Ischemia is a significant factor affecting the repair of peripheral nerve injuries,while exosomes have been shown to promote angiogenesis.To further investigate the detailed processes and efficacy of exosome thera⁃py ...Ischemia is a significant factor affecting the repair of peripheral nerve injuries,while exosomes have been shown to promote angiogenesis.To further investigate the detailed processes and efficacy of exosome thera⁃py for ischemic peripheral nerve injuries,this study utilized glucose-modified near-infrared-II(NIR-II)quantum dots(QDs)to label adipose-derived stem cell exosomes(QDs-ADSC-Exos),enabling long-term in vivo NIR-II imaging of exosome treatment for ischemic peripheral nerve damage.Experimental results confirmed that QDs can be used for non-invasive in vitro labeling of exosomes,with QDs-ADSC-Exos exhibiting strong fluorescence signals in the NIR-II window and demonstrating favorable NIR-II imaging characteristics in vivo.Notably,QDsADSC-Exos showed accumulation at the site of nerve injury in cases of ischemic peripheral nerve damage.Func⁃tional neurological assessments indicated that QDs-ADSC-Exos effectively promoted neural regeneration.This study highlights the potential of exosomes in treating ischemic peripheral nerve injuries and elucidates the spatio⁃temporal characteristics of exosome therapy,providing objective evidence for the further optimization of exosomebased treatment protocols.展开更多
Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal c...Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal carcinoma were prospectively enrolled.MR scanning,including three-dimensional liver acquisition with volume acceleration-flexible(3D LAVA_Flex)image,T2WI with fat suppression(T2WI-FS),T1WI,contrast enhancement(CE)T1WI-FS of nasopharynx and neck region were performed.The displaying rates of CN PNS were evaluated and compared between 3D LAVA_Flex and T2WI-FS,T1WI,CE-T1WI-FS at patient level,CN group level and neural level,respectively.Results The displaying rate of CN PNS in all 87 nasopharyngeal carcinoma patients by 3D LAVA_Flex sequence was 49.43%(43/87),higher than that of conventional MRI(30/87,34.48%,P=0.001).Among 59 patients with advanced nasopharyngeal carcinoma diagnosed with conventional sequences,the displaying rate of CN PNS was 71.19%(42/59)by 3D LAVA-Flex sequence,higher than that of conventional MRI(30/59,50.85%,P=0.001).At both patient level and posterior CN level,significant differences of the displaying rate of CN PNS were found between 3D LAVA-Flex sequence and T2WI-FS,T1WI,CE-T1WI-FS,while at CN level,the displaying rates of mandibular nerve PNS,CNⅨ—ⅪPNS in jugular foramen(P<0.05)and CNⅨ—ⅫPNS in carotid space of 3D LAVA_Flex sequence were all significantly higher than that of T2WI-FS,T1WI and CE-T1WI-FS(all P<0.05),of PNS of CNⅢ—Ⅴin cavernous sinus were higher than that of T2WI-FS(P<0.05),while of PNS of hypoglossal nerve were significantly higher than that of T2WI-FS and T1WI(both P<0.05).Conclusion 3D LAVA_Flex sequence could be used to effectively display CN PNS of nasopharyngeal carcinoma.展开更多
Objective To study the effect of changing heart rate on the ocular pulse and optic nerve head deformations with a viscoelastic lamina cribrosa.Methods An FE model of a healthy eye was reconstructed.The choroid was bip...Objective To study the effect of changing heart rate on the ocular pulse and optic nerve head deformations with a viscoelastic lamina cribrosa.Methods An FE model of a healthy eye was reconstructed.The choroid was biphasic and consisted of a solid phase(connective tissues)and a fluid phase(blood).The LC was viscoelastic as characterized by a stress-relaxation test.We applied arterial pressures at 18 entry sites(posterior ciliary arteries)and venous pressures at 4 exit sites(vortex veins).The heart rate was varied from 60 bpm to 120 bpm(increment:20 bpm).We reported the ocular pulse amplitude(OPA),pulse volume,optic nerve head(ONH)deformations and the dynamic modulus of the LC at different heart rates.Results With an increasing heart rate,the OPA decreased by 0.04 mmHg for every 10 bpm increase.The pulse volume also exhibited a linear relationship with heart rate,and decreased by 0.13 L.In addition,the storage modulus and the loss modulus of the LC center increased by 0.014 MPa and 0.04 MPa,respectively for every 10 pm increase in heart rate.Conclusions Our model predicted that the OPA,the pulse volume the ONH deformation decreased at a faster heartrate.We also found that the viscoelastic LC became stiffer with an increasing heart rate.Further studies are required to explore the potential links with the vascular dysregulation and axonal loss in glaucoma.展开更多
For the diagnosis of glaucoma,optical coherence tomography(OCT)is a noninvasive imaging technique for the assessment of retinal layers.To accurately segment intraretinal layers in an optic nerve head(ONH)region,we pro...For the diagnosis of glaucoma,optical coherence tomography(OCT)is a noninvasive imaging technique for the assessment of retinal layers.To accurately segment intraretinal layers in an optic nerve head(ONH)region,we proposed an automatic method for the segmentation of three intraretinal layers in eye OCT scans centered on ONH.The internal limiting membrane,inner segment and outer segment,Bruch’s membrane surfaces under vascular shadows,and interaction of multiple high-reflectivity regions in the OCT image can be accurately segmented through this method.Then,we constructed a novel spatial-gradient continuity constraint,termed spatial-gradient continuity constraint,for the correction of discontinuity between adjacent image segmentation results.In our experiment,we randomly selected 20 B-scans,each annotated three retinal layers by experts.Signed distance errors of?0.80μm obtained through this method are lower than those obtained through the state-of-art method(?1.43μm).Meanwhile,the segmentation results can be used as bases for the diagnosis of glaucoma.展开更多
Time: March 5-8, 2020Venue: Lasvegas, USWebsite: https://www.cns.org/Spine Summit 2020, the 36th Annual Meeting of the Section on Disorders of the Spine and Peripheral Nerves will take placein Lasvegas, US on March 5-...Time: March 5-8, 2020Venue: Lasvegas, USWebsite: https://www.cns.org/Spine Summit 2020, the 36th Annual Meeting of the Section on Disorders of the Spine and Peripheral Nerves will take placein Lasvegas, US on March 5-8, 2020.展开更多
Analysis of nerve agents and their degradation products constitutes an important subject for verifying the compliance to the Chemical Weapons Convention(CWC).In environmental water,the relevant degradation products of...Analysis of nerve agents and their degradation products constitutes an important subject for verifying the compliance to the Chemical Weapons Convention(CWC).In environmental water,the relevant degradation products of nerve agents are usually present at low concentration levels and mixed with a large amount of interferents.In this paper,six different kinds of solid-phase bulk sorbents were respectively investigated to improve the SPE efficiency for nerve agents degradation products from stimulant water samples,in which a large amount of background interferents were spiked.Results showed that the strong anion-exchange sorbent could selectively extract the spiking six target compounds from the matrices and showed a high recovery.展开更多
Physiological parameters of people and enact assessment standard of indoor thermal environment that are appropriate to our national conditions were explored from the perspective of physiology. From December 2005 to Ja...Physiological parameters of people and enact assessment standard of indoor thermal environment that are appropriate to our national conditions were explored from the perspective of physiology. From December 2005 to January 2006, nerve conduction velocities and skin temperatures of 20 healthy students were tested with questionnaire investigation. The results show that the nerve conduction velocities as well as skin temperatures present an obvious decline trend in a continuous draught, and that the nerve conduction velocities and skin temperatures have a definite linear relationship. Draught velocity is an important factor in winter that affects body comfort, and the subjects are sensitive to air velocity.展开更多
With the aging of the population intensified,neurodegenerative diseases have become a major problem that plagues modern people. In the organism,the pathological process common to these diseases is the damage and death...With the aging of the population intensified,neurodegenerative diseases have become a major problem that plagues modern people. In the organism,the pathological process common to these diseases is the damage and death of neurons in the central nervous system. Therefore,neurons the protection is the key issuesof neurological disease prevention and treatment. Polysaccharide is one of the important active substances in life activities,and has many biological activities. Polysaccharides are one of the most important active substances in life activities. They have many biological activities,such as energy storage,structural support,defense and antigen characterization. In addition,it is characterized by small toxicity,high safety and versatility. Polysaccharides also have other biological activities,such as anti-tumor,hypoglycemic,immune regulation,anti-inflammatory,anti-oxidation,neuroprotection and so on. As the active polysaccharide safe,non-toxic,in medicine,agriculture,food and other industries have a broad development and application value and prospects,having become a hot topic in many disciplines at home and abroad. More and more research evidence shows that polysaccharides in the neuroprotective aspects of the study more and more comprehensive and in-depth.In this paper,we reviewed the role of polysaccharides in neuroprotective mechanisms,including antioxidant,anti-inflammatory,promoting proliferation of neural cells,promoting neuronal differentiation,and inhibiting apoptosis of neurons.展开更多
OBJECTIVE To explore the synergistic effect of baicalin and geniposide(BG)on BV2 cell activation damage caused by lipopolysaccharide(LPS).METHODS BV2 murine microglial cell line was cultured in vitro,LPS(final concent...OBJECTIVE To explore the synergistic effect of baicalin and geniposide(BG)on BV2 cell activation damage caused by lipopolysaccharide(LPS).METHODS BV2 murine microglial cell line was cultured in vitro,LPS(final concentration 500 ng·m L-1)and various concentrationof Baicalin and Geniposide(BG)(final concentration12.5,25 and 50μg·m L-1)were added tointerven,the negative control was establised.MTT method was used to value the effect of LPS on the viability of BV2 cell line.The accumulated nitrite was assayed utilizing the Griess reaction method.RESULTS(1)Morphological observation:The common marphological of quesient microglia is circle,cell bodies smaller and synaptic slender.The enlargement of microglial cell bodies and an amoeboid morphology with retraction of extensions are generally induced by LPS.BG markedly suppressed the LPS-activated BV2 microglia morphological variations,meanwhile the dose-dependent was dramaticaly performed.(2)MTT test showed that LPS-stimulated BV2 cells viability was significantly decreased compared to the control group;compared to LPS treated cells,drug group(LPS+BG)effectively improves the LPS-stimulated BV2 cells viability.(3)The Griess reaction method indicated that LPS could obviously promoted the BV2 cells′NO generation contrasted to control group;while the drug group(LPS+BG)can effectively inhibited the generation of NO which activated by LPS.CONCLUSION The treatment group could significantly enhance survival rate of LPSstimulated BV2 cells,while,the level of NO was markedly decreased in BV2 induced by LPS.These findings suggest that combination of BG could attenuate BV2 microglial cells activation and injury which induced by LPS,possessed the capacity of neuroprotective.展开更多
OBJECTIVE The objective of this study was to characterize the neurotransmitter systems that cause constriction of murine airways.METHODS Murine precision cut lung slices(PCLS)and trachea were prepared,placed into perf...OBJECTIVE The objective of this study was to characterize the neurotransmitter systems that cause constriction of murine airways.METHODS Murine precision cut lung slices(PCLS)and trachea were prepared,placed into perfusion chambers equipped with platinum electrodes and stimulated transmurally(1.0 ms,50 V,0.1-30 Hz).To measure PCLS constriction,changes in airway luminal area in response to electric field stimulation(EFS)were captured as video images quantified using Image J software.For trachea,changes in isometric tension were recorded using Grass force transducers.Frequency response curves were generated in the absence and the presence of the inhibitors magnesium,atropine and capsaicin and responses analyzed and compared using a student's t-test(P<0.05).RESULTS EFS caused airway constriction in a frequency-dependent manner that was best fit by a biphasic curve.Neuron-specific stimulation was verified by Mg^(2+) blockade.Maximum airway constriction to 30 Hz EFS in PCLS was(51.8±3.0)%while tracheal constriction averaged(551±80)mg.Interestingly,in PCLS the muscarinic receptor antagonist atropine(10μmol·L^(-1))blocked(99.5±7.2)%of EFS induced constriction at 1 Hz,but only blocked(23.3±3.8)%of EFS induced constriction at 30 Hz and eliminated the first phase but not the second phase of the biphasic EFS response.Treatment with capsaicin to deplete sensory neurotransmitters significantly increased EFS constriction supporting the presence of sensory neurotransmitter systems in airways.CONCLUSION These data are consistent with parasympathetic constriction of airways by acetylcholine at lower EFS frequencies while higher frequencies release sensory dilator neurotransmitters.These data provide evidence for multiple nerve types innervating airways which may provide novel targets for treatment of lung disease.展开更多
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
基金Supported by the National Natural Science Foundation of China(82371373,W2412120)the Shanghai Natural Science Foundation(21ZR1436100).
文摘Ischemia is a significant factor affecting the repair of peripheral nerve injuries,while exosomes have been shown to promote angiogenesis.To further investigate the detailed processes and efficacy of exosome thera⁃py for ischemic peripheral nerve injuries,this study utilized glucose-modified near-infrared-II(NIR-II)quantum dots(QDs)to label adipose-derived stem cell exosomes(QDs-ADSC-Exos),enabling long-term in vivo NIR-II imaging of exosome treatment for ischemic peripheral nerve damage.Experimental results confirmed that QDs can be used for non-invasive in vitro labeling of exosomes,with QDs-ADSC-Exos exhibiting strong fluorescence signals in the NIR-II window and demonstrating favorable NIR-II imaging characteristics in vivo.Notably,QDsADSC-Exos showed accumulation at the site of nerve injury in cases of ischemic peripheral nerve damage.Func⁃tional neurological assessments indicated that QDs-ADSC-Exos effectively promoted neural regeneration.This study highlights the potential of exosomes in treating ischemic peripheral nerve injuries and elucidates the spatio⁃temporal characteristics of exosome therapy,providing objective evidence for the further optimization of exosomebased treatment protocols.
文摘Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal carcinoma were prospectively enrolled.MR scanning,including three-dimensional liver acquisition with volume acceleration-flexible(3D LAVA_Flex)image,T2WI with fat suppression(T2WI-FS),T1WI,contrast enhancement(CE)T1WI-FS of nasopharynx and neck region were performed.The displaying rates of CN PNS were evaluated and compared between 3D LAVA_Flex and T2WI-FS,T1WI,CE-T1WI-FS at patient level,CN group level and neural level,respectively.Results The displaying rate of CN PNS in all 87 nasopharyngeal carcinoma patients by 3D LAVA_Flex sequence was 49.43%(43/87),higher than that of conventional MRI(30/87,34.48%,P=0.001).Among 59 patients with advanced nasopharyngeal carcinoma diagnosed with conventional sequences,the displaying rate of CN PNS was 71.19%(42/59)by 3D LAVA-Flex sequence,higher than that of conventional MRI(30/59,50.85%,P=0.001).At both patient level and posterior CN level,significant differences of the displaying rate of CN PNS were found between 3D LAVA-Flex sequence and T2WI-FS,T1WI,CE-T1WI-FS,while at CN level,the displaying rates of mandibular nerve PNS,CNⅨ—ⅪPNS in jugular foramen(P<0.05)and CNⅨ—ⅫPNS in carotid space of 3D LAVA_Flex sequence were all significantly higher than that of T2WI-FS,T1WI and CE-T1WI-FS(all P<0.05),of PNS of CNⅢ—Ⅴin cavernous sinus were higher than that of T2WI-FS(P<0.05),while of PNS of hypoglossal nerve were significantly higher than that of T2WI-FS and T1WI(both P<0.05).Conclusion 3D LAVA_Flex sequence could be used to effectively display CN PNS of nasopharyngeal carcinoma.
文摘Objective To study the effect of changing heart rate on the ocular pulse and optic nerve head deformations with a viscoelastic lamina cribrosa.Methods An FE model of a healthy eye was reconstructed.The choroid was biphasic and consisted of a solid phase(connective tissues)and a fluid phase(blood).The LC was viscoelastic as characterized by a stress-relaxation test.We applied arterial pressures at 18 entry sites(posterior ciliary arteries)and venous pressures at 4 exit sites(vortex veins).The heart rate was varied from 60 bpm to 120 bpm(increment:20 bpm).We reported the ocular pulse amplitude(OPA),pulse volume,optic nerve head(ONH)deformations and the dynamic modulus of the LC at different heart rates.Results With an increasing heart rate,the OPA decreased by 0.04 mmHg for every 10 bpm increase.The pulse volume also exhibited a linear relationship with heart rate,and decreased by 0.13 L.In addition,the storage modulus and the loss modulus of the LC center increased by 0.014 MPa and 0.04 MPa,respectively for every 10 pm increase in heart rate.Conclusions Our model predicted that the OPA,the pulse volume the ONH deformation decreased at a faster heartrate.We also found that the viscoelastic LC became stiffer with an increasing heart rate.Further studies are required to explore the potential links with the vascular dysregulation and axonal loss in glaucoma.
基金Projects(61672542,61573380)supported by the National Natural Science Foundation of China
文摘For the diagnosis of glaucoma,optical coherence tomography(OCT)is a noninvasive imaging technique for the assessment of retinal layers.To accurately segment intraretinal layers in an optic nerve head(ONH)region,we proposed an automatic method for the segmentation of three intraretinal layers in eye OCT scans centered on ONH.The internal limiting membrane,inner segment and outer segment,Bruch’s membrane surfaces under vascular shadows,and interaction of multiple high-reflectivity regions in the OCT image can be accurately segmented through this method.Then,we constructed a novel spatial-gradient continuity constraint,termed spatial-gradient continuity constraint,for the correction of discontinuity between adjacent image segmentation results.In our experiment,we randomly selected 20 B-scans,each annotated three retinal layers by experts.Signed distance errors of?0.80μm obtained through this method are lower than those obtained through the state-of-art method(?1.43μm).Meanwhile,the segmentation results can be used as bases for the diagnosis of glaucoma.
文摘Time: March 5-8, 2020Venue: Lasvegas, USWebsite: https://www.cns.org/Spine Summit 2020, the 36th Annual Meeting of the Section on Disorders of the Spine and Peripheral Nerves will take placein Lasvegas, US on March 5-8, 2020.
文摘Analysis of nerve agents and their degradation products constitutes an important subject for verifying the compliance to the Chemical Weapons Convention(CWC).In environmental water,the relevant degradation products of nerve agents are usually present at low concentration levels and mixed with a large amount of interferents.In this paper,six different kinds of solid-phase bulk sorbents were respectively investigated to improve the SPE efficiency for nerve agents degradation products from stimulant water samples,in which a large amount of background interferents were spiked.Results showed that the strong anion-exchange sorbent could selectively extract the spiking six target compounds from the matrices and showed a high recovery.
基金Project(CSTC 2004AA7008) supported by the State I mportant Project of the Science and Technology
文摘Physiological parameters of people and enact assessment standard of indoor thermal environment that are appropriate to our national conditions were explored from the perspective of physiology. From December 2005 to January 2006, nerve conduction velocities and skin temperatures of 20 healthy students were tested with questionnaire investigation. The results show that the nerve conduction velocities as well as skin temperatures present an obvious decline trend in a continuous draught, and that the nerve conduction velocities and skin temperatures have a definite linear relationship. Draught velocity is an important factor in winter that affects body comfort, and the subjects are sensitive to air velocity.
文摘With the aging of the population intensified,neurodegenerative diseases have become a major problem that plagues modern people. In the organism,the pathological process common to these diseases is the damage and death of neurons in the central nervous system. Therefore,neurons the protection is the key issuesof neurological disease prevention and treatment. Polysaccharide is one of the important active substances in life activities,and has many biological activities. Polysaccharides are one of the most important active substances in life activities. They have many biological activities,such as energy storage,structural support,defense and antigen characterization. In addition,it is characterized by small toxicity,high safety and versatility. Polysaccharides also have other biological activities,such as anti-tumor,hypoglycemic,immune regulation,anti-inflammatory,anti-oxidation,neuroprotection and so on. As the active polysaccharide safe,non-toxic,in medicine,agriculture,food and other industries have a broad development and application value and prospects,having become a hot topic in many disciplines at home and abroad. More and more research evidence shows that polysaccharides in the neuroprotective aspects of the study more and more comprehensive and in-depth.In this paper,we reviewed the role of polysaccharides in neuroprotective mechanisms,including antioxidant,anti-inflammatory,promoting proliferation of neural cells,promoting neuronal differentiation,and inhibiting apoptosis of neurons.
基金The project suppored by National Natural Science Foundation of China(81473385)Shaanxi Province Education Department Project(13JS029)by Shaanxi Province Administration of Traditional Chinese Medicine(13-ZY016)
文摘OBJECTIVE To explore the synergistic effect of baicalin and geniposide(BG)on BV2 cell activation damage caused by lipopolysaccharide(LPS).METHODS BV2 murine microglial cell line was cultured in vitro,LPS(final concentration 500 ng·m L-1)and various concentrationof Baicalin and Geniposide(BG)(final concentration12.5,25 and 50μg·m L-1)were added tointerven,the negative control was establised.MTT method was used to value the effect of LPS on the viability of BV2 cell line.The accumulated nitrite was assayed utilizing the Griess reaction method.RESULTS(1)Morphological observation:The common marphological of quesient microglia is circle,cell bodies smaller and synaptic slender.The enlargement of microglial cell bodies and an amoeboid morphology with retraction of extensions are generally induced by LPS.BG markedly suppressed the LPS-activated BV2 microglia morphological variations,meanwhile the dose-dependent was dramaticaly performed.(2)MTT test showed that LPS-stimulated BV2 cells viability was significantly decreased compared to the control group;compared to LPS treated cells,drug group(LPS+BG)effectively improves the LPS-stimulated BV2 cells viability.(3)The Griess reaction method indicated that LPS could obviously promoted the BV2 cells′NO generation contrasted to control group;while the drug group(LPS+BG)can effectively inhibited the generation of NO which activated by LPS.CONCLUSION The treatment group could significantly enhance survival rate of LPSstimulated BV2 cells,while,the level of NO was markedly decreased in BV2 induced by LPS.These findings suggest that combination of BG could attenuate BV2 microglial cells activation and injury which induced by LPS,possessed the capacity of neuroprotective.
文摘OBJECTIVE The objective of this study was to characterize the neurotransmitter systems that cause constriction of murine airways.METHODS Murine precision cut lung slices(PCLS)and trachea were prepared,placed into perfusion chambers equipped with platinum electrodes and stimulated transmurally(1.0 ms,50 V,0.1-30 Hz).To measure PCLS constriction,changes in airway luminal area in response to electric field stimulation(EFS)were captured as video images quantified using Image J software.For trachea,changes in isometric tension were recorded using Grass force transducers.Frequency response curves were generated in the absence and the presence of the inhibitors magnesium,atropine and capsaicin and responses analyzed and compared using a student's t-test(P<0.05).RESULTS EFS caused airway constriction in a frequency-dependent manner that was best fit by a biphasic curve.Neuron-specific stimulation was verified by Mg^(2+) blockade.Maximum airway constriction to 30 Hz EFS in PCLS was(51.8±3.0)%while tracheal constriction averaged(551±80)mg.Interestingly,in PCLS the muscarinic receptor antagonist atropine(10μmol·L^(-1))blocked(99.5±7.2)%of EFS induced constriction at 1 Hz,but only blocked(23.3±3.8)%of EFS induced constriction at 30 Hz and eliminated the first phase but not the second phase of the biphasic EFS response.Treatment with capsaicin to deplete sensory neurotransmitters significantly increased EFS constriction supporting the presence of sensory neurotransmitter systems in airways.CONCLUSION These data are consistent with parasympathetic constriction of airways by acetylcholine at lower EFS frequencies while higher frequencies release sensory dilator neurotransmitters.These data provide evidence for multiple nerve types innervating airways which may provide novel targets for treatment of lung disease.
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.
