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IJCRR - 14(11), June, 2022

Pages: 37-46

Date of Publication: 03-Jun-2022


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Factors Affecting the Production of Astaxanthin in the Microalgae Haematococcus pluvialis: A Review

Author: Muhsinin Soni, Aligita Widhya, Rostinawati Tina, Levita Jutti

Category: Healthcare

Abstract:Astaxanthin, a natural red pigment that belongs to the carotenoid group, has been known as a super antioxidant due to its very strong antioxidant activity (65 times higher than vitamin C, 54 times more potent than -carotene, and 14 times higher than vitamin E). Haematococcus pluvialis is known as microalgae with a high astaxanthin content. The benefit of astaxanthin in health issues is mainly its potential as the treatment for degenerative diseases caused by reactive oxygen or nitrogen species. Thus, it is important to develop Haematococcus pluvialis microalgae as a rich source of natural astaxanthin in the health and pharmaceutical industries.

Keywords: Astaxanthin, Antioxidants, Haematococcus pluvialis, Carotenoids, Microalgae, Anticancer

Full Text:

INTRODUCTION

Astaxanthin (3,3'-dihydroxy-β-carotene-4,4'dione) is a secondary metabolite belonging to the carotenoid group.1–3 Astaxanthin has a high value in the pharmaceutical, nutraceutical, and cosmetic fields because of its potent antioxidant potential with an IC50 value of 39.1 ± 1.14 ppm.4 The antioxidant activity produced by astaxanthin is 65 times higher than that of vitamin C, 54 times more powerful than β-carotene, 14 times higher than vitamin E, and 20 times stronger than its synthetic form.5 Due to its potent antioxidant activity, astaxanthin can be used to treat several degenerative diseases caused by free radicals.6

Various sources of astaxanthin in nature can be obtained from several microorganisms such as the fungus Phaffia rhodozyma, microalgae Chlorella zofingiensis, and Haematococcus pluvialis.7–9 However, of these microorganisms, H. pluvialis is known to show the highest astaxanthin accumulation capacity of up to 4% dry weight under stress conditions.10,11

The market price of astaxanthin also varies, ranging from $2,500 to 7,000/kg. In 2014, the global market potential of astaxanthin was approximately 280 tonnes for $400 million. However, more than 95% of the market is synthetic astaxanthin types that are sourced from petrochemicals. This happens because the production cost of synthetic astaxanthin is relatively cheaper than natural astaxanthin obtained from microalgae.12 This synthetic type of astaxanthin has 20 times lower antioxidant power than the natural type.5 In addition, related to safety issues, synthetic astaxanthin types are still not allowed to be consumed by humans due to differences in stereochemical form with natural type. Therefore, its use is only permitted as feed and dye for aquaculture organisms.10

Astaxanthin production can be done by various methods, including culture, chemical synthesis, and genetic engineering. The culture method can be done by adding stress induction to microalgae because it is known that H. pluvialis is a microalgae that can accumulate astaxanthin under stress. These stress conditions can be caused by several factors, including light stress,13,14 nutritional deficiency,15 salinity stress,16,17 the addition of Fe2+,18,19 and so on. In addition, another method is chemical synthesis using asta-C15-triarylphosphonium salt and C10-dialdehyde with the Wittig reaction,20 which produces synthetic astaxanthin with antioxidant activity 20 times lower than natural astaxanthin. Then another method, genetic engineering, in several research journals has been widely reported overproduction of astaxanthin in several microorganisms such as fungi and bacteria.21 This review article contains biological and physiological conditions, biochemical content, and methods of producing astaxanthin from H. pluvialis by culture and genetic engineering.

Biology of H. pluvialis

  1. Taxonomy

H. pluvialisis a biflagellate unicellular microalgae that lives in freshwater. According to Lorenz (1999),22 the classification of H. pluvialis microalgae is as follows:

  1. Habitat

The habitat of H. pluvialisis spread evenly in the world, especially in temperate areas. This microalgae has been isolated in Europe, Africa, North America, and Himachal Pradeslv India.23,24 H. pluvialis is also found in various environmental conditions with extreme climates, which may be lethal to other types of microalgae. This is because H. pluvialis can defend itself by forming encysts (cells become closed with a thick membrane) quickly when under stress and extreme conditions.25

  1. Morphology

The cell structure of H. pluvialis is similar to that of some groups of volvocalean green microalgae. The life cycle of H. pluvialis consists of four phases with different cellular morphology, namely macrozooid (zoospore), microzooid, palmella, and hematocyst (aplanospore).10,26 The following is the morphology of H. pluvialis microalgae with descriptions (A) Motile macrozoid cells (zoospores) with a size <10 m or 20 m, (B) Microzoid cells, (C) Palmella cells with accumulation of astaxanthin, (D) Hematocyst cells with accumulation of astaxanthin with size > 50 m.

The macrozoid, microzoid, and palmella phases are also known as the green vegetative phase. The microzoid phase (zoospore) is when the cell has a spherical, elliptical or pear-shaped shape with two flagella of the same length and appears anteriorly and has cup-shaped chloroplasts (Figure 1A). In this phase, with the optimum environment, flagellated cells undergo rapid division and growth, producing 2-8 daughter cells.

Figure adapted from Shah et al. (2016),27 which is licensed under the Creative Commons Attribution License.

However, suppose the environmental conditions are unfavorable (stress). In that case, the cell will remove the flagella and begin to expand in size by forming an amorphous structure layered on the inside of the extracellular matrix and develops into non-motile cells called palmella (Figure 1B).28 In this phase, the H. pluvialis cell wall thickens and consists of three layers. The first layer is a trilaminar layer containing materials such as sporopollenin, an algaenan that is resistant to acetolysis.29 According to Kim et al. (2016),30 the content of algaenans in the cell walls of H. pluvialis microalgae will inhibit the extraction process using several solvents such as acetone, methanol, dichloromethane. The second and third layers contain mannose and cellulose.28,31,32

The hematocyst phase was also referred to as the non-motile phase with astaxanthin accumulation (Fig. 1C and 1D). This phase occurs when the state of stress continues. This stress state can be in the form of nutritional deficiency, light stress with a certain intensity, salinity stress, and the addition of certain chemicals that can induce stress. Under these conditions, the palmella will turn into an asexual form or hematocyst (aplanospore). Mature hematocysts accumulate large amounts of carotenoids, especially astaxanthin, stored in lipid droplets in the cytoplasm.28

Figure 2: Illustration of the life cycle of H. pluvialis.

Figure adapted from Wayama et al. (2013),33 which is licensed under the Creative Commons Attribution License.

After the environmental conditions return to normal and optimal, the hematocyst (aplanospore) will germinate again to form a microzoid (zoospore) which will re-initiate the start of a new vegetative growth cycle (Figure 3).33

Biochemical Content

The cellular content of the H. pluvialis microalgae varies between the green phase and the red phase due to its unique life cycle. The biochemical range of H. pluvialis in the green phase and red phase according to 34 is listed in Table 1.

Description (-): no data reported

According to Table 1, H. pluvialis produced 81.2% Astaxanthin (including ester) in the red phase. This amount is the highest compared to primary metabolites (Proteins, Lipids, Carbohydrates) and other carotenoid compounds. The green phase does not produce astaxanthin. H. pluvialis enters a logarithmic phase (growth phase) and produces more primary metabolites during this phase.

Astaxanthin

  1. Sources of Astaxanthin

Natural sources of astaxanthin are found in several organisms, including algae, bacteria, fungi, salmon, shrimp, lobster.35 But for the mass production of astaxanthin, microorganisms such as fungi and microalgae are more widely used because of their rapid growth. Some of the natural astaxanthin-producing microorganisms are listed in Table 2.

According to Table 2, H. pluvialis is the microalgae that produce the most significant amount of astaxanthin (up to 3.8%) (excluding esters). HPLC and LC-MS methods for analyzing astaxanthin compounds. The biomass of H. pluvialis was homogenized and extracted with acetone several times. The extracts were combined, evaporated with a rotavopar, and then redissolved in acetone.

  1. Astaxanthin Biosynthesis

Astaxanthin biosynthesis in H. pluvialis is a complex series of processes that occur under stress conditions along with triacylglycerol (TAG) accumulation. Both compounds are deposited in lipid droplets in the cytosol during the red phase. The formation of astaxanthin begins with the glycolysis process, which produces pyruvate and glyceraldehyde-3-phosphate (G3P). Furthermore, pyruvate, together with glyceraldehyde-3-phosphate (G3P), will form the compound Isopentenyl Pyrophosphate (IPP) as the primary precursor in the synthesis of carotenoids.

Astaxanthin belongs to the carotenoid group, is one of the C40 tetraterpenes synthesized from the isoprene unit Isopentenyl Pyrophosphate (IPP). In principle, IPP synthesis can originate from two different pathways: the mevalonate pathway (MVA) occurring in the cytosol and the non-mevalonate pathway (MEP) or the 1-deoxy-D-xylulose-5-phosphate (DOXP) pathway occurring in chloroplasts.43–45

In H. pluvialis, IPP is synthesized from the non-mevalonate pathway. Furthermore, IPP undergoes isomerization to dimethylallyl diphosphate (DMAPP). Some research results indicate that the conversion is catalyzed by the enzyme isopentenyl pyrophosphate isomerase (IPI) encoded by the ipi1 and ipi2 genes during astaxanthin accumulation.2 However, the results of another study also stated that neither of the ipi1 and ipi2 genes was increased as long as H. pluvialis cells accumulated astaxanthin.46 Another study reported that another enzyme with similar activity, namely 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (HDR), was more likely to be responsible for catalyzing the intermediate conversion of IPP to DMAPP.46–48

Elongation of the isoprene chain begins with a DMAPP molecule, and the addition of three IPP molecules is catalyzed by the enzyme geranyl-geranyl pyrophosphate synthase (GGPS).49,50 The next step of this process is the formation of the compound C20 geranyl-geranyl pyrophosphate (GGPP). GGPP is converted to C40-phytoene as a precursor of astaxanthin and other carotenoids with the help of the phytoene synthase (PSY) enzyme encoded by the psy gene coupled with the head-to-tail condensation of two GGPP molecules.50

Figure 4. Biosynthesis of astaxanthin in H. pluvialis27

The formation of lycopene takes place through four desaturation steps catalyzed by two enzymes, namely the enzyme phytoene desaturase (PDS), which is encoded by the pds gene and z-carotene desaturase (ZDS), which is encoded by the zds gene.51,52 The desaturation reaction will increase the number of conjugated double bonds in the carbon chain to form chromophore groups in carotenoids, change the colorless molecule of phytoene to the lycopene, and produce a red color.50

Lycopene undergoes cyclization catalyzed by the enzyme lycopene cyclase (LCY-e and LCY b), which is encoded by the lcy gene. Cyclization of carotenoid biosynthesis in most organisms produces a-carotene (a precursor to lutein) and β-carotene (a precursor to carotenoids including astaxanthin). The last two oxygenation processes are catalyzed by the β -carotene ketolase (BKT) enzyme encoded by the bkt gene, and the β-carotene hydroxylase (CrtR-b or BKH) enzymes encoded by the bkh or crtR-b genes are the final stages of astaxanthin synthesis.53–55

  1. Pharmacological Activity of Astaxanthin

Astaxanthin as a nutraceutical has a variety of pharmacological activities, including those in Table 3.

Description: ROS: Reactive Oxygen Species; KATO-III: Human gastric carcinoma cell line; SNU-1: Human gastric carcinoma cell line; GLUT4: Glucose transporter type 4; IRS-1: Insulin receptor substrate-1; INF-γ: Interferon -γ; IL-2: Interleukin-2; ALT: alanine aminotransferase; AST: aspartate aminotransferase.

Astaxanthin Production Method

  1. Culture Method

Culture System

In general, microalgae culture systems are divided into three: photoautotrophic, heterotrophic, and mixotrophic systems. H. pluvialis allows cultivation using all three methods, either with open or closed systems.27 In the phototropic system, microalgae are very dependent on light as an energy source and CO2 as a carbon source, both light from lamps or the sun. In heterotrophic systems, microalgae growth requires organic carbon as an energy source. Commonly used organic carbon substrate sources include glucose, acetate, and glycerol.62 In this condition, the microalgae cell density achieved was higher than the phototropic condition, so that the cost required for harvesting was lower. The mixotrophic system is a combination of phototropic and heterotropic methods. The microalgae that grow in this system can assimilate sunlight and organic carbon as energy sources simultaneously or alternately.

Culture systems, especially those that require light (photoautotrophic), are divided into 2: closed and open culture systems. Advantages and disadvantages of culture with closed and open systems can be seen in Table 4.

Cultural Conditions

The success of microalgae culture is strongly influenced by several important factors, including nutritional and environmental factors. H. pluvialis culture conditions can be seen in Table 5.

Stress Induction

H. pluvialis can accumulate astaxanthin under stress. The accumulation of astaxanthin is a response of microalgae to protect themselves from oxidative stress conditions.70 Several studies of stress induction, either physically or chemically, are listed in Table 6.

Harvesting

An efficient harvesting technique is an important step that must be done to get a high concentration of harvested biomass. Several harvesting methods commonly used for H. pluvialis are flotation and centrifugation methods.27,73

  • Centrifugation Method

Centrifugation is a method of harvesting microalgae based on the application of rotary power to precipitate microalgae cells so that they are separated from the liquid growth medium. The separation was supported by the difference in density between the microalgae cells and the liquid medium in which the cells grew. The centrifugation method can produce microalgae in a paste with a solid content of up to 15%. Several studies also show that the faster the centrifugation cycle, the microalgae biomass obtained can reach up to 95%.

  • Flotation method

This method is a separation process based on gravity where the microalgae cells attach to air or gas bubbles so that the cells float on the surface. Under these conditions, microalgae cells can be harvested easily. In certain types of microalgae, cells can flow naturally if the lipid content in the cells increases. In the flotation method, the need for operational costs will be even greater if it involves flocculants.

Extraction

Extraction methods commonly used include maceration and percolation.74 Astaxanthin is a lipophilic compound and is soluble in organic solvents and oils. Organic solvents such as acetone, DMSO, methanol, n-hexane, and vegetable oils such as olive oil, soybean oil, and corn oil have been used for astaxanthin extraction.35,74

  1. Genetic Engineering

The development of biotechnology today also supports the use of microalgae as a producer of bioactive compounds. Most of the bioactive compounds produced by microalgae are secondary metabolites, which have low cellular production. So that the mass production of bioactive compounds from microalgae culture (without modification and engineering) is still not efficient; on the other hand, the synthesis of bioactive compounds with chemicals, especially astaxanthin compounds, will produce products that are stereochemically different from the natural products so that they are not allowed to be consumed by humans.5 However, with the advancement of biotechnology, the "factory" of microalgae biomass can be made more optimal. The use of science and methods of mutagenesis and genetic engineering is a solution that must continue to be developed. Several studies on the production of carotenoid compounds such as astaxanthin by genetic engineering are listed in table 7.

CONCLUSION

This study provides valuable pieces of information on astaxanthin, particularly regarding its pharmacology activities, biosynthesis pathway, various methods of its production in microalgae, harvesting, and extracting techniques, that will add insight to uncover the critical area of astaxanthin from microalgae.

ACKNOWLEDGEMENT

The authors thank the Ministry of Education, Culture, Research, and Technology (grant No. 10/E1/KPT/2021). The funding source did not involve in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

CONFLICT OF INTEREST

None declared.

FUNDING

Source of funding from Ministry of Education, Culture, Research, and Technology (grant No. 10/E1/KPT/2021).

AUTHOR’S CONTRIBUTIONS

Soni Muhsinin (SM) is responsible for the conception of the study. SM and Widhya Aligita (WA) collected the articles, drafted them, and wrote the manuscript. Tina Rostinawati (TR) and Jutti Levita (JL) supervised, reviewed, and finalized the manuscript. All authors have read and approved the final manuscript to be published.

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66. Mascia F, Girolomoni L, Alcocer MJP, Bargigia I, Perozeni F, Cazzaniga S, et al. Functional analysis of photosynthetic pigment binding complexes in the green alga Haematococcus pluvialis reveals distribution of astaxanthin in Photosystems. Sci Rep. 2017 Dec;7(1):16319.

67. Fabregas J, Dominiguez A, Regueiro M, Maseda A, Otero A. Optimization of culture medium for the continuous cultivation of the microalga Haematococcus pluvialis. 2000;53:530–5.

68. Sarada R, Usha T, Ravishankar GA. Influence of stress on astaxanthin production in Haematococcus pluvialis grown under different culture conditions. 2002;623–7.

69. Rohimawati R, Marwani E. Produktivitas Astaxanthin dari Haematococcus pluvialis pada Pemberian Konsentrasi Nitorgen Berbeda dalam Fotobioreaktor. 2017;2:1–5.

70. Brown DR, Gough LA, Deb SK, Sparks SA, McNaughton LR. Astaxanthin in Exercise Metabolism, Performance and Recovery: A Review. Front Nutr. 2018 Jan 18;4:76.

71. Shang M, Ding W, Zhao Y, Xu JW, Zhao P, Li T, et al. Enhanced astaxanthin production from Haematococcus pluvialis using butylated hydroxyanisole. 2016;236:199–207.

72. Zhao Y, Yue C, Ding W, Li T, Xu JW, Zhao P, et al. Butylated hydroxytoluene induces astaxanthin and lipid production in Haematococcus pluvialis under high-light and nitrogen-deficiency conditions. 2018;

73. Panis G. Commercial Astaxanthin Production Derived by Green Alga Haematococcus pluvialis: A Microalgae Process Model and techno-Economic Assessment All Through Production Line [Master Thesis (45EC)]. [Netherlands]: Utrecht University; 2015.

74. Singh S, Rather AH. Extraction of Astaxanthin from The Encysted Cells of Haematococcus Pluvialis with Different Solvents. 2018;4:115.

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76. Neveen AS., GhadaSI, Shaimaa ES.,Mostafa MAE. The Potential Role of Carotenoid Pigment Isolated from a New Rhodotorula Species in Ameliorating Cerebral Ischemic Stroke Experimentally. IJCRR. 15 (1), 71-80.

77. Pinki S., Priyanka S., Shreyasi, Dubey, Ayushi S. Effect Of Different Processing Methods On Polyphenolic Content And Antioxidant Activity Of Broad Beans (Vicia faba). IJCRR. 8 (13), 6-11.

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 Dorothy Ebere Adimora et al. entitled \"Remediation for Effects of Domestic Violence on Psychological well-being, Depression and Suicide among Women During COVID-19 Pandemic: A Cross-cultural Study of Nigeria and Spain\" is awarded Best Article of Vol 14 issue 23
A study by Muhas C. et al. entitled \"Study on Knowledge & Awareness About Pharmacovigilance Among Pharmacists in South India\" is awarded Best article for Vol 14 issue 22
A study by Saurabh Suvidha entitled \"A Case of Mucoid Degeneration of Uterine Fibroid with Hydrosalphinx and Ovarian Cyst\" is awarded Best article of Vol 14 issue 21
A study by Alice Alice entitled \"Strengthening of Human Milk Banking across South Asian Countries: A Next Step Forward\" is awarded Best article of Vol 14 issue 20
A study by Sathyanarayanan AR et al. entitled \"The on-task Attention of Individuals with Autism Spectrum Disorder-An Eye Tracker Study Using Auticare\" is awarded Best article of Vol 14 issue 19
A study by Gupta P. et al. entitled \"A Short Review on \"A Novel Approach in Fast Dissolving Film & their Evaluation Studies\" is awarded Best Article of Vol 14 issue 18.
A study by Shafaque M. et al. entitled \"A Case-Control Study Performed in Karachi on Inflammatory Markers by Ciprofloxacin and CoAmoxicillin in Patients with Chronic Suppurative Otitis Media\" is awarded Best Article of Vol 14 issue 17
A study by Ali Nawaz et al. entitled \"A Comparative Study of Tubeless versus Standard Percutaneous Nephrolithotomy (PCNL) \? A Randomized Controlled Study\" is awarded Best Article for Vol 14 issue 16.
A study by Singh R. et al. entitled \"A Prospective Study to Find the Association of Astigmatism in Patients of Vernal Keratoconjunctivitis (VKC) in a Tertiary Health Care Centre in India (Vindhya Region MP)\" is awarded Best Article for Vol 14 issue 15
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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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.



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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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