Publications by authors named "Kosagi-Sharaf Rao"

6 Publications

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β-glucans: wide-spectrum immune-balancing food-supplement-based enteric (β-WIFE) vaccine adjuvant approach to COVID-19.

Hum Vaccin Immunother 2021 Mar 2:1-6. Epub 2021 Mar 2.

The Fujio-Eiji Academic Terrain (FEAT), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India.

Conventional vaccines to combat COVID-19 through different approaches are at various stages of development. The complexity of COVID-19 such as the potential mutations of the virus leading to antigenic drift and the uncertainty on the duration of the immunity induced by the vaccine have hampered the efforts to control the COVID-19 pandemic. Thus, we suggest an alternative interim treatment strategy based on biological response modifier glucans such as the AFO-202-derived β-glucan, which has been reported to induce trained immunity, akin to that induced by the Bacille Calmette-Guérin vaccine, by epigenetic modifications at the central level in the bone marrow. These β-glucans act as pathogen-associated molecular patterns, activating mucosal immunity by binding with specific pathogen recognition receptors such as dectin-1 and inducing both the adaptive and innate immunity by reaching distant lymphoid organs. β-Glucans have also been used as immune adjuvants for vaccines such as the influenza vaccine. Therefore, until a conventional vaccine is widely available, an orally consumable vaccine adjuvant that acts like biosimilars, termed as the wide-spectrum immune-balancing food-supplement-based enteric (β-WIFE) vaccine adjuvant approach, with well-reported safety is worth in-depth investigation and can be considered for a clinical trial.
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http://dx.doi.org/10.1080/21645515.2021.1880210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938654PMC
March 2021

Coagulopathy associated with COVID-19 - Perspectives & Preventive strategies using a biological response modifier Glucan.

Thromb J 2020 16;18:27. Epub 2020 Oct 16.

II Department of Surgery & Centre for Advancing Clinical Research (CACR), Yamanashi University- School of Medicine, Chuo, Japan.

Direct endothelial injury by viruses and dysregulation of clotting mechanisms due to cytokine storm are the major precipitating factors of mortality in COVID-19; both are attributed to a fundamental dysregulation of the immune system. While immune dysregulation can be attributed to several factors, the risk of associated thrombogenic disruption varies across individuals. This variation depends on several factors, such as comorbidities, including diabetes, hypertension, and cardiovascular diseases. When considering ethnic variations, the vulnerability of Caucasians, African Americans and Hispanics needs to be addressed before arriving at strategies to handle thromboembolic complications, which have been identified in recent reports as the leading causes of mortality in COVID-19. Although evaluation of D-dimer and prothrombin during admission is considered to predict prognosis and mortality, there are no preventive or prophylactic strategies before hospital admission. Herein, we present our perspectives on the effect of regular supplementation with the biological response modifier beta glucan based on its relevance to immune modulation. This effect is of paramount importance in decreasing the development of severe COVID-19 and reducing mortality against the background of coagulopathy, especially in vulnerable populations.
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http://dx.doi.org/10.1186/s12959-020-00239-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563912PMC
October 2020

Role of Immune Dysregulation in Increased Mortality Among a Specific Subset of COVID-19 Patients and Immune-Enhancement Strategies for Combatting Through Nutritional Supplements.

Front Immunol 2020 9;11:1548. Epub 2020 Jul 9.

The Mary-Yoshio Translational Hexagon, Nichi-In Centre for Regenerative Medicine, Chennai, India.

The COVID-19 pandemic has been causing varying severities of illness. Some are asymptomatic and some develop severe disease leading to mortality across ages. This contrast triggered us explore the causes, with the background that a vaccine for effective immunization or a drug to tackle COVID-19 is not too close to reality. We have discussed strategies to combat COVID-19 through immune enhancement, using simple measures including nutritional supplements. A literature search on mortality-related comorbid conditions was performed. For those conditions, we analyzed the pro-inflammatory cytokines, which could cause the draining of the immune reservoir. We also analyzed the immune markers necessary for the defense mechanism/immune surveillance against COVID-19, especially through simple means including immune enhancing nutritional supplement consumption, and we suggest strategies to combat COVID-19. Major comorbid conditions associated with increased mortality include cardiovascular disease (CVD), diabetes, being immunocompromised by cancer, and severe kidney disease with a senile immune system. Consumption of strain (AFO-202) beta 1,3-1,6 glucan supported enhanced IL-8, sFAS macrophage activity, and NK cells' cytotoxicity, which are major defense mechanisms against viral infection. People with co-morbid conditions who are more prone to COVID-19-related deaths due to immune dysregulation are likely to benefit from consuming nutritional supplements that enhance the immune system. We recommend clinical studies to validate AFO-202 beta glucan in COVID-19 patients to prove its efficacy in overcoming a hyper-inflammation status, thus reducing the mortality, until a definite vaccine is made available.
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http://dx.doi.org/10.3389/fimmu.2020.01548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363949PMC
August 2020

New perspectives on oxidized genome damage and repair inhibition by pro-oxidant metals in neurological diseases.

Biomolecules 2014 Jul 17;4(3):678-703. Epub 2014 Jul 17.

Department of Radiation Oncology, Houston Methodist Research Institute, Affiliate of Weill Medical College of Cornell University, 6550 Fannin St, Smith 8-030, Houston, TX 77030, USA.

The primary cause(s) of neuronal death in most cases of neurodegenerative diseases, including Alzheimer's and Parkinson's disease, are still unknown. However, the association of certain etiological factors, e.g., oxidative stress, protein misfolding/aggregation, redox metal accumulation and various types of damage to the genome, to pathological changes in the affected brain region(s) have been consistently observed. While redox metal toxicity received major attention in the last decade, its potential as a therapeutic target is still at a cross-roads, mostly because of the lack of mechanistic understanding of metal dyshomeostasis in affected neurons. Furthermore, previous studies have established the role of metals in causing genome damage, both directly and via the generation of reactive oxygen species (ROS), but little was known about their impact on genome repair. Our recent studies demonstrated that excess levels of iron and copper observed in neurodegenerative disease-affected brain neurons could not only induce genome damage in neurons, but also affect their repair by oxidatively inhibiting NEIL DNA glycosylases, which initiate the repair of oxidized DNA bases. The inhibitory effect was reversed by a combination of metal chelators and reducing agents, which underscore the need for elucidating the molecular basis for the neuronal toxicity of metals in order to develop effective therapeutic approaches. In this review, we have focused on the oxidative genome damage repair pathway as a potential target for reducing pro-oxidant metal toxicity in neurological diseases.
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http://dx.doi.org/10.3390/biom4030678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192668PMC
July 2014

New evidences on Tau-DNA interactions and relevance to neurodegeneration.

Neurochem Int 2010 Aug 8;57(1):51-7. Epub 2010 May 8.

Department of Biochemistry and Nutrition, Central Food Technological Research Institute, CSIR Unit, Mysore 570020, India.

Tau is mainly distributed in cytoplasm and also found to be localized in the nucleus. There is limited data on DNA binding potential of Tau. We provide novel evidence on nicking of DNA by Tau. Tau nicks the supercoiled DNA leading to open circular and linear forms. The metal ion magnesium (a co-factor for endonuclease) enhanced the Tau DNA nicking ability, while an endonuclease specific inhibitor, aurinetricarboxylic acid (ATA) inhibited the Tau DNA nicking ability. Further, we also evidenced that Tau induces B-C-A mixed conformational transition in DNA and also changes DNA stability. Tau-scDNA complex is more sensitive to DNAse I digestion indicating stability changes in DNA caused by Tau. These findings indicate that Tau alters DNA helicity and integrity and also nicks the DNA. The relevance of these novel intriguing findings regarding the role Tau in neuronal dysfunction is discussed.
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http://dx.doi.org/10.1016/j.neuint.2010.04.013DOI Listing
August 2010

Molecular understanding of aluminum-induced topological changes in (CCG)12 triplet repeats: relevance to neurological disorders.

Biochim Biophys Acta 2002 Oct;1588(1):56-64

Centre for Human Genetics, Institute of Biotechnology, G-05, Discoverer, ITPL, Whitefield Road, Bangalore, India.

Recent studies have shown that gene mutations are involved in the pathology of neurological disorders. CCG repeats cause genetic instability and are localized at the 5' end of the non-coding regions of the FMR1 gene in fragile X syndrome. Our studies for the first time showed that aluminum (Al) levels were elevated in the serum samples of fragile X syndrome and also provide evidence for the interaction of aluminum with (CCG)12-repeats. Circular dichroism spectroscopic studies of (CCG)12 indicated B-DNA conformation and in the presence of Al (10(-5) M) CCG repeats attained Z-DNA conformation. Further spectroscopic studies, which included melting profiles, ethidium bromide binding patterns and interaction of Z-DNA specific polyclonal antibodies confirmed the Z-conformation in (CCG)12-repeats in the presence of Al (10(-5) M). It is interesting to mention that Al-induced Z-conformation is stable even after the total removal of Al from CCG by desferoximine, a chelating drug. This is the first report to proof the role of Al in modulating the DNA (CCG repeats) topology and this information provides a clue about the possible involvement of Al at a molecular level in neurological/neurodegenerative disorders.
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http://dx.doi.org/10.1016/s0925-4439(02)00133-3DOI Listing
October 2002