Theranostics
·
2025
·Vol. 15
·期 9
·3877
·
IF 13.3
Yueyang Li,Yu Zhai,Tianling Wang,Siya Wang,Yu Tian,Zhiqun Bian,Yang Zhang,Chao Zhang,Minghan Liu,Changqing Li
Rationale: Nucleus pulposus (NP) fibrosis is a contributing factor to intervertebral disc degeneration (IVDD), which lacks an effective treatment. This study focuses on elucidating the role and mechanisms of the TGF-β signaling repressor SKI in NP fibrosis and exploring its therapeutic potential. Methods: Single-cell RNA sequencing (scRNA-seq) was used to investigate fibrotic nucleus pulposus cell (NPC) subsets and assess TGF-β signaling activation. Two recombinant plasmids encoding single-chain variable fragments (scFvs) targeting the fibrotic NPC marker FAP and SKI mRNA were co-transfected into HEK-293T cells to yield functionalized exosomes (EX ski+scFv ). The addition of EX ski+scFv to a gelatin/oxidized sodium alginate hydrogel produced a pH-responsive exosome/hydrogel system named Gel@EX ski+scFv . The therapeutic effects and underlying mechanism of Gel@EX ski+scFv were evaluated by RNA sequencing, molecular docking and coimmunoprecipitation. Results: A fibrotic NPC subset was characterized by elevated FAP and diminished SKI expression, along with activation of the TGF-β signaling pathway. SKI overexpression reduced fibrosis in TGF-β-treated NPCs. EX ski+scFv successfully delivered SKI mRNA to FAP-expressing fibrotic NPCs. Gel@EX ski+scFv possessed good mechanical properties, degradability, injectability, and biocompatibility. Gel@EX ski+scFv effectively alleviated NP fibrosis and IVDD in rats. RNA sequencing, molecular docking and coimmunoprecipitation revealed that SKI could interact with FOXO3 to suppress the TGF-β signaling pathway. Conclusion: This study elucidates the mechanism by which SKI -mediated TGF-β signaling inhibition alleviates NP fibrosis. The development of the Gel@EX ski+scFv system for the targeted delivery of SKI mRNA offers a promising therapeutic strategy to alleviate NP fibrosis and IVDD in the future.
研究领域:
生物医学
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分子生物学
·
组织工程
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产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2024
·
IF 3.7
Yuehua Zhao,Bo Peng,Lijun Liu,Yanming Fu,Tianyu Zhao,Weichao Chi,Dong Li,Dong Ji,Xin Wang,Dapeng Wang
To facilitate effective training for freestyle skiers on artificial dry ski slopes, it is crucial to reduce the friction coefficient of the slopes and closely match it with that of snow. Traditional lubrication methods, such as water or soapy water, come with multiple disadvantages, including water waste, which leads to environmental pollution, short-lived effectiveness, and high costs. In this study, we have successfully developed a method for the scalable preparation of a liquid-infused coating (LIC) by tandem spraying inexpensive and environmentally friendly SiO2 particles and silicone oil lubricants. Experimental results showed that the resulting LIC is capable of imparting slippery properties to various surfaces, regardless of the surface chemistry. Moreover, the presence of LIC could reduce the friction coefficient significantly. By carefully regulating the surface composition, we achieved a friction coefficient of 0.059 between a snowboard and the LIC-functionalized ski slope, closely matching that between the snowboard and snow in a typical skiing competition venue (∼0.06). We successfully applied LIC onto 103 m2 dry ski slopes, providing a training ground for professional freestyle skiers.
研究领域:
材料科学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Complementary Medicine and Therapies
·
2023
·Vol. 23
·期 1
·1-14
·
IF 3.9
Zhang Ke,Ji Xiawei,Song Zhengyang,Song Wenjing,Huang Qunjia,Yu Tiantian,Shi Dibang,Wang Fangyan,Xue Xiangyang,Guo Junping
Background Cervical cancer (CC) is a common gynecological malignancy with high morbidity worldwide. Butyrate, a short-chain fatty acid produced by intestinal flora, has been reported to inhibit cervical carcinogenesis. This study aimed to investigate the pro-apoptotic effects of butyrate on CC and the underlying mechanisms. Methods Human HeLa and Ca Ski cells were used in this study. Cell proliferation, cell migration and invasion were detected by CCK-8 and EdU staining, transwell and wound healing assay, respectively. Cell cycle, mitochondrial membrane potential and apoptosis were evaluated by flow cytometry. Western blot and RT-qPCR were carried out to examine the related genes and proteins to the mitochondrial complex Ι and apoptosis. Metabolite changes were analyzed by energy metabolomics and assay kits. The association between G protein-coupled receptor 41, 43, 109a and CC prognosis was analyzed using data from The Cancer Genome Atlas (TCGA). Results CCK-8 results showed significant inhibition of CC cell proliferation induced by butyrate treatment, which was confirmed by EdU staining and cell cycle detection. Data from the transwell and wound healing assay revealed that CC cell migration was dramatically reduced following butyrate treatment. Additionally, invasiveness was also decreased by butyrate. Western blot analysis showed that cleaved Caspase 3 and cleaved PARP, the enforcers of apoptosis, were increased by butyrate treatment. The results of Annexin V/PI staining and TUNEL also showed an increase in butyrate-induced apoptotic cells. Expression of Cytochrome C (Cytc), Caspase 9, Bax, but not Caspase 12 or 8, were up-regulated under butyrate exposure. Mechanistically, the decrease in mitochondrial NADH and NAD + levels after treatment with butyrate was observed by energy metabolomics and the NAD+/NADH Assay Kit, similar to the effects of the complex Ι inhibitor rotenone. Western blot results also demonstrated that the constituent proteins of mitochondrial complex Ι were reduced by butyrate. Furthermore, mitochondria-dependent apoptosis has been shown to be initiated by inhibition of the complex Ι. Conclusion Collectively, our results revealed that butyrate inhibited the proliferation, migration and invasion of CC cells, and induced mitochondrial-dependent apoptosis by inhibiting mitochondrial complex Ι.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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