Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we...Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive days.Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord.RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar formation.Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway.Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord.Taken together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury.展开更多
Maintaining the integrity of the blood-spinal cord barrier is critical for the recove ry of spinal cord injury.Ferro ptosis contributes to the pathogenesis of spinal cord injury.We hypothesized that ferroptosis is inv...Maintaining the integrity of the blood-spinal cord barrier is critical for the recove ry of spinal cord injury.Ferro ptosis contributes to the pathogenesis of spinal cord injury.We hypothesized that ferroptosis is involved in disruption of the blood-s pinal cord barrier.In this study,we administe red the ferroptosis inhibitor liproxstatin-1 intraperitoneally after contusive spinal co rd injury in rats.Liproxstatin-1 improved locomotor recovery and somatosensory evoked potential electrophysiological performance after spinal cord inju ry.Liproxstatin-1 maintained blood-spinal cord barrier integrity by upregulation of the expression of tight junction protein.Liproxstatin-1 inhibited ferroptosis of endothelial cell after spinal cord injury,as shown by the immunofluorescence of an endothelial cell marker(rat endothelium cell antigen-1,RECA-1) and fe rroptosis markers Acyl-CoA synthetase long-chain family member 4 and 15-lipoxygenase.Liproxstatin-1reduced brain endothelial cell ferroptosis in vitro by upregulating glutathione peroxidase 4 and downregulating Acyl-CoA synthetase long-chain family member4 and 15-lipoxygenase.Furthermore,inflammatory cell recruitment and astrogliosis were mitigated after liproxstatin-1 treatment.In summary,liproxstatin-1im proved spinal cord injury recovery by inhibiting ferroptosis in endothelial cells and maintaining blood-s pinal co rd barrier integrity.展开更多
Introduction:Lysinuric protein intolerance(LPI)is a rare genetic disorder caused by mutations in the solute carrier family 7A member 7(SLC7A7)gene.Case presentation:We presented two siblings with LPI,carrying novel mu...Introduction:Lysinuric protein intolerance(LPI)is a rare genetic disorder caused by mutations in the solute carrier family 7A member 7(SLC7A7)gene.Case presentation:We presented two siblings with LPI,carrying novel mutations of c.776delT(p.L259Rfs*18)and c.155G>T(p.G52V)in SLC7A7.The younger sibling,preferring protein-rich foods,showed severe symptoms,including alveolar proteinosis,macrophage activation syndrome,severe diarrhea,and disturbance of consciousness with involuntary movements.In contrast,the elder sibling only had mild symptoms,likely due to aversion to protein-rich food since toddler age.Conclusion:LPI is a congenital genetic metabolic disease with multisystem involvement.Initiating appropriate protein-restricted diet therapy as soon as possible could help prevent the progression of LPI.展开更多
INTRODUCTION Herpes simplex virus (HSV) is a ubiquitous human pathogen that causes a range of diseases from mild uncomplicated mucocutaneous infection to life-threatening conditions.1 HSV-1 is normally associated with...INTRODUCTION Herpes simplex virus (HSV) is a ubiquitous human pathogen that causes a range of diseases from mild uncomplicated mucocutaneous infection to life-threatening conditions.1 HSV-1 is normally associated with orofacial infections,whereas HSV-2 usually causes genital infections and can be transmitted from infected mothers to neonates.2 Less common manifestations of HSV infection,such as meningitis,encephalitis,3,4 hepatitis,5 and pneumonitis,6,7 can occur in both children and adults.After primary infection by HSV,the virus establishes a lifelong latent infection in the neuronal district,resulting in reactivation due to various triggering factors.展开更多
基金supported by the Key Project of the National Natural Science Foundation of China,No.81930070(to SF)the National Natural Science Foundation of China,No.81972074(to XY)the Key Program of Natural Science Foundation of Tianjin,No.19JCZDJC34900(to XY)。
文摘Argatroban is a synthetic thrombin inhibitor approved by U.S.Food and Drug Administration for the treatment of thrombosis.However,whether it plays a role in the repair of spinal cord injury is unknown.In this study,we established a rat model of T10 moderate spinal cord injury using an NYU Impactor ModerⅢand performed intraperitoneal injection of argatroban for 3 consecutive days.Our results showed that argatroban effectively promoted neurological function recovery after spinal cord injury and decreased thrombin expression and activity in the local injured spinal cord.RNA sequencing transcriptomic analysis revealed that the differentially expressed genes in the argatroban-treated group were enriched in the JAK2/STAT3 pathway,which is involved in astrogliosis and glial scar formation.Western blotting and immunofluorescence results showed that argatroban downregulated the expression of the thrombin receptor PAR1 in the injured spinal cord and the JAK2/STAT3 signal pathway.Argatroban also inhibited the activation and proliferation of astrocytes and reduced glial scar formation in the spinal cord.Taken together,these findings suggest that argatroban may inhibit astrogliosis by inhibiting the thrombin-mediated PAR1/JAK2/STAT3 signal pathway,thereby promoting the recovery of neurological function after spinal cord injury.
基金National Natural Science Foundation of China,No.81972074 (to XY)Natural Science Foundation of Tianjin,No.19JCZDJC34900 (to XY)National Key Research and Development Project of Stem Cell and Transformation Research,No.2019YFA0112100 (to SF)。
文摘Maintaining the integrity of the blood-spinal cord barrier is critical for the recove ry of spinal cord injury.Ferro ptosis contributes to the pathogenesis of spinal cord injury.We hypothesized that ferroptosis is involved in disruption of the blood-s pinal cord barrier.In this study,we administe red the ferroptosis inhibitor liproxstatin-1 intraperitoneally after contusive spinal co rd injury in rats.Liproxstatin-1 improved locomotor recovery and somatosensory evoked potential electrophysiological performance after spinal cord inju ry.Liproxstatin-1 maintained blood-spinal cord barrier integrity by upregulation of the expression of tight junction protein.Liproxstatin-1 inhibited ferroptosis of endothelial cell after spinal cord injury,as shown by the immunofluorescence of an endothelial cell marker(rat endothelium cell antigen-1,RECA-1) and fe rroptosis markers Acyl-CoA synthetase long-chain family member 4 and 15-lipoxygenase.Liproxstatin-1reduced brain endothelial cell ferroptosis in vitro by upregulating glutathione peroxidase 4 and downregulating Acyl-CoA synthetase long-chain family member4 and 15-lipoxygenase.Furthermore,inflammatory cell recruitment and astrogliosis were mitigated after liproxstatin-1 treatment.In summary,liproxstatin-1im proved spinal cord injury recovery by inhibiting ferroptosis in endothelial cells and maintaining blood-s pinal co rd barrier integrity.
文摘Introduction:Lysinuric protein intolerance(LPI)is a rare genetic disorder caused by mutations in the solute carrier family 7A member 7(SLC7A7)gene.Case presentation:We presented two siblings with LPI,carrying novel mutations of c.776delT(p.L259Rfs*18)and c.155G>T(p.G52V)in SLC7A7.The younger sibling,preferring protein-rich foods,showed severe symptoms,including alveolar proteinosis,macrophage activation syndrome,severe diarrhea,and disturbance of consciousness with involuntary movements.In contrast,the elder sibling only had mild symptoms,likely due to aversion to protein-rich food since toddler age.Conclusion:LPI is a congenital genetic metabolic disease with multisystem involvement.Initiating appropriate protein-restricted diet therapy as soon as possible could help prevent the progression of LPI.
基金grants from the National Major S&T Research Projects for the Control and Prevention of Major Infectious Diseases in China(2017ZX10103004-004,2018ZX10003006-001-004)the National Natural Science Foundation of China(31370203)+1 种基金the Capital Health Research and Development of Special Projects(2016-2-1142)Hospitals Foundation(QML20161201).
文摘INTRODUCTION Herpes simplex virus (HSV) is a ubiquitous human pathogen that causes a range of diseases from mild uncomplicated mucocutaneous infection to life-threatening conditions.1 HSV-1 is normally associated with orofacial infections,whereas HSV-2 usually causes genital infections and can be transmitted from infected mothers to neonates.2 Less common manifestations of HSV infection,such as meningitis,encephalitis,3,4 hepatitis,5 and pneumonitis,6,7 can occur in both children and adults.After primary infection by HSV,the virus establishes a lifelong latent infection in the neuronal district,resulting in reactivation due to various triggering factors.
