General Considerations for the Practice of Pediatric Dentistry in the Period of COVID-19 Pandemic: A Review

Context: 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. Evidence Acquisition: 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. Results: 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. Conclusions: 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.

Expert consensus on pediatric orthodontic therapies of malocclusions in children

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Emerging roles of exosomes in oral diseases progression

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.

An overview of autophagy in the differentiation of dental stem cells

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.

Poor oral health was associated with higher risk of gastric cancer: Evidence from 1431677 participants

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.

Transcriptomic and cellular decoding of scaffolds-induced suture mesenchyme regeneration

Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration.Despite extensive studies on mineralized parenchymal tissue rebuilding,regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances yet.Current knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic damage.But to date,the absence of promising therapeutic biomaterials/scaffolds remains.The reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of scaffolds.To address these issues,in this study,we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial scaffolds.Our data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses.A feasible scaffold,polylactic acid electrospinning membrane(PLA),was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center,meanwhile supporting proper osteointegration with defect bony edges.Especially,transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were deciphered.This study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing,offering clinicians potential choices for regenerating such complicated injuries.

Autophagy and circadian rhythms:interactions and clinical implications

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.

Cell membrane vesicles derived from hBMSCs and hUVECs enhance bone regeneration

Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells(BMSCs)and vascular endothelial cells(ECs).However,there are apparent limitations in stem cell-based therapy which hinder its clinic translation.Hence,we investigated the potential of alternative stem cell substitutes for facilitating bone regeneration.In this study,we successfully prepared cell membrane vesicles(CMVs)from BMSCs and ECs.The results showed that BMSC-derived cell membrane vesicles(BMSC-CMVs)possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental cells.EC-derived cell membrane vesicles(EC-CMVs)also contained BMP2 and VEGF derived from their parental cells.BMSC-CMVs enhanced tube formation and migration ability of hUVECs,while EC-CMVs promoted the osteogenic differentiation of hBMSCs in vitro.Using a rat skull defect model,we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in vivo.Therefore,our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.

Glanzmann Thrombasthenia: Managing Gingival Bleeding Triggered by Tooth Eruption—A Rare Case Report

Glanzmann thrombasthenia (GT) is a rare and often underdiagnosed congenital bleeding disorder caused by mutations in the genes encoding glycoproteins GPIIb or GPIIIa, resulting in platelet dysfunction. Inherited in an autosomal recessive manner, GT is characterized by the inability of platelets to aggregate. Clinically, it presents with mucocutaneous bleeding, such as easy and extensive bruising, severe epistaxis, menorrhagia, gingival bleeding, postpartum hemorrhage, and unexpected bleeding following procedures, despite a normal platelet count. We present a case involving a 6-year-old male patient who experienced spontaneous gingival bleeding for the past 4 weeks due to the eruption of his first permanent molars. The bleeding was particularly severe at night, disrupting the child’s sleep. The patient had been diagnosed with GT at the age of 16 months. Dental management was pursued, and the use of tranexamic acid mouthwash, combined with meticulous oral hygiene, resulted in an excellent response.

The antibiotic utilization at the university dentistry clinical center of Kosovo

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.

Porphyromonas gingivalis bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway

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.

PPAR-γactivation promotes xenogenic bioroot regeneration by attenuating the xenograft induced-oxidative stress

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.

Knockdown of PGC1α suppresses dysplastic oral keratinocytes proliferation through reprogramming energy metabolism

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.

Spatiotemporal cellular dynamics and molecular regulation of tooth root ontogeny

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.

Oral Health Management of Three Head and Neck Cancer Patients Performed by Dental Hygienists

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.

An Unusual Case of Submandibular Sialolithiasis in Early Childhood: A Case Report

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.

Salivary proteins and microbiota as biomarkers for early childhood caries risk assessment

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.

Transforming growth factor-β in stem cells and tissue homeostasis

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.

Epigenetic regulation of dental pulp stem cells and its potential in regenerative endodontics

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.

Expert consensus on early childhood caries management

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.