Publications by authors named "Ni Xia"

43 Publications

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

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

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

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

Regulatory T Cells in Chronic Heart Failure.

Front Immunol 2021 22;12:732794. Epub 2021 Sep 22.

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

Heart failure is a global problem with high hospitalization and mortality rates. Inflammation and immune dysfunction are involved in this disease. Owing to their unique function, regulatory T cells (Tregs) have reacquired attention recently. They participate in immunoregulation and tissue repair in the pathophysiology of heart failure. Tregs are beneficial in heart by suppressing excessive inflammatory responses and promoting stable scar formation in the early stage of heart injury. However, in chronic heart failure, the phenotypes and functions of Tregs changed. They transformed into an antiangiogenic and profibrotic cell type. In this review, we summarized the functions of Tregs in the development of chronic heart failure first. Then, we focused on the interactions between Tregs and their target cells. The target cells of Tregs include immune cells (such as monocytes/macrophages, dendritic cells, T cells, and B cells) and parenchymal cells (such as cardiomyocytes, fibroblasts, and endothelial cells). Next-generation sequencing and gene editing technology make immunotherapy of heart failure possible. So, prospective therapeutic approaches based on Tregs in chronic heart failure had also been evaluated.
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http://dx.doi.org/10.3389/fimmu.2021.732794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493934PMC
September 2021

Detection of Mercury Ion with High Sensitivity and Selectivity Using a DNA/Graphene Oxide Hybrid Immobilized on Glass Slides.

Biosensors (Basel) 2021 Aug 27;11(9). Epub 2021 Aug 27.

College of Biological and Pharmaceutical Engineering, West Anhui University, Moon Island, Lu'an 237012, China.

Excessive mercury ions (Hg) cause great pollution to soil/water and pose a major threat to human health. The high sensitivity and high selectivity in the Hg detection demonstrated herein are significant for the research areas of analytical chemistry, chemical biology, physical chemistry, drug discovery, and clinical diagnosis. In this study, a series of simple, low-cost, and highly sensitive biochips based on a graphene oxide (GO)/DNA hybrid was developed. Hg is detected with high sensitivity and selectivity by GO/DNA hybrid biochips immobilized on glass slides. The performance of the biosensors can be improved by introducing more phosphorothioate sites and complementary bases. The best limit of detection of the biochips is 0.38 nM with selectivity of over 10:1. This sensor was also used for Hg detection in Dendrobium. The results show this biochip is promising for Hg detection.
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http://dx.doi.org/10.3390/bios11090300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471904PMC
August 2021

Regulatory B cells improve ventricular remodeling after myocardial infarction by modulating monocyte migration.

Basic Res Cardiol 2021 07 24;116(1):46. Epub 2021 Jul 24.

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

Overactivated inflammatory responses contribute to adverse ventricular remodeling after myocardial infarction (MI). Regulatory B cells (Bregs) are a newly discovered subset of B cells with immunomodulatory roles in many immune and inflammation-related diseases. Our study aims to determine whether the expansion of Bregs exerts a beneficial effect on ventricular remodeling and explore the mechanisms involved. Here, we showed that adoptive transfer of Bregs ameliorated ventricular remodeling in a murine MI model, as demonstrated by improved cardiac function, decreased scar size and attenuated interstitial fibrosis without changing the survival rate. Reduced Ly6C monocyte infiltration was found in the hearts of the Breg-transferred mice, while the infiltration of Ly6C monocytes was not affected. In addition, the replenishment of Bregs had no effect on the myocardial accumulation of T cells or neutrophils. Mechanistically, Bregs reduced the expression of C-C motif chemokine receptor 2 (CCR2) in monocytes, which inhibited proinflammatory monocyte recruitment to the heart from the peripheral blood and mobilization from the bone marrow. Breg-mediated protection against MI was abrogated by treatment with an interleukin 10 (IL-10) antibody. Finally, IL-10 neutralization reversed the effect of Bregs on monocyte migration and CCR2 expression. The present study suggests a therapeutic value of Bregs in limiting ventricular remodeling after MI through decreasing CCR2-mediated monocyte recruitment and mobilization.
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http://dx.doi.org/10.1007/s00395-021-00886-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310480PMC
July 2021

Inhibition of fibroblast IL-6 production by ACKR4 deletion alleviates cardiac remodeling after myocardial infarction.

Biochem Biophys Res Commun 2021 04 18;547:139-147. Epub 2021 Feb 18.

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:

Fibrotic scarring is tightly linked to the development of heart failure in patients with post-myocardial infarction (MI). Atypical chemokine receptor 4 (ACKR4) can eliminate chemokines, such as C-C chemokine ligand 21 (CCL21), which is independently associated with heart failure mortality. However, the role of ACKR4 in the heart during MI is unrevealed. This study aimed to determine whether ACKR4 modulates cardiac remodeling following MI and to illuminate the potential molecular mechanisms. The expression of ACKR4 was upregulated in the border/infarct area, and ACKR4 was predominantly expressed in cardiac fibroblasts (CFs). Knockout of ACKR4 protected against adverse ventricular remodeling in mice post-MI. These protective effects of ACKR4 deficiency were independent of dendritic cell immune response but could be attributed to downregulated CF-derived IL-6, affecting CF proliferation and endothelial cell (EC) functions, which consequently inhibited cardiac fibrosis. ACKR4 promoted IL-6 generation and proliferation of CFs. Besides, ACKR4 induced endothelial-to-mesenchymal transition (EndMT) in ECs through IL-6 paracrine effect. The p38 MAPK/NF-κB signaling pathway was involved in ACKR4 facilitated IL-6 generation. Moreover, ACKR4 overexpression in vivo via AAV9 carrying a periostin promoter aggravated heart functional impairment post-MI, which was abolished by IL-6 neutralizing antibody. Therefore, our study established a novel link between ACKR4 and IL-6 post-MI, indicating that ACKR4 may be a novel therapeutic target to ameliorate cardiac remodeling.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.013DOI Listing
April 2021

A Unique Population of Regulatory T Cells in Heart Potentiates Cardiac Protection From Myocardial Infarction.

Circulation 2020 11 28;142(20):1956-1973. Epub 2020 Sep 28.

Department of Cardiology, Union Hospital, and Key Laboratory of Biological Targeted Therapy of the Ministry of Education (N.X., Y. Lu, M.G., N.L., M.L., J.J., Z.Z., J.L., D.L., T.T., B.L., S.N., M.Z., M.L., Y. Liao, X.C.), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Regulatory T cells (Tregs), traditionally recognized as potent suppressors of immune response, are increasingly attracting attention because of a second major function: residing in parenchymal tissues and maintaining local homeostasis. However, the existence, unique phenotype, and function of so-called tissue Tregs in the heart remain unclear.

Methods: In mouse models of myocardial infarction (MI), myocardial ischemia/reperfusion injury, or cardiac cryoinjury, the dynamic accumulation of Tregs in the injured myocardium was monitored. The bulk RNA sequencing was performed to analyze the transcriptomic characteristics of Tregs from the injured myocardium after MI or ischemia/reperfusion injury. Photoconversion, parabiosis, single-cell T-cell receptor sequencing, and adoptive transfer were applied to determine the source of heart Tregs. The involvement of the interleukin-33/suppression of tumorigenicity 2 axis and Sparc (secreted acidic cysteine-rich glycoprotein), a molecule upregulated in heart Tregs, was further evaluated in functional assays.

Results: We showed that Tregs were highly enriched in the myocardium of MI, ischemia/reperfusion injury, and cryoinjury mice. Transcriptomic data revealed that Tregs isolated from the injured hearts had plenty of differentially expressed transcripts in comparison with their lymphoid counterparts, including heart-draining lymphoid nodes, with a phenotype of promoting infarct repair, indicating a unique characteristic. The heart Tregs were accumulated mainly because of recruitment from the circulating Treg pool, whereas local proliferation also contributed to their expansion. Moreover, a remarkable case of repeatedly detected T-cell receptor of heart Tregs, more than that of spleen Tregs, suggests a model of clonal expansion. Besides, HeliosNrp-1 phenotype proved the mainly thymic origin of heart Tregs, with a small contribution of phenotypic conversion of conventional CD4 T cells, proved by the analysis of T-cell receptor repertoires and conventional CD4 T cells adoptive transfer experiments. The interleukin-33/suppression of tumorigenicity 2 axis was essential for sustaining heart Treg populations. Last, we demonstrated that Sparc, which was highly expressed by heart Tregs, acted as a critical factor to protect the heart against MI by increasing collagen content and boosting maturation in the infarct zone.

Conclusions: We identified and characterized a phenotypically and functionally unique population of heart Tregs that may lay the foundation to harness Tregs for cardioprotection in MI and other cardiac diseases.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046789DOI Listing
November 2020

Angelica sinensis polysaccharide attenuates CCl-induced liver fibrosis via the IL-22/STAT3 pathway.

Int J Biol Macromol 2020 Nov 20;162:273-283. Epub 2020 Jun 20.

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

Angelica sinensis polysaccharide (ASP) has hepatoprotective effects in liver injury models. However, its role and mechanism in chronic liver fibrosis have not been fully elucidated. In this study, a carbon tetrachloride (CCl)-induced chronic liver fibrosis mouse model was established. The results showed that ASP treatment reduced serum alanine aminotransferase by approximately 50% and liver fibrosis areas by approximately 70%. Hepatic stellate cell (HSC) activation was inhibited in ASP-treated mice. Furthermore, the mechanism was studied in-depth, focusing on the interleukin 22/signal transducer and activator of transcription 3 (IL-22/STAT3) axis. Concentrations of 50 μg/ml and 100 μg/ml ASP induced the secretion of IL-22 in vitro, which further increased at a concentration of 200 μg/ml. Moreover, in vivo data showed that ASP significantly promoted IL-22 production in splenocytes and liver tissues. The antifibrotic effects of ASP were abolished after IL-22 neutralization. In addition, ASP activated the STAT3 pathway in the liver, as demonstrated by a 2-fold increase compared to that of the CCl group, which was abrogated by the IL-22 antibody. Subsequently, we showed that the antifibrotic effects of ASP were abrogated by blocking STAT3 with S3I-201. In conclusion, ASP effectively alleviates chronic liver fibrosis by inhibiting HSC activation through the IL-22/STAT3 pathway.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.06.166DOI Listing
November 2020

Parallel Aligned Nickel Nanocone Arrays for Multiband Microwave Absorption.

ACS Appl Mater Interfaces 2020 May 11;12(20):23340-23346. Epub 2020 May 11.

Materials Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.

Magnetic nanostructures with conical shape are highly desired for pursuing extraordinary magnetic properties and microwave absorption. However, the fabrication of such nanostructures with controlled shape and size uniformities and alignment is not yet realized. Accordingly, the magnetic properties and their application as microwave absorber are not well understood. Here, we report on the first demonstration of controlled fabrication of soft magnetic nickel nanocone arrays with sharp geometry, large aspect ratio, uniform size, and parallel alignment. The imaginary part of the relative complex permeability shows multiband absorption in the 2-17 GHz range. Such an exceptional microwave absorption results from the uniform conical shape and size and the parallel alignment. The absorption mechanisms are discussed under the framework of natural resonance and exchange resonance. The natural resonance is dependent on the shape anisotropy and facilitated by the conical geometry. The exchange resonance is well explained by the observation of the bulk spin waves with exchange coupling at the tip of nanocones using the inelastic light scattering and is consistent with exchange theory predictions for the quantization of bulk spin waves. We expect that our work will shed light on the physical insights into the magnetic properties of nanocones and find great potential in applications of microwave absorption.
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http://dx.doi.org/10.1021/acsami.0c04247DOI Listing
May 2020

Early diagnosis and precision treatment of right ovarian vein and inferior vena cava thrombosis following caesarean section: A case report.

Exp Ther Med 2020 Apr 25;19(4):2923-2926. Epub 2020 Feb 25.

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.

Ovarian vein thrombosis (OVT) is a rare medical complication that is most often diagnosed in the post-partum period. OVT can lead to conditions, including sepsis, inferior vena cava (IVC), pulmonary emboli and mortality. The current study outlines a case of a patient who experienced pain in the lower abdomen and waist without fever postpartum following caesarean section (CS). Plasma FDP, D-Dimer and fibrinogen levels were markedly increased following CS and this was an indicator of the rapid progression of blood coagulation and fibrinolysis. Increased maternal lipid may be one of the risk factors for thrombosis. Based on the clinical presentation, a CT scan demonstrated thrombosis of the right ovarian vein and inferior vena cava, and a diagnosis of OVT and IVC thrombosis was subsequently made. In the current case, an anticoagulant therapy was started with a subcutaneous injection low molecular weight heparin calcium, an intravenous urokinase drip as a thrombolytic agent and implantation of inferior vena cava filters as a novel method of treatment for thrombosis. The patient was discharged from hospital 20 days following treatment in a good condition. The current study reports a case of OVT associated with IVC that was successfully managed without complication.
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http://dx.doi.org/10.3892/etm.2020.8548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086212PMC
April 2020

Correlation Between Diabetic Peripheral Neuropathy and Sarcopenia in Patients with Type 2 Diabetes Mellitus and Diabetic Foot Disease: A Cross-Sectional Study.

Diabetes Metab Syndr Obes 2020 13;13:377-386. Epub 2020 Feb 13.

Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.

Purpose: The present study was designed to determine the relationships between sarcopenia and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM) and diabetic foot disease (DFD) respectively.

Patients And Methods: A total of 1104 patients with T2DM and 257 patients with DFD were included in the study, which was designed as a cross-sectional study. Body composition was assessed using dual-energy X-ray-absorptiometry (DXA). The diagnosis of sarcopenia was based on the Baumgartner criteria. DPN was assessed by Neuropathy symptom score (NSS) and Neuropathy disability score (NDS), and the severity of neuropathy was divided into non-neuropathy symptom (NS), Mild NS, Moderate NS and Severe NS according to NSS. Logistic regression analyses were carried out to determine the relations of sarcopenia and DPN in patients with T2DM and NSS in patients with DFD, respectively.

Results: The prevalence of DPN was 80.0% in T2DM patients with sarcopenia and 70.3% in non-sarcopenia patients (P=0.007). Logistic regression analyses showed DPN was one of the independent risk factors for sarcopenia in T2DM patients (OR 1.564 [95% CI: 1.004, 2.435], P=0.048). The prevalence of DPN had no statistical significance in DFD patients with or without sarcopenia. However, the NSS of DFD patients with sarcopenia was higher than that of non-sarcopenia patients. In the multivariate logistic regression analysis, NSS was determined to be associated with sarcopenia in DFD patients (OR 1.387[95% CI: 1.074, 1.789], P=0.012). The appendicular lean mass (ALM) of DFD patients without NS was higher than patients with mild, moderate and severe NS (20.71±2.73 vs 16.57±3.62 vs 17.99±3.54 vs 17.23±3.29 Kg, P=0.028).

Conclusion: DPN is an independent risk factor for sarcopenia in patients with T2DM and NSS is also independently correlated with sarcopenia in patients with DFD, with the latter being more obvious with the aggravation of neurological symptoms in DFD patients.
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http://dx.doi.org/10.2147/DMSO.S237362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025667PMC
February 2020

Interleukin 35 ameliorates myocardial ischemia-reperfusion injury by activating the gp130-STAT3 axis.

FASEB J 2020 02 9;34(2):3224-3238. Epub 2020 Jan 9.

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

Myocardial ischemia-reperfusion injury (MIRI) is common clinical complication, which represents significant challenge in the treatment of acute myocardial infarction (AMI) diseases. Interleukin 35 (IL-35) exhibits anti-inflammatory properties via the engagement of the gp130, IL-12Rβ2 and IL-27Rα receptors. However, whether IL-35 plays a beneficial role in the treatment of MIRI and potential underling mechanism are unclear. We showed that IL-35 conferred protection from MIRI as demonstrated by reduced infarct size and cardiac troponin T, improved cardiac function and decreased cardiomyocyte apoptosis in a mouse model. Despite activation of both STAT3 and STAT5 phosphorylation in the heart by IL-35, signal transducers and activators of transcription 3 (STAT3) was essential for mediating the IL-35-mediated protective effect on MIRI using cardiomyocyte-specific STAT3 deficient mice. Furthermore, gp130 was required for the STAT3 activation and cardio-protection induced by IL-35. Interestingly, IL-35 induced gp130 homodimer and gp130/IL-12Rβ2 heterodimers in cardiomyocyte. Our results indicate that IL-35 can execute a protective role against MIRI through a novel signaling pathway, IL-35-gp130-STAT3 pathway, in cardiomyocytes, which may be beneficial for the development of novel and effective therapeutic approaches to treat the MIRI.
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http://dx.doi.org/10.1096/fj.201901718RRDOI Listing
February 2020

Pathologic T-cell response in ischaemic failing hearts elucidated by T-cell receptor sequencing and phenotypic characterization.

Eur Heart J 2019 12;40(48):3924-3933

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

Aims: A persistent cardiac T-cell response initiated by myocardial infarction is linked to subsequent adverse ventricular remodelling and progression of heart failure. No data exist on T-cell receptor (TCR) repertoire changes in combination with phenotypic characterization of T cells in ischaemic failing human hearts.

Methods And Results: Analysis of TCR repertoire with high-throughput sequencing revealed that compared with T cells in control hearts, those in ischaemic failing hearts showed a clonally expanded TCR repertoire but similar usage patterns of TRBV-J rearrangements and V gene segments; compared with T cells in peripheral blood, those in ischaemic failing hearts exhibited a restricted and clonally expanded TCR repertoire and different usage patterns of TRBV-J rearrangements and V gene segments, suggesting the occurrence of tissue-specific T-cell expansion in ischaemic failing hearts. Consistently, TCR clonotype sharing was prominent in ischaemic failing hearts, especially in hearts of patients who shared human leucocyte antigen (HLA) alleles. Furthermore, ischaemia heart failure (IHF) heart-associated clonotypes were more frequent in peripheral blood of IHF patients than in that of controls. Heart-infiltrating T cells displayed memory- and effector-like characteristics. Th1 cells were the predominant phenotype among CD4+ T cells; CD8+ T cells were equally as abundant as CD4+ T cells and produced high levels of interferon-γ, granzyme B, and perforin.

Conclusion: We provide novel evidence for a tissue-specific T-cell response predominated by Th1 cells and cytotoxic CD8+ T cells in ischaemic failing human hearts that may contribute to the progression of heart failure.
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http://dx.doi.org/10.1093/eurheartj/ehz516DOI Listing
December 2019

IL (Interleukin)-33 Suppresses Abdominal Aortic Aneurysm by Enhancing Regulatory T-Cell Expansion and Activity.

Arterioscler Thromb Vasc Biol 2019 03;39(3):446-458

From the Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Key Lab for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (J.L., N.X., S.W., D.L., Y.L., M.G., T.T., J.J., B.L., S.N., M.L.,Y.L., X.C.).

Objective- Inflammation occurs during the progression of abdominal aortic aneurysm (AAA). IL (interleukin)-33 is a pleiotropic cytokine with multiple immunomodulatory effects, yet its role in AAA remains unknown. Approach and Results- Immunoblot, immunohistochemistry, and immunofluorescent staining revealed increased IL-33 expression in adventitia fibroblasts from mouse AAA lesions. Daily intraperitoneal administration of recombinant IL-33 or transgenic IL-33 expression ameliorated periaorta CaPO injury- and aortic elastase exposure-induced AAA in mice, as demonstrated by blunted aortic expansion, reduced aortic wall elastica fragmentation, enhanced AAA lesion collagen deposition, attenuated T-cell and macrophage infiltration, reduced inflammatory cytokine production, skewed M2 macrophage polarization, and reduced lesion MMP (matrix metalloproteinase) expression and cell apoptosis. Flow cytometry analysis, immunostaining, and immunoblot analysis showed that exogenous IL-33 increased CD4Foxp3 regulatory T cells in spleens, blood, and aortas in periaorta CaPO-treated mice. Yet, ST2 deficiency muted these IL-33 activities. Regulatory T cells from IL-33-treated mice also showed significantly stronger activities in suppressing smooth muscle cell inflammatory cytokine and chemokine expression, macrophage MMP expression, and in increasing M2 macrophage polarization than those from vehicle-treated mice. In contrast, IL-33 failed to prevent AAA and lost its beneficial activities in CaPO-treated mice after selective depletion of regulatory T cells. Conclusions- Together, this study established a role of IL-33 in protecting mice from AAA formation by enhancing ST2-dependent aortic and systemic regulatory T-cell expansion and their immunosuppressive activities.
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http://dx.doi.org/10.1161/ATVBAHA.118.312023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393188PMC
March 2019

The detection of mercury ion using DNA as sensors based on fluorescence resonance energy transfer.

Talanta 2019 Jan 4;192:500-507. Epub 2018 Sep 4.

Institute of Life Sciences, Jiangsu University, Zhenjiang 212013, PR China; State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China. Electronic address:

Mercury ion (Hg) is a heavy metal that can cause serious water pollution. With the accumulation of large quantities in lakes, rivers, freshwater and aquatic life, Hg can pass through the food chain, entering the human body and endangering health. Hg detection has therefore become important thereby attracting extensive interests. Currently, several DNA-based sensors have been used for Hg detection because they are not easy to degrade and are very stable. This paper summarizes the application of some DNA-based sensors based on fluorescence resonance energy transfer (FRET), analyzes their characteristic, and compares their sensitivity. Future perspectives and possible challenges in this area are also outlined.
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http://dx.doi.org/10.1016/j.talanta.2018.08.086DOI Listing
January 2019

Liver-heart crosstalk controls IL-22 activity in cardiac protection after myocardial infarction.

Theranostics 2018 10;8(16):4552-4562. Epub 2018 Aug 10.

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

Interleukin (IL)-22 regulates tissue inflammation and repair. Here we report participation of the liver in IL-22-mediated cardiac repair after acute myocardial infarction (MI). We induced experimental MI in mice by ligation of the left ascending artery and evaluated the effect of IL-22 on post-MI cardiac function and ventricular remodeling. Daily subcutaneous injection of 100 µg/kg mouse recombinant IL-22 for seven days attenuated adverse ventricular remodeling and improved cardiac function in mice at 28 days after left anterior descending coronary artery ligation-induced MI. Pharmacological inhibition of signal transducer and activator of transcription (STAT3) muted these IL-22 activities. While cardiomyocyte-selective depletion of STAT3 did not affect IL-22 activities in protecting post-MI cardiac injury, hepatocyte-specific depletion of STAT3 fully muted these IL-22 cardioprotective activities. Hepatocyte-derived fibroblast growth factor (FGF21) was markedly increased in a STAT3-dependent manner following IL-22 administration and accounted for the cardioprotective benefit of IL-22. Microarray analyses revealed that FGF21 controlled the expression of cardiomyocyte genes that are involved in cholesterol homeostasis, DNA repair, peroxisome, oxidative phosphorylation, glycolysis, apoptosis, and steroid responses, all of which are responsible for cardiomyocyte survival. Supplementation of IL-22 in the first week after acute MI effectively prevented left ventricular dysfunction and heart failure. This activity of IL-22 involved crosstalk between the liver and heart after demonstrating a role of the hepatic STAT3-FGF21 axis in IL-22-induced post-MI cardiac protection.
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http://dx.doi.org/10.7150/thno.24723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134935PMC
September 2019

Genetic Regulation of the Thymic Stromal Lymphopoietin (TSLP)/TSLP Receptor (TSLPR) Gene Expression and Influence of Epistatic Interactions Between IL-33 and the TSLP/TSLPR Axis on Risk of Coronary Artery Disease.

Front Immunol 2018 3;9:1775. Epub 2018 Aug 3.

Renmin Hospital of Wuhan University, Wuhan, China.

The thymic stromal lymphopoietin (TSLP)/TSLP receptor (TSLPR) axis is involved in multiple inflammatory immune diseases, including coronary artery disease (CAD). To explore the causal relationship between this axis and CAD, we performed a three-stage case-control association analysis with 3,628 CAD cases and 3,776 controls using common variants in the genes (), and . Three common variants in the TSLP/TSLPR axis were significantly associated with CAD in a Chinese Han population [rs3806933 in  = 4.35 × 10, odds ratio (OR) = 1.18; rs6897932 in  = 1.13 × 10, OR = 1.31; g.19646A>G in  = 2.04 × 10, OR = 1.20]. Reporter gene analysis demonstrated that rs3806933 and rs6897932 could influence and expression, respectively. Furthermore, the "T" allele of rs3806933 might increase plasma TSLP levels ( = 0.175,  < 0.01). In a stepwise procedure, the risk for CAD increased by nearly fivefold compared with the maximum effect of any single variant ( = 6.99 × 10, OR = 4.85). In addition, the epistatic interaction between and produced a nearly threefold increase in the risk of CAD in the combined model of rs3806933-rs7025417 ( = 3.67 × 10, OR = 2.98). Our study illustrates that the TSLP/TSLPR axis might be involved in the pathogenesis of CAD through upregulation of mRNA or protein expression of the referenced genes and might have additive effects on the CAD risk when combined with IL-33 signaling.
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http://dx.doi.org/10.3389/fimmu.2018.01775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085432PMC
September 2019

[Photo-physiological and photo-biochemical characteristics of several herbaceous and woody species based on FvCB model].

Ying Yong Sheng Tai Xue Bao 2017 May;28(5):1482-1488

Institute of Climate Change, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA.

To explore the photosynthetic capacity and the leaf photosynthetic apparatus for plants with different life forms, CO response curves of 7 woody species and 4 herbaceous species were fitted by the modified rectangular hyperbolic model and the FvCB model, and the photosynthetic parameters, including maximum net photosynthetic rate (P), maximal Rubisco carboxylation rate (V), maximal electron transport rate (J), day respiration (R), and mesophyll resistance to CO transport (r), were compared among different woody species, among different herbaceous species, and between woody and herbaceous life-forms, respectively. The results showed P of seven woody species descended in the order of Sapium sebiferum and Boehmeria nivea > Machilus pingii and Pittosporum tobira > Cyclobalanopsis glauca, Castanopsis sclerophylla, and Quercus nuttallii. V of S. sebiferum, B. nivea, M. pingii, and P. tobira was significantly higher than that of C. glauca and C. sclerophylla. J of woody species was in descending order as S. sebiferum > B. nivea and P. tobira > Q. nuttallii, C. sclerophylla, and C. glauca. r of M. pingii and C. sclerophylla was higher than that of S. sebiferum, P. tobira and B. nivea. P of Phytolacca acinosa was significantly higher than that of Ageratum conyzoides and Achyranthes aspera. There was no significant difference in V among 4 herbaceous species. J of P. acinosa was higher than that of A. conyzoides. r of S. nigrum and A. aspera was higher than that of A. conyzoides. R of P. acinosa was higher than that of A. conyzoides and A. aspera. The photosynthetic parameters (P, V, J and r) of woody species were significantly higher than those of herbaceous species, but no significant difference was found in R between woody and herbaceous species. In conclusion, the difference in photosynthetic capacity among different species and between the two plant life-forms resulted from the difference in Rubisco carboxylation capacity, electron transport capacity, and mesophyll resistance among these species.
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http://dx.doi.org/10.13287/j.1001-9332.201705.029DOI Listing
May 2017

IL-13 may be involved in the development of CAD via different mechanisms under different conditions in a Chinese Han population.

Sci Rep 2018 04 18;8(1):6182. Epub 2018 Apr 18.

Department of cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Interleukin-13 (IL-13) has important functions in atherosclerosis, but its role in coronary artery disease (CAD) is unclear. Here, we studied the genetic role of IL-13 in CAD in a Chinese Han population using tag SNPs covering the whole IL13 gene (i.e., rs1881457, rs2069744 and rs20541) and a two-stage cohort containing 1863 CAD cases and 1841 controls. Traditional risk factors for CAD, such as age, BMI, and other factors, were used as covariates in logistic regression analysis. In the total population, we found that two haplotypes of IL13 (ATG and ATA, ordered rs1881457-rs2069744-rs20541) significantly contributed to the risk of CAD with adjusted p values less than 0.05 (p = 0.019 and p = 0.042, respectively). In subgroup population analyses, the variant rs1881457 was found to significantly contribute to a nearly two fold increase in the risk of CAD in men (p = 0.023, OR = 1.91, 95% CI: 1.09-3.33). The variant rs1881457 also significantly contributed to a nearly twofold risk of late-onset CAD (p = 0.024, OR = 1.93, 95% CI: 1.09-3.42). In conclusion, IL13 might be involved in CAD via different mechanisms under different conditions in the Chinese Han population.
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http://dx.doi.org/10.1038/s41598-018-24592-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906444PMC
April 2018

Defective Circulating Regulatory B Cells in Patients with Dilated Cardiomyopathy.

Cell Physiol Biochem 2018 20;46(1):23-35. Epub 2018 Mar 20.

Background/aims: Newly identified IL-10-producing regulatory B cells (Bregs) have been shown to play an important role in the suppression of immune responses. Chronic immune activation participates in the pathogenesis of dilated cardiomyopathy (DCM) but whether Bregs are involved in its development remains unclear. We aimed to investigate the circulating frequency and function of Bregs in DCM.

Methods: In total, 35 DCM patients (20 men and 15 women) and 44 healthy controls (23 men and 21 women) were included in the experiment, and the frequency of Bregs was detected using flow cytometry.

Results: According to our results, the frequency of circulating IL-10-producing Bregs was significantly lower in DCM patients compared with healthy controls. Furthermore, the CD24hiCD27+ B cell subset in which IL-10-producing Bregs were mainly enriched from DCM patients showed impaired IL-10 expression and a decreased ability to suppress the TNF-α production of CD4+CD25- Tconv cells and to maintain Tregs differentiation. Correlation analysis showed that the frequency of IL-10-producing Bregs and the suppressive function of CD24hiCD27+ B cells were positively correlated with left ventricular ejection fraction and negatively correlated with NT-proBNP in DCM patients.

Conclusions: In conclusion, the reduced frequency and impaired functions suggest a potential role of Bregs in the development of DCM.
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http://dx.doi.org/10.1159/000488405DOI Listing
June 2018

Highly sensitive protein detection via covalently linked aptamer to MoS and exonuclease-assisted amplification strategy.

Int J Nanomedicine 2017 25;12:7847-7853. Epub 2017 Oct 25.

Department of Physical Education, Dalian Jiaotong University, Dalian, People's Republic of China.

Molybdenum disulfide (MoS) has shown highly attractive superiority as a platform for sensing. However, DNA physisorption on the surface of MoS was susceptible to nonspecific probe displacement and false-positive signals. To solve these problems, we have developed a novel MoS-aptamer nanosheet biosensor for detecting thrombin using a covalently linked aptamer to the MoS nanosheet. Ten percent Tween 80 was used to prevent thrombin from nonspecific binding and to rapidly form thiol-DNA/gold nanoparticle (AuNP) conjugates. Furthermore, an MoS and exonuclease coassisted signal amplification strategy was developed to improve the detection limit for thrombin. We used the hybridization of the aptamer molecules and the matched strand with a 5' terminal thiol to immobilize the aptamer molecules on the surface of AuNPs in [email protected] nanocomposites. Exonuclease digested the single-strand aptamer and released the thrombin, which was then detected in the next recycle. With the coassisted amplification strategy, a 6 fM detection limit was achieved, showing that this method has higher sensitivity than most reported methods for thrombin detection. The results presented in this work show that this method of covalently attaching the aptamer and using the coassisted amplification is a promising technique for the detection of protein in medical diagnostics.
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http://dx.doi.org/10.2147/IJN.S145585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661850PMC
February 2018

IL-21 promotes myocardial ischaemia/reperfusion injury through the modulation of neutrophil infiltration.

Br J Pharmacol 2018 04 12;175(8):1329-1343. Epub 2017 Apr 12.

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

Background And Purpose: The immune system plays an important role in driving the acute inflammatory response following myocardial ischaemia/reperfusion injury (MIRI). IL-21 is a pleiotropic cytokine with multiple immunomodulatory effects, but its role in MIRI is not known.

Experimental Approach: Myocardial injury, neutrophil infiltration and the expression of neutrophil chemokines KC (CXCL1) and MIP-2 (CXCL2) were studied in a mouse model of MIRI. Effects of IL-21 on the expression of KC and MIP-2 in neonatal mouse cardiomyocytes (CMs) and cardiac fibroblasts (CFs) were determined by real-time PCR and ELISA. The signalling mechanisms underlying these effects were explored by western blot analysis.

Key Results: IL-21 was elevated within the acute phase of murine MIRI. Neutralization of IL-21 attenuated myocardial injury, as illustrated by reduced infarct size, decreased cardiac troponin T levels and improved cardiac function, whereas exogenous IL-21 administration exerted opposite effects. IL-21 increased the infiltration of neutrophils and increased the expression of KC and MIP-2 in myocardial tissue following MIRI. Moreover, neutrophil depletion attenuated the IL-21-induced myocardial injury. Mechanistically, IL-21 increased the production of KC and MIP-2 in neonatal CMs and CFs, and enhanced neutrophil migration, as revealed by the migration assay. Furthermore, we demonstrated that this IL-21-mediated increase in chemokine expression involved the activation of Akt/NF-κB signalling in CMs and p38 MAPK/NF-κB signalling in CFs.

Conclusions And Implications: Our data provide novel evidence that IL-21 plays a pathogenic role in MIRI, most likely by promoting cardiac neutrophil infiltration. Therefore, targeting IL-21 may have therapeutic potential as a treatment for MIRI.

Linked Articles: This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.
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http://dx.doi.org/10.1111/bph.13781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866974PMC
April 2018

Down-regulation of microRNA-451a facilitates the activation and proliferation of CD4 T cells by targeting Myc in patients with dilated cardiomyopathy.

J Biol Chem 2017 04 14;292(14):6004-6013. Epub 2016 Dec 14.

From the Laboratory of Cardiovascular Immunology, Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 430022 Wuhan and

CD4 T cells are abnormally activated in patients with dilated cardiomyopathy (DCM) and might be associated with the immunopathogenesis of the disease. However, the underlying mechanisms of CD4 T cell activation remain largely undefined. Our aim was to investigate whether the dysregulation of microRNAs (miRNAs) was associated with CD4 T cell activation in DCM. CD4 T cells from DCM patients showed increased expression levels of CD25 and CD69 and enhanced proliferation in response to anti-CD3/28, indicating an activated state. miRNA profiling analysis of magnetically sorted CD4 T cells revealed a distinct pattern of miRNA expression in CD4 T cells from DCM patients compared with controls. The level of miRNA-451a (miR-451a) was significantly decreased in the CD4 T cells of DCM patients compared with that of the controls. The transfection of T cells with an miR-451a mimic inhibited their activation and proliferation, whereas an miR-451a inhibitor produced the opposite effects. Myc was directly inhibited by miR-451a via interaction with its 3'-UTR, thus identifying it as an miR-451a target in T cells. The knockdown of Myc suppressed the activation and proliferation of T cells, and the expression of Myc was significantly up-regulated at the mRNA level in CD4 T cells from patients with DCM. A strong inverse correlation was observed between the Myc mRNA expression and miR-451a transcription level. Our data suggest that the down-regulation of miR-451a contributes to the activation and proliferation of CD4 T cells by targeting the transcription factor Myc in DCM patients and may contribute to the immunopathogenesis of DCM.
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http://dx.doi.org/10.1074/jbc.M116.765107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392590PMC
April 2017

Protein determination using graphene oxide-aptamer modified gold nanoparticles in combination with Tween 80.

Anal Chim Acta 2016 Oct 26;941:80-86. Epub 2016 Aug 26.

P. E. Department of Dalian Jiaotong University, Dalian 116028, PR China.

Recently, graphene oxide (GO) has shown superiority for disease detection arising from its unique physical and chemical properties. However, proteins adsorbed on the surface of GO prevent sensitivity improvement in fluorescence-based detection methods. In this paper, a label-free method based on aptamer modified gold nanoparticles (GNPs) combined with Tween 80 was shown to solve this problem using the detection of thrombin as an example. An aptamer was designed and bound to thrombin by changing its conformation. Tween 80 was used for rapid and reproducible synthesis of stable DNA-functionalized GNPs and prevented the thrombin from nonspecific binding to GO. Thrombin was detected with a limit of 0.68 pM by taking advantage of the efficient cross-linking effect of aptamer-GNPs to GO. The sensor was validated by determining thrombin concentration in human blood serum samples. The results indicate that this method has promising analytical application in medical diagnostic.
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http://dx.doi.org/10.1016/j.aca.2016.08.032DOI Listing
October 2016

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

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

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

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

Cloning and analysis of gene expression of interleukin-17 homolog in triangle-shell pearl mussel, Hyriopsis cumingii, during pearl sac formation.

Fish Shellfish Immunol 2016 May 16;52:151-6. Epub 2016 Mar 16.

School of Food Science and Biological Engineering, Jiangsu University, Zhenjiang City, 212013, China. Electronic address:

Successful allograft of mantle tissues in certain bivalve mollusks can form pearl sacs secreting nacre for pearl production. Little was known, however, about the immune consequences in response to the tissue transplantation. In the present study, interleukin (IL)-17, one of the key regulatory genes of alloimmunity, was cloned from the triangle-shell pearl mussel (HcIL-17) Hyriopsis cumingii by high-throughput sequencing of the mantle transcriptome. The sequence of HcIL-17 contains an open reading frame of 567 bp encoding a putative protein of 188 amino acid residues. Analysis of sequence characteristics, multiple sequence alignment and phylogenetic analysis indicated HcIL-17 was a novel member in the mollusk IL-17 family. Expression of the HcIL-17 gene in donor mantle tissues and in hemocytes of recipient mussel was up-regulated dramatically within 7 days in response to the mantle tissue allograft for pearl aquaculture, suggesting remarkable proinflammatory responses during pearl sac formation in triangle-shell pearl mussels. Analysis of the time-course expression of HcIL-17 gene revealed the induction of HcIL-17 was time-dependent, reflecting the different periods of alloimmune events in triangle-shell mussels. The results of this study provide essential background information for further investigation of mollusk alloimmunity.
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http://dx.doi.org/10.1016/j.fsi.2016.03.027DOI Listing
May 2016

The effects of dried root aqueous extract of Salvia miltiorrhiza and its major ingredient in acceleration of orthodontic tooth movement in rat.

Iran J Basic Med Sci 2015 Oct;18(10):1044-9

Department of Stomatology, The First College of Clinical Medical Science of China Three Gorges University, Yichang Central People's Hospital, Yichang 443003, China.

Objectives: Salvia miltiorrhiza (SM) is a popular and classic herb in traditional Chineses medicines. The objective is to confirm the effects of aqueous extract of S. miltiorrhiza (ESM) and its main ingredient on the promotion of orthodontic tooth movement and healing of periodontal ligament in rat.

Materials And Methods: Male Sprague-Dawley rats (n= 150) were divided into five groups: model control group (0.5 ml/kg phosphate-buffered saline (PBS) injection), ESM group (0.75 g/kg/day of crude drugs) and Danshensu subgroups (250, 500, 750 mg/kg/day of body weight). All rats were administered intramuscularly into the buccal vestibular mucosa of first molar of left maxillary. The indicators such as the moving distance of orthodontic tooth, nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) expression and osteoclasts were tested.

Results: The expressions of RANKL and OPG in the treatment groups were obviously enhanced compared with control group (P<0.05). The increase rate of OPG expression was slower than that of RANKL. But, RANKL decreased conspicuously after no orthodontic pressure was applied, especially in the treatment groups (Danshengsu high dose group at day 30: 2.17 versus 3.47 of control, P<0.01). ESM groups promoted osteoclasts proliferation in the first 20 days.

Conclusion: There is a relationship between RANKL/OPG ratio and the number of osteoclasts. ESM might accelerate periodontal alteration of rat orthodontic tooth via producing more osteoclasts.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686576PMC
October 2015

IL-9 aggravates the development of atherosclerosis in ApoE-/- mice.

Cardiovasc Res 2015 Jun 17;106(3):453-64. Epub 2015 Mar 17.

Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China

Aims: Recently, interleukin (IL)-9 was found to be involved in the pathogenesis of many inflammatory diseases. Here, we tested whether IL-9 was related to atherosclerosis and investigated the underlying mechanisms.

Methods And Results: IL-9R was expressed in mouse aortic endothelial cells (MAECs) and aortic tissues, and IL-9 levels were elevated in plasma and aortic arches in Apolipoprotein E-deficient (ApoE-/-) mice. ApoE-/- mice fed a western diet for 10 weeks were administered recombinant mouse IL-9 (rIL-9) or anti-IL-9 neutralizing monoclonal antibody (mAb). Mice treated with rIL-9 developed markedly larger plaques in both the aorta and aortic root. Immunohistochemical studies demonstrated increases in both vascular endothelial adhesion molecule-1 (VCAM-1) expression and the infiltration of inflammatory cells, including T cells and macrophages, in plaques. However, treatment with the anti-IL-9 mAb caused the opposite effect. The administration of rIL-9 did not affect the splenic T cell or peripheral monocyte subsets. Meanwhile, IL-9 induced VCAM-1 expression in MAECs mainly via a STAT3-dependent pathway, consequently increasing monocyte-endothelial adhesion. Moreover, treatment with anti-VCAM-1 mAb partially abrogated the IL-9-induced increase in plaque area. In addition, CD4(+)IL-9(+) T cells and IL-9 were increased in patients with acute coronary syndrome, and the levels of IL-9 in culture supernatants and soluble VCAM-1 (sVCAM-1) in plasma were significantly positively correlated in the enrolled patients.

Conclusion: Our results demonstrated that IL-9 exerted pro-atherosclerotic effects in ApoE-/- mice at least partially by inducing VCAM-1 expression, which mediated inflammatory cell infiltration into atherosclerotic lesions.
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http://dx.doi.org/10.1093/cvr/cvv110DOI Listing
June 2015

Defective circulating CD4+LAP+ regulatory T cells in patients with dilated cardiomyopathy.

J Leukoc Biol 2015 Apr 26;97(4):797-805. Epub 2015 Feb 26.

*Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan, China; Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology and Center of Human Genome Research, Huazhong University of Science and Technology, Wuhan, China; and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

There has been increasing evidence that chronic immune activation plays critical roles in the pathogenesis of DCM. CD4(+) LAP(+) Tregs are a newly identified T cell subset with suppressive function on the immune response. This study was designed to investigate whether the circulating frequency and function of CD4(+)LAP(+) Tregs would be impaired in patients with DCM. The results demonstrated that DCM patients had a significantly lower frequency of circulating CD4(+)LAP(+) Tregs compared with control donors. CD4(+)LAP(+) Tregs from DCM patients showed compromised function to suppress proliferation of CD4(+) LAP(-)CD25(int/low) T cells and proliferation and IgG production of B cells. Moreover, B cell proliferation and IgG subset production could be directly suppressed by CD4(+) LAP(+) Tregs. TGF-β and contact-dependent mechanisms were involved in CD4(+)LAP(+) Treg-mediated suppression. Correlation analysis suggested that CD4(+)LAP(+) Treg frequency was positively correlated with LVEF and negatively correlated with serum IgG3 and NT-proBNP concentration in patients with DCM. Our results are the first to demonstrate that the frequencies of CD4(+)LAP(+) Tregs in patients with DCM are reduced and that their suppressive function is compromised. Defective CD4(+) LAP(+) Tregs may be an underlying mechanism of immune activation in DCM patients.
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http://dx.doi.org/10.1189/jlb.5A1014-469RRDOI Listing
April 2015

The commonality between the perceptual adaptation mechanisms involved in processing faces and nonface objects of expertise.

Neuropsychology 2015 Sep 2;29(5):715-25. Epub 2015 Feb 2.

Department of Psychology, Vanderbilt University.

Objective: The authors designed 2 experiments to examine the commonality of the N170 component involved in processing faces and nonface objects of expertise.

Method: In Experiment 1, to investigate the N170 adaptation effect between faces and printed language, 18 bilingual participants (7 males) were recruited, and the N170 response elicited by faces and words was recorded using a 128-channel HydroCel Geodesic Sensor Net. To address whether this asymmetrical between-category N170 adaptation effect generalizes to any object of expertise, in Experiment 2, 19 participants (9 males) were recruited by training to become Greeble experts. The N170 component elicited by faces and Greebles was recorded before and after training.

Results: In Experiment 1, the authors found that only faces can affect the N170 response elicited by words but words cannot affect the N170 response elicited by face. In Experiment 2, both before and after training, Greeble adaptors did not affect the N170 response elicited by faces. It is important to note that after training, the faces decreased the N170 response elicited by the Greebles.

Conclusions: These results suggest that not only is there some commonality of N170 response elicited by face and nonface objects of expertise but also the kinds of functions associated with the N170 neural selectivity to faces were more than that to nonface expert objects.
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http://dx.doi.org/10.1037/neu0000170DOI Listing
September 2015

Activated regulatory T-cells attenuate myocardial ischaemia/reperfusion injury through a CD39-dependent mechanism.

Clin Sci (Lond) 2015 May;128(10):679-93

*Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology; Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.

Regulatory T-cells (Tregs) are generally regarded as key immunomodulators that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. However, its role in myocardial ischaemia/reperfusion injury (MIRI) remains unknown. The purpose of the present study was to determine whether Tregs exert a beneficial effect on mouse MIRI. We examined the role of Tregs in murine MIRI by depletion using 'depletion of regulatory T-cell' (DEREG) mice and adoptive transfer using Forkhead box P3 (Foxp3)-GFP knockin mice and the mechanisms of cardio protection were further studied in vivo and in vitro. Tregs rapidly accumulated in murine hearts following MIRI. Selective depletion of Tregs in the DEREG mouse model resulted in aggravated MIRI. In contrast, the adoptive transfer of in vitro-activated Tregs suppressed MIRI, whereas freshly isolated Tregs had no effect. Mechanistically, activated Treg-mediated protection against MIRI was not abrogated by interleukin (IL)-10 or transforming growth factor (TGF)-β1 inhibition but was impaired by the genetic deletion of cluster of differentiation 39 (CD39). Moreover, adoptive transfer of in vitro-activated Tregs attenuated cardiomyocyte apoptosis, activated a pro-survival pathway involving Akt and extracellular-signal-regulated kinase (ERK) and inhibited neutrophil infiltration, which was compromised by CD39 deficiency. Finally, the peripheral blood mononuclear cells of acute myocardial infarction (AMI) patients after primary percutaneous coronary intervention (PCI) revealed a decrease in CD4+CD25+CD127low Tregs and a relative increase in CD39+ cells within the Treg population. In conclusion, our data validated a protective role for Tregs in MIRI. Moreover, in vitro-activated Tregs ameliorated MIRI via a CD39-dependent mechanism, representing a putative therapeutic strategy.
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http://dx.doi.org/10.1042/CS20140672DOI Listing
May 2015
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