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The article explores the growing popularity of clear aligners in orthodontic care, driven by their effectiveness and aesthetic appeal. Topics discussed include the rising cost of orthodontic treatment, the appeal of direct-to-consumer aligners for affordability, and the trade-offs between cost and treatment quality.

Despite their high success rates, peri-implantitis can affect the stability and function of dental implants. Various treatment modalities have been investigated for the treatment of peri-implantitis to achieve re-osseointegration. An electronic literature search was performed supplemented by a manual search to identify studies published until January 2022. Articles that evaluated re-osseointegration in peri-implantitis sites in animal models following laser therapy or antimicrobial photodynamic therapy (aPDT) were included. Case reports, case series, systematic reviews, and letters to the editor were excluded. Risk of bias and GRADE assessment were followed to evaluate the quality of the evidence. Six studies out of 26 articles identified on electronic search were included in this review. The studies included animal studies conducted on canine models. Four out of six studies reported a higher degree of re-osseointegration following treatment of implants with laser therapy. The findings suggest that laser decontamination shows potential in enhancing re-osseointegration, particularly with the Er: YAG laser, which effectively decontaminated implant surfaces. However, conflicting outcomes and limitations in the evidence quality warrant caution in drawing definitive conclusions. Based on the limited available evidence, laser therapy may show a higher degree of re-osseointegration of implants than mechanical debridement. [ABSTRACT FROM AUTHOR]

Recent developments in lysosome biology have transformed our view of lysosomes from static garbage disposals that can also act as suicide bags to decidedly dynamic multirole adaptive operators of cellular homeostasis. Lysosome‐governed signaling pathways, proteins, and transcription factors equilibrate the rate of catabolism and anabolism (autophagy to lysosomal biogenesis and metabolite pool maintenance) by sensing cellular metabolic status. Lysosomes also interact with other organelles by establishing contact sites through which they exchange cellular contents. Lysosomal function is critically assessed by lysosomal positioning and motility for cellular adaptation. In this setting, mechanistic target of rapamycin kinase (MTOR) is the chief architect of lysosomal signaling to control cellular homeostasis. Notably, lysosomes can orchestrate explicit cell death mechanisms, such as autophagic cell death and lysosomal membrane permeabilization‐associated regulated necrotic cell death, to maintain cellular homeostasis. These lines of evidence emphasize that the lysosomes serve as a central signaling hub for cellular homeostasis. [ABSTRACT FROM AUTHOR]

The article focuses on the challenges posed to population health and healthcare delivery by climate change, with particular attention to its implications for dentistry. Topics discussed include the predicted negative effects of climate change on human migration patterns, demographic characteristics, disease prevalence, and dental and healthcare infrastructure, as well as the escalating insurance costs and potential withdrawal of coverage for practices in at-risk geographic areas.

(1) Background: Dental pulp stem cells (DPSCs) are derived from pulp tissue lodged within human teeth and are mesenchymal in origin. These DPSCs have been demonstrated to dissociate into clusters of various cell lineages and are very easy to isolate, culture, and expand. Melatonin, a multifaceted molecule with a spectrum of effects in the human body, is known to influence stem cell viability, proliferation, and differentiation, but little is known about the impact melatonin has on the capacity of DPSCs to differentiate into adipocytes, osteocytes, and chondrocytes. The primary objective of this research was to explore the impact that melatonin has on proliferation, and the capacity of DPSCs to differentiate into adipocytes, osteocytes, and chondrocytes. (2) Methodology: DPSCs were extracted from 12 healthy human teeth, cultured, and expanded. Flow cytometry was performed to examine the surface stem cell markers. Further, melatonin was added to the cultured DPSCs in various concentrations, to assess cytotoxicity using an MTT assay. Following this, the DPSCs were tested for their proliferative ability, as well as adipogenic, osteogenic, and chondrogenic differentiation capabilities under the influence of variable concentrations of melatonin. (3) Results: DPSCs obtained from human teeth demonstrated surface characteristics of mesenchymal stem cells, as shown by the positive expression of CD105, CD90, and CD73 markers. An MTT cytotoxicity assay revealed that melatonin was well tolerated by the cells at low (1 µM) and high (25 µM) concentrations. Assessment of DPSC cell differentiation elucidated that melatonin at 1 µM and 25 µM concentrations with the induction media stimulated DPSCs to differentiate into osteocytes, but did not have much influence on adipogenic and chondrogenic differentiation. (4) Conclusions: Melatonin could be used in stem cell and tissue engineering applications for osteogenic differentiation of DPSCs and could protect these cells due to its cytoprotective, immunomodulatory, and antioxidant roles, in addition to being an osteopromoter molecule. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Stem cells play an important role in the success of regenerative endodontic procedures. They are affected by the presence of medicaments that are used before the induction of bleeding or the creation of a scaffold for endodontic regeneration. This study examines the effects of different intracanal medicaments on the viability and survival of dental pulp stem cells at different doses and over different exposure times. Methods: Dental pulp stem cells were cultured from healthy third molar teeth using the long-term explant culture method and characterized using flow cytometry and exposed to different concentrations of calcium hydroxide, doxycycline, potassium iodide, triamcinolone, and glutaraldehyde, each ranging from 0 (control) to 1000 µg/mL. Exposure times were 6, 24, and 48 h. Cell viability was measured using the MTT assay, and apoptosis was measured using the Annexin V-binding assay. Results: All medicaments significantly reduced cell viability at different concentrations over different exposure times. Calcium hydroxide and triamcinolone favored cell viability at higher concentrations during all exposure times compared to other medicaments. The apoptosis assay showed a significant increase in cell death on exposure to doxycycline, potassium iodide, and glutaraldehyde. Conclusion: The intracanal medicaments examined in our study affected the viability of dental pulp stem cells in a time and dose-dependent manner. They also adversely affected the survival of dental pulp stem cells. Further studies are needed to better understand the effect of prolonged exposure to medicaments according to clinical protocols and their effect on the stemness of dental pulp stem cells. [ABSTRACT FROM AUTHOR]

Objective: The steady and continued increase of the Journal of Oral Pathology & Medicine's (JOPM) popularity prompted a bibliometric analysis of the journal. The purpose was to assess the significance and effect of the published research articles in the Journal from 1972 and 2020, aiding the identification of landmark articles. We performed a bibliometric analysis using the top 100 cited papers in the Journal of Oral Pathology & Medicine. Materials and Methods: An extensive review of the Web of Science was undertaken. Standard information such as author details, affiliated institutions, publication year and the country of origin was recorded. Results: The top 100 cited articles in JOPM were assessed. The maximum and minimum number of citations in the top 100 articles was 1459 and 95, respectively. A total of 16 790 citations were recorded for these 100 articles. Authors were affiliated to 28 different countries, 17 research articles from the UK and 12 from the USA. Other countries furnished seven or fewer articles. Conclusion: This bibliometric analysis provides a synopsis of research published in the journal over a 48‐year period. Recent interest in the journal shows a healthy increase in submissions and profile. [ABSTRACT FROM AUTHOR]

Background: Tobacco consumption in smoking and non‐smoking forms has been consequential in the rise of oral cancer cases. Among different forms, epidemiological studies from Middle Eastern countries and rural parts of northern India have reported increasing association of oral cancer with waterpipe (hookah) smoking. However, molecular mechanisms and role played by waterpipe smoking in the onset of oral carcinogenesis remains unexplored. Methods: In this study, immortalized normal human oral keratinocytes were chronically treated with extracts of two varieties of waterpipe tobacco—crude tobacco and processed shisha. Phenotypic changes and molecular aberrations were examined using cell culture‐based assays and mass spectrometry‐based quantitative proteomic analysis, respectively. Bioinformatics analysis was utilized to analyze proteomics data and identify dysregulated pathways. Results: Our data indicate that chronic treatment with waterpipe tobacco extracts increased proliferation, invasion, migration, and significant dysregulation of protein expression in oral keratinocytes. Altered expression of proteins involved in interferon signaling pathway were observed with both varieties of tobacco. Overexpression of cholesterol metabolism and vesicle‐mediated transport proteins were identified exclusively in cells treated with crude tobacco extract. Bioinformatics analyses revealed different oncogenic response in oral cells based on the type of waterpipe tobacco used. Conclusions: This study may serve as a useful resource in understanding the early onset of oral cancer attributed to waterpipe smoking. [ABSTRACT FROM AUTHOR]

Shammah is a smokeless tobacco product often mixed with lime, ash, black pepper and flavorings. Exposure to shammah has been linked with dental diseases and oral squamous cell carcinoma. There is limited literature on the prevalence of shammah and its role in pathobiology of oral cancer. In this study, we developed a cellular model to understand the effect of chronic shammah exposure on oral keratinocytes. Chronic exposure to shammah resulted in increased proliferation and invasiveness of non-transformed oral keratinocytes. Quantitative proteomics of shammah treated cells compared to untreated cells led to quantification of 4712 proteins of which 402 were found to be significantly altered. In addition, phosphoproteomics analysis of shammah treated cells compared to untreated revealed hyperphosphorylation of 36 proteins and hypophosphorylation of 83 proteins (twofold, p-value ≤ 0.05). Bioinformatics analysis of significantly altered proteins showed enrichment of proteins involved in extracellular matrix interactions, necroptosis and peroxisome mediated fatty acid oxidation. Kinase-Substrate Enrichment Analysis showed significant increase in activity of kinases such as ROCK1, RAF1, PRKCE and HIPK2 in shammah treated cells. These results provide better understanding of how shammah transforms non-neoplastic cells and warrants additional studies that may assist in improved early diagnosis and treatment of shammah induced oral cancer. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to systematically review the role of circulating miRNAs as potential prognostic biomarkers in head and neck cancer patients. Materials and methods: PubMed, EMBASE, Scopus, Web of Science, and gray literature from January 1990 up to and including September 2019 were searched. The study selection was performed by two independent reviewers according to eligibility criteria. Results: A total of 13 studies that met the eligibility criteria were included. Significant number of studies were executed majorly in China and predominant number of them were case-control in nature. A total of 22 different miRNAs were found to be concomitant with very poor prognosis in cancers of the head and neck region. Of these, eighteen miRNAs (miR-375, miR-1234, miR-103, miR-638, miR-200b-3p, miR-191-5p, miR-24-3p, miR-572, miR-483-5p, miR-20a, miR-22, miR-29a, miR-29b, mir-let-7c, miR-17, miR-374b-5p, miR-425-5p, and miR-196a) were upregulated and four miRNAs (miR-9, miR-29c, miR-223, and miR-187∗) were downregulated. The hazard ratio (HR) ranged from twofold to fivefold. Conclusion: Based on the results, circulating miRNA may assist in the prediction of prognosis of head and neck cancer. Further multi-center randomized controlled clinical trials with large sample size are required to validate the results of the present review. Clinical relevance: Decoding the circulating miRNA profile could aid in accurate prognostication of head and neck cancer. [ABSTRACT FROM AUTHOR]

ALERD (Acute leukoencephalopathy with restricted diffusion) is a clinico -- radiological diagnosis. Many novel causes of acute encephalopathy are emerging in children. MRI plays an important role in the diagnosis and management of such children. Many infectious and non-infectious conditions and poisonings are known to precipitate acute leukoencephalopathy. A commonly used drug like paracetamol ingested in large quantities is known to cause varied effects. We describe one such child who presented to us with paracetamol poisoning and developed acute leukoencephalopathy. He was later found to have restricted diffusion on magnetic resonance imaging. [ABSTRACT FROM AUTHOR]

Background: Long‐term follow‐ups after receiving lycopene therapy for management of oral submucous fibrosis (OSMF) are scarce. The study aimed to assess the long‐term efficacy of lycopene for management of OSMF symptoms. Methods: In this prospective clinical study, 400 clinically diagnosed early OSMF patients were assessed for the efficacy of lycopene in alleviation of burning sensation (BS) and reduced mouth opening (MO) symptoms in comparison to placebo. After 1‐year follow‐up, group A (lycopene group) was divided equally into group A1 and group A2. group A1 patients were retreated with lycopene and the A2 group was followed without retreatment. After 2‐year follow‐up, the Group A2 patients were advised retreatment but not followed as most of the patient did not agree for follow‐up. However, group A1 patients were continued to follow‐up every 6 months for a total three years. Statistical analysis was by independent sample t‐test and P‐value <.05 were considered as significant. Results: A statistically significant difference (P <.05) in BS and MO was found between group A and B with lycopene showing better results. At one‐year follow‐up, a statistically significant recurrence in the symptoms was found (P <.05) in the lycopene group (group A). After the second intervention, there was a statistically significant difference in the improvement of symptoms between the group A1 and A2 at 6 months and 1 year (P <.05) with group A1 (retreatment) showing better results. Conclusions: Treatment with lycopene led to improvement in the symptoms of OSMF in the present study. The results highlight the importance of retreatment of lycopene for its long‐term effect on alleviation the symptoms of OSMF. [ABSTRACT FROM AUTHOR]

Background: Electronic cigarettes (e-cigarettes) and other electronic vaping devices are commonly used as a method to help tobacco smoking cessation. However, the data on their safety and efficacy are currently scarce. The aim of this review was to explore the role of e-cigarettes in tobacco cessation among tobacco users.Types Of Studies Reviewed: PubMed, EMBASE, Scopus, Web of Science, and grey literature from January 1990 were searched up to and including September 2018. Two independent reviewers performed the study selection according to eligibility criteria.Results: A total of 13 studies that met the eligibility criteria were included. The majority of studies were done in the USA, and all studies were longitudinal cohort studies. The odds of increased smoking cessation in association with e-cigarette use ranged from onefold to sixfolds. No significant increase in smoking cessation was found among e-cigarette users compared with non-e-cigarette users. Pattern of e-cigarette had positive influence on smoking cessation among users.Conclusions and Practical Implications: E-cigarette use was not significantly associated with increased smoking cessation among cigarette smokers. We also found that pattern of e-cigarette may have significant effect on smoking cessation capability of e-cigarettes. Well-designed randomized controlled clinical trials are needed to assess the clinical efficacy of e-cigarettes in comparison with approved smoking cessation therapies. [ABSTRACT FROM AUTHOR]

Introduction: Toombak is a form of smokeless tobacco that is not well known in Western Society but is widely used by the Sudanese population and many others in the sub-Sahara region. However, unlike other smokeless tobacco products, information on the carcinogenic potential of toombak is scarce. The present review explored any potential epidemiological association between the use of toombak and oral leukoplakia and oral squamous cell carcinoma (OSCC).Methods: Databases including the Web of Science, SCOPUS, EMBASE and PubMed were searched for literature on the potential association between toombak and oral leukoplakia and OSCC. The search also included grey literature. The search period extended from 1990 to 2018. Following data mining, the study selection was conducted by two reviewers independently.Results: Eight studies that satisfied the inclusion criteria were included. Based on these results, there was a threefoldto sevenfold increased risk of developing the oral leukoplakia and oral squamous cell carcinoma among toombak users compared with non-users.Conclusion: Based on the results of the systematic review, there is a strong epidemiological evidence to suggest toombak to be a major risk factor for both oral leukoplakia and OSCC. Further studies are necessary to evaluate the molecular pathway of toombak-induced oral carcinogenesis. [ABSTRACT FROM AUTHOR]

Limbal stem cell deficiency (LSCD) is one of the leading causes of corneal damage. Injury or inflammation in the cornea causes LSCD, which may be unilateral or bilateral depending upon the cause. Limbal epithelial cell implants successfully improve vision in patients with chemical injury-induced LSCD. Transplantation of cultured epithelial stem cells has become a treatment of choice for numerous patients with LSCD. Bilateral LSCD is frequently observed in the general population, where no residual stem cells are available for ex vivo culture. Allografts are associated with a high risk of rejection, neoplasia, and disease transmission. In this respect, allogenic cell populations from other regions in the patient may substitute for allogenic material. In the present study, dental pulp stem cells were cultured in limbal stem cell media and these cells were characterized against limbal stem cells, revealing the significance of using dental pulp stem cell treatment in bilateral LSCD. The morphology and culture pattern of both limbal and dental pulp stem cells grown in limbal stem-specific media were similar. Polymerase chain reaction analysis revealed that stem cell markers were highly expressed in limbal stem cells compared to in dental pulp stem cells, regardless of the medium and scaffold in which they were grown. Although dental pulp stem cell molecular expression is quite low at the transcript level, the functional protein level according to immunocytochemistry and western blot analyses demonstrated that stem cells and corneal differentiation molecule levels were quite high, indicating their potential as limbal stem cells in the respective microenvironment. [ABSTRACT FROM AUTHOR]

Introduction: Transcriptomes in saliva can be used as potential biomarkers for both diagnostic and response to treatment in oral squamous cell carcinoma (OSCC). In this review, we explored their application in this increasingly common disease.Materials and Methods: PubMed, EMBASE, Scopus, Web of Science and grey literature from January 1990 to May 2017 were searched. Two independent reviewers performed the study selection according to eligibility criteria.Results: A total of nine studies were included. Three studies showed increased expression of DUSP1, IL8, IL1B, OAZ1, SAT1, S100P and two showed increased expression of miRNA-31 among study groups compared to normal healthy controls. The sensitivity ranged from 14% to 100%, while the specificity ranged from 38% to 100%. miRNA-27b had the highest AUC (write in full) of 0.9643 and DUSP1 had the minimum AUC of 0.41.Conclusion: Salivary transcriptomics may play an effective role as a robust and non-invasive biomarker sighting tool for the diagnosis and management of OSCC. [ABSTRACT FROM AUTHOR]

Background: Machine learning (ML) is powerful tool that can identify and classify patterns from large quantities of cancer genomic data that may lead to the discovery of new biomarkers, new drug targets, and a better understanding of important cancer genes. The aim of this systematic review was to evaluate the existing literature and assess the application of machine learning of genomic data in head and neck cancer (HNC).Materials and Methods: The addressed focused question was "Does machine learning of genomic data play a role in prognostic prediction of HNC?" PubMed, EMBASE, Scopus, Web of Science, and gray literature from January 1990 up to and including May 2018 were searched. Two independent reviewers performed the study selection according to eligibility criteria.Results: A total of seven studies that met the eligibility criteria were included. The majority of studies were cohort studies, one a case-control study and one a randomized controlled trial. Two studies each evaluated oral cancer and laryngeal cancer, while other one study each evaluated nasopharyngeal cancer and oropharyngeal cancer. The majority of studies employed support vector machine (SVM) as a ML technique. Among the included studies, the accuracy rates for ML techniques ranged from 56.7% to 99.4%.Conclusion: Our findings showed that ML techniques for the analysis of genomic data can play a role in the prognostic prediction of HNC. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) can aid in the diagnosis and treatment planning of periodontal disease by means of reducing subjectivity. This systematic review aimed to evaluate the efficacy of AI models in detecting radiographic periodontal bone loss (PBL) and accuracy in classifying lesions. The authors conducted an electronic search of PubMed, Scopus, and Web of Science for articles published through August 2022. Articles evaluating the efficacy of AI in determining PBL were included. The authors assessed the articles using the Quality Assessment for Studies of Diagnostic Accuracy tool. They used the Grading of Recommendations Assessment, Development and Evaluation criteria to evaluate the certainty of evidence. Of the 13 articles identified through electronic search, 6 studies met the inclusion criteria, using a variety of AI algorithms and different modalities, including panoramic and intraoral radiographs. Sensitivity, specificity, accuracy, and pixel accuracy were the outcomes measured. Although some studies found no substantial difference between AI and dental clinicians' performance, others showed AI's superiority in detecting PBL. Evidence suggests that AI has the potential to aid in the detection of PBL and classification of periodontal diseases. However, further research is needed to standardize AI algorithms and validate their clinical usefulness. Although the use of AI may offer some benefits in the detection and classification of periodontal diseases, the low level of evidence and the inconsistent performance of AI algorithms suggest that caution should be exercised when considering the use of AI models in diagnosing PBL. This review was registered at PROSPERO (CRD42022364600). [ABSTRACT FROM AUTHOR]

Introduction: Shammah is a form of smokeless tobacco commonly used in the Arabian Peninsula. The data on the harmful effects of shammah on oral health, particularly oral malignancies, are scarce. The aim of this review was to explore the association between shammah use and development of oral potentially malignant disorders (OPMD) and/or oral cancer.Materials and Methods: PubMed, EMBASE, Scopus, Web of Science and grey literature from January 1990 up to and including April 2018 were searched. Two independent reviewers performed the study selection according to eligibility criteria.Results: A total of 10 studies that met the eligibility criteria were included. The odds of developing OPMD and/or oral cancer in relation to shammah use varied, with one study reporting a 39 increased risk (39, 95% CI: 14-105). The associated increased risk was relatively low among those that have stopped using shammah and ranged from threefold (3.65; 95% CI: 1.40-9.50) to 12-fold (12.6; 95% CI: 3.3-48.2).Conclusion: Shammah use seems to increase the risk of development of OPMD and/or oral cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Shisha smoking has been associated with multiple diseases including oral cancer. However, a mechanistic study to investigate alteration of secreted proteins in oral cells due to shisha smoking is lacking. OBJECTIVES: Elucidation of differentially secreted proteins by immortalized human normal oral keratinocytes (OKF6/TERT1) upon chronic exposure to shisha. METHODS: OKF6/TERT1 was chronically treated with 0.5% shisha extract for 8 months. Conditioned media from shisha treated (OKF6/TERT1-Shisha) and untreated (OKF6/TERT1-Parental) cells were subjected to TMT-based quantitative proteomic analysis. Bioinformatics analysis of differentially secreted proteins was carried out using SignalP, SecretomeP and TMHMM. Immunoblot validation of selected proteins was carried out to confirm the proteomics results. RESULTS: Proteomic analysis of OKF6/TERT1-Parental and OKF6/TERT1-Shisha secretome resulted in the identification of 1,598 proteins, of which 218 proteins were found to be differentially secreted (⩾ 1.5-fold; p -value ⩽ 0.05) in shisha treated cells. Bioinformatics analysis using prediction tools showed secretory potential of differentially secreted proteins identified in OKF6/TERT1-Shisha. Western blotting validated the expression of AKR1C2, HSPH1 and MMP9 in OKF6/TERT1-Shisha secretome in agreement with proteomic data. CONCLUSION: This study serves as a useful resource to understand the effect of chronic shisha smoking on the milieu of secreted proteins of oral cells. In vivo studies are warranted to supplement our in vitro data to elucidate the role of these proteins as early diagnostic biomarkers for oral carcinogenesis among shisha smokers. [ABSTRACT FROM AUTHOR]

Introduction: There has been a recent rise in popularity of waterpipe smoking (WPS) among younger people. While it is a tobacco-related product, research on the possible deleterious effects on health and its relationship with cancer is sparse. In this paper, we evaluated the existing literature and association of WPS with head and neck cancer.Materials and Methods: PubMed, EMBASE, Scopus, Web of Science and grey literature from January 1990 up to and including March 2017 were searched. Two independent reviewers performed the study selection according to eligibility criteria.Results: A total of seven studies that met the eligibility criteria were included. In four studies that evaluated the associated risk of oesophageal cancer, the odds ratio (OR) ranged from 1.69 (95% CI = 0.76-3.77) to 21.4 (95% CI = 11.6-39.5). The OR for the association of WPS with nasopharyngeal cancer and oral cancer was reported to be 0.49 (95% CI = 0.20-1.43) and 4.20 (95% CI = 1.32-13.3), respectively. One study that evaluated risk in different head and neck cancers reported 2-fold OR (2.73 [95% CI = 1.65-4.41]).Conclusion: On the basis of our evaluation, there is an association of WPS with head and neck cancer. However, larger studies with standardized methods are needed to identify the possible detrimental health effects of WPS more fully. [ABSTRACT FROM AUTHOR]

Background: Tobacco is smoked in different form including cigarettes and water pipes. One popular form of water pipe smoking especially in Middle Eastern countries is shisha smoking. Shisha has been associated with various diseases including oral cancer. However, genomic alterations and gene expression changes associated with chronic shisha exposure have not been previously investigated.Objectives: Whole-exome sequencing and gene expression profiling of immortalized human oral keratinocytes (OKF6/TERT1) cells chronically treated with 0.5% shisha extract for a period of 8 months was undertaken to characterize molecular alterations associated with shisha exposure.Methods: Genomic DNA and RNA were extracted and preprocessed as per manufacturer's instruction and subjected to whole-exome and transcriptome sequencing using Illumina HiSeq2500 platform. Exome was analyzed using GATK pipeline whereas RNA-Seq data was analyzed using HiSat2 and HTSeq along with DESeq to elucidate differentially expressed genes.Results: Whole-exome sequence analysis led to identification of 521 somatic missense variants corresponding to 389 genes RNA-Seq data revealed 247 differentially expressed genes (≥2-fold, P-value<0.01) in shisha treated cells compared to parental cells. Pathway analysis of differentially expressed genes revealed that interferon-signaling pathway was significantly affected. We predict activation of MAPK1 pathway which is known to play a key role in oral cancer. We also observed allele specific expression of mutant LIMA1 based on RNA-Seq dataset.Conclusion: Our findings provide insights into genomic alterations and gene expression pattern associated with oral keratinocytes chronically exposed to shisha. [ABSTRACT FROM AUTHOR]

Introduction: Critical evidence on the therapeutic efficacy of botulinum toxins (BTX) is still lacking for most pain conditions. The aim of this review was to evaluate the therapeutic efficacy of BTX in the management of temporomandibular myofascial pain.Materials and Methods: Electronic databases PubMed, EMBASE, Scopus, Web of Science, and gray literature were searched for randomized clinical trials until February 2018 to answer a focused question "What is the effectiveness of botulinum toxin in the management of temporomandibular myofascial pain?" Two independent reviewers performed the study selection according to eligibility criteria.Results: A total of seven studies that met the eligibility criteria were included. Two studies showed a significant improvement in temporomandibular myofascial pain, and one study showed equal efficacy of BTX in comparison with facial manipulation, while the remaining studies did not report any significant difference between BTX and control group. Due to heterogeneity in the methodology and outcome assessment, a meta-analysis and recalculation of risk could not be performed.Conclusion: Based on our findings, the therapeutic efficacy of BTX was unclear. Randomized controlled trials with better methodological criteria need to be carried out to evaluate the real effectiveness of BTX. [ABSTRACT FROM AUTHOR]

Shisha (water pipe) smoking is falsely believed to be a hazard-free habit and has become a major public health concern. Studies have reported shisha smoking to be associated with oral lesions, as well as carcinomas of the lung, esophagus, bladder, and pancreas. A deeper understanding of the underlying molecular mechanisms would contribute to identification of biomarkers for targeted public health screening, therapeutic innovation, and better prognosis of associated diseases. In this study, we have established an in vitro chronic cellular model of shisha-exposed oral keratinocytes to study the effect of shisha on oral cells. Normal nontransformed, immortalized oral keratinocytes were chronically exposed to shisha extract for 8 months. This resulted in significant increase in cellular proliferation and cell invasion in shisha-exposed cells compared to the parental cells. Quantitative proteomic analysis of OKF6/TERT1-Parental and OKF6/TERT1-Shisha cells resulted in the identification of 5515 proteins. Forty-three differentially expressed proteins were found to be common across all conditions. Bioinformatic analysis of the dysregulated proteins identified in the proteomic study revealed dysregulation of interferon pathway, upregulation of proteins involved in cell growth, and downregulation of immune processes. The present findings reveal that chronic exposure of normal oral keratinocytes to shisha leads to cellular transformation and dysregulation of immune response. To the best of our knowledge, this is the first report that has developed a model of oral keratinocytes chronically exposed to shisha and identified proteomic alterations associated with shisha exposure. However, further research is required to evaluate the health burden of shisha smoking. [ABSTRACT FROM AUTHOR]

Oral vegetable granuloma represents an inflammatory lesion of foreign body origin resulting from the implantation of vegetable matter. Controversy regarding its pathogenesis is reflected by the various terminologies used to describe the lesion. Its diverse clinical presentations are due to variations in the antigenic potential of the vegetable material and the host response. As the diagnosis is solely histopathological, it is critical to differentiate vegetable granuloma from other oral granulomatous lesions like tuberculosis, sarcoidosis and Wegner's granulomatosis. Here, we report six cases with the varied clinicopathological presentation of hyaline ring granulomas in association with different pathological lesions. [ABSTRACT FROM AUTHOR]

Background: Oral submucous fibrosis (OSF) is an insidious chronic condition characterized by restricted mouth opening. Prosthetic rehabilitation is challenging for OSF patients as obtaining a good impression requires adequate mouth opening. The aim of the present review is to systematically present the data from case reports published in the English-language literature. Method: A comprehensive search of the literature databases (PubMed, Medline, SCOPUS, Web of Science and Google Scholar) along with the references of published articles on prosthetic rehabilitation in OSF patients published to date was conducted. Keywords included a combination of ‘Oral submucous fibrosis’, ‘prosthesis’, ‘dentures’ and/or ‘restricted mouth opening’. Citations from selected references and bibliographic linkages taken from similar cases were included in this review. The inclusion criteria selected for case reports on prosthetic rehabilitation in OSF patients, and cases of restricted mouth opening due to causes other than OSF were excluded from the study. Results: A total of 21 cases were identified and analysed from 17 papers published in the English-language literature. Of these, 9 cases employed the sectional denture technique, 4 cases emphasized the need-based treatment approach in which conventional methods were modified, and 4 cases used mouth exercising devices. Finally, 1 case each involved, flexible denture, oral screen prosthesis, oral stents, surgery in conjunction with dentures. Conclusion: Prosthetic rehabilitation in OSF patients is a multifaceted approach and should be patient specific, although sectional dentures have achieved the best results. [ABSTRACT FROM AUTHOR]

The article presents the study on myocarditis after BNT162b2 vaccination in Israeli Adolescents. It mentions that the results in cases of myocarditis that emerged during the symptomatic phase of Covid-19 rather than as adverse effects of the vaccine. The authors believe that their findings serve as an important basis for further investigation in this field.

Introduction: Any laboratory procedure exposes the technician and the pathologists to the hazardous effects of chemicals. Conventional procedures like decalcification and histoprocessing employed in laboratories are labour intense and time consuming thereby delaying the report dispatch. The present study was an attempt to employ a kitchen microwave to hasten the process and facilitate faster and accurate reporting; thus, benefitting the technician, pathologist and the patient. Aim: To compare conventional and microwave based decalcification, processing and staining of tooth and mandibular bone specimens using 5% nitric acid as decalcifying agent. Materials and Methods: The sample included formalin fixed 180 tooth specimens (60 incisors, 60 premolars, 60 molars) and 60 mandibular bone specimens (approx 0.5cm each). The hard tissue specimens were subjected to varying combination of conventional and microwave decalcification, processing and staining. The entire procedure was blinded and evaluated by two examiners. Results: Conventional Decalcification (CD), processing and staining produced the utmost quality, though consuming a relatively longer duration. Microwave reduced the total decalcification time by half and retained the diagnostic quality of the specimens. On the contrary the microwave based processing and staining caused significant damage to the tissues rendering sections un-diagnostic. Conclusion: A combination of Microwave Decalcification (MD) followed by Conventional Processing (CP) and staining would be ideal to hasten the overall laboratory time with minimal compromise on tissue quality. [ABSTRACT FROM AUTHOR]

Concurrent viral infections insist on dysregulated epigenetics of tumor suppressor genes (TSGs), cell cycle regulators, apoptosis, and autophagy-associated genes to manifest oral carcinogenesis. Autophagy has been projected as a strategic defense signaling cascade against viral entry and subsequent oral carcinogenesis. Compromised autophagy signaling during viral infection fuels oral cancer initiation and progression. The aberrant expression of autophagy genes and their encoded proteins is catalyzed by the dysregulated epigenome, legitimate epigenomic mutations, and post-transcriptional modifications such as hypermethylation, deacetylation of histone and non-histone targets, and hyperacetylation of histones that drive malignant transformation during oral carcinogenesis. Recent investigations have predicted epi-drugs (intriguingly methylation and deacetylation inhibitors and activators) as next-generation oral cancer therapeutic agents with a special notation for autophagy regulation. This review focuses on the epigenetic mediated post-transcriptional modulation of autophagy genes during viral manifested oral carcinogenesis with a distinctive perception of autophagy-modulating epi-drugs in oral cancer therapeutics. • Epigenetic dysregulation of candidate genes facilitate oral carcinogenesis. • Epigenetically dysregulated autophagy drives viral manifested oral carcinogenesis. • Autophagy modulating epi-drugs are the potent next generation chemotherapeutics. [ABSTRACT FROM AUTHOR]

Aim and objectives To report on the prevalence of 'lichenoid dysplasia' ( LD) in oral mucosal biopsies previously reported as oral lichen planus ( OLP), oral lichenoid lesion ( OLL) and oral epithelial dysplasia ( OED). Based on this case series, to postulate whether features of dysplasia are present in biopsies with a diagnosis of OLP or OLL and vice versa that warrant a separate diagnostic entity of 'lichenoid dysplasia'. Material and methods This retrospective, multicentre study was carried out by retrieving archival slides of cases diagnosed with OLP, OLL and OED. Diagnostic criteria for the study were based on published guidelines from seminal papers. A total of 165 cases, 70 OLP and OLL and 95 epithelial dysplasia cases, were re-examined. The diagnosis of OLPs and OLLs was first reconfirmed according to published diagnostic criteria. They were then verified for microscopic features of epithelial dysplasia. Among cases of leukoplakia diagnosed with epithelial dysplasia, we further verified for the presence of lichenoid features. Results A total of 70 cases of OLP and OLL were microscopically evaluated ( OLP-54; OLL-16). Epithelial dysplasia was noted in 11 cases ( OLP - 8 of 54; OLL - 3 of 16). Nineteen cases of OLP (19 of 54) were found to bear features of OLLs as per published diagnostic criteria. Among the OED group, 22 of the 95 cases showed lichenoid features. Conclusion The study confirms lichenoid features may be found in OEDs and epithelial dysplasia may be found in OLP/ OLL. We reconfirm that these microscopic features may coexist. Our findings require further discussion by a panel of experts to redefine the entity known as 'lichenoid dysplasia'. Future studies should address the concept of lichenoid dysplasia that may assist to resolve any controversies with regard to the malignant potential of OLP. [ABSTRACT FROM AUTHOR]

Background. Formalin, a traditionally preferred fixative in the field of pathology, has restricted usage in private settings. Since its toxicity violates the Occupational Safety and Health Administration regulations, an eco-friendly alternative would be the need of the hour. Hence an instant media which is economical and nontoxic and enables easy transport of biopsied soft tissue specimens in its original state is of vital importance. Materials and Methods. Commercially available fresh goat buccal mucosa specimens were sliced into smaller bits of equal dimensions and placed in six different containers containing 20% honey, 30% jaggery, milk, and ice for 1 hr, 6 hours, 12 hours, and 24 hours each with formalin as a positive control. After the set time interval, the specimens were fixed in 10% buffered formalin for 24 hours followed by routine processing and staining. The histologic interpretations were a blinded procedure and evaluated by two experts. Results were statistically analysed. Results. 30% jaggery proved to be an ideal transport media showing high quality preservation after 24 hours. 20% honey and ice showed optimal tissue preservation up to 6 hours following which quality deteriorated. Tissues transported in milk showed poor preservation. Conclusion. 30% jaggery can be endorsed in routine histopathological analysis as a transport media. [ABSTRACT FROM AUTHOR]

Background: Fixation is the essential step in histopathological processing of tissues. Since formal in is a corroborated biohazard, its routine use as a fixative is a major health and safety concern and hence the quest for safer alternatives is envisaged. Natural sweeteners like jaggery and honey have proved to be effective tissue preservatives over 24 h. This pioneer eco-idea needs further research to expand its application. Aim: (1) To evaluate the fixative property of jaggery and honey over 6 months and ascertaining the results using hematoxylin and eosin stain (H and E). (2) To evaluate the compatibility of jaggery and honey fixed tissues for special stains - Periodic acid Schiff (PAS) and Masson-Trichrome (MT). Materials and Methods: Equal bits of commercially available animal mucosae were preserved in 30% jaggery, 20% honey, and 10% buffered formalin (control) over 6 months at intervals. Following which, tissues were subjected to routine H and E, special stains - PAS and MT using standard operating procedures established in our group. Results: Formalin, jaggery, and honey yielded satisfactory results post 6 months for H and E and special stains, jaggery was comparable to formalin in tissue preservation. Conclusion: We propose the use of eco-friendly jaggery and honey as alternatives to formalin for long term tissue preservation. [ABSTRACT FROM AUTHOR]

Exosomes are subpopulations of extracellular vesicles (EVs) secreted by cells in normal or pathological conditions. From an oncological point of view, such vesicles are involved in cancer progression and may function as a therapeutic tool (based on EVs source), whose molecular signature plays a significant role in the investigation of cancer biomarkers. Recent research reveals the potential role of exosomes in anticancer drug delivery. In this article, we briefly discuss current theranostics perspectives on exosomes and their future orientation. [ABSTRACT FROM AUTHOR]

We evaluated the role of allicin in periodontitis using an in silico and in vitro design. An in silico docking analysis was performed to assess the plausible interactions between allicin and PD-L1. The cytokine profile of gingival crevicular fluid (GCF) samples obtained from periodontitis patients was estimated by cytometric bead array. CD3+ lymphocytes isolated from the peripheral blood were sorted and characterized using immunomagnetic techniques. Cultured and expanded lymphocytes were treated with the GCF samples to induce T-cell exhaustion. Optimum concentrations of allicin were added to exhausted lymphocytes to compare the expression of TIM-3 and LAG-3 gene expression at baseline and post-treatment. Allicin was found to bind to the PD-L1 molecule as revealed by the in-silico experiment, which is possibly an inhibitory interaction although not proven. GCF from periodontitis patients had significantly higher concentrations of TNF-α, CCL2, IL-6, IFN-γ, and CXCL8 than controls. GCF treatment of CD3+ lymphocytes from the periodontitis patients significantly increased expression of T-cell exhaustion markers TIM-3 and LAG-3. Allicin administration with GCF treatment resulted in significant lowering of the expression of exhaustion markers. Allicin may exert an immunostimulatory role and reverse immune-destructive mechanisms such as T-cell exhaustion. [ABSTRACT FROM AUTHOR]

Background: dental pulp-derived stem cells are easy to access and collect and are an excellent source of stem cells for regenerative therapy. These cells can interact with many biomolecules and scaffolds and can pass on the instructive signals to the sites of regeneration where they are used. In this regard cordycepin, a potential biomolecule derived from medicinal mushrooms with a spectrum of bioactive properties such as antioxidant, anti-inflammatory, and anticancer has not yet been tested for its effect on human dental pulp stem cells. Objective: the objective of the present study was to assess the in vitro adipogenic and osteogenic differentiation potential of human dental pulp stem cells with or without induction after administration of cordycepin. Materials and methods: human dental pulp stem cells DPSCs were isolated from a healthy permanent tooth extracted for orthodontic purposes after obtaining informed consent. Flow cytometry technique was used to assess the surface markers of these cells such as CD73, CD90, and CD105, CD34, CD45, and HLA-DR. Further, an MTT assay was performed on the cells after subjecting them to various concentrations of cordycepin. Following this, the adipogenic and osteogenic potential of the dental pulp stem cells was assessed with or without induction under the influence/absence of 5 µM of cordycepin. The results obtained were statistically analyzed and documented. Results: it was found that the dental pulp stem cells showed strong positive expression for CD73, CD90, and CD105 and faint expression of CD34, CD45, and HLA-DR. MTT assay revealed that 5 µM was the optimum concentration of cordycepin for all the assays. Concerning adipogenesis experiments, there was a statistically significant lowering of all the 4 adipogenesis-related genes PPARγ, FABP4, LPL, and C/EBPα following cordycepin treatment in the presence of induction compared to the only induction group and untreated control cells (p < 0.05). In connection with osteogenesis, was found that there was a statistically significant increase in the expression of RUNX2, COL1A1, OSX and OCN genes along with the increase in alkaline phosphatase and alizarin red staining in the DPSC treated with cordycepin along with the presence of induction and simultaneous addition of PDTC compared to the control untreated cells and cells treated with induction and simultaneous addition of PDTC (p < 0.05). Conclusion: cordycepin can be exploited for its osteopromotive properties and can be used as a bioactive molecule alongside the administration of dental pulp stem cells in the area of regenerative biology and medicine. [ABSTRACT FROM AUTHOR]

Paired box 9 (PAX9) gene belongs to the PAX family, which encodes a family of metazoan transcription factors documented by a conserved DNA binding paired domain 128-amino-acids, critically essential for physiology and development. It is primarily expressed in embryonic tissues, such as the pharyngeal pouch endoderm, somites, neural crest-derived mesenchyme, and distal limb buds. PAX9 plays a vital role in craniofacial development by maintaining the odontogenic potential, mutations, and polymorphisms associated with the risk of tooth agenesis, hypodontia, and crown size in dentition. The loss-of-function of PAX9 in the murine model resulted in a short life span due to the arrest of cleft palate formation and skeletal abnormalities. According to recent studies, the PAX9 gene has a significant role in maintaining squamous cell differentiation, odontoblast differentiation of pluripotent stem cells, deregulation of which is associated with tumor initiation, and malignant transformation. Moreover, PAX9 contributes to promoter hypermethylation and alcohol- induced oro-esophageal squamous cell carcinoma mediated by downregulation of differentiation and apoptosis. Likewise, PAX9 activation is also reported to be associated with drug sensitivity. In summary, this current review aims to understand PAX 9 function in the regulation of development, differentiation, and carcinogenesis, along with the underlying signaling pathways for possible cancer therapeutics. [Display omitted] • Paired box 9 (PAX9) gene plays an important role during embryogenesis and organogenesis. • Loss-of-function of PAX9 is associated with developmental abnormalities and short life span of the organism. • PAX9 maintains squamous cell differentiation and its deficiency is linked with tumor initiation and malignant transformation. • PAX9 is a potent inducer of apoptosis and drug sensitivity against malignancy-associated phenotypes. [ABSTRACT FROM AUTHOR]

Background: Ultrasonography is a non-invasive method of diagnosing periapical lesions while radiologic methods are more common. Periapical lesions due to endodontic infection are one of the most common causes of periapical radiolucency that need to be distinguished to help determine the course of treatment. This review aimed to examine the accuracy of ultrasound and compare it to radiographs in distinguishing these lesions in vivo. Methods: This review process followed the PRISMA guidelines. A literature search of databases (PubMed, Scopus, Embase, and Web of Science) was conducted without any restrictions on time. Articles available in English were included. The selection was done according to the inclusion and exclusion criteria. The QUADAS-2 tool was used to assess the quality of the studies. Results: The search provided a total of 87 articles, out of which, five were selected for the final review. In all the studies, ultrasound had higher accuracy in distinguishing periapical lesions. All the studies indicated a risk of bias, especially in patient selection. Conclusion: Within limitations, the study indicates that ultrasound is a better diagnostic tool to distinguish periapical lesions compared to radiographs but further studies with well-designed, rigorous protocols and low risk of bias are needed to provide stronger evidence. [ABSTRACT FROM AUTHOR]

The in vitro antifibrotic activity of Tinospora cordifolia (Thunb.) Miers (giloy) was assessed to explore its potential for the management of oral submucous fibrosis. Epithelial cells dissociated from the tissue obtained from histopathologically normal oral mucosa during surgical extraction of third molars were cultured and fibrosis was induced by TGF-β1 in the oral keratinocytes. Cell viability was assessed by MTT and comparative gene expression analysis was carried out in the fibrosis-induced oral keratinocytes treated with various concentrations of Tinospora cordifolia extract (TcE) for matricellular protein-related gene expression. Concentrations of 0.5 µg/mL and 1 µg/mL TcE demonstrated a significant reduction in the expression of CTGF, SERPINE1, COL1A1, FN1, MMP1, MMP2, MMP3, and TIMP2 and an increase in the expression of PLAU, COL3A1, TIMP1, and TIMP3. Although TcE was found to reduce the expression of several fibrotic genes and increase the expression of antifibrotic genes, a varied effect was found, causing increased expression of COL3A1 and decreased expression of TIMP2 on TGF-β1-induced human buccal epithelial cells. However, further studies are warranted to assess the exact mechanism of antifibrotic activity and its clinical applications. [ABSTRACT FROM AUTHOR]

We proposed to perform a comparative analysis of growth factors, cytokines, and chemokine receptors on the salivary cells in the saliva obtained from trigeminal neuralgia (TN) and normal subjects. Saliva was collected from TN and healthy subjects. Salivary cells were isolated by centrifugation. The expression of the cell surface marker was analyzed by flow cytometry. A cytometric bead array was done to measure the levels of cytokines and growth factors on the flow cytometer. Saliva from TN subjects showed lower growth factor levels of Angiopoietin-2, bFGF, HGF, SCF, TGF-α, and VEGF and higher cytokine levels of IL-1β, TNF-α, CCL2, IL-17A, IL-6, and CXCL8, as well as higher expression levels of chemokine receptors CCR1 (CD191), CR3 (CD11b), CCR2 (CD192), CXCR5 (CD185), and CCR5 (CD196) in the cells from TN saliva. A certain set of cytokines and growth factors in the saliva, as well as chemokine receptors on salivary cells, could be a useful tool in the diagnostics and prognostics of trigeminal neuralgia. Trigeminal neuralgia is one of the significant pathological conditions in the class of chronic diseases around the world. Many targeted approaches are being tried by various research groups to utilize the information of the inflammatory microenvironment to resolve the pathology of chronic TN. [ABSTRACT FROM AUTHOR]

Objective: To systematically review the clinicopathological features of oral warty keratoma based on published literature. Materials and Methods: PubMed and Scopus databases were searched for reports of oral warty dyskeratoma. Of the 52 identified articles, only 25 articles (43 cases) satisfied the selection criteria (case report/series in the English language reporting clinicopathologically diagnosed oral warty dyskeratoma/oral focal acantholytic keratosis/oral isolated dyskeratosis follicularis in humans). Risk of bias was assessed using the Joanna Briggs institute critical appraisal checklist for case reports and case series. Results: Most cases had well-circumscribed, white, nodular verruco-papillary lesions with a central depressed/crater-like area. Alveolar ridges were the most frequent sites of occurrence and tobacco was the most commonly associated risk factor. Histopathologically, the most pathognomonic feature was the supra-basal clefting. The cleft had dyskeratotic acantholytic cells (corps ronds, and grains). Below the cleft were projections of the connective tissue villi lined by basal cells. The basal cells in a few cases exhibited hyperplasia in the form of budding into the stroma, but epithelial dysplasia was not reported. The surface epithelium had crypts filled with keratin debris. Conclusion: Oral warty dyskeratoma is a rare solitary self-limiting benign entity, which due to its clinical and histopathological resemblance and associated habit history could be misdiagnosed as leukoplakia or carcinoma. None of the assessed articles provided molecular data, which in turn could be the reason for the lack of insight into the etiopathogenesis of this enigmatic lesion. [ABSTRACT FROM AUTHOR]

P-hacking or data dredging involves manipulation of the research data in order to obtain a statistically significant result. The reasons behind P-hacking and the consequences of the same are discussed in the present manuscript. [ABSTRACT FROM AUTHOR]

The wild-type SARS-CoV-2 has continuously evolved into several variants with increased transmissibility and virulence. The Delta variant which was initially identified in India created a devastating impact throughout the country during the second wave. While the efficacy of the existing vaccines against the latest SARS-CoV-2 variants remains unclear, extensive research is being carried out to develop potential antiviral drugs through approaches like in silico screening and drug-repurposing. This study aimed to conduct the docking-based virtual screening of 50 potential phytochemical compounds against a Spike glycoprotein of the wild-type and the Delta SARS-CoV-2 variant. Subsequently, molecular docking was performed for the five best compounds, such as Lupeol, Betulin, Hypericin, Corilagin, and Geraniin, along with synthetic controls. From the results obtained, it was evident that Lupeol exhibited a remarkable binding affinity towards the wild-type Spike protein (−8.54 kcal/mol), while Betulin showed significant binding interactions with the mutated Spike protein (−8.83 kcal/mol), respectively. The binding energy values of the selected plant compounds were slightly higher than that of the controls. Key hydrogen bonding and hydrophobic interactions of the resulting complexes were visualized, which explained their greater binding affinity against the target proteins—the Delta S protein of SARS-CoV-2, in particular. The lower RMSD, the RMSF values of the complexes and the ligands, Rg, H-bonds, and the binding free energies of the complexes together revealed the stability of the complexes and significant binding affinities of the ligands towards the target proteins. Our study suggests that Lupeol and Betulin could be considered as potential ligands for SARS-CoV-2 spike antagonists. Further experimental validations might provide new insights for the possible antiviral therapeutic interventions of the identified lead compounds and their analogs against COVID-19 infection. [ABSTRACT FROM AUTHOR]

• Lower doses of metformin do not affect the viability of the OSCC cells. • Metformin treatment at lower concentrations represses the gene expression of stemness related transcription factors. • Metformin treatment at the lower concentration of 25 μM decreases the expression of cancer stem cell marker CD44. Metformin, a common drug for diabetes treatment has shown promising characteristics against wide types of cancer cells in vitro as well as in vivo in the context of halted growth of cancer. But, it was unclear whether cancer stem cells are affected by the metformin treatment. Here, we attempt to find out the effect of metformin on cancer stem cell marker CD44 and stemness related transcription factors including OCT4, SOX2, NANOG, c-Myc and KLF4. We prepared single-cell suspension from primary oral tumors and subjected the cells to grow in vitro. Gene expression of transcription factors was assessed by real-time PCR. Further, the expression of CD44 was checked by flow Cytometry. Metformin showed downregulation in the gene expressions of stemness related transcription factors OCT4, SOX2, NANOG, c-Myc, and KLF4 in a dose-dependent as well as time-dependent manner. Also, the most effective concentration of metformin at 25 μM was found to decrease the expression of CD44 in the primary tumor cells in a time-dependent manner. Continuous treatment of lower concentrations of metformin decreases the expression of cancer stem cell markers at the transcription level and cancer stem cell-surface marker CD44 in primary oral cancer cells. [ABSTRACT FROM AUTHOR]

Tobacco in its smoke and smokeless form are major risk factors for esophageal squamous cell carcinoma (ESCC). However, molecular alterations associated with smokeless tobacco exposure are poorly understood. In the Indian subcontinent, tobacco is predominantly consumed in chewing form. An understanding of molecular alterations associated with chewing tobacco exposure is vital for identifying molecular markers and potential targets. We developed an in vitro cellular model by exposing non-transformed esophageal epithelial cells to chewing tobacco over an eight-month period. Chronic exposure to chewing tobacco led to increase in cell proliferation, invasive ability and anchorage independent growth, indicating cell transformation. Molecular alterations associated with chewing tobacco exposure were characterized by carrying out exome sequencing and quantitative proteomic profiling of parental cells and chewing tobacco exposed cells. Quantitative proteomic analysis revealed increased expression of cancer stem cell markers in tobacco treated cells. In addition, tobacco exposed cells showed the Oxidative Phosphorylation (OXPHOS) phenotype with decreased expression of enzymes associated with glycolytic pathway and increased expression of a large number of mitochondrial proteins involved in electron transport chain as well as enzymes of the tricarboxylic acid (TCA) cycle. Electron micrographs revealed increase in number and size of mitochondria. Based on these observations, we propose that chronic exposure of esophageal epithelial cells to tobacco leads to cancer stem cell-like phenotype. These cells show the characteristic OXPHOS phenotype, which can be potentially targeted as a therapeutic strategy. [ABSTRACT FROM AUTHOR]