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3篇 您的检索式:作者名="Chaofan Wan"
    题名 作者 年代 出处 被引量
1Thymosin Alpha-1 Inhibits Complete Freund’s Adjuvant-Induced Pain and Production of Microglia-Mediated Pro-inflammatory Cytokines in Spinal Cord显示文摘Activation of inflammatory responses regulates the transmission of pain pathways through an integrated network in the peripheral and central nervous systems.The immunopotentiator thymosin alpha-1(Tal)has recently been reported to have anti-inflammatory and neuroprotective functions in rodents.However,how Tα1 affects inflammatory pain remains unclear.In the present study,intraperitoneal injection of Tal attenuated complete Freund's adjuvant(CFA)-induced pain hypersensitivity,and decreased the up-regulation of pro-inflammatory cytokines(TNF-α,IL-1β,and IL-6)in inflamed skin and the spinal cord.We found that CFA-induced peripheral inflammation evoked strong microglial activation,but the effect was reversed by Tα1.Notably,Tα1 reversed the CFA-induced up-regulation of vesicular glutamate transporter(VGLUT)and down-regulated the vesicular γ-aminobutyric acid transporter(VGAT)in the spinal cord.Taken together,these results suggest that Tα1 plays a therapeutic role in inflammatory pain and in the modulation of microgliainduced pro-inflammatory cytokine production in addition to mediation of VGLUT and VGAT expression in the spinal cord.Yunlong Xu Yanjun Jiang Lin Wang Jiahua Huang Junmao Wen Hang Lv Xiaoli Wu Chaofan Wan Chuanxin Yu Wenjie Zhang Jiaying Zhao Yinqi Zhou Yongjun Chen 2019Neuroscience Bulletin2019,35,4:4
2Combining radiation and the ATR inhibitor berzosertib activates STING signaling and enhances immunotherapy via inhibiting SHP1 function in colorectal cancer显示文摘Background:Immune checkpoint inhibitors(ICIs)targeting programmed cell death protein 1(PD-1)and programmed death-ligand 1(PD-L1)have shown a moderate response in colorectal cancer(CRC)with deficient mismatch repair(dMMR)functions and poor response in patients with proficientMMR(pMMR).pMMRtumors are generally immunogenically“cold”,emphasizing combination strategies to turn the“cold”tumor“hot”to enhance the efficacy of ICIs.ATR inhibitors(ATRi)have been proven to cooperate with radiation to promote antitumor immunity,but it is unclear whether ATRi could facilitate the efficacy of IR and ICI combinations in CRCs.This study aimed to investigate the efficacy of combining ATRi,irradiation(IR),and anti-PD-L1 antibodies in CRC mouse models with different microsatellite statuses.Methods:The efficacy of combining ATRi,IR,and anti-PD-L1 antibodies was evaluated in CRC tumors.The tumor microenvironment and transcriptome signatures were investigated under different treatment regimens.The mechanisms were explored via cell viability assay,flow cytometry,immunofluorescence,immunoblotting,co-immunoprecipitation,and real-time quantitative PCR in multiple murine and human CRC cell lines.Results:Combining ATRi berzosertib and IR enhanced CD8+T cell infiltration and enhanced the efficacy of anti-PD-L1 therapy in mouse CRC models with different microsatellite statuses.The mechanistic study demonstrated that IR+ATRi could activate both the canonical cGAS-STING-pTBK1/pIRF3 axis by increasing cytosolic double-stranded DNA levels and the non-canonical STING signaling by attenuating SHP1-mediated inhibition of the TRAF6-STINGp65 axis,via promoting SUMOylation of SHP1 at lysine 127.By boosting the STING signaling,IR+ATRi induced type I interferon-related gene expression and strong innate immune activation and reinvigorated the cold tumor microenvironment,thus facilitating immunotherapy.Conclusions:The combination of ATRi and IR could facilitate anti-PD-L1 therapy by promoting STING signaling in CRC models with different microsatellite statuses.The new combination strategy raised by our study isworth investigating in the management of CRC.Chaofan Liu Xi Wang Wan Qin Jingyao Tu Chunya Li Weiheng Zhao Li Ma Bo Liu Hong Qiu Xianglin Yuan 2023Cancer Communications2023,43,4:1
3A metabolism-associated gene signature with prognostic value in colorectal cancer显示文摘Objective In this study,our goal was to explore the role of metabolism-associated genes in colorectal cancer(CRC)and construct a prognostic model for patients with CRC.Methods Differential expression analysis was conducted using RNA-sequencing data from The Cancer Genome Atlas(TCGA)dataset.Enrichment analyses were performed to determine the function of dysregulated metabolism-associated genes.The protein-protein interaction(PPI)network,Kaplan-Meier curves,and stepwise Cox regression analyses identified key metabolism-associated genes.A prognostic model was constructed using LASSO Cox regression analysis and visualized as a nomogram.Survival analyses were conducted in the TCGA and Expression Omnibus(GEO)cohorts to demonstrate the predictive ability of the model.Results A total of 332 differentially expressed metabolism-associated genes in CRC were screened from the TCGA cohort.Differentially expressed metabolism-associated genes mainly participate in the metabolism of nucleoside phosphate,ribose phosphate,lipids,and fatty acids.A PPI network was constructed out of 328 key genes.A prognostic model was established based on five prognostic genes(ALAD,CHDH,ISYNA1,NAT1,and P4HA1)and was demonstrated to predict survival in the TCGA and GEO cohorts accurately.Conclusion The metabolism-associated prognostic model can predict the survival of patients with CRC.Our work supplements previous work focusing on determining prognostic factors of CRC and lays a foundation for further mechanistic exploration.Lingyan Xiao Yongbiao Huang Wan Qin Chaofan Liu Hong Qiu Bo Liu Xianglin Yuan 2022Oncology and Translational Medicine2022,8,1:0
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