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https://www.readbyqxmd.com/read/29031068/platinum-iv-prodrugs-multiply-targeting-genomic-dna-histone-deacetylases-and-parp-1
#1
Zichen Xu, Weiwei Hu, Zhimei Wang, Shaohua Gou
Several Pt(IV) prodrugs containing SAA, a histone deacetylases inhibitor, were designed and prepared for multiply targeting genomic DNA, histone deacetylases and PARP-1. The resulting Pt(IV) prodrug had significantly strong antiproliferative activity against the tested cancer cell lines, especially SAA1, derived from the conjugation of cisplatin and SAA, had potent ability to overcome cisplatin resistance. Under the combined action of DNA platination and inhibition of HDACs and PARP-1 activity, the cytotoxic activity of SAA1 was 174-fold higher than cisplatin against cisplatin-resistant SGC7901/CDDP cancer cells...
October 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29027485/concentration-dependent-effect-of-fumonisin-b1-on-apoptosis-in-oesophageal-cancer-cells
#2
R B Khan, A Phulukdaree, A A Chuturgoon
The geographical distribution of oesophageal cancer is linked to the exposure of fumonisin B1 (FB1), a mycotoxin produced by fungi that contaminates staple food worldwide. Non-genotoxic carcinogens like FB1 disturb homeostasis through increased cell proliferation or suppression of apoptosis. This study investigated the involvement of FB1 (0-20 μM) in spindle-shaped N-cadherin (+) CD45 (-) osteoblastic (SNO) cell death. Cell viability and death were assessed using the MTS and Annexin V-Fluos assays, respectively...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29018054/the-induction-of-myeloma-cell-death-and-dna-damage-by-tetrac-a-thyroid-hormone-derivative
#3
Keren Cohen, Uri Abadi, Aleck Hercbergs, Paul J Davis, Martin Ellis, Osnat Ashur-Fabian
Multiple myeloma (MM) is a plasma cell malignancy in which involvement of the thyroid hormone-integrin αvβ3 pathway was shown and pharmacologic inhibition of this pathway is a rational approach to disease management. A thyroid hormone derivative, tetraiodothyroacetic acid (tetrac), which inhibits L-thyroxine (T4) and 3,5,3'-triiodo-L-thyronine (T3) binding to αvβ3 integrin, was studied in five MM cell lines and primary bone marrow (BM) MM cells. Tetrac inhibited MM cell proliferation (absolute cell number/viability) and induced caspase-dependent apoptosis (annexin-V/PI and cell cycle)...
October 10, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29016348/parp-1-and-parp-2-activity-in-cancer-induced-cachexia-potential-therapeutic-implications
#4
Esther Barreiro, Joaquim Gea
Skeletal muscle dysfunction and mass loss is a characteristic feature in patients with chronic diseases including cancer and acute conditions such as critical illness. Maintenance of an adequate muscle mass is crucial for the patients' prognosis irrespective of the underlying condition. Moreover, aging-related sarcopenia may further aggravate the muscle wasting process associated with chronic diseases and cancer. Poly(adenosine diphosphate-ribose) polymerase (PARP) activation has been demonstrated to contribute to the pathophysiology of muscle mass loss and dysfunction in animal models of cancer-induced cachexia...
October 26, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28992606/apoptotic-mechanism-behind-the-testicular-atrophy-in-photorefractory-and-scotosensitive-quail-involvement-of-gnih-induced-p-53-dependent-bax-caspase-3-mediated-pathway
#5
Somanshu Banerjee, Chandra Mohini Chaturvedi
In most of the avian species, daylength or photoperiod is the main environmental factor regulating reproduction. During their annual gonadal cycle, birds once sensitive to short or long day effect develop refractoriness to the same daylength and gonad develop or regress accordingly. The present study investigated the effects of photoperiodic alterations on apoptosis mediated testicular responses of photosensitive/photorefractory and scotosensitive/scotorefractory quail, Coturnix coturnix japonica. Testicular apoptosis in the quail of different photoperiodic conditions was assessed by monitoring the alterations in the local testicular expression of GnRH-I, GnIH, pro-apoptotic proteins (p53 and Bax), inactive caspase (pro-Caspase-3), executioner active-Caspase-3 and inactive/uncleaved PARP-1 (DNA repair enzyme) and TUNEL analysis...
September 29, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28991266/macroh2a1-1-regulates-mitochondrial-respiration-by-limiting-nuclear-nad-consumption
#6
Melanija Posavec Marjanović, Sarah Hurtado-Bagès, Maximilian Lassi, Vanesa Valero, Roberto Malinverni, Hélène Delage, Miriam Navarro, David Corujo, Iva Guberovic, Julien Douet, Pau Gama-Perez, Pablo M Garcia-Roves, Ivan Ahel, Andreas G Ladurner, Oscar Yanes, Philippe Bouvet, Mònica Suelves, Raffaele Teperino, J Andrew Pospisilik, Marcus Buschbeck
Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A1.1 contains a macrodomain capable of binding NAD(+)-derived metabolites. Here we report that macroH2A1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing, and that myotubes that lack macroH2A1.1 have a defect in mitochondrial respiratory capacity. We found that the metabolite-binding macrodomain was essential for sustained optimal mitochondrial function but dispensable for gene regulation...
October 9, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28983606/parp%C3%A2-1-may-be-involved-in-hydroquinone%C3%A2-induced-apoptosis-by-poly-adp%C3%A2-ribosylation-of-zo%C3%A2-2
#7
Jiaxian Liu, Qian Yuan, Xiaoxuan Ling, Qiang Tan, Hairong Liang, Jialong Chen, Lianzai Lin, Yongmei Xiao, Wen Chen, Linhua Liu, Huanwen Tang
Hydroquinone (HQ), a major reactive metabolite of benzene, contributes to benzene‑induced leukemia. The molecular mechanisms that underlie this activity remain to be elucidated. Poly ADP‑ribosylation (PARylation) is a type of reversible posttranslational modification that is performed by enzymes in the PAR polymerase (PARP) family and mediates different biological processes, including apoptosis. Zona occludens 2 (ZO‑2) is a tight junction scaffold protein, which is involved in cell proliferation and apoptosis...
September 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28978125/the-degradation-of-mixed-lineage-kinase-domain-like-protein-promotes-neuroprotection-after-ischemic-brain-injury
#8
Yanlong Zhou, Beiqun Zhou, Hui Tu, Yan Tang, Chen Xu, Yanbo Chen, Zhong Zhao, Zhigang Miao
Mixed lineage kinase domain-like (MLKL) protein was recently found to play a critical role in necrotic cell death. To explore its role in neurological diseases, we measured MLKL protein expression after ischemia injury in a mouse model. We found that MLKL expression significantly increased 12 h after ischemia/reperfusion (I/R) injury with peak levels at 48 h. Inhibition of MLKL by intraperitoneal administration of NSA significantly reduced infarct volume and improved neurological deficits after 75 min of ischemia and 24 h of reperfusion...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975372/t-buooh-induces-ferroptosis-in-human-and-murine-cell-lines
#9
Christine Wenz, Dagmar Faust, Berenike Linz, Christian Turmann, Teodora Nikolova, John Bertin, Peter Gough, Peter Wipf, Anna Sophia Schröder, Stefan Krautwald, Cornelia Dietrich
Reactive oxygen species (ROS)-induced apoptosis has been extensively studied. Increasing evidence suggests that ROS, for instance, induced by hydrogen peroxide (H2O2), might also trigger regulated necrotic cell death pathways. Almost nothing is known about the cell death pathways triggered by tertiary-butyl hydroperoxide (t-BuOOH), a widely used inducer of oxidative stress. The lipid peroxidation products induced by t-BuOOH are involved in the pathophysiology of many diseases, such as cancer, cardiovascular diseases, or diabetes...
October 3, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28974953/poly-adp-ribose-polymerase-1-in-lung-inflammatory-disorders-a-review
#10
REVIEW
Gurupreet S Sethi, Vivek Dharwal, Amarjit S Naura
Asthma, acute lung injury (ALI), and chronic obstructive pulmonary disease (COPD) are lung inflammatory disorders with a common outcome, that is, difficulty in breathing. Corticosteroids, a class of potent anti-inflammatory drugs, have shown less success in the treatment/management of these disorders, particularly ALI and COPD; thus, alternative therapies are needed. Poly(ADP-ribose)polymerases (PARPs) are the post-translational modifying enzymes with a primary role in DNA repair. During the last two decades, several studies have reported the critical role played by PARPs in a good of inflammatory disorders...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28964648/association-of-il6st-gp130-polymorphism-with-functional-outcome-following-spontaneous-intracerebral-hemorrhage
#11
Nada El Husseini, Benjamin M Hoffman, Ellen R Bennett, Yen-Wei Li, Rachel A Williamson Taylor, Claire E Hailey, Kara Richardson, Yi-Ju Li, Daniel T Laskowitz, Michael L James
BACKGROUND AND PURPOSE: Genes associated with the inflammatory response and cytostructural integrity may influence recovery following a brain injury. To examine this in the setting of spontaneous intracerebral hemorrhage (ICH), selected single nucleotide polymorphisms (SNPs) were assessed for associations with patient outcome. METHODS: A cohort of 54 patients with supratentorial ICH were enrolled. Based on known involvement with neuroinflammation and cytostructural integrity, 10 preselected SNPs from 6 candidate genes were tested for associations with 6-month functional outcome (modified Rankin Scale [mRS] ≥ 3), mortality, and in-hospital deterioration (Glasgow Coma Scale decrease by >2 within 7 days of admission) following ICH...
September 27, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28931657/neutrophil-transfer-of-mir-223-to-lung-epithelial-cells-dampens-acute-lung-injury-in-mice
#12
Viola Neudecker, Kelley S Brodsky, Eric T Clambey, Eric P Schmidt, Thomas A Packard, Bennett Davenport, Theodore J Standiford, Tingting Weng, Ashley A Fletcher, Lea Barthel, Joanne C Masterson, Glenn T Furuta, Chunyan Cai, Michael R Blackburn, Adit A Ginde, Michael W Graner, William J Janssen, Rachel L Zemans, Christopher M Evans, Ellen L Burnham, Dirk Homann, Marc Moss, Simone Kreth, Kai Zacharowski, Peter M Henson, Holger K Eltzschig
Intercellular transfer of microRNAs can mediate communication between critical effector cells. We hypothesized that transfer of neutrophil-derived microRNAs to pulmonary epithelial cells could alter mucosal gene expression during acute lung injury. Pulmonary-epithelial microRNA profiling during coculture of alveolar epithelial cells with polymorphonuclear neutrophils (PMNs) revealed a selective increase in lung epithelial cell expression of microRNA-223 (miR-223). Analysis of PMN-derived supernatants showed activation-dependent release of miR-223 and subsequent transfer to alveolar epithelial cells during coculture in vitro or after ventilator-induced acute lung injury in mice...
September 20, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28916446/cancer-derived-exosomes-as-a-delivery-platform-of-crispr-cas9-confer-cancer-cell-tropism-dependent-targeting
#13
Seung Min Kim, Yoosoo Yang, Seung Ja Oh, Yeonsun Hong, Minkoo Seo, Mihue Jang
An intracellular delivery system for CRISPR/Cas9 is crucial for its application as a therapeutic genome editing technology in a broad range of diseases. Current vehicles carrying CRISPR/Cas9 limit in vivo delivery because of low tolerance and immunogenicity; thus, the in vivo delivery of genome editing remains challenging. Here, we report that cancer-derived exosomes function as natural carriers that can efficiently deliver CRISPR/Cas9 plasmids to cancer. Compared to epithelial cell-derived exosomes, cancer-derived exosomes provide potential vehicles for effective in vivo delivery via selective accumulation in ovarian cancer tumors of SKOV3 xenograft mice, most likely because of their cell tropism...
September 12, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28914791/quercetin-attenuates-manganese-induced-neuroinflammation-by-alleviating-oxidative-stress-through-regulation-of-apoptosis-inos-nf-%C3%AE%C2%BAb-and-ho-1-nrf2-pathways
#14
Entaz Bahar, Ji-Ye Kim, Hyonok Yoon
Manganese (Mn) is an essential trace element required for the development of human body and acts as an enzyme co-factor or activator for various reactions of metabolism. While essential in trace amounts, excessive Mn exposure can result in toxic accumulations in human brain tissue and resulting extrapyramidal symptoms called manganism similar to idiopathic Parkinson's disease (PD). Quercetin (QCT) has been demonstrated to play an important role in altering the progression of neurodegenerative diseases by protecting against oxidative stress...
September 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28904196/vaccinia-virus-encodes-a-novel-inhibitor-of-apoptosis-that-associates-with-the-apoptosome
#15
Melissa R Ryerson, Monique M Richards, Marc Kvansakul, Christine J Hawkins, Joanna L Shisler
Apoptosis is an important anti-viral host defense mechanism. Here we report the identification of a novel apoptosis inhibitor encoded by the vaccinia virus (VACV) M1L gene. M1L is absent in the attenuated MVA strain of VACV, a strain that stimulates apoptosis in several types of immune cells. M1 expression increased the viability of MVA-infected THP-1 and Jurkat cells and reduced several biochemical hallmarks of apoptosis such as PARP-1 and procaspase-3 cleavage. Furthermore, ectopic M1L expression decreased staurosporine-induced (intrinsic) apoptosis in HeLa cells...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28901416/protective-role-of-berberine-and-coptischinensis-extract-on-t2md-rats-and-associated-islet-rin%C3%A2-5f-cells
#16
Yu-Yu Jiang, Han-Ming Cui, Jia-Long Wang, Hui Liu, Meng-Meng Dang, Qiu-Yan Zhang, Fang Yang, Jian-Tao Kou, Xiao-Lin Tong
The aim of the present study was to compare the different effects of berberine (Ber) and Coptischinensis extract (CCE) on a rat model of type 2 diabetes mellitus (T2DM), and the islet Rin‑5f cell line was used to examine the differences between Ber and CCE and the underlying mechanisms. CCE was extracted and purified prior to analysis. Male Sprague‑Dawley rats were provided with a high‑fat diet to induce insulin resistance prior to injecting with streptozotocinto establish the T2DM model, the T2DM rats were treated with Ber and CCE, and blood samples and pancreatic tissues were obtained and compared to examine T2DM metabolic syndromes among the groups of rats, which included healthy rats, model rats, and model rats treated with Ber and CCE at different doses between 0 and 8 weeks...
September 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28883608/gyy4137-a-hydrogen-sulfide-donor-modulates-mir194-dependent-collagen-realignment-in-diabetic-kidney
#17
A M Sashi Papu John, Sourav Kundu, Sathnur Pushpakumar, Maura Fordham, Gregory Weber, Manas Mukhopadhyay, Utpal Sen
The relationship between hydrogen sulfide (H2S), microRNAs (miRs), matrix metalloproteinases (MMPs) and poly-ADP-ribose-polymerase-1 (PARP-1) in diabetic kidney remodeling remains mostly obscured. We aimed at investigating whether alteration of miR-194-dependent MMPs and PARP-1 causes renal fibrosis in diabetes kidney, and whether H2S ameliorates fibrosis. Wild type, diabetic Akita mice as well as mouse glomerular endothelial cells (MGECs) were used as experimental models, and GYY4137 as H2S donor. In diabetic mice, plasma H2S levels were decreased while ROS and expression of its modulator (ROMO1) were increased...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28875381/differential-apoptotic-response-of-mc3t3-e1-pre-osteoblasts-to-biodegradable-magnesium-alloys-in-an-in-vitro-direct-culture-model
#18
Ehsan Bonyadi Rad, Sepideh Mostofi, Matthias Katschnig, Patrik Schmutz, Magdalena Pawelkiewicz, Regine Willumeit-Römer, Ute Schäfer, Annelie Weinberg
The biodegradable magnesium-based implants have been widely utilized in medical orthopedic applications in recent years. We have recently shown that direct culture on Pure Mg and Mg2Ag alloys lead to a progressive differentiation impairment of MC3T3-E1 pre-osteoblasts. In this study, we aimed to analyze the apoptotic reaction of MC3T3-E1 cells in response to the direct culture on Pure Mg, Mg2Ag and Extreme High Pure Mg (XHP Mg) alloy samples. Our results demonstrated that long-term culturing of MC3T3-E1 cells on Pure Mg and Mg2Ag alloys induce time-dependent expression of active caspase-3 (active casp-3) and cleaved PARP-1 (cl...
September 5, 2017: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/28871597/activation-of-the-mitochondrial-apoptotic-pathway-contributes-to-methotrexate-induced-small-intestinal-injury-in-rats
#19
Kasthuri Natarajan, Premila Abraham, Rekha Kota
The efficacy of methotrexate (MTX), a commonly used chemotherapeutic drug, is limited by intestinal injury. As the mechanism of MTX-induced small intestinal injury is not clear, there is no definitive treatment for MTX-induced gastrointestinal injury. The present study investigates the role of mitochondrial apoptotic pathway in MTX-induced small intestinal injury and examines whether aminoguanidine is effective in preventing the damage. Eight Wistar rats were administered 3 consecutive i.p. injections of 7 mg/kg body wt...
September 4, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/28853108/differences-in-poly-adp-ribose-polymerase1-parp1-and-proliferative-cell-nuclear-antigen-pcna-immunoreactivity-in-patients-who-experienced-successful-and-unsuccessful-microdissection-testicular-sperm-extraction-procedures
#20
Süleyman Akarsu, Baris Büke, Seren Gülsen Gürgen, Serkan Akdemir, Funda Gode, Merve Biçer, Mustafa Agah Tekindal, Ahmet Zeki Isik
PURPOSE: The aim of this study is to evaluate expression of deoxyribonucleic acid (DNA) synthesis and repair markers in testicular tissues of azoospermic men in whom sperm retrieval could and could not be achieved as a result of microdissection testicular sperm extraction (micro-TESE) procedure. MATERIALS AND METHODS: In this prospective cohort study, testicular tissues were retrieved from 60 Non-obstructive Azoospermia (NOA) patients who underwent micro-TESE procedure...
August 29, 2017: Urology Journal
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