Transcriptomics-driven drug repositioning for the treatment of diabetic foot ulcer

Diabetic foot ulcers (DFUs) are a common complication of diabetes and can lead to severe disability and even amputation. Despite advances in treatment, there is currently no cure for DFUs and available drugs for treatment are limited. This study aimed to identify new candidate drugs and repurpose ex...

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Main Authors: Wirawan Adikusuma, Zainul Amiruddin Zakaria, Lalu Muhammad Irham, Baiq Leny Nopitasar, Anna Pradiningsih, Firdayani Firdayani, Abdi Wira Septama, Rockie Chong
Format: Article
Language:English
English
Published: Springer Nature 2023
Subjects:
Online Access:https://eprints.ums.edu.my/id/eprint/38598/1/ABSTRACT.pdf
https://eprints.ums.edu.my/id/eprint/38598/2/FULL%20TEXT.pdf
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author Wirawan Adikusuma
Zainul Amiruddin Zakaria
Lalu Muhammad Irham
Baiq Leny Nopitasar
Anna Pradiningsih
Firdayani Firdayani
Abdi Wira Septama
Rockie Chong
author_facet Wirawan Adikusuma
Zainul Amiruddin Zakaria
Lalu Muhammad Irham
Baiq Leny Nopitasar
Anna Pradiningsih
Firdayani Firdayani
Abdi Wira Septama
Rockie Chong
author_sort Wirawan Adikusuma
collection UMS
description Diabetic foot ulcers (DFUs) are a common complication of diabetes and can lead to severe disability and even amputation. Despite advances in treatment, there is currently no cure for DFUs and available drugs for treatment are limited. This study aimed to identify new candidate drugs and repurpose existing drugs to treat DFUs based on transcriptomics analysis. A total of 31 differentially expressed genes (DEGs) were identified and used to prioritize the biological risk genes for DFUs. Further investigation using the database DGIdb revealed 12 druggable target genes among 50 biological DFU risk genes, corresponding to 31 drugs. Interestingly, we highlighted that two drugs (urokinase and lidocaine) are under clinical investigation for DFU and 29 drugs are potential candidates to be repurposed for DFU therapy. The top 5 potential biomarkers for DFU from our findings are IL6ST, CXCL9, IL1R1, CXCR2, and IL10. This study highlights IL1R1 as a highly promising biomarker for DFU due to its high systemic score in functional annotations, that can be targeted with an existing drug, Anakinra. Our study proposed that the integration of transcriptomic and bioinformatic-based approaches has the potential to drive drug repurposing for DFUs. Further research will further examine the mechanisms by which targeting IL1R1 can be used to treat DFU.
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spelling ums.eprints-385982024-04-29T02:59:43Z https://eprints.ums.edu.my/id/eprint/38598/ Transcriptomics-driven drug repositioning for the treatment of diabetic foot ulcer Wirawan Adikusuma Zainul Amiruddin Zakaria Lalu Muhammad Irham Baiq Leny Nopitasar Anna Pradiningsih Firdayani Firdayani Abdi Wira Septama Rockie Chong QH301-705.5 Biology (General) RC648-665 Diseases of the endocrine glands. Clinical endocrinology RS400-431 Pharmaceutical chemistry Diabetic foot ulcers (DFUs) are a common complication of diabetes and can lead to severe disability and even amputation. Despite advances in treatment, there is currently no cure for DFUs and available drugs for treatment are limited. This study aimed to identify new candidate drugs and repurpose existing drugs to treat DFUs based on transcriptomics analysis. A total of 31 differentially expressed genes (DEGs) were identified and used to prioritize the biological risk genes for DFUs. Further investigation using the database DGIdb revealed 12 druggable target genes among 50 biological DFU risk genes, corresponding to 31 drugs. Interestingly, we highlighted that two drugs (urokinase and lidocaine) are under clinical investigation for DFU and 29 drugs are potential candidates to be repurposed for DFU therapy. The top 5 potential biomarkers for DFU from our findings are IL6ST, CXCL9, IL1R1, CXCR2, and IL10. This study highlights IL1R1 as a highly promising biomarker for DFU due to its high systemic score in functional annotations, that can be targeted with an existing drug, Anakinra. Our study proposed that the integration of transcriptomic and bioinformatic-based approaches has the potential to drive drug repurposing for DFUs. Further research will further examine the mechanisms by which targeting IL1R1 can be used to treat DFU. Springer Nature 2023 Article NonPeerReviewed text en https://eprints.ums.edu.my/id/eprint/38598/1/ABSTRACT.pdf text en https://eprints.ums.edu.my/id/eprint/38598/2/FULL%20TEXT.pdf Wirawan Adikusuma and Zainul Amiruddin Zakaria and Lalu Muhammad Irham and Baiq Leny Nopitasar and Anna Pradiningsih and Firdayani Firdayani and Abdi Wira Septama and Rockie Chong (2023) Transcriptomics-driven drug repositioning for the treatment of diabetic foot ulcer. Scientifc Reports, 13 (10032). pp. 1-8. https://doi.org/10.1038/s41598-023-37120-1
spellingShingle QH301-705.5 Biology (General)
RC648-665 Diseases of the endocrine glands. Clinical endocrinology
RS400-431 Pharmaceutical chemistry
Wirawan Adikusuma
Zainul Amiruddin Zakaria
Lalu Muhammad Irham
Baiq Leny Nopitasar
Anna Pradiningsih
Firdayani Firdayani
Abdi Wira Septama
Rockie Chong
Transcriptomics-driven drug repositioning for the treatment of diabetic foot ulcer
title Transcriptomics-driven drug repositioning for the treatment of diabetic foot ulcer
title_full Transcriptomics-driven drug repositioning for the treatment of diabetic foot ulcer
title_fullStr Transcriptomics-driven drug repositioning for the treatment of diabetic foot ulcer
title_full_unstemmed Transcriptomics-driven drug repositioning for the treatment of diabetic foot ulcer
title_short Transcriptomics-driven drug repositioning for the treatment of diabetic foot ulcer
title_sort transcriptomics driven drug repositioning for the treatment of diabetic foot ulcer
topic QH301-705.5 Biology (General)
RC648-665 Diseases of the endocrine glands. Clinical endocrinology
RS400-431 Pharmaceutical chemistry
url https://eprints.ums.edu.my/id/eprint/38598/1/ABSTRACT.pdf
https://eprints.ums.edu.my/id/eprint/38598/2/FULL%20TEXT.pdf
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AT baiqlenynopitasar transcriptomicsdrivendrugrepositioningforthetreatmentofdiabeticfootulcer
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