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Affiliation |
Faculty of Medicine School of Medicine Department of Medical Sciences, Cardiovascular Physiology |
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Assistant Professor |
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External Link |
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MADHYASTHA Radha
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Degree 【 display / non-display 】
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Doctor (Physiology and Medical Science) ( 2004.3 Miyazaki Medical College )
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Doctor (Zoology) ( 2000.5 University of Madras, India )
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Master of Philosophy (Zoology) ( 1993.8 University of Madras, India )
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Master of Science (Zoology) ( 1992.4 University of Madras, India )
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Bachelor of Science (Zoology) ( 1990.3 University of Madras (India) )
Research Areas 【 display / non-display 】
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Life Science / Molecular biology
Papers 【 display / non-display 】
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Designer exosomes: Smart nano-communication tools for translational medicine Invited Reviewed International coauthorship
Madhyastha Harishkumar, Madhyastha Radha, Nakajima Yuichi, Gothandam Kodiveri Muthukalianan, Ohe Kaoru, Shiomori Koichiro, Watanabe Nozomi
Bioengineering 2021.10
Language：English Publishing type：Research paper (scientific journal)
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Madhyastha R., Madhyastha H., Nurrahmah Q.I., Purbasari B., Maruyama M., Nakajima Y.
Inflammation 44 ( 4 ) 1274 - 1287 2021.8
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Inflammation
MicroRNAs can regulate inflammatory responses by modulating macrophage polarization. Although microRNA miR-21 is linked to crucial processes involved in inflammatory responses, its precise role in macrophage polarization is controversial. In this study, we investigated the functional relevance of endogenous miRNA-21 and the role of exosomes. RAW 264.7 macrophages were transfected with miR-21 plasmid, and the inflammatory response was evaluated by flow cytometry, phagocytosis, and real-time PCR analysis of inflammatory cytokines. To understand the signaling pathways’ role, the cells were treated with inhibitors specific for PI3K or NFĸB. Exosomes from transfected cells were used to study the paracrine action of miR-21 on naive macrophages. Overexpression of miR-21 resulted in significant upregulation of pro-inflammatory cytokines, pushing the cells towards a pro-inflammatory phenotype, with partial involvement of PI3K and NFĸB signal pathways. The cells also secreted miR-21 rich exosomes, which, on delivery to naive macrophages, caused them to exhibit pro-inflammatory activity. The presence of miR-21 inhibitor quenched the inflammatory response. This study validates the pro-inflammatory property of miR-21 with a tendency to foster an inflammatory milieu. Our findings also reinforce the dual importance of exosomal miR-21 as a biomarker and therapeutic target in inflammatory conditions.
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Nanoceutical adjuvants as wound healing material: Precepts and prospects Reviewed International coauthorship
Banerjee K., Madhyastha R., Nakajima Y., Maruyama M., Madhyastha H.
International Journal of Molecular Sciences 22 ( 9 ) 2021.5
Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Molecular Sciences
Dermal wound healing describes the progressive repair and recalcitrant mechanism of 12damaged skin, and eventually, reformatting and reshaping the skin. Many probiotics, nutritional supplements, metal nanoparticles, composites, skin constructs, polymers, and so forth have been associated with the improved healing process of wounds. The exact mechanism of material‐cellular interaction is a point of immense importance, particularly in pathological conditions such as diabetes. Bioengineered alternative agents will likely continue to dominate the outpatient and perioperative management of chronic, recalcitrant wounds as new products continue to cut costs and improve the wound healing process. This review article provides an update on the various remedies with confirmed wound healing activities of metal‐based nanoceutical adjuvanted agents and also other nano‐based counterparts from previous experiments conducted by various researchers.
DOI： 10.3390/ijms22094748
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Nurrahmah Q.I., Madhyastha R., Madhyastha H., Purbasari B., Maruyama M., Nakajima Y.
Immunopharmacology and Immunotoxicology 43 ( 3 ) 299 - 308 2021
Language：English Publishing type：Research paper (scientific journal) Publisher：Immunopharmacology and Immunotoxicology
Context: Macrophages are essential components of the immune system, with significant roles in inflammation modulation. They can be activated into pro-inflammatory M1 or anti-inflammatory M2 phenotypes, depending on their micro-environment. Molecular factors that modulate macrophage polarization are hot targets for therapeutic strategies to counter chronic inflammatory pathological conditions. Objective: The current study aimed to elucidate the molecular mechanisms by which Retinoic acid (RA), a potent immunomodulator, suppresses LPS-induced inflammatory response in macrophages. Materials and methods: RAW 264.7 macrophages were treated with RA and/or LPS, and analyzed for inflammatory genes and miR-21 by PCR. The roles of miR-21 and NF-ĸB signaling pathway were also assessed by knock-down experiments, immunofluorescence, and ChIP assays. Results: Pretreatment with RA quenched the LPS-induced inflammatory responses, including phagocytosis, ROS generation, and NO production. RA shifted the polarization away from the M1 state by negative regulation of IKKα/β, p65, and miR-21. RA hindered the phosphorylation of IKKα/β, translocation of p65 into the nucleus, and the subsequent upregulation of miR-21. Knock-in and knock-down experiments showed that miR-21 is central for the polarization shift toward the pro-inflammatory M1 state. Conclusion: miR-21 is involved in the LPS-induced pro-inflammatory profile of macrophages and that RA negatively regulates the inflammatory response by targeting NF-ĸB/miR-21 signaling. Our data exposes RA’s potential as a pharmacological agent to manipulate miR-21 and counteract hyper-inflammatory response.
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Retinoic acid attenuates nuclear factor kappaB mediated induction of NLRP3 inflammasome Reviewed
Purbasari B., Madhyastha R., Madhyastha H., Nurrahmah Q.I., Maruyama M., Nakajima Y., Kataoka H., Watanabe N.
Pharmacological Reports 74 ( 1 ) 189 - 203 2021
Language：English Publishing type：Research paper (scientific journal) Publisher：Pharmacological Reports
Background: Acetylcholine (ACh), a neurotransmitter and a part of the cholinergic system, can modify immune responses. Expression of acetylcholine receptors (AChR) in immune cells, including macrophages, leads to modulation of their function. Inflammasomes are part of the innate immune system and have been linked to a variety of inflammatory diseases. The NLRP3/ASC/caspase-1/IL-1 axis has emerged as a critical signaling pathway in inflammation process initiation. The role of ACh in modulating inflammasomes in macrophages remains relatively under-explored. Methods: The effect of AChR agonist carbachol on inflammasome expression was investigated using murine and human macrophages. Cell lysates were assessed by western blot for protein analysis. Immunofluorescence studies were used to study the translocation of p65. The experiments were conducted in the presence of NF-ĸB inhibitor, AChR antagonists, and retinoic acid (RA) to study the role of NF-ĸB, ACh receptors, and RA, respectively. Results: We found that carbachol increased the expression of NLRP3 inflammasome (NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18). The treated cells also showed an increase in NF-ĸB activation. The effect of carbachol was diminished by NF-ĸB inhibitor and atropine, a mAChR antagonist. The addition of RA also significantly reduced the effect of carbachol on NLRP3 inflammasomes. Conclusions: Our current study suggests that carbachol induces NLRP3 inflammasome activation through mAChR and NF-ĸB, and that RA abolishes the inflammatory response. It reveals the potentials of co-administration of RA with cholinergic drugs to prevent inflammatory responses during cholinergic medications.
Books 【 display / non-display 】
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Nanotoxicology: Toxicity evaluation, risk assessment and management
Umapathi A, Kaphle A, Navya PN, Firdose N, Monnappa S, Jain D, Srinivas SP, Madhyastha HK, Madhyastha R, Daima HK（ Role： Joint author , Impact of physiochemical properties and surface chemistry of nanomaterials on toxicity）
CRC Press, Taylor and Francis group 2017.5
Language：English Book type：Scholarly book
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Vermitech: Worm powered technology
Sultan Ahmed Ismail
Institute of Research in Soil Biology and Biotechnology, Chennai, India 1999.10
Language：English Book type：General book, introductory book for general audience
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Neem: A User's Manual
K Vijayalakshmi, KS Radha and Vandana Shiva（ Role： Joint author）
Centre for Indian Knowledge Systems, Chennai and Research Foundation for Science, Technology and Resource Policy, New Delhi, India 1995.5
Language：English Book type：General book, introductory book for general audience
Presentations 【 display / non-display 】
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Silver primed nutraceutical hybrids: cellular and hematological evaluation Invited International conference
Madhyastha H, Madhyastha r., Nakajima Y., Maruyama M.
BioTERM
Event date： 2019.11.30 - 2019.12.3
Language：English Presentation type：Oral presentation (invited, special)
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Silver primed nutraceutical hybrids: cellular and hematological evaluation Invited International conference
Madhyastha H, Madhyastha r., Nakajima Y., Maruyama M.
BioTERM
Event date： 2019.11.30 - 2019.12.3
Language：English Presentation type：Oral presentation (invited, special)
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Phycocyanin hybridized silver conjugates in wound healing-cell toxicity evaluation Invited International conference
Madhyastha H, Madhyastha R., Nakajima Y., Maruyama M.
New Horizon in Biotechnology
Event date： 2019.11.20 - 2019.11.29
Language：English Presentation type：Oral presentation (invited, special)
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Phycocyanin hybridized silver conjugates in wound healing-cell toxicity evaluation Invited International conference
Madhyastha H, Madhyastha R., Nakajima Y., Maruyama M.
New Horizon in Biotechnology
Event date： 2019.11.20 - 2019.11.29
Language：English Presentation type：Oral presentation (invited, special)
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Potential of intracellular protein and its hydrolysates from epiphytic bacteria associated with brown algae, Sargassum sp. as anticancer agents.
Nur Asmi, Ahyar Ahmad, Hasnah Natsir, Muh. Nasrum Massi, Harishkumar Madhyastha, Radha Madhyastha, Yuichi Nakajima, Masugi Maruyama.
西日本生理学会 (宮崎大学)
Event date： 2019.11.1 - 2019.11.2
Language：English Presentation type：Oral presentation (general)
Venue：宮崎大学
Grant-in-Aid for Scientific Research 【 display / non-display 】
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FMR治療における病理、遺伝子発現機構からの検証に基づいた左房機能評価の意義の確立
Grant number：23K08239 2023.04 - 2027.03
独立行政法人日本学術振興会 科学研究費基金 基盤研究（C）
Authorship：Coinvestigator(s)
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MicroRNAとマクロファージ異常：難治性創傷の炎症遅延に及ぼす影響
2015.04 - 2018.03
科学研究費補助金 基盤研究(C)
Authorship：Principal investigator
最近、低分子RNAであるmicroRNA (miRNA)が様々な疾患に関与することが次々と明らかになってきた。これまで申請者は、糖尿病性創傷治癒の遅延に幾つかのmicroRNAが関与していることを示唆した。さらに，microRNAの一つであるmicroRNA21がTGFβ１増殖因子により制御されることを明らかにした。糖尿病性創傷を含む難治性創傷に起こる炎症期の遅延にmicroRNAがどのように関与しているかは未知である。本研究では，難治性創傷においての炎症期の遅延に対しmicroRNAの役割およびその機構を明らかにする。本研究の結果を通じ，難治性創傷治癒不全に関する新たな知見を与え，糖尿病患者の創傷治癒改善のために重要な情報が得られると期待できる。
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ＭｉＲ－２１とＴＧＦβシグナル経路の相互作用：難治性創傷における重要性
2012.04 - 2015.03
科学研究費補助金 基盤研究(C)
Authorship：Principal investigator
ＭｉＲ－２１とＴＧＦβシグナル経路の相互作用：難治性創傷における重要性
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創傷治癒過程に関与するｍｉＲＮＡの動態とその意義：糖尿病モデル動物を用いた研究
2009.04 - 2011.03
科学研究費補助金 若手研究(B)
Authorship：Principal investigator
創傷治癒過程に関与するｍｉＲＮＡの動態とその意義：糖尿病モデル動物を用いた研究