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https://www.readbyqxmd.com/read/28749203/cb002-a-novel-p53-tumor-suppressor-pathway-restoring-small-molecule-induces-tumor-cell-death-through-the-pro-apoptotic-protein-noxa
#1
Liz J Hernandez-Borrero, Shengliang Zhang, Amriti Lulla, David T Dicker, Wafik S El-Deiry
P53 tumor suppressor gene mutations occur in the majority of human cancers and contribute to tumor development, progression and therapy resistance. Direct functional restoration of p53 as a transcription factor has been difficult to achieve in the clinic. We performed a functional screen using a bioluminescence-based transcriptional read-out to identify small molecules that restore the p53 pathway in mutant p53-bearing cancer cells. We identified CB002, as a candidate that restores p53 function in mutant p53-expressing colorectal cancer cells and without toxicity to normal human fibroblasts...
July 27, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28749137/identification-of-antiangiogenic-potential-and-cellular-mechanisms-of-napyradiomycin-a1-isolated-from-the-marine-derived-streptomyces-sp-yp127
#2
Ji Sun Hwang, Geum Jin Kim, Hyun Gyu Choi, Min Cheol Kim, Dongyup Hahn, Joo-Won Nam, Sang-Jip Nam, Hak Choel Kwon, Jungwook Chin, Sung Jin Cho, Hayoung Hwang, Hyukjae Choi
Angiogenesis is the process of new blood vessel formation. Excessive angiogenesis is a critical factor in the progression of cancer, macular degeneration, and other chronic inflammatory diseases. When investigating the effects of crude extracts of cultured marine microorganisms, an extract of the cultured Streptomyces sp. YP127 strain was found to inhibit human umbilical vein endothelial cell (HUVEC) tube formation. Bioassay-guided fractionation and spectroscopic data analyses led to the identification of napyradiomycin A1 (1) as an antiangiogenic component of the extract...
July 27, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28748970/lane-s-type-pseudosarcoma-of-glans-penis
#3
M Filotico, R Filotico
We herein present a rare case of polypoid "pseudosarcomatous lesion" of the glans penis, associated with in situ or mini-invasive squamous carcinoma. These lesions, described by Lane, in the upper aerodigestive tract, can rarely occur elsewhere. Immunohistochemistry is crucial for a correct diagnostic interpretation, confirming that the aytpical cells are components (fibroblasts, myofibroblasts, endothelial) of granulation tissue.
June 2017: Pathologica
https://www.readbyqxmd.com/read/28748415/role-of-plasma-derived-fibrin-on-keratinocyte-and-fibroblast-wound-healing
#4
Jia Xian Law, Shiplu Roy Chowdhury, Bin Saim Aminuddin, Binti Haji Idrus Ruszymah
Fibrin has excellent biocompatibility and biological properties to support tissue regeneration and promote wound healing. However, the role of diluted fibrin in wound healing has yet to be elucidated as it is commonly used in high concentration. This study was aimed to examine the effects of diluted plasma-derived fibrin (PDF) on keratinocyte and fibroblast wound healing in term of cell proliferation, migration, extracellular matrix (ECM) production and soluble factor secretion. Two PDF concentrations, 10 and 20% (v/v) were tested on keratinocytes and fibroblasts indirectly co-cultured in the transwell system...
July 26, 2017: Cell and Tissue Banking
https://www.readbyqxmd.com/read/28748214/functionally-pathogenic-ears2-variants-in-vitro-may-not-manifest-a-phenotype-in-vivo
#5
Nathan McNeill, Alessia Nasca, Aurelio Reyes, Benjamin Lemoine, Brandi Cantarel, Adeline Vanderver, Raphael Schiffmann, Daniele Ghezzi
OBJECTIVE: To investigate the genetic etiology of a patient diagnosed with leukoencephalopathy, brain calcifications, and cysts (LCC). METHODS: Whole-exome sequencing was performed on a patient with LCC and his unaffected family members. The variants were subject to in silico and in vitro functional testing to determine pathogenicity. RESULTS: Whole-exome sequencing uncovered compound heterozygous mutations in EARS2, c.328G>A (p.G110S), and c...
August 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28747825/biological-differences-between-hanwoo-longissimus-dorsi-and-semimembranosus-muscles-in-collagen-synthesis-of-fibroblasts
#6
Sivakumar Allur Subramaniyan, Inho Hwang
Variations in physical toughness between muscles and animals are a function of growth rate and extend of collagen type I and III. The current study was designed to investigate the ability of growth rate, collagen concentration, collagen synthesizing and degrading genes on two different fibroblast cells derived from Hanwoo m. longissimus dorsi (LD) and semimembranosus (SM) muscles. Fibroblast cell survival time was determined for understanding about the characteristics of proliferation rate between the two fibroblasts...
2017: Korean Journal for Food Science of Animal Resources
https://www.readbyqxmd.com/read/28747712/2-oxoadenosine-induces-cytotoxicity-through-intracellular-accumulation-of-2-oxo-atp-and-depletion-of-atp-but-not-via-the-p38-mapk-pathway
#7
Shinji Asada, Eiko Ohta, Yoriko Akimoto, Nona Abolhassani, Daisuke Tsuchimoto, Yusaku Nakabeppu
2-Oxoadenosine (2-oxo-Ado), an oxidized form of adenosine, is cytotoxic and induces growth arrest and cell death, which has potential as an anti-cancer drug. However, it is not well understood how 2-oxo-Ado exerts its cytotoxicity. We examined the effects of 2-oxo-Ado on non-tumour cells, namely immortalized mouse embryonic fibroblast lines, and investigated mechanisms by which 2-oxo-Ado exerts its cytotoxicity. We found that cell death induced by 2-oxo-Ado is classical caspase-dependent apoptosis, and requires its sequential intracellular phosphorylation catalysed by adenosine kinase (ADK) and adenylate kinase 2, resulting in intracellular accumulation of 2-oxo-ATP accompanied by accumulation of 2-oxo-Ado in RNA and depletion of ATP...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747710/a-high-content-image-analysis-approach-for-quantitative-measurements-of-chemosensitivity-in-patient-derived-tumor-microtissues
#8
Ilmari Ahonen, Malin Åkerfelt, Mervi Toriseva, Eva Oswald, Julia Schüler, Matthias Nees
Organotypic, three-dimensional (3D) cancer models have enabled investigations of complex microtissues in increasingly realistic conditions. However, a drawback of these advanced models remains the poor biological relevance of cancer cell lines, while higher clinical significance would be obtainable with patient-derived cell cultures. Here, we describe the generation and data analysis of 3D microtissue models from patient-derived xenografts (PDX) of non-small cell lung carcinoma (NSCLC). Standard of care anti-cancer drugs were applied and the altered multicellular morphologies were captured by confocal microscopy, followed by automated image analyses to quantitatively measure phenotypic features for high-content chemosensitivity tests...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747655/strategies-to-mitigate-variability-in-engineering-human-nasal-cartilage
#9
Stephen H J Andrews, Melanie Kunze, Aillette Mulet-Sierra, Lynn Williams, Khalid Ansari, Martin Osswald, Adetola B Adesida
Skin cancer and its associated treitments can have devastating consequences for survivors; this is particularly true when cancer occurs on the nose. Recent work has applied cell-based tissue engineering (TE) strategies to develop nasal cartilage constructs for reconstruction of the nose. In this study, we have generated human nasal cartilage on a clinically approved collagen scaffold to investigate the donor-to-donor variability of TE cartilage and evaluated strategies to mitigate it. We also evaluated the gene expression of the family of fibroblast growth factor receptors (FGFR1-4) and their association with tissue quality...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747639/molecular-profiling-of-single-organelles-for-quantitative-analysis-of-cellular-heterogeneity
#10
Andrey N Kuzmin, Svitlana M Levchenko, Artem Pliss, Junle Qu, Paras N Prasad
Recent developments in Raman spectroscopy instrumentation and data processing algorithms have led to the emergence of Ramanomics - an independent discipline with unprecedented capabilities to map the distribution of distinct molecular groups in live cells. Here, we introduce a method for probing the absolute concentrations of proteins, RNA and lipids in single organelles of live cultured cells by biomolecular component analysis using microRaman data. We found significant cell-to-cell variations in the molecular profiles of organelles, thus providing a physiologically relevant set of markers of cellular heterogeneity...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747638/puma-gene-delivery-to-synoviocytes-reduces-inflammation-and-degeneration-of-arthritic-joints
#11
Saw-See Hong, Hubert Marotte, Guillaume Courbon, Gary S Firestein, Pierre Boulanger, Pierre Miossec
In rheumatoid arthritis (RA), the proliferation of fibroblast-like synoviocytes (FLS) is the cause of chronic inflammation in joints and of joint damage. Delivery of the pro-apoptotic gene PUMA to FLS via human adenovirus type 5 (HAdV5) vectors has been tested as a therapeutic approach, but efficiency is hampered by low transduction, as FLS do not express HAdV5 receptors on the cell surface. Here we show that efficient transduction of PUMA in FLS can be achieved by conjugating HAdV5 to a baculovirus, which binds to the cell surface via the envelope glycoprotein Gp64...
July 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28747595/nac-ameliorates-dental-composite-induced-dna-double-strand-breaks-and-chromatin-condensation
#12
Panorea Styllou, Marianthi Styllou, Reinhard Hickel, Christof Högg, Franz Xaver Reichl, Harry Scherthan
Released (co)monomers from dental composite components can induce DNA damage of which DNA double-strand breaks (DSBs) threaten genome integrity. Here, we tested whether the administration of the antioxidant N-acetylcysteine (NAC) is able to reduce the dental composite-induced DSBs in primary human gingiva fibroblasts. The dental composites Bis-GMA (bisphenol-A-glycerolate dimethacrylate), GMA (glycidyl methacrylate), HEMA (2-hydroxyethyl methacrylate) and TEGDMA (triethyleneglycol dimethacrylate) were found to induce co-localizing microscopic nuclear foci numbers of the DSB markers γ-H2AX and 53BP1 per cell in the order: GMA>Bis-GMA>TEGDMA>HEMA...
July 26, 2017: Dental Materials Journal
https://www.readbyqxmd.com/read/28747552/tenascin-c-and-fibronectin-in-normal-esophageal-mucosa-barrett-s-esophagus-dysplasia-and-adenocarcinoma
#13
Joni Leppänen, Sara Bogdanoff, Petri P Lehenkari, Juha Saarnio, Joonas H Kauppila, Tuomo J Karttunen, Heikki Huhta, Olli Helminen
BACKGROUND: Tenascin-C and fibronectin are adhesive glycoproteins modulating the structure of the extracellular matrix and cellular functions. Their expression and function in esophageal adenocarcinoma is poorly known. The aim of this study was to evaluate the expression of tenascin-C and fibronectin in esophageal adenocarcinoma and its precursor stages. RESULTS: Stromal tenascin-C and fibronectin expression were found in all evaluated lesion types. Expression of both molecules increased from gastric metaplasia towards adenocarcinoma (p<0...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747504/targeted-genome-sequencing-reveals-varicella-zoster-virus-open-reading-frame-12-deletion
#14
Randall J Cohrs, Katherine S Lee, Addilynn Beach, Bridget Sanford, Nicholas L Baird, Christina Como, Chiharu Graybill, Dallas Jones, Eden Tekeste, Mitchell Ballard, Xiaomi Chen, David Yalacki, Seth Frietze, Kenneth Jones, Tihana Lenac Rovis, Stipan Jonjić, Jürgen Haas, Don Gilden
The neurotropic herpesvirus varicella zoster virus (VZV) establishes a life-long latent infection in humans following primary infection. The low abundance of VZV nucleic acids in human neurons has hindered an understanding of the mechanisms that regulate viral gene transcription during latency. To overcome this critical barrier, we optimized a targeted capture protocol to enrich VZV DNA and cDNA prior to whole-genome/transcriptome sequence analysis. Since the VZV genome is remarkably stable, it was surprising to detect that VZV32, a VZV laboratory strain with no discernable growth defect in tissue culture, contained a 2158-bp deletion in open reading frame (ORF) 12...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28747486/modifying-the-dietary-carbohydrate-to-protein-ratio-alters-the-postprandial-macronutrient-oxidation-pattern-in-liver-of-ampk-deficient-mice
#15
Tristan Chalvon-Demersay, Patrick C Even, Catherine Chaumontet, Julien Piedcoq, Benoit Viollet, Claire Gaudichon, Daniel Tomé, Marc Foretz, Dalila Azzout-Marniche
Background: Hepatic AMP-activated kinase (AMPK) activity is sensitive to the dietary carbohydrate-to-protein ratio. However, the role of AMPK in metabolic adaptations to variations in dietary macronutrients remains poorly understood.Objective: The objective of this study was to determine the role of hepatic AMPK in the adaptation of energy metabolism in response to modulation of the dietary carbohydrate-to-protein ratio.Methods: Male 7-wk-old wild-type (WT) and liver AMPK-deficient (knockout) mice were fed either a normal-protein and normal-carbohydrate diet (NP-NC; 14% protein, 76% carbohydrate on an energy basis), a low-protein and high-carbohydrate diet (LP-HC; 5% protein, 85% carbohydrate), or a high-protein and low-carbohydrate diet (HP-LC; 55% protein, 35% carbohydrate) for 3 wk...
July 26, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28747359/coupling-between-phosphate-and-calcium-homeostasis-a-mathematical-model
#16
David Granjon, Olivier Bonny, Aurélie Edwards
We developed a mathematical model of calcium (Ca) and phosphate (PO4) homeostasis in the rat to elucidate the hormonal mechanisms that underlie the regulation of Ca and PO4 balance. The model represents the exchanges of Ca and PO4 between the intestine, plasma, kidneys, bone, and the intracellular compartment, and the formation of Ca-PO4-fetuin A complexes. It accounts for the regulation of these fluxes by parathyroid hormone (PTH), vitamin D3, fibroblast growth factor 23 (FGF23), and Ca2+-sensing receptors...
July 26, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28747082/construction-of-functional-pancreatic-artificial-islet-tissue-composed-of-fibroblast-modified-polylactic-co-glycolic-acid-membrane-and-pancreatic-stem-cells
#17
Liping Liu, Jing Tan, Baoyuan Li, Qian Xie, Junwen Sun, Hongli Pu, Li Zhang
Objective To improve the biocompatibility between polylactic- co-glycolic acid membrane and pancreatic stem cells, rat fibroblasts were used to modify the polylactic- co-glycolic acid membrane. Meanwhile, we constructed artificial islet tissue by compound culturing the pancreatic stem cells and the fibroblast-modified polylactic- co-glycolic acid membrane and explored the function of artificial islets in diabetic nude mice. Methods Pancreatic stem cells were cultured on the fibroblast-modified polylactic- co-glycolic acid membrane in dulbecco's modified eagle medium containing activin-A, β-catenin, and exendin-4...
January 1, 2017: Journal of Biomaterials Applications
https://www.readbyqxmd.com/read/28747035/elevated-circulating-il-32-presents-a-poor-prognostic-outcome-in-patients-with-heart-failure-after-myocardial-infarction
#18
Wanling Xuan, Weixing Huang, Ruijie Wang, Chang Chen, Yequn Chen, Yan Wang, Xuerui Tan
BACKGROUND: Interleukin-32 (IL-32) is a newly discovered proinflammatory cytokine. However, there are limited data regarding IL-32 as a biomarker for heart failure (HF). In this study, we assessed the prognostic value of IL-32 in patients with chronic HF after myocardial infarction (MI). METHODS AND RESULTS: Over a period of 1.8years, we prospectively enrolled 100 patients with chronic HF after MI. IL-32, NT-proBNP, Matrix metallopeptidase 9 (MMP-9), procollagen type I (PI) and type III (PIII) were measured at baseline...
September 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28746885/injectable-hydrogel-based-on-quaternized-chitosan-gelatin-and-dopamine-as-localized-drug-delivery-system-to-treat-parkinson-s-disease
#19
Yizhuo Ren, Xin Zhao, Xiaofeng Liang, Peter X Ma, Baolin Guo
There is still an enormous demand for designing materials to the treatment of Parkinson's disease, and dopamine-based injectable polysaccharide hydrogels as localized drug delivery system have huge potential. Here, we developed a facile approach to prepare dopamine-based and polydopamine crosslinked injectable hydrogels by simply oxidizing a mixture of quaternized chitosan, gelatin and dopamine under physiological conditions. These injectable quaternized hydrogels showed stable mechanical strength by rheometer and exhibited good degradability evaluated by in vitro degradation test...
July 23, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28746870/identification-of-a-genetic-variation-in-erap1-aminopeptidase-that-prevents-human-cytomegalovirus-mir-ul112-5p-mediated-immunoevasion
#20
Paolo Romania, Loredana Cifaldi, Benedetta Pignoloni, Nadia Starc, Valerio D'Alicandro, Ombretta Melaiu, Giuseppina Li Pira, Ezio Giorda, Rosalba Carrozzo, Monika Bergvall, Tomas Bergström, Lars Alfredsson, Tomas Olsson, Ingrid Kockum, Ilkka Seppälä, Terho Lehtimäki, Mikko A Hurme, Hartmut Hengel, Angela Santoni, Cristina Cerboni, Franco Locatelli, Mauro D'Amato, Doriana Fruci
Herein, we demonstrate that HCMV miR-UL112-5p targets ERAP1, thereby inhibiting the processing and presentation of the HCMV pp65495-503 peptide to specific CTLs. In addition, we show that the rs17481334 G variant, naturally occurring in the ERAP1 3' UTR, preserves ERAP1 from miR-UL112-5p-mediated degradation. Specifically, HCMV miR-UL112-5p binds the 3' UTR of ERAP1 A variant, but not the 3' UTR of ERAP1 G variant, and, accordingly, ERAP1 expression is reduced both at RNA and protein levels only in human fibroblasts homozygous for the A variant...
July 25, 2017: Cell Reports
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