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Neha J Pancholi, Matthew D Weitzman
During viral replication in the nucleus, the DNA genomes of adenoviruses are accessible to cellular DNA-binding proteins. Human adenovirus type 5 (Ad5) targets the cellular Mre11-Rad50-Nbs1 complex (MRN) to evade detection by the DNA damage response (DDR). Ad5 mutants that cannot target MRN have reduced viral propagation. Previous studies showed that diverse adenovirus serotypes interact differently with MRN. While these studies revealed diverse MRN interactions among serotypes, it remains unclear how these differences influence viral replication...
March 13, 2018: Virology
Ana Carla Peixoto Guissoni, Célia Maria Almeida Soares, Kareem R Badr, Fabiola Sousa Ficcadori, Ana Flávia Alves Parente, Juliana Alves Parente, Lilian Cristina Baeza, Menira Souza, Divina das Dores de Paula Cardoso
Human Adenoviruses (HAdVs) are etiological agents of different syndromes such as gastroenteritis, cystitis, ocular, and respiratory diseases, and infection by these viruses may cause alterations in cellular homeostasis. The objective of the study was the proteomic analysis of A-549 cells infected with HAdV-40 using LC-MS. At 30 h of infection, the quantitative analysis revealed 336 differentially expressed proteins. From them, 206 were induced (up-regulated) and 130 were suppressed (down-regulated). The majority of up-regulated proteins were related to energy, cellular organization, stress response, and apoptosis pathways...
March 15, 2018: Virus Genes
Peng You, Ning Chen, Lin Su, Tao Peng, Guodong Chen, Yulan Liu
Transforming growth factor β1 (TGF-β1) has a crucial role in regulating the balance of type 17 T-helper cells (Th17) and T regulatory cells (Tregs) that are involved in the pathogenesis of inflammatory bowel disease, while the function of local TGF-β1 in this process has remained to be fully elucidated. The present study investigated the effects of different local TGF-β1 levels on the Treg/Th17 balance and on the dexamethasone efficacy in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis...
April 2018: Experimental and Therapeutic Medicine
Annebel R De Vleeschauwer, Xiaocui Zhou, David J Lefebvre, Annabelle Garnier, Fleur Watier, Charly Pignon, Sandrine A Lacour, Stephan Zientara, Labib Bakkali-Kassimi, Kris De Clercq, Bernard Klonjkowski
Vaccination is a key element in the control of foot-and-mouth disease (FMD). The majority of the antigenic sites that induce protective immune responses are localized on the FMD virus (FMDV) capsid that is formed by four virus-encoded structural proteins, VP1 to VP4. In the present study, recombinant canine adenovirus type 2 (CAV2)-based FMD vaccines, Cav-P1/3C R° and Cav-VP1 R°, respectively expressing the structural P1 precursor protein along with the non-structural 3C protein or expressing the structural VP1 protein of the FMDV strain O/FRA/1/2001, were evaluated as novel vaccines against FMD...
March 12, 2018: Vaccine
Daniela Sorriento, Gaetano Santulli, Michele Ciccarelli, Angela Serena Maione, Maddalena Illario, Bruno Trimarco, Guido Iaccarino
We have recently demonstrated that the amino-terminal domain of G protein coupled receptor kinase (GRK) type 5, (GRK5-NT) inhibits NFκB activity in cardiac cells leading to a significant amelioration of LVH. Since GRK5-NT is known to bind calmodulin, this study aimed to evaluate the functional role of GRK5-NT in the regulation of calcium-calmodulin-dependent transcription factors. We found that the overexpression of GRK5-NT in cardiomyoblasts significantly reduced the activation and the nuclear translocation of NFAT and its cofactor GATA-4 in response to phenylephrine (PE)...
March 15, 2018: International Journal of Molecular Sciences
Amit Gaba, Lisanework E Ayalew, Amrutlal Patel, Pankaj Kumar, Suresh K Tikoo
Adenovirus protein VIII appears to connect core with the inner surface of the adenovirus capsid. Since protein- protein interactions are central to virus replication, identification of proteins interacting with protein VIII may help in understanding their role in adenovirus infection. Our yeast two hybrid assay indicated that protein VIII interacts with eukaryotic initiation factor 6 (eIF6). These findings were confirmed by GST-pull down assay, bimolecular fluorescent complementation assay and co-immunoprecipitation assay in plasmid DNA transfected and BAdV-3 infected cells...
March 15, 2018: Cellular Microbiology
Laura Lopez-Sanz, Susana Bernal, Carlota Recio, Iolanda Lazaro, Ainhoa Oguiza, Ana Melgar, Luna Jimenez-Castilla, Jesus Egido, Carmen Gomez-Guerrero
Oxidative stress resulting from excessive production of reactive oxygen species (ROS) or impaired antioxidant defenses is closely related to the development of diabetic vascular complications, including nephropathy and atherosclerosis. Chronic activation of Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes to diabetic complications by inducing expression of genes involved in cell proliferation, fibrosis, inflammation, and oxidative stress. Suppressors of cytokine signaling (SOCS) family of endogenous JAK/STAT regulators is an attractive target for therapeutic intervention...
March 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Bo Li, Xiangsong Wu, Hanbei Chen, Chengle Zhuang, Zhiguo Zhang, Shuangshuang Yao, Dongsheng Cai, Guang Ning, Qing Su
MicroRNAs (miRNAs) are known to contribute to many metabolic diseases, including diabetes. In this study, we investigated the role of miR199a-5p in the regulation of hepatic insulin sensitivity. Ad-anti-miR199a-5p adenoviruses were injected into male C57BL/6J WT mice fed a high-fat diet to inhibit miR199a-5p expression before the glucose levels and insulin resistance were assessed. Similarly, Ad-miR199a-5p adenoviruses were injected into male C57BL/6J WT mice to cause the overexpression of miR199a-5p. To investigate the roles of autophagy-related protein 14 (ATG14) and miR199a-5p in the regulation of insulin sensitivity, we injected Ad-miR199a-5p with or without Ad-ATG14 viruses into WT C57BL/6J mice before performing functional assays...
March 14, 2018: Cell Death & Disease
Li Wang, Yang Li, Na Ning, Jin Wang, Zi Yan, Suli Zhang, Xiangying Jiao, Xiaohui Wang, Huirong Liu
It has been recognized that myocardial apoptosis is one major factor in the development of heart dysfunction and autophagy has been shown to influence the apoptosis. In previous studies, we reported that anti-β1 -adrenergic receptor autoantibodies (β1 -AABs) decreased myocardial autophagy, but the role of decreased autophagy in cardiomyocyte apoptosis remains unclear. In the present study, we used a β1 -AAB-immunized rat model to investigate the role of decreased autophagy in cardiomyocyte apoptosis. We reported that the level of autophagic flux increased early and then decreased in an actively β1 -AAB-immunized rat model...
March 14, 2018: Cell Death & Disease
Naho Hirayama, Toshihiko Aki, Takeshi Funakoshi, Kanako Noritake, Kana Unuma, Koichi Uemura
Paraquat (PQ) is an herbicide that was once used worldwide, but is now prohibited in many nations due to its high toxicity to humans. However, there are still rare cases of the fetal intoxication of PQ, which was purchased prior to the prohibition in Japan. In this study, several cell death pathways, the mitochondrial stress response, and autophagy were examined in SH-SY5Y cells exposed to PQ. The results reveal the decrease of a mitochondrial stress sensitive-BNIP3 (Bcl-2/adenovirus E1B 19-kDa-interacting protein 3) protein, the suppression of autophagic flux, and the lack of apoptosis as well as other regulated forms of necrosis, such as necroptosis and ferroptosis...
2018: Journal of Toxicological Sciences
Beiqing Wu, Jianhui Liu, Runze Zhao, Yuju Li, Justin Peer, Alexander L Braun, Lixia Zhao, Yi Wang, Zenghan Tong, Yunlong Huang, Jialin C Zheng
BACKGROUND: Extracellular vesicles (EVs) are important in the intercellular communication of the central nervous system, and their release is increased during neuroinflammation. Our previous data demonstrated an increased release of EVs during HIV-1 infection and immune activation in glial cells. However, the molecular mechanism by which infection and inflammation increase EV release remains unknown. In the current study, we investigated the role of glutaminase 1 (GLS1)-mediated glutaminolysis and the production of a key metabolic intermediate α-ketoglutarate on EV release...
March 14, 2018: Journal of Neuroinflammation
Shelly Popowich, Ashish Gupta, Betty Chow-Lockerbie, Lisanework Ayalew, Neil Ambrose, Davor Ojkic, Thushari Gunawardana, Shanika Kurukulasuriya, Philip Willson, Suresh K Tikoo, Susantha Gomis
Historically, fowl adenovirus (FAdV) associated inclusion body hepatitis (IBH) was considered a secondary disease in broiler chickens associated with immunosuppression. However, we previously reported the occurrence of IBH as a primary disease in the broiler chicken industry in Canada as a result of infections with various FAdV serotypes. Therefore, the objectives of this study were to develop an immunization strategy in broiler breeders using live FAdV 11-1047 and FAdV8a-TR59 to confer homologous and heterologous protection in broiler progeny against IBH and to study the efficacy of natural exposure of naïve broiler breeders to a vaccine virus from live FAdV vaccinated birds as an immunization technique...
March 5, 2018: Research in Veterinary Science
Yang Yuan, Shan-Shan Pan
BACKGROUND: Late exercise preconditioning (LEP) is confirmed to have a protective effect on acute cardiovascular stress. However, the mechanisms by which mitophagy participates in EP-induced cardioprotection remain unclear. LEP may involve mitophagy mediated by the receptors PARK2 gene-encoded E3 ubiquitin ligase (Parkin) and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3) to scavenge damaged mitochondria. METHODS: Our exercise preconditioning (EP) protocol involved four 10-minute periods of running, separated by 10-minute recovery intervals, plus a period of exhaustive running at 24 hours after EP...
March 9, 2018: Journal of Cardiovascular Pharmacology
Shuo Yang, Tao Fan, Qi Hu, Weipan Xu, Jian Yang, Changwu Xu, Bofang Zhang, Jing Chen, Hong Jiang
MicroRNA-17-5p (miR-17-5p) was indicated to suppress the formation of blood vessels, which is associated with cardiac function after myocardial infarction. In this study, the relationship between miR-17-5p and cardiac function was researched. Human umbilical vein endothelial cells were infected with adenoviruses. Apoptosis was determined by Annexin V-7AAD/PI. Real-time RT-PCR was used to evaluate miR-17-5p and ERK levels. Western blotting was used to determine the levels of ERK, the anti-apoptosis protein bcl-2 and apoptosis proteins, including bax, caspase 3, and caspase 9...
March 13, 2018: Molecular Genetics and Genomics: MGG
Na Jiang, Lei Shi, Jieping Lin, Lifang Zhang, Yanxia Peng, Huiying Sheng, Ping Wu, Qingjun Pan
BACKGROUND: Rotavirus (RV) and enteric adenovirus (AdV) mainly cause infantile infectious gastroenteritis. Several separate test methods for the detection of RV or AdV are currently available, but few tests are able to simultaneously detect both RV and AdV viruses, especially in primary medical institutions. METHODS: The present study was mainly designed to compare the performance of two combined test strips for the detection of RV and AdV: a rotavirus-adenovirus strip with fluorescent microspheres for tracers (FMT); and the CerTest rotavirus-adenovirus blister strip with colored microspheres for tracers (CMT)...
March 13, 2018: Virology Journal
Raquel T Yokoda, Bolni M Nagalo, Mitesh J Borad
Gastrointestinal malignancies are challenging cancers with considerable economic and societal impacts on health care systems worldwide. While advances in surgical approaches have provided benefits to a proportion of patients, only modest improvements have been attained in the treatment of patients with advanced disease, resulting in limited improvement in survival rates in these patients. Oncolytic adenoviruses are being developed to address gastrointestinal malignancies. Each platform has evolved to maximize tumor-cell killing potency while minimizing toxicities...
March 11, 2018: Biomedicines
Angeliki Chroni, Dimitris Kardassis
The "HDL hypothesis" supporting that an elevation in HDL cholesterol (HDL-C) levels by drugs or by life style changes should be paralleled by a decrease in the risk for Cardiovascular Disease (CVD) has been challenged by recent epidemiological and clinical studies using HDL-raising drugs. HDL components such as proteins, lipids or small RNA molecules, but not cholesterol itself, possess various atheroprotective functions in different cell types and accumulating evidence supports the new hypothesis that HDL functionality is more important than HDL-C levels for CVD risk prediction...
March 12, 2018: Current Medicinal Chemistry
Yu-Na Im, Yu-Dong Lee, Jeong-Soo Park, Hae-Kyoung Kim, Suhn-Young Im, Hwa-Ryung Song, Hern-Ku Lee, Myung-Kwan Han
Many itch mediators activate G-protein coupled receptor (GPCR), and trigger itch via activation of GPCR-mediated signaling pathways. GPCRs are desensitized by G protein-coupled receptor kinases (GRKs). The aim of this study is to explore the role of GRKs in itch response and the linkage between GRKs and glutamine (Gln), an amino acid previously demonstrated as an itching reliever. Itch responses were evoked by histamine, chloroquine (CQ), and dinitrochlorobenzene (DNCB)-induced contact dermatitis (CD). Phosphorylation and protein expression were detected by immunofluorescent staining and Western blotting...
March 9, 2018: Journal of Investigative Dermatology
Yuk-Fai Lau, Wee-Hong Victor Koh, Clement Kan, Poh-Choo Alethea Dua, Ai-Sim Elizabeth Lim, Chin-Wen Jasper Liaw, Qiu-Han Gao, Jeremiah Chng, Vernon J Lee, Boon-Huan Tan, Jin-Phang Loh
BACKGROUND: Respiratory illnesses have been identified as a significant factor leading to lost training time and morbidity among Singapore military recruits. A surveillance programme has been put in place to determine etiological agents responsible for febrile, as well as afebrile respiratory illnesses in a military camp. The goal of the study is to better understand the epidemiology of these diseases and identify potential countermeasures to protect military recruits against them. METHODS: From Jan 2016 - Jan 2017, a total of 2647 respiratory cases were enrolled into the surveillance programme...
March 12, 2018: BMC Infectious Diseases
B Handan Özdemir, Şebnem Ayva, Gökçe Özdemir, Alev Ok Atılgan, Eda Akçay, F Nurhan Özdemir, Mehmet Haberal
OBJECTIVES: The interaction between calcium oxalate deposition and urinary tract infection is not well established. We aimed to identify the association between these and to determine the role of calcium oxalate deposition on interstitial fibrosis development. MATERIALS AND METHODS: Renal allograft biopsies of 967 patients were reviewed to identify those with calcium oxalate deposition in the renal allograft, with 27 (2.8%) identified. Follow-up biopsies were conducted to reevaluate for calcium oxalate presence and interstitial fibrosis development...
March 2018: Experimental and Clinical Transplantation
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