1.13-Docosenamide Enhances Oligodendrocyte Precursor Cell Differentiation via USP33-Mediated Deubiquitination of CNR1 in Chronic Cerebral Hypoperfusion.
Yuhao XU ; Yi TAN ; Zhi ZHANG ; Duo CHEN ; Chao ZHOU ; Liang SUN ; Shengnan XIA ; Xinyu BAO ; Haiyan YANG ; Yun XU
Neuroscience Bulletin 2025;41(11):1939-1956
Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals
;
Oligodendrocyte Precursor Cells/metabolism*
;
Mice
;
Cell Differentiation/drug effects*
;
Male
;
Receptor, Cannabinoid, CB1/metabolism*
;
Mice, Inbred C57BL
;
Ubiquitin Thiolesterase/metabolism*
;
Ubiquitination/drug effects*
;
Carotid Stenosis/complications*
;
Cognitive Dysfunction/drug therapy*
2.Diabetes mellitus and adverse outcomes after carotid endarterectomy: A systematic review and meta-analysis.
Fengshi LI ; Rui ZHANG ; Xiao DI ; Shuai NIU ; Zhihua RONG ; Changwei LIU ; Leng NI
Chinese Medical Journal 2023;136(12):1401-1409
BACKGROUND:
There is still uncertainty regarding whether diabetes mellitus (DM) can adversely affect patients undergoing carotid endarterectomy (CEA) for carotid stenosis. The aim of the study was to assess the adverse impact of DM on patients with carotid stenosis treated by CEA.
METHODS:
Eligible studies published between 1 January 2000 and 30 March 2023 were selected from the PubMed, EMBASE, Web of Science, CENTRAL, and ClinicalTrials databases. The short-term and long-term outcomes of major adverse events (MAEs), death, stroke, the composite outcomes of death/stroke, and myocardial infarction (MI) were collected to calculate the pooled effect sizes (ESs), 95% confidence intervals (CIs), and prevalence of adverse outcomes. Subgroup analysis by asymptomatic/symptomatic carotid stenosis and insulin/noninsulin-dependent DM was performed.
RESULTS:
A total of 19 studies (n = 122,003) were included. Regarding the short-term outcomes, DM was associated with increased risks of MAEs (ES = 1.52, 95% CI: [1.15-2.01], prevalence = 5.1%), death/stroke (ES = 1.61, 95% CI: [1.13-2.28], prevalence = 2.3%), stroke (ES = 1.55, 95% CI: [1.16-1.55], prevalence = 3.5%), death (ES = 1.70, 95% CI: [1.25-2.31], prevalence =1.2%), and MI (ES = 1.52, 95% CI: [1.15-2.01], prevalence = 1.4%). DM was associated with increased risks of long-term MAEs (ES = 1.24, 95% CI: [1.04-1.49], prevalence = 12.2%). In the subgroup analysis, DM was associated with an increased risk of short-term MAEs, death/stroke, stroke, and MI in asymptomatic patients undergoing CEA and with only short-term MAEs in the symptomatic patients. Both insulin- and noninsulin-dependent DM patients had an increased risk of short-term and long-term MAEs, and insulin-dependent DM was also associated with the short-term risk of death/stroke, death, and MI.
CONCLUSIONS
In patients with carotid stenosis treated by CEA, DM is associated with short-term and long-term MAEs. DM may have a greater impact on adverse outcomes in asymptomatic patients after CEA. Insulin-dependent DM may have a more significant impact on post-CEA adverse outcomes than noninsulin-dependent DM. Whether DM management could reduce the risk of adverse outcomes after CEA requires further investigation.
Humans
;
Endarterectomy, Carotid/adverse effects*
;
Carotid Stenosis/surgery*
;
Risk Factors
;
Treatment Outcome
;
Time Factors
;
Stents/adverse effects*
;
Diabetes Mellitus, Type 2/complications*
;
Diabetes Mellitus, Type 1
;
Stroke/complications*
;
Insulin/therapeutic use*
;
Myocardial Infarction/complications*
;
Risk Assessment
3.Meta Analysis of Risks of Cardiocerebral Vascular Events in Patients with Primary Biliary Cholangitis.
Xi XIE ; Sheng TANG ; Jia WANG ; Jin Wei CHEN ; Jing TIAN ; Ni MAO ; Yi Ming LIU ; Fen LI
Acta Academiae Medicinae Sinicae 2019;41(4):457-463
To systematically evaluate the risks of cardiocerebral vascular events in patients with primary biliary cholangitis(PBC). Methods We carried out a Meta analysis by RevMan 5.3 software to investigate literatureon the risk of cardiocerebral vascular events in patients with PBC and controls. Results Compared with non-PBC controls,PBC patients had significantly higher risk of coronary events(=1.56,=0.0002);however,the risk of cerebrovascular events showed no significant difference between these two groups(=1.01,=0.94).Subgroup analysis demonstrated a significantly lower risk of transient ischemic attack or carotid stenosis in PBC patients(=0.63,=0.03);however,there was no significant difference in the risk of stroke(=1.11,=0.40). Conclusion Patients with PBC have an increased risk of coronary events but may have a lower risk of transient ischemic attack or carotid stenosis.
Carotid Stenosis
;
etiology
;
Cholangitis
;
complications
;
Coronary Disease
;
etiology
;
Humans
;
Ischemic Attack, Transient
;
etiology
;
Liver Cirrhosis, Biliary
;
complications
;
Risk Factors
;
Stroke
;
etiology
4.Neurologic complications in patients with carotid artery stenting
Na Young KIM ; Jong Wook CHOI ; Kum WHANG ; Sung Min CHO ; Youn Moo KOO ; Jong Yeon KIM
Journal of Cerebrovascular and Endovascular Neurosurgery 2019;21(2):86-93
OBJECTIVE: Carotid artery stenting is helpful in patients with carotid artery stenosis and is a common method of treatment. However, data on the neurological consequences that might arise from, especially Asian patients after CAS is not enough. The purpose of this study was to investigate the outcome and prognostic factors affecting CAS patients.METHODS: From January 2013 to June 2018 it was enrolled 97 patients who underwent CAS with severe carotid artery stenosis in a single institution. We retrospectively reviewed neurologic complications such as restenosis, ipsilateral or contralateral stroke, and hyperperfusion during the 6-month follow-up period.RESULTS: There were no complication occured during the procedure in all 97 patients. Neurologic complications occurred in 30 patients (30.9%) after the procedure, and ipsilateral stroke 6 (6.2%), contralateral stroke 9 (9.4%), restenosis 2 (2.1%) and hyperperfusion 13 respectively. One of them had died (1.0%), of which the rest were discharged after symptoms improve. On univariate analysis, DM and pre-op NIHSS score was associated with the risk of CAS complication, exclusively. On the binary logistic regression for risk factors, DM (OR 0.144, 95% CI [0.029–0.718]), history of radiotheraphy (OR 36.103, 95% CI [1.009–1291.789]) and preoperative NIHSS (OR 1.266, 95% CI [1.059–1.513]) showed independent risk factors associated with post procedural neurological complications, statistically.CONCLUSION: Carotid artery stenting is a relatively safe and reliable long-term outcome for patients with carotid artery stenosis. However, careful observation should be taken after procedure immediately for any possible complications.
Asian Continental Ancestry Group
;
Carotid Arteries
;
Carotid Stenosis
;
Endovascular Procedures
;
Follow-Up Studies
;
Humans
;
Logistic Models
;
Methods
;
Postoperative Complications
;
Retrospective Studies
;
Risk Factors
;
Stents
;
Stroke
5.An Integrated Analysis of Risk Factors of Cognitive Impairment in Patients with Severe Carotid Artery Stenosis.
Ru Tao LUO ; Pei Jiong WANG ; Xiao Feng DENG ; Shu Jie ZHOU ; Meng ZHAO ; Jing QIAN ; Dong ZHANG ; Rong WANG ; Yan ZHANG
Biomedical and Environmental Sciences 2018;31(11):797-804
OBJECTIVE:
To investigate cognitive dysfunction in patients with carotid artery stenosis (CAS) and potential risk factors related to cognitive-especially memory-dysfunction.
METHODS:
Forty-seven patients with carotid artery stenosis were recruited into our study cohort. The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) were adopted to assess cognitive function, the Wechsler Memory Scale (WMS) to assess memory function, high-resolution MRI and enhanced ultrasound to evaluate carotid plaques, and computed tomography perfusion (CTP) imaging to evaluate intracranial blood perfusion. Single-factor analysis and multiple-factor regression analysis were used to analyze potential risk factors of cognitive impairment.
RESULTS:
Mini-Mental State Examination test results showed that 22 patients had cognitive impairment, and MoCA test results showed that 10 patients had cognitive impairment. Analysis of various risk factors indicated that the average memory quotient of female patients was higher than that of males (P = 0.024). The cognitive and memory performance of those with an educational background above high school were significantly better than those of participants with high school or lower (P = 0.045). Patients with abnormal intracranial perfusion performed worse on the MMSE test (P = 0.024), and their WMS scores were significantly lower (P = 0.007). The MMSE scores and the memory quotients were significantly lower in patients with a history of cerebral infarction (MMSE, P = 0.047, memory quotient score, P = 0.018).
CONCLUSION
A history of cerebral infarction and abnormal cerebral perfusion are associated with decline in overall cognitive function and memory in patients with carotid stenosis. Being female and having an educational background above high school may be protective factors in the development of cognitive dysfunction.
Adult
;
Aged
;
Carotid Stenosis
;
complications
;
China
;
epidemiology
;
Cognition
;
Cognitive Dysfunction
;
epidemiology
;
etiology
;
psychology
;
Cohort Studies
;
Cross-Sectional Studies
;
Female
;
Humans
;
Male
;
Memory
;
Middle Aged
;
Neuropsychological Tests
;
Risk Factors
6.Research Progress on the Risk Factors and Outcomes of Human Carotid Atherosclerotic Plaques.
Xiang-Dong XIONG ; Wei-Dong XIONG ; Shang-Shen XIONG ; Gui-Hai CHEN ;
Chinese Medical Journal 2017;130(6):722-729
OBJECTIVEAtherosclerosis is an inflammatory process that results in complex lesions or plaques that protrude into the arterial lumen. Carotid atherosclerotic plaque rupture, with distal atheromatous debris embolization, causes cerebrovascular events. This review aimed to explore research progress on the risk factors and outcomes of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention.
DATA SOURCESWe searched the PubMed database for recently published research articles up to June 2016, with the key words of "risk factors", "outcomes", "blood components", "molecular mechanisms", "cellular mechanisms", and "human carotid atherosclerotic plaques".
STUDY SELECTIONThe articles, regarding the latest developments related to the risk factors and outcomes, atherosclerotic plaque composition, blood components, and consequences of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention, were selected.
RESULTSThis review described the latest researches regarding the interactive effects of both traditional and novel risk factors for human carotid atherosclerotic plaques, novel insights into human carotid atherosclerotic plaque composition and blood components, and consequences of human carotid atherosclerotic plaque.
CONCLUSIONCarotid plaque biology and serologic biomarkers of vulnerability can be used to predict the risk of cerebrovascular events. Furthermore, plaque composition, rather than lesion burden, seems to most predict rupture and subsequent thrombosis.
Biomarkers ; blood ; Carotid Stenosis ; blood ; epidemiology ; metabolism ; pathology ; Humans ; Plaque, Atherosclerotic ; blood ; complications ; metabolism ; pathology ; Risk Factors
7.Efficacy of different types of self-expandable stents in carotid artery stenting for carotid bifurcation stenosis.
Ya-min LIU ; Hao QIN ; Bo ZHANG ; Yu-jing WANG ; Jun FENG ; Xiang WU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2016;36(1):95-98
Both open and closed loop self-expandable stents were used in carotid artery stenting (CAS) for carotid bifurcation stenosis. We sought to compare the efficacy of two types of stents in CAS. The data of 212 patients treated with CAS (42 and 170 cases implanted with closed and open loop stents, respectively) for carotid bifurcation stenosis and distal filtration protection devices were retrospectively analyzed. Between closed and open loop stents, there were no significant differences in hospitalization duration, NIHSS score before and after the treatment, stenosis at 12th month, and cumulative incidence of primary endpoint events within 30 days or from the 31st day to the 12th month; while there were significant differences in hemodynamic changes and rate of difficulty in recycling distal filtration protection devices. Use of open vs. closed loop stents for carotid bifurcation stenosis seems to be associated with similar incidence of complications, except for greater rate of hemodynamic changes and lower rate of difficulty in recycling the distal filtration protection devices.
Adult
;
Aged
;
Aged, 80 and over
;
Carotid Arteries
;
surgery
;
Carotid Stenosis
;
surgery
;
Endovascular Procedures
;
adverse effects
;
instrumentation
;
methods
;
Female
;
Hemodynamics
;
Humans
;
Male
;
Middle Aged
;
Postoperative Complications
;
Self Expandable Metallic Stents
;
adverse effects
8.Common factors for ischemic cerebral stroke in coronary artery bypass grafting in patients with concomitant carotid and coronary artery severe stenosis.
Lei HUANG ; Feng KUANG ; Zhonggui SHAN ; Yiquan LAI ; Hongwei GUO
Journal of Central South University(Medical Sciences) 2016;41(12):1340-1344
To analyze two common factors for perioperative ischemic stroke in patients with concomitant carotid and coronary artery severe stenosis and to improve the therapeutic effect.
Methods: A total of 44 patients with multi-vessel coronary artery disease combined with carotid stenosis, who admitted to the Department of Cardiac Surgery, the First Affiliated Hospital of Xiamen University from 2008 to 2014, were enrolled in this study. Among them, 32 cases were male, 12 cases was female. All patients received coronary artery bypass grafting after treatment of neck diseases. The surgical outcomes and follow-up results were analyzed retrospectively.
Results: One patient received carotid endarterectomy suffered hemiplegia, whose symptoms were improved after positive clinical treatment. One patient suffered transient ischemic attack, and 5 patients displayed the cerebrovascular syndromes a week later after surgery. Twelve patients suffered nerve function damage 48 hours later after surgery. Nine patients received intra-aortic ballon pump, 1 patient received thoracotomy hemostasis, 3 patients suffered sternal dehiscence; 27 patients showed atrial fibrillation. Two patients died after surgery. The follow-up duration ranged from 1-7 years and the follow-up rate was 90%. The ischemic symptoms were improved in 44 patients. Six patients complained the recurrence of angina, but no abnormalities were found in coronary angiography or computed tomography angiography. One patient died of malignant tumor during the follow-up duration.
Conclusion: For patients with concomitant carotid and coronary artery severe stenosis, it is more likely to suffer ischemic cerebral stroke. However, carotid stenosis is not the only factor, other key factors relevant to ischemic cerebral stroke shouldn't be ignored either.
Atrial Fibrillation
;
epidemiology
;
Blood Loss, Surgical
;
statistics & numerical data
;
Carotid Stenosis
;
complications
;
surgery
;
Cerebrovascular Disorders
;
epidemiology
;
Comorbidity
;
Constriction, Pathologic
;
Coronary Angiography
;
Coronary Artery Bypass
;
adverse effects
;
mortality
;
Coronary Artery Disease
;
complications
;
surgery
;
Coronary Stenosis
;
complications
;
surgery
;
Endarterectomy, Carotid
;
adverse effects
;
Female
;
Hemiplegia
;
epidemiology
;
Humans
;
Intra-Aortic Balloon Pumping
;
adverse effects
;
Intraoperative Complications
;
epidemiology
;
Ischemic Attack, Transient
;
epidemiology
;
Male
;
Nervous System Diseases
;
Peripheral Nerve Injuries
;
epidemiology
;
Postoperative Complications
;
epidemiology
;
Retrospective Studies
;
Risk Assessment
;
Risk Factors
;
Stroke
;
epidemiology
;
Surgical Wound Dehiscence
;
epidemiology
;
Thoracotomy
;
adverse effects
9.Qingre quyu granule stabilizes plaques through inhibiting the expression of tenascin-C in patients with severe carotid stenosis.
Yi WANG ; Wen-li CHENG ; Yong WANG ; Jing-pin PENG ; Jie YUAN ; Li CHEN ; Lin PAN ; Hong LI ; Jian GUO
Chinese journal of integrative medicine 2015;21(5):339-345
OBJECTIVETo investigate the therapeutic effects of Qingre Quyu Granule (QQG) on the patients with severe carotid stenosis, and to explore the mechanism of it.
METHODSNinety-six patients with severe carotid stenosis were enrolled in the study and were classified into a QQG group (n=48) and a control group (n=48) randomly using consecutively numbered envelopes. The patients in the QQG group were given QQG and Western medicine, those in the control group were given Western medicine merely, the course of treatment was 16 weeks. All patients went through endarterectomy after treatment. Plaques were subjected to the analysis of CD3, CD68, soluble intercellular adhesion molecule 1 (ICAM-1), matrix metalloprotease-9 (MMP-9), CD40L, tenascin-C, and collagen content lipid content by immunohistochemistry or polarized light analysis.
RESULTSBy the end of experiment, the expressions of CD3, CD68, ICAM-1, MMP9, CD40L and tenascin-C on the plaques were statistically significant lower in the QQG group compared with the control group(P<0.01). The lipid content of the plaque was also significantly lower in the QQG group compared with the control group (P<0.01). The interstitial collagen in the tissue sections of the plaques was also significantly higher in the QQG group in comparison with the control group (P<0.01).
CONCLUSIONQQG could stabilize carotid artery plaques through inhibiting pro-inflammation factors and restraining the tenascin-C and MMP9 pathway.
Aged ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; CD3 Complex ; metabolism ; CD40 Ligand ; metabolism ; Carotid Arteries ; metabolism ; pathology ; Carotid Stenosis ; blood ; complications ; drug therapy ; Collagen ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Immunohistochemistry ; Inflammation ; complications ; pathology ; Intercellular Adhesion Molecule-1 ; metabolism ; Lipids ; blood ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Plaque, Atherosclerotic ; blood ; complications ; drug therapy ; Tenascin ; metabolism
10.Hemodynamic Instability during Carotid Angioplasty and Stenting-Relationship of Calcified Plaque and Its Characteristics.
Jin Sue JEON ; Seung Hun SHEEN ; Gyojun HWANG
Yonsei Medical Journal 2013;54(2):295-300
PURPOSE: During carotid angioplasty and stenting (CAS), hemodynamic instability (HDI) can occur, possibly causing post-procedural ischemic complications. The goal of this study was to investigate the risk factors of HDI focusing on characteristics of plaque. MATERIALS AND METHODS: Thirty nine CAS patients were retrospectively evaluated for HDI. Prolonged HDI that lasted over 30 minutes was analyzed in relation to characteristics of calcified plaque. RESULTS: Nineteen (48.7%) patients had HDI. Ten of the 19 had both bradycardia and hypotension, and nine had only bradycardia. All bradycardia was treated well with a transcutaneous temporary cardiac pacemaker. But eight patients presented with prolonged hypotension in spite of recovery of bradycardia. Calcified plaque was a related factor associated with HDI (odds ratio, 8.571; 95% confidence interval, 1.321-55.62; p=0.024). Extensive and eccentric type calcified plaques were associated with prolonged hypotension (p=0.04, and p=0.028, respectively). CONCLUSION: The calcification of plaque is a predictable factor of HDI during CAS, and its extensive and eccentric calcified plaques may be related to prolonged HDI.
Aged
;
Angioplasty/*adverse effects
;
Bradycardia/complications
;
Carotid Arteries/*surgery
;
Carotid Stenosis/*physiopathology
;
Female
;
*Hemodynamics
;
Humans
;
Hypotension/complications
;
Intraoperative Complications/*etiology/radiography
;
Intraoperative Period
;
Logistic Models
;
Male
;
Middle Aged
;
Retrospective Studies
;
Risk Factors
;
Stents
;
Tomography, X-Ray Computed

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