Sexual dimorphism in neurobehavioural phenotype and gut microbial composition upon long-term exposure to structural analogues of bisphenol-A.

Bisphenol S (BPS) and Bisphenol F (BPF), the analogues of the legacy endocrine disrupting chemical, Bisphenol A (BPA) are ubiquitous in the environment and present in various consumer goods, and potentially neurotoxic. Here, we studied sex-specific responses of bisphenols on behavioural phenotypes, including their association with pro-inflammatory biomarkers and altered neurotransmitters levels, and the key gut microbial abundances. Neurobehavioural changes, using standard test battery, biochemical and molecular estimations for inflammatory cytokines, neurotransmitters, and oxido-nitrosative stress markers, gene expression analysis using qRT-PCR, H&E based histological investigations, gut permeability assays and Oxford Nanopore-based 16S-rRNA metagenomics sequencing for the gut microbial abundance estimations were performed. Bisphenol(s) exposure induces anxiety and depression-like behaviours, particularly in the male mice, with heightened pro-inflammatory cytokines levels and systemic endotoxemia, altered monoamine neurotransmitters levels/turnovers and hippocampal neuronal degeneration and inflammatory responses in the brain. They also increased gut permeability and altered microbial diversity, particularly in males. Present study provides evidence for sex-specific discrepancies in neurobehavioural phenotypes and gut microbiota, which necessitate a nuanced understanding of sex-dependent responses to bisphenols. The study contributes to ongoing discussions on the multifaceted implications of bisphenols exposure and underscores the need for tailored regulatory measures to mitigate potential health risks associated with them.

DNA methylation as an epigenetic mechanism in the regulation of LEDGF expression and biological response in aging and oxidative stress.

The physiological quantum of stress-inducible transcriptional protein, Lens Epithelium-Derived Growth Factor (LEDGF), is vital for the maintenance of cellular physiology. Erratic epigenetic reprogramming in response to oxidative stress or with advancing age is found to be a major cause in the gene silencing, leading to pathobiologies. Using aging human (h) eye lens/lens epithelial cells (LECs) coupled with redox-active Peroxiredoxin 6 (Prdx6)-deficient (Prdx6-/-) mLECs as model systems, herein, we showed that in aging/oxidative stress, the human LEDGF gene was regulated by unique methylation patterns of CGs nucleotides within and around the Sp1 binding site(s) of CpG island of the LEDGF promoter (-170 to -27nts). The process caused the repression of LEDGF and its target, Hsp27, resulting in reactive oxygen species (ROS) amplification and cellular insults. This phenomenon was opposed to the unmethylated promoter in LECs. Clinically, we observed that the loss of LEDGF in the Prdx6-/- mLECs or aging lenses/LECs, correlating with increased expression of DNMT1, DNMT3a, and DNMT3b along with the methyl CpG binding protein 2 (MeCP2). Upon oxidative stress, the expression of these molecules was increased with the dramatic reduction in LEDGF expression. While demethylating agent, 5-Aza deoxycytidine (5-AzaC) transposed the aberrant methylation status, and revived LEDGF and Hsp27 expression. Mechanistically, the chloramphenicol acetyltransferase (CAT) reporter gene driven by the LEDGF promoter (-170/ + 35) and ChIP assays uncovered that 5-AzaC acted on GC/Sp1 sites to release LEDGF transcription. The data argued, for the first time, that de novo methylation of CGs around and within Sp1 sites of the CpG island directly disrupted Sp1 activity, which ensued in LEDGF repression and its biological functions. The findings should improve our understanding of cellular insults-associated with aberrant DNMTs-mediated LEDGF's activity, and can offer strategies for therapeutic intervention to halt aging/oxidative stress-induced abnormalities.

Exploring Knowledge, Awareness, and Practices Regarding Periodontal Health Assessment and Mechanical Plaque Control Among the Shillong Population of Meghalaya, India: A Descriptive Cross-Sectional Investigation.

Background Periodontal diseases are widespread oral health conditions. However, there remains a lack of comprehensive understanding regarding the knowledge, awareness, and practices related to periodontal health assessment and mechanical plaque control among specific populations, such as those residing in Shillong, Meghalaya. Shillong, being the capital city of Meghalaya in northeastern India, represents a diverse demographic and cultural landscape. Aim This study aims to evaluate the knowledge, awareness, and practices related to mechanical plaque control among the population of Shillong City. Methodology A descriptive cross-sectional online survey was conducted among the residents of Shillong City, Meghalaya. Data collection involved the administration of an 18-item, closed-ended, self-structured questionnaire. Before the main data collection, a pilot study was conducted involving 63 individuals. Data analysis was performed using IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, NY, USA), employing the chi-square test and ANOVA with a significance level of 0.05. Results Study participants were categorized into five age groups spanning from 21 to 64 years old, with the age group of 41 to 50 years demonstrating the highest mean knowledge score. Age exhibited a statistically significant influence on knowledge scores. Conclusion The study reveals a commendable level of knowledge, awareness, and adherence to practices regarding the primary tool for oral hygiene maintenance, the toothbrush, among the residents of Shillong City.

DNA methylation in necrotizing enterocolitis.

Epigenetic modifications, such as DNA methylation, are enzymatically regulated processes that directly impact gene expression patterns. In early life, they are central to developmental programming and have also been implicated in regulating inflammatory responses. Research into the role of epigenetics in neonatal health is limited, but there is a growing body of literature related to the role of DNA methylation patterns and diseases of prematurity, such as the intestinal disease necrotizing enterocolitis (NEC). NEC is a severe intestinal inflammatory disease, but the key factors that precede disease development remain to be determined. This knowledge gap has led to a failure to design effective targeted therapies and identify specific biomarkers of disease. Recent literature has identified altered DNA methylation patterns in the stool and intestinal tissue of neonates with NEC. These findings provide the foundation for a new avenue in NEC research. In this review, we will provide a general overview of DNA methylation and then specifically discuss the recent literature related to methylation patterns in neonates with NEC. We will also discuss how DNA methylation is used as a biomarker for other disease states and how, with further research, methylation patterns may serve as potential biomarkers for NEC.

Comparative Analysis of Tissue Copper Levels in Oral Submucous Fibrosis (OSMF) Patients.

Background: Oral submucous fibrosis (OSMF) is a recognized potentially malignant oral condition linked to the consumption of areca nut. Chewing areca nut has been shown to elevate soluble copper levels in mouth fluids. Materials and Methods: Participants: The study included a panel of 30 patients with OSMF from Rama Dental College, Kanpur, India, and 30 nonareca chewing individuals serving as controls. Tissue Sample Collection and Analysis: Buccal mucosal biopsies were obtained from both OSMF patients and controls. The tissue copper concentrations were quantified using mass absorption spectrometry (MAS). Additionally, energy-dispersive X-ray microanalysis (EDX) was employed to identify the presence and distribution of copper in the tissue. Statistical Analysis: Statistical comparisons were performed using appropriate methods, with a P-value of less than 0.05 considered statistically significant. Results: MAS analysis revealed that the mean tissue copper level was 6.2 ± 3.1 micrograms per gram (µg/g) in OSMF specimens (n = 30), slightly higher than the 4.5 ± 2.0 µg/g in the nonareca chewing controls (n = 30) (P = 0.1). EDX analysis showed distinct copper peaks in both the epithelium (22/23) and connective tissue (18/23) of OSMF specimens compared to control biopsies. These findings were corroborated by secondary ion mass spectrometry (SIMS) in a subset of samples. Conclusion: The study revealed higher copper concentrations in buccal mucosal tissue of OSMF patients from Rama Dental College, Kanpur, suggesting a potential connection between copper and the initiation of OSMF.

Therapeutic potential of nicorandil beyond anti-anginal drug: A review on current and future perspectives.

Nicorandil (NIC) is a well-known anti-anginal agent, which has been recommended as one of the second-line treatments for chronic stable angina as justified by the European guidelines. It shows an efficacy equivalent to that of classic anti-anginal agents. NIC has also been used clinically in various cardiovascular diseases such as variant or unstable angina and reperfusion-induced damage following coronary angioplasty or thrombolysis. Different mechanisms have been involved in the protective effects of nicorandil in various diseases, including opening of adenosine triphosphate-sensitive potassium (KATP) channel and donation of nitric oxide (NO). In recent years, NIC has been found to show numerous pharmacological activities such as neuroprotective, nephroprotective, hepatoprotective, cardioprotective, and testicular protective effects, among other beneficial effects on the body. The present review dwells on the pharmacological potentials of NIC beyond its anti-anginal action.

The gut commensal Blautia maintains colonic mucus function under low-fiber consumption through secretion of short-chain fatty acids.

Beneficial gut bacteria are indispensable for developing colonic mucus and fully establishing its protective function against intestinal microorganisms. Low-fiber diet consumption alters the gut bacterial configuration and disturbs this microbe-mucus interaction, but the specific bacteria and microbial metabolites responsible for maintaining mucus function remain poorly understood. By using human-to-mouse microbiota transplantation and ex vivo analysis of colonic mucus function, we here show as a proof-of-concept that individuals who increase their daily dietary fiber intake can improve the capacity of their gut microbiota to prevent diet-mediated mucus defects. Mucus growth, a critical feature of intact colonic mucus, correlated with the abundance of the gut commensal Blautia, and supplementation of Blautia coccoides to mice confirmed its mucus-stimulating capacity. Mechanistically, B. coccoides stimulated mucus growth through the production of the short-chain fatty acids propionate and acetate via activation of the short-chain fatty acid receptor Ffar2, which could serve as a new target to restore mucus growth during mucus-associated lifestyle diseases.

Metagenomics analysis of mice gut microbiome to unravel the role of metal exposure and piperine.

The gut and intestinal microbiota consists of trillions of microorganisms inhabiting the human gastrointestinal tract. It plays a crucial role in human health leading to understanding the dynamic crosstalk of host-microbe interaction in the gut and has become necessary for the detection, prevention, or therapy of diseases. Gut microbiota deviations are linked with many diseases, suggesting that various pathways involved in immunity, energy, lipid, and glucose metabolism are affected. Further, it is also altered by external insults such as metal toxicity, antibiotics and pesticides. Heavy metals like arsenic, mercury, cadmium and chromium are some of the well-studied classes of environmental pollutants. Mouse models have become the model of choice for most studies in this emerging field, as they allow perturbations in the gut microbiota to be studied in a controlled experimental setup. Here, we investigate the composition and diversity of intestinal microbes utilizing cecal samples from different intervention groups: arsenic exposure (As(III)), arsenic and piperine co-administration (As +Pp), piperine per se and control group. We obtained DNA samples from these groups and performed PCR amplification and sequencing of the 16S V3-V4 region. The findings showed shift in microbial composition and abundance among different intervention groups, revealing taxa that may contribute to the microbial diversity.

Assessment of the Smear Layer Removal Efficacy of Three Different Agents on Periodontally Compromised Tooth: An In Vitro Study.

AIM: The purpose of the present study was to evaluate the smear layer removal efficacy of three various agents on periodontally compromised tooth. MATERIALS AND METHODS: The current study included 75 molar teeth that were extracted due to periodontal disease. After that, 25 samples were randomly assigned using a simple random technique to the three different agent groups, group A: Scaling and root planing (SRP) and application of SofScale agent, group B: SRP and application of QMix agent, group C: SRP and application of MTAD agent. Using a diamond circular saw, the treated portions were divided into horizontal and vertical halves. All samples were viewed under Scanning Electron Microscope. Every tooth was focused at the coronal third, middle third, and apical third portion with a magnification of 1000×. Data were recorded and statistically analyzed. RESULTS: The smear layer removal efficacy was more in the QMix agent (3.06 ± 0.04) group followed by MTAD agent (3.28 ± 0.09) and SofScale agent (4.14 ± 0.10) group on the root surface. On intra group comparison, there was a statistically significant difference found in all the intra group agents with all the three levels. On inter group evaluation, at coronal third, there was no significant difference found between the different agents. There was a significant difference found between the different agents at middle and coronal third. CONCLUSION: On conclusion, the current investigation found that, the root surfaces treated with QMix shown a greater ability to remove smear layers compared to tooth surfaces treated with MTAD and SofScale agent. CLINICAL SIGNIFICANCE: Conventional therapies such as SRP effectively eliminate calculus, plaque, and necrosed cementum; nevertheless, they leave behind a smear layer that could impede normal healing. In an effort to overcome this, root conditioning agents were applied on the root surface to remove the smear layer. The traditional root conditioning agents such as citric acid have certain disadvantages, though, such as an acidic pH that could harm the root surface. As a result, researchers have been looking for biocompatible root conditioning treatments that are more effective. How to cite this article: Singh DK, BS Raj H, Soans CR, et al. Assessment of the Smear Layer Removal Efficacy of Three Different Agents on Periodontally Compromised Tooth: An In Vitro Study. J Contemp Dent Pract 2024;25(2):156-159.

Evaluation of Stain Removal Efficacy and Color Stability of Three Different Dentifrices on Artificially Stained Enamel Surface-An In Vitro Study.

AIM: The aim of the present study was to assess the stain removal ability and color stability of three distinct dentifrices on artificially stained enamel surface. MATERIALS AND METHODS: This study included 75 intact, healthy premolars free of dental caries that were extracted during orthodontic therapy. The samples were allowed to dry for 6 hours after being submerged in the prepared tea solution for roughly 18 hours every day. Then this procedure was repeated for seven successive days. All samples were randomly divided into three experimental groups with 25 samples in each group. Group I: control dentifrice, group II: dentifrice containing hydrogen peroxide, group III: dentifrice containing papain and bromelain. A specially designed toothbrushing simulator was used to brush every sample in the relevant group. Using a spectrophotometer and a measurement program, color measurement was evaluated after staining process after 4 weeks and 8 weeks of teeth cleaning. Using a profilometer, the surface roughness values (Ra) were assessed. RESULTS: After 8 weeks of brushing of stained samples, the color stability was better in dentifrice containing hydrogen peroxide (1.14 ± 0.11) followed by dentifrice containing papain and bromelain (1.22 ± 0.08) and control group (1.30 ± 0.09). And after 8 weeks of brushing of stained samples, the surface roughness was more in dentifrice containing hydrogen peroxide (0.237 ± 0.02) followed by dentifrice containing papain and bromelain (0.229 ± 0.13) and control group (0.207 ± 0.05). CONCLUSION: The present study concluded that the dentifrice containing hydrogen peroxide showed a superior whitening effect on the stained enamel surface than dentifrice containing papain and bromelain and control dentifrice. CLINICAL SIGNIFICANCE: The development of various dentifrice products has been greatly aided by the increased demand for an improved esthetic appearance. Teeth's natural color and any external stains that could accumulate on the tooth surface combine to determine a tooth's color. Additionally, the use of whitening dental pastes to remove external stains has grown in favor. With the development of these whitening toothpastes, dentifrices' ability to lessen or eliminate extrinsic dental stains has increased. How to cite this article: Mishra D, Kamath DG, Alagla M, et al. Evaluation of Stain Removal Efficacy and Color Stability of Three Different Dentifrices on Artificially Stained Enamel Surface-An In Vitro Study. J Contemp Dent Pract 2024;25(1):68-71.

Activated fibroblasts modify keratinocyte stem niche through TET1 and IL-6 to promote their rapid transformation in a mouse model of prenatal arsenic exposure.

Early life exposure to environmental pollutants such as arsenic (As) can increase the risk of cancers in the offspring. In an earlier study, we showed that only prenatal As exposure significantly increases epidermal stem cell proliferation and accelerates skin tumorigenesis in BALB/c mouse offspring. In the present work, we have examined the role of As-conditioned dermal fibroblasts (DFs) in creating pro-tumorigenic niches for Keratinocyte stem cells (KSCs) in the offspring. DFs isolated from prenatally exposed animals showed increased levels of activation markers (α-SMA, Fibronectin, Collagen IV), induction of ten-eleven translocation methylcytosine dioxygenase 1(TET1), and secreted high levels of niche modifying IL-6. This led to enhanced proliferation, migration, and survival of KSCs. Increased IL-6 production in As-conditioned fibroblast was driven through TET1 mediated 5-mC to 5-hmC conversion at -698/-526 and -856/-679 region on its promoter. IL-6 further acted through downstream activation of JAK2-STAT3 signaling, promoting epithelial-to-mesenchymal transition (EMT) in KSCs. Inhibition of pSTAT3 induced by IL-6 reduced the EMT process in KSCs resulting in a significant decrease in their proliferation, migration, and colony formation. Our results indicate that IL-6 produced by prenatally conditioned fibroblasts plays a major role in regulating the KSC niche and promoting skin tumor development in As-exposed offspring.

Prenatal arsenic exposure alters keratinocyte stem cell fate through persistent activation of IGF2R-MAPK cascade leading to aggravated skin carcinogenesis in mice offspring.

Chronic exposure to arsenic (As) promotes skin carcinogenesis in humans and potentially disturbs resident stem cell dynamics, particularly during maternal and early life exposure. In the present study, we demonstrate how only prenatal arsenic exposure disturbs keratinocyte stem cell (KSC) conditioning using a BALB/c mice model. Prenatal As exposure alters the normal stemness (CD34, KRT5), differentiation (Involucrin), and proliferation (PCNA) program in skin of offspring with progression of age as observed at 2, 10, and 18 weeks. Primary KSCs isolated from exposed animal at Day-2 showed increased survival (Bax:Bcl-xL, TUNEL assay), proliferation (BrdU), and differentiation (KRT5, Involucrin) potential through the activation of pro-carcinogenic IGF2R-MAPK cascade (IGF2R-G(α)q-MEK1-ERK1/2). This was associated with reduced enrichment of histone H3K27me3 and its methylase, EZH2 along with increased binding of demethylase, KDM6A at Igf2r promoter. Altered KSCs conditioning through disturbed Igf2r imprint contributed to impaired proliferation and differentiation and an aggravated tumor response in offspring.

Peak Broadening in Photoelectron Spectroscopy of Amorphous Polymers: The Leading Role of the Electrostatic Landscape.

The broadening in photoelectron spectra of polymers can be attributed to several factors, such as light source spread, spectrometer resolution, the finite lifetime of the hole state, and solid-state effects. Here, for the first time, we set up a computational protocol to assess the peak broadening induced for both core and valence levels by solid-state effects in four amorphous polymers by using a combination of density functional theory, many-body perturbation theory, and classical polarizable embedding. We show that intrinsic local inhomogeneities in the electrostatic environment induce a Gaussian broadening of 0.2-0.7 eV in the binding energies of both core and semivalence electrons, corresponding to a full width at half-maximum (FWHM) of 0.5-1.7 eV for the investigated systems. The induced broadening is larger in acrylate-based than in styrene-based polymers, revealing the crucial role of polar groups in controlling the roughness of the electrostatic landscape in the solid matrix.

Cidofovir in Severe Hypoxemic Adenoviral Pneumonia.

The authors present a 16-mo-old boy with flu like symptoms, not responding to supportive management and progressed to severe hypoxemic pneumonia. Adenovirus was detected in the nasopharyngeal aspirate. He showed rapid improvement after intravenous cidofovir administration.

Fugitive road dust particulate matter emission inventory for India: A field campaign in 32 Indian cities.

This research delves into the pivotal issue of road dust emissions and their profound ramifications on air quality across diverse regions of India. In pursuit of this objective, the study initiated a comprehensive field campaign to estimate silt loading (sL) values and evaluate the distribution of vehicles at 259 locations spanning 32 Indian cities. Remarkable disparities in sL values were observed across different road types and states. Notably, sites in Rajasthan, characterized by its arid Aravalli range and industrial activities, emerged as stark outliers, exhibiting significantly elevated sL values (up to 137 g/m2) compared to their counterparts. The regional analysis goes further to elucidate the relation between climatic conditions, topography, and silt loading. As a broader trend, roads in North India have higher sL values in contrast to those in South India. Further, a comprehensive particulate matter road dust emission inventory for the entire India in the year 2022 was developed using the vehicle registration data from 1352 road transport offices nationwide, in conjunction with the data from the field campaign concerning sL values and vehicle counts. Specific states such as Rajasthan, Uttar Pradesh, Maharashtra, Karnataka, and Gujarat emerged as the predominant contributors to road dust emissions. These states not only exhibit elevated sL values, but also account for a substantial proportion of the total registered vehicles in India, thereby underscoring the pressing imperative for effective mitigation measures. Weather Research and Forecasting coupled with chemistry (WRF-Chem) simulations, using this emission inventory, reveal that PM2.5 concentrations stemming from road dust exceed the World Health Organization guidelines in 55 % of the states across India. Further analysis delineates that more than 10,000 lives are annually lost due to PM2.5 pollution attributable to road dust in India, with the potential to salvage 10 % of these lives by paving all roads throughout the country.

Influence of Different Mouthwashes on the Efficacy of Fluoridated Dentifrices in Prevention of Enamel Erosion: An In Vitro Study.

AIM: The purpose of the current study was to evaluate the impact of three various mouthwashes on the effectiveness of fluoride dentifrices in preventing enamel erosion. MATERIALS AND METHODS: A total of 120 sound intact human premolar teeth which were extracted for orthodontic treatment were selected for the study. A 3 × 3 mm window section was positioned in the middle of the coronal surface of the tooth in order to define the study area. Each sample was placed in a solution of 1% citric acid (pH 3.5) for 10 minutes in order to produce an eroded surface. All samples were divided into two main groups (60 samples each) as follows: Group A for sodium fluoride dentifrices and group B for stannous fluoride dentifrices, again it is subdivided into: CHX: Chlohex ADS®, EO: Listerine®, CPC: Colgate® Plax (20 samples in each subgroup). After that, samples underwent the pH cycling model for 5 days. Samples were examined for surface loss using a scanning electron microscope. RESULTS: In sodium fluoride dentifrices group, before intervention, the surface loss was 3.12 ± 1.03 in CHX group, 3.08 ± 1.20 in EO group, and 3.09 ± 0.96 in CPC group. After intervention, the less surface loss found with CHX group (2.18 ± 0.84), followed by CPC (2.34 ± 0.74) and EO group (2.46 ± 0.97). In stannous fluoride dentifrices group, before intervention, the surface loss in CHX group was 3.26 ± 1.19, in EO group, it was 3.18 ± 1.31, and in CPC group, it was 3.22 ± 1.06. After intervention, the less surface loss found with CHX: group (1.90 ± 0.54), followed by CPC (2.24 ± 0.28) and EO group (2.38 ± 0.20). CONCLUSION: The present study concluded that the fluoride dentifrices' preventive effects against tooth surface loss were unaffected by a different mouthwashes with varying compositions and major constituents. In terms of erosion, fluoridated toothpaste containing stannous fluoride was found to provide better surface loss protection than sodium fluoride. CLINICAL SIGNIFICANCE: Primary prevention and the eradication of contributing causes are the greatest strategies for preventing erosion. Simultaneously, antibacterial agent in the mouthwashes may help in enhancing the effect of fluoride in the enamel, owing to their high affinity for teeth structures. Therefore, in addition to cause-related treatment, further efforts to reduce tooth tissue loss are also necessary.

Prdx6 Regulates Nlrp3 Inflammasome Activation-Driven Inflammatory Response in Lens Epithelial Cells.

The continuum of antioxidant response dysregulation in aging/oxidative stress-driven Nlrp3 inflammasome activation-mediated inflammatory response is associated with age-related diseases. Peroxiredoxin (Prdx) 6 is a key antioxidant that provides cytoprotection by regulating redox homeostasis. Herein, using lens epithelial cells (LECs) derived from the targeted inactivation of Prdx6 gene and aging lenses, we present molecular evidence that Prdx6-deficiency causes oxidative-driven Nlrp3 inflammasome activation, resulting in pyroptosis in aging/redox active cells wherein Prdx6 availability offsets the inflammatory process. We observed that Prdx6-/- and aging LECs harboring accumulated reactive oxygen species (ROS) showed augmented activation of Nlrp3 and bioactive inflammatory components, like Caspase-1, IL-1ß, ASC and Gasdermin-D. Similar to lipopolysaccharide treatment, oxidative exposure led to further ROS amplification with increased activation of the Nlrp3 inflammasome pathway. Mechanistically, we found that oxidative stress enhanced Kruppel-like factor 9 (Klf9) expression in aging/Prdx6-/- mLECs, leading to a Klf9-dependent increase in Nlrp3 transcription, while the elimination of ROS by the delivery of Prdx6 or by silencing Klf9 prevented the inflammatory response. Altogether, our data identify the biological significance of Prdx6 as an intrinsic checkpoint for regulating the cellular health of aging or redox active LECs and provide opportunities to develop antioxidant-based therapeutic(s) to prevent oxidative/aging-related diseases linked to aberrant Nlrp3 inflammasome activation.