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https://www.readbyqxmd.com/read/28550782/immunofluorescence-evaluation-of-4-hydroxynonenal-and-8-hydroxy-2-deoxyguanosine-activation-in-zebrafish-daino-rerio-larvae-brain-exposed-microinjected-to-propyl-gallate
#1
Ahmet Topal, Selim Çomakli, Mustafa Özkaraca, Alper Baran, Mine Köktürk, Veysel Parlak, Yavuz Selim Sağlam, Muhammed Atamanalp, Saltuk Buğrahan Ceyhun
Propyl gallate (PG) is a chemical compound obtained by esterification of propanol with gallic acid. Due to its antioxidative properties, it is widely used in cosmetics and pharmaceutical industries as well as to protect the oils in foods such as butter, milk-based desserts, chewing gum, mayonnaise, meat, soups, cereals, spices and seasonings from rancidity. This study has been designed to assessment 8-OHdG and 4-HNE activity, and histopathological changes in the brain tissues of zebrafish larvae, which is a lecithotrophic organism, after 96 h of PG exposure via microinjecting to yolk sac of embryo...
May 19, 2017: Chemosphere
https://www.readbyqxmd.com/read/28550769/mk-8776-a-novel-chk1-inhibitor-exhibits-an-improved-radiosensitizing-effect-compared-to-ucn-01-by-exacerbating-radiation-induced-aberrant-mitosis
#2
Motofumi Suzuki, Tohru Yamamori, Tomoki Bo, Yuri Sakai, Osamu Inanami
Checkpoint kinase 1 (Chk1) is an evolutionarily conserved serine/threonine kinase that plays an important role in G2/M checkpoint signaling. Here, we evaluate the radiosensitizing effects of a novel selective Chk1 inhibitor MK-8776, comparing its efficacy with a first-generation Chk1 inhibitor UCN-01, and attempt to elucidate the mechanism of radiosensitization. In a clonogenic survival assay, MK-8776 demonstrated a more pronounced radiosensitizing effect than UCN-01, with lower cytotoxicity. Importantly, radiosensitization by MK-8776 can be achieved at doses as low as 2...
May 24, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28550753/catalase-loaded-cisplatin-prodrug-constructed-liposomes-to-overcome-tumor-hypoxia-for-enhanced-chemo-radiotherapy-of-cancer
#3
Rui Zhang, Xuejiao Song, Chao Liang, Xuan Yi, Guosheng Song, Yu Chao, Yu Yang, Kai Yang, Liangzhu Feng, Zhuang Liu
Aiming at improved therapeutic efficacies, the combination of chemotherapy and radiotherapy (chemo-radiotherapy) has been widely studied and applied in clinic. However, the hostile characteristics of tumor microenvironment such as hypoxia often limit the efficacies in both types of cancer therapies. Herein, catalase (CAT), an antioxidant enzyme, is encapsulated inside liposomes constituted by cisplatin (IV)-prodrug-conjugated phospholipid, forming CAT@Pt (IV)-liposome for enhanced chemo-radiotherapy of cancer...
May 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28550736/piperine-attenuates-uv-r-induced-cell-damage-in-human-keratinocytes-via-nf-kb-bax-bcl-2-pathway-an-application-for-photoprotection
#4
Ankit Verma, Hari N Kushwaha, Ajeet K Srivastava, Saumya Srivastava, Naseem Jamal, Kriti Srivastava, Ratan Singh Ray
Chronic ultraviolet radiation (UV-R) exposure causes skin disorders like erythema, edema, hyperpigmentation, photoaging and photocarcinogenesis. Recent research trends of researchers have focused more attention on the identification and use of photo stable natural agents with photoprotective properties. Piperine (PIP), as a plant alkaloid, is an important constituent present in black pepper (Piper nigrum), used widely in ayurvedic and other traditional medicines and has broad pharmacological properties. The study was planned to photoprotective efficacy of PIP in human keratinocyte (HaCaT) cell line...
May 19, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28550622/genomic-instability-related-to-zinc-deficiency-and-excess-in-an-in-vitro-model-is-the-upper-estimate-of-the-physiological-requirements-recommended-for-children-safe
#5
Gisel Padula, María Virginia Ponzinibbio, Rocío Celeste Gambaro, Analía Isabel Seoane
Micronutrients are important for the prevention of degenerative diseases due to their role in maintaining genomic stability. Therefore, there is international concern about the need to redefine the optimal mineral and vitamin requirements to prevent DNA damage. We analyzed the cytostatic, cytotoxic, and genotoxic effect of in vitro zinc supplementation to determine the effects of zinc deficiency and excess and whether the upper estimate of the physiological requirement recommended for children is safe. To achieve zinc deficiency, DMEM/Ham's F12 medium (HF12) was chelated (HF12Q)...
May 26, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28550500/acute-and-long-term-effects-of-intracerebroventricular-administration-of-%C3%AE-ketoisocaproic-acid-on-oxidative-stress-parameters-and-cognitive-and-noncognitive-behaviors
#6
Luciane Taschetto, Giselli Scaini, Hugo G Zapelini, Ândrea C Ramos, Giulia Strapazzon, Vanessa M Andrade, Gislaine Z Réus, Monique Michels, Felipe Dal-Pizzol, João Quevedo, Patrícia F Schuck, Gustavo C Ferreira, Emilio L Streck
Maple Syrup Urine Disease (MSUD) is biochemically characterized by elevated levels of leucine, isoleucine and valine, as well as their corresponding transaminated branched-chain α-keto acids in tissue and biological fluids. Neurological symptoms and cerebral abnormalities, whose mechanisms are still unknown, are typical of this metabolic disorder. In the present study, we evaluated the early effects (1 h after injection) and long-term effects (15 days after injection) of a single intracerebroventricular administration of α-ketoisocaproic acid (KIC) on oxidative stress parameters and cognitive and noncognitive behaviors...
May 27, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28550350/recent-advances-in-the-study-of-immunodeficiency-and-dna-damage-response
#7
REVIEW
Tomohiro Morio
DNA breaks can be induced by exogenous stimuli or by endogenous stress, but are also generated during recombination of V, D, and J genes (V(D)J recombination), immunoglobulin class switch recombination (CSR). Among various DNA breaks generated, DNA double strand break (DSB) is the most deleterious one. DNA damage response (DDR) is initiated when DSBs are detected, leading to DNA break repair by non-homologous end joining (NHEJ). The process is critically important for the generation of diversity for foreign antigens; and failure to exert DNA repair leads to immunodeficiency such as severe combined immunodeficiency and hyper-IgM syndrome...
May 26, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28549997/deep-sequencing-of-atrial-fibrillation-patients-with-mitral-valve-regurgitation-shows-no-evidence-of-mosaicism-but-reveals-novel-rare-germline-variants
#8
Emilie Gregers, Gustav Ahlberg, Thea Christensen, Javad Jabbari, Kirstine O Larsen, Cecilie B Herfelt, Kristoffer M Henningsen, Laura Andreasen, Jens J Thiis, Jens Lund, Susanne Holme, Stig Haunsø, Bo H Bentzen, Nicole Schmitt, Jesper H Svendsen, Morten S Olesen
BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Valvular heart disease is a strong predictor, yet the underlying molecular mechanisms are unknown. OBJECTIVE: We sought to investigate the prevalence of somatic variants in AF candidate genes in an AF patient population undergoing surgery for mitral valve regurgitation (MVR) to determine whether these patients are genetically predisposed to AF. METHODS: DNA was extracted from blood and left atrial tissue from 44 AF patients with MVR...
May 23, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28549842/mitochondrial-dysfunction-and-oxidative-stress-in-corneal-disease
#9
Neeru A Vallabh, Vito Romano, Colin E Willoughby
The cornea is the anterior transparent surface and the main refracting structure of the eye. Mitochondrial dysfunction and oxidative stress are implicated in the pathogenesis of inherited (e.g. Kearns Sayre Syndrome) and acquired corneal diseases (e.g. keratoconus and Fuchs endothelial corneal dystrophy). Both antioxidants and reactive oxygen species are found in the healthy cornea. There is increasing evidence of imbalance in the oxidative balance and mitochondrial function in the cornea in disease states...
May 23, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28548949/dietary-grape-seed-proanthocyanidins-inactivate-regulatory-t-cells-by-promoting-ner-dependent-dna-repair-in-dendritic-cells-in-uvb-exposed-skin
#10
Mudit Vaid, Ram Prasad, Tripti Singh, Santosh K Katiyar
Ultraviolet B (UVB) radiation induces regulatory T cells (Treg cells) and depletion of these Treg cells alleviates immunosuppression and inhibits photocarcinogenesis in mice. Here, we determined the effects of dietary grape seed proanthocyanidins (GSPs) on the development and activity of UVB-induced Treg cells. C3H/HeN mice fed a GSPs (0.5%, w/w)-supplemented or control diet were exposed to UVB (150 mJ/cm2) radiation, sensitized to 2,4-dinitrofluorobenzene (DNFB) and sacrificed 5 days later. FACS analysis indicated that dietary GSPs decrease the numbers of UVB-induced Treg cells...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548929/brd4-facilitates-dna-damage-response-and-represses-cbx5-heterochromatin-protein-1-hp1
#11
Georgios Pongas, Marianne K Kim, Dong J Min, Carrie D House, Elizabeth Jordan, Natasha Caplen, Sirisha Chakka, Joyce Ohiri, Michael J Kruhlak, Christina M Annunziata
Ovarian cancer (OC) is a heterogeneous disease characterized by defective DNA repair. Very few targets are universally expressed in the high grade serous (HGS) subtype. We previously identified that CHK1 was overexpressed in most of HGSOC. Here, we sought to understand the DNA damage response (DDR) to CHK1 inhibition and increase the anti-tumor activity of this pathway. We found BRD4 suppression either by siRNA or BRD4 inhibitor JQ1 enhanced the cytotoxicity of CHK1 inhibition. Interestingly, BRD4 was amplified and/or upregulated in a subset of HGSOC with statistical correlation to overall survival...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548877/role-of-osgin1-in-mediating-smoking-induced-autophagy-in-the-human-airway-epithelium
#12
Guoqing Wang, Haixia Zhou, Yael Strulovici-Barel, Mohammed Al-Hijji, Xuemei Ou, Jacqueline Salit, Matthew S Walters, Michelle R Staudt, Robert J Kaner, Ronald G Crystal
Enhanced macroautophagy/autophagy is recognized as a component of the pathogenesis of smoking-induced airway disease. Based on the knowledge that enhanced autophagy is linked to oxidative stress and the DNA damage response, both of which are linked to smoking, we used microarray analysis of the airway epithelium to identify smoking upregulated genes known to respond to oxidative stress and the DNA damage response. This analysis identified OSGIN1 (oxidative stress induced growth inhibitor 1) as significantly upregulated by smoking, in both the large and small airway epithelium, an observation confirmed by an independent small airway microarray cohort, TaqMan PCR of large and small airway samples and RNA-Seq of small airway samples...
May 26, 2017: Autophagy
https://www.readbyqxmd.com/read/28547180/role-of-antioxidant-treatment-on-dna-and-lipid-damage-in-the-brain-of-rats-subjected-to-a-chemically-induced-chronic-model-of-tyrosinemia-type-ii
#13
Emilio L Streck, Samira D T De Prá, Paula Ronsani Ferro, Milena Carvalho-Silva, Lara M Gomes, Jotele F Agostini, Adriani Damiani, Vanessa M Andrade, Patrícia F Schuck, Gustavo C Ferreira, Giselli Scaini
Tyrosine levels are abnormally elevated in tissues and body fluids of patients with inborn errors of tyrosine metabolism. Tyrosinemia type II, which is caused by tyrosine aminotransferase deficiency, provokes eyes, skin, and central nervous system disturbances in affected patients. However, the mechanisms of brain damage are still poorly known. Considering that studies have demonstrated that oxidative stress may contribute, along with other mechanisms, to the neurological dysfunction characteristic of hypertyrosinemia, in the present study we investigated the effects of antioxidant treatment (NAC and DFX) on DNA damage and oxidative stress markers induced by chronic administration of L-tyrosine in cerebral cortex, hippocampus, and striatum of rats...
May 25, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28547116/groove-binding-of-vanillin-and-ethyl-vanillin-to-calf-thymus-dna
#14
Kaixin Xia, Guowen Zhang, Song Li, Deming Gong
Vanillin (VAN) and ethyl vanillin (EVA) are widely used food additives as flavor enhancers, but may have a potential security risk. In this study, the properties of binding of VAN or EVA with calf thymus DNA (ctDNA) were characterized by multi-spectroscopic methods, multivariate curve resolution-alternating least-squares (MCR-ALS) algorithm and molecular simulation. The concentration profiles for the components (VAN or EVA, ctDNA and VAN-ctDNA or EVA-ctDNA complex) by the MCR-ALS analysis showed that VAN or EVA interacted with ctDNA and formed VAN-ctDNA or EVA-ctDNA complex...
May 25, 2017: Journal of Fluorescence
https://www.readbyqxmd.com/read/28546520/-omic-approach-in-non-smoker-female-with-lung-squamous-cell-carcinoma-pinpoints-to-germline-susceptibility-and-personalized-medicine
#15
Margherita Baldassarri, Chiara Fallerini, Francesco Cetta, Marco Ghisalberti, Cristiana Bellan, Simone Furini, Ottavia Spiga, Sergio Crispino, Giuseppe Gotti, Francesca Ariani, Piero Paladini, Alessandra Renieri, Elisa Frullanti
Purpose: Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease. Materials and Methods: A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibs were subjected to a novel integrative "omic" approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger...
May 26, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28546430/crosstalk-between-the-h3k36me3-and-h4k16ac-histone-epigenetic-marks-in-dna-double-strand-break-repair
#16
Lin Li, Yinsheng Wang
Post-translational modifications of histone proteins regulate numerous cellular processes. Among these modifications, trimethylation of lysine 36 in histone H3 (H3K36me3) and acetylation of lysine 16 in histone H4 (H4K16ac) have important roles in transcriptional regulation and DNA damage response signaling. However, whether these two epigenetic histone marks are mechanistically linked remains unclear. Here, we discovered a new pathway through which H3K36me3 stimulates H4K16ac upon DNA double-strand break (DSB) induction in human cells...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28546384/systematic-analysis-of-the-dna-damage-response-network-in-telomere-defective-budding-yeast
#17
Eva-Maria Holstein, Greg Ngo, Conor Lawless, Peter Banks, Matthew Greetham, Darren Wilkinson, David Lydall
Functional telomeres are critically important to eukaryotic genetic stability. Scores of proteins and pathways are known to affect telomere function. Here, we report a series of related genome-wide genetic interaction screens performed on budding yeast cells with acute or chronic telomere defects. Genetic interactions were examined in cells defective in Cdc13 and Stn1, affecting two components of CST, a single stranded DNA (ssDNA) binding complex that binds telomeric DNA. For comparison, genetic interactions were also examined in cells with defects in Rfa3, affecting the major ssDNA binding protein, RPA, which has overlapping functions with CST at telomeres...
May 25, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28546133/tissue-engineered-trachea-regeneration-using-decellularized-trachea-matrix-treated-with-laser-micropore-technique
#18
Yong Xu, Dan Li, Zongqi Yin, Aijuan He, Miaomiao Lin, Gening Jiang, Xiao Song, Xuefei Hu, Yi Liu, Jinpeng Wang, Xiaoyun Wang, Liang Duan, Guangdong Zhou
Tissue-engineered trachea provides a promising approach for reconstruction of long segmental tracheal defects. However, a lack of ideal biodegradable scaffolds greatly restricts its clinical translation. Decellularized trachea matrix (DTM) is considered a proper scaffold for trachea cartilage regeneration owing to natural tubular structure, cartilage matrix components, and biodegradability. However, cell residual and low porosity of DTM easily result in immunogenicity and incomplete cartilage regeneration. To address these problems, a laser micropore technique (LMT) was applied in the current study to modify trachea sample porosity to facilitate decellular treatment and cell ingrowth...
May 22, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28545975/quinazolinone-derivatives-as-inhibitors-of-homologous-recombinase-rad51
#19
Ambber Ward, Lilong Dong, Jonathan M Harris, Kum Kum Khanna, Fares Al-Ejeh, David P Fairlie, Adrian P Wiegmans, Ligong Liu
RAD51 is a vital component of the homologous recombination DNA repair pathway and is overexpressed in drug-resistant cancers, including aggressive triple negative breast cancer (TNBC). A proposed strategy for improving therapeutic outcomes for patients is through small molecule inhibition of RAD51, thereby sensitizing tumor cells to DNA damaging irradiation and/or chemotherapy. Here we report structure-activity relationships for a library of quinazolinone derivatives. A novel RAD51 inhibitor (17) displays up to 15-fold enhanced inhibition of cell growth in a panel of TNBC cell lines compared to compound B02, and approximately 2-fold increased inhibition of irradiation-induced RAD51 foci formation...
May 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28545970/chitosan-stabilized-camptothecin-nanoemulsions-development-evaluation-and-biodistribution-in-preclinical-breast-cancer-animal-mode
#20
Subramanian Natesan, Abimanyu Sugumaran, Chandrasekar Ponnusamy, Vignesh Thiagarajan, Rajaguru Palanichamy, Ruckmani Kandasamy
Clinical use of camptothecin (CPT) is hindered due to its poor water and oil solubility, active lactone ring instability and non-targeted toxicity. Recently we reported formulation of camptothecin microemulsions with increased solubility for the improved treatment of breast cancer. In this research chitosan stabilized camptothecin nanoemulsions (CHI-CPT-NEs) were formulated improve the cancer targeting efficiency of CPT. The developed NEs were characterized for their droplet size distribution, stability in plasma and evaluated for in-vitro drug release, in-vivo targeting potential, in-vitro hemolytic potential, cytotoxicity, genotoxicity and in-vivo biodistribution...
May 22, 2017: International Journal of Biological Macromolecules
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