Correlating Salivary Levels of Immunoglobin E and Human Eosinophil Cationic Protein in the Aseer Cohort with Recurrent Apthous Stomatitis.

Background: Repeated Aphthous Stomatitis (RAS) is the most prevalent inflammatory disorder of the oral mucosa, characterized by recurrent emergence of single or numerous painful ulcers. RAS usually affects healthy people without systemic illnesses. There is evidence linking atopy to the progression of this illness. Immunoglobulin E (IgE) and human eosinophil cationic protein (HECP) levels in the saliva of individuals with aphthous stomatitis were assessed as allergy-related indicators. Materials and Methods: Sixty people were assessed for this study. 30 patients with RAS were included in the patient group, while 30 healthy individuals made up for the control group. Sixty participants' non-stimulated saliva was taken and IgE and HECP were evaluated using enzyme-linked immunosorbent assay (ELISA). Data were analyzed in SPSS 20 through the Mann-Whitney test and p<0.05 was considered significant. Results: The salivary level of HECP was significantly (p 0.05) higher among cases (0.83 0.70) compared to controls (0.170 0.15), whereas the salivary level of IgE was not significantly (p = 0.41) higher among cases (35.60 11.19) compared to controls (67.42 18.34). Conclusion: Even though this study found a positive correlation between elevated HECP levels and RAS, additional research with larger sample sizes is required to identify the biological mechanisms responsible for the observed associations and to include salivary HECP levels in the RAS patient's evaluation.

Identification of oral immune disorders- A review and a diagnostic algorithm.

Immunological disorders are observed in various clinical presentations in the oral cavity. The pathophysiology of these disorders include but are not limited to primary oral auto-immune disease, systemic disease with oral findings, malignancies, hypersensitivity reactions, drug-induced, and infection-related. Many of these disorders have overlapping oral features, making it difficult for the clinician to diagnose and treat the disorder. There is a need to provide a simple and practical decision-making algorithm to the clinicians and provide them guidance on laboratory investigations. The present review provides a diagnostic algorithm that might minimize outpatient process delays and lead to early management. This is crucial in many cases where oral findings may be the first sign of the disorder, and early treatment can preclude dissemination and complications of the disorder.

Oral immune-mediated disorders with malignant potential/association: An overview.

A group of oral disorders or conditions, which may result from, or could be triggered by an abnormality in the normal immune response of an individual are known as oral immune-mediated disorders. Some of these disorders have malignant potential, while others are associated with malignancy. In this overview, we will discuss a few of the oral diseases (such as oral lichen planus, primary Sjogren's syndrome, systemic lupus erythematosus, dermatitis herpetiformis, and linear immunoglobulin A bullous dermatosis, to name a few), which are caused due to irregularity in the immune system and are either associated with malignancy or capable of undergoing malignant transforming, thereby increasing the morbidity and mortality rate.

Advancement in therapeutic strategies for immune-mediated oral diseases.

BACKGROUND: Immune-mediated diseases are a diverse group of conditions characterized by alteration of cellular homeostasis and inflammation triggered by dysregulation of the normal immune response. Several immune-mediated diseases exhibit oral signs and symptoms. Traditionally, these conditions are treated with corticosteroids or immunosuppressive agents, including azathioprine, cyclophosphamide, and thalidomide. Recent research into the developmental pathways of these diseases has led to the exploration of novel approaches in treatment. This review examines newer treatment modalities for the management of immune-mediated diseases with oral presentations. Topical calcineurin inhibitors (TCIs) such as tacrolimus and pimecrolimus have been employed successfully in managing oral lichen planus and pemphigus vulgaris. Biologic agents, comprising monoclonal antibodies, fusion proteins, and recombinant cytokines, can provide targeted therapy with fewer adverse effects. Neutraceutical agents comprising aloe vera, curcumin, and honey are commonly used in traditional medicine and offer a holistic approach. They may have a place as adjuvants to current standard therapeutic protocols. Photodynamic therapy (PDT) and low-level laser therapy (LLLT) utilize a specific wavelength of light to achieve desired cellular change. While the use of PDT in immune-mediated diseases is contentious, LLLT has shown positive results. Newer therapeutic modalities involve kinase inhibitors, S1P1 receptor modulators, MSCs, and iRNA providing targeted treatment of specific diseases.

Modulation of oral cancer and periodontitis using chemotherapeutic agents - A narrative review.

Periodontitis, an inflammatory condition, is linked to a higher risk of developing oral cancer. Periodontitis may be a precipitating factor for tumorigenesis and the aggressiveness of specific cancer variants. Although genetics is considered the primary etiologic factor for the development of most cancers, many factors have come to be recognized in the initiation and progression of oral cancer. Consecutively, it is suggestive that periodontitis and oral cancer are distinct disease entities but share common pathogenic mechanisms. Oxidative stress and epigenetic mechanisms are among the most researched mechanisms responsible for initiating apoptotic mechanisms implicated in periodontitis and oral cancer. Current research aims to formulate therapeutic agents to intercede in these mechanisms via host modulation therapy and epigenetic therapy. These advances can revolutionize the treatment of periodontitis and oral cancer. This review aims to shed light on the common pathogenic mechanisms of these diseases and the various host modulation agents that could be beneficial in their treatment.

Artificial Intelligence in the Diagnosis of Oral Diseases: Applications and Pitfalls.

Background: Machine learning (ML) is a key component of artificial intelligence (AI). The terms machine learning, artificial intelligence, and deep learning are erroneously used interchangeably as they appear as monolithic nebulous entities. This technology offers immense possibilities and opportunities to advance diagnostics in the field of medicine and dentistry. This necessitates a deep understanding of AI and its essential components, such as machine learning (ML), artificial neural networks (ANN), and deep learning (DP). Aim: This review aims to enlighten clinicians regarding AI and its applications in the diagnosis of oral diseases, along with the prospects and challenges involved. Review results: AI has been used in the diagnosis of various oral diseases, such as dental caries, maxillary sinus diseases, periodontal diseases, salivary gland diseases, TMJ disorders, and oral cancer through clinical data and diagnostic images. Larger data sets would enable AI to predict the occurrence of precancerous conditions. They can aid in population-wide surveillance and decide on referrals to specialists. AI can efficiently detect microfeatures beyond the human eye and augment its predictive power in critical diagnosis. Conclusion: Although studies have recognized the benefit of AI, the use of artificial intelligence and machine learning has not been integrated into routine dentistry. AI is still in the research phase. The coming decade will see immense changes in diagnosis and healthcare built on the back of this research. Clinical significance: This paper reviews the various applications of AI in dentistry and illuminates the shortcomings faced while dealing with AI research and suggests ways to tackle them. Overcoming these pitfalls will aid in integrating AI seamlessly into dentistry.

Comparative assessment of the cell-surface antigens and gene expression profiles of the gingival tissue biomarkers in subjects with fixed functional and removable functional orthodontic appliances.

Background: This study aimed to examine the cellular components of the gingiva during orthodontic treatment with fixed and removable appliances. The cellular and molecular cues of pathologies of the gingival tissue associated with the use of different orthodontic appliances could be studied. Materials and methods: Tissue samples of gingiva were received from healthy patients undergoing gingivectomy for aesthetic purpose and from patients with fixed and removable functional orthodontic appliances undergoing gingivectomy for gingival overgrowth. The collected samples were stored in a sterile container with phosphate-buffered saline and to carry out further processes it was transported to the laboratory. Results: Cells positive for ECAD and NCAD were found to be increased in fixed appliances where as CD90 and CD105 positive cells showed no significant difference in all the three groups. CD24 and CD146 positive cells were increased significantly in removable and fixed than normal whereas CD133 positive cells were decreased in removable and fixed than normal. CD44 positive cells showed no noticeable change in all three groups. The gene expression levels of KRT5, SOX2, NANOG, and CXCL5 were found to be significantly increased in removable and fixed appliance groups. However, KRT8, CXCL10, and TIMP1 were increased only in fixed appliance group but CXCL10 showed decreased expression in removable appliance group. KRT6A, MYC, and MMP9 were decreased in fixed appliance group whereas MYC and MMP9 were increased in removable appliance group. KRT6A, KRT8, and TIMP1 showed no significant difference in removable appliance group. Conclusion: This study demonstrated essential roles of various genes, showing their contribution in regulating cell proliferation and migration in both the removable and fixed functional appliances.

Structural Changes in Primary Teeth of Diabetic Children: Composition and Ultrastructure Analysis.

Diabetes affects the developing enamel by altering the mineralization process, which can have a detrimental effect on oral health. The objectives of this study were to examine the ultrastructure and composition of surface enamel in primary teeth of diabetic children and its clinical implications. Hundred extracted primary teeth from diabetic children (Test group: n = 50) and healthy children (Control group: n = 50), between 6 and 12 years of age, were subjected to scanning electron microscopy to qualitatively examine the enamel surface. Energy dispersive X-ray (EDX) analysis was performed to investigate the mass percentage of calcium (Ca) and phosphorous (P) in the surface enamel. Ultrastructural aberrations of surface enamel were observed in the test group teeth. Additionally, prism perforations were seen at the junction of rod and inter-rod enamel and the prisms were loosely packed. An even aprismatic layer of surface enamel was evident in the control group teeth. There was a statistically significant difference (p < 0.05) of Ca and P mass percentage between the test and control group teeth. The mean mass percentage rates of Ca and P were 33.75% and 16.76%, respectively. A poor surface characteristic and elemental composition of the enamel surface of primary teeth is observed in diabetic children. Therefore, appropriate caries preventive measures are mandatory to maintain the structural integrity of the tooth in these patients.

Tinospora cordifolia (Thunb.) Miers (Giloy) inhibits oral cancer cells in a dose-dependent manner by inducing apoptosis and attenuating epithelial-mesenchymal transition.

BACKGROUND: Tinospora cordifolia (Thunb.) Miers (Giloy) has been applied successfully as an anti-inflammatory, anti-diabetic, and even as an anti-cancer agent. Yet, to date, the application of Giloy has not been explored concerning oral cancer. OBJECTIVES: To assess the effect of T cordifolia (Thunb.) Miers (Giloy) extract (TcE) on an oral cancer cell line. METHODS: AW13516 (oral cancer cell line) cells were treated with the prepared aqueous extract of TcE for 24 h at various concentrations ranging between 5 µg/ml and 100 µg/ml and compared with control (cells without treatment). Thee effect of the extracts on apoptosis was assessed by through Annexin V flow cytometry assay and Luminometry based assessment of Caspase 8, 9 and caspase 3/7 activity. RNA was isolated from treated cells and gene expression of selected metastatic genes (MMP1, MMP10, and CXCL8); epithelial-mesenchymal stem cell genes (TWIST1, SNAIL, ZEB1, Oct4) and stemness related genses (Nanog, Sox2) were analyzed by using a quantitative real-time PCR system. The experiments were performed in triplicates. RESULTS: Aqueous extract of TcE was found to induce apoptosis inducer in AW13516 cells in a concentration-dependent manner and was potent even at a low concentration of 5 µg/ml. The apoptosis induction was confirmed with the caspase activity assay. Treatment of the cells with the extract for 24 h exhibited a significant decrease in the expression of EMT genes in a dose-dependent manner without an effect on the metastatic genes. CONCLUSION: Aqueous extract of TcE induces apoptosis-mediated cell death in the oral cancer cell line AW13516 while attenuating its potential for epithelial mesenchymal transition.

COVID-19 and cardiovascular system-a comprehensive review.

Coronavirus disease 2019 (COVID-19), a mystified cryptic virus has challenged the mankind that has brought life to a standstill. Catastrophic loss of life, perplexed healthcare system and the downfall of global economy are some of the outcomes of this pandemic. Humans are raging a war with an unknown enemy. Infections, irrespective of age and gender, and more so in comorbidities are escalating at an alarming rate. Cardiovascular diseases, are the leading cause of death globally with an estimate of 31% of deaths worldwide out of which nearly 85% are due to heart attacks and stroke. Theoretically and practically, researchers have observed that persons with pre-existing cardiovascular conditions are comparatively more vulnerable to the COVID-19 infection. Moreover, they have studied the data between less severe and more severe cases, survivors and non survivors, intensive care unit (ICU) patients and non ICU patients, to analyse the relationship and the influence of COVID-19 on cardiovascular health of an individual, further the risk of susceptibility to submit to the virus. This review aims to provide a comprehensive particular on the possible effects, either direct or indirect, of COVID-19 on the cardiovascular heath of an individual.

Recombinant Human Adenovirus-p53 Therapy for the Treatment of Oral Leukoplakia and Oral Squamous Cell Carcinoma: A Systematic Review.

Background and Objectives: Oral cancer is the 6th most common cancer in the world and oral leukoplakia is an oral potentially malignant disorder that could develop into oral cancer. This systematic review focusses on randomized clinical trials for recombinant adenovirus p-53 (rAD-p53) therapy for the treatment of oral leukoplakia and cancer. Materials and Methods: We searched for research articles on various databases such as Pubmed/Medline, Embase, CNKI (China National Knowledge Infra-structure), Springerlink, cochrane and Web of sciences from 2003 to 2020. MeSH (Medical Subject Headings) terms were used for the search. Inclusion criteria included original research, randomized clinical trials and articles only in English language. Exclusion criteria were any articles that were not research articles, not randomized trials, non-human studies, etc. The articles were further graded on the Jadad scale. Results: 578 articles were assessed from various databases; only 3 articles were found to be appropriate for this review. Thus, meta-analysis was not performed because of heterogeneity and lack of data. In the three studies, whether rAD-p53 was used as a standalone therapy or with other therapies, there was a beneficial effect of the therapy. Furthermore, there were no serious adverse events and the only adverse events reported were fever, pain at the local injection site, flu-like symptoms and lowered WBC count. Conclusions: Thus, we can conclude that this therapy has a potential for beneficial therapeutic effects and further clinical trials with more patients need to be performed to get better understanding of the effect of rAD-p53 therapy, which probably will pave the way to its approval in other parts of the world.

Study of ABO Blood Group Susceptibility to Coronavirus Disease - COVID-19.

Background: The pandemic outbreak of COVID-19 highlighting the zoonotic cross-over link in the present century has provoked an emergency worldwide. Recent experimental evidence supporting the proposition of ABO blood grouping and its susceptibility in certain blood group individuals has created interest among researchers to explore more. Aim: The aim of this study is to find the susceptibility of "ABO" blood group in COVID-19-positive cases. Objectives: Association of ABO blood group patterns with COVID-19-positive cases. Materials and Methods: A cross-sectional, observational study design was conducted among 728 confirmed positive COVID-19 admitted to the tertiary health care center in Maharashtra from June 01, 2020 to August 31, 2020. The inclusion criteria were COVID-19-positive cases confirmed by positive real-time reverse transcriptase-polymerase chain reaction test of severe acute respiratory syndrome coronavirus 2. We collected the demographic details, associated clinical symptoms and ABO blood groups from all the patients. The data collected were subjected to statistical analysis. Results: The most common blood group affected was B + (35.5%) followed by A + (26.10%), AB + (20.60%) and O + (11.18%) and the least common was AB- (0.96%), O- (1.51%), A- (1.65%) and B- (1.79%). Conclusions: ABO blood grouping can be used as one of the simplest yet efficient markers for COVID-19. Blood group B Rh-positive and A Rh-positive were the most prevalent blood group types in patients with COVID-19.

Diminishing reactive adipogenesis leads to disease progression of oral submucous fibrosis.

Oral fibroblasts, similar to dermal fibroblasts, have the potential to resist the local insults like trauma to the oral mucosa by differentiating into adipocytes and secreting antimicrobial peptide cathelicidin (Camp) and this physiologic process in known as reactive adipogenesis. We hypothesize that in oral submucous fibrosis (OSF), due to constant secretion and up-streaming of transforming growth factor-beta (TGF- ß), oral fibroblast lose their adipogenic differentiation potential and Camp production, which leads to progressive fibrosis in OSF. The implication of this hypothesis could open some promising vistas on still unexplored innate immune systems harboured by oral mucosa. Restoring and maintaining the adipogenic and protective potential of oral fibroblasts by inhibiting TGF- ß receptors could hinder the disease progression of OSF.

Proteomic profiling of various human dental stem cells - a systematic review.

BACKGROUND: The proteomic signature or profile best describes the functional component of a cell during its routine metabolic and survival activities. Additional complexity in differentiation and maturation is observed in stem/progenitor cells. The role of functional proteins at the cellular level has long been attributed to anatomical niches, and stem cells do not deflect from this attribution. Human dental stem cells (hDSCs), on the whole, are a combination of mesenchymal and epithelial coordinates observed throughout craniofacial bones to pulp. AIM: To specify the proteomic profile and compare each type of hDSC with other mesenchymal stem cells (MSCs) of various niches. Furthermore, we analyzed the characteristics of the microenvironment and preconditioning changes associated with the proteomic profile of hDSCs and their influence on committed lineage differentiation. METHODS: Literature searches were performed in PubMed, EMBASE, Scopus, and Web of Science databases, from January 1990 to December 2018. An extra inquiry of the grey literature was completed on Google Scholar, ProQuest, and OpenGrey. Relevant MeSH terms (PubMed) and keywords related to dental stem cells were used independently and in combination. RESULTS: The initial search resulted in 134 articles. Of the 134 full-texts assessed, 96 articles were excluded and 38 articles that met the eligibility criteria were reviewed. The overall assessment of hDSCs and other MSCs suggests that differences in the proteomic profile can be due to stem cellular complexity acquired from varied tissue sources during embryonic development. However, our comparison of the proteomic profile suffered inconsistencies due to the heterogeneity of various hDSCs. We believe that the existence of a heterogeneous population of stem cells at a given niche determines the modalities of regeneration or tissue repair. Added prominences to the differences present between various hDSCs have been reasoned out. CONCLUSION: Systematic review on proteomic studies of various hDSCs are promising as an eye-opener for revisiting the proteomic profile and in-depth analysis to elucidate more refined mechanisms of hDSC functionalities.

High altitude as a possible factor for dysbiosis of salivary microbiome in orthodontic patients.

BACKGROUND: External stressors such as high altitude and low oxygen are known to affect the human microbiome, and in light of the increased occurrence of dental caries and periodontitis in orthodontic patients, the effect of high altitude and the altered oral environment in orthodontic patients on the oral salivary microbiome was researched. MATERIALS & METHODS: 31 orthodontic patients from high altitude, Aseer region and 25 orthodontic patients, residing at sea level, as controls were included. DNA isolation was done from the saliva collected from the study participants. V3 area of 16s RNA was targeted by universal primers through PCR to decipher the salivary microbiome in both the groups. RESULTS: A total of 11 genera belonging to 4 phyla of bacteria were identified in both groups. The most abundant microbiome at the phylum level was: Firmicutes, Bacteroidetes Proteobacteria, and Cyanobacteria. The salivary microbiome was more diverse in sea level controls compared to that of the orthodontic patients at high altitude wherein the presence of only two main phyla: Firmicutes and Proteobacteria were seen. The controls revealed Firmicutes, Proteobacteria, Bacteroidetes and Cyanobacteria. CONCLUSIONS: The findings of the study suggest that the biodiversity of the salivary microbiome is severely perturbed under the cumulative influences of high altitude and presence of fixed orthodontic appliance. Under these circumstances, a strict and meticulous oral hygiene regimen should be recommended and followed to avoid harmful effects on the periodontal tissues.

Role of matrix vesicles and crystal ghosts in bio-mineralization.

Matrix vesicles (MVs) are extracellular membrane-bound vesicles of about ~ 50-200 nm in diameter that play a role in the bio-mineralization process of hard tissue formation. The present review is based on the empirical phenomenon of primary mineralization process via matrix vesicle-mediated mechanism with special reference to crystal ghosts as well as the mechanism on the organic-inorganic relationship between matrix vesicles and crystal ghosts, and the transformation that these structures undergo during bio-mineralization.

Face Validity and Psychometric Evaluation of the Available Oral Health-related Quality of Life Instruments: A Systematic Review.

PURPOSE: A growing recognition of the importance of oral health-related quality of life (OHRQoL) has led to the development of several instruments to measure their relationship with health. The objective of this review was to update the knowledge on the general and psychometric characteristics of the instruments to measure the quality of life (QoL) related to oral health that emerged after publication in 1997 of the results of the conference 'Measuring Oral Health and QoL'. MATERIALS AND METHODS: A bibliographic search was carried out to identify publications published in January from 1998 to June 2018, using EMBASE, PubMed, Scopus, CINAHL and Web of Science databases. Specific criteria were established based on international reference frameworks for the inclusion, collection, and analysis of general and psychometric properties of the instruments. RESULTS: 233 articles were identified, of which 10 met the eligibility criteria and were included. All the instruments were multidimensional, presented psychometric properties and were mostly based on prior measurement tools and the classification of impairments and disabilities. All studies presented information on the internal consistency of their instruments. Validity to discriminate was also rated positively in all of the instruments except OHRQoL-UK instrument. Among the instruments, the criterion that was found to be least was a response to change, as only three instruments met the criteria. Reliability and construct validity criteria were also present in most of the studies. CONCLUSION: The dental profession has shown great progress towards a more comprehensive measurement of the oral health needs of the population, it is necessary to move from focusing on sick patients and theories of disabilities to incorporating healthy patients and resource-based theories and capacities in their measurements of OHRQoL, that would improve patient safety, quality of care and risk management, and improve clinical decision making for healthcare professionals.

Novel therapies in the management of oral cancer: An update.

An estimated 4% of all cancers are of the oral cavity or oropharyngeal. Presently, management of the oral cancers mainly includes surgery, radiotherapy, and chemotherapy either alone or in combination depending on the individual case. Each of these techniques has their advantages and disadvantages. Surgery demands removal of cancerous tissue causing disfigurement and functional impairment. Radiotherapy has significant side effects like mucositis, myelosuppression, xerostomia and dental caries. With the advent of newer treatment methods like the targeted therapy, immune therapy and gene therapy, treatment outcomes are better with fewer side effects. This has generally improved survival rates and quality of life of cancer patients.

Comparison of the Efficacy of Sediment Cytology over Oral Brush Cytology in Oral Leukoplakia.

INTRODUCTION: A method called sediment cytology includes the investigation of smears arranged from the sediment of the biopsy specimen fixatives. The sediment from this fixative is used to prepare smears and provides a potentially rich source for cytological material. Investigation of the fixative sediment and understanding of the cytological picture with pertinent clinical and radiological information permits diagnosis in a few hours. AIM: To evaluate the diagnostic efficacy of sediment cytology and oral brush cytology compared with histopathological findings in oral leukoplakia (OL) cases. METHODS: Cytological smears were obtained from 30 clinically diagnosed OL lesions using 2 techniques: oral cytobrush and 10% formalin fixative sedimentation. Both smears were stained with Papanicolaou. Cytological smear evaluation was conducted with respect to cellularity, cell distribution, cellular clumping, and the presence of blood, debris, inflammatory cells, and microbial colonies. The cytopathological scores for all cases were compared between sediment and brush cytology and correlated with the histopathological diagnosis. For statistical analysis, the κ test and the Wilcoxon matched-pair test were used. RESULTS: The cytobrush technique had a sensitivity of 83.3% for OL cases histopathologically diagnosed as severe dysplasia, while the sediment cytology technique had a sensitivity of 16.6%. For moderate/mild dysplasia cases, the cytobrush technique had a sensitivity of 7.7%, whereas the sediment technique showed no diagnostic sensitivity. CONCLUSION: Based on the results from the present study, sediment cytology, unlike oral brush cytology, is not a useful screening tool for the preliminary diagnosis of potentially malignant oral lesions.

Current updates on dental perspectives of leprosy - Revisited.

The present review summarizes the current updates on dental perspectives on leprosy and the affording factors that are responsible for the prevalence of caries and periodontal diseases in leprosy. It also highlights immunopathological phenomena and reactional episodes of leprosy that occur due to daedal interactions between the perio-odontopathic bacteria and M. leprae. In addition, a brief introduction, historiography, classification and clinicopathological aspects are also been covered.