金supported by the Nature Science Foundation of China(31971281,32201073,82270958)Innovative Talents Program of Sichuan Province(2022JDRC0043)Research and Develop Program,West China Hospital of Stomatology Sichuan University(RD-03-202106)。
文摘Xenogenic organ transplantation has been considered the most promising strategy in providing possible substitutes with the physiological function of the failing organs as well as solving the problem of insufficient donor sources.However,the xenograft,suffered from immune rejection and ischemia-reperfusion injury(IRI),causes massive reactive oxygen species(ROS)expression and the subsequent cell apoptosis,leading to the xenograft failure.Our previous study found a positive role of PPAR-γ in antiinflammation through its immunomodulation effects,which inspires us to apply PPAR-γ agonist rosiglitazone(RSG)to address survival issue of xenograft with the potential to eliminate the excessive ROS.In this study,xenogenic bioroot was constructed by wrapping the dental follicle cells(DFC)with porcine extracellular matrix(p ECM).The hydrogen peroxide(H_(2)O_(2))-induced DFC was pretreated with RSG to observe its protection on the damaged biological function.Immunoflourescence staining and transmission electron microscope were used to detect the intracellular ROS level.SD rat orthotopic transplantation model and superoxide dismutase 1(SOD1)knockout mice subcutaneous transplantation model were applied to explore the regenerative outcome of the xenograft.It showed that RSG pretreatment significantly reduced the adverse effects of H2O2on DFC with decreased intracellular ROS expression and alleviated mitochondrial damage.In vivo results confirmed RSG administration substantially enhanced the host’s antioxidant capacity with reduced osteoclasts formation and increased periodontal ligament-like tissue regeneration efficiency,maximumly maintaining the xenograft function.We considered that RSG preconditioning could preserve the biological properties of the transplanted stem cells under oxidative stress(OS)microenvironment and promote organ regeneration by attenuating the inflammatory reaction and OS injury.
基金supported by the National Natural Science Foundations of China(82372735,82141130).
文摘Oral potentially malignant disorders(OPMDs)are precursors of oral squamous cell carcinoma(OSCC).Deregulated cellular energy metabolism is a critical hallmark of cancer cells.Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha(PGC1α)plays vital role in mitochondrial energy metabolism.However,the molecular mechanism of PGC1αon OPMDs progression is less unclear.Therefore,we investigated the effects of knockdown PGC1αon human dysplastic oral keratinocytes(DOKs)comprehensively,including cell proliferation,cell cycle,apoptosis,xenograft tumor,mitochondrial DNA(mtDNA),mitochondrial electron transport chain complexes(ETC),reactive oxygen species(ROS),oxygen consumption rate(OCR),extracellular acidification rate(ECAR),and glucose uptake.We found that knockdown PGC1αsignificantly inhibited the proliferation of DOKs in vitro and tumor growth in vivo,induced S-phase arrest,and suppressed PI3K/Akt signaling pathway without affecting cell apoptosis.Mechanistically,downregulated of PGC1αdecreased mtDNA,ETC,and OCR,while enhancing ROS,glucose uptake,ECAR,and glycolysis by regulating lactate dehydrogenase A(LDHA).Moreover,SR18292(an inhibitor of PGC1α)induced oxidative phosphorylation dysfunction of DOKs and declined DOK xenograft tumor progression.Thus,our work suggests that PGC1αplays a crucial role in cell proliferation by reprograming energy metabolism and interfering with energy metabolism,acting as a potential therapeutic target for OPMDs.
基金NSFC grants 82222015,82171001,and 82370945Research Funding from West China School/Hospital of Stomatology Sichuan University(No.RCDWJS2023-1).
文摘Tooth root development involves intricate spatiotemporal cellular dynamics and molecular regulation.The initiation of Hertwig’s epithelial root sheath(HERS)induces odontoblast differentiation and the subsequent radicular dentin deposition.Precisely controlled signaling pathways modulate the behaviors of HERS and the fates of dental mesenchymal stem cells(DMSCs).Disruptions in these pathways lead to defects in root development,such as shortened roots and furcation abnormalities.Advances in dental stem cells,biomaterials,and bioprinting show immense promise for bioengineered tooth root regeneration.However,replicating the developmental intricacies of odontogenesis has not been resolved in clinical treatment and remains a major challenge in this field.Ongoing research focusing on the mechanisms of root development,advanced biomaterials,and manufacturing techniques will enable next-generation biological root regeneration that restores the physiological structure and function of the tooth root.This review summarizes recent discoveries in the underlying mechanisms governing root ontogeny and discusses some recent key findings in developing of new biologically based dental therapies.
文摘Introduction: Oral health management is often difficult in patients after surgical tumor resection and/or radiotherapy due to defects, bulky flaps, limitation of tongue movement, and trismus. In addition, patients who have undergone radiotherapy have serious disabilities such as oral mucositis, mucosal weakening, soft tissue fibrosis, salivary gland disorder, and osteoradionecrosis. Dental hygienists must understand the characteristics of patients after surgical tumor resection and/or radiotherapy. In this report, the oral health management of three patients after maxillectomy, mandibulectomy, and radiotherapy was shown. Case Description: Case 1: A 53-year-old male patient visited our clinic after chemotherapy, radiotherapy, and partial maxillectomy for cancer of the right maxillary gingiva. Case 2: A 65-year-old male patient visited our clinic after radiotherapy for a right-sided tongue cancer, partial mandibulectomy of the right tongue to the oropharynx, a right-sided segmental mandibulectomy and a speech aid and a mandibular prosthesis were provided. Case 3: A 36-year-old female visited our clinic for radiotherapy for left-sided tongue cancer. Dental hygienists provided oral health management to the patients. In oral health management, it was suggested that intervention before cancer treatment, oral hygiene instructions tailored to patients’ symptoms, and frequent professional care are important. Conclusion: Oral health management by dental hygienists is extremely important for patients undergoing maxillofacial cancer treatment to maintain their quality of life in the long term.
文摘Sialolithiasis is the most common condition of the salivary glands and it is characterized by the development of a calcified structure within a salivary duct. This condition can lead to inflammation, bacterial infection, and abscess. The different forms of management range from the direct massage of the duct to the complete removal of the gland. This report describes an unusual case of submandibular sialolithiasis in a four-year-old girl. The main complaints were pain when eating and swelling in the floor of the mouth. The diagnosis was sialolithiasis in the duct of the submandibular gland. Since the salivary stone was palpable and located in the anterior portion of the duct, a minimally invasive procedure was planned. An excisional biopsy was performed and a unilateral salivary stone was removed. The histopathological analysis confirmed the diagnosis. Although rare in children, understanding the diagnostic process and the different treatment modalities leads to a favorable prognosis.
基金supported by the National Natural Science Foundation of China81400502(Qiong Zhang)the Young Teacher Research Start Funding of Sichuan University 2016SCU11049(Yuan Zhou)
文摘Early childhood caries (ECC) is a term used to describe dental caries in children aged 6 years or younger. Oral streptococci, such as Streptococcus mutans and Streptococcus sorbrinus, are considered to be the main etiological agents of tooth decay in children. Other bacteria, such as Prevotella spp. and Lactobacillus spp., and fungus, that is, Candida albicans, are related to the development and progression of ECC. Biomolecules in saliva, mainly proteins, affect the survival of oral microorganisms by multiple innate defensive mechanisms, thus modulating the oral microflora. Therefore, the protein composition of saliva can be a sensitive indicator for dental health. Resistance or susceptibility to caries may be significantly correlated with alterations in salivary protein components. Some oral microorganisms and saliva proteins may serve as useful biomarkers in predicting the risk and prognosis of caries. Current research has generated abundant information that contributes to a better understanding of the roles of microorganisms and salivary proteins in ECC occurrence and prevention. This review summarizes the microorganisms that cause caries and tooth-protective salivary proteins with their potential as functional biomarkers for ECC risk assessment. The identification of biomarkers for children at high risk of ECC is not only critical for early diagnosis but also important for preventing and treating the disease.
基金supported by U.S. National Institutes of Health grants (AR063943 and DK057501 to X.C. AR064833 to J.L.C.)+3 种基金the National Natural Science Foundation of China (81771099 to X.X.)the Key Project for Frontier Research of Science and Technology Department of Sichuan Province (2016JY0006 to X.Z.)Sichuan Province Science and Technology Innovation Team Program (2017TD0016 to Q.Y.).X.X.supported by the visiting scholar fellowship from West China Hospital of Stomatology, Sichuan University
文摘TGF-β 1–3 are unique multi-functional growth factors that are only expressed in mammals, and mainly secreted and stored as a latent complex in the extracellular matrix(ECM). The biological functions of TGF-β in adults can only be delivered after ligand activation, mostly in response to environmental perturbations. Although involved in multiple biological and pathological processes of the human body, the exact roles of TGF-β in maintaining stem cells and tissue homeostasis have not been well-documented until recent advances, which delineate their functions in a given context. Our recent findings, along with data reported by others, have clearly shown that temporal and spatial activation of TGF-β is involved in the recruitment of stem/progenitor cell participation in tissue regeneration/remodeling process, whereas sustained abnormalities in TGF-β ligand activation, regardless of genetic or environmental origin, will inevitably disrupt the normal physiology and lead to pathobiology of major diseases. Modulation of TGF-β signaling with different approaches has proven effective pre-clinically in the treatment of multiple pathologies such as sclerosis/fibrosis, tumor metastasis, osteoarthritis, and immune disorders. Thus, further elucidation of the mechanisms by which TGF-β is activated in different tissues/organs and how targeted cells respond in a context-dependent way can likely be translated with clinical benefits in the management of a broad range of diseases with the involvement of TGF-β.
基金supported by Cooperative Research (CR1102) of Gangneung-Wonju National University Dental Hospital
文摘The purpose of our study was to evaluate the effect of photodynamic therapy (PDT), using erythrosine as a photosensitizing agent and a dental halogen curing unit as a light source, on Streptococcus mutans in a biofilm phase. The S. mutans biofilms were formed in a 24-well cell culture cluster. Test groups consisted of biofilms divided into four groups: group 1: no photosensitizer or light irradiation treatment (control group); group 2: photosensitizer treatment alone; group 3: light irradiation alone; group 4: photosensitizer treatment and light irradiation. After treatments, the numbers of colony-forming unit (CFU) were counted and samples were examined by confocal laser scanning fluorescence microscopy (CLSM). Only group 4 (combined treatment) resulted in significant increases in cell death, with rates of 75% and 55% after 8 h of incubation, and 74% and 42% at 12 h, for biofilms formed in brain-heart infusion (BHI) broth supplemented with 0% or O. 1% sucrose, respectively. Therefore, PDT of S. mutans biofilms using a combination of erythrosine and a dental halogen curing unit, both widely used in dental clinics, resulted in a significant increase in cell death. The PDT effects are decreased in biofilms that form in the presence of sucrose.
基金Supported by National Natural Science Foundation of China,No.81800929 and No.81771033Sichuan Science and Technology Program,No.2019JDRC0096and Research and Develop Program,West China Hospital of Stomatology Sichuan University,No.LCYJ2019-24.
文摘Regenerative endodontics(RE)therapy means physiologically replacing damaged pulp tissue and regaining functional dentin–pulp complex.Current clinical RE procedures recruit endogenous stem cells from the apical papilla,periodontal tissue,bone marrow and peripheral blood,with or without application of scaffolds and growth factors in the root canal space,resulting in cementum-like and bone-like tissue formation.Without the involvement of dental pulp stem cells(DPSCs),it is unlikely that functional pulp regeneration can be achieved,even though acceptable repair can be acquired.DPSCs,due to their specific odontogenic potential,high proliferation,neurovascular property,and easy accessibility,are considered as the most eligible cell source for dentin–pulp regeneration.The regenerative potential of DPSCs has been demonstrated by recent clinical progress.DPSC transplantation following pulpectomy has successfully reconstructed neurovascularized pulp that simulates the physiological structure of natural pulp.The self-renewal,proliferation,and odontogenic differentiation of DPSCs are under the control of a cascade of transcription factors.Over recent decades,epigenetic modulations implicating histone modifications,DNA methylation,and noncoding(nc)RNAs have manifested as a new layer of gene regulation.These modulations exhibit a profound effect on the cellular activities of DPSCs.In this review,we offer an overview about epigenetic regulation of the fate of DPSCs;in particular,on the proliferation,odontogenic differentiation,angiogenesis,and neurogenesis.We emphasize recent discoveries of epigenetic molecules that can alter DPSC status and promote pulp regeneration through manipulation over epigenetic profiles.
基金supported in part by the National Institute for Dental and Craniofacial Research (NIDCR) grants DE025728 (GH),DE18023 (HK) and DE25220 (HK)
文摘To investigate how the biofilm three-dimensional(3D) architecture influences in situ pH distribution patterns on the enamel surface. Biofilms were formed on human tooth enamel in the presence of 1% sucrose or 0.5% glucose plus 0.5% fructose. At specific time points, biofilms were exposed to a neutral pH buffer to mimic the buffering of saliva and subsequently pulsed with 1% glucose to induce re-acidification. Simultaneous 3D pH mapping and architecture of intact biofilms was performed using two-photon confocal microscopy. The enamel surface and mineral content characteristics were examined successively via optical profilometry and microradiography analyses. Sucrose-mediated biofilm formation created spatial heterogeneities manifested by complex networks of bacterial clusters(microcolonies). Acidic regions(pH<5.5) were found only in the interior of microcolonies,which impedes rapid neutralization(taking more than 120 min for neutralization). Glucose exposure rapidly re-created the acidic niches, indicating formation of diffusion barriers associated with microcolonies structure. Enamel demineralization(white spots),rougher surface, deeper lesion and more mineral loss appeared to be associated with the localization of these bacterial clusters at the biofilm-enamel interface. Similar 3D architecture was observed in plaque-biofilms formed in vivo in the presence of sucrose. The formation of complex 3D architectures creates spatially heterogeneous acidic microenvironments in close proximity of enamel surface, which might correlate with the localized pattern of the onset of carious lesions(white spot like) on teeth.
基金supported by the National Natural Science Foundation of China(82170947)the International Science and Technology Innovation Cooperation Projects of Science and Technology Office of Sichuan Province(2019YFH0025)。
文摘Early childhood caries(ECC)is a significant chronic disease of childhood and a rising public health burden worldwide.ECC may cause a higher risk of new caries lesions in both primary and permanent dentition,affecting lifelong oral health.The occurrence of ECC has been closely related to the core microbiome change in the oral cavity,which may be influenced by diet habits,oral health management,fluoride use,and dental manipulations.So,it is essential to improve parental oral health and awareness of health care,to establish a dental home at the early stage of childhood,and make an individualized caries management plan.Dental interventions according to the minimally invasive concept should be carried out to treat dental caries.This expert consensus mainly discusses the etiology of ECC,caries-risk assessment of children,prevention and treatment plan of ECC,aiming to achieve lifelong oral health.
基金supported by the National Natural Science Foundation of China(82170947)the Applied Basic Research Project of Science and Technology Department of Sichuan Province(2020YJ0296)the Innovation and Collaborative Project of Science and Technology Department of Sichuan Province(2019YFH0025)。
文摘Glucosyltransferases(Gtfs)play critical roles in the etiology and pathogenesis of Streptococcus mutans(S.mutans)-mediated dental caries including early childhood caries.Gtfs enhance the biofilm formation and promotes colonization of cariogenic bacteria by generating biofilm extracellular polysaccharides(EPSs),the key virulence property in the cariogenic process.Therefore,Gtfs have become an appealing target for effective therapeutic interventions that inhibit cariogenic biofilms.Importantly,targeting Gtfs selectively impairs the S.mutans virulence without affecting S.mutans existence or the existence of other species in the oral cavity.Over the past decade,numerous Gtfs inhibitory molecules have been identified,mainly including natural and synthetic compounds and their derivatives,antibodies,and metal ions.These therapeutic agents exert their inhibitory role in inhibiting the expression gtf genes and the activities and secretion of Gtfs enzymes with a wide range of sensitivity and effectiveness.Understanding molecular mechanisms of inhibiting Gtfs will contribute to instructing drug combination strategies,which is more effective for inhibiting Gtfs than one drug or class of drugs.This review highlights our current understanding of Gtfs activities and their potential utility,and discusses challenges and opportunities for future exploration of Gtfs as a therapeutic target.
基金This work was supported by the National Natural Science Foundation of China(81771047 to J.X.,81901040 to CZ.)the China Postdoctoral Science Foundation(2019M653440)+1 种基金the Sichuan Provincial Science and Technology Department(2019YJ0101)the Young Elite Scientist Sponsorship Program by CAST(2020QNR001).
文摘Runt-related transcription factor-1(Runxl)is required for chondrocyte-to-osteoblast lineage commitment by enhancing both chondrogenesis and osteogenesis during vertebrate development.However,the potential role of Runxl in joint diseases is not well known.In the current study,we aimed to explore the role of Runxl in osteoarthritis induced by anterior cruciate ligament transaction(ACLT)surgery.We showed that chondrocyte-specific Runxl knockout(Runx1f/fCol2a1-Cre)aggravated cartilage destruction by accelerating the loss of proteoglycan and collagen II in early osteoarthritis.Moreover,we observed thinning and ossification of the growth plate,a decrease in chondrocyte proliferative capacity and the loss of bone matrix around the growth plate in late osteoarthritis.We overexpressed Runxl by adeno-associated virus(AAV)in articular cartilage and identified its protective effect by slowing the destruction of osteoarthritis in cartilage in early osteoarthritis and alleviating the pathological progression of growth plate cartilage in late osteoarthritis.ChIP-seq analysis identified new targets that interacted with Runxl in cartilage pathology,and we confirmed the direct interactions of these factors with Runxl by ChIP-qPCR.This study helps us to understand the function of Runxl in osteoarthritis and provides new clues for targeted osteoarthritis therapy.