Acute ischemic stroke (AIS) is a dangerous neurological disease associated with an imbalance in Th17/Treg cells and abnormal activation of the Wnt/β-catenin signaling pathway. This study aims to investigate whether inhibition of miR-155 can activate the Wnt/β-catenin signaling pathway to improve Th17/Treg imbalance and provide neuroprotective effects against stroke. We employed a multi-level experimental design. Firstly, we analyzed the differential gene expression between the miR-155 antagomir-treated group and the control group using high-throughput sequencing to identify potential target genes. Subsequently, we conducted functional and pathway enrichment analysis of the differentially expressed genes using bioinformatics tools. Next, we performed in vivo animal experiments using a mouse model to validate the impact of miR-155 antagomir treatment on the Wnt/β-catenin signaling pathway and improvement of Th17/Treg cell ratios. Lastly, we conducted cell experiments to validate our findings further. High-throughput sequencing results showed significant differential expression between the miR-155 antagomir-treated group and the control group (BioProject: PRJNA1152758, SRA IDs: SRR30410532, SRR30410531, SRR30410530 for the disease group; SRR30410529, SRR30410528, SRR30410527 for the control group). Bioinformatics analysis revealed potential target genes associated with the Wnt/β-catenin signaling pathway and Th17/Treg cell imbalance. experiments demonstrated that miR-155 antagomir treatment significantly activated the Wnt/β-catenin signaling pathway and improved Th17/Treg cell ratios. In vivo, animal experiment results indicated that miR-155 antagomir treatment exhibited significant neuroprotective effects against AIS. This study demonstrates that miR-155 antagomir can improve Th17/Treg cell imbalance by activating the Wnt/β-catenin signaling pathway and exhibiting neuroprotective effects against AIS in a mouse model. These findings provide crucial support for miR-155 as a potential therapeutic strategy for stroke and lay the foundation for further research. This study identifies miR-155 as a pivotal regulator of the Th17/Treg cell balance and Wnt/β-catenin signaling pathway in AIS. By inhibiting miR-155, we demonstrate the potential to enhance neuroprotection and modulate immune responses, offering a promising therapeutic avenue for stroke management. These findings contribute to the growing understanding of molecular mechanisms in stroke and provide a foundation for developing miR-155-targeted therapies.
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http://dx.doi.org/10.1523/ENEURO.0347-24.2024 | DOI Listing |
Nat Immunol
January 2025
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Hematopoietic stem cells must mitigate myriad stressors throughout their lifetime to ensure normal blood cell generation. Here, we uncover unfolded protein response stress sensor inositol-requiring enzyme-1α (IRE1α) signaling in hematopoietic stem and progenitor cells (HSPCs) as a safeguard against myeloid leukemogenesis. Activated in part by an NADPH oxidase-2 mechanism, IRE1α-induced X-box binding protein-1 (XBP1) mediated repression of pro-leukemogenic programs exemplified by the Wnt-β-catenin pathway.
View Article and Find Full Text PDFeNeuro
January 2025
Department of Neurology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362002, China.
Acute ischemic stroke (AIS) is a dangerous neurological disease associated with an imbalance in Th17/Treg cells and abnormal activation of the Wnt/β-catenin signaling pathway. This study aims to investigate whether inhibition of miR-155 can activate the Wnt/β-catenin signaling pathway to improve Th17/Treg imbalance and provide neuroprotective effects against stroke. We employed a multi-level experimental design.
View Article and Find Full Text PDFJ Clin Pathol
January 2025
Harvard Medical School, Boston, Massachusetts, USA
Aims: WNT signalling pathway dysregulation is often a critical early component in colorectal neoplasia, particularly the chromosomal instability pathway. Using two WNT reporters, and , we sought to assess whether these polyps demonstrate predictable expression patterns and if these patterns show diagnostic value.
Methods: We evaluated 23 adenomas (TA), 23 sessile serrated lesions (SSLs), 14 SSL with dysplasia and 38 traditional serrated adenomas (TSA).
Cell Genom
January 2025
National Clinical Research Center for Obstetric & Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. Electronic address:
Endometriosis is a chronic condition with limited therapeutic options. The molecular aberrations promoting ectopic attachment and interactions with the local microenvironment sustaining lesion growth have been unclear, prohibiting development of targeted therapies. Here, we performed single-cell and spatial transcriptomic profiling of ectopic lesions and eutopic endometrium in endometriosis.
View Article and Find Full Text PDFJ Transl Med
January 2025
The Comprehensive Breast Care Center, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
Background: Bone marrow mesenchymal stem cells (BMSCs) are a crucial component of the tumor microenvironment (TME), with hypoxic conditions promoting their migration to tumors. Exosomes play a vital role in cell-to-cell communication within the TME. Hypoxic TME have a great impact on the release, uptake and biofunctions of exosomes.
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