Impact of bisphenol A and analogues eluted from resin-based dental materials on cellular and molecular processes: An insight on underlying toxicity mechanisms.

Dental resin systems, used for artificial replacement of teeth and their surrounding structures, have gained popularity due to the Food and Drug Administration's (FDA) recommendation to reduce dental amalgam use in high-risk populations and medical circumstances. Bisphenol A (BPA), an endocrine-disrupting chemical, is an essential monomer within dental resin in the form of various analogues and derivatives. Leaching of monomers from resins results in toxicity, affecting hormone metabolism and causing long-term health risks. Understanding cellular-level toxicity profiles of bisphenol derivatives is crucial for conducting toxicity studies in in vivo models. This review provides insights into the unique expression patterns of BPA and its analogues among different cell types and their underlying toxicity mechanisms. Lack of a consistent cell line for toxic effects necessitates exploring various cell lines. Among the individual monomers, BisGMA was found to be the most toxic; however, BisDMA and BADGE generates BPA endogenously and found to elicit severe adverse reactions. In correlating in vitro data with in vivo findings, further research is necessary to classify the elutes as human carcinogens or xenoestrogens. Though the basic mechanisms underlying toxicity were believed to be the production of intracellular reactive oxygen species and a corresponding decline in glutathione levels, several underlying mechanisms were identified to stimulate cellular responses at low concentrations. The review calls for further research to assess the synergistic interactions of co-monomers and other components in dental resins. The review emphasizes the clinical relevance of these findings, highlighting the necessity for safer dental materials and underscoring the potential health risks associated with current dental resin systems.

Salivary stimulatory effect of novel low level transcutaneous electro neurostimulator in geriatric patients with xerostomia.

BACKGROUND: Xerostomia (dryness of the mouth) is one of the most common long-term consequences of ageing, and it causes a tremendous impact on the function and morphology of the salivary ductal system. As a consequence, it leads to a decrease in the amount of salivary output and also affects the overall quality of life. The purpose of this study was to determine whether electrostimulation using a custom designed transcutaneous electrical nerve stimulation (TENS) device will help to improve the quality of secreted saliva following electrostimulation. METHODS: One hundred thirty-five participants underwent the intervention for three months, twice daily (80 Hz). Pre-intervention and post-intervention unstimulated saliva were collected. Parameters such as salivary pH, cortisol level, salivary antioxidants, total protein, the viscosity of saliva, and microbial carriage were analysed. RESULTS: Salivary pH, cortisol, microbial cultures, viscosity, and antioxidants showed a significant difference at the end of the 3rd month (p < 0.05). Irrespective of the patient's age, gender, and common underlying systemic illnesses (diabetes and hypertension), a significant change in the quality of the salivary analytes was observed. CONCLUSION: The study emphasises the use of a custom designed TENS device in improving the quality of secreted saliva among old patients with oral dryness.

Anticipatory in silico vaccine designing based on specific antigenic epitopes from Streptococcus mutans against diabetic pathogenesis.

The metabolic disorder Type 2 Diabetes Mellitus (T2DM) is characterized by hyperglycaemia, causing increased mortality and healthcare burden globally. Recent studies emphasize the impact of metabolites in the gut microbiome on T2DM pathogenesis. One such microbial metabolite, imidazole propionate (Imp) derived from histidine metabolism, is shown to interfere with insulin signalling and other key metabolic processes. The key enzyme urocanate reductase (UrdA) is involved in ImP production. Hence, we propose to develop a novel therapeutic vaccine against the gut microbe producing Imp based on UrdA as a target for treating T2DM using immunoinformatics approach. Antigenic, non-allergic, non-toxic, and immunogenic B cell and T cell potential epitopes were predicted using immunoinformatics servers and tools. These epitopes were adjoined using linker sequences, and to increase immunogenicity, adjuvants were added at the N-terminal end of the final vaccine construct. Further, to confirm the vaccine's safety, antigenic and non-allergic characteristics of the developed vaccine construct were assessed. The tertiary structure of the UrdA vaccine sequence was predicted using molecular modelling tools. A molecular docking study was utilized to understand the vaccine construct interaction with immune receptors, followed by molecular dynamics simulation and binding free energy calculations to assess stability of the complex. In silico cloning techniques were employed to evaluate the expression and translation effectiveness of the developed vaccine in pET vector. In conclusion, this study developed an in silico epitope-based vaccine construct as a novel adjunct therapeutic for T2DM.

Unraveling the interaction of bisphenol A with collagen and its effect on conformational and thermal stability.

Evidence suggests the association of bisphenol A (BPA) with increased collagen (COL) expression in the development of fibrosis. Ultraviolet and fluorescence spectra on collagen-BPA interaction showed that 100 ng/ml of BPA initiated loosening of protein backbone through unfolding with exposure of tyrosine residues resulting in an intermediate "Molten Globule" state, which later aggregated with 1 µg/ml of BPA indicated with an apparent red-shift. Conformational changes with CD and ATR-FTIR showed disappearance of negative band with broadening and shifting of peptide carbonyl groups. Light scattering findings with TEM images presented initial dissolution followed by unordered thick fibrillar bundles with 30 µg/ml BPA. The complex was pH sensitive, with calorimetric thermogram revealing increased thermal stability requiring 83°C to denature. Hydrogen bonds of 2.8 Å with hydrophobic interactions of BPA in all grooves of collagen molecule with same pattern and binding energy (-4.1 to -3.9 kcal/mol) confirmed the intensity of aggregate formation via in-silico docking.

Association of MICA gene Exon-5 polymorphism in oral submucous fibrosis.

OBJECTIVE: The present study was conducted to explore the allele frequencies of MICA gene Exon-5 transmembrane and to measure the circulatory MICA levels in various histologic grades of patients with oral submucous fibrosis (OSF) compared to healthy individuals. STUDY DESIGN: We enrolled a total of 595 patients for this cross-sectional study and divided them into 2 groups: healthy controls (n = 320) and patients with OSF (n = 275). Further, patients with OSF were subdivided based on their histologic gradings. The genomic DNA was extracted followed by a polymerase chain reaction and genotyping using the ABI Prism DNA Sequencer (ThermoFisher Scientific, Inc., Waltham, MA, USA). RESULTS: Our study showed that the A5 allele of the MICA gene in the Exon-5 region conferred significant risk for patients with OSF. With reference to the histologic gradings of OSF, we found that the MICA gene conferred statistically significant risk among patients with grade III OSF. On the other hand, the A8 allele of MICA gene in the Exon-5 region conferred significant protection among the overall OSF cohort and in the grade III of histologic grade. Finally, the circulatory human MICA levels were found to have a stepwise increase from grade I toward grade III in patients with OSF. CONCLUSION: Our results suggested that the A5 allele in MICA might confer risk for the progression of OSF among the South Indian ethnic population.

Elucidating the inhibitory mechanism of yeast α-glucosidase by phytocompounds from Scoparia dulcis through in vitro and in silico approach.

Antidiabetic activity of herb Scoparia dulcis Linn (SD) used in traditional medicine is well established, yet, the molecular mechanism is not understood. In this study, in vitro α-glucosidase inhibitory effects of SD aqueous extract and its kinetics were investigated and in silico analysis was carried out. SD showed potent inhibition of α-glucosidase with low IC50value (30 µg/mL). Enzyme kinetics analysis revealed the inhibition to be a mixed type of inhibition. From literature screening, we found that six compounds of SD to exhibit potent anti-diabetic activity, namely apigenin, betulinic acid, hispidulin, luteolin, scopadulcic-acid-B and scutellarein. These compounds were subjected to molecular docking. Docking studies revealed scopadulcic acid B and betulunic acid to show optimum binding constant and low free energy. Molecular dynamics simulation was carried out to further understand the interaction and stability between glucosidase and ligands of SD. Taken together, the study reveals that the potency of SD is due to synergistic effect of active phytochemicals in it and suggest that their properties can be utilized for anti-diabetic treatment strategies.Communicated by Ramaswamy H. Sarma.

Role of bioglass in enamel remineralization: Existing strategies and future prospects-A narrative review.

Enamel, once formed, loses the ability to regenerate due to the loss of the formative ameloblasts. It is subjected to constant damaging events due to exposure to external agents and oral microbiomes. An enamel remineralization process targets to replenish the lost ionic component of the enamel through a multitude of methods. Enamel remineralization is highly challenging as it has a complex organized hierarchical microstructure. Hydroxyapatite nanocrystals of the enamel vary in size and orientation along alignment planes inside the enamel rod. The inability of the enamel to remodel unlike other mineralized tissues is another substantial deterrent. One of the well-known biomaterials, bioglass (BG) induces apatite formation on the external surface of the enamel in the presence of saliva or other physiological fluids. Calcium, sodium, phosphate, and silicate ions in BG become responsive in the presence of body fluids, leading to the precipitation of calcium phosphate. Studies have also demonstrated the bactericidal potential of BG against Streptococcus mutans biofilms. The anticariogenicity and antibacterial activity were found to be enhanced when BG was doped with inorganic ions such as F, Ag, Mg, Sr, and Zn. Due to the versatility of BG, it has been combined with a variety of agents such as chitosan, triclosan, and amelogenin to biomimic remineralization process. Key strategies that can aid in the development of contemporary enamel remineralization agents are also included in this review.

Association of serum and salivary tumor necrosis factor-α with histological grading in oral cancer and its role in differentiating premalignant and malignant oral disease.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is an important malignancy throughout the world; early detection is an important criterion for achieving high cure rate. Out of the many reported markers for OSCC, this study validated the efficacy of tumor necrosis factor-α (TNF- α) in differentially diagnosing premalignant oral lesions and OSCC. Also, the study aimed to correlate the levels of salivary and serum TNF- α with clinicopathologic factors. MATERIALS AND METHODS: A prospective experimental laboratory study was designed. Serum and salivary samples from 100 subjects in each group of healthy control, premalignant disease (PMD) and OSCC were collected for the study following appropriate exclusion and inclusion criteria. Serum and salivary level of TNF-α was analysed by enzyme linked immunosorbent assay. The data obtained were subjected to appropriate statistical analysis. RESULTS: Increased level of both serum and salivary TNF- α was observed in OSCC subjects compared to healthy control and PMD group. Receiver operator characteristic curve analysis and area under curve values showed high specificity and sensitivity for salivary TNF-α in differentiating OSCC from PMD and healthy controls. There was significant increase in TNF- α level in moderately and poorly differentiated lesion compared to well differentiated lesion and in stage IV of clinical stage. A positive correlation was observed only with histological grading of OSCC and TNF- α. CONCLUSIONS: Salivary TNF-α is proved to be superior for detecting OSCC. Increase in TNF-α with histological grading and clinical staging suggests a role in prognosis.