Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins ...Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous repair.These proteins are thus candidate targets for spinal cord injury therapy.Our previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model animals.However,the specific mechanism and potential targets involved remain to be clarified.In this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive days.We found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal cord.Bioinformatics analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed molecules.Immunofluorescence staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord tissue.The expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve rsican.Furthermore,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB 202190.This suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulation.In summary,our findings show that photobiomodulation modulates the expression of chondroitin sulfate proteoglycans,and versican is one of the key target molecules of photo biomodulation.MAPK/Sox9 and Smad3/Sox9 pathways may play a role in the effects of photo biomodulation on chondroitin sulfate proteoglycan accumulation after spinal cord injury.展开更多
目的:探讨SOX10在乳腺导管上皮普通性增生(usual ductal hyperplasia,UDH)、非典型增生(atypical hyperplasia,ADH)、导管内癌(ductal carcinoma in situ,DCIS)及不同亚型浸润性导管癌中的表达情况。方法:收集我院病理科2021年12月至202...目的:探讨SOX10在乳腺导管上皮普通性增生(usual ductal hyperplasia,UDH)、非典型增生(atypical hyperplasia,ADH)、导管内癌(ductal carcinoma in situ,DCIS)及不同亚型浸润性导管癌中的表达情况。方法:收集我院病理科2021年12月至2023年06月进行了SOX10免疫组化染色的乳腺标本共197例,其中UDH 48例、ADH 20例、DCIS 40例、伴大汗腺分化的癌10例、luminal A 20例、luminal B 27例、Her2过表达10例及三阴性乳腺癌(triple-negative breast carcinoma,TNBC)22例,分析不同乳腺导管上皮性病变中SOX10的表达差异。结果:SOX10在48例UDH呈马赛克样斑驳着色,而20例ADH及40例DCIS中均不表达,差异具有统计学意义(P<0.001);SOX10在三阴性乳腺癌中阳性率为68.20%(15/22),而在luminal A型、luminal B型、Her2过表达型浸润性乳腺癌中均不表达,差异具有统计学意义(P<0.001);SOX10在AR阴性的三阴性乳腺癌中表达率高达86.67%(13/15),在AR阳性三阴型乳腺癌中仅有28.57%(2/7),而在伴大汗腺分化乳腺癌(AR均为阳性)中不表达,差异具有统计学意义(P<0.001);SOX10在所有正常乳腺导管周围肌上皮表达,而在32.5%(13/40)DCIS导管周围肌上皮缺失。结论:SOX10免疫组化染色是鉴别诊断UDH和ADH的特异性指标,但不能区分ADH和DCIS,且在导管内癌特别是高级别导管内癌肌上皮中可表达丢失,用来鉴别DCIS和浸润性癌特别是微浸润性乳腺癌有一定的风险;SOX10是三阴性乳腺癌相对特异的指标且与AR的表达呈负相关;正确判读SOX10的免疫组化染色模式,有利于我们更好的识别不同乳腺导管上皮性病变。展开更多
基金supported by the National Natural Science Foundation of China,Nos.81070996(to ZW),81572151(to XH)Shaanxi Provincial Key R&D Program,Nos.2020ZDLSF02-05(to ZW),2021ZDLSF02-10(to XH)+1 种基金Everest Project of Military Medicine of Air Force Medical University,No.2018RCFC02(to XH)Boosting Project of the First Affiliated Hospital of Air Force Medical University,No.XJZT19Z22(to ZW)。
文摘Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury treatment.The cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous repair.These proteins are thus candidate targets for spinal cord injury therapy.Our previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model animals.However,the specific mechanism and potential targets involved remain to be clarified.In this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive days.We found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal cord.Bioinformatics analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed molecules.Immunofluorescence staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord tissue.The expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve rsican.Furthermore,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB 202190.This suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulation.In summary,our findings show that photobiomodulation modulates the expression of chondroitin sulfate proteoglycans,and versican is one of the key target molecules of photo biomodulation.MAPK/Sox9 and Smad3/Sox9 pathways may play a role in the effects of photo biomodulation on chondroitin sulfate proteoglycan accumulation after spinal cord injury.
文摘目的:探讨SOX10在乳腺导管上皮普通性增生(usual ductal hyperplasia,UDH)、非典型增生(atypical hyperplasia,ADH)、导管内癌(ductal carcinoma in situ,DCIS)及不同亚型浸润性导管癌中的表达情况。方法:收集我院病理科2021年12月至2023年06月进行了SOX10免疫组化染色的乳腺标本共197例,其中UDH 48例、ADH 20例、DCIS 40例、伴大汗腺分化的癌10例、luminal A 20例、luminal B 27例、Her2过表达10例及三阴性乳腺癌(triple-negative breast carcinoma,TNBC)22例,分析不同乳腺导管上皮性病变中SOX10的表达差异。结果:SOX10在48例UDH呈马赛克样斑驳着色,而20例ADH及40例DCIS中均不表达,差异具有统计学意义(P<0.001);SOX10在三阴性乳腺癌中阳性率为68.20%(15/22),而在luminal A型、luminal B型、Her2过表达型浸润性乳腺癌中均不表达,差异具有统计学意义(P<0.001);SOX10在AR阴性的三阴性乳腺癌中表达率高达86.67%(13/15),在AR阳性三阴型乳腺癌中仅有28.57%(2/7),而在伴大汗腺分化乳腺癌(AR均为阳性)中不表达,差异具有统计学意义(P<0.001);SOX10在所有正常乳腺导管周围肌上皮表达,而在32.5%(13/40)DCIS导管周围肌上皮缺失。结论:SOX10免疫组化染色是鉴别诊断UDH和ADH的特异性指标,但不能区分ADH和DCIS,且在导管内癌特别是高级别导管内癌肌上皮中可表达丢失,用来鉴别DCIS和浸润性癌特别是微浸润性乳腺癌有一定的风险;SOX10是三阴性乳腺癌相对特异的指标且与AR的表达呈负相关;正确判读SOX10的免疫组化染色模式,有利于我们更好的识别不同乳腺导管上皮性病变。
