Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein ...Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this effect.In this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic analysis.The results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer pain.In addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain hypersensitivity.Furthermore,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression.Moreover,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was enhanced.Mechanistically,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F.Additionally,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 methylation.These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.展开更多
目的:探讨血清抗着丝粒蛋白F抗体(anti-centromere protein F antibody,anti-CENPF)在乳腺癌中的临床价值。方法:收集100例初诊乳腺癌(breast cancer,BC)患者、40例乳腺良性疾病(non breast cancer,non-BC)患者和40名健康体检者(healthy...目的:探讨血清抗着丝粒蛋白F抗体(anti-centromere protein F antibody,anti-CENPF)在乳腺癌中的临床价值。方法:收集100例初诊乳腺癌(breast cancer,BC)患者、40例乳腺良性疾病(non breast cancer,non-BC)患者和40名健康体检者(healthy control,HC)血清,采用酶联免疫吸附试验检测血清中的anti-CENPF水平,同时化学发光法测定血清糖类抗原153(carbohydrate antigen 153,CA153)的水平。结果:BC组血清anti-CENPF水平高于non-BC组和HC组,差异有统计学意义(P<0.05)。anti-CENPF和CA153诊断乳腺癌中的曲线下面积(area under the curve,AUC)分别为0.714和0.672,两者联合检测的AUC为0.739。有淋巴结转移、远处转移或者人表皮生长因子受体2(human epidermal growth factor receptor-2,HER-2)阴性的乳腺癌患者血清anti-CENPF浓度明显升高(P<0.05)。不同肿瘤大小、临床分期、分子分型乳腺癌患者血清anti-CENPF水平比较,差异有统计学意义(P<0.05)。组间比较显示Ⅳ期和Ⅲ期血清anti-CENPF浓度高于Ⅰ期和Ⅱ期,HER-2过表达型、Luminal B型血清anti-CENPF水平低于三阴性乳腺癌(triple negative breast cancer,TNBC)患者。雌激素受体(receptors estrogen,ER)阳性的乳腺癌患者中,HER-2阴性组的anti-CENPF浓度高于HER-2阳性组,差异有统计学意义(P=0.026)。结论:血清antiCENPF在乳腺癌的诊断、临床分期及分子分型中发挥了重要作用,其水平可能与乳腺癌预后呈负相关,有望成为乳腺癌潜在的疾病标志物。展开更多
近年来,受秸秆粗放还田、气候变化等因素影响,由禾谷镰孢复合种(Fusarium graminearum species complex)引起的小麦赤霉病在我国频繁暴发流行,成为长江中下游和黄淮海等小麦主产区的主要病害,严重影响小麦稳产丰收。病菌产生的脱氧雪腐...近年来,受秸秆粗放还田、气候变化等因素影响,由禾谷镰孢复合种(Fusarium graminearum species complex)引起的小麦赤霉病在我国频繁暴发流行,成为长江中下游和黄淮海等小麦主产区的主要病害,严重影响小麦稳产丰收。病菌产生的脱氧雪腐镰刀菌烯醇和玉米赤霉烯酮等真菌毒素也严重威胁小麦质量安全。当前,由于缺乏高抗小麦品种,化学防治仍然是赤霉病防控的重要措施,但随着单一作用方式药剂的长期使用,病菌抗药性问题也逐渐加重。本文综述了禾谷镰孢复合种对苯并咪唑类杀菌剂、甾醇脱甲基抑制剂、肌球蛋白抑制剂、琥珀酸脱氢酶抑制剂等几类常用药剂的抗性现状和抗性机制。在此基础上,探讨禾谷镰孢复合种的抗药性治理对策。展开更多
基金supported by the National Natural Science Foundation of China,Nos.82001178(to LW),81901129(to LH),82001175(to FX)Shanghai Sailing Program,No.20YF1439200(to LW)+1 种基金the Natural Science Foundation of Shanghai,China,No.23ZR1450800(to LH)and the Fundamental Research Funds for the Central Universities,No.YG2023LC15(to ZX)。
文摘Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this effect.In this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic analysis.The results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer pain.In addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain hypersensitivity.Furthermore,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression.Moreover,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was enhanced.Mechanistically,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F.Additionally,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 methylation.These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.
文摘目的:探讨血清抗着丝粒蛋白F抗体(anti-centromere protein F antibody,anti-CENPF)在乳腺癌中的临床价值。方法:收集100例初诊乳腺癌(breast cancer,BC)患者、40例乳腺良性疾病(non breast cancer,non-BC)患者和40名健康体检者(healthy control,HC)血清,采用酶联免疫吸附试验检测血清中的anti-CENPF水平,同时化学发光法测定血清糖类抗原153(carbohydrate antigen 153,CA153)的水平。结果:BC组血清anti-CENPF水平高于non-BC组和HC组,差异有统计学意义(P<0.05)。anti-CENPF和CA153诊断乳腺癌中的曲线下面积(area under the curve,AUC)分别为0.714和0.672,两者联合检测的AUC为0.739。有淋巴结转移、远处转移或者人表皮生长因子受体2(human epidermal growth factor receptor-2,HER-2)阴性的乳腺癌患者血清anti-CENPF浓度明显升高(P<0.05)。不同肿瘤大小、临床分期、分子分型乳腺癌患者血清anti-CENPF水平比较,差异有统计学意义(P<0.05)。组间比较显示Ⅳ期和Ⅲ期血清anti-CENPF浓度高于Ⅰ期和Ⅱ期,HER-2过表达型、Luminal B型血清anti-CENPF水平低于三阴性乳腺癌(triple negative breast cancer,TNBC)患者。雌激素受体(receptors estrogen,ER)阳性的乳腺癌患者中,HER-2阴性组的anti-CENPF浓度高于HER-2阳性组,差异有统计学意义(P=0.026)。结论:血清antiCENPF在乳腺癌的诊断、临床分期及分子分型中发挥了重要作用,其水平可能与乳腺癌预后呈负相关,有望成为乳腺癌潜在的疾病标志物。
文摘近年来,受秸秆粗放还田、气候变化等因素影响,由禾谷镰孢复合种(Fusarium graminearum species complex)引起的小麦赤霉病在我国频繁暴发流行,成为长江中下游和黄淮海等小麦主产区的主要病害,严重影响小麦稳产丰收。病菌产生的脱氧雪腐镰刀菌烯醇和玉米赤霉烯酮等真菌毒素也严重威胁小麦质量安全。当前,由于缺乏高抗小麦品种,化学防治仍然是赤霉病防控的重要措施,但随着单一作用方式药剂的长期使用,病菌抗药性问题也逐渐加重。本文综述了禾谷镰孢复合种对苯并咪唑类杀菌剂、甾醇脱甲基抑制剂、肌球蛋白抑制剂、琥珀酸脱氢酶抑制剂等几类常用药剂的抗性现状和抗性机制。在此基础上,探讨禾谷镰孢复合种的抗药性治理对策。
