Synthesis and analyses of injectable fluoridated-bioactive glass hydrogel for dental root canal sealing.

This study aimed to synthesize fluoride-doped bioactive glass (F-BG) based thermo-sensitive injectable hydrogel for endodontic applications. The structural and phase analyses were done with Fourier Transform Infrared spectroscopy and X-ray Diffraction, respectively. The setting time of prepared injectable was investigated at 21°C (in the presence and absence of an ultrasonic scalar) and at 37°C. Flowability was tested according to ISO-6876:2012 specifications, whereas injectability was checked by extrusion method using 21-, 22-, and 23-gauge needles. The in vitro bio-adhesion and push-out bond strength were studied on days 7 and 90 and compared with the commercially available TotalFill®. The ion release profile was analyzed for up to 30 days with Inductively Coupled Plasma Optical Emission Spectroscopy. The fluoride release analysis was conducted periodically for up to 21 days in deionized water and artificial saliva using an ion-selective electrode. The final setting time at 21°C, 21°C+ultrasonic scalar, and 37°C were 38.66±3.21, 29.12±1.23, and 32±3.46 min, respectively. The flowability was 25±3.94 mm, and the injectability coefficient was ≥70.3 for 22, 21, and 57% in a 23-gauge needle. Fluoride release in deionized water was found to be significantly higher than in artificial saliva and increased with time. A significant difference in bond strength was found between days 7 and 90, where the strength was increased, and a new apatite layer was formed on the tooth surface. A rapid release of calcium, phosphate, and silicon ions was seen initially, whereby the continuous release of these ions was observed for up to 30 days. The prepared F-BG injectable hydrogel has shown promising results and has the potential to be used as an endodontic sealer.

Irisin: A Myokine With Therapeutic And Diagnostic Potential In Clinical Dentistry.

Irisin is a novel adipomyokine which has extensive systemic and local effects in different tissues of the body. The scientific interest in understanding the physiological roles of irisin in the body has increased tremendously in the past few years due to its vast therapeutic potential in different fields of medicine. The current narrative review was planned to describe the molecular mechanisms by which irisin regulates oral hard and soft tissues. The information gleaned provided useful insights for future researchers to investigate newly discovered roles of irisin in craniofacial health and disease, and to explore the potential of irisin as a promising therapeutic and diagnostic agent in clinical dentistry.

Tideglusib-incorporated nanofibrous scaffolds potently induce odontogenic differentiation.

Pulp-Dentin regeneration is a key aspect of maintain tooth vitality and enabling good oral-systemic health. This study aimed to investigate a nanofibrous scaffold loaded with a small molecule i.e. Tideglusib to promote odontogenic differentiation. Tideglusib (GSK-3ß inhibitor) interaction with GSK-3ß was determined using molecular docking and stabilization of ß-catenin was examined by confocal microscopy. 3D nanofibrous scaffolds were fabricated through electrospinning and their physicochemical characterizations were performed. Scaffolds were seeded with mesenchymal stem cells or pre-odontoblast cells to determine the cells proliferation and odontogenic differentiation. Our results showed that Tideglusib (TG) binds with GSK-3ß at Cys199 residue. Stabilization and nuclear translocation of ß-catenin was increased in the odontoblast cells treated with TG. SEM analysis revealed that nanofibers exhibited controlled architectural features that effectively mimicked the natural ECM. UV-Vis spectroscopy demonstrated that TG was incorporated successfully and released in a controlled manner. Both kinds of biomimetic nanofibrous matrices (PCLF-TG100, PCLF-TG1000) significantly stimulated cells proliferation. Furthermore, these scaffolds significantly induced dentinogenic markers (ALP, and DSPP) expression and biomineralization. In contrast to current pulp capping material driving dentin repair, the sophisticated, polymeric scaffold systems with soluble and insoluble spatiotemporal cues described here can direct stem cell differentiation and dentin regeneration. Hence, bioactive small molecule-incorporated nanofibrous scaffold suggests an innovative clinical tool for dentin tissue engineering.

Adipokines: Diagnostic and prognostic markers for oral diseases.

Adipose tissue or fat tissue is a loose connective tissue that consists mainly of adipocytes. Adipocytes are classified on the basis of their secretory origin, differentiation, distribution, cell characteristics, such as amount of mitochondria, size and type of lipid droplets, and expression of uncoupled protein-1. Adipocytes secrete adipokines that are divided as white adipokines, brown adipokines and beige adipokines. Adipokines have been used as diagnostic and prognostic markers for different oral diseases. Irisin, chemerin, resistin, adiponectin, zinc alpha 2 macroglobulin, leptin, visfatin, tumour necrosis factor-alpha and interleukin-6 are some important adipokines associated with oral diseases, such as dental caries, periodontal diseases, recurrent aphthous stomatitis, oral cancers, oral premalignant lesions, Sjogren's syndrome, Kawasaki disease and Behcet's disease. The current narrative review was planned to focus on the pathophysiological role of adipokines in oral diseases and their role as biomarkers for early diagnosis and prompt treatment.

Salivary aquaporin-3 as a screening biomarker for xerostomia in patients with periodontal disease and the effects of xerostomia on oral health-related quality of life.

Xerostomia is a subjective condition of dryness of the oral cavity that may lead to several oral problems deteriorating oral health-related quality of life. This study aimed to (1) determine the prevalence of xerostomia, (2) compare the general health status, unstimulated salivary flow rate, and oral health-related quality of life in xerostomics and non-xerostomics, and (3) investigate the potential of salivary aquaporin-3 (AQP-3) as a screening biomarker for xerostomia in patients with periodontal disease. Demographics and systemic health data were collected from 109 healthy participants, 20 to 55 years old, with Community Periodontal Index (CPI) score ≥ 3. For subjective assessment of xerostomia, Shortened Xerostomia Inventory (SXI) was used. For objective assessment of xerostomia, unstimulated salivary flow rate was measured. Shortened Oral Health Impact Profile (S-OHIP) was utilized for oral health-related quality of life assessment. The collected saliva samples were processed and stored at -80°C. Quantification of salivary AQP-3 protein was done with enzyme-linked immunosorbent assay. Xerostomia was reported in 78% of the subjects based on SXI score. Median concentration of AQP-3 was significantly higher in xerostomics compared to non-xerostomics, p = 0.001. Moreover, oral health-related quality of life was significantly poor in xerostomics compared to non-xerostomics, p = 0.002. Furthermore, there were significant correlations between AQP-3 and SXI (r = 0.21, p = 0.025), AQP-3 and S-OHIP (r = 0.2, p = 0.042), S-OHIP and SXI (r = 0.37, p < 0.001), unstimulated salivary flow rate and random blood glucose level (r = 0.32, p = 0.001), and body mass index and mean arterial pressure (r = 0.44, p < 0.001). Regression analysis showed that body mass index, CPI score 3, and salivary AQP-3 were suitable predictors for presence of xerostomia. AQP-3 could be a potential screening biomarker for xerostomia in patients with periodontal disease for its early identification may help improve oral health-related quality of life of the individuals.

Association of Candida Species with Novel SARS-CoV-2 and Biomarkers for Fungal Premalignant Oral Lesions.

Oral fungal infections can be caused by certain species of fungi among which candida albicans is the most implicated. Oral candidiasis is correlated with multiple conditions, such as coronavirus disease-2019, oral leukoplakia and oral erythroplakia. Tenascin is a glycoprotein and is present at the site of tissue injury and chronic inflammation, and tends to be over-expressed in cases of malignancy. Matrix metalloproteinase-9 belongs to a family of zinc-dependent endopeptidases and is involved in the degradation of extracellular matrix, leading to tissue invasion and metastasis. The current narrative review was planned to shed light on the fungal co-infections of coronavirus disease-2019 and molecular mechanisms of matrix metalloproteinase-9 and tenascin involved in the pathogenesis of fungus-associated oral leukoplakia and oral erythroplakia.

Salivary Irisin and periodontal clinical parameters in patients of chronic periodontitis and healthy individuals: A novel salivary myokine for periodontal disease.

OBJECTIVE: To evaluate changes in the levels of salivary irisin in chronic periodontitis, and to correlate the two. METHODS: The analytical cross-sectional study was conducted at Fatima Memorial Hospital & College of Dentistry, Lahore, Pakistan, from September 2017 to March 2018, and comprised patients of either gender visiting the periodontic out-patient department. The subjects were divided into group I, which had periodontally healthy controls, and group II, which had an equal number of chronic periodontitis patients. Chronic periodontitis was assessed on basis of pocket probing depth, clinical attachment level, plaque percentage and bleeding on probing. Also, 4ml of un-stimulated saliva was collected for the quantification of irisin protein using enzyme-linked immunosorbent assay. Data was analysed using SPSS 25. RESULTS: Of the 40 subjects, there were 20 (50%) in group I with 10 (50%) males and 10 (50%) females having an overall mean age of 37.60±2.58 years. The remaining 20 (50%) subjects were in group II with 16 (80%) males and 4 (20%) females having an overall mean age of 43.25±6.10 years. Mean salivary irisin level in group II was 6.80±3.97ng/ml compared to 3.99±2.48 ng/ml in group I (p=0.009). Periodontal clinical parameters in both the groups were positively but non-significantly correlated with salivary irisin levels (p>0.05) except for decreased plaque percentage in group I (p<0.05). CONCLUSION: Salivary irisin levels increased in chronic periodontitis and decreased with decreasing plaque percentage in healthy individuals, indicating that this myokine can act as a biomarker for chronic periodontal disease.

Aquaporins; systemic, functional and therapeutic correlations in health and disease.

Aquaporins are transcellular proteins that majorly consist of a tetrametric hour-glass-like structure. Aquaporins have a definitive function in transpositioning of water and solutes across cell membranes. The current review was planned to provide information regarding structure, expression and functions of aquaporins in the human body, and to generate a comprehensive summary of physiological and pathophysiological correlations related to aquaporins and their therapeutic implications. Absence or mutations of different aquaporins are believed to be linked to clinical diseases, including Sjogren's syndrome, nephrogenic diabetes insipidus, liver dysfunction and obesity. Modern therapeutic techniques are utilising aquaporins in gene therapy for Sjogren's syndrome and cholestasis. The narrative review aims at providing a comprehensive description of localisation, function, abnormal clinical conditions and therapeutic implications of aquaporin proteins.

Salivary and imaging-based biomarkers of radiation therapy-induced xerostomia.

Biomarkers are anatomical characteristics or naturally occurring measurable molecules indicating physiological or pathological state of an individual. These biomarkers have the potential to detect or predict diseases at an early stage, which is particularly beneficial in timely management of common complications of radiation therapy done in head and neck cancer treatment regime. Xerostomia is one of the most common oral complaints of radiation therapy. Saliva has an abundance of protein biomarkers; however, those related to post-radiation therapy xerostomia need to be explored further. Textural and imaging-based biomarkers are helpful in predicting xerostomia in such patients. This narrative review provides an account of salivary protein and imaging-based biomarkers of radiation therapy-induced xerostomia in head and neck cancer patients.

Molecular events in the clinicopathological diagnosis of alveolar osteitis.

Alveolar osteitis (AO) is an extremely distressing outcome following extraction of a tooth. Its pathophysiology is poorly understood due to varied nature of presentation of the condition. However, a delay in the healing process of bone due to fibrinolysis is believed to be the underlying pathophysiology. This review highlights three major risk factors - trauma, bacterial accumulation due to poor oral hygiene, and smoking - in causing alveolar osteitis, and describes underlying related molecular events. Fibrinolysis results due to traumatic tooth extraction as well as due to accumulation of certain microorganisms which leads to the development of alveolar osteitis. Tumour necrosis factor-alpha (TNF-a), Runt-related transcription factor 2 (Runx 2) and osteocalcin (OCN) can be used as molecular markers for evaluating alveolar osteitis. Assessment assays of such biomarkers can lead to a better understanding of the pathological process in providing a clearer picture to researchers and clinicians.

Desmosomal protein regulation and clinical implications in oral mucosal tissues.

Cell-adhesion complex within a tissue is important for its stability, structural integrity, functioning, cellular migration and morphogenesis. Disruption of desmosomal cell-adhesions complex results in epithelial conditions such as epidermolysis bullosa and bullous pemphigoid. Desmosome assembly and disassembly is regulated post-translationally by calcium, kinase/phosphatase activity, proteolytic processing, and also through adhesive junctions. Altered functions of desmosomal proteins desmocollin and desmoglein can cause blistering disorders, such as pemphigus foliaceus and pemphigus vulgaris, and non-Hodgkin Lymphoma while defective desmoplakin can cause supra-basal clefting in epithelium and conditions such as Carvajal syndrome, palmo-plantar keratoderma etc. This review summarises major functions of demosomal complex family and how mis-regulation of demosomal structural proteins occur in pathogenesis of non-, pre- and malignant oral lesions with disrupted epithelium.

Smart injectable self-setting bioceramics for dental applications.

A thermo-responsive injectable bioactive glass (BAG) that has the ability to set at body temperature was prepared using pluronic F127 and hydroxypropyl methylcellulose as the carrier. The injectable composite has the advantage to fill irregular shape implantation sites and quick setting at body temperature. The structural and morphological analysis of injectable BAG before and after setting was done by using Fourier Transform Infrared spectroscopy (FTIR), and Scanning Electron Microscope (SEM). The effect of an ultrasonic scaler for a quick setting of injectable BAG was also investigated. The ultrasonic scaler sets the BAG formulation three-folds faster than at body temperature and homogenized the dispersion. The in vitro bio-adhesion was studied in the bovine tooth in both artificial saliva and deionized water for periodic time intervals, i.e., day 7, 30, 90, and 180, which confirmed the apatite layer formation. The mineral density analysis was used to differentiate the newly formed apatite with tooth apatite. In the MTT assay, the experimental material showed continuous proliferation and cell growth. This indicated that injectable hydrogel promoted cell growth, facilitated proliferation, and had no cytotoxic effect. The SEM and micro-CT results (performed after in vitro bioactivity testing) showed that the injectable BAG had the ability to regenerate dentin, hence this material has the potential to be used for dental and biomedical applications including tooth and bone regeneration in minimally invasive procedures in future.

Marital Status as a Stress Indicator in Postgraduate Dental Students.

The objective of this study was to explore perceived causes of stress and to analyse the influence of marital status and gender as indicators of these causes. Modified Graduate Dental Stress Environment Questionnaire was used on postgraduate students of basic dental sciences at a public sector university in Pakistan. Mean±SD was calculated for all stress-related items and statistical analysis was done through Mann Whitney-U test and multiple linear regression analysis. Out of 53 stress-related items, 15 (28.3%) factors were perceived as mildly stressful, 33 (62.26%) as moderately stressful and 9.4% as highly stressful. A significant relationship was found between 6 stress-related items and marital status. In the questionnaire majority of these items came under the domain of selfefficacy. Single students were more stressed in four areas relating to future career, academic responsibilities and confidence in their decision-making ability, while married students experienced higher stress when competing for research experience in their learning programmes.

WNT signalling pathway in oral lesions.

Wingless-Integrated/Beta-catenin (WNT/-catenin) signalling pathway is one of the principal intercellular signalling pathways in humans. It plays an intrinsic role in the cellular proliferation, differentiation and regeneration along with many other cellular functions. Epigenetic deoxyribonucleic acid methylations and silencing of WNT signalling pathway genes have a significant role in malignant transformation of oral lesions such as oral submucous fibrosis, oral leukoplakia, oral lichen planus and erythroplakia. The increase in WNT inhibitory proteins along with inflammatory factors cause bone loss in periapical lesions, such as chronic apical periodontitis. This review discusses the molecular genetics of potentially malignant oral lesions, sheds light on our understanding of WNT/-catenin signalling in bone loss pertaining to periapical lesions, and alteration of this pathway for therapeutic benefits.

Developing a synthetic composite membrane for cleft palate repair.

An oronasal fistula is a passage between the oral and nasal cavity. Currently, surgical procedures use mucosal flaps or collagen grafts to make a barrier between oral and nasal cavities. Our aim was to develop a cell-free synthetic repair material for closure of nasal fistulas. We surface functionalized electrospun polyurethane (PU) and poly-L-lactic acid (PLLA) and composite polymer (PU-PLLA) membranes with acrylic acid through plasma polymerization. Membranes were treated in a layer-by-layer approach to develop highly charged electrostatic layer that could bind heparin as a pro-angiogenic glycosaminoglycan. The properties were evaluated through physical, chemical, and mechanical characterization techniques. Cytotoxicity was tested with MC3T3 pre-osteoblast cell lines for 3, 7, and 14 days, and vasculogenesis was assessed by implantation into the chorio-allantoic membrane in chick embryos for 7 days. In vivo biocompatibility was assessed by subcutaneous implantation in rats for 1, 3, and 6 weeks. The membranes consisted of random fibers of PLLA-PU with fiber diameters of 0.47 and 0.12 µm, respectively. Significantly higher cell proliferation and migration of MC3T3 cells at 3, 7, and 14 days were shown on plasma-coated membranes compared with uncoated membranes. Further, it was found that plasma-coated membranes were more angiogenic than controls. In vivo implantation of membranes in rats did not reveal any gross toxicity to the materials, and wound healing was comparable with the native tissue repair (sham group). We therefore present a plasma-functionalized electrospun composite polymer membrane for use in the treatment of fistulas. These membranes are flexible, non-cytotoxic, and angiogenic, and we hope it should lead to permanent closure of oronasal fistula.

Myokines: Discovery Challenges and Therapeutic Impediments.

Physical activity has been linked with maintenance of bodily health and prevention of numerous pathologies which might arise in its absence. Physical surge renders the skeletal muscles of the body to come into action which then, besides per forming the basic functions of locomotion and maintenance of body posture, produce various proteinaceous secretions. These secretions contain skeletal muscle-released biochemical products known as myokines. More than 650 myokines have been identified and this list is increasing so rapidly that this branch of proteomics can now be designated as a 'myokinome'. This review was planned to describe the major challenges faced in myokine discovery, barriers in use of myokines as a treatment modality and the techniques utilised to overcome these scientific hurdles. Establishment of correlation of myokines with the state of health and disease can help improve clinical diagnostics and will ultimately improve the quality of life of patients.

Fabrication, in vitro and in vivo studies of bilayer composite membrane for periodontal guided tissue regeneration.

Development of a guided occlusive biodegradable membrane with controlled morphology in order to restrict the ingrowth of epithelial cells is still a challenge in dental tissue engineering. A bilayer membrane with a non-porous upper layer (polyurethane) and porous lower layer (polycaprolactone and bioactive glass composite) with thermoelastic properties to sustain surgery treatment was developed by lyophilization. Morphology, porosity, and layers attachment were controlled by using the multi-solvent system. In vitro and in vivo biocompatibility, cell attachment, and cell proliferation were analyzed by immunohistochemistry and histology. The cell proliferation rate and cell attachment results showed good biocompatibility of both surfaces, though cell metabolic activity was better on the polycaprolactone-bioactive glass surface. Furthermore, the cells were viable, adhered, and proliferated well on the lower porous bioactive surface, while non-porous polyurethane surface demonstrated low cell attachment, which was deliberately designed and a pre-requisite for guided tissue regeneration/guided bone regeneration membranes. In addition, in vivo studies performed in a rat model for six weeks revealed good compatibility of membranes. Histological analysis (staining with hematoxylin and eosin) indicated no signs of inflammation or accumulation of host immune cells. These results suggested that the fabricated biocompatible bilayer membrane has the potential for use in periodontal tissue regeneration.

Angina bullous haemorrhagica: Case report and review of literature.

Angina Bullosa Haemorrhagica (ABH) is a benign lesion of the oral cavity categorized by sudden onset of single or multiple blood filled lesions that burst leaving an ulcer that usually heals in 7-10 days without leaving a scar. We report a case of ABH diagnosed on the basis of history, clinical examination and blood, renal and liver function tests. The case findings and its management is discussed. Literature of the cases presented in the last 5 years was searched from Google Scholar and Pubmed. The review was summarized in a tabulated form.

The buccohypophyseal canal is an ancestral vertebrate trait maintained by modulation in sonic hedgehog signaling.

BACKGROUND: The pituitary gland is formed by the juxtaposition of two tissues: neuroectoderm arising from the basal diencephalon, and oral epithelium, which invaginates towards the central nervous system from the roof of the mouth. The oral invagination that reaches the brain from the mouth is referred to as Rathke's pouch, with the tip forming the adenohypophysis and the stalk disappearing after the earliest stages of development. In tetrapods, formation of the cranial base establishes a definitive barrier between the pituitary and oral cavity; however, numerous extinct and extant vertebrate species retain an open buccohypophyseal canal in adulthood, a vestige of the stalk of Rathke's pouch. Little is currently known about the formation and function of this structure. Here we have investigated molecular mechanisms driving the formation of the buccohypophyseal canal and their evolutionary significance. RESULTS: We show that Rathke's pouch is located at a boundary region delineated by endoderm, neural crest-derived oral mesenchyme and the anterior limit of the notochord, using CD1, R26R-Sox17-Cre and R26R-Wnt1-Cre mouse lines. As revealed by synchrotron X-ray microtomography after iodine staining in mouse embryos, the pouch has a lobulated three-dimensional structure that embraces the descending diencephalon during pituitary formation. Polaris(fl/fl); Wnt1-Cre, Ofd1(-/-) and Kif3a(-/-) primary cilia mouse mutants have abnormal sonic hedgehog (Shh) signaling and all present with malformations of the anterior pituitary gland and midline structures of the anterior cranial base. Changes in the expressions of Shh downstream genes are confirmed in Gas1(-/-) mice. From an evolutionary perspective, persistence of the buccohypophyseal canal is a basal character for all vertebrates and its maintenance in several groups is related to a specific morphology of the midline that can be related to modulation in Shh signaling. CONCLUSION: These results provide insight into a poorly understood ancestral vertebrate structure. It appears that the opening of the buccohypophyseal canal depends upon Shh signaling and that modulation in this pathway most probably accounts for its persistence in phylogeny.

Multiple postnatal craniofacial anomalies are characterized by conditional loss of polycystic kidney disease 2 (Pkd2).

Polycystin 2 (Pkd2), which belongs to the transient receptor potential family, plays a critical role in development. Pkd2 is mainly localized in the primary cilia, which also function as mechanoreceptors in many cells that influence multiple biological processes including Ca(2+) influx, chemical activity and signalling pathways. Mutations in many cilia proteins result in craniofacial abnormalities. Orofacial tissues constantly receive mechanical forces and are known to develop and grow through intricate signalling pathways. Here we investigate the role of Pkd2, whose role remains unclear in craniofacial development and growth. In order to determine the role of Pkd2 in craniofacial development, we located expression in craniofacial tissues and analysed mice with conditional deletion of Pkd2 in neural crest-derived cells, using Wnt1Cre mice. Pkd2 mutants showed many signs of mechanical trauma such as fractured molar roots, distorted incisors, alveolar bone loss and compressed temporomandibular joints, in addition to abnormal skull shapes. Significantly, mutants showed no indication of any of these phenotypes at embryonic stages when heads perceive no significant mechanical stress in utero. The results suggest that Pkd2 is likely to play a critical role in craniofacial growth as a mechanoreceptor. Pkd2 is also identified as one of the genes responsible for autosomal dominant polycystic kidney disease (ADPKD). Since facial anomalies have never been identified in ADPKD patients, we carried out three-dimensional photography of patient faces and analysed these using dense surface modelling. This analysis revealed specific characteristics of ADPKD patient faces, some of which correlated with those of the mutant mice.