Publications by authors named "Aijun Ma"

46 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

Heat stress-induced HSP90 expression is dependent on ERK and HSF1 activation in turbot (Scophthalmus maximus) kidney cells.

Cell Stress Chaperones 2021 Jan 6;26(1):173-185. Epub 2020 Oct 6.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, No.106 Nanjing Road, Qingdao, 266071, China.

Mitogen-activated protein kinases (MAPKs) and heat shock proteins (HSPs) are ubiquitous proteins that are functional mediators in both normal and stressed states of the cell. In this study, we performed heat stress (37 °C) experiments on turbot kidney (TK) cells. Heat stress expression patterns of HSP90, as well as the expression and phosphorylation levels of extracellular-regulated signal kinases (ERKs) and the transcription factor HSF1 and c-Fos, were examined. The results show that heat stress activates ERK1/2 and HSF1, and induces HSP90 gene expression in TK cells. Inhibition of ERK activation attenuates heat stress-induced HSP90 gene expression. The double luciferase reporter gene experiment showed that HSF1 is an important transcription factor for heat-induced HSP90 gene expression. Likewise, c-Fos does not directly regulate the heat-induced expression of HSP90 in turbot kidney cells. To our knowledge, this is the first study to report a signaling pathway that regulates the heat shock response in turbot cells. Our results may facilitate an understanding of the underlying molecular mechanisms of the cellular stress response in marine fish.
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http://dx.doi.org/10.1007/s12192-020-01166-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736437PMC
January 2021

Transcriptome analysis provides insights into the effects of myo-inositol on the turbot Scophthalmus maximus.

Fish Shellfish Immunol 2020 Nov 23;106:691-704. Epub 2020 Jul 23.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Shandong Key Laboratory of Marine Fisheries Biotechnology and Genetic Breeding, Qingdao Key Laboratory for Marine Fish Breeding and Biotechnology, Qingdao, 266071, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266071, China. Electronic address:

Myo-inositol is an essential vitamin for most animals, and it can modulate multiple physiological functions. In this study, we performed transcriptome gene expression profiling of gill tissue from turbot Scophthalmus maximus fed different concentrations of myo-inositol (0, 300, 600, 900, 1200 mg/kg). Results of expression tendency analysis, Weighted Gene Co-Expression Network Analysis (WGCNA), integrated transcriptome analyses, and KEGG annotation analysis of all differentially expressed genes (DEGs) demonstrated that the cytokine-cytokine receptor interaction played a core role in effects of myo-inositol on turbot, which was followed by the Jak-STAT signaling pathway. The results of qRT-PCR also showed myo-inositol mediated the gene expression of the cytokine-cytokine receptor interaction and the Jak-STAT signaling pathway in turbot. The ELISA assay indicated that myo-inositol affected the concentration change of interleukins (IL-2 and IL-10). Consequently, the interleukins associated with immune functions in the cytokine-cytokine receptor interaction played a core role in the effects of myo-inositol on turbot, which was followed by the Jak-STAT signaling pathway. Additionally, 10 hub genes associated with myo-inositol-traits were identified via WGCNA.
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http://dx.doi.org/10.1016/j.fsi.2020.07.019DOI Listing
November 2020

Molecular cloning, characterization and expression analysis of p53 from turbot Scophthalmus maximus and its response to thermal stress.

J Therm Biol 2020 May 26;90:102560. Epub 2020 Feb 26.

Yantai Tianyuan Aquatic Limited Corporation, Yantai, 264006, China.

The tumor suppressor protein, p53 plays a crucial role in protecting genetic integrity. Once activated by diverse cell stresses, p53 reversibly activates downstream target genes to regulate cell cycle and apoptosis. However, few studies have investigated the effects of thermal stress in turbot, specifically the p53 signaling pathway. In this study, the rapid amplification of cDNA ends was used to obtain a full-length cDNA of the turbot p53 gene (Sm-p53) and perform bioinformatics analysis. The results showed that the cDNA of the Sm-p53 gene was 2928 bp in length, encoded a 381 amino acid protein, with a theoretical isoelectric point of 6.73. It was composed of a DNA binding and a tetramerization domain. Expression of Sm-p53 in different tissues was detected and quantified by qRT-PCR, and was highest in the liver. We also investigated the expression profiles of Sm-p53 in different tissue and TK cells after thermal stress. These result suggested that Sm-p53 plays a key role, and provides a theoretical basis for Sm-p53 changes in environmental stress responses in the turbot.
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http://dx.doi.org/10.1016/j.jtherbio.2020.102560DOI Listing
May 2020

Molecular characterization, expression analysis of 14-3-3 beta/alpha and the effect of RNA interference on ion transporter protein Na-K-ATPase, Na-H-exchanger and CFTR in turbot (Scophthalmus maximus).

Comp Biochem Physiol B Biochem Mol Biol 2020 Aug - Sep;246-247:110458. Epub 2020 May 17.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Shandong Key Laboratory of Marine Fisheries Biotechnology and Genetic Breeding, Qingdao Key Laboratory for Marine Fish Breeding and Biotechnology, Qingdao 266071, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China; College of Fisheries and Life Science, Shanghai Ocean University, Ministry of Education, Shanghai 201306, China.

To understand the role of 14-3-3 beta/alpha in hypoosmotic regulation of turbot (Scophthalmus maximus), we characterized the 14-3-3 beta/alpha gene and analyzed the tissue distribution and its gene transcriptional patterns in the main expressed tissues under low salt stress. The 14-3-3 beta/alpha cDNA is 892 bp in length, incorporating an ORF of 774 bp with a putative primary structure of 257 residues. The deduced amino acid sequences shared highly conserved structures with other eukaryotes. Quantitative real-time PCR results showed that the 14-3-3 beta/alpha transcripts were widely expressed in various tissues of turbot, with most abundant in the gill (P < .05), to a lesser extent in the kidney, intestine, brain and spleen, and at low levels in the pituitary and other tissues examined. And the expression of turbot 14-3-3 beta/alpha exhibited a trend of increasing first and then decreasing with the time of stress under low salt stress, and the highest value appeared in 12 h (P < .05). After injecting different concentrations of dsRNA, the mRNA expression of 14-3-3 gene decreased significantly during the monitoring period, and the best interference effect was achieved 12 h after injecting 4 μg/g dsRNA. For the first time, the gene was silenced in fish by intramuscular injection of dsRNA. It also provides a new and effective way to study gene function at the individual level. Moreover, the mRNA interference of 14-3-3 beta/alpha would cause changes in the expression of several ion channel proteins, for example, the decrease of Na-K-ATPase and Na-H-exchanger and the increase of CFTR. As a result, 14-3-3 beta/alpha appears to be an important molecular regulator for osmosensory signal transduction in gill of turbot.
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http://dx.doi.org/10.1016/j.cbpb.2020.110458DOI Listing
January 2021

Comparative transcriptomic analysis reveals mechanisms of divergence in osmotic regulation of the turbot Scophthalmus maximus.

Fish Physiol Biochem 2020 Aug 7;46(4):1519-1536. Epub 2020 May 7.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences; Shandong Key Laboratory of Marine Fisheries Biotechnology and Genetic Breeding, Qingdao Key Laboratory for Marine Fish Breeding and Biotechnology, Qingdao, 266071, China.

The turbot Scophthalmus maximus has evolved extensive physiological ability to adapt to multiple environmental salinities. The morphological changes of the kidney indicated the adaptability difference and similarity of turbot to salinity stress. Identify transcriptome-wide differences between low-salinity seawater (LSW, salinity 5)- and high-salinity seawater (HSW, salinity 50)-acclimated kidneys of turbot to decipher the osmotic regulation mechanism. We identified 688 differentially expressed genes (DEGs) in the LSW-acclimated kidneys and 2441 DEGs in the HSW-acclimated kidneys of turbot compared with seawater-acclimated kidneys, respectively. We investigated three patterns of gene regulation to salinity stress that involved in ion channels and transporters, functions of calcium regulation, organic osmolytes, energy demand, cell cycle regulation, and cell protection. Additionally, protein-protein interaction (PPI) analysis of DEGs suggested the presence of a frequent functional interaction pattern and that crucial genes in the PPI network are involved in hyper-osmotic regulation. Based on the analysis of comparative transcriptome data and related literature reports, we conclude that the mechanisms responsible for osmotic regulation and its divergence in turbot are related to various genes that are involved in canonical physiological functions. These findings provide insight into the divergence in osmoregulation of turbot and valuable information about osmoregulation mechanisms that will benefit other studies in this field.
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http://dx.doi.org/10.1007/s10695-020-00808-6DOI Listing
August 2020

Myo-inositol enhances the low-salinity tolerance of turbot (Scophthalmus maximus) by modulating cortisol synthesis.

Biochem Biophys Res Commun 2020 06 10;526(4):913-919. Epub 2020 Apr 10.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Shandong Key Laboratory of Marine Fisheries Biotechnology and Genetic Breeding, Qingdao Key Laboratory for Marine Fish Breeding and Biotechnology, Qingdao, 266071, China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology, Qingdao, 266071, China.

Myo-inositol is a major intracellular osmolyte that can be accumulated to protect cells from a variety of stresses, including fluctuations in the osmolality of the environment, and cortisol is thought to be an osmotic hormone in teleost fish. In this study, dietary myo-inositol resulted in increased Na-K-ATPase activity and gene expression of partial ion channel genes and prolonged survival time of turbot (Scophthalmus maximus) under low salinity. The cortisol regulated by dietary myo-inositol also was correlated with these outcomes. The optimal concentrations of cortisol stimulated gill Na-K-ATPase activity and increased the expression of ion channel genes to enhance low salinity tolerance, as indicated by longer survival time under low salinity. When cortisol level was suppressed, myo-inositol failed to increase the survival time of turbot under low salinity, and strong correlations between cortisol concentration and Na-K-ATPase activity, expression of partial ion channel genes, and survival time of turbot were detected. These results showed that myo-inositol enhanced the low salinity tolerance of turbot by modulating cortisol synthesis.
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http://dx.doi.org/10.1016/j.bbrc.2020.04.004DOI Listing
June 2020

Metabolic responses in Scophthalmus maximus kidney subjected to thermal stress.

Fish Shellfish Immunol 2020 Aug 8;103:37-46. Epub 2020 Apr 8.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Shandong Key Laboratory of Marine Fisheries Biotechnology and Genetic Breeding, Qingdao Key Laboratory for Marine Fish Breeding and Biotechnology, Qingdao, 266071, China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266237, China.

Turbot (Scophthalmus maximus) is an economically important marine fish cultured in China. In this study, fish in the experimental group were exposed to four temperatures: 15, 20, 25 and 28 °C. Metabolomics analysis and quantitative real-time PCR were used to assess changes in metabolic profiling and gene expression associated with thermal stress. The results showed the levels of heat shock protein 70 (HSP70), heat shock protein 90 (HSP90), blood creatinine and cortisol in S. maximus were all significantly upregulated (P < 0.05), indicating a stress response at 25 °C or higher. Challenge with thermal stress significantly increased expression levels of succinate dehydrogenase (SDH), fructose-1, 6-bisphosphatase (FBPase), malate dehydrogenase (MDH), cytosolic phosphoenolpyruvate carboxykinase (cPEPCK), glucose-6-phosphatase (G6Pase) and aspartate aminotransferase (AST) (P < 0.05). However, there was no effect on the expression levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and mitochondrial phosphoenolpyruvate carboxykinase (mPEPCK). Moreover, high temperature decreased levels of glycogenic amino acids, including histidine, threonine, glutamine, phenylalanine, arginine, serine, tyrosine, methionine and isoleucine. These findings suggest a significant correlation between gene expression and regulation of carbohydrate and amino acid metabolism in heat-stressed S. maximus kidney. In addition, the maintenance of aerobic metabolism and activation of gluconeogenesis appeared to be a critical metabolic strategy in combating heat stress in turbot kidney.
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http://dx.doi.org/10.1016/j.fsi.2020.04.003DOI Listing
August 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

Cloning and molecular characterization of PRL and PRLR from turbot (Scophthalmus maximus) and their expressions in response to short-term and long-term low salt stress.

Fish Physiol Biochem 2020 Apr 22;46(2):501-517. Epub 2020 Jan 22.

Yantai Tianyuan Aquatic Limited Corporation, Yantai, 264003, China.

The pituitary hormone prolactin (PRL) regulates salt and water homeostasis by altering ion retention and water uptake through peripheral osmoregulatory organs. To understand the role of PRL and its receptor (PRLR) in hypoosmoregulation of turbot (Scophthalmus maximus), we characterized the PRL and PRLR gene and analyzed the tissue distribution of the two genes and their gene transcriptional patterns in the main expressed tissues under long-term and short-term low salt stress. The PRL cDNA is 1486 bp in length, incorporating an ORF of 636 bp with a putative primary structure of 211 residues. And the PRLR cDNA is 2849 bp in length, incorporating an ORF of 1944 bp with a putative primary structure of 647 residues. The deduced amino acid sequences of these two genes shared highly conserved structures with those from other teleosts. Quantitative real-time PCR results showed that PRL transcripts were strongly expressed in the pituitary and very weakly in brain, but were hardly expressed in other tissues. PRLR transcripts were most abundant in the kidney, to a lesser extent in the gill, intestine, brain, and spleen, and at low levels in the pituitary and other tissues examined. The expression of PRL in the pituitary increased after short-term or long-term low salt stress, and the highest expression level appeared 12 h after stress (P < 0.05). And there is no significant difference between both low salt group (5 ppt and 10 ppt) at each sampling point. The variation of PRLR expression in gill under short-term low salt stress is similar to that of PRL gene in pituitary, with highest value in 12 h (P < 0.05). However, the expression under long-term low salt stress was significantly higher than control group even than 12 h group under 5 ppt (P < 0.05). The expression of PRLR in the kidney increased first and then decreased after low salt stress, and the highest value also appeared in 12 h after stress and there was no significant difference between the salinity groups. After long-term low salt stress, the expression level also increased significantly (P < 0.05), but it was flat with 24 h, which was lower than 12 h. The variation of PRLR expression in the intestine was basically consistent with that in the kidney. The difference was that the expression level of 24 h after stress in the 5 ppt group was significantly higher than that of the 10 ppt group (P < 0.05). After a comprehensive analysis of the expression levels of the two genes, it can be found that the expression level increased and peaked at 12 h after short-term low salt stress, indicating that this time point is the key point for the regulation of turbot in response to low salt stress. This also provides very important information for studying the osmotic regulation of turbot. In addition, our results also showed that the expression of PRLR was stable in the kidney and intestine after long-term low salt stress, while the expression in the gill was much higher than short-term stress. It suggested that PRL and its receptors mainly exert osmotic regulation function in the gill under long-term low salt stress. At the same time, such a result also brings a hint for the low salt selection of turbot, focusing on the regulation of ion transport in the gill.
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http://dx.doi.org/10.1007/s10695-019-00699-2DOI Listing
April 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

Osmoregulation by the myo-inositol biosynthesis pathway in turbot Scophthalmus maximus and its regulation by anabolite and c-Myc.

Comp Biochem Physiol A Mol Integr Physiol 2020 04 15;242:110636. Epub 2019 Dec 15.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Shandong Key Laboratory of Marine Fisheries Biotechnology and Genetic Breeding, Qingdao Key Laboratory for Marine Fish Breeding and Biotechnology, Qingdao 266071, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China; College of Fisheries and Life Science, Shanghai Ocean University, Ministry of Education, Shanghai 201306, China.

The induction of the myo-inositol biosynthesis (MIB) pathway in euryhaline fishes is an important component of the cellular response to osmotic challenge. The MIPS and IMPA1 genes were sequenced in turbot and found to be highly conserved in phylogenetic evolution, especially within the fish species tested. Under salinity stress in turbot, both MIPS and IMPA1 showed adaptive expression, a turning point in the level of expression occurred at 12 h in all tissues tested. We performed an RNAi assay mediated by long fragment dsRNA prepared by transcription in vitro. The findings demonstrated that knockdown of the MIB pathway weakened the function of gill osmotic regulation, and may induce a genetic compensation response in the kidney and gill to maintain physiological function. Even though the gill and kidney conducted stress reactions or compensatory responses to salinity stress, this inadequately addressed the consequences of MIB knockdown. Therefore, the survival time of turbot under salinity stress after knockdown was obviously less than that under seawater, especially under low salt stress. Pearson's correlation analysis between gene expression and dietary myo-inositol concentration indicated that the MIB pathway had a remarkable negative feedback control, and the dynamic equilibrium mediated by negative feedback on the MIB pathway played a crucial role in osmoregulation in turbot. An RNAi assay with c-Myc in vivo and the use of a c-Myc inhibitor (10058-F4) in vitro demonstrated that c-Myc was likely to positively regulate the MIB pathway in turbot.
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http://dx.doi.org/10.1016/j.cbpa.2019.110636DOI Listing
April 2020

Transcriptome analysis and weighted gene co-expression network reveals potential genes responses to heat stress in turbot Scophthalmus maximus.

Comp Biochem Physiol Part D Genomics Proteomics 2020 03 1;33:100632. Epub 2019 Nov 1.

Yantai Tianyuan Aquatic Limited Corporation, Yantai 264006, China.

Turbot (Scophthalmus maximus) is an economically important marine fish cultured in China. In this study, we performed transcriptome gene expression profiling of kidney tissue in turbot exposed to heat stress (20, 23, 25 and 28 °C); control fish were maintained at 14 °C. We investigated gene relationships based on weighted gene co-expression network analysis (WGCNA). Accordingly, enrichment analyses of GO terms and KEGG pathways showed that several pathways (e.g., fat metabolism, cell apoptosis, immune system, and insulin signaling) may be involved in the response of turbot to heat stress. Moreover, via WGCNA, we identified 19 modules: the dark grey module was mainly enriched in pathways associated with fat metabolism and the FOXO and Jak-STAT signaling pathways. The ivory module was significantly enriched in the P53 signaling pathway. Furthermore, the key hub genes CBP, AKT3, CCND2, PIK3r2, SCOS3, mdm2, cyc-B, and p48 were enriched in the FOXO, Jak-STAT and P53 signaling pathways. This is the first study reporting co-expression patterns of a gene network after heat stress in marine fish. Our results may contribute to our understanding of the underlying molecular mechanism of thermal tolerance.
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http://dx.doi.org/10.1016/j.cbd.2019.100632DOI Listing
March 2020

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

Expression and localization study of pIgR in the late stage of embryo development in turbot (Scophthalmus maximus).

Fish Shellfish Immunol 2019 Apr 8;87:315-321. Epub 2019 Jan 8.

QingDao Agricultural University, China. Electronic address:

The receptor responsible for maternofetal transmission of immunoglobulin (Igs) in the teleosts is not clear. Polymeric immunoglobulin receptor (pIgR) specifically binds with IgA and IgM and mediates the transcytosis of intracellular polymeric immunoglobulins (pIgs) at the mucosal surface to protect against pathogens. Hence there is a possibility that it may be involved in the transmission of maternal Igs. The aim of the present study was to detect the expression and localization of pIgR during embryonal development in turbot (Scophthalmus maximus). pIgR gene was first cloned from eggs and embryos of turbot with or without parent immunization. The expression and distribution of pIgR in unfertilized egg and in embryos ranging from day 1 to day 5 after fertilization were analyzed using reverse transcriptase quantitative polymerase chain reaction and in situ hybridization. pIgR gene was detected in all eggs and embryos at different stages of development, with the highest level detected on the 5th day. pIgR mRNA was observed to be first located in the whole blastoderm and enveloped the yolk sac. Later, it was located around entoderm including primary digestive tract and pronephric tubule tract, and finally it was located at the joint of abdomen and vitelline membrane. Then, Eukaryotic expression plasmid carrying pIgR gene was constructed and transfected into HEK293T cells. Results showed mature pIgR protein located on the cellular membrane, and could bound IgM in vitro. Our findings provide information for studying the involvement of pIgR in maternal Igs transportation in turbot.
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http://dx.doi.org/10.1016/j.fsi.2019.01.010DOI 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

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

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