BACKGROUND Anoxic brain injury is a potentially lethal condition characterized by cerebral hypoperfusion and irreversible neuronal injury.Arterial spin-labeling(ASL)perfusion and diffusion-weighted imaging(DWI)magneti...BACKGROUND Anoxic brain injury is a potentially lethal condition characterized by cerebral hypoperfusion and irreversible neuronal injury.Arterial spin-labeling(ASL)perfusion and diffusion-weighted imaging(DWI)magnetic resonance imaging(MRI)have been proposed as tools to detect cerebral ischemic changes and may aid in the assessment of anoxic injury.AIM To explore the relationship between regional ASL perfusion patterns and clinical outcomes following cardiac arrest.METHODS We performed a retrospective review to identify patients with clinical suspicion of anoxic brain injury who underwent MRI within 15 days of cardiac arrest.Receiver operator characteristic(ROC)analysis and univariate logistic regression were used to evaluate associations between ASL perfusion scores,DWI signal intensity,and the following clinical features:(1)Myoclonus status epilepticus(MSE)within 24 hours;(2)Absent extensor or motor reflexes(EMR)at day 3 post-arrest;and(3)Absent brainstem reflexes(BSR)within 15 days.RESULTS Twenty-eight patients met inclusion criteria.Increased ASL signal in the left occipital lobe was significantly associated with MSE(P=0.038),while a trend was observed between right frontal ASL signal and EMR(P=0.078).ROC analysis showed that ASL scores≥7 were associated with higher odds of absent BSR(OR 2.14,P=0.53),though this did not reach statistical significance.DWI signal intensity did not show significant associations with clinical outcomes.The overall discriminatory performance of ASL for predicting outcomes was limited(AUC≈0.52).CONCLUSION This exploratory study suggests that regional ASL hyperperfusion,particularly in the left occipital and right frontal lobes,may be associated with adverse clinical signs following cardiac arrest.However,most findings did not reach statistical significance,and the study was underpowered to detect small-to-moderate effects.These preliminary results should be interpreted with caution and considered hypothesis-generating.Larger,prospective studies are warranted to clarify the prognostic value of ASL perfusion imaging in anoxic brain injury.展开更多
Site-directed spin-labeling with continuous wave electron paramagnetic resonance spectroscopy was used to monitor autoproteolysis of HIV-1 protease, an enzyme essential for viral maturation. Two protein constructs wer...Site-directed spin-labeling with continuous wave electron paramagnetic resonance spectroscopy was used to monitor autoproteolysis of HIV-1 protease, an enzyme essential for viral maturation. Two protein constructs were examined, namely subtype F and the circulating recombinant form CRF01_A/E. As the protease undergoes self-cleavage, protein unfolds and small peptide fragments containing the spin label are generated, which collectively give rise to a sharp spectral component that is easily discernable in the high-field resonance line in the EPR spectrum. By monitoring the intensity of this spectral component over time, the autoproteolytic stability of each construct was characterized under various conditions. Data were collected for samples stored at 4 °C, 25 °C, and 37 °C, and on a subtype F HIV-1 protease sample stored at 25 °C and containing the FDA-approved protease inhibitor Tipranavir. As expected, the rate of autoproteolysis decreased as the storage temperature was lowered. Minimal autoproteolysis was seen for the sample that contained Tipranavir, providing direction for future spectroscopic studies of active protease samples. When compared to standard methods of monitoring protein degradation such as gel electrophoresis or chromatographic analyses, spin-labeling with CW EPR offers a facile, real-time, non-consuming way to monitor autoproteolysis or protein degradation. Additionally, mass spectrometry studies revealed that the N-termini of both constructs are sensitive to degradation and that the sites of specific autoproteolysis vary.展开更多
We have studied the effect of concanavaline A (Con A) on conformational changes of membrane glycoproteins of mouse ascites hepatoma cells with a maleimide spin label, showing that conformational changes or a physical ...We have studied the effect of concanavaline A (Con A) on conformational changes of membrane glycoproteins of mouse ascites hepatoma cells with a maleimide spin label, showing that conformational changes or a physical arrangement of membrane glycoproteins could be induced quickly by the cross-linking of Con A with membrane receptors. We have also studied the effect of Con A on the mobility展开更多
This study was carried out to determine the possible protective effect of 1-ethyl-3-[4-(2, 2, 6, 6-tetramethylpiperidine-1-oxyl)]-1-nitrosourea (SLENU), recently synthesised in our laboratory on doxorubicin and bleomy...This study was carried out to determine the possible protective effect of 1-ethyl-3-[4-(2, 2, 6, 6-tetramethylpiperidine-1-oxyl)]-1-nitrosourea (SLENU), recently synthesised in our laboratory on doxorubicin and bleomycin-induced oxidative toxicity in C57 black tumour-bearing mice. Specifically, alterations in some biomarkers of oxidative stress, such as lipid peroxidation products measured as malondialdehyde (MDA) levels and activities of the antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), were studied in lung, heart and kidney homogenates isolated from C57 black tumor-bearing mice after i.p. treatment with solutions of DOX (60 mg/kg) and BLM (60 mg/kg). The same biomarkers were also measured after i.p. pretreatment of mice with SLENU (100 mg/kg). After treatment with doxorubicin, heart and kidney homogenates of mice had significantly higher productions of lipid peroxidation compared to lung homogenates. It was accompanied by increased activity of the antioxidant defence enzyme superoxide dismutase and decreased activity of catalase. Bleomycin-induced oxidative stress was confirmed by significantly higher production of lipid peroxidation in lungs compared to heart homogenates, elevation of the anti-oxidant activity of superoxide dismutase and decreased activity of catalase enzymes. After pre-treatment of the mice with SLENU, the levels of all studied oxidative stress biomarkers were significantly improved in comparison with those of the mice treated alone with either bleomycin, or doxorubicin. The present results and those from a previously demonstrated superoxide scavenging activities (SSA) of the nitrosourea SLENU have enabled us to explain the protective effect of the spin-labelled nitrosourea on doxorubicin and bleomycin-induced oxidative stress by scavenging of??O2- and increased NO release.展开更多
Background:The effect of arteriosclerotic intracranial arterial vessel wall enhancement(IAVWE)on downstream collateral flow found in vessel wall imaging(VWI)is not clear.Regardless of the mechanism underlying IAVWE on...Background:The effect of arteriosclerotic intracranial arterial vessel wall enhancement(IAVWE)on downstream collateral flow found in vessel wall imaging(VWI)is not clear.Regardless of the mechanism underlying IAVWE on VWI,damage to the patient’s nervous system caused by IAVWE is likely achieved by affecting downstream cerebral blood flow.The present study aimed to investigate the effect of arteriosclerotic IAVWE on downstream collateral flow.Methods:The present study recruited 63 consecutive patients at the Second Hospital of Hebei Medical University from January 2021 to November 2021 with underlying atherosclerotic diseases and unilateral middle cerebral artery(MCA)M1-segment stenosis who underwent an magnetic resonance scan within 3 days of symptom onset.The patients were divided into 4 groups according to IAVWE and the stenosis ratio(Group 1,n=17;Group 2,n=19;Group 3,n=13;Group 4,n=14),and downstream collateral flow was analyzed using three-dimensional pseudocontinuous arterial spin labeling(3D-pCASL)and RAPID software.The National Institutes of Health Stroke Scale(NIHSS)scores of the patients were also recorded.Two-factor multivariate analysis of variance using Pillai’s trace was used as the main statistical method.Results:No statistically significant difference was found in baseline demographic characteristics among the groups.IAVWE,but not the stenosis ratio,had a statistically significant significance on the late-arriving retrograde flow proportion(LARFP),hypoperfusion intensity ratio(HIR),and NIHSS scores(F=20.941,P<0.001,Pillai’s trace statistic=0.567).The between-subject effects test showed that IAVWE had a significant effect on the three dependent variables:LARFP(R^(2)=0.088,F=10.899,P=0.002),HIR(R^(2)=0.234,F=29.354,P<0.001),and NIHSS(R^(2)=114.339,F=33.338,P<0.001).Conclusions:Arteriosclerotic IAVWE significantly reduced downstream collateral flow and affected relevant neurological deficits.It was an independent factor affecting downstream collateral flow and NIHSS scores,which should be a focus of future studies.Trial Registration:ChiCTR.org.cn,ChiCTR2100053661.展开更多
文摘BACKGROUND Anoxic brain injury is a potentially lethal condition characterized by cerebral hypoperfusion and irreversible neuronal injury.Arterial spin-labeling(ASL)perfusion and diffusion-weighted imaging(DWI)magnetic resonance imaging(MRI)have been proposed as tools to detect cerebral ischemic changes and may aid in the assessment of anoxic injury.AIM To explore the relationship between regional ASL perfusion patterns and clinical outcomes following cardiac arrest.METHODS We performed a retrospective review to identify patients with clinical suspicion of anoxic brain injury who underwent MRI within 15 days of cardiac arrest.Receiver operator characteristic(ROC)analysis and univariate logistic regression were used to evaluate associations between ASL perfusion scores,DWI signal intensity,and the following clinical features:(1)Myoclonus status epilepticus(MSE)within 24 hours;(2)Absent extensor or motor reflexes(EMR)at day 3 post-arrest;and(3)Absent brainstem reflexes(BSR)within 15 days.RESULTS Twenty-eight patients met inclusion criteria.Increased ASL signal in the left occipital lobe was significantly associated with MSE(P=0.038),while a trend was observed between right frontal ASL signal and EMR(P=0.078).ROC analysis showed that ASL scores≥7 were associated with higher odds of absent BSR(OR 2.14,P=0.53),though this did not reach statistical significance.DWI signal intensity did not show significant associations with clinical outcomes.The overall discriminatory performance of ASL for predicting outcomes was limited(AUC≈0.52).CONCLUSION This exploratory study suggests that regional ASL hyperperfusion,particularly in the left occipital and right frontal lobes,may be associated with adverse clinical signs following cardiac arrest.However,most findings did not reach statistical significance,and the study was underpowered to detect small-to-moderate effects.These preliminary results should be interpreted with caution and considered hypothesis-generating.Larger,prospective studies are warranted to clarify the prognostic value of ASL perfusion imaging in anoxic brain injury.
文摘Site-directed spin-labeling with continuous wave electron paramagnetic resonance spectroscopy was used to monitor autoproteolysis of HIV-1 protease, an enzyme essential for viral maturation. Two protein constructs were examined, namely subtype F and the circulating recombinant form CRF01_A/E. As the protease undergoes self-cleavage, protein unfolds and small peptide fragments containing the spin label are generated, which collectively give rise to a sharp spectral component that is easily discernable in the high-field resonance line in the EPR spectrum. By monitoring the intensity of this spectral component over time, the autoproteolytic stability of each construct was characterized under various conditions. Data were collected for samples stored at 4 °C, 25 °C, and 37 °C, and on a subtype F HIV-1 protease sample stored at 25 °C and containing the FDA-approved protease inhibitor Tipranavir. As expected, the rate of autoproteolysis decreased as the storage temperature was lowered. Minimal autoproteolysis was seen for the sample that contained Tipranavir, providing direction for future spectroscopic studies of active protease samples. When compared to standard methods of monitoring protein degradation such as gel electrophoresis or chromatographic analyses, spin-labeling with CW EPR offers a facile, real-time, non-consuming way to monitor autoproteolysis or protein degradation. Additionally, mass spectrometry studies revealed that the N-termini of both constructs are sensitive to degradation and that the sites of specific autoproteolysis vary.
文摘We have studied the effect of concanavaline A (Con A) on conformational changes of membrane glycoproteins of mouse ascites hepatoma cells with a maleimide spin label, showing that conformational changes or a physical arrangement of membrane glycoproteins could be induced quickly by the cross-linking of Con A with membrane receptors. We have also studied the effect of Con A on the mobility
文摘This study was carried out to determine the possible protective effect of 1-ethyl-3-[4-(2, 2, 6, 6-tetramethylpiperidine-1-oxyl)]-1-nitrosourea (SLENU), recently synthesised in our laboratory on doxorubicin and bleomycin-induced oxidative toxicity in C57 black tumour-bearing mice. Specifically, alterations in some biomarkers of oxidative stress, such as lipid peroxidation products measured as malondialdehyde (MDA) levels and activities of the antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), were studied in lung, heart and kidney homogenates isolated from C57 black tumor-bearing mice after i.p. treatment with solutions of DOX (60 mg/kg) and BLM (60 mg/kg). The same biomarkers were also measured after i.p. pretreatment of mice with SLENU (100 mg/kg). After treatment with doxorubicin, heart and kidney homogenates of mice had significantly higher productions of lipid peroxidation compared to lung homogenates. It was accompanied by increased activity of the antioxidant defence enzyme superoxide dismutase and decreased activity of catalase. Bleomycin-induced oxidative stress was confirmed by significantly higher production of lipid peroxidation in lungs compared to heart homogenates, elevation of the anti-oxidant activity of superoxide dismutase and decreased activity of catalase enzymes. After pre-treatment of the mice with SLENU, the levels of all studied oxidative stress biomarkers were significantly improved in comparison with those of the mice treated alone with either bleomycin, or doxorubicin. The present results and those from a previously demonstrated superoxide scavenging activities (SSA) of the nitrosourea SLENU have enabled us to explain the protective effect of the spin-labelled nitrosourea on doxorubicin and bleomycin-induced oxidative stress by scavenging of??O2- and increased NO release.
基金Beijing Scholar 2015(No.2015-160)Health Commission of Hebei Province(No.20200919)Scientific Research Fund Project of the Second Hospital of Hebei Medical University(No.2HC202056)
文摘Background:The effect of arteriosclerotic intracranial arterial vessel wall enhancement(IAVWE)on downstream collateral flow found in vessel wall imaging(VWI)is not clear.Regardless of the mechanism underlying IAVWE on VWI,damage to the patient’s nervous system caused by IAVWE is likely achieved by affecting downstream cerebral blood flow.The present study aimed to investigate the effect of arteriosclerotic IAVWE on downstream collateral flow.Methods:The present study recruited 63 consecutive patients at the Second Hospital of Hebei Medical University from January 2021 to November 2021 with underlying atherosclerotic diseases and unilateral middle cerebral artery(MCA)M1-segment stenosis who underwent an magnetic resonance scan within 3 days of symptom onset.The patients were divided into 4 groups according to IAVWE and the stenosis ratio(Group 1,n=17;Group 2,n=19;Group 3,n=13;Group 4,n=14),and downstream collateral flow was analyzed using three-dimensional pseudocontinuous arterial spin labeling(3D-pCASL)and RAPID software.The National Institutes of Health Stroke Scale(NIHSS)scores of the patients were also recorded.Two-factor multivariate analysis of variance using Pillai’s trace was used as the main statistical method.Results:No statistically significant difference was found in baseline demographic characteristics among the groups.IAVWE,but not the stenosis ratio,had a statistically significant significance on the late-arriving retrograde flow proportion(LARFP),hypoperfusion intensity ratio(HIR),and NIHSS scores(F=20.941,P<0.001,Pillai’s trace statistic=0.567).The between-subject effects test showed that IAVWE had a significant effect on the three dependent variables:LARFP(R^(2)=0.088,F=10.899,P=0.002),HIR(R^(2)=0.234,F=29.354,P<0.001),and NIHSS(R^(2)=114.339,F=33.338,P<0.001).Conclusions:Arteriosclerotic IAVWE significantly reduced downstream collateral flow and affected relevant neurological deficits.It was an independent factor affecting downstream collateral flow and NIHSS scores,which should be a focus of future studies.Trial Registration:ChiCTR.org.cn,ChiCTR2100053661.
