Computational analysis of phytocompounds in Centella asiatica for its antifibrotic and drug-likeness properties - Herb to drug study.

Oral submucous fibrosis (OSMF) is a potentially malignant disorder with no permanent cure that affects the quality of life due to trismus. Computational pharmacology has accelerated the discovery of drug candidates for the treatment of incurable diseases. The present study aimed to screen the compounds of the miracle herb Centella asiatica with drug-likeness properties based on the absorption, distribution, metabolism, and excretion (ADME) properties. The pharmacological actions of these screened compounds against OSMF were identified by network pharmacology, gene ontology, pathway enrichment analysis, molecular docking, and simulation. Fifteen drug-like ligands were identified after virtual screening viz; asiatic acid, kaempferol, quercetin, luteolin, apigenin, bayogenin, gallic acid, isothankunic acid, madecassic acid, madasiatic acid, arjunolic acid, terminolic acid, catechin, epicatechin, and nobiletin. 850 potential targets were predicted for the ligands, which were analyzed against 354 proteins associated with OSMF. Compound pathway analysis and disease pathway analysis identified 53 common proteins. The GO enrichment analysis identified 472 biological process terms, 76 molecular function terms, and 44 cellular component terms. Pathway enrichment analysis predicted 142 KEGG pathways, 35 Biocarta pathways, and 236 Reactome pathways for the target proteins. The analysis revealed that the herb targets crucial events of fibrosis such as inflammation, oxidative stress, apoptosis, collagen deposition, and epithelial-mesenchymal transition. The common 53 proteins were used for protein-protein interaction (PPI) network analysis, which revealed 4 key proteins interacting with the phytocompounds viz; transforming growth factor-ß1 (TGF-ß1), mothers against decapentaplegic-3 (SMAD-3), mitogen-activated protein kinase-1 (MAPK-1) and proto-oncogene tyrosine-protein kinase (SRC). Molecular docking revealed that all ligands had a good binding affinity to the target proteins. Bayogenin had the highest binding affinity towards MAPK-1 (-9.7 kcal/mol), followed by isothankunic acid towards SRC protein (-9.3 kcal/mol). Madasiatic acid had the highest binding affinity to SMAD-3 (-7.6 kcal/mol) and TGF-ß1 (-7.1 kcal/mol). Molecular dynamics simulation demonstrated stable ligand protein interactions of bayogenin and MAPK complex, isothankunic acid and SRC complex. This in silico study is the first to identify potential phytochemicals present in Centella asiatica and their target molecules, which might be responsible for reversing OSMF.

Natural products and diet for the prevention of oral cancer: Research from south and southeast Asia.

Medicinal plants are of prime importance in the discovery of drugs. They are an inherent source of naturally available phytochemicals that can help in the prevention and treatment of several diseases including cancer. This article reviews the experimental and clinical evidence of phytochemicals available in natural dietary products that are used in everyday life across South Asia and South-East Asia for their perceived effectiveness in the management of Potentially Malignant Disorders and prevention of Oral Cancer. The review also highlights the active phytometabolites, their in vitro anti-proliferative properties and targeted signalling pathways, biological activities in in vivo models and translative potential for clinical trials in humans.

Molecular pathways of oral submucous fibrosis and its progression to malignancy.

OBJECTIVE: The review aims to comprehend various factors engaged in the alteration of molecular events resulting in Oral submucous fibrosis (OSMF) and its malignant transformation. DESIGN: Literature pertinent to pathways involved in OSMF were explored in databases such as PubMed, Scopus and Google Scholar. The relevant literature was reviewed and critically appraised in this narrative review. RESULTS: Areca nut components influence myriad of cellular molecules such as cytokines, growth factors, myofibroblasts, non-coding RNAs and alter their expression. These aberrantly expressed molecules drive the progression of OSMF from localized inflammation to fibrosis of buccal mucosa. The oral tissue suffers from oxidative stress, hypoxia, autophagy, aberration of cell cycle and DNA damage. Apoptosis of epithelial layer results in its atrophy facilitating deeper penetration of areca nut elements. With the advance of disease, epithelial-mesenchymal transition eventuates and promotes dysplasia. The jeopardized expression of various cellular molecules, suppressed apoptosis, along with increased genetic alterations and neovascularization favors the malignant transformation. CONCLUSION: OSMF is a progressive disorder with complex mechanism of pathogenesis initiated by inflammation of oral mucosa. Continuous habit of areca nut chewing and the resulting insult to the tissues prevents healing process and is destined to debilitating disease which affects the quality of life with a higher probability of progression to malignancy.

A non-destructive dielectric based approach for the rapid determination of tributyl phosphate in dodecane.

Reliable determination of tributyl phosphate (TBP) in suitable diluents is indispensable in studies related to nuclear fuel reprocessing. Herein, we present a rapid and non-destructive dielectric based approach to determine TBP in mixtures of TBP and n-dodecane in the quality control as well as research laboratories associated with nuclear fuel reprocessing. The measurement is based on an in-house developed new class of sensors called pulsating sensors. The heart of the instrument consists of a three gate oscillator circuit that generates the first electronic response directly in the digital domain. With a single capacitive type probe and using a standalone embedded unit, two different ranges of measurement are covered. A detailed investigation on the various factors affecting the probe output is carried out to achieve maximum sensitivity and precision in analysis. It takes less than a minute to take a measurement. The precision in analysis in the reported range of measurement (0.7-35% v/v TBP) lies between 0.15% and 11.4% relative standard deviation, while the absolute error in measurement lies between ±0.02 and ±0.43% (v/v). The response time and limit of quantification are 4.5 s and 0.1% (v/v), respectively. The measurements made with the proposed technique are compared with the well-established gas chromatographic technique.

Asymptomatic palatal mass: A case report.

Accidental detection of asymptomatic clinically suspicious lesions is a common occurrence in routine clinical examination of the oral cavity. In certain cases, these lesions may mimic benign lesions further adding to confusion. In this case report, we have discussed the case of a 51-year-old male patient with an asymptomatic palatal mass which was detected during a routine dental check-up and subsequently confirmed to be an adenoid cystic carcinoma (ACC) arising from the minor salivary glands. The patient underwent right partial maxillectomy followed by radiation therapy and has been disease-free for 6 years and is on follow-up. ACC is a malignant tumour of the salivary glands commonly occurring in the palate, characterized by a slow indolent growth phase, with a high predilection for late recurrences which can be local or systemic. This article describes the importance of recognizing this clinical entity as a differential diagnosis in the evaluation of asymptomatic palatal lesions to enable early diagnosis and institution of appropriate treatment to successfully treat the disease.

Association of Human Papilloma Virus in Oral Squamous Cell Carcinoma: An Alarming Need for Human Papillomavirus 16 Screening in Cancer Patients.

BACKGROUND: The percentage of cancers of the tongue and palatine tonsils has continued to increase by 2%-4% among younger men. This increased prevalence of a subsection of oropharyngeal carcinoma can be associated with human papillomavirus (HPV). Among the head-and-neck cancers, a strong association with HPV infection is evident with oropharyngeal cancers, particularly tonsillar and basal tongue cancers. OBJECTIVES: Oral carcinoma, with an overall incidence of 16.1 adults per 100,000, is one of the leading malignancies worldwide, presenting a noticeable geographic variation in its distribution. Squamous cell carcinoma (SCC) being the most common of all oral malignancies, the objective of the study is to detect the HPV antigen p16 over-expression in patients with oral SCC using immunohistochemistry (IHC). MATERIALS AND METHODS: Oral SCC (OSCC) diagnosed formalin-fixed-paraffin embedded blocks were processed for IHC. RESULTS: Out of 50 cases, 3 were deferred due to insufficient tumor sample and 2/47 cases were p16 positive and the site was the lateral border of the tongue. CONCLUSION: The HPV antigen overexpression in patients with OSCC was investigated to detect the incidence of HPV in SCC of oral cavity. P16 was used as a marker for the detection of OSCC using IHC in HPV-induced OSCC. Positives were detected thus concluding the significance of studying HPV expression during diagnosis.

Correlation of Clinical and Histopathological Grades in Oral Submucous Fibrosis Patients with Oxidative Stress Markers in Saliva.

This study aimed to correlate the oxidative stress marker levels in saliva with the clinical stage based on mouth opening, fibrotic bands and histopathological grades of oral submucous fibrosis (OSF) patients. The study included patients clinically diagnosed with OSF (n = 63) and equal number of age and gender matched controls. Patients with OSF were defined by mouth opening stage, fibrotic bands and histopathological grades. Unstimulated saliva from both control and OSF patients were analysed for oxidative markers like lipid peroxides (LPO), non-enzymic antioxidants [reduced glutathione (GSH), vitamin A, vitamin E, vitamin C] and enzymatic antioxidants [glutathione peroxidase (GPx), superoxide dismutase (SOD)] and correlated with different stages and grades. Total salivary protein and LPO were significantly increased in OSF group with no significant change in the levels of GSH compared to controls. In OSF patients, a significant decrease in the levels of vitamins A, C and E was observed. The activities of salivary SOD and GPx were significantly decreased in OSF patients compared to controls. These changes significantly correlated with the increasing and differing grades of OSF that reflects increased oxidative stress with the progress of OSF.

Evaluation of the Role Played by Cyclin D1 as a Diagnostic and Prognostic Marker in the Progression of Oral Carcinogenesis.

ABSTRACT: Cyclin D1 is linked with the development and progression of oral squamous cell carcinoma (OSCC). This case-control study was directed to characterise the immunoreactivity of the protein cyclin D1 and its correlation with the clinicopathological parameters of patients with OSCC and potentially malignant disorders (PMD). A group of patients with OSCC were followed up after treatment, and the cyclin D1 expression was reviewed for correlation of cyclin D1 expression with prognosis of the patients. METHODOLOGY: Sixty individuals were included in this study: OSCC (20), PMD (20) and Control (20). Immunohistochemistry assay was evaluated. The clinicopathological parameters were correlated with the staining intensity of cyclin D1. The results were subjected to Pearson's correlation test. RESULTS: Age, gender and site showed no statistically significant correlation with cyclin D1 expression in OSCC and PMD. The cyclin D1 score did not show a significant difference with histopathological diagnosis of OSCC. Cyclin D1 was not expressed in 60% of the Control and 30% PMD cases while the expression of cyclin D1 was seen in 100% of OSCC cases although cyclin D1 score did not show a statistically significant association in the prognosis of the disease among the OSCC patients.

Comparative Evaluation of Dental and Skeletal Fluorosis in an Endemic Fluorosed District, Salem, Tamil Nadu.

BACKGROUND: High levels of fluoride in the drinking water, especially ground water, results in skeletal fluorosis which involves the bone and major joints. This study was conducted to assess the prevalence of skeletal fluorosis to compare with dental fluorosis in an endemically fluorosed population in the District of Salem, Tamil Nadu. MATERIALS AND METHODS: Institutional ethical clearance was obtained. A total of 206 patients who reported to the Department of Hematology for blood investigations were the participants in this study. Age, sex, place, weight, height, dental fluorosis, and skeletal complaints were noted down. Body mass index was calculated, and statistical analysis was performed. RESULTS: Dental fluorosis was present in 63.1% and absent in 36.9% of the samples reported. Skeletal fluorosis was present in 24.8% and was absent in 75.2%. A large number of the patients had knee pain and difficulty in bending. Chi-square test was used for statistical analysis. Skeletal fluorosis and age were compared and P value was 0.00 and was significant. Dental fluorosis and skeletal fluorosis were compared and P value was found to be 0.000 and significant. DISCUSSION AND CONCLUSION: There is a need to take measures to prevent dental and skeletal fluorosis among the residents of Salem district. Calcium balance should be maintained, and fluoride intake should be minimized to reduce the symptoms. The government should provide water with low fluoride level for drinking and cooking. Once the symptoms develop, treatment largely remains symptomatic, using analgesics and physiotherapy.

Mini review: Multifaceted role played by cyclin D1 in tumor behavior.

The objective of this paper is to discuss and put forward the various diversified roles of cyclin D1 in cancer. Neoplasia is defined by abnormal regulation of the cell cycle. Cyclin D1 could be a protein derived from the PRAD1, CCND1, or bcl-1 sequence on body 11q13 that is concerned in each traditional regulation of the cell cycle and pathologic process. Within the G1 (resting) part of the cell cycle, cyclin D1 in conjunction with its cyclin-dependent enzyme (cyclin-dependent kinase) partner is accountable for transition to the S (DNA synthesis) part by phosphorylating the merchandise of the metastatic tumor sequence (protein retinoblastoma) that then releases transcription factors vital within the initiation of DNA replication. Amplification of the sequence or overexpression of the cyclin D1 releases a cell from its traditional controls and causes transformation to a malignant composition. Analysis of those changes provides vital diagnostic information in oral carcinogenesis and is of prognostic value in several cancers. Data of cyclin D1's role in malignancy at the assorted sites provide a basis on which future treatment directed against this molecule will proceed.

Histopathological Parameters predicting Occult Nodal Metastases in Tongue Carcinoma Cases: An Indian Perspective.

BACKGROUND: It is a well-established fact that in squamous cell carcinoma cases, the presence of lymph node metastases decreased the 5-year survival rate by 50% and also caused the recurrence of the primary tumor with development of distant metastases. Till date, the predictive factors for occult cervical lymph nodes metastases in cases of tongue squamous cell carcinoma remain inconclusive. Therefore, it is imperative to identify patients who are at the greatest risk for occult cervical metastases. This study was thus performed with the aim to identify various histopathologic parameters of the primary tumor that predict occult nodal metastases. MATERIALS AND METHODS: The clinicopathologic features of 56 cases of lateral tongue squamous cell carcinoma with cT1NoMo/cT2NoMo as the stage and without prior radiotherapy or chemotherapy were considered. The surgical excision of primary tumor was followed by elective neck dissection. The glossectomy specimen along with the neck nodes were fixed in formalin and 5 urn thick sections were obtained. The hematoxylin & eosin stained sections were then subjected to microscopic examination. The primary tumor characteristics that were analyzed include tumor grade, invading front, depth of tumor, lymphovascular invasion, perineural invasion and inflammatory response. The nodes were examined for possible metastases using hematoxylin & eosin followed by cytokeratin immunohistochemistry. RESULT: A total of 12 cases were found with positive occult nodal metastases. On performing univariate analysis, the histopathologic parameters that were found to be statistically significant were lymphovascular invasion (p = 0.004) and perineural invasion (p = 0.003) along with a cut-off depth of infiltration more than 5 mm (p = 0.01). CONCLUSION: Histopathologic assessment of the primary tumor specimen therefore continues to provide information that is central to guide clinical management, particularly in cases of occult nodal metastases. Clinical significance The study highlights the importance of extensive histopathological screening, which holds the key for establishing occult metastases. Pathological upgrading of tumors is possible following histopathological studies similar to the present one. Presence of occult metastases justify neck dissection in these clinically N0 cases. In an Indian setting, histopathological evaluation assumes a bigger role than other expensive and advanced techniques.

OPN -Revisited.

Osteopontin (OPN), a matrix extracellular glyco-phosphoprotein is found in various tissues such as epithelium lined tissues, kidney, bone and teeth .It is also detected in all body fluids including blood and breast milk. OPN plays role in a number of physiological and pathologic events such as cell adhesion, migration and cell survival, angiogenesis, apoptosis, inflammation and wound healing. This review summarizes the current data of the biological activities of OPN in the development of tumour, its progression and metastasis.

Efficacy of oral exfoliative cytology in diabetes mellitus patients: a light microscopic and confocal microscopic study.

AIM: Diabetes mellitus (DM) has become a global problem. By monitoring the health status of these individuals, diabetic complications can be prevented. We aimed to analyze alterations in the morphology and cytomorphometry of buccal epithelial cells of type 2 DM patients using oral exfoliative cytology technique and determine its importance in public health screening, diagnosis and monitoring of diabetes mellitus. MATERIALS AND METHODS: The study was carried out in 100 type 2 DM patients and 30 healthy individuals. Smears were taken from the right buccal mucosa and stained by the Papanicolaou technique. Staining with Acridine orange was carried out to view qualitative changes with confocal laser scanning microscope (LSM-510 Meta). The cytomorphometry was evaluated using IMAGE PRO PLUS 5.5 software with Evolution LC camera. All findings were statistically analyzed. RESULTS: The results showed that with increase in fasting plasma glucose levels, there is significant increase in nuclear area, decrease in cytoplasmic area, and increase in nuclear cytoplasmic ratio (p < 0.05) when compared to the control group. Various qualitative changes were noted, such as cell degeneration, micronuclei, binucleation, intracytoplasmic inclusion, candida and keratinization. CONCLUSION: In the present study, we found significant alterations in the cytomorphometry and cytomorphology of buccal epithelial cells of type 2 DM patients. This study supports and extends the view that these cellular changes can alert the clinician to the possibility of diabetes and aid in monitoring of diabetes throughout the lifetime of the patient.

Evaluation of Glycemic Control in Type 2 Diabetes Mellitus using Cytomorphometry of Buccal Cells and Correlation with Glycosylated Hemoglobin.

BACKGROUND: To study cytological alterations in the exfoliated buccal cells of diabetic patients. To analyze the cytomorphometric findings in the smears of uncontrolled and controlled diabetic patients and compare it with that of normal healthy controls. To establish a correlation between cytomorphometric changes and glycosylated hemoglobin (HbA1c) in diabetics and normal controls, for evaluation of glycemic control. MATERIALS AND METHODS: The study was carried out in 40 confirmed diabetic patients from a hospital out-patient diabetic ward and 20 healthy individuals as controls (Group A: n = 20), in Chennai. Specific exclusion criteria were used to select the study group from a larger group of subjects. Based on HbA1c values, the diabetic patients were categorized into Group B = Controlled diabetics (n = 20) (HbA1c <7%) and Group C = Uncontrolled diabetics (n = 20) (HbA1c >9%). After informed consent, buccal smear was collected from clinically normal appearing mucosa and stained with papanicoloau (PAP) stain. Cytomorphometric analysis of selective PAP stained cells was done using image analysis software, Image Pro Plus 5.5 (Olympus) and parameters determined were average cytoplasmic area (CA), average nuclear area (NA) and cytoplasmic:nuclear (C: N) ratio for an average of 50 cells/patient. RESULTS: Comparing the average NA among three groups, an increase through Group A, B, C, with a maximum significance between Group C and A was seen. The average C: N ratio showed a statistically significant difference between all three groups. Significant correlation existed between the HbA1c values and both the C: N ratio and average NA in all the three groups. CONCLUSIONS: Cytomorphometric analysis of buccal smears using the C: N ratio alteration as a reliable criteria, may serve as yet another non-invasive tool for screening programs for diabetic detection. And the technique may possibly be used also for evaluation of glycemic control in known diabetics.

Level monitoring system with pulsating sensor--application to online level monitoring of dashpots in a fast breeder reactor.

An innovative continuous type liquid level monitoring system constructed by using a new class of sensor, viz., pulsating sensor, is presented. This device is of industrial grade and it is exclusively used for level monitoring of any non conducting liquid. This instrument of unique design is suitable for high resolution online monitoring of oil level in dashpots of a sodium-cooled fast breeder reactor. The sensing probe is of capacitance type robust probe consisting of a number of rectangular mirror polished stainless steel (SS-304) plates separated with uniform gaps. The performance of this novel instrument has been thoroughly investigated. The precision, sensitivity, response time, and the lowest detection limit in measurement using this device are <0.01 mm, ∼100 Hz/mm, ∼1 s, and ∼0.03 mm, respectively. The influence of temperature on liquid level is studied and the temperature compensation is provided in the instrument. The instrument qualified all recommended tests, such as environmental, electromagnetic interference and electromagnetic compatibility, and seismic tests prior to its deployment in nuclear reactor. With the evolution of this level measurement approach, it is possible to provide dashpot oil level sensors in fast breeder reactor for the first time for continuous measurement of oil level in dashpots of Control & Safety Rod Drive Mechanism during reactor operation.

Expression of podoplanin in oral premalignant and malignant lesions and its potential as a biomarker.

AIM: To analyze and compare the expression of podoplanin in normal oral tissues, leukoplakia and oral squamous cell carcinoma (OSCC) and to predict its use as a biomarker. MATERIALS AND METHODS: Ninety-two formalin fixed paraffin embedded tissue samples comprising of 32 cases of leukoplakia, 50 cases of OSCCs and ten normal gingival samples. The samples were retrieved from archives and immunohistochemically analyzed using podoplanin. Appendix tissue samples were used for control purposes. The results were tabulated and statistically analyzed using ANOVA/Kruskal-Wallis test with post-hoc tests, where demographic details are compared and analyzed using Pearson Chi-square test. RESULTS: The study results showed, absence of podoplanin expression in the epithelium of all the gingival samples (Group I). Positive podoplanin expression noticed in 19 out of 32 (59.4%) cases of leukoplakia (Group II) and 41 out of 50 (82%) cases of OSCCs (Group III). The expression of podoplanin among different groups was highly significant (P = 0.000). CONCLUSION: The podoplanin may be considered as a predictor marker in assessing malignant transformation of premalignancies and prognosis of oral malignancy. Indeed it is believed that podoplanin might play a role in tumor progression though exact mechanism is not fully elucidated. Further research is required to understand its exact pathophysiology.

Evaluation of myofibroblasts by expression of alpha smooth muscle actin: a marker in fibrosis, dysplasia and carcinoma.

OBJECTIVE: Evaluation of Myofibroblasts by studying expression of Alpha smooth muscle actin: A marker of Fibrosis, Dysplasia and Carcinoma. BACKGROUND: Myofibroblasts are cells that have contractile properties and are involved in inflammation, wound healing, fibrosis and oncogenesis in most of the organs and tissues. They are involved in healing and granulation tissue formation which occur after tissue injuries, also produce inflammatory mediators, growth factors and help in extracellular matrix reorganization by secretion of proteins like collagen, fibronectin, etc. Because of their component, Alpha smooth muscle actin ([alpha]-SMA), they are involved in the contraction of extracellular matrix and aid in tissue contraction. The myofibroblasts disappear by apoptosis after completion of repair, but their persistence causes a dysfunction in the repair mechanism, leading to excessive contraction and extracellular matrix (ECM) secretion and thus, fibrosis. The purpose of this study was to evaluate the presence of myofibroblasts in cases of Oral Submucous fibrosis (OSMF), which consisted of very early, early and moderately advanced OSMF, OSMF with dysplasia and oral squamous cell carcinoma (OSCC), by detecting (alpha)-SMA, which is a specific marker for myofibroblasts. MATERIALS AND METHODS: The study sample consisted of three groups which comprised of 41 cases of OSMF, 10 cases of OSMF with dysplasia and 11 cases of OSCC. All the cases were subjected to immunohistochemistry by using (alpha)-SMA antibody for detection of myofibroblasts. RESULTS: The presence of myofibroblasts was significantly higher in oral squamous cell carcinomas as compared to that in OSMF with dysplasia and OSMF. A statistical significance was also noted between the staining index and age of the individuals and the staining index and duration of the habit. CONCLUSION: Myofibroblasts play a role in fibrosis, as was seen in OSMF. Activated myofibroblasts secrete proteolytic enzymes and cause matrix degradation, which is instrumental in cancer cell invasion and metastasis. Further studies in which the myofibroblasts are targetted, may help in providing therapeutic regimens in fibrosis, dysplasia and cancer.

Health hazards of xylene: a literature review.

Xylene, an aromatic hydrocarbon is widely used in industry and medical laboratory as a solvent. It is a flammable liquid that requires utmost care during its usage. On exposure the vapours are rapidly absorbed through the lungs and the slowly through the skin. Prolonged exposure to xylene leads to significant amount of solvent accumulation in the adipose and muscle tissue. This article reviews the various acute and chronic health effects of xylene through various routes of exposure.