International Journal of Current Research and Review
ISSN: 2231-2196 (Print)ISSN: 0975-5241 (Online)
logo
slider
slider
slider
slider
Bootstrap Slider

Indexed and Abstracted in: Crossref, CAS Abstracts, Publons, Google Scholar, Open J-Gate, ROAD, Indian Citation Index (ICI), ResearchGATE, Ulrich's Periodicals Directory, WorldCat (World's largest network of library content and services)

Search Articles

Track manuscript

Full Html

IJCRR - Vol 05 Issue 14, July, 2013

Pages: 16-23

Date of Publication: 29-Jul-2013


Print Article   Download XML  Download PDF

INDUCTION PROTOCOLS FOR NEURONAL TRANSFORMATION OF GLOBOSE BASAL STEM CELLS

Author: Avinash Thakur, Duraimurugan Muniswami, George Tharion, Indirani Kanakasabapathy

Category: Healthcare

Abstract:Objective(s): Consistent efforts with increasing optimistic outcome are being made to identify a candidate (neuron- progenitor cell) for a reliable therapeutic intervention of CNS injury. In this venture, recent years witnessed an increasing bang on the olfactory epithelium for suitable neuripotent stem cells. In this research work we aim at exploring the cultural characteristics and standardizing induction media for neuronal transformation of the potential multipotent Globose basal stem cells (GBC) residing in the basal compartment of the olfactory epithelium of rat olfactory mucosa. Methodology: GBC were isolated in pure form from olfactory mucosa of albino wistar rats using GBC-III monoclonal antibody and fluorescence activated cell sorting (FACS). Two different induction protocols were defined for the transformation of GBC into functional neurons. Results: GBC transformed into neurons and astrocytes in both the induction media. The neurons and astrocytes hence formed were immunohistologically characterized. Conclusion: This research work conclusively elucidates the cultural characteristics of a novel multipotent candidate (GBC) which can be induced into functional neurons using specific external niche and can prove to be beneficial for further research in neuro-regenerative therapies.

Keywords: Globose basal cell, olfactory mucosa, multipotent, induction, neuron, astrocytes

Full Text:

INTRODUCTION
For many decades neuroscientific researchers have been in the search of an ideal cell with the properties of absolute totipotency and regenerability in vitro and in vivo. Science has come very close to the quest, but still many unanswered questions remain. In this research work we aim at analyzing the neuronal potency of a group of very specialized stem cells present in the olfactory epithelium called the Globose basal cells (GBC) and evaluate their ability for continued renewal and transformation into neurons in culture environment using two different induction protocols with modifications of the existing protocols proposed by Greco et al 1 and Xiufang Guo et al 2. This would allow us to manipulate these cells to a therapeutic grade and assay their value for CNS injury treatment in humans using rat GBC or human GBC. GBC are small, round, morphologically non-descript and cyto-keratin negative cells that sit between the horizontal basal cells (HBC) below and the immature olfactory receptor neurons above, that proliferate at a high rate in the normal OE, are limited to the OE and are poorly characterized at the level of their molecular phenotype.

Neurogenesis is a process by which new neurons are generated from a precursor cell. This process requires the proliferation, differentiation and migration of neurogenic stem cells into neurons. It was believed for many decades that in mammals neurogenesis occurred only during embryonic life, but recent work in this field has made it evident that neuronal regeneration occurs even after birth in specific tissues like the hippocampus, dentate gyrus, subventricular zone and olfactory epithelium 3. The formation of neurospheres in olfactory epithelium and other tissues like spinal cord 4, eye 5, ear 6 and hippocampus 7 has been extremely important in determining the role of stem and progenitor cells in trans-differentiation into neuronal elements.  In marked contrast to other parts of the nervous system, there is substantial anatomical and functional recovery of the olfactory epithelium and its projection into the CNS even in the face of overwhelming injury. For example, in the case of epithelial lesions caused by a single exposure to methyl bromide (MeBr), the olfactory epithelium is restored to a status that is indistinguishable from unlesioned epithelium within 6–8 weeks after damage 8. In the past few decades, variety of fetal, embryonic and adult stem and progenitor cells have been tried with conflicting outcome for cell therapy of central nervous system injury and diseases9. Transplantation of adult animal and human olfactory epithelium (OE) cells has been used in the past for experimental and clinical correction of spinal injuries10. Embryonic stem cells have enormous ability to regenerate into different types of cells in the body; but they also share the possibilities of immune rejection, adverse effects of immunosuppressive therapy and many ethical issues which exclude them as an ideal candidate for clinical work.  Olfactory mucosa is readily accessible, easily biopsied for autologous cell transplantation and regenerates completely without any loss of function. These properties make the olfactory epithelial stem cells as the ideal candidate for use in clinical research and therapy. The adult OE is a unique and a complex tissue containing heterogeneous population of epithelial cells.  Apart from the support cells and neruoreceptor cells, this complex is said to retain a kind of progenitor cells that are competent to make neurons (neural stem cells) and non- neural support cells 11,12,13. This study has been undertaken to understand the culture requirements, proliferative and differentiative properties of Globose Basal Cells since there is shortage of data regarding these properties of GBCs because of non-conclusive trials in the past to prove their multipotency. This research work conclusively establishes that GBC are the group of neural stem cells capable of such neuronal differentiation.

MATERIALS AND METHODS
Six Albino wistar rats were used at different occasions and their nasal septum was completed excised along three surgical lines: the arc of the perpendicular plate, the cribriform plate and the ceiling of the oral cavity to obtain the olfactory mucosa and the respiratory mucosa was discarded. Olfactory mucosa of humans and rat was stained with haematoxylin and eosin and also with toulidine blue to do comparative study of the histological characteristics of the OE and its basal compartments (fig.1a, b). The OE was separated from the mucosa under Leica EZ2HD dissecting microscope by enzymatic treatment with 0.5 ml of Dispase-II for 45 minutes. The epithelial cells were separated from each other with the use of an enzymatic cocktail containing collagenase – 1 mg/ml, hyaluronidase – 1.5 mg/ml, trypsin inhibitor – 0.1 mg/ml and cultured in the epithelial medium composed of Dulbeco’s modified Eagle medium / F12 (1: 1) – 47.5 ml, 2% fetal bovine serum – 1.0 ml, N2 supplement – 0.5 ml, epidermal growth factor (25 ng / ml) – 12.5 µl and L-glutamine – 0.5 ml for generation of neurospheres. GBC were isolated in pure form (fig.2a) from the epithelial cells by tagging them with a highly specific monoclonal antibody GBC-III (fig.2b) and sorting them with fluorescence activated cell sorter (FACS). GBC-III is a mouse monoclonal IgM antibody which recognizes a 40 kDa surface antigen which is a laminin receptor surface protein. It is highly specific as a marker for GBCs, unlike the earlier antibodies used like GBC-I which were nonspecific markers for GBCs and showed positive reaction even with HBCs, Sus and duct cells14. GBC-III was received with courtesy from TUFTS University (USA) in powdered form. It was reconstituted into the recommended volume of 250 µl. It was used in a concentration of 1:100 for immunostaining.

Two different induction media were used to trans- differentiate GBC into neurons and glial cells. Induction medium I was composed of Ham’s F12 media, fetal bovine serum – 2%, B-27 supplement– 1%, retinoic Acid (RA) – 20 mM and bFGF (beta fibroblast growth factor) - 12.5 ng/ml. GBC were cultured in this medium for 12 days and morphological changes were recorded regularly. GBC were also plated for 21 days on induction medium II which was composed of neurobasal medium, B-27 supplement - 2%, L-Glutamine - 0.5 mM, Penicillin - 100 µl, Streptomycin - 100 µl and Amphotericin - 200 µl.

Differentiated neurons and astrocytes were characterized immunologically using numerous primary antibodies for neuron specific markers like microtubule associated protein-2 (MAP-2), beta III tubulin, neuronal nuclei (NeuN), neurofilament H, M and glial fibrillary acidic protein (GFAP for astrocytes). Cover slips coated with poly D-lysine were plated with the differentiated neuronal cells from both the induction media. 4% paraformaldehyde was used as the fixative. Glass slides were prepared and kept moist for mounting the cover slips. After blocking with 2% goat serum and 0.1% triton X the slides were treated with the primary antibodies and incubated overnight at 40C. Slides were then treated with the respective secondary antibodies and incubated at 370C for 1 hour. The slides were then examined under immunofluorescent microscope.

RESULTS

Striking similarities were found during the staining of human and rat olfactory mucosa. The ciliated, pseudostratified OE was made of the similar three basic cell types, namely; olfactory receptor neurons (ORNs), basal cells and sustentacular cells. ORNs and sustentacular cells were similar in morphology and their location in the OE. The basal compartment of the rat OE consisted of two types of cells, namely; HBC located closer to the basal lamina and GBCs located in a layer above the HBCs (fig. 1b). The basal compartment of human OE consisted of only one type of cells which were globose in shape which are also called GBC (fig. 1a). This has been described earlier in the literature and it has been suggested that these human GBCs act and possess the properties of both the cell types present in rodents 15. The lamina propria was much thicker comparatively in the human OM with higher density of bowman’s glands.

Neurosphere formation began in the olfactory epithelial medium by the end of 3 days (fig. 3a). These neurospheres were passaged on the 6th day to obtain the 2nd generation of neurospheres (fig. 3b). Multiple neurospheres were formed by the end of 2 weeks. The self renewal potential of olfactory stem cells was evident from the formation of multiple generations of neurospheres. During this period of 2 weeks, many of the neurospheres had started to proliferate. Hence an effective method of generating neurospheres from olfactory epithelial cells was established. EGF and N-2 supplement seem to play a significant role in providing an optimum external niche for formation of multiple generations of neurospheres from epithelial stem cells. Epidermal growth factor (EGF) is a potential stem cell mitogen allowing cell proliferation through activating signaling pathway and inducing the production of beta fibroblast growth factor (bFGF) from the progenitor cells. It was also established that neurosphere generation depended on the initial plating density. An ideal cell density to be plated on the culture plates is required to avoid excessive or minimal growth of cells and neurosphere formation. Cell density of 10 X 105 was found to be ideal for optimal growth of epithelial stem cells and for formation of multiple generations of neurospheres. 99% pure GBC were isolated using GBC-III antibody and FACS.

Two different induction media; medium I and medium II were used to differentiate GBCs into neurons (fig.4a, b). These media were composed to meet the culture and differential needs of the growing GBCs and assist them to easily and effectively transform into neuronal cell types. Retinoic acid was used in medium I and hence all the work while handling the medium was done under dark conditions. B-27 supplement was also used to assist the cell differentiation and growth. bFGF was added to the medium II to assist in cell growth. Antibiotics were added to the media to avoid contamination with bacterial agents. 2nd passage GBC was plated in medium-I for 14 days and in medium-II for 21 days. Medium-I was left unchanged whereas medium-II was changed every 3 days using all sterile precautions. GBC plated onto the two different induction media for different number of days transformed into mature neurons and other glial cells by the end of the induction protocol in both the media (fig.4c, d). These neurons demonstrated a single, long primary process and multiple numbers of smaller secondary processes. GBC also transformed into astrocytes in both the induction media.
The differentiated neurons were positive for all the neuron specific markers (fig. 5a, b, c, d), hence proving the viability and functionality of the differentiated neurons. The differentiated cells were also positive for GFAP (glial fibrillary acidic protein), hence proving the transformation of GBCs and the viability of these astrocytes (fig. 5e). Mature neurons of rat were also stained with neural markers as positive control (fig. 5f). Electrophysiological characterisation of the differentiated neurons was tried using a whole cell voltage clamp. The cell membranes of the neurons were extremely fragile and it was not possible to obtain a high resistance seal on them. Hence voltage gated channels present on these neurons could not be identified. Further studies on characterizing the ion gated channels in the differentiated neurons would be extremely helpful in the future to determine the functionality and excitability of these neurons.

DISCUSSION
Neurogenesis begins in the early embryonic period (4th week) and continues 10 to 12 years after birth 16. The nervous system development is completed only during the adolescent period when myelination of the neurons of major tracts is completed 17. Neurogenesis in adults has been a topic of discussion in the field of neuroscience for decades with varying opinions from different researchers in this field. Early researchers believed the nervous system to be fixed and incapable of proliferation and regeneration based on the their opinions that neurons and non-neuronal cells in the nervous system could not divide actively by mitosis and they lacked the potential to transform from simple to more complex forms of neuronal morphologies. Another reason for such belief was inability in the past to demonstrate progenitor stem cells residing in the nervous system niche by specific markers. Cells in the nervous system could be demonstrated only by negative staining which was very non-specific13,18,19. Two important factors play a significant role in neurogenesis in adults. First being the microenvironment in which the stem cells responsible for neurogenesis reside and the other being the germ cell lineage of these stem cells. Hence it is important to provide these external and internal factors to the stem cells to promote their induction into neuronal cells. This research work studies one such population of stem cells residing in the olfactory epithelium which have the niche required to get accepted in the CNS environment and they are derived from the same germ line as the neuronal cells. This gives a hint that these might be the ideal neural progenitor cells which can be easily harvested and used for autologous transplantations.

The most recent development in this field of research has been the demonstration of neurogenesis in the olfactory system including the olfactory bulbs and more importantly in the olfactory mucosa. This finding proved very beneficial for working on the neural stem cells because of the easy accessibility of the olfactory mucosa. Numerous researchers have proved that there is ongoing neurogenesis throughout life in the basal compartment of the olfactory epithelium but they have not been able to define concretely, the lineage of cells responsible for this neuropotency. The dilemma still remains that whether HBC or GBC are the main colony of cells responsible for this ongoing neurogenesis. This research work on GBC has been able to prove with certain solidarity that it’s the GBC that behave as neural progenitor cells in the basal compartment of the OE. We study and standardize the microenvironment required for these cells to transform into neuronal cells.

CONCLUSIONS
This research work has been able to clarify with solidarity the prevailing ambiguity of the olfactory stem cells and has derived some definite conclusions about the cellular characteristics and cultural requirements of GBC for their neuronal transformation. It has now conclusively been made evident that Globose basal cells are the colony of neural stem cells residing in the basal compartment of the olfactory epithelium responsible for the ongoing neurogenesis in the OE throughout adult life and GBC require an ideal external microenvironment containing both internal and external factors for their proliferation, neurosphere formation and differentiation.

References:

  1. Fricker RA, Carpenter MK, Winkler C, Greco C, Gates MA, Björklund A. Site-specific migration and neuronal differentiation of human neural progenitor cells after transplantation in the adult rat brain. J Neurosci. 1999;19(14):5990-6005. 
  2. Guo X, Johe K, Molnar P, Davis H, Hickman J. Characterization of a human fetal spinal cord stem cell line, NSI-566RSC, and its induction to functional motoneurons. J Tissue Eng Regen Med. 2010;4(3):181-93.
  3. G. J. Brewer. Regeneration and proliferation of embryonic and adult rat hippocampal neurons in culture. Exp. Neurol. 1999; 159, No. 1, 237-247.
  4. Rossi SL, Nistor G, Wyatt T, Yin HZ, Poole AJ, Weiss JH, Gardener MJ, Dijkstra S, Fischer DF, Keirstead HS. Histological and functional benefit following transplantation of motor neuron progenitors to the injured rat spinal cord. PLoS One. 2010;29;5(7):e11852.  
  5. Ahmad S, Osei-Bempong C, Dana R, Jurkunas U. The culture and transplantation of human limbal stem cells. J Cell Physiol. 2010;225(1):15-9. 
  6. Guo QC, Zhang Y, Wang YF, Tang HF, Wu PY, Liu ZY, Li ZQ. Distribution and differentiation of marrow stem cells transplanted by different ways in ischemic myocardium and other organs in rabbits. Clin Transplant. 2010; 10.1111/j.1399-0012.2010.01375.x .
  7. Shetty AK, Turner DA. In vitro survival and differentiation of neurons derived from epidermal growth factor-responsive postnatal hippocampal stem cells: inducing effects of brain-derived neurotrophic factor. J Neurobiol. 15. 1998;35(4):395-425.
  8. Schwob, J.E., Youngentob, S.L. and Mezza, R.C Reconstitution of the rat olfactory epithelium after methyl bromide-induced lesion. J. Comp. Neurol. 1995; 359, 15–37.
  9. V. Viktorov and G. T. Sukhikh, Vestn. Rossiisk. Akad. Medico-biological aspects of using stem cells. Med. Nauk. 2002; No. 4, 24-30.
  10. S. C. Barnett and J. S. Riddell. Olfactory ensheathing cells (OECs) and the treatment of CNS injury: advantages and possible caveats. J. Anat. 2004; 204, No. 1, 57-67.
  11. Ramon-Cueto, F. Valverde. Olfactory bulb ensheathing glia: a unique cell type with axonal growth-promoting properties. Glia. 1995; 14 163– 173.
  12. Jang W, Lambropoulos J, Woo JK, Peluso CE, Schwob JE. Maintaining epitheliopoietic potency when culturing olfactory progenitors. Exp Neurol. 2008;214(1):25-36.
  13. M. Caggiano, J.S. Kauer, D.D. Hunter. Globose basal cells are neuronal progenitors in the olfactory epithelium: a lineage analysis using a replication-incompetent retrovirus. Neuron. 1994; 13 339– 352.
  14. Jang W, Kim KP, Schwob JE. Nonintegrin laminin receptor precursor protein is expressed on olfactory stem and progenitor cells. J Comp Neurol. 2007;502(3):367-81.
  15. C.G. Hahn, L.Y. Han, N.E. Rawson, N. Mirza, K. Borgmann-Winter, R.H. Lenox, S.E. Arnold. In vivo and in vitro neurogenesis in human olfactory epithelium. J. Comp. Neurol. 2005;483, 154– 163.
  16. T. Paus et al. Structural maturation of neural pathways in children and adolescents: In vivo study. Science. 1999; 283, 1908.
  17. Flechsig, Paul. Developmental (myelogenetic) localisation of the cerebral cortex in the human subject. The Lancet. 1901; 1028.
  18. A.L. Calof, J.S. Mumm, P.C. Rim, J. Shou. The neuronal stem cell of the olfactory epithelium. J. Neurobiol. 1998; 36 190– 205.
  19. L.A. Carter, J.L. MacDonald, A.J. Roskams. Olfactory horizontal basal cells demonstrate a conserved multipotent progenitor phenotype. J. Neurosci. 2004;24 5670–5683.

Announcements

Dr. Pramod Kumar Manjhi joined Editor-in-Chief since July 2021 onwards

COPE guidelines for Reviewers

SCOPUS indexing: 2014, 2019 to 2021


Awards, Research and Publication incentive Schemes by IJCRR

Best Article Award: 

One article from every issue is selected for the ‘Best Article Award’. Authors of selected ‘Best Article’ are rewarded with a certificate. IJCRR Editorial Board members select one ‘Best Article’ from the published issue based on originality, novelty, social usefulness of the work. The corresponding author of selected ‘Best Article Award’ is communicated and information of award is displayed on IJCRR’s website. Drop a mail to editor@ijcrr.com for more details.

Women Researcher Award:

This award is instituted to encourage women researchers to publish her work in IJCRR. Women researcher, who intends to publish her research work in IJCRR as the first author is eligible to apply for this award. Editorial Board members decide on the selection of women researchers based on the originality, novelty, and social contribution of the research work. The corresponding author of the selected manuscript is communicated and information is displayed on IJCRR’s website. Under this award selected women, the author is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.

Emerging Researcher Award:

‘Emerging Researcher Award’ is instituted to encourage student researchers to publish their work in IJCRR. Student researchers, who intend to publish their research or review work in IJCRR as the first author are eligible to apply for this award. Editorial Board members decide on the selection of student researchers for the said award based on originality, novelty, and social applicability of the research work. Under this award selected student researcher is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.


Best Article Award

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


RSS feed

Indexed and Abstracted in


Antiplagiarism Policy: IJCRR strongly condemn and discourage practice of plagiarism. All received manuscripts have to pass through "Plagiarism Detection Software" test before Toto Macau forwarding for peer review. We consider "Plagiarism is a crime"

IJCRR Code of Conduct: To achieve a high standard of publication, we adopt Good Publishing Practices (updated in 2022) which are inspired by guidelines provided by Committee on Publication Ethics (COPE), Open Access Scholarly Publishers Association (OASPA) and International Committee of Medical Journal Editors (ICMJE)

Disclaimer: 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.



ABOUT US

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

Contact

148, IMSR Building, Ayurvedic Layout,
        Near NIT Complex, Sakkardara,
        Nagpur-24, Maharashtra State, India

editor@ijcrr.com

editor.ijcrr@gmail.com


Copyright © 2022 IJCRR. Specialized online journals by ubijournal .Website by Ubitech solutions