The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arth...The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine storms.Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains unclear.To address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury.Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory toxicity.Furthermore,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic branching.Collectively,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.展开更多
This article describes the characteristics of natural dusts, artificial dusts and industrial dusts, such as mineral phases, chemical components, morphological observation and size. Quartz and calcite are the main phas...This article describes the characteristics of natural dusts, artificial dusts and industrial dusts, such as mineral phases, chemical components, morphological observation and size. Quartz and calcite are the main phases of natural dusts and industrial dusts with high SiO2, CaO and low K2O, Na2O on the chemical composition. Natural dusts are mainly irregular shaped and some particle aggregation made of small dusts on the surface of large dust. Industrial dusts are globular and blob-like, but artificial dusts are columnar and fibrous. The fine particles are mainly in the range of 0.3-5 μm,of which the dusts of less than 5 μm are over 99%.The dissolution and electrochemical action of dusts in glutamic acid liquor at the simulated human body temperature (37 ℃) in 32 hours were investigated. The changes of pH values and electric conductivity of those dusts were similar, increased slowly in first 8 hours, and then the pH values increased rapidly. The total amount of dissolved ions of K, Ca, Na, Mg was 35.4-429 mg/L, particularly Ca was maximal of 20-334 mg/L. The total amount of dissolved ions of Fe, Zn, Mn, Pb, Ba was 0.18-5.59 ppm and the Al, Si was 3.0-21.7 mg/L. Each element dissolved rapidly relatively in first 16 hours. The relative solubility order of dusts in glutamic acid are: wollastonite > serpentine > sepiolite, the cement plant industrial dusts > power plant industrial dusts, and natural dusts have similar solubility. The wollastonite and power plant industrial dusts have highest solubility, which have high content of CaO; this shows there are a poorer corrosion-resisting ability and lower bio-resistibility. Sepiolite and cement plant industrial dusts have lowest solubility, which have high content of SiO2; this shows there are a higher corrosion-resisting ability and stronger bio-resistibility.展开更多
基金supported by the National Natural Science Foundation of China,No.82272484(to XC).
文摘The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury.Ruxolitinib,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine storms.Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains unclear.To address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury.Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory toxicity.Furthermore,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic branching.Collectively,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.
基金Project supported by National Natural Science Fundation of China (No. 41130746).
文摘This article describes the characteristics of natural dusts, artificial dusts and industrial dusts, such as mineral phases, chemical components, morphological observation and size. Quartz and calcite are the main phases of natural dusts and industrial dusts with high SiO2, CaO and low K2O, Na2O on the chemical composition. Natural dusts are mainly irregular shaped and some particle aggregation made of small dusts on the surface of large dust. Industrial dusts are globular and blob-like, but artificial dusts are columnar and fibrous. The fine particles are mainly in the range of 0.3-5 μm,of which the dusts of less than 5 μm are over 99%.The dissolution and electrochemical action of dusts in glutamic acid liquor at the simulated human body temperature (37 ℃) in 32 hours were investigated. The changes of pH values and electric conductivity of those dusts were similar, increased slowly in first 8 hours, and then the pH values increased rapidly. The total amount of dissolved ions of K, Ca, Na, Mg was 35.4-429 mg/L, particularly Ca was maximal of 20-334 mg/L. The total amount of dissolved ions of Fe, Zn, Mn, Pb, Ba was 0.18-5.59 ppm and the Al, Si was 3.0-21.7 mg/L. Each element dissolved rapidly relatively in first 16 hours. The relative solubility order of dusts in glutamic acid are: wollastonite > serpentine > sepiolite, the cement plant industrial dusts > power plant industrial dusts, and natural dusts have similar solubility. The wollastonite and power plant industrial dusts have highest solubility, which have high content of CaO; this shows there are a poorer corrosion-resisting ability and lower bio-resistibility. Sepiolite and cement plant industrial dusts have lowest solubility, which have high content of SiO2; this shows there are a higher corrosion-resisting ability and stronger bio-resistibility.
