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https://www.readbyqxmd.com/read/28930993/confocal-imaging-of-neuropeptide-y-phluorin-a-technique-to-visualize-insulin-granule-exocytosis-in-intact-murine-and-human-islets
#1
Madina Makhmutova, Tao Liang, Herbert Gaisano, Alejandro Caicedo, Joana Almaça
Insulin secretion plays a central role in glucose homeostasis under normal physiological conditions as well as in disease. Current approaches to study insulin granule exocytosis either use electrophysiology or microscopy coupled to the expression of fluorescent reporters. However most of these techniques have been optimized for clonal cell lines or require dissociating pancreatic islets. In contrast, the method presented here allows for real time visualization of insulin granule exocytosis in intact pancreatic islets...
September 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28929517/neural-differentiation-of-bone-marrow-mesenchymal-stem-cells-with-human-brain-derived-neurotrophic-factor-gene-modified-in-functionalized-self-assembling-peptide-hydrogel-in-vitro
#2
Hongbin Luo, Changsheng Xu, Zhiwei Liu, Lin Yang, Yunda Hong, Guisheng Liu, Huifen Zhong, Xinyi Cai, Xuping Lin, Xiaokun Chen, Changsheng Wang, Nanwen Zhang, Weihong Xu
OBJECTIVE: To investigate the biocompatibility and differentiation of human brain-derived neurotrophic factor (hBDNF) gene-modified bone marrow mesenchymal stem cells (hBDNF-rMSCs) in a functionalized self-assembling peptide hydrogel. METHODS: hBDNF were engineered in rMSCs using adenovirus vector and the enhanced green fluorescence protein (eGFP) was used as a reporter gene. MSC-specific surface markers (CD90,CD29 and CD45)were used for identifying rMSCs. Fluorescence microscope was used to detect the transfection of rMSCs...
September 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28929492/potent-antitumor-effect-of-tumor-microenvironment-targeted-oncolytic-adenovirus-against-desmoplastic-pancreatic-cancer
#3
Yan Li, JinWoo Hong, Joung-Eun Oh, A-Rum Yoon, Chae-Ok Yun
Pancreatic cancer is a leading cause of cancer-related death. Desmoplastic pancreatic tumors exhibit excessive extracellular matrix (ECM) and are thus highly resistant to anticancer therapeutics, since the ECM restricts drug penetration and dispersion. Here, we designed and generated two hypoxia-responsive and cancer-specific hybrid promoters, H(mT)E and H(E)mT. Transgene expression driven by each hybrid promoter was markedly higher under hypoxic conditions than normoxic conditions. Moreover, H(E)mT-driven transgene expression was highly cancer-specific and was superior to that of H(mT)E-driven expression...
September 20, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28928817/dichloroacetate-induces-protective-autophagy-in-esophageal-squamous-carcinoma-cells
#4
Hong-Yu Jia, He-Nan Wang, Feng-Yu Xia, Yan Sun, Hong-Li Liu, Li-Li Yan, Shan-Shan Li, Dong-Chun Jiang, Mei-Mei Xu
Dichloroacetate (DCA) is an inhibitor of pyruvate dehydrogenase kinase, which promotes the flux of carbohydrates into mitochondria and enhances the aerobic oxidation of glucose. DCA has previously been demonstrated to exhibit antitumor properties. The present study revealed that treatment with DCA induced increased levels of autophagy-associated proteins in esophageal squamous carcinoma cells while minimally affecting apoptosis. The present study examined the localization of light chain (LC)-3 by adenovirus infection with a green fluorescent protein (FP)-red FP-LC3 reporter construction and confirmed that DCA treatment induced significant autophagy...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927755/protein-kinase-ck2-inhibition-suppresses-neointima-formation-via-a-proline-rich-homeodomain-dependent-mechanism
#5
K S Wadey, B A Brown, G B Sala-Newby, P-S Jayaraman, K Gaston, S J George
Neointimal hyperplasia is a product of VSMC replication and consequent accumulation within the blood vessel wall. In this study, we determined whether inhibition of protein kinase CK2 and the resultant stabilisation of proline-rich homeodomain (PRH) could suppress VSMC proliferation. Both silencing and pharmacological inhibition of CK2 with K66 antagonised replication of isolated VSMCs. SiRNA-induced knockdown as well as ectopic overexpression of proline-rich homeodomain indicated that PRH disrupts cell cycle progression...
September 16, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28927006/emerging-roles-of-heparanase-in-viral-pathogenesis
#6
REVIEW
Neel Thakkar, Tejabhiram Yadavalli, Dinesh Jaishankar, Deepak Shukla
Heparan sulfate (HS) is ubiquitously expressed on mammalian cells. It is a polysaccharide that binds growth factors, cytokines, and chemokines, and thereby controls several important physiological functions. Ironically, many human pathogens including viruses interact with it for adherence to host cells. HS functions can be regulated by selective modifications and/or selective cleavage of the sugar chains from the cell surface. In mammals, heparanase (HPSE) is the only known enzyme capable of regulating HS functions via a selective endoglycosidase activity that cleaves polymeric HS chains at internal sites...
September 18, 2017: Pathogens
https://www.readbyqxmd.com/read/28925992/efficacy-of-combining-ing4-and-trail-genes-in-cancer-targeting-gene-virotherapy-strategy-first-evidence-in-preclinical-hepatocellular-carcinoma
#7
A G El-Shemi, A M Ashshi, E Oh, B-K Jung, M Basalamah, A Alsaegh, C-O Yun
Current treatments of hepatocellular carcinoma (HCC) are ineffective and unsatisfactory in many aspects. Cancer-targeting gene virotherapy using oncolytic adenoviruses (OAds) armed with anticancer genes has shown efficacy and safety in clinical trials. Nowadays, both inhibitor of growth 4 (ING4); as a multimodal tumor suppressor gene, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL); as potent-apoptosis inducing gene, are experiencing a renaissance in cancer gene therapy. Herein we investigated the antitumor activity and safety of mono-and combined therapy with OAds armed with ING4 (Ad-ΔB/ING4) and TRAIL (Ad-ΔB/TRAIL) gene, respectively, on preclinical models of human HCC...
September 19, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28925655/pleuritic-chest-pain-sorting-through-the-differential-diagnosis
#8
Brian V Reamy, Pamela M Williams, Michael Ryan Odom
Pleuritic chest pain is characterized by sudden and intense sharp, stabbing, or burning pain in the chest when inhaling and exhaling. Pulmonary embolism is the most common serious cause, found in 5% to 21% of patients who present to an emergency department with pleuritic chest pain. A validated clinical decision rule for pulmonary embolism should be employed to guide the use of additional tests such as d-dimer assays, ventilation-perfusion scans, or computed tomography angiography. Myocardial infarction, pericarditis, aortic dissection, pneumonia, and pneumothorax are other serious causes that should be ruled out using history and physical examination, electrocardiography, troponin assays, and chest radiography before another diagnosis is made...
September 1, 2017: American Family Physician
https://www.readbyqxmd.com/read/28923683/a-hydrogel-matrix-prolongs-persistence-and-promotes-specific-localization-of-an-oncolytic-adenovirus-in-a-tumor-by-restricting-nonspecific-shedding-and-an-antiviral-immune-response
#9
Bo-Kyeong Jung, Eonju Oh, JinWoo Hong, Yunki Lee, Ki Dong Park, Chae-Ok Yun
Currently, intratumoral injection of an oncolytic adenovirus (Ad) is the conventional administration route in clinical trials. Nonetheless, the locally administered Ad disseminates to the surrounding nontarget tissues and has short biological activity due to immunogenicity of Ad, thus necessitating multiple injections to achieve a sufficient therapeutic index. In the present study, a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-expressing oncolytic Ad (oAd-TRAIL) was encapsulated in a gelatin hydrogel (oAd-TRAIL/gel) to enhance and prolong antitumor efficacy of the virus after a single intratumoral injection...
September 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28923509/the-complete-genome-sequence-of-human-adenovirus-84-a-highly-recombinant-new-human-mastadenovirus-d-type-with-a-unique-fiber-gene
#10
Győző L Kaján, Adriana E Kajon, Alexis Castillo Pinto, Dániel Bartha, Niklas Arnberg
A novel human adenovirus was isolated from a pediatric case of acute respiratory disease in Panama City, Panama in 2011. The clinical isolate was initially identified as an intertypic recombinant based on hexon and fiber gene sequencing. Based on the analysis of its complete genome sequence, the novel complex recombinant Human mastadenovirus D (HAdV-D) strain was classified into a new HAdV type: HAdV-84, and it was designated Adenovirus D human/PAN/P309886/2011/84[P43H17F84]. HAdV-D types possess usually an ocular or gastrointestinal tropism, and respiratory association is scarcely reported...
September 15, 2017: Virus Research
https://www.readbyqxmd.com/read/28923104/phase-1-study-of-intravenous-administration-of-the-chimeric-adenovirus-enadenotucirev-in-patients-undergoing-primary-tumor-resection
#11
Rocio Garcia-Carbonero, Ramon Salazar, Ignacio Duran, Ignacio Osman-Garcia, Luis Paz-Ares, Juan M Bozada, Valentina Boni, Christine Blanc, Len Seymour, John Beadle, Simon Alvis, Brian Champion, Emiliano Calvo, Kerry Fisher
BACKGROUND: Enadenotucirev (formerly ColoAd1) is a tumor-selective chimeric adenovirus with demonstrated preclinical activity. This phase 1 Mechanism of Action study assessed intravenous (IV) delivery of enadenotucirev in patients with resectable colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), urothelial cell cancer (UCC), and renal cell cancer (RCC) with a comparator intratumoral (IT) dosed CRC patient cohort. METHODS: Seventeen patients scheduled for primary tumor resection were enrolled...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28918350/expression-and-functional-characterization-of-the-bnip3-protein-in-renal-cell-carcinomas
#12
Stephan Macher-Goeppinger, Martina Keith, Gencay Hatiboglu, Markus Hohenfellner, Peter Schirmacher, Wilfried Roth, Katrin E Tagscherer
BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein 3) is a BH3-only protein that regulates apoptosis and autophagy. BNIP3 plays also an important role in hypoxia-induced cell response and is regulated by HIF1. Here, we studied a possible association of BNIP3 expression and the prognosis of patients with renal cell carcinomas (RCCs) and examined the functional relevance of BNIP3 in the regulation of cell survival and apoptosis of renal carcinoma cells. BNIP3 expression was determined by immunohistochemistry in RCC tumor tissue samples of 569 patients using a tissue microarray...
September 14, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28918074/rapid-adenovirus-typing-method-for-species-identification
#13
Fabienne Rayne, Linda Wittkop, Clément Bader, Somar Kassab, Camille Tumiotto, Sylvie Berciaud, Harald Wodrich, Marie-Edith Lafon
Adenoviruses are characterized by a large variability, reflected by their classification in species A to G. Certain species, eg A and C, could be associated with increased clinical severity, both in immunocompetent and immunocompromised hosts suggesting that in some instances species identification provides clinically relevant information. Here we designed a novel "pVI rapid typing method" to obtain quick, simple and cost effective species assignment for Adenoviruses, thanks to combined fusion temperature (Tm) and amplicon size analysis...
September 13, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28918073/a-directed-evolution-approach-to-select-for-novel-adeno-associated-virus-capsids-on-an-hiv-1-producer-t-cell-line
#14
Dawn P Wooley, Priyanka Sharma, John R Weinstein, Poornima Kotha Lakshmi Narayan, David V Schaffer, Katherine J D A Excoffon
A directed evolution approach was used to select for Adeno-associated virus (AAV) capsids that would exhibit more tropism toward an HIV-1 producer T cell line with the long-term goal of developing improved gene transfer vectors. A library of AAV variants was used to infect H9T cells previously infected or uninfected by HIV-1 followed by AAV amplification with wild-type adenovirus. Six rounds of biological selection were performed, including negative selection and diversification after round three. The H9T cells were successfully infected with all three wild-type viruses (AAV, adenovirus, and HIV-1)...
September 13, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28918031/anti-adenoviral-artificial-micrornas-expressed-from-aav9-vectors-inhibit-human-adenovirus-infection-in-immunosuppressed-syrian-hamsters
#15
Katrin Schaar, Anja Geisler, Milena Kraus, Sandra Pinkert, Markian Pryshliak, Jacqueline F Spencer, Ann E Tollefson, Baoling Ying, Jens Kurreck, William S Wold, Robert Klopfleisch, Karoly Toth, Henry Fechner
Infections of immunocompromised patients with human adenoviruses (hAd) can develop into life-threatening conditions, whereas drugs with anti-adenoviral efficiency are not clinically approved and have limited efficacy. Small double-stranded RNAs that induce RNAi represent a new class of promising anti-adenoviral therapeutics. However, as yet, their efficiency to treat hAd5 infections has only been investigated in vitro. In this study, we analyzed artificial microRNAs (amiRs) delivered by self-complementary adeno-associated virus (scAAV) vectors for treatment of hAd5 infections in immunosuppressed Syrian hamsters...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918014/artificial-zinc-finger-transcription-factor-of-a20-suppresses-restenosis-in-sprague-dawley-rats-after-carotid-injury-via-the-ppar%C3%AE-pathway
#16
Zhaoyou Meng, Pan Gao, Lin Chen, Jing Peng, Jialu Huang, Min Wu, Kangning Chen, Zhenhua Zhou
The inhibition of inflammation and vascular smooth muscle cell (VSMC) proliferation is an ideal strategy to suppress intimal hyperplasia after percutaneous transluminal angioplasty (PTA). Evidence has indicated that overexpression of A20 suppresses neointima formation, but its low transfection efficiency limits its application. Hence, we upregulated A20 expression via transfection of rAd.ATF (recombinant adenovirus vector of artificial transcription factor) and rAd.A20 in rat carotid arteries after balloon dilatation (in vivo) and isolated VSMCs (in vitro)...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918012/gene-editing-with-helper-dependent-adenovirus-can-efficiently-introduce-multiple-changes-simultaneously-over-a-large-genomic-region
#17
Donna J Palmer, Nathan C Grove, Dustin L Turner, Philip Ng
Helper-dependent adenoviral vectors (HDAds) possess long homology arms that mediate high-efficiency gene editing. These long homology arms may permit simultaneous introduction of multiple modifications into a large genomic region or may permit a single HDAd to correct many different individual mutations spread widely across a gene. We investigated this important potential using an HDAd bearing 13 genetic markers in the region of homology to the target CFTR locus in human iPSCs and found that all markers can be simultaneously introduced into the target locus, with the two farthest markers being 22...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28915437/temporal-characterization-of-the-non-structural-adenovirus-type-2-proteome-and-phosphoproteome-using-high-resolving-mass-spectrometry
#18
Malin Källsten, Arina Gromova, Hongxing Zhao, Alberto Valdés, Anne Konzer, Ulf Pettersson, Sara Bergström Lind
The proteome and phosphoproteome of non-structural proteins of Adenovirus type 2 (Ad2) were time resolved using a developed mass spectrometry approach. These proteins are expressed by the viral genome and important for the infection process, but not part of the virus particle. We unambiguously confirm the existence of 95% of the viral proteins predicted to be encoded by the viral genome. Most non-structural proteins peaked in expression at late time post infection. We identified 27 non-redundant sites of phosphorylation on seven different non-structural proteins...
September 12, 2017: Virology
https://www.readbyqxmd.com/read/28915257/outbreaks-of-epidemic-keratoconjunctivitis-caused-by-human-adenovirus-type-8-in-the-tibet-autonomous-region-of-china-in-2016
#19
Zhenqiang Lei, Zhen Zhu, Bai Ma Ci Wang, Hong Mei, Hong Li, Dan Zeng Gong Ga, Guo Jie, Mi Ma Bu Chi, Sheng Zhang, Chaofeng Ma, Wenbo Xu
From April to November 2016, two outbreaks of epidemic keratoconjunctivitis (EKC) occurred successively at primary and middle schools in the Tibet Autonomous Region of China, and a total of 197 clinically diagnosed cases were reported. Real-time PCR analyses confirmed that human adenovirus (HAdV) infection was related to these outbreaks. Further studies involving sequence determination and phylogenetic analysis based on the penton base, hexon, and fiber genes indicated that human adenovirus type 8 (HAdV-8), belonging to species D, was responsible for the outbreaks...
2017: PloS One
https://www.readbyqxmd.com/read/28913988/prevalence-of-respiratory-viral-infections-in-korean-adult-asthmatics-with-acute-exacerbations-comparison-with-those-with-stable-state
#20
Ki Hyun Seo, Da Jeong Bae, Ji Na Kim, Ho Sung Lee, Yong Hoon Kim, Jong Sook Park, Myung Shin Kim, Hun Soo Chang, Ji Hye Son, Dong Gyu Baek, Jun Suk Lee, Choon Sik Park
PURPOSE: Viral infections are involved in ~50% of exacerbations among Caucasian adult asthmatics. However, there have been few reports on the causative virus of exacerbations in Korean adult asthmatics. Thus, we compared frequencies and types of viruses between lower respiratory tract illnesses (LRTIs) with exacerbations (exacerbated LRTIs) and those without exacerbations (stable LRTIs) to evaluate contribution of respiratory viruses to exacerbations. METHODS: Viral RNA was extracted from sputum using the Viral Gene-spin™ Kit...
November 2017: Allergy, Asthma & Immunology Research
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