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https://www.readbyqxmd.com/read/29038511/gene-delivery-of-hypoxia-inducible-vegf-targeting-collagen-effectively-improves-cardiac-function-after-myocardial-infarction
#1
Jing-Bo Xia, Hai-Yan Wu, Bing-Lin Lai, Li Zheng, Deng-Cheng Zhou, Zao-Shang Chang, Cheng-Zhou Mao, Guang-Hui Liu, Kyu-Sang Park, Hui Zhao, Soo-Ki Kim, Guo-Hua Song, Dong-Qing Cai, Xu-Feng Qi
Vascular endothelial growth factor (VEGF) plays important roles in improvement of cardiac function following myocardial infarction (MI). However, the lack of a steerable delivery system of VEGF targeting the infarcted myocardium reduces the therapeutic efficacy and safety. Here, we constructed a series of lentiviral vector systems which could express a fusion protein consisted of a collagen-binding domain (CBD) and hVEGF (CBDhVEGF), under the control of 5HRE-hCMVmp (5HRE), the hypoxia-inducible promoter consists of five copies of the hypoxia-responsive element (HRE) and a human cytomegalovirus minimal promoter (hCMVmp)...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29037975/modular-cell-based-platform-for-high-throughput-identification-of-compounds-that-inhibit-a-viral-interferon-antagonist-of-choice
#2
Andri Vasou, Christina Paulus, Janina Narloch, Zoe O Gage, Marie-Anne Rameix-Welti, Jean-François Eléouët, Michael Nevels, Richard E Randall, Catherine S Adamson
Viral interferon (IFN) antagonists are a diverse class of viral proteins that counteract the host IFN response, which is important for controlling viral infections. Viral IFN antagonists are often multifunctional proteins that perform vital roles in virus replication beyond IFN antagonism. The critical importance of viral IFN antagonists is highlighted by the fact that almost all viruses encode one of these proteins. Inhibition of viral IFN antagonists has the potential to exert pleiotropic antiviral effects and thus this important protein class represents a diverse plethora of novel therapeutic targets...
October 13, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29029297/cytomegalovirus-specific-t-cell-transfer-for-refractory-cytomegalovirus-infection-after-haploidentical-stem-cell-transplantation-the-quantitative-and-qualitative-immune-recovery-for-cytomegalovirus
#3
Xu-Ying Pei, Xiang-Yu Zhao, Ying-Jun Chang, Jing Liu, Lan-Ping Xu, Yu Wang, Xiao-Hui Zhang, Wei Han, Yu-Hong Chen, Xiao-Jun Huang
Background: The efficiency and mechanisms of adoptive transfer of cytomegalovirus (CMV)specific T cells for refractory CMV infection after haploidentical stem cell transplantation (haplo-SCT) remain largely unknown. Methods: Thirty-two patients with refractory CMV infection who accepted treatment with adoptive CMV-specific T-cell infusion following haplo-SCT were prospectively enrolled. Another 32 patients with nonrefractory CMV infection after haplo-SCT were selected as control subjects...
September 23, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29027455/-construction-and-verification-of-nf-%C3%AE%C2%BAb-luciferase-reporter-gene-system
#4
Zhilan Guo, Luyang Che, Jingzhe Li, Zhenxiao Sun, Changzhen Liu
To quantify the transcriptional activity of NF-κB and to screen drugs related to the regulation of NF-κB activation, we constructed a recombinant plasmid through deleting the original CMV promoter of retrovirus vector pQCXIP and inserting the NF-κB enhancer and NanoLuc luciferase sequence into the vector. Then, using the recombinant plasmid we constructed a cell line in which the expression of NanoLuc luciferase (NLuc) was regulated by NF-κB. The inserted sequences were verified by restriction endonuclease digestion and sequencing...
October 25, 2016: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/29024250/non-invasive-detection-of-bladder-cancer-via-expression-targeted-gene-delivery
#5
Yunlan Fang, B Wolfson, W T Godbey
BACKGROUND: Because of the time and expense associated with the procedures and possible distress to the patient, cystoscopy or other imaging techniques are typically not used for bladder cancer detection before symptoms become present. Alternatively, commercial assays for urinary tumor markers exist but are marred by low sensitivity and high cost. There is a need for a simple and sensitive means of tumor detection, such as via the analysis of urine. METHODS: Plasmids encoding the secretable reporter Gaussia luciferase (G...
October 11, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/29023479/evaluating-the-efficiency-of-chef-and-cmv-promoter-with-ires-and-furin-2a-linker-sequences-for-monoclonal-antibody-expression-in-cho-cells
#6
Saeedeh Ebadat, Samira Ahmadi, Maryam Ahmadi, Fatemeh Nematpour, Farzaneh Barkhordari, Reza Mahdian, Fatemeh Davami, Fereidoun Mahboudi
In recent years, monoclonal antibodies (mAbs) have been developed as powerful therapeutic and diagnostic agents and Chinese hamster ovary (CHO) cells have emerged as the dominant host for the recombinant expression of these proteins. A critical step in recombinant expression is the utilization of strong promoters, such as the Chinese Hamster Elongation Factor-1α (CHEF-1) promoter. To compare the strengths of CHEF with cytomegalovirus (CMV) promoter for mAb expression in CHO cells, four bicistronic vectors bearing either internal ribosome entry site (IRES) or Furin/2A (F2A) sequences were designed...
2017: PloS One
https://www.readbyqxmd.com/read/29021395/hcmv-utilizes-a-non-traditional-stat1-activation-cascade-via-signaling-through-egfr-and-integrins-to-efficiently-promote-the-motility-differentiation-and-polarization-of-infected-monocytes
#7
Donna Collins-McMillen, Emily V Stevenson, Jung Heon Kim, Byeong-Jae Lee, Stephen J Cieply, Maciej T Nogalski, Gary C Chan, Robert W Frost, Caroline R Spohn, Andrew D Yurochko
Human cytomegalovirus infects peripheral blood monocytes and triggers biological changes that promote viral dissemination and persistence. We have shown that HCMV induces a pro-inflammatory state in infected monocytes, resulting in enhanced monocyte motility and transendothelial migration, prolonged monocyte survival, and differentiation toward a long-lived M1-like macrophage phenotype. Our data indicate that HCMV triggers these changes, in the absence of de novo viral gene expression and replication, through engagement and activation of EGFR and integrins on the surface of monocytes...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29018427/human-cytomegalovirus-ie2-86-kda-protein-induces-sting-degradation-and-inhibits-cgamp-mediated-ifn-%C3%AE-induction
#8
Jung-Eun Kim, Young-Eui Kim, Mark F Stinski, Jin-Hyun Ahn, Yoon-Jae Song
Stimulator of interferon genes (STING) is a critical signaling molecule in the innate immune response against DNA viruses by either directly sensing intracellular DNA or functioning as an adaptor molecule to activate the type I interferon (IFN) signaling pathway. We determined the functional interaction between STING and human cytomegalovirus (HCMV). A cDNA library containing 133 HCMV ORFs was screened to identify viral genes that inhibit STING-induced IFN-β promoter activation. Among the screened ORFs, UL122, which encodes the immediate-early 2 86 kDa (IE86) protein, strongly abolished STING-induced IFN-β promoter activation...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28993776/human-cytomegalovirus-delays-neutrophil-apoptosis-and-stimulates-the-release-of-a-prosurvival-secretome
#9
Joanna M Pocock, Daniel M L Storisteanu, Matthew B Reeves, Jatinder K Juss, Mark R Wills, Andrew S Cowburn, Edwin R Chilvers
Human cytomegalovirus (HCMV) is a major cause of viral disease in the young and the immune-suppressed. At sites of infection, HCMV recruits the neutrophil, a cell with a key role in orchestrating the initial immune response. Herein, we report a profound survival response in human neutrophils exposed to the clinical HCMV isolate Merlin, but not evident with the attenuated strain AD169, through suppression of apoptosis. The initial survival event, which is independent of viral gene expression and involves activation of the ERK/MAPK and NF-κB pathways, is augmented by HCMV-stimulated release of a secretory cytokine profile that further prolongs neutrophil lifespan...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28988741/smad7-alleviates-glomerular-mesangial-cell-proliferation-via-the-ros-nf-%C3%AE%C2%BAb-pathway
#10
Nana Lin, Zequan Ji
OBJECTIVE: The aim of this study was to demonstrate that altered gene expression of Smad7regulated NF-κB expression and ROS production on Ang II (Angiotensin II)-induced rat glomerular mesangial cell (GMC) proliferation. METHODS: pAdTrack-CMV-Smad7 was transduced into rat GMC by adeno-transduction using an ADV (adenovirus)-mediated vector in vivo. Diphenylene iodonium chloride (DPI) pre-treated GMC, and blocked ROS generation as determined by DCFH-DA method. Altered expressions of IκBα and p65 were monitored by Western blot analysis and immunofluorescence...
October 5, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28983234/a-novel-retinal-ganglion-cell-promoter-for-utility-in-aav-vectors
#11
Killian S Hanlon, Naomi Chadderton, Arpad Palfi, Alfonso Blanco Fernandez, Peter Humphries, Paul F Kenna, Sophia Millington-Ward, G Jane Farrar
Significant advances in gene therapy have enabled exploration of therapies for inherited retinal disorders, many of which are in preclinical development or clinical evaluation. Gene therapy for retinal conditions has led the way in this growing field. The loss of retinal ganglion cells (RGCs) is a hallmark of a number of retinal disorders. As the field matures innovations that aid in refining therapies and optimizing efficacy are in demand. Gene therapies under development for RGC-related disorders, when delivered with recombinant adeno associated vectors (AAV), have typically been expressed from ubiquitous promoter sequences...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28982328/effect-of-oral-nonionic-polymeric-micelles-delivered-parathyroid-hormone-cdna-on-bone-density-and-microarchitecture
#12
Sung-Hsiung Chen, Jih-Yang Ko, Fong-Fu Chou
INTRODUCTION: Parathyroid hormone (PTH) is an effective therapeutic agent for osteoporosis, but the treatment requires long-term daily injections. Oral gene delivery is a less invasive alternative to daily injections. The aim of this study is to investigate the effect of orally administered nonionic polymeric micelles of plasmid cDNA containing human cytomegalovirus promoter (PCMV)-PTH (1-34) plus EDTA on body mineral density and bone microstructure in ovariectomized rats. A total of 27 Spraque-Dawley female rats were subjected to a bilateral ovariectomy...
October 4, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28981114/essential-role-of-hcmv-deubiquitinase-in-promoting-oncogenesis-by-targeting-anti-viral-innate-immune-signaling-pathways
#13
Puja Kumari, Irene Saha, Athira Narayanan, Sathish Narayanan, Akinori Takaoka, Nachimuthu Senthil Kumar, Prafullakumar Tailor, Himanshu Kumar
Cancer is a multifactorial disease and virus-mediated carcinogenesis is one of the crucial factors, which is poorly understood. Human cytomegalovirus (HCMV) is a herpesvirus and its components have been evidenced to be associated with cancer of different tissue origin. However, its role in cancer remains unknown. Here, we identified a conserved herpesviral tegument protein known as pUL48 of HCMV, encoding deubiquitinase enzyme, as having a key role in carcinogenesis. We show using deubiquitinase sufficient- and deficient-HCMV that HCMV deubiquitinase is a key in inducing enhanced cellular metabolic activity through upregulation of several anti-apoptotic genes and downregulation of several pro-apoptotic genes expression...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28980193/expression-of-thiaminase-in-zebrafish-danio-rerio-is-lethal-and-has-implications-for-use-as-a-biocontainment-strategy-in-aquaculture-and-invasive-species
#14
Sandra Noble, Vishal Saxena, Marc Ekker, Robert Devlin
As the world increasingly relies on aquaculture operations to meet rising seafood demands, reliable biocontainment measures for farmed fish stocks are desired to minimize ecological impacts arising from interactions of cultured fish with wild populations. One possible biocontainment strategy is to induce a dietary dependence on a vitamin, such as thiamine (vitamin B1), required for survival. Fish expressing thiaminase (an enzyme that degrades thiamine) within a confined aquaculture facility could receive supplemental thiamine to allow survival and normal growth, whereas escapees lacking this dietary rescue would die from thiamine deficiency...
October 5, 2017: Marine Biotechnology
https://www.readbyqxmd.com/read/28945471/host-pathogen-interactions-and-chronic-lung-allograft-dysfunction
#15
John Belperio, Scott M Palmer, S Sam Weigt
Lung transplantation is now considered to be a therapeutic option for patients with advanced-stage lung diseases. Unfortunately, due to post-transplant complications, both infectious and noninfectious, it is only a treatment and not a cure. Infections (e.g., bacterial, viral, and fungal) in the immunosuppressed lung transplant recipient are a common cause of mortality post transplant. Infections have more recently been explored as factors contributing to the risk of chronic lung allograft dysfunction (CLAD)...
September 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28944856/systemic-overexpression-of-the-11%C3%AE-%C3%A2-hsd1-promotes-endoplasmic-reticulum-stress-in-multiple-tissues-and-the-development-of-metabolic-syndrome-in-mice
#16
Chenxiao Li, Jihan Xia, Wenjuan Zhu, Leilei Xin, Cuiping An, Shulin Yang, Kui Li
Glucocorticoids are associated with lipid metabolism and their abnormal expression has an important function in the development of metabolic syndrome. The 11β‑hydroxysteroid dehydrogenase type 1 (11β‑HSD1) is a metabolic enzyme of glucocorticoids and may be a potential drug target for the treatment of metabolic syndrome. However, the association between the systemic expression of 11β‑HSD1 and metabolic syndrome remains to be elucidated. The present study used a cytomegalovirus promoter to obtain mice that systemically overexpressed the 11β‑HSD1 gene...
September 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28942324/morphological-changes-in-different-populations-of-bladder-afferent-neurons-detected-by-herpes-simplex-virus-hsv-vectors-with-cell-type-specific-promoters-in-mice-with-spinal-cord-injury
#17
Nobutaka Shimizu, Mark F Doyal, William F Goins, Katsumi Kadekawa, Naoki Wada, Anthony J Kanai, William C de Groat, Akihide Hirayama, Hirotsugu Uemura, Joseph C Glorioso, Naoki Yoshimura
Functional and morphological changes in C-fiber bladder afferent pathways are reportedly involved in neurogenic detrusor overactivity (NDO) after spinal cord injury (SCI). This study examined the morphological changes in different populations of bladder afferent neurons after SCI using replication-defective herpes simplex virus (HSV) vectors encoding the mCherry reporter driven by neuronal cell-type-specific promoters. Spinal intact (SI) and SCI mice were injected into the bladder wall with HSV mCherry vectors driven by the cytomegalovirus (CMV) promoter, CGRP promoter, TRPV1 promoter or neurofilament 200 (NF200) promoter...
September 20, 2017: Neuroscience
https://www.readbyqxmd.com/read/28941824/improving-transcriptional-activity-of-human-cytomegalovirus-major-immediate-early-promoter-by-mutating-nf-%C3%AE%C2%BAb-binding-sites
#18
Danyang Wang, Wei Dai, Jian Wu, Jinke Wang
Many mammalian gene expression vectors express the transferred genes under the control of the cytomegalovirus (CMV) major immediate-early promoter (MIEP). The human MIEP has been known as the strongest promoter in mammalian cells and utilized widely in mammalian expression systems. There are four NF-κB binding sites (named as κBs) in the human MIEP. In this study, we have constructed multiple mutated MIEPs by changing the natural κBs in the human MIEP into the high-affinity artificial sequences that were in vitro selected by using systematic evolution of ligands by exponential enrichment (SELEX) and predicted by bioinformatics...
September 21, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28941260/glial-fibrillary-acidic-protein-promoter-determines-transgene-expression-in-satellite-glial-cells-following-intraganglionic-adeno-associated-virus-delivery-in-adult-rats
#19
Hongfei Xiang, Hao Xu, Fan Fan, Seung-Min Shin, Quinn H Hogan, Hongwei Yu
Recombinant adeno-associated viral (AAV)-mediated therapeutic gene transfer to dorsal root ganglia (DRG) is an effective and safe tool for treating chronic pain. However, AAV with various constitutively active promoters leads to transgene expression predominantly to neurons, while glial cells are refractory to AAV transduction in the peripheral nervous system. The present study evaluated whether in vivo satellite glial cell (SGC) transduction in the DRG can be enhanced by the SGC-specific GFAP promoter and by using shH10 and shH19, which are engineered capsid variants with Müller glia-prone transduction...
September 23, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28938099/plasmid-dna-launches-live-attenuated-japanese-encephalitis-virus-and-elicits-virus-neutralizing-antibodies-in-balb-c-mice
#20
Brian Nickols, Irina Tretyakova, Alexander Tibbens, Elena Klyushnenkova, Peter Pushko
We describe novel plasmid DNA that encodes the full-length Japanese encephalitis virus (JEV) genomic cDNA and launches live-attenuated JEV vaccine in vitro and in vivo. The synthetic cDNA based on the sequence of JEV SA14-14-2 live-attenuated virus was placed under transcriptional control of the cytomegalovirus major immediate-early promoter. The stability and yields of the plasmid in E. coli were optimized by inserting three synthetic introns that disrupted JEV cDNA in the structural and nonstructural genes...
September 19, 2017: Virology
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