Publications by authors named "Xudong Pan"

60 Publications

BNP combined with echocardiographic parameters to predict the risk of cardioembolic stroke.

J Clin Neurosci 2021 Jun 16;88:213-218. Epub 2021 Apr 16.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China. Electronic address:

Background: Previous studies have found that BNP and some indicators of cardiac structure and function are closely associated with atrial fibrillation, so we aim to investigate the potential role of BNP and echocardiographic parameters to identify the acute ischemic stroke with atrial fibrillation patients who have high risks of cardioembolic stroke based on it.

Methods: 436 AIS patients were divided into an AF group and non-AF group on the basis of the electrocardiogram and Holter results. Then we compared vascular risk factors, laboratory test indicators, and echocardiographic parameters among different groups.

Results: AIS with AF group had significantly higher age, CHD, previous medication, creatinine, d-dimer, fibrinogen, CRP, BNP, LAD, LVDd, LVDs and lower cholesterol, triglyceride, LDL and ejection fraction than the non-AF group (P < 0.05). Increased BNP, LAD, LVDd, LVDs and ejection fraction reduction were independent risk factors to predict cardioembolic stroke. BNP and LAD could be the two most effective indicators of the high risk of cardioembolic stroke. The area under the curve (AUC) of BNP and LAD were 0.791 [95%CI (0.743-0.838), p < 0.001), 0.786 [95%CI (0.739-0.833), p < 0.001]. The combined score we designed improved the prediction effect of single-indicator. The AUC of it was 0.822 with a sensitivity of 69.5% and specificity of 83.9%.There was an apparent positive correlation between BNP and LAD in AIS patients (r = 0.327, P < 0.001).

Conclusion: BNP combined with echocardiographic parameters has outstanding value to predict the risk of cardioembolic stroke, especially for BNP and LAD.
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http://dx.doi.org/10.1016/j.jocn.2021.04.002DOI Listing
June 2021

Serum LRG1 as a novel biomarker for cardioembolic stroke.

Clin Chim Acta 2021 Aug 8;519:83-91. Epub 2021 Apr 8.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China. Electronic address:

Background: In recent years, LRG1 was found to be closely related to atrial fibrillation, heart failure, and myocardial remodeling after myocardial infarction. While its role in cerebral infarction was still controversial. We aimed to explore the value of LRG1 to identify the cardioembolic stroke.

Methods: 283 acute ischemic stroke(AIS) patients and 169 controls were enrolled. The AIS patients were divided into a CE(cardiogenic embolism) group and a non-CE group. Serum LRG1 levels were quantified by ELISA.

Results: The serum LRG1 levels were decreased in the AIS patients. CE group had higher serum LRG1 levels than the non-CE group. LRG1 was an independent risk factor for cardioembolic stroke. The area under the curve (AUC) was 0.768 with a sensitivity of 72.5% and specificity of 69.5%, which was not second to BNP and LAD. The combined predictive model we designed, including LRG1, BNP, and LAD, greatly improved the prediction effect. A positive correlation was shown between LRG1 and stroke severity in the CE group. Those who experienced poor outcomes had higher serum LRG1 levels compared with good ones.

Conclusion: Serum LRG1 was a promising indicator to predict cardioembolic stroke, as well as stroke severity and the 3-month prognosis of it.
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http://dx.doi.org/10.1016/j.cca.2021.04.002DOI Listing
August 2021

The Potential of Exosomal RNAs in Atherosclerosis Diagnosis and Therapy.

Front Neurol 2020 11;11:572226. Epub 2021 Feb 11.

The Affiliated Hospital of Qingdao University, Qingdao, China.

Atherosclerosis is an inflammatory disease that can lead to cardiovascular disorders and stroke. In the atherosclerosis microenvironment, exosomes secreted from various cells, especially macrophage-derived exosomes, play an important role in cell-cell communication and cellular biological functions. In this article, we review previous studies on exosomal RNAs and discuss their potential value in atherosclerosis diagnosis and therapy. Based on our research, we concluded that macrophage exosomes have potential value in atherosclerosis diagnosis and therapy. However, there is a need for future studies to further investigate methods of exosome isolation and targeting.
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http://dx.doi.org/10.3389/fneur.2020.572226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905228PMC
February 2021

Fucoidan Inhibits NLRP3 Inflammasome Activation by Enhancing p62/SQSTM1-Dependent Selective Autophagy to Alleviate Atherosclerosis.

Oxid Med Cell Longev 2020 6;2020:3186306. Epub 2020 Aug 6.

Department of Critical Care Medicine, The Affiliated Hospital of Qingdao University, Shandong 266100, China.

NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation contributes to the progression of atherosclerosis, and autophagy inhibits inflammasome activation by targeting macrophages. We investigated whether fucoidan, a marine sulfated polysaccharide derived from brown seaweeds, could reduce NLRP3 inflammasome activation by enhancing sequestosome 1 (p62/SQSTM1)-dependent selective autophagy to alleviate atherosclerosis in high-fat-fed ApoE-/- mice with partial carotid ligation and differentiated THP-1 cells incubated with oxidized low-density lipoprotein (oxLDL). Fucoidan significantly ameliorated lipid accumulation, attenuated progression of carotid atherosclerotic plaques, deregulated the expression of NLRP3 inflammasome, autophagy receptor p62, and upregulated microtubule-associated protein light chain 3 (LC3)-II/I levels. Transmission electron microscopy and GFP-RFP-LC3 lentivirus transfection further demonstrated that fucoidan could activate autophagy. Mechanistically, fucoidan remarkably inhibited NLRP3 inflammasome activation, which was mostly dependent on autophagy. The inhibitory effects of fucoidan on NLRP3 inflammasome were enhanced by autophagy activator rapamycin (Rapa) and alleviated by autophagy inhibitor 3-methyladenine (3-MA). Fucoidan promoted the colocalization of NLRP3 and p62. Knockdown of p62 and ATG5 by small interfering RNA significantly reduced the inhibitory effects of fucoidan treatment on NLRP3 inflammasome. The data suggest that fucoidan can inhibit NLRP3 inflammasome activation by enhancing p62/SQSTM1-dependent selective autophagy to alleviate atherosclerosis.
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http://dx.doi.org/10.1155/2020/3186306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812546PMC
May 2021

Mesenchymal stem-cell-derived exosomal miR-145 inhibits atherosclerosis by targeting JAM-A.

Mol Ther Nucleic Acids 2021 Mar 4;23:119-131. Epub 2020 Nov 4.

Department of Neurology, The Affiliated Hospital of Qingdao University, Shandong 266100, China.

Atherosclerosis is a chronic inflammatory disease associated with the development of plaques that can be converted into an acute clinical event by thrombosis or plaque rupture. Mesenchymal stem cells (MSCs) exhibit therapeutic effects for the treatment of various diseases, including atherosclerosis. In this study, we show that microRNA-145 (miR-145) is associated with atherosclerosis by microRNA sequencing and bioinformatics analysis. MSC-derived miR-145-rich exosomes could efficiently deliver miR-145 from MSCs to human umbilical vein endothelial cells (HUVECs). Treatment of miR-145-rich exosomes could downregulate JAM-A, inhibit migration , and reduce atherosclerotic plaque . Our study suggests that MSC-derived miR-145-rich exosomes have great potential for atherosclerosis prevention.
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http://dx.doi.org/10.1016/j.omtn.2020.10.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732974PMC
March 2021

The nervous system-A new territory being explored of SARS-CoV-2.

J Clin Neurosci 2020 Dec 28;82(Pt A):87-92. Epub 2020 Oct 28.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China. Electronic address:

In December 2019, COVID-19 outbroke in Wuhan, then sweeping the mainland of China and the whole world rapidly. On March 4, Beijing Ditan Hospital confirmed the existence of SARS-CoV-2 in the cerebrospinal fluid by gene sequencing, indicating the neurotropic involvement of SARS-CoV-2. Meanwhile, neurological manifestations in the central nervous system, peripheral nervous system and skeletal muscular were also observed, indicating the potential neuroinvasion of SARS-CoV-2. In particular, we focused on its neurological manifestations and specific pathogenesis, as well as its comparison with other viral respiratory infections. Finally, we further summarized the significance of the neuroinvasion and the follow-up issues that need to be paid attention to by scientists, so as to help neurologists understand the influence of SARS-CoV-2 on nervous system better and promote the accurate diagnosis and efficient treatment of COVID-19.
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http://dx.doi.org/10.1016/j.jocn.2020.10.056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598569PMC
December 2020

Serum miR-133 as a Potential Biomarker in Acute Cerebral Infarction Patients.

Clin Lab 2020 Oct;66(10)

Background: The study explores the expression and significance of miR-133 expression in peripheral blood of patients with acute cerebral infarction (ACI), so as to provide new evidence for the diagnosis and treatment of ACI.

Methods: Serum levels of miR-133, interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) were examined using RT-PCR and ELISA, respectively. Pearson's correlation assay was used to analyze the relationship between the level of serum miR-133 and inflammatory factors. Kaplan-Meier method was used to analyze the 10-year survival rate of ACI patients with different levels of miR-133 expression.

Results: The level of serum miR-133 in the ACI group was significantly higher than that in healthy group. Mean-while, the level of serum miR-133 in the large infarction group, middle infarction group, small infarction group, and lacunar infarction group was higher than in the healthy group. Moreover, the serum levels of miR-133 in patients with atherosclerotic thrombotic cerebral infarction (AT) and cardioembolic stroke (CE) were significantly higher than those in healthy subjects and small artery occlusive cerebral infarction (SAD) subjects. Serum levels of IL-6, IL-8, CRP and TNF-α in ACI group were significantly higher than those in healthy group. The correlation analysis showed that serum miR-133 was positively correlated with IL-6, IL-8, CRP, and TNF-α in ACI patients. The 10-year survival rate of the low-expression group was significantly higher than that of the high-expression group.

Conclusions: Serum level of miR-133 may indicate the onset and progression of cerebral infarction and may be a potential biomarker for the diagnosis of ACI.
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http://dx.doi.org/10.7754/Clin.Lab.2019.190933DOI Listing
October 2020

A Geometrical Perspective on Image Style Transfer with Adversarial Learning.

IEEE Trans Pattern Anal Mach Intell 2020 Jul 23;PP. Epub 2020 Jul 23.

Recent years witness the booming trend of applying Generative Adversarial Nets (GAN) and its variants to image style transfer. Although many reported results strongly demonstrate the power of GAN on this task, there is still little known about neither the interpretations of several fundamental phenomenons of image style transfer by generative adversarial learning, nor its underlying mechanism. To bridge this gap, this paper presents a general framework for analyzing style transfer with adversarial learning through the lens of differential geometry. To demonstrate the utility of our proposed framework, we provide an in-depth analysis of Isola et al.'s pioneering style transfer model pix2pix and reach a comprehensive interpretation on their major experimental phenomena. Furthermore, we extend the notion of generalization to conditional GAN and derive a condition to control the generalization capability of the pix2pix model. From a higher viewpoint, we further prove a learning-free condition to guarantee the existence of infinitely many perfect style transfer mappings. Besides, we also provide a number of practical suggestions on model design and dataset construction based on these derived theoretical results to facilitate further researches.
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http://dx.doi.org/10.1109/TPAMI.2020.3011143DOI Listing
July 2020

Identification of clinically relevant variants by whole exome sequencing in Chinese patients with sporadic non-syndromic type A aortic dissection.

Clin Chim Acta 2020 Jul 21;506:160-165. Epub 2020 Mar 21.

Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children; Genetics and Birth Defects Control Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China; Henan Key Laboratory of Pediatric Inherited & Metabolic Diseases, Henan Children's Hospital, Zhengzhou Hospital of Beijing Children's Hospital, Zhengzhou, China. Electronic address:

Purpose: Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease, of which genetic abnormalities are considered as important risk factors. The present research aims at identifying causal variants in Chinese patients with sporadic non-syndromic type A TAAD (ATAAD).

Materials And Methods: Whole exome sequencing (WES) was performed on 73 sporadic Chinese patients with ATAAD, 30 TAAD associated genes were curated for bioinformatic analyses. Clinical differences were compared between patients with and without causal variants.

Results: 15 pathogenic/likely pathogenic variants were identified (8 novel and 7 previously described) in 4 known TAAD-causal genes (FBN1, TGFBR2, SMAD3 and ACTA2) in 15 individuals, including 11 variants in FBN1 (7 missense, 3 truncating, and 1 splicing variants), 2 missense variants in TGFBR2, 1 ACTA2 frameshift variant and 1 SMAD3 frameshift variant. Significant clinical differences were found between patients with and without causal variants. Patients with TAAD-causal variants proved to have an earlier onset age, a more dilated aorta, and relatively intractable subtypes. Even without risk factor like hypertension, they might still suffer from TAAD with TAAD-causal variants.

Conclusions: The variants identified in our research might not only result in the occurrence of ATAAD, but also add complexities and difficulties to the clinical practice. Our data demonstrated that WES was an effective tool for determining genetic etiologies of non-syndromic ATAAD and could be helpful in genetic counseling for ATAAD patients and their at-risk family members.
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http://dx.doi.org/10.1016/j.cca.2020.03.029DOI Listing
July 2020

SIRT1 protects against aortic dissection by regulating AP-1/decorin signaling-mediated PDCD4 activation.

Mol Biol Rep 2020 Mar 18;47(3):2149-2159. Epub 2020 Feb 18.

Beijing Anzhen Hospital, Beijing Aortic Disease Center, Capital Medical University, Anzhen Road 2#, Chaoyang District, Beijing, China.

Medial degeneration of aorta wall is the principal feature of aortic dissection (AD). Sirtuin 1 (SIRT1) plays essential protective effect on many aortic-associated disease. However, it is still unclear whether SIRT1participates in the process of medial degeneration-mediated AD. The purpose of this study is to explore the association between SIRT1 and AD process. qRT-PCR was used to evaluate the transcriptional level of genes involved in study. Protein levels and acetylation detection were measured by Western blotting. The regulatory relations between AP-1 and decorin was assessed by luciferase reporter gene assay. Acute aortic dissection (AAD) mice model was constructed by feeding with β-aminopropionitrile monofumarate (BAPN). Haematoxylin and eosin (HE) and Mallory staining were performed for pathological analysis. In clinical aorta tissue of thoracic aortic dissection (TAD), the expression of SIRT1, activator protein 1 (AP-1) and decorin were in accordant trend. AP-1 expression which acts on Decorin promoter region is possibly regulated in a SIRT1-mediated deacetylation dependent manner. Resveratrol or SRT1720-initiated SIRT1 activation ameliorated BAPN-induced AAD symptoms accompanied by the activation of AP-1/decorin signaling and decorin-mediated programmed cell death 4 (PDCD4) expression by inhibiting miR-21 and miR-181b. These data suggest that SIRT1/AP-1/decorin signal cascades possibly play a part role in the process of AD. Our research demonstrate that activation of SIRT1 protects against AAD symptoms by enhancing AP-1-mediated decorin expression and downstream PDCD4 signaling pathway. Possibly, SIRT1 is served as a protective factor of AD and targeting SIRT1 therapy might be an attractive therapeutic approaches for AD treatment.
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http://dx.doi.org/10.1007/s11033-020-05314-9DOI Listing
March 2020

Clinical features of right-to-left shunt in the different subgroups of migraine.

Brain Behav 2020 03 3;10(3):e01553. Epub 2020 Feb 3.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.

Objective: Several investigations have documented an association between migraine and right-to-left shunt (RLS). However, whether there are specific clinical features that can distinguish between migraine patients with and without RLS is unclear. This study aims to explore whether there are specific clinical features that can distinguish between migraine patients with and without RLS, and to investigate the relationship between the degree of shunt and clinical parameters of headache.

Methods: In this study, we enrolled consecutive migraineurs who underwent a structured, standardized questionnaire for family and personal history and for detailed migraine features. RLS was diagnosed based on a contrast enhancement transcranial Doppler (c-TCD) examination.

Results: Overall, 113 migraine with aura (MA) and 192 migraine without aura (MO) patients were included. Patients with MA and RLS (MARLS+) had a higher frequency for sensory aura symptoms than those with MA without RLS (MARLS-) (27.4% vs. 10.0%, p = .03). Patients with MO and RLS (MORLS+) presented with significantly younger initial age of migraine onset and experienced more severe pain intensity than those with MO without RLS (MORLS-) (mean ± SD, 25.6 ± 8.9 vs. 29.8 ± 12.7 years, p = .008 and 5.9 ± 1.4 vs. 5.3 ± 1.3, p = .006, respectively). There was no relationship between the degree of shunt and the clinical parameters of headache.

Conclusions: Our results indicate that MO patients presented with a younger initial age of migraine onset and that sensory aura symptoms in MA patients may predict the presence of RLS. However, we did not find support for relationship between the degree of shunt and clinical parameters of headache.
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http://dx.doi.org/10.1002/brb3.1553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066358PMC
March 2020

K63 ubiquitin chains target NLRP3 inflammasome for autophagic degradation in ox-LDL-stimulated THP-1 macrophages.

Aging (Albany NY) 2020 01 29;12(2):1747-1759. Epub 2020 Jan 29.

Department of Neurology, the Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China.

Inflammation, especially involving the NLRP3 inflammasome, is critical to atherosclerotic plaque formation. Enhanced autophagy can inhibit the development of atherosclerosis, and recent studies have revealed that NLRP3 inflammasome can be degraded by autophagy in atherosclerosis. In the present study, we established a foam-cell model to investigate the impact of oxidized low density lipoproteins (ox-LDLs) on autophagy and the inflammasome in atherosclerosis-related inflammation. We observed that ox-LDLs activated NLRP3 inflammasomes in macrophages and restricted autophagy in a time-and dose-dependent manner. We further observed through immunoprecipitation and siRNA knockdown that autophagic degradation of the NLRP3 inflammasome is dependent on K63 polyubiquitation of its NLRP3 subunit and subsequent binding by the adaptor protein p62. Our findings uncover a mechanism by which autophagy inhibits inflammation in atherosclerosis and the role of K63 in that process.
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http://dx.doi.org/10.18632/aging.102710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053591PMC
January 2020

MicroRNA-155 promotes the ox-LDL-induced activation of NLRP3 inflammasomes via the ERK1/2 pathway in THP-1 macrophages and aggravates atherosclerosis in ApoE-/- mice.

Ann Palliat Med 2019 Nov;8(5):676-689

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266100, China.

Background: Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation can induce the secretion of IL-1β and IL-18 and after promoting the development of atherosclerosis. MiR-155 is an important microRNA that modulates inflammation in atherosclerosis, but the role of miR-155 in the regulation of the NLRP3 inflammasome is still unknown.

Methods: The atherosclerosis model was set up using ApoE-/- mice, and the lentiviral vector (LV) was used to interfere the expression of miR-155. HE stains was used for plaque morphology, immunohistochemistry (IHC) and western blot were used for protein expression quantification. We used oxidized low-density lipoprotein (ox-LDL) to incubate PMA-preprocessed THP-1 macrophages and detected NLRP3 inflammasome activation and ERK1/2 phosphorylation by western blot and Enzyme-linked immunosorbent assay.

Results: HE stains showed that the intravascular plaques in the miR-155-up group were remarkably increased, compared with negative control (NC) group. Results of IHC showed that the expression of caspase-1 and IL-1β in the miR-155-up group was the highest of four groups, consist with the Western blot analysis. The results of in vitro experiment show that ox-LDL promoted NLRP3 inflammasome activation and ERK1/2 phosphorylation. Blocking the ERK1/2 pathway could inhibit ox-LDL-induced NLRP3 inflammasome activation. Moreover, we found that the overexpression of miR-155 promoted the activation of the ox-LDL-induced NLRP3 inflammasome, which could also be blocked by the ERK inhibitor U0126.

Conclusions: MiR-155 aggravates the carotid AS lesion in ApoE-/- mice and exerts a regulatory effect on NLRP3 inflammasome activation in ox-LDL-induced macrophages via the ERK1/2 pathway.
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http://dx.doi.org/10.21037/apm.2019.10.11DOI Listing
November 2019

Potential therapeutic drugs for ischemic stroke based on bioinformatics analysis.

Int J Neurosci 2019 Nov 7;129(11):1098-1102. Epub 2019 Aug 7.

Department of Neurology , The Affiliated Hospital of Qingdao University , Qingdao , China.

Ischemic stroke (IS) is a complex disease affected by various environmental factors, genetic factors and their interactions. Because genetic factors occupy an irreplaceable place in the pathogenesis of IS, the identification of genetic factors has become one of the hot spots in the current research. In the present study, we aimed to identify possible gene targets and relevant drug molecules in the pathogenesis of IS. Microarray dataset of GSE16561 was downloaded from Gene Expression Omnibus database. The differentially expressed genes (DEGs) between IS group and control group were obtained using limma package in R. Ground-Operation Simulation package in R language was used to cluster DEGs according to their biological process, cellular components and molecular functions with respect to the GO annotation. The DEGs were analyzed by Search Tool for the Retrieval of Interacting Genes online database and Cytoscape software to predict their interaction relationship. Finally, the DEGs were submitted to DGIdb dataset and related drug molecules were retrieved. 20 DEGs were identified from IS group including 1 downregulated and 19 upregulated genes. The function enrichment analysis revealed that the DEGs were enriched in three GO terms, mainly including inflammatory response, positive regulation of protein kinase activity and innate immune response. Finally, 10 drug molecules were identified from the DEGs. Our study identified some potential biological targets and drug molecules for the treatment of IS.
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http://dx.doi.org/10.1080/00207454.2019.1634072DOI Listing
November 2019

Plasma Osteoprotegerin Correlates with Stroke Severity and the Occurrence of Microembolic Signals in Patients with Acute Ischemic Stroke.

Dis Markers 2019 2;2019:3090364. Epub 2019 May 2.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China.

Background: Instability of atherosclerotic plaques is associated with the occurrence of stroke. Microembolic signals (MESs) are an indicator of unstable plaque. A relationship between plasma osteoprotegerin (OPG) and ischemic stroke has already been identified. The aim of this study was to investigate whether plasma OPG levels have a relationship with MESs and to evaluate the feasibility of OPG as a biomarker of stroke severity and occurrence of MESs.

Methods: Our study consisted of 127 patients with large artery atherosclerosis stroke and 56 controls. Patients were classified into subgroups based on stroke severity and the occurrence of MESs. MES-monitoring was performed for 60 min using transcranial Doppler within 72 h of stroke onset. Stroke severity at admission was assessed by the National Institutes of Health Stroke Scale.

Results: Plasma OPG levels were significantly associated with stroke, MESs, and stroke severity at admission (adjusted OR [95% CI]: 1.002 [1.001-1.003] < 0.001; 1.002 [1.001-1.003] = 0.001; 1.001 [1.000-1.002] = 0.028). When plasma OPG levels were used to determine the stroke severity, the area under the receiver-operating characteristic curve (AUC) was 0.734 (95% CI: 0.625-0.843) based on a cutoff value of 1998.44 pg/ml; the sensitivity and specificity of this test were 80.6% and 65.6%, respectively. Furthermore, when the levels of OPG were used to distinguish the presence of MESs, the AUC was 0.766 (95% CI: 0.672-0.860); the cutoff value was 2107.91 pg/ml. The sensitivity of this cutoff value was 68.8% and the specificity was 73.7%.

Conclusions: Plasma OPG levels correlate with stroke severity and the occurrence of MESs.
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http://dx.doi.org/10.1155/2019/3090364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525837PMC
December 2019

Gene Polymorphisms Are Associated with Susceptibility to Large Artery Atherosclerotic Stroke and Microembolic Signals.

Dis Markers 2019 5;2019:2193835. Epub 2019 May 5.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China.

Large artery atherosclerotic stroke (LAAS) is the most common ischemic stroke (IS) subtype, and microemboli may be clinically important for indicating increased risk of IS. The inflammatory process of atherosclerosis is well known, and lymphoid phosphatase (Lyp), which is encoded by the protein tyrosine phosphatase nonreceptor type 22 () gene, plays an important role in the inflammatory response. Our study was intended to evaluate the relationship between gene and LAAS and microembolic signals (MES). Three loci of the gene (rs2476599, rs1217414, and rs2488457) were analyzed in 364 LAAS patients and 369 control subjects. A genotyping determination was performed using the TaqMan assay. The G allele of rs2488457 might be related to a higher risk for developing LAAS and MES (odds ratio (OR) = 1.456, 95% confidence interval (CI) 1.156-1.833, = 0.001; OR = 1.652, 95% CI 1.177-2.319, = 0.004, respectively). In the LAAS group, the prevalence of the GTG haplotype was higher ( < 0.001) and the prevalence of the GCC haplotype was lower ( = 0.001). An interaction analysis of rs2488457 with smoking showed that smokers with the CG/GG genotypes had a higher risk of LAAS, compared to nonsmokers with the rs2488457 CC genotype (OR = 2.492, 95% CI 1.510-4.114, < 0.001). Our research indicated that the rs2488457 might be related to the occurrence of LAAS and MES in the Han Chinese population. In addition, the rs2488457 polymorphism and the environmental factor of smoking jointly influenced the susceptibility of LAAS.
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http://dx.doi.org/10.1155/2019/2193835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525845PMC
November 2019

Letter to the Editor Regarding "Effect of Early Brain Infarction After Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis".

World Neurosurg 2019 04;124:472

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China. Electronic address:

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http://dx.doi.org/10.1016/j.wneu.2018.11.233DOI Listing
April 2019

MicroRNA-181a regulates the activation of the NLRP3 inflammatory pathway by targeting MEK1 in THP-1 macrophages stimulated by ox-LDL.

J Cell Biochem 2019 08 2;120(8):13640-13650. Epub 2019 Apr 2.

Department of Neurology, The Affiliated Hospital of the Qingdao University, Medical School of Qingdao University, Qingdao, Shandong, China.

Atherosclerosis (AS) is a chronic inflammatory disease that is characterized by the deposition of lipids in the vascular wall and the formation of foam cells. Macrophages play a critical role in the development of this chronic inflammation. An increasing amount of research shows that microRNAs affect many steps of inflammation. The goal of our study was to investigate the regulatory effect of miR-181a on the NLRP3 inflammasome pathway and explore its possible mechanism. Compared with the control group, the expression of miR-181a was downregulated in the carotid tissue of AS group mice, while the expression of MEK1 and NLRP3-related proteins was upregulated significantly. In vitro, when THP-1 macrophages were stimulated with oxidized low-density lipoprotein (ox-LDL), the expression of miR-181a was decreased, the MEK/ERK/NF-κB inflammatory pathways were activated and the expression of NLRP3 inflammasome-related proteins was upregulated. Exogenous overexpression of miR-181a downregulated the activation of the MEK/ERK/NF-κB pathway and decreased the expression of NLRP3 inflammasome-related proteins (such as NLRP3, caspase-1, interleukin-18 [IL-18], IL-1β, etc). Exogenous miR-181a knockdown showed the opposite results to those of overexpression group. A luciferase reporter assay proved that miR-181a inhibited the expression of MEK1 by binding to its 3'-untranslated region. When we knocked down miR-181a and then treated cells with U0126 before ox-LDL stimulation, we found that U0126 reversed the increased activation of the MEK/ERK/NF-κB pathway and upregulation of NLRP3 inflammasome-related proteins (NLRP3, caspase-1, IL-18, IL-1β) that resulted from miR-181a knockdown. Our study suggests that miR-181a regulates the activation of the NLRP3 inflammatory pathway by altering the activity of the MEK/ERK/NF-κB pathway via targeting of MEK1.
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http://dx.doi.org/10.1002/jcb.28637DOI Listing
August 2019

LPS induces CXCL16 expression in HUVECs through the miR-146a-mediated TLR4 pathway.

Int Immunopharmacol 2019 Apr 30;69:143-149. Epub 2019 Jan 30.

Department of Neurology, The Affiliated Hospital of the Qingdao University, Medical School of Qingdao University, Qingdao, Shandong Province 266100, China. Electronic address:

Endothelial inflammation characterizes the early stages of atherosclerosis. CXCL16 is a protein that functions as both a chemokine and adhesion molecule, playing a crucial role in the pathogenesis of atherosclerosis. However, it is uncertain if LPS, a major inducer of inflammation, affects CXCL16 expression in endothelial cells and whether miR-146a, a negative regulator of atherosclerosis, participates in this process. The present study showed that exposure of human umbilical vein endothelial cells (HUVECs) to LPS induced the overexpression of CXCL16, TLR4 and NF-κB, and this induction was blocked by the TLR4 inhibitor TAK-242. In addition, LPS induced the upregulation of miR-146a in HUVECs. Overexpression or inhibition of miR-146a either inhibited or increased the LPS-induced expression CXCL16, TLR4 and NF-κB protein production, respectively. Additionally, miR-146a-induced CXCL16 expression was blocked by TAK-242. Thus, in this study, we demonstrate that LPS stimulates CXCL16 expression via the TLR4/NF-κB signaling pathway, and simultaneously, miR-146 negatively regulates LPS-induced CXCL16 expression through a TLR4-dependent mechanism.
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http://dx.doi.org/10.1016/j.intimp.2019.01.011DOI Listing
April 2019

LncRNA MALAT1 promotes oxidized low-density lipoprotein-induced autophagy in HUVECs by inhibiting the PI3K/AKT pathway.

J Cell Biochem 2019 03 28;120(3):4092-4101. Epub 2018 Nov 28.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

Emerging evidence suggests that long noncoding RNAs (lncRNAs) are involved in many biological processes, such as cell growth, differentiation, apoptosis, and autophagy. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), highly expressed in endothelial cells, is well conserved and implicated in endothelial cell migration and proliferation. However, whether MALAT1 participates in oxidized low-density lipoprotein (ox-LDL)-induced autophagy regulation in human umbilical vein endothelial cells (HUVECs) remains unknown. In this study, we observed that autophagy was upregulated and MALAT1 expression was markedly increased in HUVECs treated with ox-LDL. The ox-LDL-induced autophagy of HUVECs is significantly associated with the PI3K/AKT pathway. Furthermore, we found that MALAT1 overexpression inhibited PI3K, Akt and p70S6K phosphorylation and downregulated RHEB expression, simultaneously increasing ox-LDL-induced autophagy. MALAT1 silencing caused higher phosphorylated PI3K, Akt and p70S6K levels, upregulated RHEB expression and markedly suppressed autophagy. These results indicated that lncRNA MALAT1 promotes ox-LDL-induced autophagy in HUVECs partly through the PI3K/AKT signaling pathway.
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http://dx.doi.org/10.1002/jcb.27694DOI Listing
March 2019

Association between interleukin-18 (137G/C and 607C/A) gene polymorphisms and risk of ischemic stroke: a meta-analysis.

Neuroreport 2019 01;30(2):89-94

Department of Neurology, The Affiliated Hospital of Qingdao University.

Over the years, numerous researchers have explored the relationship between ischemic stroke (IS) and interleukin-18 (IL-18) gene polymorphisms. However, those studies reported conflicting and ambiguous results. The effects of IL-18 (137G/C and 607C/A) genetic variants on IS were investigated in this article. We performed a systematic search that was comprehensively executed in online databases for studies published up to 30 April 2018. Calculation of pooled odds ratios (ORs) and 95% confidence intervals was applied to assess the intensity of correlation using Stata.12.0. The overall outcome showed that 137G allele increased the risk of IS under the homozygous model (OR=1.36, P=0.027). Nevertheless, on the basis of ethnicity for the subgroup analysis (Asian and Egyptian), it was disclosed that the association was only found in the Egyptian population under the allelic model (OR=2.72, P=0.001) and recessive model (OR=5.04, P=0.000). In the overall analysis, 607C allele increased the risk of IS under all hereditary models (C vs. A: OR=1.26, P=0.002; CC vs. AA: OR=1.67, P=0.002; CA vs. AA: OR=1.30, P=0.001; CC+CA vs. AA: OR=1.41, P=0.000; CC vs. AA+CA: OR=1.48, P=0.000); a similar trend was observed in the Asian population. However, 607C allele was linked to decreased IS risk in the Egyptian population under all genetic models except the heterozygous model (C vs. A: OR=0.48, P=0.006; CC vs. AA: OR=0.19, P=0.007; CA vs. AA: OR=0.47, P=0.078; CC+CA vs. AA: OR=0.39, P=0.020; CC vs. AA+CA:OR=0.30, P=0.030). Although two polymorphisms were associated with IS, the association varied significantly in different countries. Large epidemiological studies will be required to verify these findings in the future.
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http://dx.doi.org/10.1097/WNR.0000000000001165DOI Listing
January 2019

Coping with drought: stress and adaptive mechanisms, and management through cultural and molecular alternatives in cotton as vital constituents for plant stress resilience and fitness.

Biol Res 2018 Nov 14;51(1):47. Epub 2018 Nov 14.

The Key Laboratory of Oasis Eco-agriculture, Xinjiang Production and Construction Group, Shihezi University, Shihezi, 832003, People's Republic of China.

Increased levels of greenhouse gases in the atmosphere and associated climatic variability is primarily responsible for inducing heat waves, flooding and drought stress. Among these, water scarcity is a major limitation to crop productivity. Water stress can severely reduce crop yield and both the severity and duration of the stress are critical. Water availability is a key driver for sustainable cotton production and its limitations can adversely affect physiological and biochemical processes of plants, leading towards lint yield reduction. Adaptation of crop husbandry techniques suitable for cotton crop requires a sound understanding of environmental factors, influencing cotton lint yield and fiber quality. Various defense mechanisms e.g. maintenance of membrane stability, carbon fixation rate, hormone regulation, generation of antioxidants and induction of stress proteins have been found play a vital role in plant survival under moisture stress. Plant molecular breeding plays a functional role to ascertain superior genes for important traits and can offer breeder ready markers for developing ideotypes. This review highlights drought-induced damage to cotton plants at structural, physiological and molecular levels. It also discusses the opportunities for increasing drought tolerance in cotton either through modern gene editing technology like clustered regularly interspaced short palindromic repeat (CRISPR/Cas9), zinc finger nuclease, molecular breeding as well as through crop management, such as use of appropriate fertilization, growth regulator application and soil amendments.
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http://dx.doi.org/10.1186/s40659-018-0198-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234603PMC
November 2018

Associations of miR-146a, miR-149, miR-196a2, and miR-499 Polymorphisms with Ischemic Stroke in the Northern Chinese Han Population.

Med Sci Monit 2018 Oct 15;24:7366-7374. Epub 2018 Oct 15.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).

BACKGROUND Recently, miR-146a C>G, miR- 149 T>C, miR-196a2 T>C and miR-499 A>G polymorphisms have been associated with susceptibility to many diseases, including ischemic stroke (IS). However, results have been reported inconsistency in IS, especially in the Chinese population. This study aimed to investigate the polymorphisms of the 4 miRNAs and IS risk in the Chinese population. MATERIAL AND METHODS We used a case-control study to explore these associations in 396 patients with IS and 378 healthy controls. According to TOAST standards, the selected patients were divided into subgroups: the large artery atherosclerosis (LAA) subgroup and the small artery occlusion (SAO) subgroup. The method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotypes. RESULTS The miR-146a C>G polymorphism was remarkably different (CC vs. CG+GG: P=0.027; CC+CG vs. GG: P=0.020; C vs. G: P=0.006). The miR-149 T>C polymorphism was also remarkably different (TT vs. TC+CC: P=0.017; TT+TC vs. CC: P=0.020; T vs. C: P=0.004). The miR-146a and miR-149 polymorphisms were also remarkably different in the LAA subgroup (P<0.05). However, we did not find an association of miR-196a2 T>C or miR-499 A>G polymorphisms with IS (P>0.05); we did not find any association in the LAA subgroup or the SAO subgroup (P>0.05). CONCLUSIONS Our study suggested that miR-146a C>G and miR-149 T>C polymorphisms might remarkably increase the risk of IS, which might be mainly associated with an increased risk in LAA stroke; however, the miR-196a2 T>C and miR-499 A>G polymorphisms might not be associated with IS risk in the northern Chinese Han population.
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http://dx.doi.org/10.12659/MSM.909935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198714PMC
October 2018

Plasma miR-126 and miR-143 as Potential Novel Biomarkers for Cerebral Atherosclerosis.

J Stroke Cerebrovasc Dis 2019 Jan 9;28(1):38-43. Epub 2018 Oct 9.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Background: Cerebral atherosclerosis is the most important mechanism for ischemic stroke. However, specific plasma biomarkers to assess atherosclerosis susceptibility are still lacking. Circulating miRNAs have been shown to be promising biomarkers for various pathologic conditions. We investigated whether plasma miR-126 and miR-143 could be used as biomarkers for identifying and evaluating cerebral atherosclerosis. Results showed that miR-143 and miR-126 might participate in the process of atherosclerosis and were minimally affected by cerebral infarction. Using Pearson correlation analysis, we showed that miR-126 and miR-143 were correlated with the presence and severity of cerebral atherosclerosis. The ability of miR-126 and miR-143 to differentiate atherosclerosis patients from healthy controls was demonstrated via a receiving operating characteristic curve with high specificity and sensitivity. Our data thus indicate that miR-126 and miR-143 may be potential specific biomarkers for atherosclerosis.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.09.008DOI Listing
January 2019

Independent factors related to preoperative acute lung injury in 130 adults undergoing Stanford type-A acute aortic dissection surgery: a single-center cross-sectional clinical study.

J Thorac Dis 2018 Jul;10(7):4413-4423

Department of Anaesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100000, China.

Background: Previous retrospective study suggested that acute lung injury (ALI) is frequent (78.49%) in patients undergoing aortic dissection surgery, and accompanied by a number of untoward consequences, and even induces death.

Methods: This prospective single-center cross-sectional study, registered in the ClinicalTrials.gov (Identifier: NCT01894334), assessed the preoperative clinical variables and serological results from 130 adult patients scheduled for Stanford type-A acute aortic dissection (AAD) surgery at Beijing Anzhen Hospital between January 2013 and July 2014. Exclusion criteria included patients with coronary heart disease, severe heart failure, severe cardiac tamponade and severe nervous system abnormalities. Preoperative ALI was identified according to oxygenation index (OI) calculated by PaO/FiO ratio after anesthesia induction, and all the patients were divided into two groups: non-ALI (OI ≥300 mmHg) and ALI (OI <300 mmHg). The primary endpoint was the incidence of preoperative ALI. The secondary endpoints were the independent factors affecting the occurrence of preoperative ALI.

Results: The incidence of preoperative ALI was 53.8%. With adjusted multiple logistic regression analysis, age [odds ratio (OR) 1.14, confidence interval (CI), 1.06-1.22; P=0.0002], body mass index (BMI) (OR 1.31, CI, 1.09-1.56; P=0.0033), preoperative diastolic blood pressure (DBP) (OR 0.94, CI, 0.89-0.99; P=0.0109), interleukin-6 (IL-6) (OR 1.03, 95% CI, 1.01-1.06; P=0.0053), and prostaglandin I/thromboxane B (PGI/TXB) ratio (OR 0.25, 95% CI, 0.09-0.67; P=0.0055) were significantly related to the occurrence of preoperative ALI. The decreased risk of ALI was related to the preoperative DBP value up to 44 mmHg (OR 0.935, 95% CI, 0.895-0.978; P=0.0033). Interactions analysis revealed that serum lactic acid mediated the relationship between DBP and ALI before Stanford type-A AAD surgery.

Conclusions: In adults undergoing Stanford type-A AAD surgery, the incidence of preoperative ALI was 53.8%, and age, BMI, preoperative DBP, IL-6, and PGI2/TXB2 ratio were independent factors related to the occurrence of pre-operative ALI. Trial Registration: ClinicalTrials.gov, Identifier: NCT01894334.
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http://dx.doi.org/10.21037/jtd.2018.06.140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105969PMC
July 2018

Pulmonary static inflation with 50% xenon attenuates decline in tissue factor in patients undergoing Stanford type A acute aortic dissection repair.

J Thorac Dis 2018 Jul;10(7):4368-4376

Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.

Background: The Stanford type A acute aortic dissection (AAD) carries a high risk of mortality and morbidity, and patients undergoing AAD surgery often bleed excessively and require blood products and transfusions. Thus, we studied how xenon alters coagulation using thromboelastography (TEG) and conventional hemostatic tests for patients with AAD undergoing aortic arch surgery involving cardiopulmonary bypass (CPB)/deep hypothermic circulatory arrest (DHCA).

Methods: This prospective single-center nonrandomized controlled clinical trial, registered in the Chinese Clinical Trial Registry (ChiCTR-ICR-15006435), assessed perioperative clinical variables and serological results from 50 subjects undergoing pulmonary static inflation with 50% nitrogen/50% oxygen from January 2013 to January 2014 and 50 subjects undergoing pulmonary static inflation with 50% xenon/50% oxygen from January 2014 to December 2014 during CPB for Stanford type A AAD. Repeated measures ANOVA were used to identify the effects of xenon on coagulation after surgery. The primary endpoint was perioperative changes in coagulation and fibrinolysis after intubation and 10 minutes, and 6 hours after the operation. The secondary endpoint was to assess the perioperative changes in serum level of tissue factor (TF), tissue factor pathway inhibitor (TFPI) and tissue plasminogen activator (tPA) after intubation and 10 minutes, and 6 hours after the operation.

Results: Mean prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), median fibrinogen degradation product (FDP), and D-dimer peaked and then decreased over 6 hours after surgery. TEG followed a similar trend. From the start to the end of surgery and until 6 h after surgery, mean TF decreased in controls (β -2.61, P<0.001 and β -2.83, P<0.001, respectively), but was maintained relatively stable in xenon group (β -0.5, P<0.001 and β -0.96, P<0.001, respectively).

Conclusions: Deterioration of coagulation function and activated fibrinolysis was confirmed by conventional tests and TEG analysis after Stanford type A AAD repair. Pulmonary static inflation with 50% xenon attenuates decline in TF in patients undergoing Stanford type A AAD repair.
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http://dx.doi.org/10.21037/jtd.2018.06.95DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106010PMC
July 2018

l-Homocarnosine, l-carnosine, and anserine attenuate brain oxidative damage in a pentylenetetrazole-induced epilepsy model of ovariectomized rats.

3 Biotech 2018 Aug 9;8(8):363. Epub 2018 Aug 9.

3Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, 266100 Shandong China.

In this study, we investigated the protective effect of l-homocarnosine, l-carnosine, and anserine (HCA) on seizure-induced brain injuries. We evaluated the protective effect of HCA on brain oxidative damage in a pentylenetetrazole (PTZ)-induced epilepsy model using ovariectomized (OVX) rats. The experimental groups were as follows: group I, sham; group II, sham + PTZ; group III, sham + HCA + PTZ; group IV, OVX; group V, OVZ + PTZ; and group VI, OVX + HCA + PTZ. We determined the levels of lipid peroxidation, glutathione peroxidase (Gpx), reduced glutathione (GSH), catalase, superoxide dismutase (SOD), and thiol in brain hippocampal and cortical tissue. The biochemical markers were significantly altered in the brain tissue of OVX rats. HCA supplementation significantly reduced lipid peroxidation and increased GSH, Gpx, SOD, catalase, and thiol levels in PTZ-treated OVX rats. Rats with an ovariectomy showed a significant protective effect against PTZ through elevation of the latency of generalized tonic-clonic seizures (GTCS). HCA substantially increased minimal clonic seizure and GTCS latency in the OVX-PTZ and sham-PTZ groups. In summary, our experimental data indicate that combined supplementation of HCA substantially increased anticonvulsant activity. Moreover, combined HCA supplementation reduced oxidative damage by decreasing lipid peroxidation and increasing antioxidant levels in the brain of a PTZ-induced seizure rodent model.
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http://dx.doi.org/10.1007/s13205-018-1357-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085213PMC
August 2018

MicroRNA‑155 promotes ox‑LDL‑induced autophagy in human umbilical vein endothelial cells by targeting the PI3K/Akt/mTOR pathway.

Mol Med Rep 2018 Sep 29;18(3):2798-2806. Epub 2018 Jun 29.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.

Endothelial cell autophagy has a protective role in inhibiting inflammation and preventing the development of atherosclerosis, which may be regulated by microRNA (miR)‑155. The present study aimed to investigate the mechanisms of autophagy in the development of atherosclerosis. Human umbilical vein endothelial cells model in vitro and using oxidized low‑density lipoprotein (ox‑LDL) stimulated cells to simulate the atherosclerosis. MiR‑155 mimics, miR‑155 inhibitors, and a negative control were respectively transfected in human umbilical vein endothelial cells to analyzed alterations in the expression of miR‑155. It was demonstrated that overexpression of miR‑155 promoted autophagic activity in oxidized low‑density lipoprotein‑stimulated human umbilical vein endothelial cells, whereas inhibition of the expression of miR‑155 reduced autophagic activity. Overexpression of miR‑155 revealed that it regulated autophagy via the phosphatidylinositol‑3 kinase (PI3K)/RAC‑α serine/threonine‑protein kinase (Akt)/mechanistic target of rapamycin pathway (mTOR) signaling pathway. A luciferase reporter assay demonstrated that miR‑155 directly bound to the PI3K catalytic subunit a and Ras homolog enriched in brain 3'‑untranslated region and inhibited its luciferase activity. Therefore, the results of the present study suggested that miR‑155 promoted autophagy in vascular endothelial cells and that this may have occurred via targeting of the PI3K/Akt/mTOR pathway. Thus, miR‑155 may be considered as a potential therapeutic target for the treatment of atherosclerosis.
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http://dx.doi.org/10.3892/mmr.2018.9236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102700PMC
September 2018

Rs4612666 Polymorphism of the NLRP3 Gene Is Associated with the Occurrence of Large Artery Atherosclerotic Ischemic Strokes and Microembolic Signals.

Biomed Res Int 2018 23;2018:6345805. Epub 2018 Apr 23.

Department of Neurology, The Affiliated Hospital of Qingdao University, 59 Haier Road, Qingdao, Shandong 266000, China.

Purpose: Large artery atherosclerosis (LAA) ischemic stroke (IS) is the most common IS subtype, and microemboli are clinically important for indicating an increased risk of IS. Nucleotide-binding domain-like receptor protein 3 (NLRP3) plays a crucial role in the pathogenesis of atherosclerosis. The aim of this study is to investigate the relationship between NLRP3 gene polymorphisms and susceptibility for LAA IS and microembolic signals (MES) in the Chinese Han population.

Methods: We studied 293 patients diagnosed with LAA IS and 265 controls. Transcranial Doppler (TCD) was used to monitor the MES in all of the patients. Depending on the presence or absence of MES, the patients were divided into MES-positive and MES-negative subgroups. PCR-RFLP or direct sequencing were used to analyze three NLRP3 gene polymorphisms.

Results: Seventy-six patients presented with MES and the MES-positive rate was 25.94%. Logistic regression analysis showed that the TT genotype frequency for the rs4612666 gene polymorphism was higher in study patients than in the controls (adjusted = 0.001) and higher in MES-positive patients compared to MES-negative patients (adjusted = 0.015). The T allele of rs4612666 was associated with an increased risk for developing LAA IS and MES ( = 0.001; = 0.015, resp.). Prevalence of the CCC haplotype was higher in the controls than in the patients ( = 0.009) and prevalence of the TGT haplotype was lower in the controls than in the patients ( = 0.019).

Conclusions: The NLRP3 rs4612666 gene polymorphism may be related to the occurrence of LAA IS and MES, suggesting that the NLRP3 gene polymorphism increases the susceptibility of LAA IS by changing the plaque vulnerability.
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http://dx.doi.org/10.1155/2018/6345805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937605PMC
October 2018

Correction to: Knockdown of miR-155 protects microglia against LPS-induced inflammatory injury via targeting RACK1: a novel research for intracranial infection.

J Inflamm (Lond) 2018 3;15. Epub 2018 Apr 3.

4Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, 266000 China.

[This corrects the article DOI: 10.1186/s12950-017-0162-7.].
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http://dx.doi.org/10.1186/s12950-018-0183-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5883406PMC
April 2018