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Single-cell transcriptomics and network pharmacology reveal therapeutic targets of Jianpi Yiqi Bugan Yishen decoction in immune cell subsets of children with myasthenia gravis

BACKGROUND: Myasthenia gravis (MG) is an acquired autoimmune disease of the neuromuscular junction. As immunosuppressive agents used to treat MG have a significant impact on the growth and development of children, treatment is extremely challenging. Jianpi Yiqi Bugan Yishen Decoction (JYBYD) has bee...

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Autores principales: Liu, Peng, Qi, Guoyan, Gu, Shanshan, Dong, Huimin, Liu, Chaoying, Yang, Hongxia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9834954/
https://www.ncbi.nlm.nih.gov/pubmed/36643680
http://dx.doi.org/10.21037/tp-22-593
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author Liu, Peng
Qi, Guoyan
Gu, Shanshan
Dong, Huimin
Liu, Chaoying
Yang, Hongxia
author_facet Liu, Peng
Qi, Guoyan
Gu, Shanshan
Dong, Huimin
Liu, Chaoying
Yang, Hongxia
author_sort Liu, Peng
collection PubMed
description BACKGROUND: Myasthenia gravis (MG) is an acquired autoimmune disease of the neuromuscular junction. As immunosuppressive agents used to treat MG have a significant impact on the growth and development of children, treatment is extremely challenging. Jianpi Yiqi Bugan Yishen Decoction (JYBYD) has been developed to treat MG and has achieved satisfactory results in clinical practice. This study aimed to explore its action mechanism and evaluate its active ingredients and potential therapeutic targets. METHODS: Single-cell transcriptome sequencing of peripheral blood immune cells of children with MG was performed to reveal the changes in immune cell profiles before and after JYBYD treatment. Lewis rats were included in the model, with classic MG induced by subcutaneous injection of the immunogen acetylcholine receptor (AChR). Twenty rats were divided into two groups and administered normal saline and JYBYD by gavage daily. RESULTS: An increase in cell populations characterized by cortactin expression was observed, which has a potential effect on the recovery of lesions at the neuromuscular junction in patients with MG. Based on the differential expression of genes in various immune cells and the predicted targets of traditional Chinese medicine (TCM) compounds, the possible therapeutic targets of JYBYD in different cell subsets were identified, among which STAT1, MCL1, and FOS were the most frequent. Comprehensive network pharmacological analysis suggested quercetin, luteolin, and resveratrol as important active ingredients of JYBYD for the treatment of children with MG. JYBYD could relieve myasthenia symptoms and reduce the AChR-Ab titer in the rat model. Immunohistochemistry results of the muscle showed that JYBYD treatment decreased the expression of STAT1, MCL1, and c-FOS proteins in the muscles of MG rat models. CONCLUSIONS: The results of this study are of significance for the clinical application of JYBYD and drug development against MG in children.
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spelling pubmed-98349542023-01-13 Single-cell transcriptomics and network pharmacology reveal therapeutic targets of Jianpi Yiqi Bugan Yishen decoction in immune cell subsets of children with myasthenia gravis Liu, Peng Qi, Guoyan Gu, Shanshan Dong, Huimin Liu, Chaoying Yang, Hongxia Transl Pediatr Original Article BACKGROUND: Myasthenia gravis (MG) is an acquired autoimmune disease of the neuromuscular junction. As immunosuppressive agents used to treat MG have a significant impact on the growth and development of children, treatment is extremely challenging. Jianpi Yiqi Bugan Yishen Decoction (JYBYD) has been developed to treat MG and has achieved satisfactory results in clinical practice. This study aimed to explore its action mechanism and evaluate its active ingredients and potential therapeutic targets. METHODS: Single-cell transcriptome sequencing of peripheral blood immune cells of children with MG was performed to reveal the changes in immune cell profiles before and after JYBYD treatment. Lewis rats were included in the model, with classic MG induced by subcutaneous injection of the immunogen acetylcholine receptor (AChR). Twenty rats were divided into two groups and administered normal saline and JYBYD by gavage daily. RESULTS: An increase in cell populations characterized by cortactin expression was observed, which has a potential effect on the recovery of lesions at the neuromuscular junction in patients with MG. Based on the differential expression of genes in various immune cells and the predicted targets of traditional Chinese medicine (TCM) compounds, the possible therapeutic targets of JYBYD in different cell subsets were identified, among which STAT1, MCL1, and FOS were the most frequent. Comprehensive network pharmacological analysis suggested quercetin, luteolin, and resveratrol as important active ingredients of JYBYD for the treatment of children with MG. JYBYD could relieve myasthenia symptoms and reduce the AChR-Ab titer in the rat model. Immunohistochemistry results of the muscle showed that JYBYD treatment decreased the expression of STAT1, MCL1, and c-FOS proteins in the muscles of MG rat models. CONCLUSIONS: The results of this study are of significance for the clinical application of JYBYD and drug development against MG in children. AME Publishing Company 2022-12 /pmc/articles/PMC9834954/ /pubmed/36643680 http://dx.doi.org/10.21037/tp-22-593 Text en 2022 Translational Pediatrics. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Liu, Peng
Qi, Guoyan
Gu, Shanshan
Dong, Huimin
Liu, Chaoying
Yang, Hongxia
Single-cell transcriptomics and network pharmacology reveal therapeutic targets of Jianpi Yiqi Bugan Yishen decoction in immune cell subsets of children with myasthenia gravis
title Single-cell transcriptomics and network pharmacology reveal therapeutic targets of Jianpi Yiqi Bugan Yishen decoction in immune cell subsets of children with myasthenia gravis
title_full Single-cell transcriptomics and network pharmacology reveal therapeutic targets of Jianpi Yiqi Bugan Yishen decoction in immune cell subsets of children with myasthenia gravis
title_fullStr Single-cell transcriptomics and network pharmacology reveal therapeutic targets of Jianpi Yiqi Bugan Yishen decoction in immune cell subsets of children with myasthenia gravis
title_full_unstemmed Single-cell transcriptomics and network pharmacology reveal therapeutic targets of Jianpi Yiqi Bugan Yishen decoction in immune cell subsets of children with myasthenia gravis
title_short Single-cell transcriptomics and network pharmacology reveal therapeutic targets of Jianpi Yiqi Bugan Yishen decoction in immune cell subsets of children with myasthenia gravis
title_sort single-cell transcriptomics and network pharmacology reveal therapeutic targets of jianpi yiqi bugan yishen decoction in immune cell subsets of children with myasthenia gravis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9834954/
https://www.ncbi.nlm.nih.gov/pubmed/36643680
http://dx.doi.org/10.21037/tp-22-593
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