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https://www.readbyqxmd.com/read/28186704/mesenchymal-stromal-cells-modulate-monocytes-trafficking-in-coxsackievirus-b3-induced-myocarditis
#1
Kapka Miteva, Kathleen Pappritz, Muhammad El-Shafeey, Fengquan Dong, Jochen Ringe, Carsten Tschöpe, Sophie Van Linthout
Mesenchymal stromal cell (MSC) application in Coxsackievirus B3 (CVB3)-induced myocarditis reduces myocardial inflammation and fibrosis, exerts prominent extra-cardiac immunomodulation, and improves heart function. Although the abovementioned findings demonstrate the benefit of MSC application, the mechanism of the MSC immunomodulatory effects leading to a final cardioprotective outcome in viral myocarditis remains poorly understood. Monocytes are known to be a trigger of myocardial tissue inflammation. The present study aims at investigating the direct effect of MSC on the mobilization and trafficking of monocytes to the heart in CVB3-induced myocarditis...
January 3, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28176833/transmissible-endoplasmic-reticulum-stress-from-myocardiocytes-to-macrophages-is-pivotal-for-the-pathogenesis-of-cvb3-induced-viral-myocarditis
#2
Hui Zhang, Yan Yue, Tianle Sun, Xuejie Wu, Sidong Xiong
Infiltrating macrophages have been proven as a pivotal pathological inflammatory cell subset in coxsackievirus B3 (CVB3) induced viral myocarditis. However, the mechanisms underlying the initiation and promotion of macrophage pro-inflammatory responses are still blur. We previously reported that cardiac ER stress contributed to CVB3-induced myocarditis by augmenting inflammation. In this study, we focused on the influence of ER stress on the macrophage inflammatory responses in the viral myocarditis. We found that ER stress was robustly induced in the cardiac infiltrating macrophages from CVB3-infected mice, and robustly facilitated the production of pro-inflammatory cytokines (IL-6, IL-12, MCP-1 and IP-10)...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174228/profiling-subcellular-protein-phosphatase-responses-to-coxsackievirus-b3-infection-of-cardiomyocytes
#3
Millie Shah, Christian M Smolko, Sarah Kinicki, Zachary D Chapman, David L Brautigan, Kevin A Janes
Cellular responses to stimuli involve dynamic and localized changes in protein kinases and phosphatases. Here, we report a generalized functional assay for high-throughput profiling of multiple protein phosphatases with subcellular resolution and apply it to analyze coxsackievirus B3 (CVB3) infection counteracted by interferon signaling. Using on-plate cell fractionation optimized for adherent cells, we isolate protein extracts containing active endogenous phosphatases from cell membranes, the cytoplasm, and the nucleus...
February 7, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28148910/intein-mediated-backbone-cyclization-of-vp1-protein-enhanced-protection-of-cvb3-induced-viral-myocarditis
#4
Xingmei Qi, Sidong Xiong
CVB3 is a common human pathogen to be highly lethal to newborns and causes viral myocarditis and pancreatitis in adults. However, there is no vaccine available for clinical use. CVB3 capsid protein VP1 is an immunodominant structural protein, containing several B- and T-cell epitopes. However, immunization of mice with VP1 protein is ineffective. Cyclization of peptide is commonly used to improve their in vivo stability and biological activity. Here, we designed and synthesizd cyclic VP1 protein by using engineered split Rma DnaB intein and the cyclization efficiency was 100% in E...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28137624/incorporation-of-a-bi-functional-protein-fimh-enhances-the-immunoprotection-of-chitosan-pvp1-vaccine-against-coxsackievirus-b3-induced-myocarditis
#5
Xiangmei Fan, Yan Yue, Sidong Xiong
Viral myocarditis is a common clinical cardiovascular disease mainly induced by coxsackievirus B3 (CVB3) with no effective therapeutic measures. Induction of efficient mucosal immune responses is very critical against CVB3-induced myocarditis. FimH is an Escherichia coli (E. coli)-derived protein, which possesses an M cell-targeting property and functions as a TLR4 agonist. In this study, we introduced the recombinant FimH protein, into our previously developed CVB3 mucosal vaccine chitosan (CS)-pVP1, aiming to provoke more efficient mucosal immune responses and immunoprotection against CVB3-induced myocarditis...
January 28, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28131843/inhibition-of-drp1-attenuates-mitochondrial-damage-and-myocardial-injury-in-coxsackie-virus-b3-induced-myocarditis
#6
Lin Lin, Ming Zhang, Rui Yan, Hu Shan, Jiayu Diao, Jin Wei
Viral myocarditis (VMC) is closely related to apoptosis, oxidative stress, innate immunity, and energy metabolism, which are all linked to mitochondrial dysfunction. A close nexus between mitochondrial dynamics and cardiovascular disease with mitochondrial dysfunction has been deeply researched, but there is still no relevant report in viral myocarditis. In this study, we aimed to explore the role of Dynamin-related protein 1 (Drp1)-linked mitochondrial fission in VMC. Mice were inoculated with the Coxsackie virus B3 virus (CVB3) and treated with mdivi1 (a Drp1 inhibitor)...
January 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28129450/viral-encephalitis-after-haplo-identical-hematopoietic-stem-cell-transplantation-causative-viral-spectrum-characteristics-and-risk-factors
#7
Xiao-Hui Zhang, Jia-Min Zhang, Wei Han, Huan Chen, Yu-Hong Chen, Feng-Rong Wang, Jing-Zhi Wang, Yuan-Yuan Zhang, Xiao-Dong Mo, Yao Chen, Yu Wang, Ying-Jun Chang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang
OBJECTIVE: To retrospectively identify characteristics and risk factors of viral encephalitis (VE) in patients who underwent a haplo-identical hematopoietic stem cell transplant (HSCT). METHODS: A nested case-control study was designed. Cases with VE and controls were identified from a cohort composed of 1274 patients who underwent a haplo-identical HSCT from 2012 to 2015. RESULTS: VE was identified in 30 patients (2.4%).The median time from HSCT to diagnosis was 144...
January 27, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28123495/effects-of-the-mapk-pathway-and-the-expression-of-car-in-a-murine-model-of-viral-myocarditis
#8
Ling Niu, Chunli Li, Zhenzhou Wang, Hui Xu, Xinjiang An
The pathogenesis of viral myocarditis (VMC) is not fully understood. This study aimed to examine the relationship between coxsackie-adenovirus receptor (CAR) and the p38 mitogen activated protein kinase (MAPK) pathway mechanisms in a mouse model. Three groups of mice were established: 5 mice in a control group injected with saline, 15 in the model group injected with coxsackie virus B3 (CVB) and 15 in the intervention group injected with CVB3 but treated with the p38 MAPK inhibitor SB203580. Mice were sacrificed at days 1, 5, 10, 15 and 30 and cardiac tissues were isolated to perform the tests...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28110209/expansion-of-cd11b-ly-6c-myeloid-derived-suppressor-cells-mdscs-driven-by-galectin-9-attenuates-cvb3-induced-myocarditis
#9
Yingying Zhang, Mengying Zhang, Xueqin Li, Zongsheng Tang, Ling He, Kun Lv
Galectin-9 is known to play a role in the modulation of innate and adaptive immunity to ameliorate CVB3-induced myocarditis. In the present study, we found that galectin-9 induced the expansion of CD11b(+)Ly-6C(+) myeloid-derived suppressor cells (MDSCs) in the heart from CVB3-infected mice. Adoptive transfer of CD11b(+)Ly-6C(+) MDSCs significantly alleviated myocarditis accompanied by increased Th2 and Treg frequency and anti-inflammatory cytokines expression in the heart tissue. Moreover, Ly6C(+) MDSCs, but not Ly6G(+) cells, expressed Arg-1 and NOS2, and suppressed CD4(+) T cell proliferation in vitro in an Arg-1-dependent mechanism; an event that was reversed with treatment of either an Arg-1 inhibitor or addition of excess l-arginine...
January 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28109785/novel-12n-substituted-matrinanes-as-potential-anti-coxsackievirus-agents
#10
Ying-Hong Li, Sheng Tang, Yu-Huan Li, Xin-Yue Cheng, Xin Zhang, Yan-Xiang Wang, Feng Su, Dan-Qing Song
A series of novel 12N-substituted matrinane derivatives were synthesized and evaluated for their activities against coxsackievirus type B3 (CVB3) taking compound 1 as the lead. SAR analysis indicated that the introduction of a suitable heteroaromatic ring on the 12N-atom might be beneficial for the activity. Among them, compound 8a exhibited the highest potency against all CVB serotypes as well as CVA16 with IC50 values ranging from 2.02μM to 7.41μM, indicating a broad-spectrum anti-coxsackieviruse effect...
January 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28100612/sex-dependent-intestinal-replication-of-an-enteric-virus
#11
Christopher M Robinson, Yao Wang, Julie K Pfeiffer
: Coxsackievirus is an enteric virus that initiates infection in the gastrointestinal tract before disseminating to peripheral tissues to cause disease, but intestinal factors that influence viral replication are understudied. Furthermore, a sex bias for severe sequelae from coxsackievirus infections has been observed in humans. While mouse models mimicking human pathogenesis have been well characterized, many of these experiments use intraperitoneal injection of coxsackievirus to infect mice, bypassing the intestine...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28095607/heat-shock-protein-70-promotes-coxsackievirus-b3-translation-initiation-and-elongation-via-akt-mtorc1-pathway-depending-on-activation-of-p70s6k-and-cdc2
#12
Fengping Wang, Ye Qiu, Huifang M Zhang, Paul Hanson, Xin Ye, Guangze Zhao, Ronald Xie, Lei Tong, Decheng Yang
We previously demonstrated that coxsackievirus B3 (CVB3) infection upregulated heat shock protein 70 (Hsp70) and promoted CVB3 multiplication. Here, we report the underlying mechanism by which Hsp70 enhances viral RNA translation. By using an Hsp70-overexpressing cell line infected with CVB3, we found that Hsp70 enhanced CVB3 VP1 translation at two stages. First, Hsp70 induced upregulation of VP1 translation at the initiation stage via upregulation of internal ribosome entry site trans-acting factor lupus autoantigen protein and activation of eIF4E binding protein 1, a cap-dependent translation suppressor...
January 17, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28041873/il-33-enhances-macrophage-m2-polarization-and-protects-mice-from-cvb3-induced-viral-myocarditis
#13
Chao Wang, Chunsheng Dong, Sidong Xiong
Viral myocarditis is the inflammation caused by myocardial virus infection, and the coxsackievirus group B3 virus (CVB3) is the most common pathogen. An efficient therapeutic agent against viral myocarditis is currently unavailable. IL-33, a new member of the IL-1 cytokine superfamily, exhibits potential immunotherapeutic effect against inflammatory and autoimmune diseases. However, the functional role of IL-33 in viral myocarditis has not been investigated. To examine the therapeutic role of IL-33 in viral myocarditis, an IL-33 overexpression plasmid (pDisplay-IL-33) and IL-33 knockdown plasmid (pLL3...
December 29, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28018858/coxsackievirus-b3-directly-induced-th17-cell-differentiation-by-inhibiting-nup98-expression-in-patients-with-acute-viral-myocarditis
#14
Qi Long, Yu-Hua Liao, Yu Xie, Wei Liang, Xiang Cheng, Jing Yuan, Miao Yu
Th17 cells play a key role in the progression of coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVMC). However, the direct effect of virus on Th17 cell differentiation is still unknown. Recently, nucleoporin (Nup) 98 has been proved to be associated with lymphocyte differentiation. Therefore, we investigated whether Nup98 mediated Th17 cell differentiation in AVMC. In our study, patients with AVMC and healthy controls were recruited. The results showed that CVB3 could enter into the CD4(+) T cells in AVMC patients and healthy controls...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27940223/mops-and-coxsackievirus-b3-stability
#15
Steven D Carson, Susan Hafenstein, Hyunwook Lee
Study of coxsackievirus B3 strain 28 (CVB3/28) stability using MOPS to improve buffering in the experimental medium revealed that MOPS (3-morpholinopropane-1-sulfonic acid) increased CVB3 stability and the effect was concentration dependent. Over the pH range 7.0-7.5, virus stability was affected by both pH and MOPS concentration. Computer-simulated molecular docking showed that MOPS can occupy the hydrophobic pocket in capsid protein VP1 where the sulfonic acid head group can form ionic and hydrogen bonds with Arg95 and Asn211 near the pocket opening...
January 15, 2017: Virology
https://www.readbyqxmd.com/read/27886550/v%C3%AE-1-%C3%AE-%C3%AE-t-early-cardiac-infiltrated-innate-population-dominantly-producing-il-4-protect-mice-against-cvb3-myocarditis-by-modulating-ifn%C3%AE-t-response
#16
Fangfang Wan, Kepeng Yan, Dan Xu, Qian Qian, Hui Liu, Min Li, Wei Xu
Viral myocarditis (VMC) is an inflammation of the myocardium closely associated with Coxsackievirus B3 (CVB3) infection. Vγ1(+)γδT cells, one of early cardiac infiltrated innate population, were reported to protect CVB3 myocarditis while the precise mechanism not fully addressed. To explore cytokine profiles and kinetics of Vγ1(+)γδT and mechanism of protection against VMC, flow cytometry was conducted on cardiac Vγ1 cells in C57BL/6 mice following CVB3 infection. The level of cardiac inflammation, transthoracic echocardiography and viral replication were evaluated after monoclonal antibody depletion of Vγ1γδT...
January 2017: Molecular Immunology
https://www.readbyqxmd.com/read/27793649/coxsackievirus-b3-induces-the-formation-of-autophagosomes-in-cardiac-fibroblasts-both-in-vitro-and-in-vivo
#17
Xia Zhai, Ying Qin, Yang Chen, Lexun Lin, Tianying Wang, Xiaoyan Zhong, Xiaoyu Wu, Sijia Chen, Jing Li, Yan Wang, Fengmin Zhang, Wenran Zhao, Zhaohua Zhong
Coxsackievirus group B (CVB) is one of the common pathogens that cause myocarditis and cardiomyopathy. Evidence has shown that CVB replication in cardiomyocytes is responsible for the damage and loss of cardiac muscle and the dysfunction of the heart. However, it remains largely undefined how CVB would directly impact cardiac fibroblasts, the most abundant cells in human heart. In this study, cardiac fibroblasts were isolated from Balb/c mice and infected with CVB type 3 (CVB3). Increased double-membraned, autophagosome-like vesicles in the CVB3-infected cardiac fibroblasts were observed with electron microscope...
October 25, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27792321/antiviral-triterpenes-from-the-twigs-and-leaves-of-lyonia-ovalifolia
#18
Xiao-Jing Lv, Yong Li, Shuang-Gang Ma, Jing Qu, Yun-Bao Liu, Yu-Huan Li, Dan Zhang, Li Li, Shi-Shan Yu
Eleven new 9,10-seco-cycloartan triterpene glycosides (1-11), seven new lanostane triterpene glycosides (12-18), and two new ursane triterpenoids (19-20) were isolated from the twigs and leaves of Lyonia ovalifolia. The structures of these compounds were elucidated by extensive MS and NMR spectroscopic analysis. The absolute configuration of compound 1a (the aglycone of 1) was established by X-ray crystallography, and that of C-24 in compounds 2, 7, and 12 was established by Mo2(OAc)4-induced electronic circular dichroism experiments...
November 23, 2016: Journal of Natural Products
https://www.readbyqxmd.com/read/27766098/il-9-inhibits-viral-replication-in-coxsackievirus-b3-induced-myocarditis
#19
Miao Yu, Qi Long, Huan-Huan Li, Wei Liang, Yu-Hua Liao, Jing Yuan, Xiang Cheng
Myocardial injuries in viral myocarditis (VMC) are caused by viral infection and related autoimmune disorders. Recent studies suggest that IL-9 mediated both antimicrobial immune and autoimmune responses in addition to allergic diseases. However, the role of IL-9 in viral infection and VMC remains controversial and uncertain. In this study, we infected Balb/c mice with Coxsackievirus B3 (CVB3), and found that IL-9 was enriched in the blood and hearts of VMC mice on days 5 and 7 after virus infection. Most of IL-9 was secreted by CD8(+) T cells on day 5 and CD4(+) T cells on day 7 in the myocardium...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27753702/green-tea-polyphenol-epigallocatechin-3-gallate-alleviated-coxsackievirus-b3-induced-myocarditis-through-inhibiting-viral-replication-but-not-through-inhibiting-inflammatory-responses
#20
Xiran He, Bo Gao, Lei Zhou, Sidong Xiong
Viral myocarditis, which is mainly caused by coxsackievirus B3 (CVB3), affects about 5%-20% of the world population and still lacks efficient treatments. Green tea, a tonic and healthful beverage that was originated in ancient China, has been receiving considerable attention for its protective effect on cardiovascular diseases in recent years. In the present investigation, we aimed to explore the effect of green tea polyphenol epigallocatechin-3-gallate (EGCG) on CVB3-induced myocarditis and its underlying mechanism...
January 2017: Journal of Cardiovascular Pharmacology
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