International Journal of Current Research and Review
ISSN: 2231-2196 (Print)ISSN: 0975-5241 (Online)
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IJCRR - Vol 06 Issue 12, June, 2014

Pages: 33-42

Date of Publication: 23-Jun-2014


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\"CYCLOOXYGENASE-2\" - A VIBRANT CHEMICAL MEDIATOR IN A PLETHORA OFORAL LESIONS

Author: Aditi Amit Byatnal, Subhalakshmi Sen, Amit Byatnal, Monica Charlotte Solomon

Category: Healthcare

Abstract:Cyclooxygenase (COX) is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Constituting a key regulatory enzyme of the ecosanoid biosynthetic pathway, COX catalyzes the conversion of arachidonic acid to protaglandinG2 (PGG2) and PGH2 and subsequently to a variety of eicosanoids. COX-2 is one of the isoforms of COX, which was upheld mainly as an inflammatory, inducible enzyme, having role different than that of COX-1. However, more recent studies are beginning to reveal additional functions of COX-2, especially in oral lesions.Most commonly studied area of interest being oral squamous cell carcinoma, along with salivary gland tumors, reactive inflammatory lesions and so on. The objective of this review is to discuss the role of COX-2 in various oral lesions.

Keywords: Cyclooxygenase, prostanoids

Full Text:

INTRODUCTION

The fascinating ability to treat fever and inflammation dates back about 3500 (400 B.C.) years ago to a time when the Greek physician Hippocrates prescribed an extract from willow bark and leaves. Later in the 17th century, the active ingredient of willow bark salicin was identified in Europe. The Kolbe company in Germany started mass producing salicylic acid in 1860. Acetylsalicyclic acid 1 (aspirin) the more palatable form of salicyclic acid was introduced into the market by Bayer in 18991 . However, the mechanism of action of anti-inflammatory and analgesic agents such as aspirin and indomethacin 2 remained elusive until the early 1960?s. This all changed in the seventies, when John Vane discovered the mechanism of action of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) thereby increasing our ability to develop novel anti-inflammatory therapies1 . The success of NSAIDs in treating various inflammatory conditions such as rheumatoid arthritis (RA) and osteoarthritis (OA) validated inhibition of the enzyme prostaglandin H synthase (PGHS) or cyclooxygenase (COX) as a highly suitable target in anti-inflammatory therapies1,2 . However, the gastrointestinal (GI) toxicities associated with widespread NSAID use proved to be a major drawback during long term therapy3 . COX, a central enzyme in the biosynthetic pathway to prostaglandins from arachidonic acid, is a protein that was purified more than 20 years ago and cloned in 1988. In the early 90?s, Needleman, Simmons and Herschman?s group reported the presence of an inducible isoform of the enzyme COX later identified as Cyclooxygenase-2 (COX-2)4,5. This discovery led to the hypothesis that anti-inflammatory prostaglandins (PGs) were produced through constitutive expression of Cyclooxygenase -1 (COX-)1, whereas the proinflammatory PGs were produced via induction of the COX-2 isoform6 .

DISCUSSION

COX-2 and inflammation

During the inflammatory process, the COX-1 micro RNA (mRNA) and protein activity do not change whereas a dramatic increase in COX-2 levels occurs leading to increased production of proinflammatoryPGs.The expression of COX-2 has been studied extensively in animal models of inflammation which provided strong evidence that induction of COX-2 enzyme is associated with inflammation. The COX-1 enzyme does not appear to be affected by the inflammatory process since similar levels of mRNA and protein are detected in both normal and inflamed tissue in animal models. PGs such as PGE2 and PGI2 produced via the COX-2 pathway magnify the degree of inflammation initiated by other mediators of inflammation such as histamine and bradykinin leading to increased vascular permeability and edema7 . COX-2 is not detectable in normal tissue but is detectable after induction by inflammatory stimuli. Selective COX-2 inhibitors exhibit good anti-inflammatory and analgesic activities in various animal models. In humans, COX-1 is found to be constitutively expressed in a wide range of tissues including the kidney, lung, stomach, small intestine and colon. Hence, COX-1 is considered a housekeeping enzyme responsible for maintaining basal prostaglandin levels, which is important for tissue homeostasis. In contrast, most tissues do not routinely express COX-2 constitutively. It is only in the central nervous system8 and seminal vesicles9where COX-2 has been demonstrated to be expressed normally. However, the stimulation of COX-2 in Src-transformed fibroblasts10 , endothelial cells and monocytes treated with the tumor promoter tetradecanoyl-phorbol-acetate or lipopolysaccharide create a notion that COX-2 is an inducible enzyme that produces prostaglandins during inflammatory and tumorigenic settings. Cyclooxygenase-2 and its function One of the first studies conducted after the discovery of two isoforms of COX was a screening of existing NSAIDs for those that had differential effects on inhibition of COX-1 vs. COX-2, and some were found to have a 20- to 70- fold selective preference11 . As a result, studies were done using differential inhibition of COX-1 or COX-2 activities to sort out the relative contributions of these isoforms under a variety of experimental conditions. COX-2 in Cancer Several population-based studies have detected a 40–50% decrease in relative risk for colorectal cancer in persons who regularly use aspirin and other NSAIDs12. Initial attempts to determine the molecular basis for these observations found that both human and animal colorectal tumors express high levels of COX-2, whereas the normal intestinal mucosa has low to undetectable COX-2 expression13. These findings led to the hypothesis that COX-2 may be playing a role in colon cancer growth and progression. Studies on cell culture models have shown that COX-2 expression contributes significantly to the tumorigenic potential of epithelial cells by increasing adhesion to extracellular matrix and making them resistant to apoptosis14. These phenotypic changes were shown to be reversible by treatment with a highly selective COX-2 inhibitor. Very recent work indicates that cyclooxygenase may play a vital role in the regulation of angiogenesis associated with neoplastic tumor cells15 . Hence, COX inhibitors may block the growth of blood vessels into developing tumors. COX-independent pathways also play an important role in the cancer chemopreventive properties of NSAIDs. Thus, it is understood that both COX-dependent and COXindependent pathways are involved in cancer chemoprevention

COX-2 in oral epithelial dysplasia and cancer

Expression of COX-2 has been evaluated in oral epithelial dysplasia and oral cancer. Results obtained are observed to be varying as depicted in ble 116-28 . It is well known that cancer cell development and survival is a multifactorial process, involving genetic mutation of normal cells as well as physiological changes within both cancer cells and also the body?s defense mechanisms29. Immune response to cancer cell development and progression is of particular importance as it might play a potential role in tumor formation. Unresolved immune responses, such as chronic inflammation, can promote the growth and progression of cancer. Within the immune system, cytotoxic CD8+ and CD4+ T cells, along with their characteristically produced cytokine interferon- γ (IFN-γ) function as the major anti-tumor immune effector cells, whereas tumor associated macrophages (TAM) or myeloidderived suppressive cells (MDSC) and their derived cytokines Interlukin-6, Tumor Necrosis Factor, Interlukin-1β and Interlukin-23 are generally recognized as dominant tumorpromoting forces. However, the roles played by CD4+, CD25+, Forkhead box (Fox) p3+ regulatory T lymphocytes and immunoregulatory cytokines such as Transforming Growth Factor -β in tumor development and survival remain elusive. These immune cells and the cellular factors produced from them, including both immunosuppressive and inflammatory cytokines, play dual roles in promoting or discouraging cancer development, and their ultimate role in cancer progression may rely heavily on the tumor microenvironment and the events leading to initial propagation of carcinogenesis30 . COX-2/PGE2 pathway has been demonstrated to influence every hallmark of cancer, including oral cancer. COX-2/PGE2 pathway has been suggested to play a role in suppression of apoptosis, via activation of the Ras-mitogen activated protein kinase (MAPK/ERK) pathway31. PGE2 has been reported to activate pro-survival pathways including PI3K/AKT pathway, protein kinase A signaling32 and activation of Epidermal Growth Factor (EGFR) signaling33. In addition to the apoptosis-suppressive effects of COX-2-derived PGE2, deregulated expression of COX-2 protein itself might also alter the susceptibility of cells to undergo apoptosis by reducing the cellular pool of its substrate arachidonic acid, which can stimulate apoptosis34. Aberrant activation of COX-2/PGE2 pathway might phenocopy activating mutations in the PI3K/ AKT and/or Ras-MAPK pathways, which could play an important role in promoting tumor progression. Indeed, deregulation of the COX-2/PGE2 pathway has been shown to behave in a similar manner to constitutively active Ras in murine intestinal adenomas, resulting in a positive feedback loop that boosts COX-2 expression and further stimulation of tumor growth35. COX2/PGE2 pathway prevents the receipt of antigrowth signals since over-expression of COX-2 has been reported to cause down-regulation of the TGFb type II receptor 14. The COX-2/PGE2 pathway, by enhancing cell survival and growth, serves to assist the cells for acquisition of further cellular alterations that contribute to immortalization and the progression towards the full malignant phenotype. Over-expression of COX-2 induces the production of angiogenic factors such as VEGF and basic fibroblast growth factor, which are instrumental in stimulating the formation of new blood vessels – a requirement for tumors should they wish to develop beyond a few millimeters in size36. The mechanism through which COX-2 might promote tumour vascularization is via the production of PGE2 and prostaglandin I2. These factors have been shown to participate in inducing endothelial cell dispersion and migration by integrin αVb3- mediated activation of the small guanosine 5?- triphosphatases Cdc42 and Rac37 . In vitro experiments have revealed that cells overexpressing COX-2 undergo phenotypic changes that could enhance their tumorigenic potential, such as exhibition of an increased adhesion to extracellular matrix proteins and resistance to apoptosis. It is believed that this proliferative activity of COX-2 primarily mediated by PGs14 . order to achieve metastases, cancer cells must exhibit a more motile, invasive phenotype, dissociate from neighboring cells within the tumour, invade through extracellular matrix components and intravasate into local blood or lymphatic channels38. Having made their escape from the primary tumour, cancer cells must then extravasate from the blood or lymphatics into the surrounding tissue in order to colonize distant sites. Several lines of evidence indicate that COX2 and the prostaglandins play important roles in aiding these processes – more specifically, PGE2 is thought to promote a more metastatic phenotype in cancer14 . Over-expression of COX-2 can modulate the adhesive properties of cancer cells and increase matrix metalloproteinase activity to promote invasion39. PGE2 promotes cytoskeletal reorganization and increases cancer cell migration and invasion via PI3K signaling. The stimulation of invasion and motility by PGE2 is dependent on the intracellular Src-mediated transactivation of EGFR40. Furthermore, hepatocyte growth factor signaling, which is classically associated with loss of cell-cell contact (or scattering) and invasive growth41, is also transactivated by PGE2 in an EGFR-dependent approach. COX-2, hepatocyte growth factor and β-catenin are co-expressed at the invasive front of tumor specimens42 , suggesting their interplay in tumorigenesis. COX2 has been identified as one of the four key „metastasis progression? genes, which collectively synergize to mediate both tumor development and metastasis to other organs43 . The contribution of COX-2 in carcinogenesis is due to its involvement in several key mechanisms including the conversion of pro-carcinogens to carcinogens as a consequence of arachidonic acid metabolism, stimulation of cell growth, inhibition of apoptosis through p53 suppression and bcl2 induction, stimulation of VEGF and angiogenesis, promotion of invasion and metastasis via matrix metalloproteinases induction and immunosuppression by IL-10 induction36,44. Cox-2 in potentially malignant oral lesions Along with numerous studies in conducted to evaluate the role of COX-2 in oral cancer, few studies have also been carried out to appraise if COX-2 plays a similar role in few of the lesions considered as potentially malignant oral lesions. As depicted in table 2 45-48, COX-2 has been shown to be overexpressed in oral submucous fibrosis (OSMF), oral lichen planus (OLP) and even in oral lichenoid reactions (OLR), as compared to the normal oral mucosa. It is well known that OLP is a chronic inflammatory disease for which the pathogenesis is not fully understood. OLP has autoimmune features and auto immunity has been suggested as a potential cause, whereas WHO has classified OLP as a premalignant condition. Association between chronic inflammation and cancer is known and chronic inflammation is one of the characteristics of OLP47. Increased expression of COX-2 suggests its definite role in OLP. COX-2 has been connected to both malignant development and autoimmunity but as malignant development of OLP is quite rare it was suggested that the increased levels of COX-2 support an autoimmune cause of the disease. As against, Lysitaet al48 suggest that sustained overexpression of COX-2 in the late stage of the disease could play a role in the malignant transformation of some OLP. In case of OSMF, very few studies have been conducted to assess the role of COX-2 in its pathogenesis. Aberrant and persistent tissue inflammations are believed to play an important role on the occurrence of tissue fibrosis. Tsai et al45 in their study demonstrated that COX-2 expression was significantly higher in OSMF specimens and expressed mainly by epithelial cells, endothelial cells, and cells with fibroblast morphology. Simultaneously they also observed the COX-2 expression in cells treated with arecoline and noticed that COX-2 expression was up-regulated as early as half an hour. This indicated that COX-2 expression is an early cellular response and regulated by arecoline at transcriptional level. Cox-2 in odontogenic cysts and tumors of the jaw Limitations in the number of studies related to expression of COX-2 in odontogenic cysts and tumors (table 3)49,50 makes it difficult to understand its exact role in pathogenesis of these lesions. Radicular cyst, being an inflammatory cyst, shows high expression of COX-2 in the lining epithelium, subepithelial fibroblasts, macrophages and endothelial cells, suggesting the role of COX-2 in their pathogenesis. KCOT is a benign neoplasm of odontogenic origin with an occasionally aggressive behavior leading to high recurrence rates. High COX-2 expression in the epithelial lining of KCOT the current knowledge of the role played by COX-2 in tumorigenesis further strengthen the current concept that the KCOT should be regarded as a neoplasm. Furthermore, the multitude of markers known to be overexpressed in KCOTs is suggestive of what could be called a 'network addiction' pattern, rather than a pathological mechanism dependant on a specific activated/suppressed gene, thus explaining its aggressive behavior50 . Cox-2 in salivary gland tumors Salivary gland tumors, most of which are rare benign tumors, represent a histologically heterogenous group with the greatest diversity of morphological and cellular features. Restricted number of studies has been conducted as to evaluate the role of COX-2 in few of the salivary gland tumors (table 4)51-55. Few studies showed no quantitative difference in COX-2 expression in different benign tumors51, while others exhibited considerable overexpression in the same52 . Warthin?s tumor showed COX-2 expression only in the epithelial component, with no expression in the lymphoid components54. These findings support the hypothesis that Warthin's tumors originate from heterotopic ductal epithelial cells of the parotid gland. However, the role of COX-2 expression in the pathogenesis of Warthin's tumors remains to be determined. Likewise, COX-2 expression has also been studied in malignant salivary gland tumors since overexpression of cyclooxygenase (COX)-2 in several human carcinomas suggests that COX-2 is related to carcinogenesis. However, the exact mechanism is still not understood55 . COX-2 in oral reactive lesions Most of the reactive lesions being inflammatory in process, have demonstrated COX-2 overexpression (table 5)56,57. Pulpal inflammation associated with dental caries56 andperiapical granuloma and periapicalcyst57have shown overexpression of COX-2. COX-2 -positive cells were detected in the epithelial cells and inflammatory cells. These studies suggest that COX-2 might play more important roles in the pathogenesis and development of periapical

CONCLUSION

Cyclooxygenase- 2 is chemical mediator that has a low to undetectable expression in normal tissues. It is a crucial element that functions through the production of prostaglandins. This molecule is particularly abundant in activated macrophages and cells at the site of inflammation. Its role in the disease process of various oral lesions is recognized. This mediator is a key factor in many regulatory pathways of the carcinogenic process. Understanding the role of cyclooxygenase -2 in the oral lesions can facilitate the incorporation of treatment protocols that target this molecule.

ACKNOWLEDGEMENT

Authors acknowledge the immense help received from the scholars whose articles have been cited and included in the references of this manuscript. The authors are also grateful to authors/ editor/ Publishers of all those articles, journal and books from where the literature for this article has been reviewed and discussed.

 

References:

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A Study by Humaira Tahir et al. entitled "Comparison of First Analgesic Demand after Major Surgeries of Obstetrics and Gynecology between Pre-Emptive Versus Intra-Operative Groups by Using Intravenous Paracetamol: A Cross-Sectional Study" is awarded Best Article for Vol 14 issue 14
A Study by Monica K. entitled "Risk Predictors for Lymphoma Development in Sjogren Syndrome - A Systematic Review" is awarded Best Article for Vol 14 issue 13
A Study by Mokhtar M Sh et al. entitled "Prevalence of Hospital Mortality of Critically Ill Elderly Patients" is awarded Best Article for Vol 14 issue 12
A Study by Vidya S. Bhat et al. entitled "Effect of an Indigenous Cleanser on the Microbial Biofilm on Acrylic Denture Base - A Pilot Study" is awarded Best Article for Vol 14 issue 11
A Study by Pandya S. et al. entitled "Acute and 28-Day Repeated Dose Subacute Toxicological Evaluation of Coroprotect Tablet in Rodents" is awarded Best Article for Vol 14 issue 10
A Study by Muhammad Zaki et al. entitled "Effect of Hemoglobin Level on the Severity of Acute Bronchiolitis in Children: A Case-Control Study" is awarded Best Article for Vol 14 issue 09
A Study by Vinita S & Ayushi S entitled "Role of Colour Doppler and Transvaginal Sonography for diagnosis of endometrial pathology in women presenting with Abnormal Uterine Bleeding" is awarded Best Article for Vol 14 issue 08
A Study by Prabhu A et al. entitled "Awareness of Common Eye Conditions among the ASHA (Accredited Social Health Activist) Workers in the Rural Communities of Udupi District- A Pilot Study" is awarded Best Article for Vol 14 issue 07
A Study by Divya MP et al. entitled "Non-Echoplanar Diffusion-Weighted Imaging and 3D Fiesta Magnetic Resonance Imaging Sequences with High Resolution Computed Tomography Temporal Bone in Assessment and Predicting the Outcome of Chronic Suppurative Otitis Media with Cholesteatoma" is awarded Best Article for Vol 14 issue 06
A Study by Zahoor Illahi Soomro et al. entitled "Functional Outcomes of Fracture Distal Radius after Fixation with Two Different Plates: A Retrospective Comparative Study" is awarded Best Article for Vol 14 issue 05
A Study by Ajai KG & Athira KN entitled "Patients’ Gratification Towards Service Delivery Among Government Hospitals with Particular Orientation Towards Primary Health Centres" is awarded Best Article for Vol 14 issue 04
A Study by Mbungu Mulaila AP et al. entitled "Ovarian Pregnancy in Kindu City, D.R. Congo - A Case Report" is awarded Best Article for Vol 14 issue 03
A Study by Maryam MJ et al. entitled "Evaluation Serum Chemerin and Visfatin Levels with Rheumatoid Arthritis: Possible Diagnostic Biomarkers" is awarded Best Article for Vol 14 issue 02
A Study by Shanthan KR et al. entitled "Comparison of Ultrasound Guided Versus Nerve Stimulator Guided Technique of Supraclavicular Brachial Plexus Block in Patients Undergoing Upper Limb Surgeries" is awarded Best Article for Vol 14 issue 01
A Study by Amol Sanap et al. entitled "The Outcome of Coxofemoral Bypass Using Cemented Bipolar Hemiarthroplasty in the Treatment of Unstable Intertrochanteric Fracture of Femur in a Rural Setup" is awarded Best Article Award of Vol 13 issue 24
A Study by Manoj KP et al. entitled "A Randomized Comparative Clinical Trial to Know the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block Against Multimodal Analgesia for Postoperative Analgesia Following Caesarean Section" is awarded Best Article Award of Vol 13 issue 23
A Study by Karimova II et al. entitled "Changes in the Activity of Intestinal Carbohydrases in Alloxan-Induced Diabetic Rats and Their Correction with Prenalon" is awarded Best Article of Vol 13 issue 22
A Study by Ashish B Roge et al. entitled "Development, Validation of RP-HPLC Method and GC MS Analysis of Desloratadine HCL and It’s Degradation Products" is awarded Best Article of Vol 13 issue 21
A Study by Isha Gaurav et al. entitled "Association of ABO Blood Group with Oral Cancer and Precancer – A Case-control Study" is awarded Best Article for Vol 13 issue 20
A Study by Amr Y. Zakaria et al. entitled "Single Nucleotide Polymorphisms of ATP-Binding Cassette Gene(ABCC3 rs4793665) affect High Dose Methotrexate-Induced Nephrotoxicity in Children with Osteosarcoma" is awarded Best Article for Vol 13 issue 19
A Study by Kholis Ernawati et al. entitled "The Utilization of Mobile-Based Information Technology in the Management of Dengue Fever in the Community Year 2019-2020: Systematic Review" is awarded Best Article for Vol 13 issue 18
A Study by Bhat Asifa et al. entitled "Efficacy of Modified Carbapenem Inactivation Method for Carbapenemase Detection and Comparative Evaluation with Polymerase Chain Reaction for the Identification of Carbapenemase Producing Klebsiella pneumonia Isolates" is awarded Best Article for Vol 13 issue 17
A Study by Gupta R. et al. entitled "A Clinical Study of Paediatric Tracheostomy: Our Experience in a Tertiary Care Hospital in North India" is awarded Best Article for Vol 13 issue 16
A Study by Chandran Anand et al. entitled "A Prospective Study on Assessment of Quality of Life of Patients Receiving Sorafenib for Hepatocellular Carcinoma" is awarded Best article for Vol 13 issue 15
A Study by Rosa PS et al. entitled "Emotional State Due to the Covid – 19 Pandemic in People Residing in a Vulnerable Area in North Lima" is awarded Best Article for Vol 13 issue 14
A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13
A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12
A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11
A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10
A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09
A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08
A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07
A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness
A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health
A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06
A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia
A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05
A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04
A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03
A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


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International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

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