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We carefully read the study published by Hou et al. in Front. Pharmacol, which explored how tauroursodeoxycholic acid (TUDCA) regulates macrophage/monocyte distribution and improves spinal microenvironment to promote nerve regeneration through inhibiting NF-κB signaling pathway in spinal cord injury (
We would like to offer a few suggestions that could further strengthen the study’s reliability and completeness.
Preclinical studies have shown that TUDCA works not only by regulating and inhibiting the apoptotic cascade, but also by reducing oxidative stress, protecting mitochondria, producing anti-inflammatory effects, and serving as a chemical partner to maintain protein stability and correct folding (
In addition, although the author used RAW264.7 mouse monocyte macrophage line and primary spinal cord neural stem cell NSCs, other cell types related to the spinal cord microenvironment were not included. Microglia and astrocytes are pivotal in neuroinflammation and neural repair. Including these cells will clarify TUDCA’s role in modulating glial responses and its indirect effects on NSCs/macrophages. We suggest that new experiments using primary microglia and astrocytes isolated from rodent spinal cord tissue to evaluate TUDCA’s effects on these cells. These experiments will include: Functional assays (e.g., phagocytosis, cytokine secretion in microglia; reactive astrogliosis markers in astrocytes). Cross-talk analysis via co-culture systems (e.g., microglia-NSC or astrocyte-macrophage interactions) to mimic
Finally, although the author found through GO analysis and GSEA that TUDCA regulates inflammation and development related pathways, functional validation of the key differentially expressed gene NF-κB pathway was not conducted. We suggest that the author knock out the NF-κB differentially expressed gene to further validate the experimental results. This will provide a more comprehensive understanding of the mechanism of NF-κB signaling pathway in regulating nerve regeneration in spinal cord injury.
We commend the authors’innovative work and believe that their findings greatly deepen our understanding of TUDCA in spinal cord injury repair. This study provided evidence that TUDCA treatment regulated monocyte/macrophage distribution and improved the microenvironment to promote nerve regeneration in SCI mice. We look forward to further exploring TUDCA and its regulatory mechanisms in this context.
YC: Writing – review and editing, Writing – original draft. LW: Writing – review and editing. RM: Writing – review and editing.
The author(s) declare that financial support was received for the research and/or publication of this article. This research received funding from Zhejiang Chinese Medicine University Postgraduate Scientific Research Fund Project (No. Y202351285).
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The author(s) declare that no Generative AI was used in the creation of this manuscript.
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