Publications by authors named "Xueqi Li"

66 Publications

Ivabradine protects rats against myocardial infarction through reinforcing autophagy via inhibiting PI3K/AKT/mTOR/p70S6K pathway.

Bioengineered 2021 Dec;12(1):1826-1837

Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, P.R. China.

Ivabradine (Iva), a heart rate reducing agent that specifically inhibits the pacemaker ionic current, has been demonstrated to be cardioprotective in many cardiovascular diseases. Autophagy is an evolutionarily conserved metabolic process that regulates cardiac homeostasis. This study is aimed to explore whether autophagy is functionally involved in the cardioprotective effect of Iva in a rat model of myocardial infarction (MI). We observed that Iva treatment (po, 10 mg/kg/day) showed significant recovery on the hemodynamics parameters in MI rats, including left ventricular systolic pressure, left ventricular end diastolic pressure, and maximal ascending/descending rate of left ventricular pressure. Also, Iva treatment dramatically decreased infarct size, inhibited myocardial apoptosis, and reduced the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in MI rats. Moreover, Iva treatment enhanced autophagy and inhibited PI3K/AKT/mTOR/p70S6K pathway in MI rats. Simultaneously, we observed that autophagy enhancer rapamycin (ip, 10 mg/kg/day) showed similar cardioprotective effects with Iva. Furthermore, we observed that addition of autophagy inhibitor 3-methyladenine (ip, 10 mg/kg/day) counteracted the therapeutic effect of Iva, addressing that Iva attenuated post-MI cardiac injury by enhancing autophagy. In summary, these findings demonstrated that Iva attenuated MI in rats by enhancing autophagy, and PI3K/AKT/mTOR/p70S6K pathway might be involved in the process. Autophagy activation by Iva may be a potential therapeutic strategy for the treatment of MI.
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http://dx.doi.org/10.1080/21655979.2021.1925008DOI Listing
December 2021

The safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in Chinese adults aged 18-59 years: A phase I randomized, double-blinded, controlled trial.

Vaccine 2021 05 9;39(20):2746-2754. Epub 2021 Apr 9.

Institute of Medical Biology, Chinese Academy of Medicine Sciences & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development for Severe Infectious Diseases, Kunming 650118, China.

Background: This study examined the safety and immunogenicity of an inactivated SARS-CoV-2 vaccine.

Method: In a phase I randomized, double-blinded, placebo-controlled trial involving 192 healthy adults 18-59 years old, two injections of three doses (50 EU, 100 EU, 150 EU) of an inactivated SARS-CoV-2 vaccine or placebo were administered intramuscularly at a 2- or 4-week interval. The safety and immunogenicity of the vaccine were evaluated.

Results: Vaccination was completed in 191 subjects. Forty-four adverse reactions occurred within 28 days, most commonly mild pain and redness at the injection site or slight fatigue. At days 14 and 28, the seroconversion rates were 87.5% and 79.2% (50 EU), 100% and 95.8% (100 EU), and 95.8% and 87.5% (150 EU), respectively, with geometric mean titers (GMTs) of 18.1 and 10.6, 54.5 and 15.4, and 37.1 and 18.5, respectively, for the schedules with 2-week and 4-week intervals. Seroconversion was associated with synchronous upregulation of antibodies against the S protein, N protein and virion and a cytotoxic T lymphocyte (CTL) response. No cytokines and immune cells related to immunopathology were observed. Transcriptome analysis revealed the genetic diversity of immune responses induced by the vaccine.

Interpretation: In a population aged 18-59 years in this trial, this inactivated SARS-CoV-2 vaccine was safe and immunogenic.

Trial Registration: CTR20200943 and NCT04412538.
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http://dx.doi.org/10.1016/j.vaccine.2021.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040531PMC
May 2021

Effects of Supplementary Selenium and Vitamin E on the Growth Performance, Antioxidant Enzyme Activity, and Gene Expression of Sea Cucumber Apostichopus japonicus.

Biol Trace Elem Res 2021 Apr 16. Epub 2021 Apr 16.

Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, Shandong, China.

A 60-day feeding experiment was conducted to evaluate the effects of single selenomethionine (Se) and its mixture with vitamin E (VE) on the growth, antioxidant enzyme activities, and gene expression of juvenile sea cucumber Apostichopus japonicus. The design of the experiment contained two factors and 5 × 2 levels by means of adding various levels of Se and VE in the feed, i.e., combination of 0, 0.3, 0.6, 0.9, or 1.2 mg Se kg and 0 or 200 mg VE kg. The results revealed that the specific growth rate and weight gain rate were the highest in the group with 0.3 mg Se kg and 200 mg VE kg, followed by the group with 0.6 mg Se kg without VE. Se significantly improved the activities of amylase and protease with VE also imposed positive effect on the amylase activity. Glutathione peroxidase (GPX) activity was highest in the group with 1.2 mg Se kg and lowest with the basal diet. The activity of catalase (CAT) was increased while glutathione reductase (GR) activity was decreased in response to the addition of Se. No significant interactive effects of Se and VE on the enzyme activities were found except superoxide dismutase (SOD) activity. While relative expressions of GPX, CAT, and SOD genes were significantly responsive to the addition of dietary Se, VE significantly promoted the gene expression of SOD. The results suggested that Se and VE might have beneficial effects on the growth and antioxidant responses of A. japonicus.
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http://dx.doi.org/10.1007/s12011-021-02602-8DOI Listing
April 2021

Circ_0093887 upregulates CCND2 and SUCNR1 to inhibit the ox-LDL-induced endothelial dysfunction in atherosclerosis by functioning as a miR-876-3p sponge.

Clin Exp Pharmacol Physiol 2021 Apr 12. Epub 2021 Apr 12.

Department of Cardiology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

Circular RNAs (circRNAs) are widely expressed in mammals and act as regulatory targets in the atherogenesis. The objective of this study was to research the biological role and molecular mechanism of circ_0093887 in oxidized low-density lipoprotein (ox-LDL)-induced atherosclerosis (AS) of human aortic endothelial cells (HAECs). Cell viability detection was performed by CCK-8 assay. Inflammatory molecules were examined using ELISA. Flow cytometry was used to measure cell-cycle progression and cell apoptotic rate. Caspase 3 activity was determined using caspase 3 activity assay. The expression levels of circ_0093887, miR-876-3p, CCND2 and SUCNR1 were assayed by quantitative real-time polymerase chain reaction (qRT-PCR). Dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were used for the target analysis. EdU assay, wound healing assay/transwell assay and tube formation assay were, respectively, used to assess the effects of circ_0093887/miR-876-3p axis on cell proliferation, migration and tube formation. Oxidized low-density lipoprotein inhibited cell viability and cell-cycle progression but induced the inflammatory response and cell apoptosis. Circ_0093887 was downregulated and miR-876-3p was upregulated in AS patients and ox-LDL-treated HAECs. Functionally, the overexpression of circ_0093887 abrogated the cell injury of HAEC exposed to ox-LDL. For the functional mechanism, we found that circ_0093887 was a sponge for miR-876-3p and miR-876 targeted CCND2 or SUCNR1. The reverted experiment indicated that the function of circ_0093887 was achieved by sponging miR-876-3p. Meanwhile, miR-876-3p inhibitor relieved the inhibitory regulation of circ_0093887 knockdown in cell proliferation, migration and tube formation. Downregulation of miR-876-3p also alleviated the ox-LDL-induced cell injury by upregulating the expression of CCND2 or SUCNR1. Furthermore, circ_0093887 was validated to regulate the levels of CCND2 and SUCNR1 via the sponge effect on miR-876-3p. The protective effects of circ_0093887 on HAECs from ox-LDL were also ​alleviated by repressing the CCND2 and SUCNR1 levels. These findings suggested that circ_0093887 protected HAEC against the ox-LDL-induced inflammatory and apoptotic damages by targeting the miR-876-3p/CCND2 or miR-876/SUCNRA axis. Circ_0093887 could act as a potential therapeutic biomarker for AS patients.
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http://dx.doi.org/10.1111/1440-1681.13504DOI Listing
April 2021

The role of multiple SARS-CoV-2 viral antigens in a vaccine-induced integrated immune response.

Vaccine 2021 04 22;39(18):2500-2503. Epub 2021 Mar 22.

Institute of Medical Biology, Chinese Academy of Medicine Sciences & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development for Severe Infectious Diseases, Kunming 650118, China. Electronic address:

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http://dx.doi.org/10.1016/j.vaccine.2021.03.067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983451PMC
April 2021

In Vivo Three-Photon Imaging of Lipids using Ultrabright Fluorogens with Aggregation-Induced Emission.

Adv Mater 2021 Mar 11;33(11):e2007490. Epub 2021 Feb 11.

Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117585, Singapore.

Fluorescent probes capable of in vivo lipids labeling are highly desirable for studying lipid-accumulation-related metabolic diseases, such as nonalcoholic fatty liver disease, type-2 diabetes, and atherosclerosis. However, most of the current lipid-specific fluorophores cannot be used for in vivo labeling due to their strong hydrophobicity. Herein, organic dots from bright luminogens with aggregation-induced emission (AIEgen) are developed for in vivo labeling and three-photon fluorescence imaging of lipid-rich tissues, such as fatty liver, atherosclerotic plaques in brain vasculatures, and carotid arteries. The organic dots show excellent stability in an aqueous medium with high targeting specificity to lipids and strong three-photon fluorescence in the far-red/near-infrared (NIR) region under NIR-II laser excitation, which enables efficient in vivo labeling and imaging of lipids in deep tissues. The study will inspire the development of lipid-targeting fluorophores for in vivo applications.
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http://dx.doi.org/10.1002/adma.202007490DOI Listing
March 2021

Nanostructure of Functional Larotaxel Liposomes Decorated with Guanine-Rich Quadruplex Nucleotide-Lipid Derivative for Treatment of Resistant Breast Cancer.

Small 2021 Apr 31;17(13):e2007391. Epub 2021 Jan 31.

State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.

Breast cancer is the most common malignant disease in women all over the world and its chemotherapy outcome is restricted by multidrug resistance. Here, a nanostructure by functional larotaxel liposomes decorated with guanine-rich quadruplex nucleotide-lipid derivative for treatment of resistant breast cancer is developed. The studies are performed on the resistant breast cancer cells and the cancer-bearing mice. The nucleotide-lipid derivative (DSPE-PEG -C -GT28nt) is synthesized by introducing a hydrophobic hexyl linkage between GT-28nt (containing 17 guanines and 11 thymidines) and DSPE-PEG -NHS, and is incorporated on the functional larotaxel liposomes for specific binding with nucleolin receptor on the resistant cancer cells. The studies demonstrate that the liposomes had long circulatory effect, targeted capability, and significant anticancer efficacy in resistant cancer-bearing mice. The studies further reveal their action mechanism, consisting of blocking depolymerization of microtubules, arresting cell cycle, blocking JAK-STAT signaling pathway, and inhibiting activity of antiapoptotic proteins. In conclusion, the functional larotaxel liposomes can be used for effective treatment of drug-resistant breast cancer, and this study also offers a novel targeted nanomedicine based on nucleotide-lipid derivative.
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http://dx.doi.org/10.1002/smll.202007391DOI Listing
April 2021

EgMIXTA1, a MYB-Type Transcription Factor, Promotes Cuticular Wax Formation in Leaves.

Front Plant Sci 2020 22;11:524947. Epub 2020 Oct 22.

Key Laboratory of Saline-alkali Vegetation Ecology Restoration, Ministry of Education, College of Life Science, Northeast Forestry University, Harbin, China.

In the aerial plant organs, cuticular wax forms a hydrophobic layer that can protect cells from dehydration, repel pathogen attacks, and prevent organ fusion during development. The gene encodes an MYB-like transcription factor, which is associated with epicuticular wax biosynthesis to increase the wax load on the surface of leaves. In this study, the -homologous gene was functionally characterized in the . was ubiquitously, but highly, expressed in leaves and buds. We identified the MIXTA homolog and developed the plants for overexpression. EgMIXTA1-overexpressing plants had more wax crystal deposition on the leaf surface compared to wild-type and considerably more overall cuticular wax. In the leaves of the overexpression line, the cuticular transpiration occurred more slowly than in those of non-transgenic plants. Analysis of gene expression indicated that several genes, such as , , , , , and , which are known to be involved in wax biosynthesis, were induced by EgMIXTA1-overexpression lines. Expression of another gene, , encoding a transcription factor that stimulates the production of cutin, was also significantly higher in the overexpressors than in wild-type. However, the expression of a lipid-related gene, , did not change relative to the wild-type. These results suggest that is involved in the biosynthesis of cuticular waxes.
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http://dx.doi.org/10.3389/fpls.2020.524947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641950PMC
October 2020

Vitamin D Decreases Plasma Trimethylamine-N-oxide Level in Mice by Regulating Gut Microbiota.

Biomed Res Int 2020 5;2020:9896743. Epub 2020 Oct 5.

The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

As a metabolite generated by gut microbiota, trimethylamine-N-oxide (TMAO) has been proven to promote atherosclerosis and is a novel potential risk factor for cardiovascular disease (CVD). The objective of this study was to examine whether regulating gut microbiota by vitamin D supplementation could reduce the plasma TMAO level in mice. For 16 weeks, C57BL/6J mice were fed a chow (C) or high-choline diet (HC) without or with supplementation of vitamin D (CD3 and HCD3) or a high-choline diet with vitamin D supplementation and antibiotics (HCD3A). The results indicate that the HC group exhibited higher plasma trimethylamine (TMA) and TMAO levels, lower richness of gut microbiota, and significantly increased Firmicutes and decreased Bacteroidetes as compared with group C. Vitamin D supplementation significantly reduced plasma TMA and TMAO levels in mice fed a high-choline diet. Furthermore, gut microbiota composition was regulated, and the Firmicutes/Bacteroidetes ratio was reduced by vitamin D. Spearman correlation analysis indicated that and were negatively correlated with plasma TMAO in the HC and HCD3 groups. Our study provides a novel avenue for the prevention and treatment of CVD with vitamin D.
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http://dx.doi.org/10.1155/2020/9896743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558778PMC
May 2021

Experiential learning for children's dental anxiety: a cluster randomized trial.

BMC Oral Health 2020 07 31;20(1):216. Epub 2020 Jul 31.

Shenzhen Nanshan Maternal and Child Health Care Hospital, Shenzhen, 518054, China.

Background: Dental anxiety (DA) has an impact on the quality of dental treatment and may have long-lasting implications for children. A recent study introducing experiential learning (EL) into children's oral health promotion resulted in better oral hygiene. The purpose of the study is to evaluate whether EL can reduce children's DA.

Methods: In September 2018, we recruited 988 children aged 7-8 years from 24 classes to participate in a cluster-randomized trial. Classes were randomly assigned to EL (in which children received a lively presentation on oral health and participated in a role play in a simulated dental clinic in the classroom) or the Tell-Show-Do (TSD) group (in which children received a conventional TSD behavior management). The primary outcome was the prevalence of high DA after the procedure of pit and fissure sealant (PFS), assessed by a modified Children's Fear Survey Schedule-Dental Subscale. Secondary outcomes were changes in blood pressures (BP) and pulse rates (PR) before and after the PFS procedure. The intervention effects were estimated by means of mixed effect models, which included covariates of gender and school (and baseline value for BP and PR only), and a random cluster effect.

Results: In 396 children of the EL group who received the PFS treatment, the prevalence of high DA (score ≥ 38) was 18.5%, compared with 24.3% in 391 children of the TSD group (OR = 0.65; 95% confidence interval, 0.46-0.93; P = 0.019). The increases in BP and PR after the PFS were also significantly less in the EL group.

Conclusion: School-based experiential learning intervention before a dental visit is feasible and effective in reducing children's dental anxiety during PFS.

Trial Registration: The trial was registered in Chinese Clinical Trial Registry on 5 January 2020 (No.: ChiCTR2000028878 , retrospectively registered).
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http://dx.doi.org/10.1186/s12903-020-01204-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395402PMC
July 2020

The Mutation of the Genes Related to Neurovirulence in HSV-2 Produces an Attenuated Phenotype in Mice.

Viruses 2020 07 17;12(7). Epub 2020 Jul 17.

Institute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming 650118, China.

HSV-2 (Herpes simplex virus type 2) is a critical viral agent that mainly causes genital herpes and life-long latent infection in the dorsal root ganglia. Gene modification via CRISPR/Cas9 Clustered regularly interspaced short palindromic repeat sequences/CRISPR associated 9) was used here to construct HSV-2 mutant strains through the deletion of fragments of the (Repeat Long element 1) and/or (Latency-associated Transcript) genes. The HSV-2 mutant strains HSV-2 and HSV-2 present different biological properties. The proliferation of HSV-2 in nerve cells was decreased significantly, and the plaques induced by HSV-2 in Vero cells were smaller than those induced by HSV-2 mutant and wild-type strains. The observation of mice infected with these two mutants compared to mice infected with the wild-type strain indicated that the mutant HSV-2 has an attenuated phenotype with reduced pathogenicity during both acute and latent infections and induces a stronger specific immune response than the wild-type strain, whereas the attenuation effect was not found in mice infected with the HSV-2 mutant containing the gene deletion. However, the simultaneous mutation of both the and genes did not completely restrict viral proliferation in nerve cells, indicating that multiple HSV genes are involved in viral replication in the neural system. This work suggests that the HSV-2 genes RL1 and/or LAT might be involved in the virulence mechanisms in mouse infections.
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http://dx.doi.org/10.3390/v12070770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412103PMC
July 2020

Butyrate mitigates TNF-α-induced attachment of monocytes to endothelial cells.

J Bioenerg Biomembr 2020 08 25;52(4):247-256. Epub 2020 Jun 25.

Department of Cardiology, the Fourth Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.

A major cause of late-life health complications is the cardiovascular disease known as atherosclerosis. The process of atherogenesis is marked by endothelial cell dysfunction, the development of atherogenic lesions, and plaque buildup on the intima of the arterial endothelium. This process is fueled primarily by the adhesion of monocytes to endothelial cells via the actions of the cellular adhesion molecules VCAM-1 and E-selectin. When expressed at their basal levels, these molecules are vital to various cellular processes, but when in a state of overproduction, they drive the progression of atherosclerosis by recruiting monocytes to roll along and adhere to the endothelium. TNF-α is theorized to play a causal role in the development of atherosclerosis, but the exact mechanism remains poorly understood. This cytokine is known to upregulate various factors associated with inflammation and oxidative stress, both of which greatly contribute to endothelial dysfunction and atherogenesis. In the present study, we aimed to elucidate the effect of butyrate on these atherogenic processes. Previously not known to have atheroprotective effects, this natural compound shows promise as a treatment for atherosclerosis. In the present study, we found butyrate to exert various anti-inflammatory and downstream regulatory effects. Namely, butyrate ameliorated the overproduction of adhesion molecules, including VCAM-1 and E-selectin, reduced oxidative stress by reducing the levels of ROS and 4-HNE, and suppressed inflammation via inhibition of MCP-1 and IL-8. Additionally, butyrate rescued the reduced expression of the protective factor KLF2, which was mediated through the ERK5 pathway. Thus, butyrate may serve as a promising treatment against atherosclerosis.
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http://dx.doi.org/10.1007/s10863-020-09841-9DOI Listing
August 2020

Distinct infection process of SARS-CoV-2 in human bronchial epithelial cell lines.

J Med Virol 2020 11 14;92(11):2830-2838. Epub 2020 Jul 14.

Institute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming, Yunnan, China.

Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leads to a series of clinical symptoms of respiratory and pulmonary inflammatory reactions via unknown pathologic mechanisms related to the viral infection process in tracheal or bronchial epithelial cells. Investigation of this viral infection in the human bronchial epithelial cell line (16HBE) suggests that SARS-CoV-2 can enter these cells through interaction between its membrane-localized S protein with the angiotensin-converting enzyme 2 molecule on the host cell membrane. Further observation indicates distinct viral replication with a dynamic and moderate increase, whereby viral replication does not lead to a specific cytopathic effect but maintains a continuous release of progeny virions from infected cells. Although messenger RNA expression of various innate immune signaling molecules is altered in the cells, transcription of interferons-α (IFN-α), IFN-β, and IFN-γ is unchanged. Furthermore, expression of some interleukins (IL) related to inflammatory reactions, such as IL-6, IL-2, and IL-8, is maintained at low levels, whereas that of ILs involved in immune regulation is upregulated. Interestingly, IL-22, an IL that functions mainly in tissue repair, shows very high expression. Collectively, these data suggest a distinct infection process for this virus in respiratory epithelial cells, which may be linked to its clinicopathological mechanism.
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http://dx.doi.org/10.1002/jmv.26200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323243PMC
November 2020

Step-wise immobilization of multi-enzymes by zirconium-based coordination polymer in situ self-assembly and specific absorption.

J Inorg Biochem 2020 07 4;208:111093. Epub 2020 May 4.

State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China. Electronic address:

The simple and quick method for co-immobilization of multiple enzymes with clear spatial distribution has presented great challenges for decades. Herein, Zr and 2-methylimidazole (2MIm) coordination polymers (CPs) were used to synthetize co-immobilized nanoreactor by a simple two-step procedure in aqueous environment. The CPs was first self-assembled in situ encapsulating glucose-6-phosphate dehydrogenase (G6PD) and then utilized coordination unsaturated metal sites on the surface of CPs to selectively adsorb hexahistidine-tagged α, β-unsaturated ketoreductase (his-tagged KRED). The obtained multi-enzymes system (G6PD@Zr-2MIm/KRED) was employed as an enzymatic reactor involving coenzymes regeneration. G6PD@Zr-2MIm/KRED still exhibited good repeatability and storage stability. The bi-enzymatic reactor could achieve more than 95% chalcone conversion ratio after 15 min and good tolerance at high temperature and different pH, retained about 70% and 80% of its initial activity after storage for 4 days and after 4 cycles, respectively. This step-wise enzyme immobilization method is easy to operate and can be used to prepare multi-enzyme systems with clear spatial distribution of the biocatalysts and allowing the coenzymes regeneration.
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http://dx.doi.org/10.1016/j.jinorgbio.2020.111093DOI Listing
July 2020

Specific Near-Infrared Probe for Ultrafast Imaging of Lysosomal β-Galactosidase in Ovarian Cancer Cells.

Anal Chem 2020 04 3;92(8):5772-5779. Epub 2020 Apr 3.

Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117576, Singapore.

Reactivity based fluorescent probes have been widely investigated as a powerful and noninvasive tool for disease diagnosis in recent years. β-Galactosidase (β-gal), one of the typical lysosomal glycosidases, is reported to be a vital biomarker overexpressed in primary ovarian cancer cells. Fluorescent probes with excellent performance for endogenous β-gal detection offer a unique option for visualization and diagnosis of primary ovarian cancer cells. Herein, a near-infrared fluorescent probe Lyso-Gal with lysosome-targeting ability was developed for lysosomal β-gal detection and imaging in ovarian cancer cells (SKOV-3 cells). Lyso-Gal exhibits weak fluorescence in aqueous solution but emits bright NIR fluorescence at 725 nm after incubation with β-gal. Highly selective imaging of ovarian cancer cells has been achieved upon incubation with Lyso-Gal for only 1 min. The detection time is extremely short. In comparison with a similar hemicyanine probe, Hx-Gal, without lysosome-targeting ability, Lyso-Gal realizes endogenous β-gal visualization in lysosomes and shows brighter fluorescence than Hx-Gal in SKOV-3 cells. This work demonstrates the potential of Lyso-Gal for detection of primary ovarian cancer cells by using β-gal as the biomarker.
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http://dx.doi.org/10.1021/acs.analchem.9b05121DOI Listing
April 2020

Investigating COD and Nitrate-Nitrogen Flow and Distribution Variations in the MUCT Process Using ORP as a Control Parameter.

ACS Omega 2020 Mar 28;5(9):4576-4587. Epub 2020 Feb 28.

College of Civil Engineering and Architecture, Changchun Sci-Tech University, Changchun City 130600, Jilin Province, The People's Republic of China.

This study aimed to reveal the flow and distribution lows of chemical oxygen demand (COD) and nitrate-nitrogen under different main anoxic stage oxidation-reduction potential (ORP) conditions based on the analysis of material balance in each reaction stage of the modified university of cape town (MUCT) process, combined with the biochemical reaction principles of activated sludge. The rule of the carbon source saving effect was also clarified. The study adopted the programmable logic controller automatic control system and the feedback control structure using the inner circulation flow of nitrate as the controlled variable. The ORP setting values of control parameters were -140, -125, -110, -95, -70, and -60 mV, respectively. The results showed that when the ORP setting value was -95 mV, COD distribution ratios of phosphorus-accumulating bacteria reached the highest in the anaerobic stage and preanoxic stage, with the values of 51.74 and 7.70%, respectively. The COD was distributed between heterotrophic bacteria and denitrifying bacteria in the main anoxic stage, and the distribution ratios were 4.40 and 7.19%, respectively, when the ORP setting value was -95 mV. The study also showed the distribution of nitrate-nitrogen between denitrifying bacteria and denitrifying phosphorus-accumulating bacteria in the main anoxic stage, and when ORP increased from -140 to -60 mV, the distribution ratios of denitrifying phosphate-accumulating bacteria increased from 76.46 to 86.32%. When there was no denitrification and phosphorus absorption, the acetic acid dosage increased from 20.33 g/d at -140 mV to 24.76 g/d at -95 mV, and the carbon source saving rate increased from 23.19 to 26.56% under similar conditions. Therefore, in the MUCT process, the regulation of ORP changed the material flow direction and mass quality distribution of COD and nitrate nitrogen. When ORP set value was -95 mV, COD and nitrate-nitrogen got the best distribution and the carbon source saving effect was the most significant.
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http://dx.doi.org/10.1021/acsomega.9b04016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066563PMC
March 2020

Biodegradable polymer-coated versus durable polymer-coated sirolimus-eluting stents: the final 5-year outcomes of the I-LOVE-IT 2 trial.

EuroIntervention 2021 Apr 2;16(18):e1518-e1526. Epub 2021 Apr 2.

General Hospital of Northern Theater Command, Shenyang, China.

Aims: This analysis presents the final five-year results of the I-LOVE-IT 2 trial, a non-inferiority study comparing a biodegradable polymer (BP) sirolimus-eluting stent (SES) with a durable polymer (DP) SES in patients with coronary artery disease.

Methods And Results: Overall, 2,737 Chinese patients eligible for coronary stenting were treated with BP-SES or DP-SES in a 2:1 ratio. Patients who were randomised to the BP-SES group were additionally re-randomised to receive either six-month or 12-month dual antiplatelet therapy (DAPT) in a 1:1 ratio. The primary endpoint was 12-month target lesion failure (TLF: cardiac death, target vessel myocardial infarction (MI), or clinically indicated target lesion revascularisation). At five years, the overall follow-up rate was 90.8%, and the cumulative incidence of TLF as the primary endpoint was similar between BP-SES and DP-SES (hazard ratio [HR] 1.01, 95% confidence interval [CI]: 0.79 to 1.28), as was that for the patient-oriented composite endpoint (PoCE: all-cause death, all MI and any revascularisation) (HR 1.03, 95% CI: 0.86 to 1.23), or definite/probable stent thrombosis (ST) (HR 0.91, 95% CI: 0.70 to 1.77). Cumulative events were also similar between the six-month DAPT and 12-month DAPT groups after BP-SES implantation.

Conclusions: I-LOVE-IT 2 showed that the five-year safety and efficacy of BP-SES and DP-SES were similar, as were those between six months and 12 months of DAPT after BP-SES implantation.
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http://dx.doi.org/10.4244/EIJ-D-19-00865DOI Listing
April 2021

Study of the minor fraction of virgin olive oil by a multi-class GC-MS approach: Comprehensive quantitative characterization and varietal discrimination potential.

Food Res Int 2019 11 26;125:108649. Epub 2019 Aug 26.

Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Ave. Fuentenueva s/n, E-18071 Granada, Spain. Electronic address:

For the first time, a multi-class GC-MS method was applied to perform the quantitative-profiling of the minor fraction of VOOs (considering >40 compounds) in a single run. This comprehensive methodology has demonstrated a remarkable profiling ability on five groups of compounds (phenolic and triterpenic compounds, tocopherols, sterols and free fatty acids) with wide range of polarities/volatilities and chemical entities. After the complete analytical validation of the method, 32 VOO samples from eight different cultivars (some of them very scarcely studied before) were analyzed and the quantitative results were subjected to both non-supervised and supervised multivariate statistics for testing the capability of the determined VOO minor compounds to discriminate the varietal origin of the samples. Typical compositional profiles were defined for each cultivar and promising potential varietal markers were pointed out. The models built to discriminate Cayon and Maurino samples from the rest exhibited the best quality parameters. The relative levels of tocopherols together with characteristic concentration of luteolin, β-sitosterol and tyrosol were, for instance, the most specific features of Cayon VOOs.
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http://dx.doi.org/10.1016/j.foodres.2019.108649DOI Listing
November 2019

Longitudinal safety impacts of cooperative adaptive cruise control vehicle's degradation.

J Safety Res 2019 06 14;69:177-192. Epub 2019 Mar 14.

Jiangsu Key Laboratory of Urban ITS, Southeast University, Si Pai Lou #2, Nanjing 210096, China; Jiangsu Province Collaborative Innovation Center of Modern Urban Traffic Technologies, Southeast University, Si Pai Lou #2, Nanjing 210096, China; School of Transportation, Southeast University, Si Pai Lou #2, Nanjing 210096, China. Electronic address:

Introduction: The adaptive cruise control (ACC) and cooperative ACC (CACC) systems are critical parts of self-driving vehicles. The ACC vehicles detect front vehicle' information via vehicle-mounted sensors and make longitudinal reactions automatically, while CACC vehicles enhance the performance by vehicle-to-vehicle (V2V) wireless communication. However, CACC vehicles may abruptly degrade to ACC mode in reality due to various reasons, including communication failures, driver manipulations, and cyber-attacks. The sudden degradation will definitely bring negative influences on safety.

Method: This study quantitatively evaluated the longitudinal safety impacts of vehicles' degradation in a CACC fleet based on microscopic simulations. The realistic CACC and ACC models proposed by the California Partners for Advanced Transit and Highways (PATH) were used for simulation experiments. The time integrated time-to-collision (TIT) was measured to quantify the collision risks. Extensive simulations were conducted via a fleet of 10 CACC vehicles and speed profiles of vehicles in different scenarios were compared. Key factors, including the leading vehicle's deceleration rate, the number of vehicles between degraded vehicles (NVDVs), threshold of TTC, and visibility were also examined via sensitivity analyses.

Results And Conclusions: Simulation results indicate that degradation has significant negative influences on longitudinal safety of degraded vehicles under the driving state of deceleration. Degradation at middle positions in a CACC fleet, such as fourth and fifth positions, is much safer than that at others. Moreover, nonadjacent degradation is much riskier than adjacent degradation at the front positions of a fleet. NVDVs can bring inverse impacts on safety with different degradation positions. Speed profiles imply that the hysteresis of degraded vehicles' speed control is the major reason for high collision risks. Practical applications: Appropriately, hierarchical countermeasures have the potential to reduce the longitudinal safety impacts of degradation. Findings of this study can contribute to determining the applicable length of CACC fleets.
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http://dx.doi.org/10.1016/j.jsr.2019.03.002DOI Listing
June 2019

Marek's Disease Virus Disables the ATR-Chk1 Pathway by Activating STAT3.

J Virol 2019 05 17;93(9). Epub 2019 Apr 17.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China

Oncogenic virus replication often leads to genomic instability, causing DNA damage and inducing the DNA damage response (DDR) pathway. The DDR pathway is a cellular pathway that senses DNA damage and regulates the cell cycle to maintain genomic stability. Therefore, the DDR pathway is critical for the viral lifecycle and tumorigenesis. Marek's disease virus (MDV), an alphaherpesvirus that causes lymphoma in chickens, has been shown to induce DNA damage in infected cells. However, the interaction between MDV and the host DDR is unclear. In this study, we observed that MDV infection causes DNA strand breakage in chicken fibroblast (CEF) cells along with an increase in the DNA damage markers p53 and p21. Interestingly, we showed that phosphorylation of STAT3 was increased during MDV infection, concomitantly with a decrease of Chk1 phosphorylation. In addition, we found that MDV infection was enhanced by VE-821, an ATR-specific inhibitor, but attenuated by hydroxyurea, an ATR activator. Moreover, inhibition of STAT3 phosphorylation by Stattic eliminates the ability of MDV to inhibit Chk1 phosphorylation. Finally, we showed that MDV replication was decreased by Stattic treatment. Taken together, these results suggest that MDV disables the ATR-Chk1 pathway through STAT3 activation to benefit its replication. MDV is used as a biomedical model to study virus-induced lymphoma due to the similar genomic structures and physiological characteristics of MDV and human herpesviruses. Upon infection, MDV induces DNA damage, which may activate the DDR pathway. The DDR pathway has a dual impact on viruses because it manipulates repair and recombination factors to facilitate viral replication and also initiates antiviral action by regulating other signaling pathways. Many DNA viruses evolve to manipulate the DDR pathway to promote virus replication. In this study, we identified a mechanism used by MDV to inhibit ATR-Chk1 pathways. ATR is a cellular kinase that responds to broken single-stranded DNA, which has been less studied in MDV infection. Our results suggest that MDV infection activates STAT3 to disable the ATR-Chk1 pathway, which is conducive to viral replication. This finding provides new insight into the role of STAT3 in interrupting the ATR-Chk1 pathway during MDV replication.
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http://dx.doi.org/10.1128/JVI.02290-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475774PMC
May 2019

Improvement of the Fourier Transform Near Infrared Method to Evaluate Extra Virgin Olive Oils by Analyzing 1,2-Diacylglycerols and 1,3-Diacylglycerols and Adding Unesterified Fatty Acids.

Lipids 2018 11 16;53(11-12):1097-1112. Epub 2019 Jan 16.

Guelph Food Research Center, Agriculture and Agri-Food Canada, Guelph, 10 Eringate Walk, Cambridge, Ontario, N1S 4Y6, Canada (Retired).

Extra virgin olive oils (EVOO) command higher prices because they contain health-promoting nutrients and desirable sensory characteristics. Many targeted methods have limited success in determining olive oil authenticity. Therefore, attention has been paid to rapid spectroscopic methods that provide the composition of multiple components. A Fourier transform near infrared (FT-NIR) method was reported that identified five major fatty acids and volatiles in EVOO, plus four models that identify common adulterants and their content. However, it did not include diacylglycerol (DAG) and unesterified fatty acids (FFA) known to be associated with freshness of the oil. The newly improved FT-NIR method now includes 1,2-DAG and 1,3-DAG models based on the DAG isomer content in freshly prepared EVOO, and a FFA model based on quantitative addition of oleic acid. The new FT-NIR method was used to reassess previously used EVOO products to evaluate their freshness. Based on these results and review of the published data, we propose several revisions to the EVOO regulation: limit FFA to ≤0.5%, include 1,2-DAG and 1,3-DAG in standard, place no limit on 1,2-DAG because it characterizes the oils, set the 1,3-DAG content to ≤1.0%, and lower the content of 18:2n-6 to 1.5%.
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http://dx.doi.org/10.1002/lipd.12113DOI Listing
November 2018

Effects of the presence of nanoscale zero-valent iron on the degradation of polychlorinated biphenyls and total organic carbon by sediment microbial fuel cell.

Sci Total Environ 2019 Mar 22;656:39-44. Epub 2018 Nov 22.

School of Resources and Materials, Northeastern University at Qinhuangdao, Qinhuangdao 066004, China.

The degradation of polychlorinated biphenyls (PCBs) and total organic carbon (TOC) by sediment microbial fuel cell (SMFC) with/without nanoscale zero-valent iron (NZVI) addition was investigated. It was found that the combined application led to the highest removal efficiencies of PCBs (37.55 ± 1.11%) and TOC (49.72 ± 1.54%) in all circumstances and produced a higher power density (108.89 mW/m) and a corresponding lower internal resistance (264 Ω) than operation employing SMFC only. The TOC removal efficiency and the total production of electricity were linear. High-throughput sequencing of anodic microbial communities indicated that the electrode participation can increase the abundance of electrogenic bacteria (Geobacter and Pseudomonas) and the NZVI addition can reduce the oxidation reduction potential of the system and therefore enrich some bacteria (Longilinea and Desulfofustis) beneficial to the degradation of organic matter.
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http://dx.doi.org/10.1016/j.scitotenv.2018.11.326DOI Listing
March 2019

Safety and efficacy of zotarolimus-eluting stents in the treatment of diabetic coronary lesions in Chinese patients: The RESOLUTE-DIABETES CHINA Study.

J Diabetes 2019 Mar 7;11(3):204-213. Epub 2018 Sep 7.

Department of Cardiology, Zhejiang Hospital, Hangzhou, China.

Background: The RESOLUTE-DIABETES CHINA study was specifically designed to investigate the safety and efficacy of Resolute zotarolimus-eluting stents (ZES; Medtronic, Santa Rosa, CA, USA) in the treatment of diabetic coronary lesions in the Chinese population.

Methods: In all, 945 patients with de novo native coronary lesions and type 2 diabetes mellitus were recruited at 32 cardiac centers across the Chinese mainland and were implanted with Resolute ZES. The primary endpoint was target vessel failure (TVF); secondary endpoints were clinical outcomes, namely all-cause death, stroke, bleeding, target lesion revascularization (TLR), target vessel revascularization (TVR), non-TVR, and stent thrombosis (ST). The follow-up period for all endpoints was 12 months after the procedure.

Results: In all, 933 patients (98.73%) had clinical follow-up at 12 months. The rate of TVF was 11.60%, whereas the rate of occurrence of secondary endpoints was 5.47%, with four patients (0.43%) having subacute or late ST. There were no significant differences in TVF rates comparing patients with different HbA1c levels or receiving different glucose control treatments (all P > 0.05). Patients with multivessel lesions had higher TVF rates (95% confidence intervals) than those with single-vessel lesions (16.76% [12.10%-22.97%) vs 9.72% [7.79%-12.11%], respectively; P = 0.006). There were no significant differences in TVF rates in patients with or without small vessels, bifurcated lesions, or chronic total occlusions (all P > 0.05). [Correction added on 17 January 2019, after first online publication: in the second sentence of Results section, "TLF" was changed to "TVF".].

Conclusions: Resolute ZES may perform well in the Chinese diabetic population, especially in those with poor glucose control, complex lesions, and certain unfavorable clinical features. Further studies are needed to determine why ZES perform well in this population.
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http://dx.doi.org/10.1111/1753-0407.12832DOI Listing
March 2019

Oleocanthal-rich extra virgin olive oil demonstrates acute anti-platelet effects in healthy men in a randomized trial.

J Funct Foods 2017 Sep 3;36:84-93. Epub 2017 Jul 3.

Department of Nutrition, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA.

The phenolic profiles of extra virgin olive oils (EVOOs) may influence their cardiovascular benefits. In a randomized crossover of acute EVOO intake on platelet function, participants (n=9) consumed 40 mL of EVOO weekly. EVOOs were matched for total phenolic content and were either tyrosol-poor with 1:2 oleacein/oleocanthal (D20.5), or 2:1 oleacein/oleocanthal (D22), or predominantly tyrosol (D20). Ibuprofen provided a platelet inhibition control. Blood was collected pre- and 2 hr post-EVOO intake. D20.5 and D22 reduced 1 µg/mL collagen-stimulated maximum platelet aggregation (Pmax), with effects best correlated to oleocanthal intake (R=0.56, =0.002). Total phenolic intake was independently correlated to eicosanoid production inhibition, suggesting that cyclooxygenase blockade was not responsible for the Pmax inhibition. Five participants exhibited >25% ΔPmax declines with D20.5 and D22 intake and plasma metabolomic profiles discriminated subjects by oil responsivity. Platelet responses to acute EVOO intake are associated with oil phenolic composition and may be influenced by diet.
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http://dx.doi.org/10.1016/j.jff.2017.06.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995573PMC
September 2017

Deep insight into the minor fraction of virgin olive oil by using LC-MS and GC-MS multi-class methodologies.

Food Chem 2018 Sep 11;261:184-193. Epub 2018 Apr 11.

Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Ave. Fuentenueva s/n, E-18071 Granada, Spain. Electronic address:

Several analytical methods are available to evaluate virgin olive oil (VOO) minor compounds; however, multi-class methodologies are yet rarely studied. Herewith, LC-MS and GC-MS platforms were used to develop two methods capable of simultaneously determine more than 40 compounds belonging to different VOO minor chemical classes within a single run. A non-selective and highly efficient liquid-liquid extraction protocol was optimized for VOO minor components isolation. The separation and detection conditions were adjusted for determining phenolic and triterpenic compounds, free fatty acids and tocopherols by LC-MS, plus sterols and hydrocarbons by GC-MS. Chromatographic analysis times were 31 and 50 min, respectively. A comparative assessment of both methods in terms of analytical performance, easiness, cost and adequacy to the analysis of each class was carried out. The emergence of this kind of multi-class analytical methodologies greatly increases throughput and reduces cost, while avoiding the complexity and redundancy of single-chemical class determinations.
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http://dx.doi.org/10.1016/j.foodchem.2018.04.006DOI Listing
September 2018

Comparison between two biodegradable polymer-based sirolimus-eluting stents with differing drug elution and polymer absorption kinetics: two-year clinical outcomes of the PANDA III trial.

EuroIntervention 2018 Oct 12;14(9):e1029-e1037. Epub 2018 Oct 12.

Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing, China.

Aims: In the PANDA III trial, the novel poly-lactide-co-glycolide polymer-based BuMA sirolimus-eluting stent (SES) was non-inferior to the polylactide polymer-based Excel SES for the primary endpoint of one-year target lesion failure (TLF), with a lower incidence of stent thrombosis. We sought to investigate whether the effectiveness profile of BuMA SES, with more rapid drug elution and polymer absorption kinetics, would persist at two years.

Methods And Results: A total of 2,348 patients (mean age, 61.2±10.6 years; 24.3% diabetics; 31.2% with acute myocardial infarction within one month) were randomly assigned to receive either BuMA SES (n=1,174) or Excel SES (n=1,174) in the "all-comer" PANDA III trial. Two-year clinical follow-up was available for 2,262 (96.3%) patients. The incidence of TLF and the patient-oriented composite endpoint (PoCE) was low and similar between the BuMA and Excel groups (7.4% vs. 6.9%, p=0.67, and 13.1% vs. 10.9%, p=0.11, respectively). The rate of any revascularisation was significantly higher with the BuMA SES (6.8% vs. 4.6%, p=0.03). Definite and probable thrombosis occurred in 0.7% and 1.4% of patients in the BuMA and Excel groups, respectively (p=0.10).

Conclusions: Two-year rates of TLF and PoCE events were low and similar between the two biodegradable polymer-based SES.
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http://dx.doi.org/10.4244/EIJ-D-17-00946DOI Listing
October 2018

LncRNA BANCR facilitates vascular smooth muscle cell proliferation and migration through JNK pathway.

Oncotarget 2017 Dec 7;8(70):114568-114575. Epub 2017 Oct 7.

Department of Cardiology, The Fourth Hospital of Harbin Medical University, Harbin, China.

Deregulated migration and proliferation of vascular smooth muscle cells (VSMCs) acts a crucial role in the pathogenesis of many cardiovascular diseases such as atherosclerosis, coronary heart disease and hypertension. Long noncoding RNAs (lncRNAs) play crucial functional roles in a lot of biological processes such as cell development, cell proliferation, differentiation and invasion. In our study, we demonstrated that the BANCR expression level was upregulated in the atherosclerotic plaques tissues compared to in the normal vessels tissues. TNF-α could emhance the VSMCs proliferation. The expression level of BANCR and p-JNK were upregulated and activated in the proliferating VSMCs. Overexpression of BANCR enhanced VSMCs proliferation and migration. Elevated expression of BANCR induced JNK activation, which can be decreased by the specific JNK inhibitor SP600125. We demonstrated that ectopic expression of BANCR increased the VSMCs proliferation and migration through activating JNK pathway. These data suggested that lncRNA BANCR acts a crucial role in the regulating VSMCs proliferation and migration partly by activating the JNK pathway.
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http://dx.doi.org/10.18632/oncotarget.21603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777714PMC
December 2017

α-Solanine as potential therapeutic target in pulmonary artery hypertension.

J Hypertens 2017 12;35(12):2377-2379

aDepartment of Cardiology, Yanbian University Hospital, Yanji, Jilin, China bDepartment of Cardiology, Gifu Prefectural, Tajimikenlitsu Hospital, Tajimi, Gifu Prefecture, Japan cDepartment of Cardiology, The Forth Hospital of Harbin Medical University, Harbin, Heilongjiang, China dDepartment of Internal Medicine, Kyung Hee University, Seoul, South Korea eInstitute of Innovation for the Future Society, Nagoya University Graduate School of Medicine, Nagoya, Aichi Prefecture, Japan.

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http://dx.doi.org/10.1097/HJH.0000000000001483DOI Listing
December 2017

Association study to evaluate TFPI gene in CAD in Han Chinese.

BMC Cardiovasc Disord 2017 07 17;17(1):188. Epub 2017 Jul 17.

Department of Human Population Genetics, Institute of Molecular Medicine, Peking University, Beijing, 100871, China.

Background: Tissue factor pathway inhibitor (TFPI) is the main physiological inhibitor of TF-induced blood coagulation process, and may play essential roles in the pathogenesis of major adverse cardiac events. This study was designed to determine whether the variation of TFPI was related with coronary artery disease (CAD) in the Han Chinese populations.

Methods: A total of 1271 patients with coronary atherosclerosis and 1287 normal individuals from northern China were enrolled in the present study. Four tagging single-nucleotide polymorphisms (SNPs) (rs7586970, rs6434222, rs10153820 and rs8176528) from TFPI were selected and genotyped by direct sequencing. And the genotypes of the above SNPs were determined in all these participants.

Results: In the populations from Beijing and Harbin, no significant case-control differences in the frequencies of TFPI polymorphism (rs10153820 and rs8176528) were observed between CAD patients and controls. Meanwhile, two SNPs of TFPI (rs7586970 and rs6434222) were found to be associated with CAD in both groups. In stratified analyses based on gender, smoking, hypertension, diabetes mellitus and hyperlipidemia, we further determined that the investigated genetic variations of the TFPI genes seemed to be related with diabetes mellitus in CAD patients.

Conclusions: Genetic variations of the TFPI genes seem to be related with CAD, which likely cooperate with metabolic risk factor (diabetes mellitus) and play critical roles in the pathogenesis of coronary artery disease.
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http://dx.doi.org/10.1186/s12872-017-0626-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514508PMC
July 2017

miRNA‑504 inhibits p53‑dependent vascular smooth muscle cell apoptosis and may prevent aneurysm formation.

Mol Med Rep 2017 Sep 28;16(3):2570-2578. Epub 2017 Jun 28.

Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150006, P.R. China.

Abdominal aortic aneurysm (AAA) is a common disease that is associated with the proliferation and apoptosis of vascular smooth muscle cells (VSMCs). VSMCs are regulated by microRNAs (miRNA). The aim of the present study was to identify miRNA sequences that regulate aortic SMCs during AAA. miRNA‑504 was identified using a miRNA PCR array and by reverse transcription‑quantitative polymerase chain reaction analysis, and its expression levels were observed to be downregulated in the aortic cells derived from patients with AAA when compared with controls. Transfection of SMCs with pMSCV‑miRNA‑504 vector was performed, and cell proliferation and the expression levels of proliferating cell nuclear antigen (PCNA), replication factor C subunit 4 (RFC4), B‑cell lymphoma‑2 (Bcl‑2) and caspase‑3/9 were measured by western blotting. The mechanisms underlying the effects of miRNA‑504 was then analyzed. The results demonstrated that overexpression of miRNA‑504 significantly upregulated the expression levels of PCNA, RFC4 and Bcl‑2, while caspase‑3/9 expression was significantly inhibited when compared with non‑targeting controls. In addition, miRNA‑504 overexpression was observed to promote the proliferation of SMCs. The expression level of the tumor suppressor, p53, which is known to be a direct target of miRNA‑504, was inhibited following transfection of SMCs with pMSCV‑miRNA‑504. In addition, the expression of the downstream targets of p53, p21 and Bcl‑like protein‑4, were significantly reduced following overexpression of miRNA‑504. These results revealed the anti‑apoptotic role of miRNA‑504 in SMCs derived from patients with AAA via direct targeting of p53.
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http://dx.doi.org/10.3892/mmr.2017.6873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548046PMC
September 2017