Publications by authors named "Qinfu Wang"

9 Publications

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Mannosylated gelatin nanoparticles enhanced inactivated PRRSV targeting dendritic cells and increased T cell immunity.

Vet Immunol Immunopathol 2021 May 5;235:110237. Epub 2021 Apr 5.

College of Life Science and Technology, Dalian University, Dalian, 116622, PR China; Institute of Immunology, Dalian University, Dalian, 116622, PR China. Electronic address:

The objective of the present work was to evaluate the efficacy of a novel antigen carrier using mannosylated gelatin nanoparticles with entrapped inactivated porcine reproductive and respiratory syndrome virus (PRRSV) in inducing T cell mediated immunity in vitro. Gelatin nanoparticles (GNP) were modified with mannose to form mannosylated gelatin nanoparticles (MnGNP), which can efficiently and specifically target monocyte derived dendritic cells (MoDCs). The inactivated PRRSV was encapsulated in the MnGNP and GNP, referred to as MnGNP-PRRSV and GNP-PRRSV, respectively. All these prepared nanometer particles were characterized for size, surface charge, drug encapsulation efficiency, and drug release. The efficacy of MnGNP in targeting MoDCs was investigated, as well as the subsequent MoDCs maturation and T cell mediated cytotoxicity. The developed MnGNP-PRRSV particle was characterized with a nanometric size of 302.67 ± 3.2 nm, surface charge of 23.81 ± 1.26 mV, and PRRSV encapsulation efficiency of 63.2 ± 1.85 %. The maximum uptake of MnGNP in MoDCs in vitro was 15.5 times higher than GNP with a shorter reaction time that peaked 4 h earlier. The uptake of MnGNP-PRRSV induced maturation of MoDCs and significantly enhanced expression of SWC-3a, CD80, CD1, SLA I, SLA II on MoDCs, compared to PRRSV (p < 0.001). The cytokine secretion of IL-1β, IL-6, IL-10, and IL-12 was also increased in MoDCs when treated with MnGNP-PRRSV, compared to PRRSV (p < 0.05). The matured MoDCs triggered T lymphocytes in autologous peripheral blood mononuclear cells (PBMCs) activation, proliferation, and differentiation into effector cytotoxic T lymphocyte, suggesting increased amount of activated T cells after MnGNP-PRRSV treatment. Additionally, the function of T cells to kill PRRSV infected cells was 83.98 ± 2.62 % when triggered by MnGNP-PRRSV, compared to 60 ± 4.7 % in PRRSV group (p < 0.001). These results indicate that MnGNP with entrapped inactivated PRRSV can effectively and specifically target dendritic cells for maturation and activation, and subsequently improve T cell activation, proliferation and function to kill PRRSV infected cells.
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http://dx.doi.org/10.1016/j.vetimm.2021.110237DOI Listing
May 2021

Protective effects of valsartan administration on doxorubicin‑induced myocardial injury in rats and the role of oxidative stress and NOX2/NOX4 signaling.

Mol Med Rep 2020 Nov 17;22(5):4151-4162. Epub 2020 Sep 17.

Department of Cardiology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China.

Clinical application of doxorubicin (DOX) is hampered by its potential cardiotoxicity, however angiotensin receptor blockers could attenuate DOX‑induced cardiomyopathy. The present study tested the hypothesis that simultaneous administration of valsartan (Val) with DOX could prevent DOX‑induced myocardial injury by modulating myocardial NAD(P)H oxidase (NOX) expression in rats. Eight‑week‑old male Sprague‑Dawley rats were randomly divided into control (CON), DOX, and DOX+Val groups. After 10 weeks, surviving rats underwent echocardiography examination, myocardial mRNA and protein expression detection of NOX1, NOX2 and NOX4. H9C2 cells were used to perform in vitro experiments, reactive oxygen species (ROS) production and apoptosis were observed under the conditions of down‑ or upregulation of NOX2 and NOX4 in DOX‑ and DOX+Val‑treated H9C2 cells. Cardiac function was significantly improved, pathological lesion and collagen volume fraction were significantly reduced in the DOX+Val group compared with the DOX group (all P<0.05). Myocardial protein and mRNA expression of NOX2 and NOX4 was significantly downregulated in DOX+Val group compared with in the DOX group (all P<0.05). In vitro, ROS production and apoptosis in DOX‑treated H9C2 cells was significantly reduced by NOX2‑small interfering (si)RNA and NOX4‑siRNA, and significantly increased by overexpressing NOX2 and NOX4. To conclude, Val applied simultaneously with DOX could prevent DOX‑induced myocardial injury and reduce oxidative stress by downregulating the myocardial expression of NOX2 and NOX4 in rats.
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http://dx.doi.org/10.3892/mmr.2020.11521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533445PMC
November 2020

Heterogeneity and plasticity of porcine alveolar macrophage and pulmonary interstitial macrophage isolated from healthy pigs .

Biol Open 2019 Oct 24;8(10). Epub 2019 Oct 24.

College of Life Science and Technology, Dalian University, Dalian 116622, China

This study investigated the heterogeneity and plasticity of porcine alveolar macrophages (PAM) and pulmonary interstitial macrophages (IM) isolated from healthy pigs, including phenotype, function and gene expression. Dynamic changes of nitric oxide (NO) levels secreted by PAM and IM with stimulation of different doses of lipopolysaccharide (LPS) were investigated by Griess method, and the viability of the PAM and IM cells was investigated by MTT assay. Flow cytometry, fluorescence quantitative PCR and ELISA techniques were used to measure cell phenotype, gene expression and cytokine secretion, respectively. The PAM and IM cells in normal healthy pigs showed heterogeneity with 95.42±1.51% and 31.99±5.84% of CD163+ macrophage, respectively. The NO level in IM was significantly higher versus PAM after LPS treatment. Consistently, the ratio of Arg I/iNOS in IM was much lower than that in PAM, suggesting that the PAM belong to M2 macrophages and the IM belong to M1 macrophages. The PAM and IM cells in normal healthy pigs also showed plasticity. The Arg I/iNOS ratio and TIMP1/MMP12 ratio were significantly decreased in LPS- or LPS+IFNγ-treated PAM and IM, suggesting that cells were polarized towards M1 macrophages under LPS or LPS+IFNγ stimulation. On the contrary, IL-4 and IL-13 stimulation on PAM and IM lead to M2 polarization. A similar result was found in IL-1β gene expression and TNFα secretion. In conclusion, porcine macrophages have shown heterogeneity and plasticity on polarization under the stimulation of LPS, IFNγ, IL-4 and IL-13.
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http://dx.doi.org/10.1242/bio.046342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826289PMC
October 2019

Illumina MiSeq Sequencing Investigation of Microbiota in Bronchoalveolar Lavage Fluid and Cecum of the Swine Infected with PRRSV.

Curr Microbiol 2019 Feb 15;76(2):222-230. Epub 2018 Dec 15.

Institute of Immunology, College of Life Science and Technology, Dalian University, Dalian, 116622, Liaoning, China.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant animal morbidity and mortality and economic losses worldwide. In this study, we analyzed the microbiota in bronchoalveolar lavage fluid (BAL), mucosa, and feces in cecum of the PRRSV-challenged pigs using the Illumina MiSeq sequencing platform, to investigate the role of microbiota in the pathogenesis and development of porcine reproductive and respiratory syndrome (PRRS). Quantitative insights into microbial ecology analyses indicated that the dominant bacterial groups in the lung from the PRRSV-challenged pigs were Haemophilus parasuis and Mycoplasma hyorhinis, with a relative abundance of 35-48% and 27-41%, respectively. Our results were consistent with the clinical observation that the PRRSV-infected pigs are always co-infected with other bacteria, such as Haemophilus and Mycoplasma. On the other hand, Campylobacter and Clostridium became the two most abundant bacteria in the mucosal and luminal microbiota of the cecum of the PRRSV-challenged pigs, and the relative abundance was four times higher than that in the healthy pigs. This suggested that Campylobacter and Clostridium might be associated with the pathogenesis of diarrhea in PRRS. Linear discriminant analysis effect size reveals significant microbial dysbiosis of BAL, mucosa, and feces in cecum of the PRRSV-challenged pigs. We have identified a structural imbalance of the microbiota, characterized by a reduced diversity of microbiota and abundance alterations of certain bacteria in the PRRSV-challenged pigs. The observed microbiota dysbiosis in this study provides insight into the roles of the microbiota in the complications of the PRRSV infection.
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http://dx.doi.org/10.1007/s00284-018-1613-yDOI Listing
February 2019

TAK1 knockdown enhances lipopolysaccharide-induced secretion of proinflammatory cytokines in myeloid cells via unleashing MEKK3 activity.

Cell Immunol 2016 12 21;310:193-198. Epub 2016 Sep 21.

Institute of Immunology, College of Life Science & Technology, Dalian University, Dalian, Liaoning, China. Electronic address:

TGF-β activating protein kinase 1 (TAK1) belongs to the MAP kinase kinase kinase (MAP3K) family. TAK1 is involved in many signaling pathways, especially the innate and adaptive immune responses. TAK1 mediates nuclear factor κB (NF-κB) and MAPK signaling pathway in response to interleukin-1, tumor necrosis factor-α (TNFα), and toll-like receptor agonists, such as lipopolysaccharide (LPS). The regulatory roles of TAK1 in LPS-induced proinflammatory cytokines production are dependent on the cell types. In this study, we examined the effects of TAK1 on the LPS induced production of proinflammatory cytokines in myeloid cells. Knockdown of TAK1 enhanced the secretion of interleukin 1-beta (IL-1β) and TNFα induced by LPS. In addition, LPS-activated TAK1 negatively regulates mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3 (MEKK3). Moreover, TAK1 inhibited MEKK3 activation, which, in turn, activated NF-κB. These results indicate that TAK1 negatively regulates LPS-induced cytokine secretion in myeloid cells by inhibiting MEKK3 activities.
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http://dx.doi.org/10.1016/j.cellimm.2016.09.011DOI Listing
December 2016

Identification of genes associated with renal cell carcinoma using gene expression profiling analysis.

Oncol Lett 2016 Jul 16;12(1):73-78. Epub 2016 May 16.

Department of Communicable Diseases Control and Prevention, Laiwu Center for Disease Control and Prevention, Laiwu, Shandong 271100, P.R. China.

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and accounts for ~80% of all kidney cancer cases. However, the pathogenesis of RCC has not yet been fully elucidated. To interpret the pathogenesis of RCC at the molecular level, gene expression data and bio-informatics methods were used to identify RCC associated genes. Gene expression data was downloaded from Gene Expression Omnibus (GEO) database and identified differentially coexpressed genes (DCGs) and dysfunctional pathways in RCC patients compared with controls. In addition, a regulatory network was constructed using the known regulatory data between transcription factors (TFs) and target genes in the University of California Santa Cruz (UCSC) Genome Browser (http://genome.ucsc.edu) and the regulatory impact factor of each TF was calculated. A total of 258,0427 pairs of DCGs were identified. The regulatory network contained 1,525 pairs of regulatory associations between 126 TFs and 1,259 target genes and these genes were mainly enriched in cancer pathways, ErbB and MAPK. In the regulatory network, the 10 most strongly associated TFs were FOXC1, GATA3, ESR1, FOXL1, PATZ1, MYB, STAT5A, EGR2, EGR3 and PELP1. GATA3, ERG and MYB serve important roles in RCC while FOXC1, ESR1, FOXL1, PATZ1, STAT5A and PELP1 may be potential genes associated with RCC. In conclusion, the present study constructed a regulatory network and screened out several TFs that may be used as molecular biomarkers of RCC. However, future studies are needed to confirm the findings of the present study.
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http://dx.doi.org/10.3892/ol.2016.4573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906613PMC
July 2016

TAK1 negatively regulates NF-κB and p38 MAP kinase activation in Gr-1+CD11b+ neutrophils.

Immunity 2012 Jan 5;36(1):43-54. Epub 2012 Jan 5.

Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.

Stringent control of NF-κB and mitogen-activated protein kinase (MAPK) signaling is critical during innate immune responses. TGF-β activated kinase-1 (TAK1) is essential for NF-κB activation in T and B cells but has precisely the opposite activity in myeloid cells. Specific deletion of TAK1 (Map3k7(ΔM/ΔM)) led to development of splenomegaly and lymphomegaly associated with neutrophilia. Compared with wild-type cells, TAK1-deficient neutrophils enhanced the phosphorylation of the kinases IKK, p38, and JNK and the production of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and reactive oxygen species (ROS) after lipopolysaccharide (LPS) stimulation. Map3k7(ΔM/ΔM) mice were significantly more susceptible to LPS-induced septic shock and produced higher amounts of IL-1β, IL-6, and TNF-α in plasma than do wild-type mice. Specific ablation of p38 rescued the phenotype and functional properties of Map3k7(ΔM/ΔM) mice. Our findings identify a previously unrecognized role of TAK1 as a negative regulator of p38 and IKK activation in a cell type-specific manner.
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http://dx.doi.org/10.1016/j.immuni.2011.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750978PMC
January 2012

NLRX1 negatively regulates TLR-induced NF-κB signaling by targeting TRAF6 and IKK.

Immunity 2011 Jun;34(6):843-53

Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.

Tight regulation of NF-κB signaling is essential for innate and adaptive immune responses, yet the molecular mechanisms responsible for its negative regulation are not completely understood. Here, we report that NLRX1, a NOD-like receptor family member, negatively regulates Toll-like receptor-mediated NF-κB activation. NLRX1 interacts with TRAF6 or IκB kinase (IKK) in an activation signal-dependent fashion. Upon LPS stimulation, NLRX1 is rapidly ubiquitinated, disassociates from TRAF6, and then binds to the IKK complex, resulting in inhibition of IKKα and IKKβ phosphorylation and NF-κB activation. Knockdown of NLRX1 in various cell types markedly enhances IKK phosphorylation and the production of NF-κB-responsive cytokines after LPS stimulation. We further provide in vivo evidence that NLRX1 knockdown in mice markedly enhances susceptibility to LPS-induced septic shock and plasma IL-6 level. Our study identifies a previously unrecognized role for NLRX1 in the negative regulation of TLR-induced NF-κB activation by dynamically interacting with TRAF6 and the IKK complex.
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http://dx.doi.org/10.1016/j.immuni.2011.02.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150212PMC
June 2011

Dendritic cell based personalized immunotherapy based on cancer antigen research.

Front Biosci 2008 Jan 1;13:1952-8. Epub 2008 Jan 1.

Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University, School of Medicine, Tokyo, Japan.

Human tumor antigens were identified using various immunological and genetic methods, and immune responses to the identified antigens were evaluated in cancer patients. Autologous tumor specific unique antigens derived from genetic alterations in cancer cells were isolated from patients with favorable prognosis after immunotherapy, indicating that they are attractive targets for immunotherapy. Immunogenicity of shared antigens was found to differ among patients due to antigen expression in cancer cells and patients' immunoreactivity. These observations suggest that personalization may be applied for cancer immunotherapy. We therefore developed intratumoral DC administration protocols that are able to induce immune responses to both unique and shared tumor antigens expressed in each individual cancer. By combining cryoablative tumor pretreatment and TLR stimulated DC, the anti-tumor effect of the intratumoral DC administration was significantly augmented in a murine tumor model. This improved protocol enhanced systemic induction of anti-tumor CD8+ CTL, and was able to regress relatively large remote untreated tumors. In clinical trials, systemic immune induction was observed by intratumoral DC administration following cryoablative tumor treatment, although anti-tumor effects are relatively weak, indicating that additional interventions are required for more effective immunotherapy.
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http://dx.doi.org/10.2741/2814DOI Listing
January 2008