Publications by authors named "Yunjia Song"

21 Publications

  • Page 1 of 1

Compensatory role of endogenous sulfur dioxide in nitric oxide deficiency-induced hypertension.

Redox Biol 2021 Nov 18;48:102192. Epub 2021 Nov 18.

Department of Pediatrics, Peking University First Hospital, Beijing, China. Electronic address:

Objective: This study aimed to determine the communicational pattern of gaseous signaling molecules sulfur dioxide (SO) and nitric oxide (NO) between vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs), and elucidate the compensatory role and significance of endogenous SO in the development of hypertension due to NO deficiency.

Approach And Results: Blood pressure was monitored by the tail-cuff and implantable physiological signal telemetry in L-nitro-arginine methyl ester (l-NAME)-induced hypertensive mice, and structural alterations of mouse aortic vessels were detected by the elastic fiber staining method. l-NAME-treated mice showed decreased plasma NO levels, increased SO levels, vascular remodeling, and increased blood pressure, and application of l-aspartate-β-hydroxamate, which inhibits SO production, further aggravated vascular structural remodeling and increased blood pressure. Moreover, in a co-culture system of HAECs and HASMCs, NO from HAECs did not influence aspartate aminotransferase (AAT)1 protein expression but decreased AAT1 activity in HASMCs, thereby resulting in the inhibition of endogenous SO production. Furthermore, NO promoted S-nitrosylation of AAT1 protein in HASMCs and purified AAT1 protein. Liquid chromatography with tandem mass spectrometry showed that the Cys192 site of AAT1 purified protein was modified by S-nitrosylation. In contrast, dithiothreitol or C192S mutations in HASMCs blocked NO-induced AAT1 S-nitrosylation and restored AAT1 enzyme activity.

Conclusion: Endothelium-derived NO inhibits AAT activity by nitrosylating AAT1 at the Cys192 site and reduces SO production in HASMCs. Our findings suggest that SO acts as a compensatory defense system to antagonize vascular structural remodeling and hypertension when the endogenous NO pathway is disturbed.
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http://dx.doi.org/10.1016/j.redox.2021.102192DOI Listing
November 2021

Shenlijia Attenuates Doxorubicin-Induced Chronic Heart Failure by Inhibiting Cardiac Fibrosis.

Evid Based Complement Alternat Med 2021 16;2021:6659676. Epub 2021 Jul 16.

School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, China.

Application of the anticancer drug doxorubicin (DOX) is restricted due to its adverse, cardiotoxic side effects, which ultimately result in heart failure. Moreover, there are a limited number of chemical agents for the clinical prevention of DOX-induced cardiotoxicity. Based on the theories of traditional Chinese medicine (TCM) on chronic heart failure (CHF), Shenlijia (SLJ), a new TCM compound, has been developed to fulfill multiple functions, including improving cardiac function and inhibiting cardiac fibrosis. In the present study, the protective effects and molecular mechanisms of SLJ on DOX-induced CHF rats were investigated. The CHF rat model was induced by intraperitoneal injection of DOX for six weeks with the cumulative dose of 15 mg/kg. All rats were then randomly divided into the control, CHF, CHF + SLJ (3.0 g/kg per day), and CHF + captopril (3.8 mg/kg per day) groups and treated for further four weeks. Echocardiography and the assessment of hemodynamic parameters were performed to evaluate heart function. A protein chip was applied to identify proteins with diagnostic values that were differentially expressed following SLJ treatment. The data from these investigations showed that SLJ treatment significantly improved cardiac function by increasing the left ventricular ejection fraction, improving the hemodynamic index, and inhibiting interstitial fibrosis. Protein chip analysis revealed that SLJ upregulated MCP-1, MDC, neuropilin-2, TGF-3, thrombospondin, TIE-2, EG-VEGF/PK1, and TIMP-1/2/3 expressions and downregulated that of MMP-13. In addition, immunohistochemistry and western blot results further confirmed that SLJ promoted TIMP-1/2/3 and inhibited MMP-13 expression. The results of the present study suggest that SLJ was effective against DOX-induced CHF rats and is related to the improvement of heart function and ultrastructure and the inhibition of myocardial fibrosis.
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http://dx.doi.org/10.1155/2021/6659676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310442PMC
July 2021

Genomic insights into a complete deletion of the mgrB locus in colistin-resistant Klebsiella pneumoniae ST2268 isolated from a human infection.

J Glob Antimicrob Resist 2021 Jul 17;27:75-78. Epub 2021 Jul 17.

Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China. Electronic address:

Objectives: The emergence of colistin-resistant Klebsiella pneumoniae (CoRKp) is a serious public-health issue as colistin is the last line of defence against infections caused by multidrug-resistant Gram-negative bacteria. In this study, we generated a draft genome sequence for CoRKp strain P094-1 isolated from a sputum sample of an infected patient.

Methods: Whole genomic DNA of strain P094-1 was sequenced using a PacBio sequencing platform. Generated reads were de novo assembled using Hierarchical Genome Assembly Process (HGAP) v.3.0. Colistin resistance-related genes were predicted from the genome sequence and were validated experimentally.

Results: The genome of strain P094-1 lacked a 20.3-kb region, including complete deletion of the mgrB gene. Molecular and genome sequencing-based analyses revealed that the observed colistin resistance of P094-1 could not be attributed to plasmid-borne genes mcr-1 to mcr-9 or to alteration of the pmr and pho operons (deletions, insertions or substitutions), but was conferred by an insertion sequence 1 (IS1)-induced total deletion of mgrB.

Conclusion: This is the first reported whole-genome sequence of an unusual CoRKp isolate containing an IS1-induced deletion of mgrB.
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http://dx.doi.org/10.1016/j.jgar.2021.07.004DOI Listing
July 2021

Endogenous sulfur dioxide is a novel inhibitor of hypoxia-induced mast cell degranulation.

J Adv Res 2021 03 8;29:55-65. Epub 2020 Sep 8.

Department of Pediatrics, Peking University First Hospital, Beijing, China.

Introduction: Mast cell (MC) degranulation is an important step in the pathogenesis of inflammatory reactions and allergies; however, the mechanism of stabilizing MC membranes to reduce their degranulation is unclear.

Methods: SO content in MC culture supernatant was measured by HPLC-FD. The protein and mRNA expressions of the key enzymes aspartate aminotransferase 1 (AAT1) and AAT2 and intracellular AAT activity were detected. The cAMP level in MCs was detected by immunofluorescence and ELISA. The release rate of MC degranulation marker β-hexosaminidase was measured. The expression of AAT1 and cAMP, the MC accumulation and degranulation in lung tissues were detected.

Objectives: To exam whether an endogenous sulfur dioxide (SO) pathway exists in MCs and if it serves as a novel endogenous MC stabilizer.

Results: We firstly show the existence of the endogenous SO/AAT pathway in MCs. Moreover, when AAT1 was knocked down in MCs, MC degranulation was significantly increased, and could be rescued by a SO donor. Mechanistically, AAT1 knockdown decreased the cyclic adenosine monophosphate (cAMP) content in MCs, while SO prevented this reduction in a dose-independent manner. Pretreatment with the cAMP-synthesizing agonist forskolin or the cAMP degradation inhibitor IBMX significantly blocked the increase in AAT1 knockdown-induced MC degranulation. Furthermore, in hypoxia-stimulated MCs, AAT1 protein expression and SO production were markedly down regulated, and MC degranulation was activated, which were blunted by AAT1 overexpression. The cAMP synthesis inhibitor SQ22536 disrupted the suppressive effect of AAT1 overexpression on hypoxia-induced MC degranulation. In a hypoxic environment, mRNA and protein expression of AAT1 was significantly reduced in lung tissues of rats. Supplementation of SO elevated the cAMP level and reduced perivascular MC accumulation and degranulation in lung tissues of rats exposed to a hypoxic environment .

Conclusion: SO serves as an endogenous MC stabilizer via upregulating the cAMP pathway under hypoxic circumstance.
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http://dx.doi.org/10.1016/j.jare.2020.08.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020161PMC
March 2021

Persulfidation of transcription factor FOXO1 at cysteine 457: A novel mechanism by which HS inhibits vascular smooth muscle cell proliferation.

J Adv Res 2021 Jan 1;27:155-164. Epub 2020 Jul 1.

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

Introduction: The proliferation of vascular smooth muscle cells (VSMCs) is an important physiological and pathological basis for many cardiovascular diseases. Endogenous hydrogen sulfide (HS), the third gasotransmitter, is found to preserve vascular structure by inhibiting VSMC proliferation. However, the mechanism by which HS suppresses VSMC proliferation has not been fully clear.

Objectives: This study aimed to explore whether HS persulfidates the transcription factor FOXO1 to inhibit VSMC proliferation.

Methods: After the proliferation of VSMC A7r5 cells was induced by endothelin-1 (ET-1), FOXO1 phosphorylation and proliferating cell nuclear antigen (PCNA) expression were detected by Western blotting, the degree of FOXO1 nuclear exclusion and PCNA fluorescent signals in the nucleus were detected by immunofluorescence, and the persulfidation of FOXO1 was measured through a biotin switch assay.

Results: The results showed that ET-1 stimulation increased cell proliferation, FOXO1 phosphorylation and FOXO1 nuclear exclusion to the cytoplasm in the cells. However, pretreatment with NaHS, an HS donor, successfully abolished the ET-1-induced increases in the VSMC proliferation, FOXO1 phosphorylation, and FOXO1 nuclear exclusion to the cytoplasm. Mechanistically, HS persulfidated the FOXO1 protein in A7r5 and 293T cells, and the thiol reductant DTT reversed this effect. Furthermore, the C457S mutation of FOXO1 abolished the HS-induced persulfidation of FOXO1 in the cells and the subsequent inhibitory effects on FOXO1 phosphorylation at Ser256, FOXO1 nuclear exclusion to the cytoplasm and cell proliferation.

Conclusion: Thus, our findings demonstrated that HS might inhibit VSMC proliferation by persulfidating FOXO1 at Cys457 and subsequently preventing FOXO1 phosphorylation at Ser256.
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http://dx.doi.org/10.1016/j.jare.2020.06.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728583PMC
January 2021

Suppression of Ionic Doping by Molecular Dopants in Conjugated Polymers for Improving Specificity and Sensitivity in Biosensing Applications.

ACS Appl Mater Interfaces 2020 Oct 25;12(40):45036-45044. Epub 2020 Sep 25.

Department of Materials Science and Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, Maryland 21218-2608, United States.

Ionic doping effects in conjugated polymers often cause nonspecific signaling and a low selectivity of bioelectronic sensing. Using remote-gate field-effect transistor characterization of molecular and ionic doping in poly(3-hexylthiophene) (P3HT) and acid-functionalized polythiophene, poly[3-(3-carboxypropyl) thiophene-2,5-diyl] (PT-COOH), we discovered that proton doping effects on the interfacial potential occurring in P3HT could be suppressed by sequentially doping P3HT by 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ). To be specific, intrinsic pH sensitivity shown by pure P3HT (18 mV/pH in a range from pH 3 to 9) was fully dissipated for doped P3HT:F4TCNQ. However, F4TCNQ sequential doping instead increases pH sensitivity of acid-functionalized polythiophene, PT-COOH (40 mV/pH), compared to that of a pure PT-COOH (30 mV/pH). Interactions between polythiophene backbone and side chains, which constrain the activity of COOH, are weakened by stronger F4TCNQ doping leaving behind responsive COOH groups exposed to aqueous solutions. This is supported by the reduced pH sensitivity of PT-COOH sequentially doped by a weaker dopant, tetracyanoethylene (TCNE) (21 mV/pH). Thus, doping is shown to stabilize a nonpolar conjugated polymer to pH-induced fluctuations on one hand, and to activate a COOH side chain to pH-induced response on the other.
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http://dx.doi.org/10.1021/acsami.0c11125DOI Listing
October 2020

Qiliqiangxin improves cardiac function and attenuates cardiac remodelling in doxorubicin-induced heart failure rats.

Pharm Biol 2020 Dec;58(1):417-426

School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, P. R. China.

Therapeutic doxorubicin administration is restricted as this anticancer drug may be cardiotoxic. The traditional Chinese medicine qiliqiangxin has been approved for clinical treatment of chronic heart failure. To explore the protective effects and molecular mechanisms of qiliqiangxin on doxorubicin-induced congestive heart failure (CHF) in rats. A CHF rat model was established via intraperitoneal DOX injections (2.5 mg/kg/week) for 6 weeks. The rats were randomly assigned to control, CHF, CHF + QL (1.0 g/kg/d), or captopril (3.8 mg/kg/d) treatment groups ( = 10) for 4 weeks. MicroRNA sequencing elucidated the molecular mechanisms of qiliqiangxin on doxorubicin-induced CHF in rats. Unlike in the CHF group, QL significantly reduced Bax:Bcl-2 (2.05 ± 0.23 vs. 0.94 ± 0.09,  < 0.05) and the levels of collagen I (0.19 ± 0.02 vs. 0.15 ± 0.01,  < 0.05), collagen III (0.19 ± 0.02 vs. 0.14 ± 0.02,  < 0.05), TGF-β1 (5.28 ± 0.89 vs. 2.47 ± 0.51,  < 0.05), Smad3 (1.23 ± 0.12 vs. 0.78 ± 0.09,  < 0.05), MMP-2 (0.89 ± 0.01 vs. 0.53 ± 0.05,  < 0.05), and TIMP-2 (0.24 ± 0.03 vs. 0.44 ± 0.03,  < 0.05). QL also upregulated TGF-β3 (0.65 ± 0.06 vs. 0.96 ± 0.10,  < 0.05) and Smad7 (0.09 ± 0.01 vs. 0.19 ± 0.023,  < 0.05). Moreover, Smad3 was a target of miR-345-3p. The beneficial effects of QL on DOX-induced CHF in rats are mediated by reduction in myocardial fibrosis, promotion of TGF-β3/Smad7, and inhibition of TGF-β1/Smad3. QL may also modulate specific miRNAs. These results provide evidence that QL might be an effective treatment for DOX-induced CHF.
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http://dx.doi.org/10.1080/13880209.2020.1761403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301709PMC
December 2020

Zn-Incorporated TiO Nanotube Surface Improves Osteogenesis Ability Through Influencing Immunomodulatory Function of Macrophages.

Int J Nanomedicine 2020 27;15:2095-2118. Epub 2020 Mar 27.

School of Dentistry, Stomatological Hospital, Tianjin Medical University, Tianjin, People's Republic of China.

Purpose: Zinc (Zn), an essential trace element in the body, has stable chemical properties, excellent osteogenic ability and moderate immunomodulatory property. In the present study, a Zn-incorporated TiO nanotube (TNT) was fabricated on titanium (Ti) implant material. We aimed to evaluate the influence of nano-scale topography and Zn on behaviors of murine RAW 264.7 macrophages. Moreover, the effects of Zn-incorporated TNT surface-regulated macrophages on the behaviors and osteogenic differentiation of murine MC3T3-E1 osteoblasts were also investigated.

Methods: TNT coatings were firstly fabricated on a pure Ti surface using anodic oxidation, and then nano-scale Zn particles were incorporated onto TNTs by the hydrothermal method. Surface topography, chemical composition, roughness, hydrophilicity, Zn release pattern and protein adsorption ability of the Zn-incorporated TiO nanotube surface were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), surface profiler, contact angle test, Zn release test and protein adsorption test. The cell behaviors and both pro-inflammatory (M1) and pro-regenerative (M2) marker gene and protein levels in macrophages cultured on Zn-incorporated TNTs surfaces with different TNT diameters were detected. The supernatants of macrophages were extracted and preserved as conditioned medium (CM). Furthermore, the behaviors and osteogenic properties of osteoblasts cultured in CM on various surfaces were evaluated.

Results: The release profile of Zn on Zn-incorporated TNT surfaces revealed a controlled release pattern. Macrophages cultured on Zn-incorporated TNT surfaces displayed enhanced gene and protein expression of M2 markers, and M1 markers were moderately inhibited, compared with the LPS group (the inflammation model). When cultured in CM, osteoblasts cultured on Zn-incorporated TNTs showed strengthened cell proliferation, adhesion, osteogenesis-related gene expression, alkaline phosphatase activity and extracellular mineralization, compared with their TNT counterparts and the Ti group.

Conclusion: This study suggests that the application of Zn-incorporated TNT surfaces may establish an osteogenic microenvironment and accelerate bone formation. It provided a promising strategy of Ti surface modification for a better applicable prospect.
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http://dx.doi.org/10.2147/IJN.S244349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109325PMC
July 2020

Negative auto-regulation of sulfur dioxide generation in vascular endothelial cells: AAT1 S-sulfenylation.

Biochem Biophys Res Commun 2020 Feb 19. Epub 2020 Feb 19.

Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China. Electronic address:

Recently, endogenous sulfur dioxide (SO) has been found to exert an important function in the cardiovascular system. However, the regulatory mechanism for SO generation has not been entirely clarified. Hence, we aimed to explore the possible auto-regulation of endogenous SO generation and its mechanisms in vascular endothelial cells. We showed that SO did not affect the protein expression of aspartate aminotransferase 1 (AAT1), a major SO synthesis enzyme, but significantly inhibited AAT activity in primary human umbilical vein endothelial cells (HUVECs) and porcine purified AAT1 protein. An AAT1 enzymatic kinetic study showed that SO reduced the Vmax (1.89 ± 0.10 vs 2.55 ± 0.12, μmol/mg/min, P < 0.05) and increased the Km (35.97 ± 9.54 vs 19.33 ± 1.76 μmol/L, P < 0.05) values. Furthermore, SO induced S-sulfenylation of AAT1 in primary HUVECs and purified AAT1 protein. LC-MS/MS analysis indicated that SO sulfenylated AAT1 at Cys192. Mechanistically, thiol reductant DTT treatment or C192S mutation prevented SO-induced AAT1 sulfenylation and the subsequent inhibition of AAT activity in purified AAT1 protein and primary HUVECs. Our findings reveal, for the first time, a mechanism of auto-regulation of SO generation through sulfenylation of AAT1 at Cys192 to suppress AAT activity in vascular endothelial cells. These findings will greatly deepen the understanding of regulatory mechanisms in the cardiovascular homeostasis.
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http://dx.doi.org/10.1016/j.bbrc.2020.02.040DOI Listing
February 2020

Surface Immobilization of TiO Nanotubes with Bone Morphogenetic Protein-2 Synergistically Enhances Initial Preosteoblast Adhesion and Osseointegration.

Biomed Res Int 2019 26;2019:5697250. Epub 2019 Mar 26.

Stomatological Hospital, Tianjin Medical University, Tianjin 300070, China.

Although titanium (Ti) alloys have been widely used as implant materials, the bioinertness of pristine Ti impairs their bioactivity and early osseointegration. In the present work, we prepared TiO nanotubes (TNT) layer on the titanium (Ti) surface by anodic oxidation. The anodized surface was functionalized with human bone morphogenetic protein-2 coating to form the hBMP-2/TNT surface. The release behavior of hBMP-2 on the hBMP-2/TNT surface displayed a controlled and sustained pattern, compared to that on the hBMP-2/Ti surface, which showed a rapid release. cellular activity tests demonstrated that both TNT and hBMP-2/Ti surfaces, particularly the hBMP-2/TNT surface, enhanced adhesion, proliferation, and differentiation of osteoblast cells. Increased cell adhesion, improved cytoskeleton organization, and immunofluorescence staining of vinculin were observed on the modified surfaces. The TNT, hBMP-2/Ti, and hBMP-2/TNT surfaces, especially the hBMP-2/TNT surface, further displayed an upregulated gene expression of adhesion and osteogenic markers , collagen type 1, osteopontin, and osteocalcin, compared to the pristine Ti surface. experiments using a rat model demonstrated that the TNT and hBMP-2/Ti surfaces, in particular the hBMP-2/TNT surface, improved osseointegration and showed a superior bone bonding ability compared to Ti. Our study revealed a synergistic role played by TiO nanotubes nanotopography and hBMP-2 in promoting initial osteoblast adhesion, proliferation, differentiation, and osseointegration, thus suggesting a promising method for better modifying the implant surface.
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http://dx.doi.org/10.1155/2019/5697250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457305PMC
August 2019

Establishing an osteoimmunomodulatory coating loaded with aspirin on the surface of titanium primed with phase-transited lysozyme.

Int J Nanomedicine 2019 5;14:977-991. Epub 2019 Feb 5.

School of Dentistry, Stomatological Hospital, Tianjin Medical University, Tianjin, People's Republic of China,

Background: To improve osseointegration and enhance the success rate of implanted biomaterials, the surface modification technology of bone implants has developed rapidly. Intensive research on osteoimmunomodulation has shown that the surfaces of implants should possess favorable osteoimmunomodulation to facilitate osteogenesis.

Methods: A novel, green and efficient phase-transited lysozyme (PTL) technique was used to prime titanium discs with a positive charge. In addition, sodium hyaluronate (HA) and self-assembled type I collagen containing aspirin (ASA) nanoparticles were decorated on PTL-primed Ti discs via electrostatic interaction.

Results: The behaviors of bone marrow stromal cells (BMSCs) on the Ti disc surfaces containing ASA were analyzed in different conditioned media (CM) generated by macrophages. Additionally, the secretion of inflammation-related cytokines of macrophages on the surfaces of different Ti discs was investigated in in vitro experiments, which showed that the Ti surface containing ASA not only supported the migration, proliferation and differentiation of BMSCs but also reduced the inflammatory response of macrophages compared with Ti discs without surface modification. After implantation in vivo, the ASA-modified implant can significantly contribute to bone formation around the implant, which mirrors the evaluation in vitro.

Conclusion: This study highlights the significant effects of appropriate surface characteristics on the regulation of osteogenesis and osteoimmunomodulation around an implant. Implant modification with ASA potentially provides superior strategies for the surface modification of biomaterials.
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http://dx.doi.org/10.2147/IJN.S190766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368129PMC
March 2019

Improved osteoblast adhesion and osseointegration on TiO nanotubes surface with hydroxyapatite coating.

Dent Mater J 2019 Mar 11;38(2):278-286. Epub 2018 Dec 11.

Stomatological Hospital, Tianjin Medical University.

To improve initial osteoblast adhesion and subsequent osseointegration, TiO nanotubes layer was constructed on the titanium (Ti) surface by anodic oxidation (AO), with an additional hydroxyapatite (HA) coating to form the AO/HA surface. Tests on in vitro cellular activity displayed that the AO surface, especially the AO/HA surface, promoted initial adhesion, proliferation and differentiation of osteoblast cells. The modified AO and AO/HA surfaces further presented an up-regulated gene expression of osteogenic and adhesion markers collagen type 1 (COL), osteopontin (OPN), osteocalcin (OCN) and vinculin. In addition, in vivo experiments with a rat model demonstrated that the AO surface, particularly the AO/HA surface, achieved earlier osseointegration and a superior bone bonding ability compared with Ti. Our study shed light on a synergistic role played by nanotopography and HA in promoting osteoblast adhesion, proliferation, differentiation and osseointegration, thus suggesting a promising method for better modifying the implant surface.
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http://dx.doi.org/10.4012/dmj.2018-118DOI Listing
March 2019

Loading icariin on titanium surfaces by phase-transited lysozyme priming and layer-by-layer self-assembly of hyaluronic acid/chitosan to improve surface osteogenesis ability.

Int J Nanomedicine 2018 23;13:6751-6767. Epub 2018 Oct 23.

School of Dentistry, Stomatological Hospital, Tianjin Medical University, Tianjin, China,

Purpose: Icariin (ICA) is one of the main active constituents of for improving osteogenesis. It is necessary to create a simple and efficient method to load ICA onto the surface of titanium (Ti) implant. The purpose of this study was to establish a local ICA delivery system via a layer-by-layer (LbL) self-assembly system on phase-transited lysozyme (PTL)-primed Ti surface.

Materials And Methods: A PTL nanofilm was first firmly coated on the pristine Ti. Then, the ICA-loaded hyaluronic acid/chitosan (HA/CS) multilayer was applied via the LbL system to form the HA/CS-ICA surface. This established HA/CS-ICA surface was characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and contact angle measurement. The ICA release pattern of the HA/CS-ICA surface was also examined. MC3T3-E1 osteoblast culture test and a rat model were used to evaluate the effects of the HA/CS-ICA surface in vitro and in vivo.

Results: SEM, XPS and contact angle measurement demonstrated successful fabrication of the HA/CS-ICA surface. The HA/CS-ICA surfaces with different ICA concentrations revealed a controlled release profile of ICA during a 2-week monitoring span. Osteoblasts grown on the coated substrates displayed higher adhesion, viability, proliferation and ALP activity than those on the polished Ti surface. Furthermore, in vivo histological evaluation revealed much obvious bone formation in the ICA-coated group by histological staining and double fluorescent labeling at 2 weeks after implantation.

Conclusion: The present study demonstrated that ICA-immobilized HA/CS multilayer on the PTL-primed Ti surface had a sustained release pattern of ICA which could promote the osteogenesis of osteoblasts in vitro and improve early osseointegration in vivo. This study provides a novel method for creating a sustained ICA delivery system to improve osteoblast response and osseointegration.
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http://dx.doi.org/10.2147/IJN.S174953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204858PMC
December 2018

Surface modification of titanium with hydroxyapatite layer induced by phase-transited lysozyme coating.

Mater Sci Eng C Mater Biol Appl 2018 Nov 23;92:206-215. Epub 2018 Jun 23.

School and Hospital of Stomatology, Tianjin Medical University, 12 Observatory Road, Heping District, Tianjin 30070, China. Electronic address:

Surface modification of titanium with a hydroxyapatite (HAP) coating can improve the bioactivity of pristine titanium. The traditional techniques for coating HAP on titanium involve nonmild treatments using strong bases or acids or high temperatures. In this study, the coating of HAP was carried out by a novel methodology called phase-transited lysozyme-assisted hydroxyapatite formation (PAH); in this process of biomimetic mineralization, the abundant functional carboxyl groups of phase-transited lysozyme (PTL) were responsible for the nucleation of HAP crystals by concentrating Ca ions at the interface between PTL and CaCl solution and for the subsequent growth of HAP crystals occurring in simulated body fluid (SBF). In vitro and in vivo experiments verified that the surface of titanium modified with the HAP/PTL-Ti multilayer was endowed with improved biocompatibility and osteoinductivity compared with those of pristine titanium. Therefore, PAH is a simple, rapid, low-cost and green process for the surface modification of titanium with an HAP coating and thus will be a promising methodology for the surface modification of titanium implants.
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http://dx.doi.org/10.1016/j.msec.2018.05.055DOI Listing
November 2018

Carbon nanotube-modified oxidized regenerated cellulose gauzes for hemostatic applications.

Carbohydr Polym 2018 Mar 16;183:246-253. Epub 2017 Dec 16.

MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, State Key Laboratory of Urban Water Resource and Environment, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China.

Functionalized carbon nanotubes have recently received interest because of their unique properties, especially in the biomedical field. In this research, unmodified multiwalled carbon nanotubes (MWCNTs), and functionalized carbon nanotubes with amino groups (MWCNTs-NH) and carboxyl groups (MWCNTs-COOH) were grafted to oxidized regenerated cellulose (ORC) gauze to fabricate novel functionalized ORC, and the performance of the functionalized gauze was investigated. The functionalized ORC was characterized by FT-IR, XPS and SEM, which showed the different kinds of CNTs grafted on its surface. The XPS results demonstrated the successful incorporation of functionalized MWCNTs in the active layer of modified ORC gauze. Meanwhile, the specific surface area of the CNTs modified functionalized ORC gauze was improved in varying degrees, whereas the porosity was slightly decreased. Furthermore, hydrophilicity experiment results presented a significant increment in water uptake of the functionalized CNTs grafted to the surface of the ORC gauze. Results of the hemostatic performance test on rabbit ear artery and liver showed that compared with the original ORC gauze, the bleeding time was significantly reduced when using the functionalized CNTs modified ORC hemostatic gauze. Moreover, the results also showed that the MWCNTs-COOH/ORC functionalized gauze had outstanding hemostatic efficiency.
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http://dx.doi.org/10.1016/j.carbpol.2017.12.035DOI Listing
March 2018

Fabrication of Z-scheme magnetic MoS/CoFeO nanocomposites with highly efficient photocatalytic activity.

J Colloid Interface Sci 2018 Mar 29;514:664-674. Epub 2017 Dec 29.

Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China. Electronic address:

MoS thin nanosheets decorated with CoFeO nanoparticles have been successfully synthesized via a simple hydrothermal method. The nanocomposites are characterized by XRD, TEM, HRTEM, BET, XPS, UV-Vis DRS, PL and magnetic property analysis. The Z-scheme mechanism at the interface of MoS and CoFeO is formed. When the mass ratio of MoS and CoFeO is 1:3, the MoS/CoFeO nanocomposites present excellent photocatalytic performance. The degradation rate of rhodamine B (RhB) and congo red (CR) is 93.80% and 94.43% in 90 and 50 min, respectively, under visible light irradiation. The highly photocatalytic activity could be mainly ascribed to the formed Z-scheme mechanism which facilitates the separation of photoinduced electron-hole pairs. Besides, the MoS thin nanosheets not only provide the most active sites for photocatalytic reactions, but also act as the backing material for CoFeO nanoparticles to effectively disperse and avoid the magnetic aggregation. Moreover, the MoS/CoFeO nanocomposites present a good recyclability and the degradation rate of RhB and CR is still beyond 82% after seven runs. In addition, the nanocomposites can be easily separated by an external magnet.
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http://dx.doi.org/10.1016/j.jcis.2017.12.079DOI Listing
March 2018

Characterisation of clinical isolates of oxacillin-susceptible mecA-positive Staphylococcus aureus in China from 2009 to 2014.

J Glob Antimicrob Resist 2017 12 17;11:1-3. Epub 2017 Jul 17.

Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, People's Republic of China.

Objectives: The aim of this study was to investigate the prevalence and molecular characteristics of clinical oxacillin-susceptible mecA-positive Staphylococcus aureus (OS-MRSA) isolates in China from July 2009 to June 2014.

Methods: A total of 2068 non-duplicate S. aureus isolates were collected from 21 hospitals. Antimicrobial susceptibility testing was performed by the agar dilution method. All OS-MRSA strains were screened for the presence of the genes mecA, mecC and nuc as well as the Panton-Valentine leukocidin gene (pvl). Staphylococcal cassette chromosome mec (SCCmec) typing, staphylococcal protein A (spa) typing and multilocus sequence typing (MLST) were performed to analyse the isolate genotypes.

Results: A total of 34 S. aureus isolates were mecA-positive but were susceptible to oxacillin [minimum inhibitory concentration (MIC)≤2mg/L]. All OS-MRSA isolates were resistant to cefoxitin and most were also multiresistant to other antibiotics besides β-lactams. Among the 34 OS-MRSA isolates, nine spa and three SCCmec types were detected and, combined with MLST, ST338/59-t437-SCCmecV (47%; 16/34) was the predominant clone. In addition, 17 strains (50%) carried the pvl gene.

Conclusions: The most frequent clone of OS-MRSA isolates in China was ST338-t437-SCCmecV. Most of the OS-MRSA isolates were susceptible to the majority of antibacterial agents except macrolides, clindamycin and chloramphenicol.
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http://dx.doi.org/10.1016/j.jgar.2017.05.009DOI Listing
December 2017

cfr-mediated linezolid-resistant clinical isolates of methicillin-resistant coagulase-negative staphylococci from China.

J Glob Antimicrob Resist 2017 03 5;8:1-5. Epub 2016 Nov 5.

School of Public Health, Peking University Health Science Center, Beijing, People's Republic of China.

Three linezolid-resistant coagulase-negative staphylococci (LR-CoNS), including two Staphylococcus cohnii and one Staphylococcus capitis, were isolated from 1104 clinical staphylococcal isolates across China in 2013-2014. Antibiotic susceptibilities of the bacteria were determined by the agar dilution method. PCR and DNA sequencing were performed to determine the potential molecular mechanism of linezolid resistance. The two linezolid-resistant S. cohnii isolates were subjected to pulsed-field gel electrophoresis (PFGE) to investigate their genetic relatedness. Primer walking, S1 nuclease PFGE and Southern blot hybridisation were conducted to ascertain the location and environment of the cfr gene. All three isolates were positive for the cfr gene. Amino acid mutations S158F and S158Y in the ribosomal protein L3 were identified in S. cohnii 13B289 and 13L105, respectively, both of which also had an additional substitution (D159Y) in L3. PFGE indicated that the two S. cohnii isolates belonged to diverse clonal strains. S1 nuclease PFGE and Southern blotting experiments indicated that the cfr gene of the three isolates resided on plasmids of similar size (ca. 35.4kb). The cfr-harbouring segments of S. capitis 13G350 and S. cohnii 13L105 were identical to plasmid pSS-01 reported previously. The cfr-carrying fragment of S. cohnii 13B289 was indistinguishable from the formerly described plasmid pSS-02. In conclusion, the presence of the cfr gene located on a plasmid was the main mechanism contributing to resistance to linezolid in the three staphylococcal isolates. Hence, timely detection and judicious use of antibiotics are essential to prevent further transmission of this resistance mechanism.
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http://dx.doi.org/10.1016/j.jgar.2016.09.008DOI Listing
March 2017

Nationwide Surveillance of Novel Oxazolidinone Resistance Gene optrA in Enterococcus Isolates in China from 2004 to 2014.

Antimicrob Agents Chemother 2016 12 21;60(12):7490-7493. Epub 2016 Nov 21.

Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China.

A total of 2,201 nonduplicate enterococcal isolates collected from 29 hospitals in 23 cities in China between 2004 and 2014 were screened for the oxazolidinone resistance gene optrA; 45 isolates (2.0%) were optrA positive with 11 OptrA variants identified. The positive rate of optrA increased from 0.4% to 3.9% during the 10-year surveillance period. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence type (MLST) analysis revealed that 37 optrA-positive Enterococcus faecalis isolates clustered into 25 PFGE patterns and 21 sequence types, while 6 Enterococcus faecium isolates represented 6 PFGE patterns and 6 sequence types. The present study underscores the importance of routine and persistent monitoring of oxazolidinone resistance and optrA gene.
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http://dx.doi.org/10.1128/AAC.01256-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119033PMC
December 2016

Titanium Surface Priming with Phase-Transited Lysozyme to Establish a Silver Nanoparticle-Loaded Chitosan/Hyaluronic Acid Antibacterial Multilayer via Layer-by-Layer Self-Assembly.

PLoS One 2016 19;11(1):e0146957. Epub 2016 Jan 19.

School of Dentistry, Hospital of Stomatology, Tianjin Medical University, Tianjin, PR China.

Objectives: The formation of biofilm around implants, which is induced by immediate bacterial colonization after installation, is the primary cause of post-operation infection. Initial surface modification is usually required to incorporate antibacterial agents on titanium (Ti) surfaces to inhibit biofilm formation. However, simple and effective priming methods are still lacking for the development of an initial functional layer as a base for subsequent coatings on titanium surfaces. The purpose of our work was to establish a novel initial layer on Ti surfaces using phase-transited lysozyme (PTL), on which multilayer coatings can incorporate silver nanoparticles (AgNP) using chitosan (CS) and hyaluronic acid (HA) via a layer-by-layer (LbL) self-assembly technique.

Methods: In this study, the surfaces of Ti substrates were primed by dipping into a mixture of lysozyme and tris(2-carboxyethyl)phosphine (TCEP) to obtain PTL-functionalized Ti substrates. The subsequent alternating coatings of HA and chitosan loaded with AgNP onto the precursor layer of PTL were carried out via LbL self-assembly to construct multilayer coatings on Ti substrates.

Results: The results of SEM and XPS indicated that the necklace-like PTL and self-assembled multilayer were successfully immobilized on the Ti substrates. The multilayer coatings loaded with AgNP can kill planktonic and adherent bacteria to 100% during the first 4 days. The antibacterial efficacy of the samples against planktonic and adherent bacteria achieved 65%-90% after 14 days. The sustained release of Ag over 14 days can prevent bacterial invasion until mucosa healing. Although the AgNP-containing structure showed some cytotoxicity, the toxicity can be reduced by controlling the Ag release rate and concentration.

Conclusions: The PTL priming method provides a promising strategy for fabricating long-term antibacterial multilayer coatings on titanium surfaces via the LbL self-assembly technique, which is effective in preventing implant-associated infections in the early stage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146957PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718720PMC
July 2016
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