Publications by authors named "Shankargouda Patil"

412 Publications

Angiogenesis induction in breast cancer: A paracrine paradigm.

Cell Biochem Funct 2021 Sep 9. Epub 2021 Sep 9.

Department of Stem Cell and Regenerative Medicine, D. Y. Patil Education Society, Kolhapur, India.

Breast cancer is the most prevalent type of cancer among women globally. Angiogenesis contributes significantly to breast cancer progression and dissemination. Neovascularization is concurrent with the progression and growth of breast cancer. Breast cancer cells control angiogenesis by secreting pro-angiogenic factors like fibroblast growth factor, vascular endothelial growth factor, interleukin, transforming growth factor-β, platelet-derived growth factor and several others. These pro-angiogenic factors trigger neovascularization, and thereby lead to breast cancer development and metastasis. The hypoxia-inducible factor (HIF)-regulated angiogenesis cascade is a crucial underlying factor in breast cancer growth and metastasis. To that end, several efforts have been made to identify druggable targets within the HIF-angiogenesis components. However, escape pathways are a major hindrance for targeted therapies against angiogenesis. Thus, understanding the key factors that trigger breast cancer angiogenesis is critical in elucidating ways to inhibit breast cancer. The current review provides an overview of the key growth factors that trigger breast cancer angiogenesis.
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http://dx.doi.org/10.1002/cbf.3663DOI Listing
September 2021

Allicin May Promote Reversal of T-Cell Dysfunction in Periodontitis via the Pathway.

Int J Mol Sci 2021 Aug 25;22(17). Epub 2021 Aug 25.

Department of Oral Pathology and Microbiology, Sri Venkateswara Dental College and Hospital, Chennai 600130, India.

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 . 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 and gene expression at baseline and post-treatment. Allicin was found to bind to the 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 and . 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.
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http://dx.doi.org/10.3390/ijms22179162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431528PMC
August 2021

The Expression of Allele Changes in NLRP3 (rs35829419) and IL-1β (+3954) Gene Polymorphisms in Periodontitis and Coronary Artery Disease.

Materials (Basel) 2021 Sep 6;14(17). Epub 2021 Sep 6.

Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan 45142, Saudi Arabia.

Background: Inflammasomes have been shown to play a pivotal role in periodontal disease pathogenesis. However, their role in periodontitis subjects with coronary heart disease remains unclear. This study aimed to obtain the expression of NLRP3 (rs35829419) and IL-1β (+3954) gene polymorphisms in the subgingival plaque and blood samples of generalized periodontitis (GP) subjects with and without coronary heart disease (CHD).

Methods: A total of 70 subjects were grouped into two; GP and GP with CHD. Demographic variables and periodontal and cardiac parameters were recorded from both the groups. Subgingival plaque and blood samples were obtained from both the groups and were further subjected to the identification of NLRP3 (rs35829419) and IL-1β (+3954) expression and allele change using a conventional polymerase chain reaction (PCR) and gene sequencing (Sanger's method).

Results: Amongst the demographic variables, age and monthly income were statistically significant between the two groups. Plaque index (PI), clinical attachment level (CAL), high-density lipoprotein (HDL), and low density-lipoprotein (LDL) exhibited statistically significant levels between the two groups. The NLRP3 (rs35829419) and IL-1β (+3954) genes showed a statistically significant association with allele change (frequency) among the groups. The general comparison of all the parameters with the allele change of NLRP3 (rs35829419) and IL-1β (+3954) in the subgingival plaque and blood samples showed statistically significant associations among the two groups.

Conclusion: The present study highlighted an allele change in IL-1β (+3954) gene polymorphisms which may play an important role in the pathogenesis of periodontitis and coronary heart disease.
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http://dx.doi.org/10.3390/ma14175103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433916PMC
September 2021

Recent progress of autophagy signaling in tumor microenvironment and its targeting for possible cancer therapeutics.

Semin Cancer Biol 2021 Sep 6. Epub 2021 Sep 6.

Cancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, Rourkela 769008, Odisha, India. Electronic address:

Autophagy, a lysosomal catabolic process, involves degradation of cellular materials, protein aggregate, and dysfunctional organelles to maintain cellular homeostasis. Strikingly, autophagy exhibits a dual-sided role in cancer; on the one hand, it promotes clearance of transformed cells and inhibits tumorigenesis, while cytoprotective autophagy has a role in sustaining cancer. The autophagy signaling in the tumor microenvironment (TME) during cancer growth and therapy is not adequately understood. The review highlights the role of autophagy signaling pathways to support cancer growth and progression in adaptation to the oxidative and hypoxic context of TME. Furthermore, autophagy contributes to regulating the metabolic switch for generating sufficient levels of high-energy metabolites, including amino acids, ketones, glutamine, and free fatty acids for cancer cell survival. Interestingly, autophagy has a critical role in modulating the tumor-associated fibroblast resulting in different cytokines and paracrine signaling mediated angiogenesis and invasion of pre-metastatic niches to secondary tumor sites. Moreover, autophagy promotes immune evasion to inhibit antitumor immunity, and autophagy inhibitors enhance response to immunotherapy with infiltration of immune cells to the TME niche. Furthermore, autophagy in TME maintains and supports the survival of cancer stem cells resulting in chemoresistance and therapy recurrence. Presently, drug repurposing has enabled the use of lysosomal inhibitor-based antimalarial drugs like chloroquine and hydroxychloroquine as clinically available autophagy inhibitors in cancer therapy. We focus on the recent developments of multiple autophagy modulators from pre-clinical trials and the challenges in developing autophagy-based cancer therapy.
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http://dx.doi.org/10.1016/j.semcancer.2021.09.003DOI Listing
September 2021

Prevalence of Trismus and Its Impact on Oral Health-Related Quality of Life in Patients Treated for Oral Squamous Cell Carcinoma.

Asian Pac J Cancer Prev 2021 Aug 1;22(8):2437-2444. Epub 2021 Aug 1.

Department of Community Dentistry and Oral Epidemiology, College of Dentistry, Qassim University, Buraydah, Kingdom of Saudi Arabia.

Oral squamous cell carcinoma, one of the most common malignancies, has a poor prognosis due to impairment in oral functions secondary to treatment. Trismus one of the major causes of impairment of oral function. The present study investigated the prevalence of trismus and its impact on oral health-related quality of life (OHRQoL) in patients treated for oral squamous cell carcinoma (OSCC). The maximum inter-incisal mouth opening of hundred OSCC patients was recorded at post-treatment and 3 months post-treatment. OHRQoL questionnaire (OHIP-14) was intervened to assess the OHRQoL of patients post-treatment and 3 months follow-up, with emphasis on correlation with grades of trismus. The prevalence of trismus was 16% pre-treatment, 72% post-treatment, and 62% at 3 months after treatment. The overall OHIP-14 scores indicated that patients with trismus reported greater impairment of OHRQoL than those without trismus at the end of treatment and 3 months follow-up. At the end of treatment, patients with severe trismus demonstrated a higher mean OHIP-14 score (23.47 ±3.34) than those with moderate (17.72 ±2.83) and mild trismus (12.66 ±3.84) with statistically significant differences (p <0.001). Equivalent results were obtained at 3 months follow-up period. Patients with trismus suffer greater impairment of OHRQoL. The findings demand the need of identifying risk factors for developing trismus and early institution of newer/modified treatment approaches for better OHRQoL in OSCC survivors.
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http://dx.doi.org/10.31557/APJCP.2021.22.8.2437DOI Listing
August 2021

Role of Periodontal Bacteria, Viruses, and Placental in Chronic Periodontitis and Preeclampsia-A Genetic Microbiological Study.

Curr Issues Mol Biol 2021 Jul 29;43(2):831-844. Epub 2021 Jul 29.

Division of Oral Pathology, Department of Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia.

Previous studies assessed the involvement and impact of periodontal bacteria in preeclamptic women with chronic periodontitis. To explore further, the current study aimed to associate periodontal viruses and bacteria with levels in placental tissues of preeclamptic women with generalized chronic periodontitis. Four-hundred 45 pregnant women, 18-35 years of age, were selected and divided into four groups (controls, A, B, and C) where the Controls included 145 systemically and periodontally healthy pregnant women Group A-100 systemically healthy pregnant women with chronic periodontitis, Group B- 100 preeclamptic women with chronic periodontitis, Group C- 100 preeclamptic women without chronic periodontitis. Age, BMI, SES, and periodontal parameters such as PI, BOP, PPD, and CAL were noted. Periodontal pathogens such as , HSV, EBV, and HCMV were tested in subgingival plaque, placental tissues, and mir155. We observed that PI, BOP, PPD, CAL, and EBV were highly significant in Group B. We found a higher number of periodontal bacteria, viruses, and 155 in Group B showing a higher risk of preeclampsia. More genetic studies in this field are advised to ascertain the role of periodontopathogens and 155 in preeclampsia and periodontal inflammation. What is already known on this subject? Periodontal diseases pose an increased risk of developing preeclampsia and delivering preterm and/or low-birth-weight babies. What do the results of this study add? Periodontal variables such as PI, pocket depth, BOP, and clinical attachment levels, were found to be increased in the preeclamptic women with chronic periodontitis. The significant difference was seen in the relative fold expression of mir155 with higher gene expression of mir155 in groups B and A as compared to group C and controls. What are the implications of these findings for clinical practice and/or further research? In our study, 155 correlation with the periodontal parameters and periodontal pathogens further strengthen the evidence of periodontal inflammation as a risk of preeclampsia in pregnant women especially when associated with chronic periodontitis. 155 can be considered to be one of the genetic biomarkers and can be used as a diagnostic tool for the early detection of PE.
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http://dx.doi.org/10.3390/cimb43020060DOI Listing
July 2021

miRNA-146a and miRNA-126 as Potential Biomarkers in Patients with Coronary Artery Disease and Generalized Periodontitis.

Materials (Basel) 2021 Aug 20;14(16). Epub 2021 Aug 20.

Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan 45142, Saudi Arabia.

The present study aims to compare the levels of micro-RNA-146a and micro-RNA-126 in oral subgingival plaque and coronary plaque from artery walls in patients with coronary artery disease who suffer from generalized periodontitis. A total of 75 participants were selected and grouped into three categories of 25 patients each: GP+CAD, GP, and HP groups. GP+CAD consisted of patients diagnosed with generalized periodontitis (GP) and coronary artery disease (CAD). The GP+CAD group was further divided into two groups-GP+CADa: where subgingival plaque samples were collected; GP+CADb group: where coronary plaque samples were collected while the patient underwent a coronary artery bypass grafting surgery. The GP group consisted of 25 patients diagnosed with only generalized periodontitis. The HP group consisted of 25 systemically and periodontally healthy controls. miRNA-146a and miRNA126 levels were assessed in subgingival plaque (SP) samples from all groups. Results revealed that miRNA-146a was expressed at higher levels and miRNA-126 was downregulated in the GP+CAD group. microRNAs in subgingival plaque samples showed a significant correlation with the coronary plaque samples in the GP+CAD group. miRNA-146a and miRNA-126 were present in coronary artery disease patients with periodontitis. These micro-RNAs may serve as risk biomarkers for coronary artery disease and generalized periodontitis.
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http://dx.doi.org/10.3390/ma14164692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398247PMC
August 2021

Dose-Dependent Effect of Cordycepin on Viability, Proliferation, Cell Cycle, and Migration in Dental Pulp Stem Cells.

J Pers Med 2021 Jul 26;11(8). Epub 2021 Jul 26.

Division of Oral Pathology, Department of Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry Jazan University, Jazan 45142, Saudi Arabia.

Objective: To examine the effect of Cordycepin on the viability, proliferation, and migratory properties of dental pulp-derived mesenchymal stem cells.

Materials And Methods: The pulp was derived from human premolar teeth extracted for orthodontic purposes after obtaining informed consent. The samples were transferred to the laboratory for processing. DPSCs were expanded and characterized using flow cytometry and differentiation to the bone, adipose, and cartilage cells was examined. MTT Assay was performed using various concentrations of Cordycepin. The growth curve was plotted for 13 days. Cell cycle analysis was performed by flow cytometry. Migratory ability was assessed by wound healing assay. ROS generation was detected by flow cytometry. Gene expression was quantified by RT-qPCR. Statistical analysis was performed. < 0.05 was considered as significant and < 0.01 was considered as highly significant (* < 0.05, and ** < 0.01).

Results: DPSCs expressed characteristic MSC-specific markers and trilineage differentiation. Cordycepin at lower concentrations did not affect the viability of DPSCs. The growth curve of cells showed a dose-dependent increase in cell numbers till the maximum dose. DPSCs treated with 2.5 µM Cordycepin was found to have a reduced G1 phase cell percentage. DPSCs treated with 2.5 µM and 5 µM Cordycepin showed a significant decrease in G2 phase cells. No significant difference was observed for S phase cells. Cordycepin treatment affected the migratory ability in DPSCs in a concentration-dependent manner.

Conclusion: Cordycepin can be used at therapeutic doses to maintain stem cells.
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http://dx.doi.org/10.3390/jpm11080718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398271PMC
July 2021

Taurodontism in maxillary and mandibular molars using cone beam computed tomography in a dental center in Saudi Arabia.

Ann Saudi Med 2021 Jul-Aug;41(4):232-237. Epub 2021 Aug 22.

From the Department of Maxillofacial Surgery and Diagnostic Sciences, Faculty of Dentistry, Jazan University, Jazan Saudi Arabia.

Background: Taurodontism is a dental anomaly characterized by altered crown root ratio that is often diagnosed by radiographic evaluation. A three-dimensional cone beam computed tomography (CBCT) can aid in the diagnosis and treatment of taurodontic teeth. Only one study has reported the prevalence of taurodontism in a Saudi population.

Objective: Determine prevalence and other characteristics of taurodontism in permanent maxillary and mandibular molars, by CBCT in a dental center in Saudi Arabia.

Design: Cross-sectional.

Setting: College of dentistry.

Subjects And Methods: The first and second molars, maxillary and mandibular, from study participants of Saudi origin from Jazan region of Saudi Arabia were evaluated for taurodontism based on the criteria of Shifman and Chanannel. The degree of taurodontism was determined by the taurodontism index. Results were tabulated for analysis and the chi-square test was applied for the differences between age groups, genders, and maxillary and mandibular teeth.

Main Outcome Measures: Characteristics of taurodontism.

Sample Size: 1839 teeth in 300 individuals.

Results: Taurodontism was seen in 24 (8%) of the study participants and in 71 teeth (3.9%). Taurodontism was significantly more prevalent in individuals between 21 and 40 years of age. Hypotaurodontism (67.6%, n=48) was most prevalent, followed by mesotaurodontism (23.9%, n=17) and hypertaurodontism (8.5%, n=6). The maxillary molars were more commonly involved than mandibular, but the results were not statistically significant. No significant differences in gender were observed.

Conclusions: Dental clinicians should be familiar with the condition due to the clinical implications in oral surgery, endodontics and prosthodontics. The possibilities of a complex root canal system, an additional canal, difficulties in canal negotiation, instrumentation and subsequent obturation can be challenging for the clinician.

Limitations: Conducted in a single dental center hence future studies with larger sample sizes in different regions of Saudi Arabia should be conducted to more accurately measure the prevalence.

Conflicts Of Interest: None.
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http://dx.doi.org/10.5144/0256-4947.2021.232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380279PMC
September 2021

Metformin pre-conditioning enhances the angiogenic ability of the secretome of dental pulp stem cells.

Saudi Pharm J 2021 Aug 16;29(8):908-913. Epub 2021 Jul 16.

Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan, Saudi Arabia.

The aim of the present study was to assess the influence of metformin on the angiogenic ability of secretomes from dental pulp stem cells. The stem cells were obtained from the dental pulp (DPSCs) (n = 3) using the explant culture method. We treated the DPSCs with different concentrations of metformin and assessed the expression of the angiogenesis-related genes. We also tested the angiogenic effect of the secretomes on the yolk sac membrane of the chick embryos by counting the quaternary blood vessel formations on the yolk sac membrane. We found that metformin treatment enhanced the angiogenic potential of the stem cell secretome in a dose-dependent manner. This was evidenced by the increase in the quaternary blood vessel formations in the yolk sac membrane with lower to higher concentrations of metformin. Pre-treatment with metformin modulates the angiogenic potential of the stem cell-conditioned media in a dose-dependent manner. The augmentation of the angiogenic potential of the DPSCs can aid regeneration, especially in scenarios requiring the regeneration of vacuoles.
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http://dx.doi.org/10.1016/j.jsps.2021.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363104PMC
August 2021

COVID-19 pandemic and lock-down protocols: Impact in an indian tertiary cancer center.

Oral Oncol 2021 Aug 11:105484. Epub 2021 Aug 11.

Department of Oral Pathology and Microbiology, Sri Venkateswara Dental College and Hospital, Chennai, India. Electronic address:

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http://dx.doi.org/10.1016/j.oraloncology.2021.105484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354800PMC
August 2021

Ultrasound Imaging versus Radiographs in Differentiating Periapical Lesions: A Systematic Review.

Diagnostics (Basel) 2021 Jul 3;11(7). Epub 2021 Jul 3.

Department of Oral and Maxillofacial Sciences, Sapienza University, University of Rome, 00161 Rome, Italy.

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.
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http://dx.doi.org/10.3390/diagnostics11071208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303698PMC
July 2021

Metabostemness in cancer: Linking metaboloepigenetics and mitophagy in remodeling cancer stem cells.

Stem Cell Rev Rep 2021 Aug 5. Epub 2021 Aug 5.

Cancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, Rourkela, Odisha, 769008, India.

Cancer stem cells (CSCs) are rare populations of malignant cells with stem cell-like features of self-renewal, uninterrupted differentiation, tumorigenicity, and resistance to conventional therapeutic agents, and these cells have a decisive role in treatment failure and tumor relapse. The self-renewal potential of CSCs with atypical activation of developmental signaling pathways involves the maintenance of stemness to support cancer progression. The acquisition of stemness in CSCs has been accomplished through genetic and epigenetic rewiring following the metabolic switch. In this context, "metabostemness" denotes the metabolic parameters that essentially govern the epitranscriptional gene reprogramming mechanism to dedifferentiate tumor cells into CSCs. Several metabolites often referred to as oncometabolites can directly remodel chromatin structure and thereby influence the operation of epitranscriptional circuits. This integrated metaboloepigenetic dimension of CSCs favors the differentiated cells to move in dedifferentiated macrostates. Some metabolic events might perform as early drivers of epitranscriptional reprogramming; however, subsequent metabolic hits may govern the retention of stemness properties in the tumor mass. Interestingly, selective removal of mitochondria through autophagy can promote metabolic plasticity and alter metabolic states during differentiation and dedifferentiation. In this connection, novel metabostemness-specific drugs can be generated as potential cancer therapeutics to target the metaboloepigenetic circuitry to eliminate CSCs.
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http://dx.doi.org/10.1007/s12015-021-10216-9DOI Listing
August 2021

Aqueous extract of tobacco induces mitochondrial potential dependent cell death and epithelial-mesenchymal transition in gingival epithelial cells.

Saudi J Biol Sci 2021 Aug 1;28(8):4613-4618. Epub 2021 May 1.

Department of Orthodontics, College of dentistry, King Abdulaziz University, Saudi Arabia.

Smokeless tobacco habits are detrimental to oral health. A correlation between tobacco use and local epithelial tissue damage exists. Yet, the underlying cellular mechanism is not precisely characterized. This study assessed the dose-dependent action of Smokeless tobacco extract on gingival epithelial cells. Gingival tissue was taken from 5 healthy donors. Gingival epithelial cells were isolated by an enzymatic method and cultured up to passage 2. The cultured cells were treated with smokeless tobacco extract at 10%, 25%, 50%, and 75% volume concentration. After 48 h of incubation, MTT assay, Annexin V/PI assay, and DiIC1(5) assay were used to evaluate viability, apoptosis, and mitochondrial potential of the cells. RT-qPCR was used to determine the expression of BAX, BCL2, ECAD, NCAD, and TWIST. The Smokeless tobacco extract reduced cell viability by disrupting the mitochondrial potential and inducing apoptosis. Further, the Smokeless tobacco extract induced a dose-dependent epithelial-mesenchymal-transition in gingival epithelial cells. Apoptotic cellular death caused by tobacco extract on the gingival epithelial system was dependant on the mitochondrial potential of the cell. The results demonstrate that smokeless tobacco causes detrimental metabolic alterations of the periodontium.

Featured Application: This study elucidates the mechanism by which Smokeless tobacco products cause cellular damage to the gingival epithelium. The use of Smokeless tobacco products can lead to major cellular and surface changes in the gingiva and its appearance. The consequences of these changes are not limited to oral cancer but also increases a person's risk for dental and periodontal disease.
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http://dx.doi.org/10.1016/j.sjbs.2021.04.068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324949PMC
August 2021

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

Saudi J Biol Sci 2021 Aug 27;28(8):4553-4559. Epub 2021 Apr 27.

Logical Life Science Private Limited, Pune, India.

Background: has been applied successfully as an anti-inflammatory, anti-diabetic, and even as an anti-cancer agent. Yet, to date, the application of Giloy has not been explored concerning oral cancer.

Objectives: To assess the effect of extract (TcE) on an oral cancer cell line.

Methods: AW13516 (oral cancer cell line) cells were treated with the prepared aqueous extract of TcE for 24 h at various concentrations ranging between 5 μg/ml and 100 μg/ml and compared with control (cells without treatment). Thee effect of the extracts on apoptosis was assessed by through Annexin V flow cytometry assay and Luminometry based assessment of Caspase 8, 9 and caspase 3/7 activity. RNA was isolated from treated cells and gene expression of selected metastatic genes (MMP1, MMP10, and CXCL8); epithelial-mesenchymal stem cell genes (TWIST1, SNAIL, ZEB1, Oct4) and stemness related genses (Nanog, Sox2) were analyzed by using a quantitative real-time PCR system. The experiments were performed in triplicates.

Results: Aqueous extract of TcE was found to induce apoptosis inducer in AW13516 cells in a concentration-dependent manner and was potent even at a low concentration of 5 μg/ml. The apoptosis induction was confirmed with the caspase activity assay. Treatment of the cells with the extract for 24 h exhibited a significant decrease in the expression of EMT genes in a dose-dependent manner without an effect on the metastatic genes.

Conclusion: Aqueous extract of TcE induces apoptosis-mediated cell death in the oral cancer cell line AW13516 while attenuating its potential for epithelial mesenchymal transition.
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http://dx.doi.org/10.1016/j.sjbs.2021.04.056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324948PMC
August 2021

Lipid metabolism in cancer: A systematic review.

J Carcinog 2021 6;20. Epub 2021 May 6.

Department of Oral and Maxillofacial Surgery, Faculty of Dental Sciences, M.S. Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India.

Preclinical studies and clinical trials have emphasized the decisive role of lipid metabolism in tumor proliferation and metastasis. This systematic review aimed to explore the existing literature to evaluate the role and significance of the genes and pathways most commonly involved in the regulation of lipid metabolism in cancer. The literature search was performed as per Preferred Reporting Items for Systematic Reviews and Meta-analyses. Approximately 2396 research articles were initially selected, of which 215 were identified as potentially relevant for abstract review. Upon further scrutiny, 62 of the 215 studies were reviews, seminars, or presentations, and 44 were original study articles and were thus included in the systematic review. The predominant gene involved in lipid metabolism in cancer was stearoyl-coenzyme A desaturase 1 (SCD1), followed by fatty acid synthase (FASN). The pathway most commonly involved in lipid metabolism in cancer was the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, followed by the mitogen activated protein kinase (MAPK) pathway. SCD1 and FASN play significant roles in the initiation and progression of cancer and represent attractive targets for potentially effective anti-cancer treatment strategies. The regulation of cancer metabolism by the Akt kinases will be an interesting topic of future study.
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http://dx.doi.org/10.4103/jcar.JCar_15_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312377PMC
May 2021

COVID-19 and Dentistry: An Updated Overview of Dental Perspectives and a Recommended Protocol for Dental Care and Emergency Dental Treatment.

J Contemp Dent Pract 2021 May 1;22(5):572-586. Epub 2021 May 1.

School of Dental Medicine, University of Nevada, Las Vegas, Nevada, United States.

Aim And Objective: This manuscript aims to provide an overview of the coronavirus disease-2019 (COVID-19) pandemic from dental perspectives, and presents standards and guidelines of dental care provision based on available research in this field as well as clinical experience and practice.

Background: The current COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading around the globe and interferes with the provision of dental care for many individuals from different communities and backgrounds. A search for the literature on PubMed, ISI Web of Science, Scopus, EMBASE, and Cochrane Library from March 1, 2020 to December 30, 2020 was conducted. Also, the bibliographies included in the indicated articles were used to identify further literature. Recommendations by health authorities in different countries were also consulted.

Results: COVID-19 is causing many fatalities and is disrupting people's daily life and the economy in many countries around the world. Due to the potential of cross-infection through dental treatments, especially dental aerosol generation procedures, the dental profession has been disrupted during this pandemic. Dental care provision has been ceased completely or partially (limited to emergency or urgent treatment) in most countries around the world. Until this pandemic is controlled by new suitable treatments and/or vaccination, there is an urgent need to adopt immediate guidelines and standards for the safe provision of dental care to meet patients' demands, especially for the dental aerosols.

Conclusion: Guidelines and standards for dental treatment amidst the COVID-19 pandemic are required. This manuscript provides an overview of the COVID-19 pandemic from dental perspectives and presents standards and guidelines of dental care provision based on available research in this field as well as clinical experience and practice.

Clinical Significance: This manuscript provides guidelines and standards for dental treatment and clinical management within dental settings amidst the COVID-19 pandemic, and resembles part of the quest to set the golden standards for dental care during the current circumstances. How to cite this article: AL-Omiri MK, Al-Shayyab MH, Al Nazeh AA, . COVID-19 and Dentistry: An Updated Overview of Dental Perspectives and a Recommended Protocol for Dental Care and Emergency Dental Treatment. J Contemp Dent Pract 2021;22(5):572-586.
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May 2021

Impact of COVID-19 Lockdown on Oral Oncology-related Outpatient Volume at Indian Dental Institutions.

J Contemp Dent Pract 2021 May 1;22(5):501-505. Epub 2021 May 1.

Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan, Saudi Arabia.

Aim And Objective: This study aimed to evaluate the impact of the lockdown on oral oncology-related out-patient volume at Indian dental institutions.

Materials And Methods: The total number of newly diagnosed cases of oral submucous fibrosis, oral leukoplakia, oral lichen planus, and oral cancers, recorded at two dental institutional settings before lockdown (January-March 2020) and after lockdown (June-August 2020), were included retrospectively and compared.

Results: The study included a total of 797 cases at both institutions. At Institution-I, a total of 312 cases were recorded before the lockdown, and 63 cases were recorded after the lockdown. At Institution-II, a total of 311 cases were reported before lockdown, and 111 cases were recorded after lockdown. Comparisons between the pre-lockdown and post-lockdown data yielded a significant change in the proportions of oral sub-mucous fibrosis, oral leukoplakia, oral lichen planus, and oral cancers at both institutions (Chi-square test; < 0.001). Following the lockdown, a substantial reduction was observed in the proportion of oral submucous fibrosis (OSMF) cases at both institutions, and the proportion of oral cancers increased at both institutions. There was a significant difference between the proportions of cases reported before lockdown at both institutions ( < 0.001). However, after-lockdown, no such differences were noted ( = 0.69); the absence of significance could most likely be due to the low sample size or low-power during the post-lockdown period.

Conclusion: The oral potentially malignant disorders (OPMD) and oral cancer (OC) patient volumes reduced substantially following lockdown. During the post-lockdown period, the proportion of oral cancers increased, whereas the proportion of OSMF cases decreased. Results indicate that OPMD and oral cancer patients were impacted differently by the lockdown.

Clinical Significance: This study provides insight into the impact of lockdown and highlights the importance of reestablishing oral oncology-related patient care. A vital discussion is also provided on useful compensatory strategies that may reduce delays during the ongoing crisis. How to cite this article: Panta P, Reddy P, Misra SR, . Impact of COVID-19 Lockdown on Oral Oncology-related Outpatient Volume at Indian Dental Institutions. J Contemp Dent Pract 2021;22(5):501-505.
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May 2021

Why do Only Certain Cases of Oral Submucous Fibrosis Undergo Malignant Transformation?

J Contemp Dent Pract 2021 May 1;22(5):463-464. Epub 2021 May 1.

Division of Oral Pathology, Department of Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, Jazan University, Jazan, Saudi Arabia.

Oral submucous fibrosis (OSMF) causes desmoplasia and rigidity of submucosa of the oral cavity, resulting in reduced mouth opening, and in advanced stage causes difficulty in swallowing. OSMF has poor morbidity in terms of oral function as well as general health due to loss of oral function, such as eating. In severe conditions, it can cause dysphagia and hearing loss. Various clinicians have tried the different treatment modalities to reverse the disease process, but with limited success and that too in alleviating the associated symptoms.
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May 2021

Complete Obturation-Cold Lateral Condensation vs. Thermoplastic Techniques: A Systematic Review of Micro-CT Studies.

Materials (Basel) 2021 Jul 18;14(14). Epub 2021 Jul 18.

Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan 45142, Saudi Arabia.

To prevent re-infection and provide a hermetic seal of the root canal system, an endodontist must aim to produce a void-free obturation. This review aimed to compare the completeness of root canal obturation between the two most prevalent methods-cold lateral condensation and warm gutta-percha techniques-using micro-CT (PROSPERO reg no. 249815).

Materials And Methods: A search of Scopus, Embase, PubMed (Medline via PubMed), and Web of Science databases was done without any time restriction according to the PRISMA protocol. Articles that compared both techniques and were published in English were included. Data was extracted and the risk of bias was assessed using an adapted tool based on previous studies.

Results: A total of 141 studies were identified by the search. Following the screening and selection of articles, 9 studies were included for review. Data was extracted manually and tabulated. Most studies had a moderate risk of bias. None determined operator skill in both methods before comparison. The data extracted from the included studies suggests that both techniques produce voids in the obturation. The thermoplasticized gutta-percha techniques may result in fewer voids compared to cold lateral condensation.

Conclusion: Considering the limitations of the included studies, it was concluded that neither technique could completely obturate the root canal. Thermoplasticized gutta-percha techniques showed better outcomes despite a possible learning bias in favor of cold lateral condensation. Establishing operator skills before comparison may help reduce this bias.
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http://dx.doi.org/10.3390/ma14144013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304925PMC
July 2021

Using the Exploratory Sequential Mixed Methods Design to Investigate Dental Patients' Perceptions and Needs Concerning Oral Cancer Information, Examination, Prevention and Behavior.

Int J Environ Res Public Health 2021 07 16;18(14). Epub 2021 Jul 16.

Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan 45142, Saudi Arabia.

Objectives: The objective of this study was to investigate dental patients' behavior, thoughts, opinions and needs for oral cancer information, and dentists' behavior regarding prevention and examination of oral cancer.

Materials And Methods: This study utilized an exploratory sequential mixed methods design. Semi-structured interviews with open-ended questions were conducted for forty dental patients of both sexes. Based on the qualitative analysis, a structured questionnaire was developed and distributed among the participants. Data were analyzed for 315 participants to quantify their thoughts, needs, behavior and behavior expected from dentists regarding oral cancer. Frequency, percentages and cumulative percentages were calculated.

Results: This study reveals that patients' oral cancer knowledge levels were adequate, but most reported that their dentist had never examined them for oral cancer. Additionally, the participants had never performed self-examinations for oral cancer, nor were they aware of the possibility of doing so. Participants showed a preference for being examined and educated by their dentist about oral cancer and believed it would help early detection.

Conclusions: The study participants are aware of oral cancer and its risk factors. The practice of oral cancer examinations and patient education of its risk factors by dental practitioners is limited. Patients feel a need for more attention to be paid to oral cancer examinations, preventive measures and targeted information on oral cancer risk factors.
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http://dx.doi.org/10.3390/ijerph18147562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307210PMC
July 2021

Hemorrhagic areas as a histological prognosticator in oral cancer: A novel proposition.

Med Hypotheses 2021 Sep 6;154:110642. Epub 2021 Jul 6.

Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan, Saudi Arabia.

Determination of prognosis in oncology practice is a major challenge and many histological prognosticators have been applied because of the ease and simplicity of using them in day-to-day practice. Our histopathologic observation on 96 oral squamous cell carcinoma (OSCC) specimens revealed 34 cases associated with frank hemorrhagic areas, which were close to tumor cells. Hence, we propose that there could be a cross-talk between tumor cells and RBCs which can modulate the biological behavior of the tumor and prognosis of the patient. In the present paper, a scientific foundation is provided for this proposition. Furthermore, an experimental approach is recommended which will facilitate the identification of extracellular metabolites within the tumor microenvironment near RBCs. Such studies may pave the way for a better understanding of the clinical heterogeneity of oral cancer due to differential heme content of red blood cells (RBCs) in the tumor microenvironment (TME).
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http://dx.doi.org/10.1016/j.mehy.2021.110642DOI Listing
September 2021

Oral Cancer in Young vs Old Individuals: A Systematic Review.

J Contemp Dent Pract 2021 Apr 1;22(4):435-451. Epub 2021 Apr 1.

Department of Preventive Dental Sciences, College of Dentistry, Jazan University, Jazan, Kingdom of Saudi Arabia.

Aim: To compare various parameters associated with oral cancer in young and old patients and systematically compile the data on prognosis or outcome of oral cancer in young and old patients that include case series, matched-pair analyses, institutional series, and database reviews.

Background: Though oral cancer is considered a disease of old age, a recent clinical scenario witnesses its increasing incidence among young persons. When compared to old patients, young patients with oral cancer are exposed to the carcinogens for a very petite period of time suggesting underlying pathogenesis to be distinct from that in older individuals. Literature reports several studies about the occurrence of oral cancer in young patients; however, no unanimous opinion exists about its prognosis and treatment outcomes when compared to older patients. Keeping this in mind, we have extensively studied all the possible aspects (location, local and regional recurrence, nodal and distant metastasis, overall survival, etc.) from the English literature and systematically compiled the available data on prognosis or outcomes of oral cancer.

Review Results: The overall outcome of the case series shows poorer prognosis in young patients, matched-pair analyses, and institutional series suggesting no significant differences whereas the databases favored a better prognosis in young patients. The mean overall survival rate was found to be better for young patients in the database and institutional review whereas worse in the matched-pair analyses. The mean 5-year survival rate was found to be more in young individuals in matched-pair analyses, database reviews, and institutional series as compared to older oral cancer patients.

Conclusion: Though data extracted from various study designs are heterogeneous, the present review gives a scoping view of the papers published on oral cancer in young vs old patients. More prospective studies are suggested with a larger sample size in the future.

Clinical Significance: The present review will help to better understand the nature, course, and biologic behavior of oral cancer in young patients leading to the development of specific treatment strategies to manage the patients based on their age-groups.
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April 2021

COVID-19 and cardiovascular system-a comprehensive review.

Rev Cardiovasc Med 2021 06;22(2):343-351

Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, 45142 Jazan, Saudi Arabia.

Coronavirus disease 2019 (COVID-19), a mystified cryptic virus has challenged the mankind that has brought life to a standstill. Catastrophic loss of life, perplexed healthcare system and the downfall of global economy are some of the outcomes of this pandemic. Humans are raging a war with an unknown enemy. Infections, irrespective of age and gender, and more so in comorbidities are escalating at an alarming rate. Cardiovascular diseases, are the leading cause of death globally with an estimate of 31% of deaths worldwide out of which nearly 85% are due to heart attacks and stroke. Theoretically and practically, researchers have observed that persons with pre-existing cardiovascular conditions are comparatively more vulnerable to the COVID-19 infection. Moreover, they have studied the data between less severe and more severe cases, survivors and non survivors, intensive care unit (ICU) patients and non ICU patients, to analyse the relationship and the influence of COVID-19 on cardiovascular health of an individual, further the risk of susceptibility to submit to the virus. This review aims to provide a comprehensive particular on the possible effects, either direct or indirect, of COVID-19 on the cardiovascular heath of an individual.
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http://dx.doi.org/10.31083/j.rcm2202041DOI Listing
June 2021

Minimal Invasive Surgical Management of Familial Arteriovenous Malformation.

Case Rep Dent 2021 9;2021:5564470. Epub 2021 Jun 9.

Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan, Saudi Arabia.

Introduction: Familial arteriovenous malformations are exceedingly rare. They are often noted at birth. They can also present during childhood or adolescence. Sclerotherapy has proven to have a favorable outcome. . The present case report describes the treatment of arteriovenous malformations on the tongue, labial mucosa, and vermilion border in siblings treated with boiling saline injections.

Conclusion: Sclerotherapy using boiling saline had shown to effectively treat arteriovenous malformations in the oral region without any significant morbidity.
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http://dx.doi.org/10.1155/2021/5564470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211530PMC
June 2021

P-Cadherin and WNT5A expression in assessment of lymph node metastasis in oral squamous cell carcinoma.

Clin Oral Investig 2021 Jul 3. Epub 2021 Jul 3.

Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan, Saudi Arabia.

Background: Oral cancer progression is a multi-step process in which adhesion molecules play a pivotal role in the development of recurrent, invasive, and distant metastasis. The aim of this study was to adopt prognostic biomarkers to assess the lymph node metastasis of OSCC that will facilitate in deciding the treatment modality by the surgeons.

Objectives: The objectives of the study were to assess the biological behaviour of OSCC by correlating the expression levels of P-Cadherin and WNT5A immunohistochemically.

Methods: A total of 60 selected OSCCs cases (lymph node metastasis n = 30, non-metastatic n = 30) and 10 normal healthy controls were quantitatively and qualitatively analysed by immunohistochemistry for P-Cadherin and WNT5A. A survival analysis was also performed.

Results: The expression levels of P-Cadherin and WNT5A in OSCC groups were statistically significant between metastatic and non-metastatic groups (p < 0.001). P-Cadherin and WNT5A expression in metastatic (lymph node metastasis) and non-metastatic cases showed a significant correlation coefficient of 0.753 at (p < 0.01). The present study also found that the aberrant expression (high) of P-Cadherin was associated with diminished survival of patients with metastatic OSCC.

Conclusion: The present study demonstrated the aberrant expression of P-Cadherin and WNT5A could serve as important prognosticator in OSCC.

Clinical Relevance: P-Cadherin and WNT5A could be used as significant predictors of disease outcome.
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http://dx.doi.org/10.1007/s00784-021-03996-4DOI Listing
July 2021

Pharmacological Means of Pain Control during Separator Placement: A Systematic Review.

J Contemp Dent Pract 2021 Mar 1;22(3):316-323. Epub 2021 Mar 1.

Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Kingdom of Saudi Arabia. e-mail:

Aim: To assess the effectiveness of adjuvant analgesics/anesthetics in pain control after separator placement compared with no medication.

Background: Separator placement to create space for cementing bands is the first clinical procedure done in orthodontics. Pain in this stage can negatively affect patient compliance and trust in the clinician. To date, there is no universally accepted regimen for pain control.

Materials And Methods: Electronic databases of PubMed, Scopus, and Web of Science were searched. One hundred and thirty-two potentially relevant studies were found. A total of eight randomized clinical trials including 642 subjects were selected. Data were extracted into customized forms, and selected studies were assessed for risk of bias using the Joanna Briggs Institute.

Results: Results showed the use of analgesics led to lower reported pain scores at almost all time intervals. NSAIDs resulted in a statistically significant reduction in pain compared to a control group.

Conclusion: According to the available literature, the use of analgesics is effective in controlling orthodontic pain due to separators. Acetaminophen and ibuprofen show a stable analgesic effect.

Clinical Implication: Acetaminophen 650 mg or ibuprofen 400 mg taken 1 hour prior to separator placement can reduce pain associated with the procedure.
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March 2021

Florid Cemento-osseous Dysplasia: A Report of Two Cases and Literature Review.

J Contemp Dent Pract 2021 Mar 1;22(3):304-309. Epub 2021 Mar 1.

Department of Oral Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, United States.

Aim: This report aims to provide the clinical and radiographic features of two symptomatic Indian patients with florid cemento-osseous dysplasia (FCOD), along with a discussion of the differential diagnosis, potential challenges, and therapeutic implications.

Background: FCOD is a rare, multifocal, periapical, and bilateral condition involving the premolar and molar region of the posterior mandible and sometimes the maxilla.

Case Description: The first patient is a 30-year-old female with a recent history of dental pain. The patient was otherwise healthy and the medical history was unremarkable. The second patient is a 50-year-old female with a history of orthodontic therapy. Radiographic evaluation using cone-beam computed tomography (CBCT) revealed bilateral involvement of the posterior mandible, sparing the entire maxilla in both patients Clinical significance: For a pathognomonic condition like FCOD, a radiology survey alone is often sufficient to arrive at the final diagnosis, and therefore surgical interventions should ideally be avoided.
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March 2021

Facial Masking and SAMPPs: Potential "Variolation" in COVID-19.

J Contemp Dent Pract 2021 Mar 1;22(3):205-206. Epub 2021 Mar 1.

Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan, Saudi Arabia.

Variolation is an important phenomenon in the field of immunology and has a rich historical background that has changed the perception of immunity reinforcement in human beings. This methodology was first used to immunize humans against smallpox infection by inoculating the infective material taken from infected patients. The intention was to induce a mild form of infection that would germane antibody response for tackling the future smallpox infection. To be more precise the procedure involves the application of powered smallpox scabs or fluid obtained from the pustules of the infected patients. This application is on the superficial scratches made on the skin surface of normal healthy individuals. Thus, the variolation is the process in which the virus is inoculated in the patient to produce an antibody response. This process produces signs and symptoms similar to the intended viral infection but usually of the milder form, possibly due to mild quantum exposure of virus particles. In the case of smallpox, this methodology was first used in China, India, and the Middle East before it was introduced into England and North America in the 1720s. Due to advancements done in the field of vaccination, this crude method is no longer used today. However, this process was a milestone in science that has led to the development of many vaccines available nowadays.
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March 2021

Potential Application of an Aqueous Extract of (Thunb.) Miers (Giloy) in Oral Submucous Fibrosis-An In Vitro Study.

Materials (Basel) 2021 Jun 18;14(12). Epub 2021 Jun 18.

Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan 45142, Saudi Arabia.

The in vitro antifibrotic activity of (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 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.
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http://dx.doi.org/10.3390/ma14123374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234184PMC
June 2021
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