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Melatonin is a key hormone that regulates the sleep–wake cycle and plays an important role in maintaining circadian rhythm and sleep onset. The daily rise in melatonin secretion is associated with an increased tendency to sleep, occurring approximately 2 h before bedtime. This correlation between melatonin levels and sleep onset makes it a reliable biomarker for circadian rhythm sleep–wake disorders. An accurate assessment of dim light melatonin onset (DLMO) is vital for understanding circadian timing and diagnosing sleep–wake cycle disruptions. However, the traditional methods for detecting melatonin in saliva are either complex or lack the sensitivity required for the accurate assessment of DLMO, especially at low concentrations. Here, we present a novel competitive enzyme-linked aptamer-based assay developed to detect melatonin in saliva. Unlike conventional assays, this technique utilizes chemically synthesized single-stranded DNA or RNA aptamers, which bind to melatonin with high specificity and sensitivity. The assay measures melatonin, attaining a linear dynamic range from 8.62 × 10 ‒6  M to 3.9 × 10 ‒11  M, with a detection limit of 2.5 × 10 ‒12  M (~ 0.57 pg/mL). Additionally, the aptamer showed small binding to its counter targets and acceptable recovery of melatonin when spiked in four times diluted saliva in assay buffer. Overall, the assay portrayed the potential of aptamers to detect low melatonin levels in saliva that could be beneficial in accurately determining DLMO, particularly in individuals with very low melatonin levels, such as the elderly or those with neurodegenerative conditions. Determining precise measurement of DLMO will facilitate the accurate diagnosis of circadian rhythm disruption, enabling healthcare providers to optimize the timing and selection of therapeutic and behavioural interventions tailored to an individual’s unique circadian rhythm.

Oral squamous cell carcinoma (OSCC), which encompasses the oral cavity-derived malignancies, is a devastating disease causing substantial morbidity and mortality in both men and women. It is the most common subtype of the head and neck squamous cell carcinoma (HNSCC), which is ranked the sixth most common malignancy worldwide. Despite promising advancements in the conventional therapeutic approaches currently available for patients with oral cancer, many drawbacks are still to be addressed; surgical resection leads to permanent disfigurement, altered sense of self and debilitating physiological consequences, while chemo- and radio-therapies result in significant toxicities, all affecting patient wellbeing and quality of life. Thus, the development of novel therapeutic approaches or modifications of current strategies is paramount to improve individual health outcomes and survival, while early tumour detection remains a priority and significant challenge. In recent years, drug delivery systems and chronotherapy have been developed as alternative methods aiming to enhance the benefits of the current anticancer therapies, while minimizing their undesirable toxic effects on the healthy non-cancerous cells. Targeted drug delivery systems have the potential to increase drug bioavailability and bio-distribution at the site of the primary tumour. This review confers current knowledge on the diverse drug delivery methods, potential carriers (e.g., polymeric, inorganic, and combinational nanoparticles; nanolipids; hydrogels; exosomes) and anticancer targeted approaches for oral squamous cell carcinoma treatment, with an emphasis on their clinical relevance in the era of precision medicine, circadian chronobiology and patient-centred health care.

Injectable hydrogels, as carriers, offer great potential to incorporate cells or growth factors for dental tissue regeneration. Notably, the development of injectable hydrogels with appropriate structures and properties has been a challenging task, leaving much to be desired in terms of cytocompatibility, antibacterial and self-healing properties, as well as the ability to support dental stem cell functions. This paper presents our study on the development of a novel self-cross-linkable hydrogel composed of oxidized alginate and carboxymethyl chitosan and its characterization as a cell carrier for dental enamel regeneration in vitro. Oxidized alginate was synthesized with 60% theoretical oxidation degree using periodate oxidation and characterized by Fourier Transform Infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and Ultraviolet-visible absorption spectroscopy. Then, hydrogels were prepared at three varying weight ratios of oxidized alginate to carboxymethyl chitosan (4:1, 3:1, and 2:1) through Schiff base reactions, which was confirmed by Fourier Transform Infrared spectroscopy. The hydrogels were characterized in terms of gelation time, swelling ratio, structure, injectability, self-healing, antibacterial properties, and in vitro characterization for enamel regeneration. The results demonstrated that, among the three hydrogels examined, the one with the highest ratio of oxidized alginate (i.e., 4:1) had the fastest gelation time and the lowest swelling ability, and that all hydrogels were formed with highly porous structures and were able to be injected through a 20-gauge needle without clogging. The injected hydrogels could be rapidly reformed with the self-healing property. The hydrogels also showed antibacterial properties against two cariogenic bacteria: Streptococcus mutans and Streptococcus sobrinus. For in vitro enamel regeneration, a dental epithelial cell line, HAT-7, was examined, demonstrating a high cell viability in the hydrogels during injection. Furthermore, HAT-7 cells encapsulated in the hydrogels showed alkaline phosphatase production and mineral deposition, as well as maintaining their round morphology, after 14 days of in vitro culture. Taken together, this study has provided evidence that the oxidized alginate-carboxymethyl chitosan hydrogels could be used as an injectable cell carrier for dental enamel tissue engineering applications.

Dental caries is considered a major health burden, and preventive strategies are needed to improve oral health. It is suggested that natural essential oils possess anti-plaque formation properties and exhibit strong antimicrobial activity; however, in vivo studies to support these concepts are scarce. We evaluated the effects of tea tree oil (TTO) on caries initiation and progression in vivo to generate supportive data for clinical studies in patients at high risk of caries. We first assessed TTO in vitro against Streptococcus mutans and Streptococcus sobrinus , two of the most common oral bacteria associated with dental caries development, using bacterial growth assays, biofilm formation, and adhesion assays. TTO efficacy on caries initiation and caries lesion progression was then evaluated in vivo, where complex biofilms are formed on dental enamel. Our results showed that TTO demonstrates strong antimicrobial efficacy by inhibiting bacterial growth and biofilm formation while preventing bacterial adhesion on human teeth. In vivo, TTO application reduced the number and depth of carious lesions. Specifically, the number of caries lesions was lower in the TTO-treated group compared to the control group (13 vs. 19 lesions), and the lesion area was significantly smaller in the TTO-treated group compared to the untreated group ( p  = 0.003). TTO did not affect the extent of reparative dentin formation. The clinical relevance is primarily for individuals who have difficulties brushing their teeth or those at high risk of developing dental caries, serving as an adjunct to preventive dentistry.

IntroductionDecades of evidence have demonstrated a lack of workforce diversity and sustaining disparities in academic dentistry and professional practice. Underrepresented minority students may face challenges and implicit bias during the dental schools‘ admission/selection process. This review collected papers from different countries to summarize the Equity-Diversity-Inclusion (EDI)-related strategies that dental schools worldwide have used in their admissions process to increase diversity.MethodsA comprehensive search using MEDLINE (via PubMed), ERIC, Cochrane Reviews, Cochrane Trials, American Psychological Association Psyc Info (EBSCO) and Scopus was done between January and March-2023. All types of articles-designs were included, except comments and editorials, and all articles selected were in English. Two independent investigators screened the articles. Extracted data were general characteristics, study objectives, and EDI-related strategies.ResultsSixteen publications were used to construct this manuscript. The year with the greatest number of publications was 2022. Type of studies were case studies/critical reviews (50%), cross-sectional (including survey and secondary data analysis) (n = 5, 31.25%), qualitative methods of analysis (n = 2, 12.5%), and retrospective/secondary data collection (n = 1, 6.25%). The strategies described in the articles were related to (1) considering the intersectionality of diversity, (2) using noncognitive indicators during the school admissions process to construct a holistic selection process, (3) diversifying, professionalizing, and providing training to admissions persons who had leadership roles with the support from the dental school and the university, and (4) allocating financial investments and analyzing current policies and procedures regarding EDI.ConclusionsThis review aggregated interesting findings, such as: some schools are considering the intersectionality of diversity as a way to include underrepresented minorities and to diversify the students-body. The recent growth in publications on EDI during dental admission/selection process might indicate a positive movement in this field.

Streptococcus mutans and Streptococcus sobrinus are the main causative agents of human dental caries. Current strategies for treating caries are costly and do not completely eradicate them completely. Passive immunization using nonhuman antibodies against Streptococcal surface antigens has shown success in human trials, however they often invoke immune reactions. We used phage display to generate human antigen-binding fragments (Fabs) against S . mutans and S . sobrinus . These Fabs were readily expressed in E . coli and bound to the surface S . mutans and S . sobrinus . Fabs inhibited sucrose-induced S . mutans and S . sobrinus biofilm formation in vitro and a combination of S . mutans and S . sobrinus Fabs prevented dental caries formation in a rat caries model. These results demonstrated that S . mutans and S . sobrinus Fabs could be used in passive immunization strategies to prevent dental caries. In the future, this strategy may be applied towards a caries therapy, whereby Fabs are topically applied to the tooth surface.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Since December 2019, the global burden of the COVID-19 pandemic has increased rapidly and has impacted nearly every country in the world, affecting those who are elderly or with underlying comorbidities or immunocompromised states. Aim of this systematic review is to summarize lung histopathological characteristics of COVID-19, not only for diagnostic purpose but also to evaluate changes that can reflect pathophysiological pathways that can inform clinicians of useful treatment strategies. We identified following histopathological changes among our patients:: hyaline membranes; endothelial cells/ interstitial cells involvement; alveolar cells, type I pneumocytes/ type II pneumocytes involvement; interstitial and/ or alveolar edema; evidence of hemorrhage, of inflammatory cells, evidence of microthrombi; evidence of fibrin deposition and of viral infection in the tissue samples. The scenario with proliferative cell desquamation is typical of Acute Respiratory Distress Syndrome (ARDS) that can be classified as diffuse alveolar damage (DAD) and not DAD-ARDS. The proposed pathological mechanism concerns the role of both innate and adaptive components of the immune system. COVID-19 lethal cases present themselves as a heterogeneous disease, characterized by the different simultaneous presence of different histological findings, which reflect histological phases with corresponding different pathological pathways (epithelial, vascular and fibrotic changes), in the same patient.

Heparan sulfate proteoglycans (HSPGs) surround the surface of odontoblasts, and their modification affects their affinity for Wnt ligands. This study proposes applying Matching Transformation System ® (MA-T), a novel chlorinated oxidant, to enhance dentinogenesis. MA-T treatment in odontoblasts decreased sulfation of HSPG and upregulated the expression of dentin sialophosphoprotein ( Dspp ) and Dentin Matrix Protein 1 ( Dmp1 ) via activation of canonical Wnt signaling in vitro . Ex vivo application of MA-T also enhanced dentin matrix formation in developing tooth explants. Reanalysis of a public single-cell RNA-seq dataset revealed significant Wnt activity in the odontoblast population, with enrichment for Wnt10a and Wnt6 . Silencing assays showed that Wnt10a and Wnt6 were redundant in inducing Dspp and Dmp1 mRNA expression. These Wnt ligands’ expression was upregulated by MA-T treatment, and TCF/LEF binding sites are present in their promoters. Furthermore, the Wnt inhibitors Notum and Dkk1 were enriched in odontoblasts, and their expression was also upregulated by MA-T treatment, together suggesting autonomous maintenance of Wnt signaling in odontoblasts. This study provides evidence that MA-T activates dentinogenesis by modifying HSPG and through subsequent activation of Wnt signaling.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a member of the coronavirus family that causes the novel coronavirus disease first diagnosed in 2019 (COVID‐19). Although many studies have been carried out in recent months to determine why the disease clinical presentations and outcomes can vary significantly from asymptomatic to severe or lethal, the underlying mechanisms are not fully understood. It is likely that unique individual characteristics can strongly influence the broad disease variability; thus, tailored diagnostic and therapeutic approaches are needed to improve clinical outcomes. The circadian clock is a critical regulatory mechanism orchestrating major physiological and pathological processes. It is generally accepted that more than half of the cell‐specific genes in any given organ are under circadian control. Although it is known that a specific role of the circadian clock is to coordinate the immune system's steady‐state function and response to infectious threats, the links between the circadian clock and SARS‐CoV‐2 infection are only now emerging. How inter‐individual variability of the circadian profile and its dysregulation may play a role in the differences noted in the COVID‐19‐related disease presentations, and outcome remains largely underinvestigated. This review summarizes the current evidence on the potential links between circadian clock dysregulation and SARS‐CoV‐2 infection susceptibility, disease presentation and progression, and clinical outcomes. Further research in this area may contribute towards novel circadian‐centred prognostic, diagnostic and therapeutic approaches for COVID‐19 in the era of precision health. SARS‐CoV‐2 entry happens through the oral and nasal cavities. Oral and/or nasal preexisting dysbiosis may affect COVID‐19 susceptibility, severity and outcomes. Bidirectional interactions between gut microbiota and the oral/nasal/lung microbiota may be involved in regulating the immune responses to SARS‐CoV‐2, which may involve the circadian clock