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7. Icariin promotes functional recovery in rats after spinal cord injury by inhibiting YAP and regulating PPM1B ubiquitination to inhibiting the activation of reactive astrocytes.

Author

Feng, Sa, Liu, Linyan, Cheng, Yuelin, Zhou, Mengmeng, Zhu, Haoqiang, Zhao, Xinyan, Chen, Ziyu, Kan, Shunli, Fu, Xuanhao, Hu, Wei, and Zhu, Rusen

Subjects
LABORATORY rats, SPINAL cord injuries, YAP signaling proteins, WESTERN immunoblotting, PHOSPHOPROTEIN phosphatases
Abstract

Objective: The limited ability to regenerate axons after spinal cord injury (SCI) is influenced by factors such as astrocyte activation, reactive proliferation, and glial scar formation. The TGF-β/Smad (transforming growth factor-β/mothers against decapentaplegic homolog) pathway, associated with astrocytic scarring, plays a crucial role in recovery post-injury. This study aims to investigate how icariin (ICA) interacts with reactive astrocytes in the treatment of spinal cord injury. Methods: A rat SCI model was constructed, and the recovery of motor function was observed after treatment with ICA.HE staining, LFB staining, immunofluorescence staining, and Western blotting were employed to assess ICA's ability to inhibit astrocyte proliferation in rats following spinal cord injury by modulating YAP, as well as to evaluate the reparative effects of ICA on the injured spinal cord tissue. Primary astrocytes were isolated and cultured. Immunoprecipitation-Western Blot (IP-WB) ubiquitination and cytoplasm-nuclear separation were employed to assess PPM1B ubiquitination and nuclear translocation. Results: The CatWalk XT gait analysis, BBB (Basso, Beattie, and Bresnahan) score, electrophysiological measurements, HE staining, and LFB staining collectively demonstrated that ICA promotes motor function and tissue recovery following spinal cord injury in rats. Immunofluorescence staining and Western Blot analyses revealed that ICA inhibits astrocyte proliferation in rats post-spinal cord injury by suppressing YAP activity. Furthermore, the activation of YAP by XMU-MP-1 was shown to compromise the efficacy of ICA in these rats after spinal cord injury. Additional immunofluorescence staining and Western Blot experiments confirmed that ICA inhibits TGFβ1-induced astrocyte activation through the regulation of YAP. The knockdown of PPM1B (protein phosphatase, Mg2+/Mn2+-dependent 1B) in astrocytes was found to inhibit TGFβ signaling. Additionally, YAP was shown to regulate PPM1B ubiquitination and nuclear translocation through immunoprecipitation-Western blot analysis, along with the segregation of cytoplasm and nucleus. Conclusion: Icariin promotes functional recovery in rats after spinal cord injury by inhibiting YAP and regulating PPM1B ubiquitination to inhibiting the activation of reactive astrocytes. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Corrigendum: Network pharmacology integrated with experimental validation to explore the therapeutic role and potential mechanism of Epimedium for spinal cord injury

Author

Fu, Xuanhao, primary, Ma, Boyuan, additional, Zhou, Mengmeng, additional, Cheng, Yuelin, additional, Liu, Linyan, additional, Kan, Shunli, additional, Liu, Chengjiang, additional, Zhao, Xinyan, additional, Feng, Sa, additional, Zhu, Haoqiang, additional, Hu, Wei, additional, Jiang, Zehua, additional, and Zhu, Rusen, additional

Published
2023
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13. Network pharmacology integrated with experimental validation to explore the therapeutic role and potential mechanism of Epimedium for spinal cord injury

Author

Fu, Xuanhao, Ma, Boyuan, Zhou, Mengmeng, Cheng, Yuelin, Liu, Linyan, Kan, Shunli, Liu, Chengjiang, Zhao, Xinyan, Feng, Sa, Zhu, Haoqiang, Hu, Wei, Jiang, Zehua, and Zhu, Rusen

Subjects
Cellular and Molecular Neuroscience, Molecular Biology
Abstract

ObjectiveEpimedium (EPI) is a common Chinese herb with neuroprotective effects against a variety of central nervous system disorders, especially spinal cord injury (SCI). In this study, we performed network pharmacology and molecular docking analyses to reveal the mechanism underlying EPI treatment of SCI, then validated its efficacy using animal models.MethodsThe active ingredients and targets of EPI were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) and their targets annotated on the UniProt platform. SCI-related targets were searched from OMIM, TTD, and GeneCards databases. We employed the STRING platform to construct a protein–protein interaction (PPI) network then visualized the results using Cytoscape (3.8.2) software. We also subjected key EPI targets to ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, then docked the main active ingredients with the key targets. Finally, we established an SCI rat model to evaluate efficacy of EPI in treating SCI and validate the effects of different biofunctional modules predicted by network pharmacology.ResultsA total of 133 EPI targets were associated with SCI. GO terms and KEGG pathway enrichment results showed that EPI’s effect in treating SCI was significantly associated with inflammatory response, oxidative stress and the PI3K/AKT signaling pathway. Molecular docking results indicated that EPI’s active ingredients have a high affinity for the key targets. Results from animal experiments revealed that EPI not only markedly improved Basso, Beattie, and Bresnahan scores in SCI rats, but also significantly improved p-PI3K/PI3K and p-AKT/AKT ratio. Moreover, EPI treatment not only mediated a significant decrease in malondialdehyde (MDA) but also increased both superoxide dismutase (SOD), and glutathione (GSH). However, this phenomenon was successfully reversed by LY294002, a PI3K inhibitor.ConclusionEPI improves behavioral performance in SCI rats through anti-oxidative stress, which may be mediated by activation of the PI3K/AKT signaling pathway.

Published
2023
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17. Corrigendum: Icariin promotes functional recovery in rats after spinal cord injury by inhibiting YAP and regulating PPM1B ubiquitination to inhibiting the activation of reactive astrocytes.

Author

Feng, Sa, Liu, Linyan, Cheng, Yuelin, Zhou, Mengmeng, Zhu, Haoqiang, Zhao, Xinyan, Chen, Ziyu, Kan, Shunli, Fu, Xuanhao, Hu, Wei, and Zhu, Rusen

Subjects
CHINESE medicine, SPINAL cord injuries, SCHOLARLY periodical corrections, CONSTRUCTION projects, GLIOSIS, UBIQUITINATION
Abstract

The correction notice in the journal "Frontiers in Pharmacology" addresses an error in the Funding statement of an article on icariin's role in promoting functional recovery after spinal cord injury. The missing funding details from the Tianjin Municipal Health Commission's Integrated Traditional Chinese Medicine and Western Medicine Project Key Project (2023057) have been included to acknowledge their support for the research. The authors have apologized for the oversight, emphasizing that it does not impact the scientific conclusions of the article. [Extracted from the article]

Published
2024
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19. Long-term intravenous administration of carboxylated single-walled carbon nanotubes induces persistent accumulation in the lungs and pulmonary fibrosis via the nuclear factor-kappa B pathway [Corrigendum]

Author

Qin,Yue, Li,Suning, Zhao,Gan, Fu,Xuanhao, Xie,Xueping, Huang,Yiyi, Cheng,Xiaojing, Wei,Jinbin, Liu,Huagang, Lai,Zefeng, Qin,Yue, Li,Suning, Zhao,Gan, Fu,Xuanhao, Xie,Xueping, Huang,Yiyi, Cheng,Xiaojing, Wei,Jinbin, Liu,Huagang, and Lai,Zefeng

Abstract

Yue Qin, Suning Li, Gan Zhao, et al. Int J Nanomedicine. 2017;12:263–277.Page 266. In the right column the data range “6 to 15 nm” should be “5 to 15 nm”.Page 267. In Figure 1 Notes “wt%” should be “wt‰ in SWNTs powder”.Page 268. In Figure 2 Notes “1 mL per rat” should be “1 mL/kg body weight”.Read the original article.&nbsp

Published
2017

20. Long-term intravenous administration of carboxylated single-walled carbon nanotubes induces persistent accumulation in the lungs and pulmonary fibrosis via the nuclear factor-kappa B pathway [Corrigendum]

Author

Qin, Yue, primary, Li, Suning, additional, Zhao, Gan, additional, Fu, Xuanhao, additional, Xie, Xueping, additional, Huang, Yiyi, additional, Cheng, Xiaojing, additional, Wei, Jinbin, additional, Liu, Huagang, additional, and Lai, Zefeng, additional

Published
2017
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21. Long-term intravenous administration of carboxylated single-walled carbon nanotubes induces persistent accumulation in the lungs and pulmonary fibrosis via the nuclear factor-kappa B pathway

Author

Qin,Yue, Li,Suning, Zhao,Gan, Fu,Xuanhao, Xie,Xueping, Huang,Yiyi, Cheng,Xiaojing, Wei,Jinbin, Liu,Huagang, Lai,Zefeng, Qin,Yue, Li,Suning, Zhao,Gan, Fu,Xuanhao, Xie,Xueping, Huang,Yiyi, Cheng,Xiaojing, Wei,Jinbin, Liu,Huagang, and Lai,Zefeng

Abstract

Yue Qin,1,* Suning Li,2,* Gan Zhao,2,* Xuanhao Fu,1 Xueping Xie,1 Yiyi Huang,1 Xiaojing Cheng,3 Jinbin Wei,1 Huagang Liu,1 Zefeng Lai1 1Pharmaceutical College, Guangxi Medical University, 2Department of Pharmacy, The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, 3Life Sciences Institute, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China *These authors contributed equally to this work Abstract: Numerous studies have demonstrated promising application of single-walled carbon nanotubes (SWNTs) in drug delivery, diagnosis, and targeted therapy. However, the adverse health effects resulting from intravenous injection of SWNTs are not completely understood. Studies have shown that levels of “pristine” or carboxylated carbon nanotubes are very high in mouse lungs after intravenous injection. We hypothesized that long-term and repeated intravenous administration of carboxylated SWNTs (c-SWNTs) can result in persistent accumulation and induce histopathologic changes in rat lungs. Here, c-SWNTs were administered repeatedly to rats via tail-vein injection for 90 days. Long-term intravenous injection of c-SWNTs caused sustained embolization in lung capillaries and granuloma formation. It also induced a persistent inflammatory response that was regulated by the nuclear factor-kappa B signaling pathway, and which resulted in pulmonary fibrogenesis. c-SWNTs trapped within lung capillaries traversed capillary walls and injured alveolar epithelial cells, thereby stimulating production of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and pro-fibrotic growth factors (transforming growth factor-beta 1). Protein levels of type-I and type-III collagens, matrix metalloproteinase-2, and the tissue inhibitor of metalloproteinase-2 were upregulated after intravenous exposure to c-SWNTs as determined by immunohistochemical assays and Western blotting, which suggested collagen depos

Published
2016

23. Effect of Paravertebral Muscle Degeneration on Lumbar and Pelvic Sagittal Alignment in Patients With Degenerative Scoliosis

Author

Liu, Linyan, Jiang, Zehua, Fu, Xuanhao, Cheng, Yuelin, Feng, Sa, Zhou, Mengmeng, Zhao, Xinyan, and Zhu, Rusen

Abstract

Study Design Retrospective study.Objectives To explore the relationship between lumbar spine muscle mass and lumbar pelvic sagittal parameters in patients with degenerative scoliosis.Methods This study included ADS patients who were treated in our hospital from 2019 to 2023. The spinal parameters were evaluated through X-rays, and the relative muscle volume (RMV) and fat infiltration (FI) were measured through three-dimensional reconstruction. Patients were categorized into 3 groups based on SRS-Schwab sagittal balance correction (0, +, ++), and into 3 groups based on GAP score (proportioned, moderately dis-proportioned, severely dis-proportioned). Finally, patients were classified into low-quality and high-quality groups based on the FI of Paraspinal muscles (PSM).Results The study included a total of 63 patients. Significant statistical differences were observed in the FI and RMV of MF, ES and PS among patients classified by SRS-Schwab PT classification. Additionally, significant statistical differences were found in the RMV of MF and PS among patients classified by SRS-Schwab PI-LL classification and GAP score. Furthermore, a significant correlation was found between the FI and RMV of PSM and lumbopelvic sagittal parameters. The ordinal regression model analysis revealed that FI of ES significantly impacted PT imbalance, while RMV of MF significantly impacted PI-LL imbalance. Moreover, significant differences were noted in PT and PI between the low-quality and high-quality multifidus groups.Conclusions As sagittal imbalance worsens, PSM degeneration also intensifies, primarily characterized by an increase in FI and a decrease in RMV. Notably, PT and PI-LL are positively correlated with RMV and negatively correlated with FI.

Published
2024
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