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Therapeutic potential of nanoceria pretreatment in preventing the development of urological chronic pelvic pain syndrome: Immunomodulation via reactive oxygen species scavenging and SerpinB2 downregulation
Bioengineering & Translational Medicine ( IF 6.1 ) Pub Date : 2022-06-07 , DOI: 10.1002/btm2.10346
Wei-Chih Lien, Xin-Ran Zhou, Ya-Jyun Liang, Congo Tak-Shing Ching, Chia-Yih Wang, Fu-I Lu, Huei-Cih Chang, Feng-Huei Lin, Hui-Min David Wang

Urological chronic pelvic pain syndrome (UCPPS) manifests as pelvic pain with frequent urination and has a 10% prevalence rate without effective therapy. Nanoceria (cerium oxide nanoparticles [CNPs]) were synthesized in this study to achieve potential long-term pain relief, using a commonly used UCPPS mouse model with cyclophosphamide-induced cystitis. Transcriptome sequencing analysis revealed that serpin family B member 2 (SerpinB2) was the most upregulated marker in mouse bladder, and SerpinB2 was downregulated with CNP pretreatment. The transcriptome sequencing analysis results agreed with quantitative polymerase chain reaction and western blot analysis results for the expression of related mRNAs and proteins. Analysis of Gene Expression Omnibus (GEO) datasets revealed that SerpinB2 was a differentially upregulated gene in human UCPPS. In vitro SerpinB2 knockdown downregulated proinflammatory chemokine expression (chemokine receptor CXCR3 and C-X-C motif chemokine ligand 10) upon treatment with 4-hydroperoxycyclophosphamide. In conclusion, CNP pretreatment may prevent the development of UCPPS, and reactive oxygen species (ROS) scavenging and SerpinB2 downregulation may modulate the immune response in UCPPS.

中文翻译:


纳米陶瓷预处理预防泌尿科慢性盆腔疼痛综合征发展的治疗潜力:通过活性氧清除和 SerpinB2 下调进行免疫调节



泌尿科慢性盆腔疼痛综合征(UCPPS)表现为盆腔疼痛伴尿频,若无有效治疗,患病率为10%。本研究使用常用的患有环磷酰胺诱发膀胱炎的 UCPPS 小鼠模型,合成了 Nanoceria(氧化铈纳米颗粒 [CNP]),以实现潜在的长期疼痛缓解。转录组测序分析显示,丝氨酸蛋白酶抑制剂家族 B 成员 2 (SerpinB2) 是小鼠膀胱中表达最上调的标记物,并且经 CNP 预处理后,丝氨酸蛋白酶抑制剂 B2 下调。转录组测序分析结果与相关mRNA和蛋白表达的定量聚合酶链反应和蛋白质印迹分析结果一致。对基因表达综合 (GEO) 数据集的分析表明,SerpinB2 是人类 UCPPS 中差异上调的基因。体外,用 4-氢过氧环磷酰胺处理后,SerpinB2 敲低可下调促炎趋化因子表达(趋化因子受体 CXCR3 和 CXC 基序趋化因子配体 10)。总之,CNP 预处理可能会阻止 UCPPS 的发生,而活性氧 (ROS) 清除和 SerpinB2 下调可能会调节 UCPPS 的免疫反应。
更新日期:2022-06-07
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