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
Based on the collected multiwavelength data, namely in the radio(NVSS, FIRST, RATAN-600), IR(WISE),optical(Pan-STARRS), UV(GALEX), and X-ray(ROSAT, Swift-XRT) ranges, we have performed a cluster analysis for the blaza...Based on the collected multiwavelength data, namely in the radio(NVSS, FIRST, RATAN-600), IR(WISE),optical(Pan-STARRS), UV(GALEX), and X-ray(ROSAT, Swift-XRT) ranges, we have performed a cluster analysis for the blazars of the Roma-BZCAT catalog. Using two machine learning methods, namely a combination of PCA with k-means clustering and Kohonen's self-organizing maps(SOMs), we have constructed an independent classification of the blazars(five classes) and compared the classes with the known Roma-BZCAT classification(FSRQs, BL Lacs, galaxy-dominated BL Lacs, and blazars of an uncertain type) as well as with the high synchrotron peaked(HSP) blazars from the 3HSP catalog and blazars from the TeVCat catalog. The obtained groups demonstrate concordance with the BL Lac/FSRQ classification along with a continuous character of the change in the properties. The group of HSP blazars stands out against the overall distribution. We examine the characteristics of the five groups and demonstrate distinctions in their spectral energy distribution shapes. The effectiveness of the clustering technique for objective analysis of multiparametric arrays of experimental data is demonstrated.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Based on the collected multiwavelength data, namely in the radio(NVSS, FIRST, RATAN-600), IR(WISE),optical(Pan-STARRS), UV(GALEX), and X-ray(ROSAT, Swift-XRT) ranges, we have performed a cluster analysis for the blazars of the Roma-BZCAT catalog. Using two machine learning methods, namely a combination of PCA with k-means clustering and Kohonen's self-organizing maps(SOMs), we have constructed an independent classification of the blazars(five classes) and compared the classes with the known Roma-BZCAT classification(FSRQs, BL Lacs, galaxy-dominated BL Lacs, and blazars of an uncertain type) as well as with the high synchrotron peaked(HSP) blazars from the 3HSP catalog and blazars from the TeVCat catalog. The obtained groups demonstrate concordance with the BL Lac/FSRQ classification along with a continuous character of the change in the properties. The group of HSP blazars stands out against the overall distribution. We examine the characteristics of the five groups and demonstrate distinctions in their spectral energy distribution shapes. The effectiveness of the clustering technique for objective analysis of multiparametric arrays of experimental data is demonstrated.