In-vitro analysis on the potential use of dental pulp mesenchymal stem cells on arecoline-induced oral epithelial cells.

To assess the protective role of the secretome of dental pulp mesenchymal stem cells on arecoline-induced epithelial-mesenchymal transition and senescence on epithelial cells of the oral mucosa. Effect of varying concentrations of arecoline extract and dental pulp mesenchymal stem cell condition media (DPSC-CM) were noted on oral mucosal epithelial cells. MTT assay, Annexin V-FITC/PI assay, and the quantitative gene expressions of BCL2, PUMA, BAD, BAX, CASP3, CASP9, CASP12, TGFB1, CST3, COL1A2, COL3A1, TIMP1, TIMP2, CDH1, and CDH2 were assessed. Oral mucosal epithelial cells exposed only to the arecoline were the control. 50% and 100% DPSC-CM decreased apoptosis-related gene expression in the cells exposed with 25 µM arecoline compared to the control. 50% DPSC-CM attenuated the expression of all fibrotic genes and EMT-related genes. 20% and 100% DPSC-CM showed differential effects on fibrotic and EMT-related genes. DPSC-CM inhibited apoptosis, and attenuated expression of fibrotic and EMT-related genes on arecoline treated human oral epithelial cells.

Is Palatal Rugae Pattern a Reliable Tool for Personal Identification following Orthodontic Treatment? A Systematic Review and Meta-Analysis.

BACKGROUND: To qualitatively and quantitatively review the reliability of palatal rugae as a tool for personal identification following orthodontic treatment. METHODS: Cross-sectional retrospective studies assessing the accuracy of matching palatal rugae pattern pre- and post-orthodontic treatment were identified from PubMed and SCOPUS databases. The title and abstract of the articles identified in the search were screened for potential duplicates and relevancy to the topic of interest. The full text of the articles selected in the screening was analyzed using the inclusion and exclusion criteria. Quantitative analysis of the studies representing coherent data in terms of age and treatment choice was performed using RevMan software. RESULTS: Out of 64 screened articles, only 18 articles fulfilled the eligibility criteria and were included in the systematic review. Out of these 18 articles, only 3 studies had data compatible with the quantitative analysis. Significant changes were noted in lateral first rugae in transverse bilateral direction (p = 0.02) and between second and third lateral rugae of the left side in the anteroposterior direction (p = 0.04). Despite the dimensional changes, observers in most studies were able to accurately (>90%) match the palatal rugae pre- and post-orthodontic treatment through visual observation. CONCLUSION: The accuracy of the visual matching, despite the significant dimensional changes, indicates that morphology could have potentially been the major matching factor. Thus, a combination of dimensional and morphological evaluation of the palatal rugae could potentially increase the accuracy of personal identification.

Evaluating fluoride uptake of dentin from different restorative materials at various time intervals - In vitro study.

BACKGROUND: Glass ionomer cement is very popular in clinical practice due to their antibacterial and cariostatic properties, which is totally dependant on the amount of fluoride release and uptake by dentine. The short-term and long-term fluoride uptake by dentine from commercially available restorative materials like nano-ionomer, zirconia reinforced glass ionomer cement and flowable composite is of clinical interest. OBJECTIVE: To evaluate and compare Nano-ionomer, Zirconia reinforced glass ionomer, and flowable composite resin for the fluoride uptake by dentin at different time intervals. RESULTS: One-way ANOVA (Tukey-Kramer Multiple Comparison Test) was applied to test the comparison of mean values of all parameters compared together. The student's paired 't' test was applied to compare groups. The fluoride uptake was evaluated at 3 days and 42 days. At 3 days dentin showed higher fluoride uptake with Zirconomer (Group Z) as compared to Ketac N100 and SDR Composite which was statistically significant. At 42 days higher fluoride uptake was seen in Ketac N100 (Group K) as compared to Zirconomer and SDR composite which was also statistically significant. CONCLUSION: Fluoride uptake by dentine was seen in all study materials. Fluoride uptake by dentine at 3 days was seen maximum in Zirconomer, whereas fluoride uptake at 42 days was more in Ketac N100.

Melatonin levels in periodontitis vs. the healthy state: A systematic review and meta-analysis.

The aim was to provide a comprehensive qualitative and quantitative assessment of any potential differences in melatonin levels in periodontitis vs. the healthy state. The keyword combination "melatonin" AND "periodontitis" was searched in Web of Science, PubMed, and Scopus. Qualitative analysis and quantitative analysis were performed on articles satisfying the inclusion criteria. Only 14 studies were included in the systematic review, out of which only 10 had quantitative data compatible with a meta-analysis. Ten studies demonstrated low melatonin in periodontitis, three studies demonstrated an initial reduction in melatonin levels followed by elevation with worsening of periodontitis, and one study showed an elevation in melatonin levels in the transition from a healthy state to periodontitis. Grading of recommendations assessment, development, and evaluation revealed that all the included studies had low to very low overall evidence. The meta-analysis revealed a significant reduction (p < .0001) in salivary melatonin levels in chronic periodontitis (3.26 ± 3.44 pg/ml) compared with healthy controls (5.27 ± 5.39 pg/ml), with a mean difference of 2.65 ± 7.84 and a confidence interval of 1.94-3.36. The significantly lower salivary melatonin levels in periodontitis must be inferred with caution given the low quality of the included studies.

Melatonin as a Topical/Systemic Formulation for the Management of Periodontitis: A Systematic Review.

OBJECTIVES: To qualitatively and quantitatively review the use of melatonin as a topical/systemic formulation for the management of periodontitis. MATERIALS AND METHODS: PubMed; Scopus; and Web of Science databases were searched using the MesH terms "melatonin" and "periodontitis". Title and abstracts were screened to eliminate irrelevant and duplicate articles. The full text data of the screened articles were assessed using the selection criteria. RESULTS: Of 176 identified articles (PubMed-66; Scopus-56; Web of Science-52; Cross-reference-2), only 12 studies qualified to be included in the systematic review. Four studies assessed the independent effect of 1% topical melatonin formulation while 8 articles assessed the adjunctive use of systemic melatonin formulation (1-10 mg) following scaling and root planing (SRP). All studies showed an improvement in periodontal parameters such as pocket depth, clinical attachment loss, periodontal disease index, community periodontal index, gingival bleeding scores, and prognostic marker levels in saliva and serum. A meta-analysis of data from 2 studies revealed that 1-2 mg (systemic) melatonin supplementation reduced pocket depth; although the difference was not statistically significant and hence cannot be interpreted or used for conclusive evidence. Risk of Bias Assessment tool (RoBANS) and Cochrane Collaboration RoB tool elicited a high risk of bias in the included studies. GRADE (recommendation assessment, development, and evaluation) inferred a weak recommendation for the use of melatonin in periodontitis management. CONCLUSIONS: Melatonin supplementation (topical and systemic) in periodontitis patients improved key periodontal parameters including pocket depth and clinical attachment loss. CLINICAL RELEVANCE: Melatonin could be a potential host modulatory agent for periodontitis management; although the data from the present review should be interpreted carefully due to the associated high risk of bias.

Reply to the letter regarding "Chronic mechanical irritation and oral squamous cell carcinoma: A systematic review and meta-analysis".

Dear Editor, We thank Dr. Jian Xie for the valuable inputs on our paper titled 'Chronic mechanical irritation and oral squamous cell carcinoma: A systematic review and meta-analysis [1].' The first concern of Dr. Xie was that we had included two studies that were based on the same population. We re-examined these papers, one was published in 2010 [2] and the other in 2017 [3] by the same group of authors. Given the significant time difference between the two papers, we did not want to presume they were from the same sample population. There is no clear evidence that they are from the same sample population. Read more in PDF.

Genetic Mutations Associated with Pierre Robin Syndrome/Sequence: A Systematic Review.

Pierre Robin syndrome/sequence (PRS) is associated with a triad of symptoms that includes micrognathia, cleft palate, and glossoptosis that may lead to respiratory obstruction. The syndrome occurs in 2 forms: nonsyndromic PRS (nsPRS), and PRS associated with other syndromes (sPRS). Studies have shown varying genetic mutations associated with both nsPRS and sPRS. The present systematic review aims to provide a comprehensive collection of published literature reporting genetic mutations in PRS. Web of Science, PubMed, and Scopus were searched using the keywords: "Pierre Robin syndrome/sequence AND gene mutation." The search resulted in 208 articles, of which 93 were excluded as they were duplicates/irrelevant. The full-text assessment led to the further exclusion of 76 articles. From the remaining 39 articles included in the review, details of 324 cases were extracted. 56% of the cases were sPRS, and 22% of the cases were associated with other malformations and the remaining were nsPRS. Genetic mutations were noted in 30.9% of the 300 cases. Based on the review, SOX9 was found to be the most common gene associated with both nsPRS and sPRS. The gene mutation in sPRS was specific to the associated syndrome. Due to the lack of original studies, a quantitative analysis was not possible. Thus, future studies must focus on conducting large-scale cohort studies. Along with generating data on genetic mutation, future studies must also conduct pedigree analysis to assess potential familial inheritance, which in turn could provide valuable insights into the etiopathogenesis of PRS.

Chronic mechanical irritation and oral squamous cell carcinoma: A systematic review and meta-analysis.

The objective of the present article was to qualitatively and quantitatively review the association between chronic mechanical irritation and oral squamous cell carcinoma (OSCC). PubMed, SCOPUS, and Web of Science databases were searched using the keyword combinations "chronic trauma and oral squamous cell carcinoma; chronic irritation and oral squamous cell carcinoma; chronic irritation and oral cancer; and chronic trauma and oral cancer." Duplicates and irrelevant articles were excluded after the title and abstract screening. The full texts of the remaining articles were assessed using selection criteria. A total of 375 (PubMed-126; SCOPUS-152; WOS-97) articles were screened, and 343 duplicates and irrelevant articles were excluded from the study. Only 9 of the remaining 32 articles met the selection criteria and were included in the qualitative analysis. Buccal mucosa and tongue, being highly prone to chronic irritation through the dental prosthesis, were the common sites for OSCC. Edentulous subjects with ill-fitting dentures were at a high risk of developing chronic irritation associated-OSCC. According to the Joanna Briggs Institute of risk assessment, eight of the nine included studies had a low risk of bias. The quantitative analysis showed a significant association (p < 0.00001) between the chronic oral mucosal irritation and OSCC with an overall risk ratio of 2.56 at a confidence interval of 1.96-3.35. Chronic oral mucosa irritation has a significant association with OSCC, and the nature of association could be that of a potential co-factor (dependent risk factor) rather than an independent risk factor.

Assessing the potential use of chitosan scaffolds for the sustained localized delivery of vitamin D.

Vitamin D is a commonly used bone modulator in regenerative medicine. Several modalities have been explored for the delivery of vitamin D including nanoparticles and scaffold. The present study aimed to assess the potential use of a bio-degradable chitosan scaffold for the delivery of vitamin D. The objectives included fabrication of a bio-degradable chitosan scaffold, integration of vitamin D into the scaffold, characterization of the vitamin D integrated scaffold. Characterization was carried out using, X-ray diffraction, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The structure of the scaffold was assessed by scanning electron microscopy. The scaffold was placed in phosphate buffer saline and the release duration of vitamin D was observed using UV spectrophotometry. Dental pulp mesenchymal stem cells were added to the scaffold to study the scaffold associated toxicity and the functionality of the scaffold released vitamin D. The vitamin D release period from the scaffold was estimated to be for 80 hrs. MTT assay of the stem cells was comparable to that of the control group (stem cells cultured in media) inferring that the scaffold is not toxic towards the stem cells. The positive alizarin red S staining, a higher expression of alkaline phosphatase, osteocalcin, and RunX2 confirmed the functional capability (osteogenic differentiation of the stem cells) of the released vitamin D. Based on the data from the present study, it can be inferred that chitosan scaffold can be used for the sustained delivery of functional vitamin D for 3-5 days.

Oral candidiasis in human immunodeficiency virus-infected patients under highly active antiretroviral therapy.

Human immunodeficiency virus has plagued mankind since the 1980's when the first case was documented. Human immunodeficiency virus-induced immunocompromised state can lead to several systemic and local manifestations, which often culminates in mortality. Oral candidiasis was one of the most prevalent opportunistic infections noted in human immunodeficiency virus-infected patients. The advent of highly active antiretroviral therapy has led to a significant reduction in both the mortality and the morbidity of infected patients. The combined antiretroviral therapy has also led to a decrease in the incidence of opportunistic infections including oral candidiasis. Thus, the presence of well-established oral candidiasis in human immunodeficiency virus-infected patients under highly active antiretroviral therapy could be considered as an indicator of potential treatment failure. The present manuscript aims to review the published literature assessing the effect of highly active antiretroviral therapy on the incidence of oral candidiasis in human immunodeficiency virus-infected patients.

Assessing the effect of human mesenchymal stem cell-derived conditioned media on human cancer cell lines: A systematic review.

BACKGROUND: Mesenchymal stem cells (MSCs) exhibit differential effect (augmentation or inhibition) on cancer cells depending on the tissue of origin. Given the increasing demand to use MSCs in regenerative medicine, it is vital to ensure that the MSCs being employed are not pro-carcinogenic. OBJECTIVE: To assess the effect of human MSC derived conditioned media (CM) on human cancer cell lines. MATERIALS AND METHODS: PubMed, SCOPUS, and Web of Science were searched using the keyword combination 'human mesenchymal stem cell and conditioned media and human cancer cell line and in-vitro'. RESULTS: MSC-CM pro-carcinogenic molecules were IL-6, IL-8, FGF10, VEGF, PDGF, TGF-b1, IGF-1, GRO-a, OSP, MMPs, TNFα, IL-4, IL-10, IL-13, IL-17, IL-1 ß, G-CSF, MCP­1, MIP­1α, MIP­1ß, RANTES, MIG, IP­10, HGFa, ETX, DKK1; anti-carcinogenic molecules were IFN-ß, OST, LIGHT, FRTK3, INF-γ, IP-10, LAP, IL­1RA, IL­2, IL-5, IL-7, IL-12, IL-15, IFN-α, IFN­Î³. Effector pathways were STAT 1, JAK2/STAT3, Ras-Raf-MEK-ERK, Wnt/ß-catenin, NF-κB, ERK1/2, PI3K/ Akt/mTOR, MAPK/ERK. BMSC, ADMSC, UCMSC, WJMSC DPMSC, AMSC, and UTCMSC had a differential effect on carcinogenesis. GMSC, LMSC, FDMSC were anti-carcinogenic. OMSC was pro-carcinogenic. CONCLUSION: Use of MSC-CM with a pro-carcinogenic effect must be restricted in cancer patients irrespective of the nature of the application.

Hypothesizing the therapeutic potential of mesenchymal stem cells in oral submucous fibrosis.

Oral submucous fibrosis is the direct consequence of a sustained pro-inflammatory environment characterized by excessive collagen deposition causing tissue fibrosis, and progressive degeneration of vital structures including muscle. The pathogenesis of oral submucous fibrosis is largely mediated by the pro-inflammatory, pro-fibrotic cytokines, excessive oxidative stress, abnormal angiogenesis, and epithelial to mesenchymal transition. Mesenchymal stem cells largely known for their regenerative potential have shown to have an immunomodulatory, anti-fibrotic, anti-oxidative, and angiogenic potential. Thus, mesenchymal stem cells, when introduced in an oral submucous fibrosis micro-environment, could potentially counter the progressive fibrosis. The present hypotheses discuss the various pathogenic aspects of oral submucous fibrosis and the properties of mesenchymal stem cells which could aid in halting the disease progression.

Efficacy of scaffold-mediated localized chemotherapy in cancer: A systematic review of current research.

OBJECTIVE: To assess the efficacy of scaffold-mediated localized chemotherapy in cancer. METHODS: Databases including PubMed, Cochrane Library, and SCOPUS were searched for articles reporting the use of scaffold-mediated localized drug delivery in cancer. Essential data including scaffold fabrication material and methods, drug dosage and release duration and its effect on the cancer cells were extracted. RESULTS: 15 articles out of 60 screened, fulfilled the eligibility criteria. Among the 15 studies, 5 studies included only cell lines and 2 studies were on mouse models, while 8 studies involved a combination of cell lines and mouse models. Scaffold materials included both synthetic polymers such as poly-lactide, polycaprolactone and natural materials including d-periosteum and human micro-fragmented adipose tissueA wide number of other variables included the fabrication procedure, drugs used, and the methods used to assess the effects on cancer. As a result, it was not possible to make any direct comparison of the efficacy of the therapeutic strategy used in each of these studies. CONCLUSION: Irrespective of the many variables, a common consensus in all the included studies was that scaffold mediated localized drug delivery effectively reduced cancer cell viability by increasing drug bioavailability to the target tissue, while its localized effect reduced the risk of systemic toxicity.

Assessing the potential association between Epstein-Barr virus and oral squamous cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: This study aims to qualitatively and quantitatively review the association between Epstein-Barr virus (EBV) and oral squamous cell carcinoma (OSCC). METHODS: PubMed, Scopus, and Web of Science databases were searched using the keywords "EBV or Epstein Barr virus and Oral cancer or Oral squamous cell carcinoma" for published case-control studies in the English language upto August 2019. RESULTS: The search yielded 985 articles out of which 966 articles were excluded by screening their titles and abstracts as they were irrelevant or duplicates. Based on the full-text assessment of the remaining 19 articles, only 7 satisfied the inclusion criteria and were included in the qualitative analysis, out of which only 4 were compatible to be included in the meta-analysis. The diagnostic modalities used included immunohistochemistry, in situ hybridization and polymerase chain reaction. The diagnostic targets included latent membrane protein (LMP)-1, EBV determined nuclear antigen-1, EBV-encoded small non-polyadenylated RNA-2. The meta-analysis showed that there is an association between the EBV and OSCC. CONCLUSIONS: Determining the association of EBV with OSCC is highly tedious due to the contrasting data obtained from individuals' studies which in turn is due to the wide variations in the sensitivity and specificity of the diagnostic modalities used and diagnostic targets selected. Although the meta-analysis revealed an association between EBV and OSCC, the number and the quality of the studies included in the meta-analysis are limited, thus the association requires further validation for any conclusive inference.

Assessing the nature of the association of human papillomavirus in oral cancer with and without known risk factors.

BACKGROUND: Published studies assessing the association of human papillomavirus (HPV) and oral cancer, often include cases with additional confounders such as alcohol, tobacco, thus, precluding the assessment of HPV as a independent risk factor. Further apart from eliciting the mere presence of HPV, it is vital that the nature of the association is delineated for eliciting a causal inference. Thus, the present study assessed the presence and nature of the association of HPV in oral cancer cases with and without known risk factors. METHODS: The study compares the prevalence of HPV in oral cancer cases with known risk factors (group 1, n=15) to oral cancer (group 2, n=15) and oral epithelial dysplasia (group 3, n=15) cases with no known risk factors using PCR. Cases which are positive for HPV were subjected to p16 and p53 immunostaining to determine potential causal inference. RESULTS: HPV 16 was detected in only 1 case of group I, 3 cases of group II, and was absent in group III. HPV 18 was negative in all the 3 groups. All the HPV positive cases were negative for p16 and positive for p53 immunostaining. CONCLUSIONS: Only a minor proportion of oral cancer cases without risk factors were positive for HPV 16. Even among these HPV 16 positive cases, the immunostaining profile (p53 positive and p16 negative) excludes the involvement of E6 and E7 mediated carcinogenesis. Thus even the weak HPV association noted in the present study cases may not be of causal nature.

Intrastromal bevacizumab in the management of corneal neovascularization: a retrospective review.

PURPOSE: To evaluate the long-term safety and efficacy of intrastromal bevacizumab for treatment of deep corneal neovascularization in candidates for high-risk cornea grafting. METHODS: A single-center retrospective study involving 14 eyes of 14 patients with chronic deep corneal neovascularization, treated with intrastromal bevacizumab by a single provider from 2011 to present. Intrastromal bevacizumab (0.05-0.1 mL of 2.5 mg/0.1 mL) was administered every 4-8 weeks. On average 1-3 intrastromal injections were performed prior to corneal grafting (penetrating keratoplasty or deep anterior lamellar keratoplasty). RESULTS: 64.2% patients had neurotrophic keratitis secondary to herpes zoster or simplex. Neovascularization was encroaching the visual axis in 50% and was paracentral in 42.8%. After intrastromal bevacizumab injection, 14.2% had complete regression of neovascularization, avoiding the need of future corneal transplant. Persistent neovascularization was noticed in 21.4%. Successful penetrating keratoplasty was performed in 57% of patients. Minimal adverse effects were noted; temporary epithelial defect was seen in two eyes and self-limited intrastromal hemorrhage in one. There was no evidence of recurrence of neovascularization or graft rejection in the transplant group (mean follow-up 3 years). CONCLUSION: Intrastromal bevacizumab appears to be a safe and effective modality in the treatment of chronic corneal neovascularization, producing durable regression of corneal neovascularization and allowing for durable success of subsequent corneal transplants in high-risk patients.

Association of Helicobacter pylori with oral potentially malignant disorders and oral squamous cell carcinoma-a systematic review and meta-analysis.

OBJECTIVE: To assess any potential association between Helicobacter pylori and oral squamous cell carcinoma/oral potentially malignant disorders. MATERIALS AND METHODS: Data mining was done using PubMed, Cochrane Library, and SCOPUS databases. The search included articles published up to May 2019. Newcastle-Ottawa scale was used to score the quality of the included articles. Data including the type of study, the sample population, the type of oral lesion, and the resulting statistical data were extracted. RESULTS: Out of 131 screened articles, only 15 articles fulfilled the eligibility criteria. Among the 15 studies, 9 focused on oral squamous cell carcinoma and 6 focused on oral potentially malignant disorders. Eight out of the 9 oral squamous cell carcinoma studies were included in the meta-analysis. Forest plot was generated using the odds ratio and confidence intervals calculated for each of the included studies. Due to the lack of sufficient studies, the meta-analysis was not performed for oral potentially malignant disorders. CONCLUSION: Due to the contradictory results of the included studies, it was not possible to make any conclusive statement on the potential association of H. pylori with oral squamous cell carcinoma. The variations in the methodology, especially the differences in the sensitivity/specificity of the diagnostic modalities could be the cause for differential results. CLINICAL RELEVANCE: Although the association of H. pylori with oral squamous cell carcinoma could not be confirmed, it is vital to reduce the excess oral microbial load, especially in patients exhibiting oral mucosal changes with no history of associated risk factors.

Assessing the effect of ceramic additives on the physical, rheological and mechanical properties of conventional glass ionomer luting cement - An in-vitro study.

AIM: To evaluate the effect of the addition of conventional ceramics on the physical, rheological and mechanical properties of conventional glass ionomer luting cement. MATERIALS AND METHODS: 5%, 10%, 15% and 20% (w/w) of Enamel and Body conventional ceramic additives (E44 Enamel and B96/c4 Body) were reinforced in the two commercially available glass ionomer luting cement - GC Fuji I (GC Corporation Tokyo, Japan) and Ketac Cem Radiopaque (3M ESPE AG). Setting time, film thickness and compressive strength of the cement was measured according to the American Dental Association Specification number 96 for luting cement. Enthalpy change of the cement reaction was measured with the help of Differential Scanning Calorimetry analysis. Compatibility between the sizes of powder particles was measured with the help of a particle size analyzer. RESULTS: 5% of ceramic additive could not improve much of the compressive strength. Compressive strength increased significantly (p < 0.05) with the addition of 10% of ceramic additive, beyond which, there was a gradual decrease in strength. Although the setting time and film thickness were also shown to increase due to the additive, the former did not exceed the limit specified by the American Dental Association Specification number 96 (2-8 min for setting time and 25 microns for film thickness). CONCLUSION: Addition of 10% of conventional ceramics resulted in a significant increase in the compressive strength of GIC Luting Cement without any significant compromise in its setting time. The substantial increase in film thickness is a major limitation. Use of ceramic additives with physical properties compatible with that of the glass ionomer cement may aid in increasing the compressive strength without compromising its setting time or film thickness.