OBJECTIVE The proteasome inhibitor bortezomib(BTZ)is a first-line anti-multi⁃ple myeloma drug.BTZ-induced peripheral neu⁃ropathy(BIPN)is a main adverse effect that char⁃acterized by neuropathic pain.There is still no ...OBJECTIVE The proteasome inhibitor bortezomib(BTZ)is a first-line anti-multi⁃ple myeloma drug.BTZ-induced peripheral neu⁃ropathy(BIPN)is a main adverse effect that char⁃acterized by neuropathic pain.There is still no strategy to prevent or treat BIPN,attributed to the unidentified mechanisms underlying BIPN.Previous studies suggested that BTZ impairs Schwann cells and thus leads to axonal demye⁃lination,whereas it remained not fully understood how BTZ cause Schwann cell death.It was observed that BTZ upregulates the autophagy marker LC3-Ⅱprotein in Schwann cells.However,it remains unclear whether BTZ causes autopha⁃gy-lysosome dysfunction in Schwann cells.METHODS The male C57BL/6 mice were intra⁃venous injection of BTZ(1 mg·kg-1 per day,twice weekly for a total of 4 weeks).The paw withdraw⁃al latency was tested by the Von Frey test and Hargreaves test to reflect the neuropathic pain.The conduction velocity and the action potential amplitude of the tail nerve were tested by neuro⁃physiological assessment to reflect peripheral nerve function.The histomorphology of the sciat⁃ic nerves was detected by immunofluorescence and transmission electron microscopy to reflect the demyelination and axonal degeneration.The RSC96 cells,the Schwann cell-like immortal cells,were cultured and exposed to BTZ.The lysosomal function was determined by Lyso⁃Tracker and DQ-BSA staining.Autophagy-relat⁃ed proteins,including p62 and LC3,and lysosom⁃al hydrolase cathepsin B were determined by Western blotting.RESULTS①BTZ induced mechano-allodynia,neurological conduction abnormalities of the tail nerve,demyelination and axonal degeneration of the sciatic nerves.②BTZ caused lysosomal dysfunction,resulting in the blockade of autophagy flux in Schwann cells and sciatic nerves.③The lysosomal activator Torin1 reversed lysosomal dysfunction caused by BTZ in Schwann cells.④Torin1 improved BTZ-induced mechano-allodynia and demyelination of sciatic nerves.CONCLUSION BTZ led to lyso⁃somal dysfunction in Schwann cells and contrib⁃uted to BIPN.Lysosomal activation could be a promising strategy for BIPN intervention.展开更多
OBJECTIVE Diabetic peripheral neuropathy(DPN)is the cause of considerable morbidity and mortality indiabetic patients.The loss of nerve fibersis the main pathological characteristics of the DPN and the pathway of Oct6...OBJECTIVE Diabetic peripheral neuropathy(DPN)is the cause of considerable morbidity and mortality indiabetic patients.The loss of nerve fibersis the main pathological characteristics of the DPN and the pathway of Oct6-Krox20 plays an important role in the formation of myelin sheath.In our previous study,we found that Fuzi(Radix aconite lateral ispreparata)could significantly improve the nerve conduction deficits and thermal hypoalgesia deficits in the diabetic rats,but the underlying molecular mechanisms have not been established.The aim of this study is to investigate the expression of Oct6,Krox20,myelin basic protein(Mbp)and myelin protein zero(Mpz)in Schwann cells and analyze the effect of Fuzi in the formation of myelin sheath.METHODS There were six groups in the study.In the control group,thecells weresupplemented with normal cell culture medium.In the mannitol group,the cells were fed with normal glucose plus mannitol.In the model group,the cells were supplemented with high glucose medium(75 mmol·L-1).In the other group,the cells weretreated with high glucose medium(75mmol·L-1)plus different concentrations of Fuzi(0.1,1.0 and 10.0μg·mL-1).After three days,real-time PCR was used to detect gene expression.RESULTS Compared with the control group,the model group showed lowerexpression of Oct6,Krox20,Mbp and Mpz.In comparison to the model group,Fuzi(0.1,1.0and 10.0μg·mL-1)increased the expression of Oct6,Krox20,Mbp and Mpz.CONCLUSION These results demonstrate that Fuzi enhances the protein of myelin sheath through impacting the pathway of Oct6-Krox20.展开更多
目的:本研究采用文献计量学方法,分析了关于间充质干细胞在周围神经损伤(PNI)和再生中的研究热点以及未来发展趋势。方法:通过在Web of Science数据库中使用关键词进行筛选,收集了从2013年1月1日到2024年6月1日之间发表的相关文章数据...目的:本研究采用文献计量学方法,分析了关于间充质干细胞在周围神经损伤(PNI)和再生中的研究热点以及未来发展趋势。方法:通过在Web of Science数据库中使用关键词进行筛选,收集了从2013年1月1日到2024年6月1日之间发表的相关文章数据。随后,我们利用可视化分析软件Cite Space和VOS viewer,从文献的发表数量、作者、所属国家、机构、关键词以及热门研究主题等多个角度进行综合评估。结果:在本研究中,我们广泛检索了Web of Science数据库,总计获取了386篇相关文献。我们分析了文献的年度发表量、国家分布、发表量前十的作者、被引用次数最多的10篇文章以及发表量前十的机构,更全面地了解最近10年周围神经损伤(PNI)治疗再生研究的现状和趋势。结论:间充质干细胞治疗周围神经损伤方法为周围神经损伤的治疗提供了新的可能性,为周围神经再生治疗领域提供了数据和理论支持,推动了间充质干细胞治疗在临床应用中的发展,有望为患者提供更有效的治疗选择,从而改善他们的生活质量和康复进程。展开更多
文摘OBJECTIVE The proteasome inhibitor bortezomib(BTZ)is a first-line anti-multi⁃ple myeloma drug.BTZ-induced peripheral neu⁃ropathy(BIPN)is a main adverse effect that char⁃acterized by neuropathic pain.There is still no strategy to prevent or treat BIPN,attributed to the unidentified mechanisms underlying BIPN.Previous studies suggested that BTZ impairs Schwann cells and thus leads to axonal demye⁃lination,whereas it remained not fully understood how BTZ cause Schwann cell death.It was observed that BTZ upregulates the autophagy marker LC3-Ⅱprotein in Schwann cells.However,it remains unclear whether BTZ causes autopha⁃gy-lysosome dysfunction in Schwann cells.METHODS The male C57BL/6 mice were intra⁃venous injection of BTZ(1 mg·kg-1 per day,twice weekly for a total of 4 weeks).The paw withdraw⁃al latency was tested by the Von Frey test and Hargreaves test to reflect the neuropathic pain.The conduction velocity and the action potential amplitude of the tail nerve were tested by neuro⁃physiological assessment to reflect peripheral nerve function.The histomorphology of the sciat⁃ic nerves was detected by immunofluorescence and transmission electron microscopy to reflect the demyelination and axonal degeneration.The RSC96 cells,the Schwann cell-like immortal cells,were cultured and exposed to BTZ.The lysosomal function was determined by Lyso⁃Tracker and DQ-BSA staining.Autophagy-relat⁃ed proteins,including p62 and LC3,and lysosom⁃al hydrolase cathepsin B were determined by Western blotting.RESULTS①BTZ induced mechano-allodynia,neurological conduction abnormalities of the tail nerve,demyelination and axonal degeneration of the sciatic nerves.②BTZ caused lysosomal dysfunction,resulting in the blockade of autophagy flux in Schwann cells and sciatic nerves.③The lysosomal activator Torin1 reversed lysosomal dysfunction caused by BTZ in Schwann cells.④Torin1 improved BTZ-induced mechano-allodynia and demyelination of sciatic nerves.CONCLUSION BTZ led to lyso⁃somal dysfunction in Schwann cells and contrib⁃uted to BIPN.Lysosomal activation could be a promising strategy for BIPN intervention.
文摘OBJECTIVE Diabetic peripheral neuropathy(DPN)is the cause of considerable morbidity and mortality indiabetic patients.The loss of nerve fibersis the main pathological characteristics of the DPN and the pathway of Oct6-Krox20 plays an important role in the formation of myelin sheath.In our previous study,we found that Fuzi(Radix aconite lateral ispreparata)could significantly improve the nerve conduction deficits and thermal hypoalgesia deficits in the diabetic rats,but the underlying molecular mechanisms have not been established.The aim of this study is to investigate the expression of Oct6,Krox20,myelin basic protein(Mbp)and myelin protein zero(Mpz)in Schwann cells and analyze the effect of Fuzi in the formation of myelin sheath.METHODS There were six groups in the study.In the control group,thecells weresupplemented with normal cell culture medium.In the mannitol group,the cells were fed with normal glucose plus mannitol.In the model group,the cells were supplemented with high glucose medium(75 mmol·L-1).In the other group,the cells weretreated with high glucose medium(75mmol·L-1)plus different concentrations of Fuzi(0.1,1.0 and 10.0μg·mL-1).After three days,real-time PCR was used to detect gene expression.RESULTS Compared with the control group,the model group showed lowerexpression of Oct6,Krox20,Mbp and Mpz.In comparison to the model group,Fuzi(0.1,1.0and 10.0μg·mL-1)increased the expression of Oct6,Krox20,Mbp and Mpz.CONCLUSION These results demonstrate that Fuzi enhances the protein of myelin sheath through impacting the pathway of Oct6-Krox20.
文摘目的:本研究采用文献计量学方法,分析了关于间充质干细胞在周围神经损伤(PNI)和再生中的研究热点以及未来发展趋势。方法:通过在Web of Science数据库中使用关键词进行筛选,收集了从2013年1月1日到2024年6月1日之间发表的相关文章数据。随后,我们利用可视化分析软件Cite Space和VOS viewer,从文献的发表数量、作者、所属国家、机构、关键词以及热门研究主题等多个角度进行综合评估。结果:在本研究中,我们广泛检索了Web of Science数据库,总计获取了386篇相关文献。我们分析了文献的年度发表量、国家分布、发表量前十的作者、被引用次数最多的10篇文章以及发表量前十的机构,更全面地了解最近10年周围神经损伤(PNI)治疗再生研究的现状和趋势。结论:间充质干细胞治疗周围神经损伤方法为周围神经损伤的治疗提供了新的可能性,为周围神经再生治疗领域提供了数据和理论支持,推动了间充质干细胞治疗在临床应用中的发展,有望为患者提供更有效的治疗选择,从而改善他们的生活质量和康复进程。
