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Zhao Shuqi Xi Dalin Cai Junwei Chen Wenting Xiang Jing Peng Na Wang Juan Jiang Yong Mei Zhuzhong Liu Jinghua 《中国科学:生命科学英文版》2020,63(3):401-409
Bacterial cell wall component-induced tolerance represents an important protective mechanism during microbial infection.Tolerance induced by the TLR2 agonist bacterial lipoprotein (BLP) has been shown to attenuate the inflammatory response,and simultaneously to augment antimicrobial function,thereby conferring its protection against microbial sepsis.However,the underlying mechanism by which BLP tolerance augments bactericidal activity has not been fully elucidated.Here,we reported that the induction of BLP tolerance in murine macrophages upregulated the expression of Rab20,a membrane trafficking regulator,at both the mRNA and protein levels upon bacterial infection.The knockdown of Rab20 with Rab20 specific siRNA(siRab20) did not affect the phagocytosis of Escherichia coli (E.coli),but substantially impaired the intracellular killing of the ingested E.coli in BLP-tolerized macrophages.Furthermore,Rab20 was associated with GFP-E.coli containing phagosomes,and BLP tolerization resulted in the enhanced maturation of GFP-E.coli-containing phagosomes associated with Rab20 and strong lysosomal acidification.The knockdown of Rab20 substantially diminished lysosome acidification and disturbed the fusion of GFP-E.coli containing phagosomes with lysosomes in BLP-tolerized macrophages.These results demonstrate that Rab20 plays a critical role in BLP tolerization-induced augmentation of bactericidal activity via promoting phagosome maturation and the fusion of bacteria containing phagosomes with lysosomes. 相似文献
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Xing Zhou Xiao Jiang Luzhou Liu Xiaoxiong Wang Chuan Li Yutang Yao Ying Kou Jiaqi Shen Taipeng Shen Zeng Li Shengke Yang Shukui Zhou Hong Liao Zhifu Luo Xiaoai Wu Shirong Chen Zhuzhong Cheng 《Translational oncology》2022,15(1)
PurposeProstate-specific membrane antigen (PSMA) ligands targeting has shown promising results in staging of prostate cancer (PCa). The aim of present study was to evaluate the value of 18F-PSMA-1007 PET/CT in PCa patients with biochemical recurrence.Methods71 patients with PCa after radical prostatectomy (RP) were included in the present study. Median prostate-specific antigen (PSA) level was 1.27 ng/mL (range 0.01–67.40 ng/mL, n = 69). All patients underwent whole-body PET/CT imaging after injection of 333±38 MBq 18F-PSMA-1007. The distribution of PSMA-positive lesions was assessed. The influence of PSA level, androgen deprivation therapy and primary Gleason score on PSMA-positive finding and uptake of 18F-PSMA-1007 were evaluated.Results56 (79%) patients showed at least one pathological finding on 18F-PSMA-1007 PET/CT. The rates of positive scans were 50%, 80%, 100%, 100% among patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/mL, respectively. The median Gleason score was 8 (range 7–10), and higher Gleason score (≤7 vs. ≥8) leads to higher detection rates (58.3% (14/24) vs. 88.9% (32/36), P = 0.006). The median SUVmax of positive findings in patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/mL were 4.51, 4.27, 11.50 and 14.08, respectively. The median SUVmax in patients with PSA level >2.0 ng/mL was significantly higher than that in patients with PSA ≤2.0 ng/mL (14.08 vs. 6.13, P<0.001).Conclusion18F-PSMA-1007 PET/CT demonstrated a high detection rate for patients with a raised PSA level after radical prostatectomy even in patients with extremely low PSA level (eg. PSA level ≤0.5 ng/mL), which was essential for further clinical management for PCa patients. 相似文献
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