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Xin-Yue Cheng, Yu-Huan Li, Sheng Tang, Xin Zhang, Yan-Xiang Wang, Sheng-Gang Wang, Jian-Dong Jiang, Ying-Hong Li, Dan-Qing Song
Twenty-eight new 12N-benzenesulfonyl matrinic butane and halogenated 12N-sulfonyl matrinic butane/ethane derivatives were designed, synthesized and evaluated for their anti-coxsakievirus activities against CVB3 taking compound 1 as the lead. SAR analysis indicated the introduction of a fluoro atom on the 1'-position might be helpful for keeping potency. Among them, compound 8a exhibited potential activities against all CVBs with IC50 ranging from 0.69 to 5.14 μM, suggesting a broad-spectrum anti-coxsackievirus B feature...
September 30, 2016: European Journal of Medicinal Chemistry
Xiao-Qiang Li, Xiao-Xiao Liu, Xue-Ying Wang, Yan-Hua Xie, Qian Yang, Xin-Xin Liu, Yuan-Yuan Ding, Wei Cao, Si-Wang Wang
The chemical property of cinnamaldehyde is unstable in vivo, although early experiments have shown its obvious therapeutic effects on viral myocarditis (VMC). To overcome this problem, we used cinnamaldehyde as a leading compound to synthesize derivatives. Five derivatives of cinnamaldehyde were synthesized: 4-methylcinnamaldehyde (1), 4-chlorocinnamaldehyde (2), 4-methoxycinnamaldehyde (3), α-bromo-4-methylcinnamaldehyde (4), and α-bromo-4-chlorocinnamaldehyde (5). Neonatal rat cardiomyocytes and HeLa cells infected by coxsackievirus B3 (CVB3) were used to evaluate their antiviral and cytotoxic effects...
October 17, 2016: Biomolecules & Therapeutics
Haibin Jin, Xiaoming Guo
BACKGROUND: Viral myocarditis, which is often caused by coxsackievirus B3 (CVB3), is a serious clinical disorder characterized by excessive myocardial inflammation. Valproic acid (VPA) is described as a histone deacetylase inhibitor that has anti-inflammatory effects in several inflammatory diseases. However, the role and the detailed mechanism of VPA in viral myocarditis remain unclear. METHODS: Experimental CVB3-induced myocarditis was induced in mice by intraperitoneally (i...
October 10, 2016: Virology Journal
Chaoyu Sun, Lei Tong, Wenran Zhao, Yan Wang, Yuan Meng, Lexun Lin, Bingchen Liu, Yujia Zhai, Zhaohua Zhong, Xueqi Li
Coxsackievirus B3 (CVB3) is a common causative agent in the development of inflammatory cardiomyopathy. However, whether the expression of peripheral blood microRNAs (miRNAs) is altered in this process is unknown. The present study investigated changes to miRNA expression in the peripheral blood of CVB3-infected mice. Utilizing miRNA microarray technology, differential miRNA expression was examined between normal and CVB3-infected mice. The present results suggest that specific miRNAs were differentially expressed in the peripheral blood of mice infected with CVB3, varying with infection duration...
October 2016: Experimental and Therapeutic Medicine
Tuanjie Wang, Jian Zhang, Aiju Xiao, Weiqing Liu, Yun Shang, Jindou An
Viral myocarditis (VMC) is characterized as an inflammatory process of the myocardium and can be fatal in infants and children. Melittin is a major polypeptide in honey bee venom that has been traditionally used against inflammation. However, its effect on VMC and the underlying molecular mechanism has not been reported. In this study, BALB/c mice were intraperitoneally injected with CVB3 to build a VMC model and treated with melittin. The results showed that melittin increased the mice's body weight and inhibited CVB3 replication...
September 28, 2016: Biochemical and Biophysical Research Communications
Ning Dong, Chunsheng Dong, Sidong Xiong
BACKGROUND: Coxsackievirus (CVB3) infection is the most common cause of viral myocarditis (VMC) characterized by viral infection and myocardial inflammation. ADAR1, the interferon (IFN)-inducible adenosine deaminase acting on RNA, has been reported to be functional in various viruses. Recent studies have demonstrated that ADAR1 holds an antiviral role or promotes viral replication depending on virus type. OBJECTIVES: This study aims to investigate whether or not ADAR1 affects CVB3-induced VMC...
November 15, 2016: International Journal of Cardiology
Ageng Wiyatno, Ungke Antonjaya, Chairin Nisa Ma'roef, Silvita Fitri Riswari, Hofiya Djauhari, I Made Artika, Corina Monagin, Bradley S Schneider, Khin Saw Myint, Bachti Alisjahbana, Dodi Safari, Herman Kosasih
INTRODUCTION: Coxsackievirus B3 (CVB3) virus has been implicated as the causative agent of various outbreaks of clinical disease, including hand, foot, and mouth diseases, aseptic meningitis, acute myocarditis, and inflammatory cardiomyopathy. METHODOLOGY: Two hundred and nine undiagnosed cryopreserved specimens obtained from factory workers in Bandung, Indonesia, who displayed symptoms of acute febrile illness were gathered. Total RNA was isolated from serum and tested by conventional polymerase chain reaction (PCR) using Enterovirus genus-level primers and confirmed by sequencing...
2016: Journal of Infection in Developing Countries
Nicole Ettischer-Schmid, Andrea Normann, Martina Sauter, Lisa Kraft, Hubert Kalbacher, Reinhard Kandolf, Bertram Flehmig, Karin Klingel
Human enteroviruses, e.g. coxsackieviruses, induce a variety of severe acute and chronic forms of disease, including myocarditis, meningitis and diabetes mellitus type 1. To visualize enterovirus infection with a diagnostic intent, many studies have applied a commercially available antibody (anti-CVB5 VP1, clone 5-D8/1, Dako, Hamburg, Germany) that identifies VP1 of different enteroviral serotypes. Many antibodies, however, have been found to bind non-specifically to proteins of cardiomyocytes and in the interstitial space, resulting in non-specific staining in immunohistochemistry...
August 27, 2016: Virchows Archiv: An International Journal of Pathology
Yun-Gyeong Lee, Jung-Ho Park, Eun-Seok Jeon, Jin-Hee Kim, Byung-Kwan Lim
Coxsackievirus B3 (CVB3) is the main cause of acute myocarditis and dilated cardiomyopathy. Plant extract is considered as useful materials to develop new antiviral drug. We select the candidate plant extract, which showed anti-inflammatory effect previously. We examined the antiviral effects by using a HeLa cell survival assay. Among these extracts, we chose the Amomi Cardamomi (Amomi) extract, which showed strong antiviral effect and preserved cell survival in CVB3 infection. We investigated the mechanisms underlying the ability of Amomi extract to inhibit CVB3 infection and replication...
August 24, 2016: Journal of Microbiology and Biotechnology
Minghui Li, Yangang Su, Yong Yu, Ying Yu, Xinggang Wang, Yunzeng Zou, Junbo Ge, Ruizhen Chen
BACKGROUND: Viral myocarditis (VMC) treatment has long been lacking of effective methods. Our former studies indicated roles of calpain in VMC pathogenesis. This study aimed at verifying the potential of calpain in Coxsackievirus B3 (CVB3)-induced myocarditis treatment. METHODS: A transgenic mouse overexpressing the endogenous calpain inhibitor, calpastatin, was introduced in the study. VMC mouse model was established via intraperitoneal injection of CVB3 in transgenic and wild mouse respectively...
October 15, 2016: International Journal of Cardiology
H M van der Schaar, C E Melia, J A C van Bruggen, J R P M Strating, M E D van Geenen, A J Koster, M Bárcena, F J M van Kuppeveld
Like all other positive-strand RNA viruses, enteroviruses generate new organelles (replication organelles [ROs]) with a unique protein and lipid composition on which they multiply their viral genome. Suitable tools for live-cell imaging of enterovirus ROs are currently unavailable, as recombinant enteroviruses that carry genes that encode RO-anchored viral proteins tagged with fluorescent reporters have not been reported thus far. To overcome this limitation, we used a split green fluorescent protein (split-GFP) system, comprising a large fragment [strands 1 to 10; GFP(S1-10)] and a small fragment [strand 11; GFP(S11)] of only 16 residues...
July 2016: MSphere
Shengyang Jiang, Shunli Tian, Xueming Wu, Yijia Tao, Donglin Jiang
Excessive fibroblast proliferation and collagen production are the major pathogenic mechanisms in the progression of viral myocarditis, which is most frequently associated with infection by coxsackievirus B3 (CVB3). AMP-activated protein kinase (AMPK) has been confirmed to be involved in the progression of myocardial remodeling. However, it remains unclear whether AMPK has an effect on CVB3-induced cardiac fibroblast proliferation. In the present study, the effects of AMPK on cardiac fibroblast proliferation and collagen secretion induced by CVB3 were investigated...
June 2016: Experimental and Therapeutic Medicine
Nicole R Sexton, Everett Clinton Smith, Hervé Blanc, Marco Vignuzzi, Olve B Peersen, Mark R Denison
UNLABELLED: Positive-sense RNA viruses encode RNA-dependent RNA polymerases (RdRps) essential for genomic replication. With the exception of the large nidoviruses, such as coronaviruses (CoVs), RNA viruses lack proofreading and thus are dependent on RdRps to control nucleotide selectivity and fidelity. CoVs encode a proofreading exonuclease in nonstructural protein 14 (nsp14-ExoN), which confers a greater-than-10-fold increase in fidelity compared to other RNA viruses. It is unknown to what extent the CoV polymerase (nsp12-RdRp) participates in replication fidelity...
August 15, 2016: Journal of Virology
Li-ying Xuan, Xie-xin Tao, Ya-jun Zhao, Hong-yan Ge, Li-hong Bao, Da-peng Wang, Ming Zhao
OBJECTIVE: To investigate the effect of total flavonoids of astragalus on the expression of endoplasmic reticulum chaperone, calumenin and connecxin 43 (CX43) in suckling mouse myocardium with myocarditis caused by coxsackievirus B3 (CVB3). METHODS: The primary culture of suckling mouse myocardium cells were randomly divided into control group, CVB3 infected group and total flavonoids of astragalus group. Firstly, to confirm the identity of the suckling mouse myocardium, α-SMA was monitored by immunohistochemistry method...
January 2016: Chinese Journal of Applied Physiology
Xiaodan Shi, Zijian Chen, Shengjie Tang, Fei Wu, Sidong Xiong, Chunsheng Dong
Autophagy is an intrinsic cellular process that can degrade cytoplasmic components. It has been reported that several pathogens hijack this process to facilitate their replication. Coxsackievirus B3 (CVB3), a member of the family Picornaviridae, induces autophagy upon infection. However, the details of CVB3-induced autophagy remain a subject of debate. This study applied a combination of multiple assays for the measurement of autophagy and demonstrated that CVB3 induces a complete autophagic flux. Experiments with infected HEK293A cells revealed that autophagosomes were induced upon CVB3 infection...
August 2016: Archives of Virology
Shengyang Jiang, Donglin Jiang, Peng Zhao, Xinlong He, Shunli Tian, Xueming Wu, Yijia Tao
Collagen deposition is the major cause of myocardial fibrosis, contributing to impaired cardiac contractile function in coxsackie virus B3 (CVB3)-infected hearts. Adenosine monophosphate-activated protein kinase (AMPK) has been considered as a cellular fuel gauge and super metabolic regulator, however, whether AMPK has an effect on collagen production in CVB3‑infected heart remains to be elucidated. In the present study, the association between AMPK activation and CVB3‑infected neonatal rat cardiac fibroblasts (NRCFs) was investigated...
July 2016: Molecular Medicine Reports
Bo-Eun Kwon, Jae-Hyoung Song, Hyuk-Hwan Song, Ju Won Kang, Sam Noh Hwang, Ki-Jong Rhee, Aeri Shim, Eun-Hye Hong, Yeon-Jeong Kim, Sang-Min Jeon, Sun-Young Chang, Dong-Eun Kim, Sungchan Cho, Hyun-Jeong Ko
The flavonoids mosloflavone, oroxylin A, and norwogonin, which were purified from Scutellaria baicalensis Georgi, significantly protected Vero cells against Coxsackievirus B3 (CVB3)-induced cell death. To investigate the in vivo antiviral activity of oroxylin A, we intraperitoneally inoculated CVB3 into 4-week-old BALB/c mice. Body weights and blood glucose levels of the mice were decreased after CVB3 infection, and these changes were attenuated by the administration of oroxylin A. Importantly, treatment of mice with oroxylin A reduced viral titers in the pancreas and decreased the serum levels of the inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α...
2016: PloS One
Bo-Kyoung Kim, Hyojin Ko, Eun-Seok Jeon, Eun-Seon Ju, Lak Shin Jeong, Yong-Chul Kim
Human coxsackievirus B3 (CVB3) 3C protease plays an essential role in the viral replication of CVB3, which is a non-enveloped and positive single-stranded RNA virus belonging to Picornaviridae family, causing acute viral myocarditis mainly in children. During optimization based on SAR studies of benserazide (3), which was reported as a novel anti-CVB3 3C(pro) agent from a screening of compound libraries, the 2,3,4-trihydroxybenzyl moiety of 3 was identified as a key pharmacophore for inhibitory activity against CVB3 3C(pro)...
September 14, 2016: European Journal of Medicinal Chemistry
Heng Wu, Xia Zhai, Yang Chen, Ruixue Wang, Lexun Lin, Sijia Chen, Tianying Wang, Xiaoyan Zhong, Xiaoyu Wu, Yan Wang, Fengmin Zhang, Wenran Zhao, Zhaohua Zhong
Coxsackievirus B (CVB) belongs to Enterovirus genus within the Picornaviridae family, and it is one of the most common causative pathogens of viral myocarditis in young adults. The pathogenesis of myocarditis caused by CVB has not been completely elucidated. In CVB infection, autophagy is manipulated to facilitate viral replication. Here we report that protein 2B, one of the non-structural proteins of CVB3, possesses autophagy-inducing capability. The autophagy-inducing motif of protein 2B was identified by the generation of truncated 2B and site-directed mutagenesis...
2016: Viruses
Chun Wen, Gui Xie, Ping Zeng, Lin-Feng Huang, Chun-Yuan Chen
OBJECTIVE: To investigate the effect of tranilast on myocardial fibrosis in mice with viral myocarditis (VMC). METHODS: Male balb/c mice (n=72) were randomly divided into control, VMC and tranilast groups (n=24 each). In the VMC and tranilast groups, the mice were infected with Coxsackie virus B3 (CVB3) to prepare VMC model, while the control group was treated with Eagle's medium. After modeling, the tranilast group was administrated with tranilast [200 mg/(kg...
May 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
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