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Elucidating shared biomarkers and pathways in kidney stones and diabetes: insights into novel therapeutic targets and the role of resveratrol

BACKGROUND: The pathogenic mechanisms shared between kidney stones and diabetes at the transcriptional level remain elusive, and the molecular mechanisms by which resveratrol exerts its protective effects against these conditions require further investigation. METHODS: To address these gaps in knowl...

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Autores principales: Shen, Shanlin, Wei, Jiafeng, Kang, Weiting, Wang, Tengteng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10360253/
https://www.ncbi.nlm.nih.gov/pubmed/37480086
http://dx.doi.org/10.1186/s12967-023-04356-4
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author Shen, Shanlin
Wei, Jiafeng
Kang, Weiting
Wang, Tengteng
author_facet Shen, Shanlin
Wei, Jiafeng
Kang, Weiting
Wang, Tengteng
author_sort Shen, Shanlin
collection PubMed
description BACKGROUND: The pathogenic mechanisms shared between kidney stones and diabetes at the transcriptional level remain elusive, and the molecular mechanisms by which resveratrol exerts its protective effects against these conditions require further investigation. METHODS: To address these gaps in knowledge, we conducted a comprehensive analysis of microarray and RNA-seq datasets to elucidate shared biomarkers and biological pathways involved in the pathogenesis of kidney stones and diabetes. An assortment of bioinformatic approaches was employed to illuminate the common molecular markers and associated pathways, thereby contributing to the identification of innovative therapeutic targets. Further investigation into the molecular mechanisms of resveratrol in preventing these conditions was conducted using molecular docking simulation and first-principles calculations. RESULTS: The study identified 11 potential target genes associated with kidney stones and diabetes through the intersection of genes from weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) screening. Among these, Interleukin 11 (IL11) emerged as a pivotal hub gene and a potential diagnostic biomarker for both conditions, particularly in males. Expression analysis of IL11 demonstrated elevated levels in kidney stones and diabetes groups compared to controls. Additionally, IL11 exhibited correlations with specific cell types and differential expression in normal and pathological conditions. Gene set enrichment analysis (GSEA) highlighted significant disparities in biological processes, pathways, and immune signatures associated with IL11. Moreover, molecular docking simulation of resveratrol towards IL11 and a first-principles investigation of Ca adsorption on the resveratrol surface provided structural evidence for the development of resveratrol-based drugs for these conditions. CONCLUSIONS: Overall, this investigation illuminates the discovery of common molecular mechanisms underlying kidney stones and diabetes, unveils potential diagnostic biomarkers, and elucidates the significance of IL11 in these conditions. It also provides insights into IL11 as a promising therapeutic target and highlights the role of resveratrol. Nonetheless, further research is warranted to enhance our understanding of IL11 targeting mechanisms and address any limitations in the study. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04356-4.
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spelling pubmed-103602532023-07-22 Elucidating shared biomarkers and pathways in kidney stones and diabetes: insights into novel therapeutic targets and the role of resveratrol Shen, Shanlin Wei, Jiafeng Kang, Weiting Wang, Tengteng J Transl Med Research BACKGROUND: The pathogenic mechanisms shared between kidney stones and diabetes at the transcriptional level remain elusive, and the molecular mechanisms by which resveratrol exerts its protective effects against these conditions require further investigation. METHODS: To address these gaps in knowledge, we conducted a comprehensive analysis of microarray and RNA-seq datasets to elucidate shared biomarkers and biological pathways involved in the pathogenesis of kidney stones and diabetes. An assortment of bioinformatic approaches was employed to illuminate the common molecular markers and associated pathways, thereby contributing to the identification of innovative therapeutic targets. Further investigation into the molecular mechanisms of resveratrol in preventing these conditions was conducted using molecular docking simulation and first-principles calculations. RESULTS: The study identified 11 potential target genes associated with kidney stones and diabetes through the intersection of genes from weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) screening. Among these, Interleukin 11 (IL11) emerged as a pivotal hub gene and a potential diagnostic biomarker for both conditions, particularly in males. Expression analysis of IL11 demonstrated elevated levels in kidney stones and diabetes groups compared to controls. Additionally, IL11 exhibited correlations with specific cell types and differential expression in normal and pathological conditions. Gene set enrichment analysis (GSEA) highlighted significant disparities in biological processes, pathways, and immune signatures associated with IL11. Moreover, molecular docking simulation of resveratrol towards IL11 and a first-principles investigation of Ca adsorption on the resveratrol surface provided structural evidence for the development of resveratrol-based drugs for these conditions. CONCLUSIONS: Overall, this investigation illuminates the discovery of common molecular mechanisms underlying kidney stones and diabetes, unveils potential diagnostic biomarkers, and elucidates the significance of IL11 in these conditions. It also provides insights into IL11 as a promising therapeutic target and highlights the role of resveratrol. Nonetheless, further research is warranted to enhance our understanding of IL11 targeting mechanisms and address any limitations in the study. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04356-4. BioMed Central 2023-07-21 /pmc/articles/PMC10360253/ /pubmed/37480086 http://dx.doi.org/10.1186/s12967-023-04356-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Shen, Shanlin
Wei, Jiafeng
Kang, Weiting
Wang, Tengteng
Elucidating shared biomarkers and pathways in kidney stones and diabetes: insights into novel therapeutic targets and the role of resveratrol
title Elucidating shared biomarkers and pathways in kidney stones and diabetes: insights into novel therapeutic targets and the role of resveratrol
title_full Elucidating shared biomarkers and pathways in kidney stones and diabetes: insights into novel therapeutic targets and the role of resveratrol
title_fullStr Elucidating shared biomarkers and pathways in kidney stones and diabetes: insights into novel therapeutic targets and the role of resveratrol
title_full_unstemmed Elucidating shared biomarkers and pathways in kidney stones and diabetes: insights into novel therapeutic targets and the role of resveratrol
title_short Elucidating shared biomarkers and pathways in kidney stones and diabetes: insights into novel therapeutic targets and the role of resveratrol
title_sort elucidating shared biomarkers and pathways in kidney stones and diabetes: insights into novel therapeutic targets and the role of resveratrol
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10360253/
https://www.ncbi.nlm.nih.gov/pubmed/37480086
http://dx.doi.org/10.1186/s12967-023-04356-4
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