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The potential molecular markers of inflammatory response in KOA with AD based on single-cell transcriptome sequencing analysis and identification of ligands by virtual screening

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Abstract

Alzheimer's disease (AD) and osteoarthritis (OA) are both senile degenerative diseases. Clinical studies have found that OA patients have a significantly increased risk of AD in their later life. This study hypothesized that chronic aseptic inflammation might lead to AD in KOA patients. However, current research has not yet clarified the potential mechanism between AD and KOA. Therefore, this study intends to use KOA transcriptional profiling and single-cell sequencing analysis technology to explore the molecular mechanism of KOA affecting AD development, and screen potential molecular biomarkers and drugs for the prediction, diagnosis, and prognosis of AD in KOA patients. It was found that the higher the expression of TXNIP, MMP3, and MMP13, the higher the risk coefficient of AD was. In addition, the AUC of TXNIP, MMP3, and MMP13 were all greater than 0.70, which had good diagnostic significance for AD. Finally, through the virtual screening of core proteins in FDA drugs and molecular dynamics simulation, it was found that compound Cobicistat could be targeted to TXNIP, Itc could be targeted to MMP3, and Isavuconazonium could be targeted to MMP13. To sum up, TXNIP, MMP3, and MMP13 are prospective molecular markers in KOA with AD, which could be used to predict, diagnose, and prognosis.

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Graphical abstract of the potential molecular markers of inflammatory response in KOA with AD.

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Funding

This research was financially supported by Basic and Applied Basic Research Project of Guangdong Province (2023A1515012615) and Province-Enterprise Joint Fund General Project of Guangdong Province (2022A1515220157) to Wengang Liu.

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  1. Yufeng Wu and Weijian Chen have contributed equally to this work.

Authors and Affiliations

  1. Traditional Chinese Medicine Hospital of Zhongshan, Zhongshan, 528400, Guangdong, China

    Yufeng Wu & Dawei Gao

  2. Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China

    Yufeng Wu, Weijian Chen, Junde Jian, Weinian Liu, Haibin Wang, Dawei Gao & Wengang Liu

  3. The Fifth Clinical College of Guangzhou, University of Chinese Medicine, Guangzhou, 510095, China

    Weijian Chen & Wengang Liu

  4. Guangdong Provincial Second Hospital of Traditional Chinese Medicine (Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine), Guangzhou, 510095, China

    Weijian Chen & Wengang Liu

  5. Guangzhou Orthopedic Hospital, Guangdong Province, Guangzhou University of Chinese Medicine, Guangzhou, 510045, China

    Junde Jian & Weinian Liu

  6. The First Clinical Medical College, Guangdong Province, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China

    Haibin Wang

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  1. Yufeng Wu
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Yufeng Wu, Weijian Chen, and Wengang Liu were responsible for the design and implementation of the study presented. Weijian Chen, Junde Jian, and Weinian Liu were responsible for the inclusions and literature review. Yufeng Wu and Weijian Chen prepared the initial draft of the manuscript. Haibin Wang, Dawei Gao, and Wengang Liu gave critical feedback. All authors have read and approved the final manuscript to be submitted.

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Correspondence to Wengang Liu.

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Wu, Y., Chen, W., Jian, J. et al. The potential molecular markers of inflammatory response in KOA with AD based on single-cell transcriptome sequencing analysis and identification of ligands by virtual screening. Mol Divers (2024). https://doi.org/10.1007/s11030-024-10854-4

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