Yizheng Yao

Chronic low back pain (LBP), predominantly driven by intervertebral disc degeneration (IVDD) is a major public health burden, yet the molecular mechanisms linking disc pathology to inflammation and pain remain poorly understood. Here, we identify a fibrotic, late-stage population of nucleus pulposus (NP) cells in degenerating intervertebral discs that aberrantly upregulate Colony Stimulating Factor 1 (CSF1). NP-derived CSF1 activates the CSF1 Receptor (CSF1R) on infiltrating macrophages, triggering a sustained pro-inflammatory cascade within the microenvironment. Using a murine model of disc injury, we demonstrate that either genetic ablation of Csf1r or pharmacologic inhibition with the selective CSF1R antagonist GW2580 markedly attenuates disc degeneration, confirmed by longitudinal MRI and histopathology, and significantly reduces associated neuropathic pain behaviors. These findings establish the CSF1–CSF1R axis as a central mechanistic link between fibrotic NP cell remodeling and macrophage-driven inflammation, highlighting it as a promising therapeutic target for mitigating disc degeneration and alleviating chronic LBP. One Sentence Summary: Blocking CSF1 signaling alleviates intervertebral disc degeneration and neuropathic pain

Although Helicobacter pylori (H.pylori) is the dominant gastrointestinal pathogen, the genetic and molecular mechanisms underlying H.pylori-related diseases have not been fully elucidated. Long non-coding RNAs (lncRNAs) have been identified in eukaryotic cells, many of which play important roles in regulating biological processes and pathogenesis. However, the expression changes of lncRNAs in human infected by H.pylori have been rarely reported. This study aimed to identify the dysregulated lncRNAs in human gastric epithelial cells and tissues infected with H.pylori. The aberrant expression profiles of lncRNAs and mRNAs in GES-1 cells with or without H.pylori infection were explored by microarray analysis. LncRNA-mRNA co-expression network was constructed based on Pearson correlation analysis. Gene Ontology (GO) and KEGG Pathway analyses of aberrantly expressed mRNAs were performed to identify the related biological functions and pathologic pathways. The expression changes of target lncRNAs were validated by qRT-PCR to confirm the microarray data in both cells and clinical specimens. Three hundred three lncRNAs and 565 mRNAs were identified as aberrantly expressed transcripts (≥2 or ≤0.5-fold change, P < 0.05) in cells with H.pylori infection compared to controls. LncRNA-mRNA co-expression network showed the core lncRNAs/mRNAs which might play important roles in H.pylori-related pathogenesis. GO and KEGG analyses have indicated that the functions of aberrantly expressed mRNAs in H.pylori infection were related closely with inflammation and carcinogenesis. QRT-PCR data confirmed the expression pattern of 8 (n345630, XLOC_004787, n378726, LINC00473, XLOC_005517, LINC00152, XLOC_13370, and n408024) lncRNAs in infected cells. Additionally, four down-regulated (n345630, XLOC_004787, n378726, and LINC00473) lncRNAs were verified in H.pylori-positive gastric samples. Our study provided a preliminary exploration of lncRNAs expression profiles in H.pylori-infected cells by microarray. These dysregulated lncRNAs might contribute to the pathological processes during H.pylori infection.