Publications by authors named "Hongsong Zhang"

22 Publications

  • Page 1 of 1

Genetic association analysis between IL9 and coronary artery disease in a Chinese Han population.

Cytokine 2021 Nov 20;150:155761. Epub 2021 Nov 20.

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address:

Interleukin-9 (IL-9) plays important role in coronary artery disease (CAD). However, the exact relationship between them is not explored yet. Here, four tag SNPs covering IL9 (rs31563, rs2069868, rs2069870 and rs31564) were selected to conduct case-control association analyses in a total of 3704 individuals from Chinese Han population (1863 CAD vs 1841 control). Results showed that: first, rs2069868 was associated with CAD combined with hypertension (P = 0.027); second, IL9 haplotype (CGAT) was associated with CAD (P = 0.035), and the combination genotype of "rs31563_CC/rs31564_TT" would remarkably decrease the risk of CAD (P = 0.001); third, significant associations were found between rs2069870 and decreased LDL-c levels and decreased total cholesterol levels, and between rs31563 and increased HDL-c levels (P < 0.05). Therefore, we conclude that IL9 might play a causal role in CAD by interacted with CAD traditional risk factors, which might confer a new way to improve the prevention and treatment of CAD.
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http://dx.doi.org/10.1016/j.cyto.2021.155761DOI Listing
November 2021

Loss of myeloid Bmal1 exacerbates hypertensive vascular remodelling through interaction with STAT6 in mice.

Cardiovasc Res 2021 Nov 2. Epub 2021 Nov 2.

CUHK Shenzhen Research Institute, School of Biomedical Sciences, Heart and Vascular Institute, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR.

Aims: In addition to its involvement of inflammatory responses, limited information is available on the phenotype and behaviour of vascular macrophages during hypertensive vascular remodelling. Here we aim at studying the contribution of BMAL1 to the pro-fibrotic macrophage phenotype in the vasculature during hypertension, which leads to enhanced vascular remodelling and promoted blood pressure increase.

Methods And Results: Wild type Bmal1f/f and myeloid cell selective Bmal1 knockout Bmal1f/f; LysMCre/+ mice were infused with AngII for four weeks to induce hypertension. AngII-induced blood pressure increase, vascular media thickness and vascular dysfunction were enhanced in Bmal1f/f; LysMCre/+ mice, accompanied with a pro-fibrotic M2 phenotype of the vascular macrophages. Bmal1f/f; LysMCre/+ mice also have more upregulations of MMP9 and MMP13 expression in the vascular wall, accompanied by enhanced collagen deposition after AngII infusion. Loss of Bmal1 in bone marrow derived macrophages enhanced STAT6 activation induced by IL4, and the subsequent MMP13 upregulation and activity. In macrophages, loss of Bmal1 enhanced the phosphorylation and nuclear translocation of STAT6 triggered by IL4, through possibly a direct interaction between BMAL1 and STAT6. To further determine whether IL4 induced signalling in macrophage contributes to enhanced vascular remodelling in hypertensive mice, we showed that deletion of myeloid IL4Rα in Il4raf/f; LysMCre/+ mice attenuated blood pressure increase and hypertensive vascular remodelling after AngII infusion.

Conclusions: Our results suggested a tonic effect of BMAL1 deletion on hypertensive vascular remodelling. BMAL1 might inhibit IL4-STAT6 signalling in macrophages through the interaction with STAT6 to reduce STAT6 activation and target gene transcription, especially MMP9 and MMP13, contributing to vascular remodelling.

Translational Perspective: Many recent studies emphasized the contribution of macrophage, especially those reside within the vasculture, in modulating vessel function and structure, under physiological and pathological conditions such as hypertension. Our study showed that clock gene BMAL1 not only regulates rhythmic gene expression in macrophages, but also interacts with other factors to maintain homeostasis of macrophage functon. Pro-fibrotic M2 macrophages contributes to hypertensive vascular remodeling. These findings add the complexity of blood pressure regulation and vascular remodeling, also indicate that it is important to consider the individual differences for blood pressure control and anti-hypertensive treatments.
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http://dx.doi.org/10.1093/cvr/cvab336DOI Listing
November 2021

Two New Methods of Supine Venographically Guided Popliteal Vein Puncture: A Retrospective Study.

Eur J Vasc Endovasc Surg 2021 10 7;62(4):622-628. Epub 2021 Jul 7.

Department of Vascular Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, the First Hospital of Hebei Medical University, Hebei, PR China. Electronic address:

Objective: Presently, the prone position is necessary for popliteal vein puncture access, but it makes the patients uncomfortable and does not allow traditional femoral or jugular access. To address these deficiencies, this study introduces two new methods, anterior and medial access carried out in the supine position.

Methods: Venous interventions with punctures in the popliteal vein of 120 limbs in 97 patients were performed during the period from February 2017 to April 2019. After puncture, venographic guidance was achieved by dorsal vein injection of contrast medium. Interventional therapy was performed after puncture and insertion of the introducer sheath.

Results: In all, 120 limbs were punctured in the popliteal vein, with technical success in 118 (98.3% in total) cases: 100%, 96.1%, and 100% successful punctures in, respectively, 32 anterior, 49 medial, and 37 posterior access cases. A comparison of the three groups revealed that the fluoroscopy time and duration of puncture were longer in the medial and anterior access groups than in the posterior access group. The rate of intra-operative and post-operative complications was 7.5% (9/120), with no statistically significant difference between the three access groups. Compared with the pre-operative median score of 2.5, the post-operative SVS (Society of Vascular Surgery) score of the popliteal vein was reduced to 1.5 in the anterior and 0.5 in the medial groups.

Conclusion: Medial and anterior puncture of the popliteal vein in the supine position can be used as a safe alternative in venous endovascular therapy. The two new methods can mitigate frailty or respiratory problems resulting from the prone position and facilitate traditional femoral and jugular access.
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http://dx.doi.org/10.1016/j.ejvs.2021.05.011DOI Listing
October 2021

KLF2 Mediates the Suppressive Effect of Laminar Flow on Vascular Calcification by Inhibiting Endothelial BMP/SMAD1/5 Signaling.

Circ Res 2021 Aug 23;129(4):e87-e100. Epub 2021 Jun 23.

Heart and Vascular Institute, Shenzhen Research Institute and Li Ka Shing Institute of Health Sciences (J.H., Y.P., L.H., C.-L.Z., C.K.C., Yuhong Huang, C.W.L., L.W., Yu Huang, J.-Y.L.), Chinese University of Hong Kong, China.

[Figure: see text].
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http://dx.doi.org/10.1161/CIRCRESAHA.120.318690DOI Listing
August 2021

Study on the predictive effect of fibrinogen on vascular calcification.

Vascular 2021 Dec 11;29(6):952-958. Epub 2021 Jan 11.

Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, the First Hospital of Hebei Medical University, Shijiazhuang, China.

Background: Fibrinogen, lipoprotein, and high-density lipoprotein levels were associated with vascular calcification, but their predictive capacity for a vascular calcification was not reported.

Aims: The purpose of this study was to evaluate the predictive efficacy of fibrinogen, lipoprotein, and high-density lipoprotein by retrospective analysis of fibrinogen, lipoprotein, and high-density lipoprotein levels in patients with vascular calcification, to explore the effective predictive indexes of vascular calcification, to predict the occurrence and development of vascular calcification, and to provide a simple and effective method for the diagnosis and prevention of vascular calcification. Fibrinogen is a good prediction of vascular calcification.

Methods: Univariate and multivariate analyses were used to assess the effects of fibrinogen, lipoprotein, and high-density lipoprotein on the CV, and the ROC curve of the predictive model was used to assess its predictive effectiveness. We collected the relevant indicators of 462 patients admitted to the Department of Vascular Surgery of the First Hospital of Hebei Medical University from August 2018 to July 2020, including 189 patients with vascular calcification (40.9%) and 273 patients without vascular calcification (59.1%); 75% of the collected data is used for modeling (modeling group) and 25% for verification (verification group).

Results: Results from the multivariate analysis showed fibrinogen, lipoprotein, and high-density lipoprotein to be independent predictors of vascular calcification. Next, the three-factor models are developed respectively. The area below the ROC curve in the fibrinogen, lipoprotein, and high-density lipoprotein forecast model was 0.8018, 0.7348, and 0.7019, respectively.

Conclusions: Fibrinogen is more predictive than high-density lipoprotein and lipoprotein in patients with arteriosclerosis.
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http://dx.doi.org/10.1177/1708538120985243DOI Listing
December 2021

pH-Responsive Host-Guest Complexations Between a Water-Soluble Pillar[6]arene Dodecyl-Ammonium Chloride and Aromatic Sulfonic Acids.

Front Chem 2020 15;8:588201. Epub 2020 Sep 15.

Henan International Joint Laboratory of Rare Earth Composite Materials, School of Materials and Chemical Engineering, Henan University of Engineering, Zhengzhou, China.

In the present work, new host-guest binding motifs based on a water-soluble pillar[6]arene dodecyl-ammonium chloride (CP6) with two aromatic sulfonic acids in aqueous media were fabricated. In accordance with the integrated results of H NMR, 2D NOESY, and florescence titration experiments, it was demonstrated that the host-guest binding of CP6 with the two aromatic sulfonic acids in aqueous solution not only has high binding constants but also has pH-responsiveness.
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http://dx.doi.org/10.3389/fchem.2020.588201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533581PMC
September 2020

Oscillating Magnetic Field Regulates Cell Adherence and Endothelialization Based on Magnetic Nanoparticle-Modified Bacterial Cellulose.

ACS Appl Mater Interfaces 2020 Nov 10;12(47):52467-52478. Epub 2020 Nov 10.

Chemicobiology and Functional Materials Institute, School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, P.R. China.

Despite the widely explored biomaterial scaffolds in vascular tissue engineering applications lately, no ideal platform has been provided for small diameter synthetic vascular grafts mainly due to the thrombosis issue. Endothelium is the only known completely non-thrombogenic material; so, functional endothelialization onto vascular biomaterials is critical in maintaining the patency of vascular networks. Bacterial cellulose (BC) is a natural biomaterial with superior biocompatibility and appropriate hydrophilicity as potential vascular grafts. In previous studies, surface modification of active peptides such as Arg-Gly-Asp (RGD) sequences onto biomaterials has been proven to achieve accelerated and selective endothelial cell (EC) adhesion. In our study, we demonstrated a new strategy to remotely regulate the adhesion of endothelial cells based on an oscillating magnetic field and achieve successful endothelialization on the modified BC membranes. In details, we synthesized bacterial cellulose (BC), magnetic BC (MBC), and RGD peptide-grafted magnetic BC (RMBC), modified with the HOOC-PEG-COOH-coated iron oxide nanoparticles (PEG-IONs). The endothelial cells were cultured on the three materials under different frequencies of an oscillating magnetic field, including "stationary" (0 Hz), "slow" (0.1 Hz), and "fast" (2 Hz) groups. Compared to BC and MBC membranes, the cells on RMBC membranes generally show better adhesion and proliferation. Meanwhile, the "slow" frequency of a magnetic field promotes this phenomenon on RMBC and achieves endothelialization after culture for 4 days, whereas "fast" inhibits the cellular attachment. Overall, we demonstrate a non-invasive and convenient method to regulate the endothelialization process, with promising applications in vascular tissue engineering.
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http://dx.doi.org/10.1021/acsami.0c17213DOI Listing
November 2020

Calix[n]arene/Pillar[n]arene-Functionalized Graphene Nanocomposites and Their Applications.

Front Chem 2020 12;8:504. Epub 2020 Jun 12.

School of Materials and Chemical Engineering, Henan University of Engineering, Zhengzhou, China.

Calix[n]arenes and pillar[n]arenes, which contain repeating units of phenol and methane, are class of synthetic cyclic supramolecules. Their rigid structure, tunable cavity size, flexible functionalization, and rich host-guest properties make them ideal surface modifiers to construct functional hybrid materials. Introduction of the calix[n]arene/pillar[n]arene species to the graphene may bring new interesting or enhanced physicochemical/biological properties by combining their individual characteristics. Reported methods for the surface modification of graphene with calix[n]arene/pillar[n]arene utilize either covalent or non-covalent approaches. This mini-review presents the recent advancements in the functionalization of graphene nanomaterials with calix[n]arene/pillar[n]arene and their applications. At the end, the future outlook and challenges for the continued research of calix[n]arene/pillar[n]arene-functionalized graphene nanohybrids in the development of applied nanoscience are thoroughly discussed.
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http://dx.doi.org/10.3389/fchem.2020.00504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304259PMC
June 2020

Prognostic significance of preoperative albumin to fibrinogen ratio associated nomograms in patients with breast invasive ductal carcinoma.

Medicine (Baltimore) 2020 Jun;99(26):e20681

Department of Breast Surgery, the Fourth Hospital of Hebei Medical University.

Plasma albumin to fibrinogen ratio is involved in human cancer, but its prognostic significance in breast cancer is controversy. In the context of breast invasive ductal carcinoma, this research aims to retrospectively evaluate by preoperative plasma albumin to fibrinogen ratio (AFR) and forecast oncological outcome and recurrence.This retrospective study comprised 230 patients with non-metastatic breast invasive ductal carcinoma who underwent surgery between January 2009 and April 2012 in Fourth Hospital of Hebei Medical University. Patients were categorized base on an optimal value of preoperative plasma fibrinogen (Fib) and albumin. Progression-free and cancer-specific survival were assessed using Kaplan-Meier method. The associations between albumin to fibrinogen ratio and clinical outcomes were assessed with univariate and multivariate analysis. A number of risk factors were used to form nomograms to evaluate survival, and Harrell concordance index (C-index) was used to evaluate the predictive accuracy.Plasma AFR was significantly associated with diminished disease-free survival (DFS) and overall survival (OS). Multivariate analysis revealed that plasma AFR was an independent prognostic indicator for DFS (HR = 1.346; 95% CI: 1.107-1.636; P = .03) and overall survival (OS) (HR = 1.485; 95% CI: 1.106-1.993; P = .008). Two prediction model of 3-, 5-years OS and DFS based on the AFR was developed.Elevated preoperative plasma AFR is an independent prognostic factor for oncological outcomes in patients with breast invasive ductal carcinoma. The formulated nomogram showed superior predictive accuracy for DFS and OS.
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http://dx.doi.org/10.1097/MD.0000000000020681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328933PMC
June 2020

Facile One-Step Electrodeposition Preparation of Cationic Pillar[6]arene-Modified Graphene Films on Glassy Carbon Electrodes for Enhanced Electrochemical Performance.

Front Chem 2020 4;8:430. Epub 2020 Jun 4.

School of Materials and Chemical Engineering, Henan University of Engineering, Zhengzhou, China.

In the present work, we have developed a facile one-step route for preparing electrochemically reduced graphene oxide-cationic pillar[6]arene (ErGO-CP6) nanocomposite films on glassy carbon electrodes (GCEs) directly from graphene oxide-cationic pillar[6]arene (GO-CP6) colloidal solution by using a pulsed electrodeposition technique. The electrocatalytic activity of ErGO-CP6 was examined by studying the oxidations of five purine bases [adenine (A), guanine (G), xanthine (X), hypoxanthine (HX), and uric acid (UA)]. It enhanced the oxidation currents of A, G, X, HX, and UA when compared to unmodified ErGO films and bare GCE, which is considered to be the synergetic effects of the graphene (excellent electrical properties and large surface area) and CP6 molecules (high inclusion complexation and enrichment capability).
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http://dx.doi.org/10.3389/fchem.2020.00430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287394PMC
June 2020

Aqueous Inflammation and Ischemia-Related Biomarkers in Neovascular Glaucoma with Stable Iris Neovascularization.

Curr Eye Res 2020 12 18;45(12):1504-1513. Epub 2020 May 18.

Department of Ophthalmology, China-Japan Friendship Hospital , Beijing, China.

: To characterize the aqueous levels of inflammation and ischemia-related biomarkers in a spectrum of retinal ischemic conditions, including neovascular glaucoma (NVG) with stable iris neovascularization after pan retinal photocoagulation (PRP) and anti-VEGF treatment. : Aqueous samples were collected from 139 eyes including NVG (n = 12), stable NVG (n = 26), CRVO (n = 11), NPDR (n = 18), PACG (n = 18), PDR (n = 25), BRVO (n = 7) and cataract (n = 22). The levels of VEGF-A, IL-8 and EPO were measured with ELISA. : Aqueous VEGF-A significantly decreased after anti-VEGF and PRP, from 983.79 ± 821.16 pg/ml in the NVG group (n = 11) to 256.50 ± 51.14 pg/ml in the stable NVG group (n = 24) ( = .015). Aqueous VEGF-A in stable NVG group (256.50 ± 51.14 pg/ml, n = 24) was significantly higher (ANOVA, < .001) than in CRVO (212.10 ± 19.84 pg/ml, n = 7, = .017), NPDR (221.18 ± 38.21 pg/ml, n = 14, = .015), BRVO (213.14 ± 48.50 pg/ml, n = 6, = .028) and cataract group (185.30 ± 34.35 pg/ml, n = 22, < .001). Aqueous IL-8 in stable NVG group (74.82 ± 10.78 pg/ml, n = 24) was significantly higher (ANOVA, < .001) than in CRVO (65.19 ± 15.34 pg/ml, n = 11, = .032) and cataract group (54.11 ± 12.28 pg/ml, n = 22, < .001). Aqueous EPO in stable NVG group (17.48 ± 3.02 pg/ml, n = 24) was significantly higher (ANOVA, < .001) than in BRVO (14.98 ± 2.57 pg/ml, n = 7, = .034) and cataract group (13.50 ± 2.65 pg/ml, n = 22, < .001). Aqueous concentrations of VEGF-A and IL-8 correlated positively with IOP (r = 0.413, < .001, r = 0.349, < .001, respectively, r = correlation coefficient). VEGF-A correlated positively with IL-8 and EPO ( < .001, = .002, respectively). IL-8 correlated positively with EPO ( < .001). : The aqueous levels of VEGF-A, IL-8 and EPO in NVG patients with stable iris neovascularization, who had received PRP and anti-VEGF, were still significantly higher than in control groups with some retinal ischemic conditions.
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http://dx.doi.org/10.1080/02713683.2020.1762226DOI Listing
December 2020

Angiogenic and inflammatory biomarker levels in aqueous humor and vitreous of neovascular glaucoma and proliferative diabetic retinopathy.

Int Ophthalmol 2020 Feb 4;40(2):467-475. Epub 2019 Dec 4.

Department of Ophthalmology, China-Japan Friendship Hospital, Yinghua Donglu, Chaoyang District, Beijing, 100029, China.

Purpose: To explore the relationships between the aqueous and vitreous levels of vascular endothelial growth factor-A (VEGF-A), interleukin-8 (IL-8), placental growth factor (PlGF) and erythropoietin (EPO) in proliferative diabetic retinopathy (PDR) and neovascular glaucoma (NVG).

Methods: Aqueous and vitreous samples were obtained from patients with PDR and NVG during surgery. Aqueous and vitreous concentrations of VEGF-A, IL-8, PlGF and EPO were measured via enzyme-linked immunosorbent assay.

Results: No correlation between the aqueous and vitreous levels of VEGF-A, IL-8, PlGF or EPO was found in both the PDR and the NVG eyes. Aqueous VEGF-A was significantly higher in the NVG group (317.55 ± 36.25 pg/ml, n = 15) than that in the PDR group (256.23 ± 46.11 pg/ml, n = 17, P < 0.001). The level of VEGF-A in aqueous (317.55 ± 36.25 pg/ml, n = 15) was significantly higher than that in vitreous (224.74 ± 60.32 pg/ml, n = 15, P < 0.001) in NVG patients. The level of IL-8 in aqueous (76.55 ± 10.88 pg/ml, n = 17) was significantly higher than that in vitreous (63.55 ± 10.74 pg/ml, n = 17, P = 0.001) in PDR patients. The level of EPO in aqueous (18.62 ± 2.87 mIU/ml, n = 15) was significantly higher than that in vitreous (15.97 ± 3.11 mIU/ml, n = 15, P = 0.022) in NVG patients. The ratio of aqueous versus vitreous for VEGF-A was significantly higher in the NVG group (1.475 ± 0.289, n = 15) than that in the PDR group (0.996 ± 0.227, n = 17, P < 0.001).

Conclusion: Aqueous levels of VEGF-A, IL-8, PlGF and EPO do not correlate with vitreous levels of those proteins. The relationship between protein levels in aqueous humor and vitreous might be dependent on different disease status or protein types investigated.
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http://dx.doi.org/10.1007/s10792-019-01207-4DOI Listing
February 2020

Acid/base- and base/acid-switchable complexation between anionic-/cationic-pillar[6]arenes and a viologen ditosylate salt.

Org Biomol Chem 2019 05;17(18):4430-4434

School of Materials and Chemical Engineering, Henan University of Engineering, Zhengzhou, 450006, China.

Two new host-guest complexes between water-soluble anionic pillar[6]arene (WP6) or cationic pillar[6]arene (CP6) and a viologen ditosylate salt G·2TsO were constructed, among which one formed from WP6 and G2+ ions can be controlled by the sequential addition of an acid and a base (HCl and NaOH, respectively), whereas the other fabricated from CP6 and TsO- ions can be switched through the sequential addition of basic and acidic reagents (NaOH and HCl, respectively).
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http://dx.doi.org/10.1039/c9ob00398cDOI Listing
May 2019

Metabolomics studies on db/db diabetic mice in skeletal muscle reveal effective clearance of overloaded intermediates by exercise.

Anal Chim Acta 2018 Dec 20;1037:130-139. Epub 2017 Dec 20.

State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, PR China. Electronic address:

Type 2 diabetes mellitus (T2DM) is characterized by hyperinsulinemia, hyperglycemia and insulin resistance, which correlated with high mortality worldwide. Exercise is one of the effective lifestyle interventions in maintaining blood glucose level in the normal range and lowering risk factors. Metabolomics approaches are powerful tools in systematic study of overall metabolic changes in response to disease or interventions. In this study, mass spectrometry-based metabolomics studies were performed to investigate the regulatory effect of moderate intensity of exercise on db/db diabetic mice in skeletal muscle. Both liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) have been carried out to monitor a wide range of regulated metabolites. Ninety-five metabolites were identified which contributing to the discrimination of db/m  + control and db/db diabetic mice. The regulatory effects of exercise on these metabolites were mainly focusing on attenuating the levels of long-chain fatty acids (C14 to C18) and medium-to long-chain acylcarnitines (C12 to C18), indicated that exercise might play a positive role in inhibiting the accumulation of excessive lipids, which is positively related to insulin resistance. In addition, uric acid, which is a risk factor for inflammation, cardiovascular complications, and fatty liver in diabetic patients, together with its intermediates (such as inosinic acid, hypoxanthine, etc.) in purine metabolism pathway, were also substantially down regulated after exercise, indicating exercise might also be protective against hyperuricemia related risks in T2DM. These findings reveal that moderate intensity of exercise might play a positive role in improving the efficiency of lipid metabolism in skeletal muscle and meanwhile enhancing uric acid clearance to prevent lipid accumulation, which might contribute to improved body fitness and body muscle composition.
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http://dx.doi.org/10.1016/j.aca.2017.11.082DOI Listing
December 2018

Exploring the Molecular Mechanism of Thoracic Aortic Aneurysm via Bioinformatics Analysis.

Med Sci Monit 2018 Mar 14;24:1533-1539. Epub 2018 Mar 14.

Department of Vascular Surgery, The First Hospital of Hebei Medical University, Hebei, Shijiazhuang, China (mainland).

BACKGROUND The aim of this study was to identify some key genes related to the pathogenesis of thoracic aortic aneurysm (TAA) and gain more insights to the molecular mechanism of TAA. MATERIAL AND METHODS The expression profile of GSE9106 was downloaded from the Gene Expression Omnibus (GEO) database. The data contained 58 TAA peripheral blood samples and 36 normal peripheral blood samples. The differently expressed genes (DEGs) between the TAA samples and the normal samples were identified via limma package of R. Functional enrichment analysis of the DEGs were performed via the Database for Annotation, Visualization and Integrated Discovery (DAVID). The differentially co-expressed genes in TAA samples compared to normal samples were identified via the DCGL package in R. The protein-protein interaction (PPI) network of the DEGs was constructed through the Search Tool for the Retrieval of Interacting Proteins (STARING) database and visualized by Cytoscape software. RESULTS A total of 407 DEGs were obtained in TAA samples compared with normal samples. The DEGs were enriched in 29 Gene Ontology (GO) terms. There were 1,441 co-expression gene pairs that had significant changes in the co-expression status in TAA samples compared with normal samples and a differential co-expression network was constructed based on them. Moreover, a PPI network of the DEGs was constructed, containing 101 nodes. CONCLUSIONS Bioinformatics methods could identify significant biological processes and genes related to TAA. KRTDAP, BICD1, and genes in the OR family might play an important role in TAA.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865405PMC
http://dx.doi.org/10.12659/msm.905970DOI Listing
March 2018

Comprehensive Analysis of Acylcarnitine Species in db/db Mouse Using a Novel Method of High-Resolution Parallel Reaction Monitoring Reveals Widespread Metabolic Dysfunction Induced by Diabetes.

Anal Chem 2017 10 12;89(19):10368-10375. Epub 2017 Sep 12.

State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University , Hong Kong 999077, P. R. China.

Acylcarnitines are exerting a variety of biological functions depending on the differences in lengths, saturation levels, and conjugation groups, which to a great extent contribute to the challenges of acylcarnitines quantifications due to various kinds of isomers. Here, we describe a novel method by using high-resolution parallel reaction monitoring (PRM) liquid chromatography-tandem mass spectrometry (LC-MS/MS). Both reversed-phase and normal-phase column were used in order to get accurate, reliable, widespread quantification of acylcarnitines, and without tedious sample preparation procedure. The method provided the most comprehensive acylcarnitine profile with high-resolution MS and MS/MS confirmation to date. A total of 117 acylcarnitines were detected from plasma and urine samples. The application of targeted profiling of acylcarnitines in db/m+ control and db/db diabetic mice indicated incomplete amino acid and fatty acid oxidation on diabetic mice. Interestingly, the reduction of medium odd-numbered chain acylcarnitines in urine samples was first observed between db/m+ and db/db mice. The high-resolution PRM method makes it possible to monitor the widespread metabolic changes of the acylcarnitines in response to stimuli. Besides, the accurate MS and MS/MS spectra data of the 117 acylcarnitines could be used as mass spectrometric resources for the identification of acylcarnitines.
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http://dx.doi.org/10.1021/acs.analchem.7b02283DOI Listing
October 2017

Inhibition of miR-92a Suppresses Oxidative Stress and Improves Endothelial Function by Upregulating Heme Oxygenase-1 in db/db Mice.

Antioxid Redox Signal 2018 02 7;28(5):358-370. Epub 2017 Aug 7.

1 Institute of Vascular Medicine, Shenzhen Research Institute and Li Ka Shing Institute of Health Sciences , Hong Kong, China .

Aims: Inhibition of microRNA-92a (miR-92a) is reported to suppress endothelial inflammation and delay atherogenesis. We hypothesize that miR-92a inhibition protects endothelial function through suppressing oxidative stress in diabetic db/db mice.

Results: In this study, we found elevated expression of miR-92a in aortic endothelium from db/db mice and in renal arteries from diabetic subjects. Endothelial cells (ECs) exposed to advanced glycation end products (AGEs) and oxidized low-density lipoprotein express higher level of miR-92a. Overexpression of miR-92a impairs endothelium-dependent relaxations (EDRs) in C57BL/6 mouse aortas. Overexpression of miR-92a suppresses expression of heme oxygenase-1 (HO-1), a critical cytoprotective enzyme, whereas inhibition of miR-92a increases HO-1 expression in human umbilical vein ECs (HUVECs) and db/db mouse aortas. Importantly, miR-92a inhibition by Ad-anti-miR-92a improved EDRs and reduced reactive oxygen species (ROS) production in db/db mouse aortas. HO-1 inhibition by SnMP or HO-1 knockdown by shHO-1 reversed the suppressive effect of miR-92a inhibition on ROS production induced by AGE treatment in C57BL/6 mouse aortas. In addition, SnMP reversed miR-92a inhibition-induced improvement of EDRs in AGE-treated C57BL/6 mouse aortas and in db/db mouse aortas.

Innovation: Expression of miR-92a is increased in diabetic aortic endothelium and inhibition of miR-92a exerts vasoprotective effect in diabetic mice through HO-1 upregulation in ECs.

Conclusion: MiR-92a expression is elevated in diabetic ECs. MiR-92a overexpression impairs endothelial function and suppresses HO-1 expression in ECs. Inhibition of miR-92a attenuates oxidative stress and improves endothelial function through enhancing HO-1 expression and activity in db/db mouse aortas. Antioxid. Redox Signal. 28, 358-370.
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http://dx.doi.org/10.1089/ars.2017.7005DOI Listing
February 2018

Myeloid deletion increases monocyte recruitment and worsens atherosclerosis.

FASEB J 2017 03 7;31(3):1097-1106. Epub 2016 Dec 7.

Institute of Vascular Medicine, Chinese University of Hong Kong, Hong Kong;

BMAL1, the nonredundant transcription factor in the core molecular clock, has been implicated in cardiometabolic diseases in mice and humans. BMAL1 controls the cyclic trafficking of Ly6c monocytes to sites of acute inflammation. Myeloid deficiency of also worsens chronic inflammation in diet-induced obesity. We studied whether myeloid deletion promotes atherosclerosis by enhancing monocyte recruitment to atherosclerotic lesions. By generating ;LysM mice on the Apoe background, we showed that deletion in myeloid cells increased the size of atherosclerotic lesions. deficiency in monocytes and macrophages resulted in an increased total number of lesional macrophages in general and Ly6c infiltrating monocyte-macrophages in particular, accompanied by skewed M2 to M1 macrophage phenotype. Ly6c and/or Ly6c monocyte subsets in blood, spleen, and bone marrow were not altered. Cell tracking and adoptive transfer of Ly6c monocytes showed deficiency induced more trafficking of Ly6c monocytes to atherosclerotic lesions, preferential differentiation of Ly6c monocytes into M1 macrophages, and increased macrophage content and lesion size in the carotid arteries. We demonstrated that deficiency in macrophages promotes atherosclerosis by enhancing recruitment of Ly6c monocytes to atherosclerotic lesions.-Huo, M., Huang, Y., Qu, D., Zhang, H., Wong, W. T., Chawla, A., Huang, Y., Tian, X. Y. Myeloid deletion increases monocyte recruitment and worsens atherosclerosis.
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http://dx.doi.org/10.1096/fj.201601030RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191064PMC
March 2017

Analysis of the genetic association between IL27 variants and coronary artery disease in a Chinese Han population.

Sci Rep 2016 05 12;6:25782. Epub 2016 May 12.

Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Interleukin-27 (IL-27) is an important cytokine in inflammatory diseases, including coronary artery disease (CAD). To explore the precise role of IL-27 in CAD, we investigated the genetic association between IL27 and CAD in the GeneID Chinese Han population. A two-stage case control association analysis was performed for 3075 CAD cases and 2802 controls. Logistic regression analysis was used to adjust the traditional risk factors for CAD. Results showed that a promoter variant, rs153109, tended to be marginally associated with CAD in the discovery population (Padj = 0.028, OR = 1.27, 95%CI: 1.03-1.58). However, this association was not replicated in the validation stage (Padj = 0.559, OR = 1.04, 95%CI: 0.90-1.21). In addition, when we classified the combined population into two subgroups according to the age at disease onset or disease state, we again obtained no significant associations. Finally, we estimated the severity of coronary stenosis using the Gensini Scoring system and determined that the rs153109 genotypes were still not associated with the Gensini scores of the CAD patients. In conclusion, our study failed to find an association between common variants in the functional region of IL27 and CAD in a Chinese Han population, which indicated that IL-27 might only be an inflammatory marker during the development of CAD.
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http://dx.doi.org/10.1038/srep25782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865940PMC
May 2016

[Study of prevention and control of delirium in ventilated patients by simulating blockage of circadian rhythm with sedative in intensive care unit].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2016 Jan;28(1):50-6

Department of Critical Care Medicine, the Second Hospital of Lanzhou University, Lanzhou 730030, Gansu, China. Corresponding author: Dong Chenming, Email:

Objective: To explore the effect of giving sedatives according to the circadian rhythm in prevention of occurrence of delirium and the prognosis of patients undergoing mechanical ventilation in intensive care unit (ICU).

Methods: A prospective double-blinded randomized controlled trial (RCT) was conducted. The patients admitted to Department of Critical Care Medicine of the Second Hospital of Lanzhou University from July 2014 to February 2015, undergoing invasive mechanical ventilation over 12 hours were enrolled. All the patients were given fentanyl for analgesia, and they were randomly divided into simulated circadian clock group (study group, n = 35) and non-simulated circadian clock group (control group, n = 35). The patients in each group were subdivided into three subgroups according to the kinds of sedative drugs, namely dexmedetomidine group (n = 8), propofol group (n = 14), and dexmedetomidine combined with propofol group (combination group, n = 13). Visual analogue scale (VAS) standard and Richmond agitation-sedation scale (RASS) were used to control the analgesic and to quantify the depth of sedation by titrating the dose of sedative drugs, the simulated circadian clock was set to control the RASS score at 0-1 during the day, and -1 to -2 at night in study group. The RASS score in the control group was set at -1 to -2 day and night. The urine 6-hydroxy acid melatonin (aMT6s) levels at different time points in the first diurnal rhythm (06:00, 12:00, 18:00, 24:00) were determined by enzyme linked immunosorbent assay (ELISA). The incidence of delirium, severe hypotension, severe bradycardia and other adverse reactions, duration of mechanical ventilation and the time of extubation, length of ICU stay, amount of sedative and analgesic drugs used were recorded. The correlation between delirium and other indexes was analyzed by using Spearman correlation analysis.

Results: (1) There were no significant differences in gender, age, acute physiology and chronic health evaluation II (APACHEII) score among groups. (2) Urine aMT6s levels did not show circadian rhythm in both groups, aMT6s level at 06:00 in study group showed an increasing tendency as compared with the control group, but the difference was not statistically significant. (3) Compared with the control group, the incidence of delirium was significantly lowered in the study group (14.3% vs. 37.1%, P = 0.029), but no significant differences were found in the incidence of severe hypotension or severe bradycardia (20.0% vs. 25.7%, 11.4% vs. 20.0%, both P > 0.05). In simulated circadian clock group, the incidence of delirium in dexmedetomidine group was significantly lower than that of the propofol group (6.3% vs. 32.1%, P < 0.05). (4) Compared with control group with the same sedative, the duration of mechanical ventilation, extubation time, length of ICU stay were significantly shortened, and the dosage of sedative drugs used was reduced in study group (all P < 0.05). In simulated circadian clock group, the duration of mechanical ventilation in dexmedetomidine group was significantly shorter than that of propofol group and combination group (hours: 75.75±26.78 vs. 102.00±26.31 and 100.31±25.38, both P < 0.05), and the length of ICU stay was significantly shorter than that of propofol group (days: 5.75±1.04 vs. 7.00±1.52, P < 0.05). (5) The occurrence of delirium was positively correlated with duration of mechanical ventilation (r = 0.705), extubation time (r = 0.704), length of ICU stay (r = 0.666, all P = 0.000), and no correlation was found between the occurrence of delirium and aMT6s level at 06:00, 12:00, 18:00, and 24:00 (r = -0.135, r = 0.163, r = 0.269, r = -0.077, all P > 0.05).

Conclusions: Administration of sedatives according to simulating circadian time could decrease the duration of mechanical ventilation, extubation time, and the length of ICU stay, decrease the dosage of sedative drugs, and reduce the incidence of delirium. Dexmedetomidine could reduce the incidence of delirium, and improve the prognosis of patients.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2016.01.010DOI Listing
January 2016

[Ventilator bundle treatment of acute respiratory distress syndrome and its correlation with biomarkers of inflammation].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2014 Aug;26(8):544-8

Department of Critical Care Medicine, Second Hospital of Lanzhou University, Lanzhou 730030, Gansu, China, Corresponding author: Dong Chenming, Email:

Objective: To observe the levels of blood soluble urokinase plasminogen activator receptor (suPAR), receptor of advanced glycation end products (RAGE), procalcitonin (PCT) and C-reactive protein (CRP), and to investigate the effect of ventilator bundle (VB) on prognosis of patients with acute respiratory distress syndrome (ARDS).

Methods: A prospective controlled study was conducted. A total of 54 cases of ARDS patients admitted to Department of Critical Care Medicine of the Second Hospital of Lanzhou University who received treatment of invasive mechanical ventilation between January 2013 and December 2013 were enrolled. All of the patients were given VB, and then divided into completely dependent group (VB group, n=29) and non-completely dependent group (NVB group, n=25) according to the dependence. The mechanical ventilation time, intensive care unit (ICU) length of stay, the incidence of ventilator associated pneumonia (VAP), the incidence of complications and 28-day mortality rate were compared between two groups. The blood suPAR, RAGE, PCT and CRP levels before and after treatment were determined. The correlations between oxygenation index (PaO(2)/FiO(2)) and other variables were analyzed by Pearson correlation and linear regression analysis.

Results: (1) There was no significant difference in gender, age, acute physiology and chronic health evaluationII (APACHE II) score and PaO(2)/FiO(2), as well as other basic state between two groups. (2) There was no obvious difference in suPAR, RAGE, PCT and CRP levels before treatment between two groups. The levels of above parameters were significantly decreased after treatment. The blood suPAR and RAGE levels in VB group were significantly decreased compared with those in NVB group [suPAR: 189.87 (135.57) ng/L vs. 309.38 (278.00) ng/L, RAGE: 2.17 (0.75) μg/L vs. 3.17 (2.64) μg/L, both P<0.01]. (3) Compared with NVB group, the mechanical ventilation time, ICU length of stay, and the incidence of VAP in VB group were significantly reduced (mechanical ventilation time: 131.52 ± 44.94 hours vs. 166.28 ± 38.09 hours, t=-3.039, P=0.004; ICU length of hospital stay: 171.14 ± 74.25 hours vs. 210.92 ± 54.89 hours, t=-2.208, P=0.032; incidence of VAP: 17.24% vs. 44.00%, χ² = 4.611, P=0.041), but 28-day mortality rate (27.59% vs. 36.00%, χ² = 0.441, P=0.566) and rates of other related complication showed no significant difference between VB group and NVB group. (4) Correlation analysis showed that PaO(2)/FiO(2) was negatively correlated with age (r=-0.290, P=0.033), suPAR (r=-0.898, P=0.000), RAGE (r=-0.898, P=0.000), PCT (r=-0.486, P=0.000) and CRP (r=-0.280, P=0.040). (5) The linear regression analysis showed PaO(2)/FiO(2) and suPAR (t=2.645, P=0.011), RAGE (t=-2.885, P=0.006), PCT (t=2.649, P=0.011) were significantly negatively co-related.

Conclusions: Blood suPAR, RAGE, PCT and CRP levels were correlated with the severity of ARDS patients. Compliance of VB can affect the prognosis of patients with ARDS. The high compliance of patients can significantly decrease the levels of blood pro-inflammatory markers, shorten the mechanical ventilation time and ICU length of stay, reduce the incidence of VAP, and it showed a positive impact on patients' prognosis.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2014.08.004DOI Listing
August 2014

The IL-33-ST2L pathway is associated with coronary artery disease in a Chinese Han population.

Am J Hum Genet 2013 Oct 26;93(4):652-60. Epub 2013 Sep 26.

Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan 430074, China.

The effects of interleukin-33 (IL-33) on the immune system have been clearly demonstrated; however, in cardiovascular diseases, especially in coronary artery disease (CAD), these effects have not yet been clarified. In this study, we investigate the genetic role of the IL-33-ST2L pathway in CAD. We performed three-stage case-control association analyses on a total of 4,521 individuals with CAD and 4,809 controls via tag SNPs in the genes encoding IL-33 and ST2L-IL-1RL1. One tag SNP in each gene was significantly associated with CAD (rs7025417(T) in IL33, padj = 1.19 × 10(-28), OR = 1.39, 95% CI: 1.31-1.47; rs11685424(G) in IL1RL1, padj = 6.93 × 10(-30), OR = 1.40, 95% CI: 1.32-1.48). Combining significant variants in two genes, the risk for CAD increased nearly 5-fold (padj = 8.90 × 10(-21), OR = 4.98, 95% CI: 3.56-6.97). Traditional risk factors for CAD were adjusted for the association studies by SPSS with logistic regression analysis. With the two variants above, both located within the gene promoter regions, reporter gene analysis indicated that the rs7025417 C>T and rs11685424 A>G changes resulted in altered regulation of IL33 and IL1RL1 gene expression, respectively (p < 0.005). Further studies revealed that the rs7025417 genotype was significantly associated with plasma IL-33 levels in the detectable subjects (n = 227, R(2) = 0.276, p = 1.77 × 10(-17)): the level of IL-33 protein increased with the number of rs7025417 risk (T) alleles. Based on genetic evidence in humans, the IL-33-ST2L pathway appears to have a causal role in the development of CAD, highlighting this pathway as a valuable target for the prevention and treatment of CAD.
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http://dx.doi.org/10.1016/j.ajhg.2013.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791271PMC
October 2013
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