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Genetic Evidence That Captured Retroviral Envelope < i > syncytins < /i > Contribute to Myoblast Fusion and Muscle Sexual Dimorphism in Mice
by Fran çois Redelsperger, Najat Raddi, Agathe Bacquin, Cécile Vernochet, Virginie Mariot, Vincent Gache, Nicolas Blanchard-Gutton, Stéphanie Charrin, Laurent Tiret, Julie Dumonceaux, Anne Dupressoir, Thierry HeidmannSyncytins are envelope genes from endogenous retroviruses, “captured” for a role in placentation. They mediate cell-cell fusion, resulting in the formation of a syncytium (the syncytiotrophoblast) at the fetomaternal interface. These genes have been found in all placental mammals in which they have been searched for. Cell-cell fusion is also pivotal for muscle fiber formation and repair, where the myotu...
Source: PLoS Genetics - September 1, 2016 Category: Genetics & Stem Cells Authors: Fran çois Redelsperger Source Type: research

Regulating gene expression towards solving ocular surface diseases
SummaryTreatment of genetic eye disease poses significant medical and surgical challenges. We used a bioluminescent corneal reporter gene mouse model to assess efficacy and potency of a number of gene therapy approaches for corneal dystrophy. Various modalities were assessed for delivery of short interfering RNA (siRNA) targeting one of five mutant alleles present in the corneal bioluminescent mouse model enabling assessment of topical, subconjunctival and intrastromal delivery. Potent and sustained in vivo gene silencing >50% for up to 7 days was observed. This siRNA therapy only provides a transient silencing of the ...
Source: Acta Ophthalmologica - September 13, 2016 Category: Opthalmology Authors: T. Moore, S. Atkinson, E. Maurizi, D. Schiroli, L. Mairs, K. Christie, I. McLean, E. Allen, D.L. Pedrioli, J. Moore, A. Nesbit Tags: Abstracts from the 2016 European Association for Vision and Eye Research Conference Source Type: research

Homology directed repair is unaffected by the absence of siRNAs in Drosophila melanogaster
Small interfering RNAs (siRNAs) defend the organism against harmful transcripts from exogenous (e.g. viral) or endogenous (e.g. transposons) sources. Recent publications describe the production of siRNAs induced by DNA double-strand breaks (DSB) in Neurospora crassa, Arabidopsis thaliana, Drosophila melanogaster and human cells, which suggests a conserved function. A current hypothesis is that break-induced small RNAs ensure efficient homologous recombination (HR). However, biogenesis of siRNAs is often intertwined with other small RNA species, such as microRNAs (miRNAs), which complicates interpretation of experimental re...
Source: Nucleic Acids Research - September 28, 2016 Category: Research Authors: Schmidts, I., Böttcher, R., Mirkovic-Hösle, M., Förstemann, K. Tags: Genome Integrity, Repair and Replication Source Type: research

DDIS-06. Ku 70/80 IN GLIOMA - TARGETING WITH APTAMERS
CONCLUSIONS:Certain aptamers appear to readily bind to DNA repair proteins Ku70 and Ku80 and could be used for developing targeted therapy towards glioma. Western and knockdown analysis, confirm the specificity of binding and leads the way for in-vivo testing of aptamers.
Source: Neuro-Oncology - November 6, 2016 Category: Cancer & Oncology Authors: Arora, M., Davis, C., Dawson, T., Alder, J., Lawrence, C., Shaw, L. Tags: DRUG DISCOVERY Source Type: research

HIC1 (hypermethylated in cancer 1) SUMOylation is dispensable for DNA repair but is essential for the apoptotic DNA damage response (DDR) to irreparable DNA double-strand breaks (DSBs).
Authors: Paget S, Dubuissez M, Dehennaut V, Nassour J, Harmon BT, Spruyt N, Loison I, Abbadie C, Rood BR, Leprince D Abstract The tumor suppressor gene HIC1 (Hypermethylated In Cancer 1) encodes a transcriptional repressor mediating the p53-dependent apoptotic response to irreparable DNA double-strand breaks (DSBs) through direct transcriptional repression of SIRT1. HIC1 is also essential for DSB repair as silencing of endogenous HIC1 in BJ-hTERT fibroblasts significantly delays DNA repair in functional Comet assays. HIC1 SUMOylation favours its interaction with MTA1, a component of NuRD complexes. In contrast with...
Source: Oncotarget - December 10, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Molecules, Vol. 22, Pages 139: Oligonucleotide Therapy for Obstructive and Restrictive Respiratory Diseases
Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD) and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF). The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects. Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue re...
Source: Molecules - January 16, 2017 Category: Chemistry Authors: Wupeng Liao Jinrui Dong Hong Peh Lay Tan Kah Lim Li Li Wai-Shiu Wong Tags: Review Source Type: research

Abstract P2-12-03: Prospective study of acupuncture in the rehabilitation of women undergoing surgical treatment of breast cancer in relation to the strength and quality of life
Conclusion: DAPK1 is a novel, promising target for the treatment of triple-negative p53-mutant breast cancer. Our studies demonstrate that DAPK1 inhibition sensitizes TNBCs to the cytotoxic effects of cisplatin or the PARP inhibitor. We are now conducting studies to determine whether DAPK1 inhibition will sensitize TNBC tumors and patient-derived TNBC xenografts to the effects of cisplatin and PARP inhibition. These studies suggest that the combination of DAPK1 inhibition with drugs that interfere with DNA repair will be useful for the treatment of the most aggressive form of breast cancer, triple-negative breast cancer.Fu...
Source: Cancer Research - February 13, 2017 Category: Cancer & Oncology Authors: PS Giron, CA Haddad, SL Rizzi, TL Pinheiro, RP Luz, AP Nazario, G Facina Tags: Poster Session Abstracts Source Type: research

Enhanced SOCS3 in osteoarthiritis may limit both proliferation and inflammation.
Abstract Osteoarthritis (OA) is a degenerative joint disease that is characterized by localized inflammatory and secondary proliferative changes. Suppressor of cytokine signaling 3 (SOCS3) is elevated during OA development. We investigated the effects of this protein on human chondrocyte survival in OA and the inflammatory response together with the mechanisms of these effects. Small interfering RNA (siRNA) was used to knock down the expression of SOCS3 in interleukin(IL)-1β-induced primary human osteoarthritic chondrocytes. We found that siRNA-mediated SOCS3 knock-down in human osteoarthritic chondrocytes increa...
Source: Biotechnic and Histochemistry - March 19, 2017 Category: Research Authors: Gui T, He BS, Gan Q, Yang C Tags: Biotech Histochem Source Type: research

Translesion Synthesis DNA Polymerase Kappa Is Indispensable for DNA Repair Synthesis in Cisplatin Exposed Dorsal Root Ganglion Neurons
AbstractIn the peripheral nervous system (PNS) in the absence of tight blood barrier, neurons are at increased risk of DNA damage, yet the question of how effectively PNS neurons manage DNA damage remains largely unanswered. Genotoxins in systemic circulation include chemotherapeutic drugs that reach peripheral neurons and damage their DNA. Because neurotoxicity of platinum-based class of chemotherapeutic drugs has been implicated in PNS neuropathies, we utilized an in vitro model of Dorsal Root Ganglia (DRGs) to investigate how peripheral neurons respond to cisplatin that forms intra- and interstrand crosslinks with their...
Source: Molecular Neurobiology - April 8, 2017 Category: Neurology Source Type: research

Silencing of DNA repair sensitizes pediatric brain tumor cells to ɣ-irradiation using gold nanoparticles
We present a nanoparticle (NP)-mediated delivery vehicle that effectively carries and protects siRNA in pediatric ependymoma (EP) and medulloblastoma (MB) cells. The delivery vehicle consists of gold NPs coated with a polymeric shell comprising polyethylene glycol (PG), chitosan and polyethyleneimine (Au-CP-PEI). NPs loaded with siRNA knocked down Ape1 expression by over 75% in both MB and EP cells. Further, this reduction in Ape1 expression is associated with an increase in DNA damage after irradiation. The results indicate that NP-associated delivery of siApe1 is a feasible approach to circumventing pediatric brain tumor...
Source: Environmental Toxicology and Pharmacology - April 28, 2017 Category: Environmental Health Source Type: research

Silencing of DNA repair sensitizes pediatric brain tumor cells to γ-irradiation using gold nanoparticles
We present a nanoparticle (NP)-mediated delivery vehicle that effectively carries and protects siRNA in pediatric ependymoma (EP) and medulloblastoma (MB) cells. The delivery vehicle consists of gold NPs coated with a polymeric shell comprising polyethylene glycol (PG), chitosan and polyethyleneimine (Au-CP-PEI). NPs loaded with siRNA knocked down Ape1 expression by over 75% in both MB and EP cells. Further, this reduction in Ape1 expression is associated with an increase in DNA damage after irradiation. The results indicate that NP-associated delivery of siApe1 is a feasible approach to circumventing pediatric brain tumor...
Source: Environmental Toxicology and Pharmacology - May 11, 2017 Category: Environmental Health Source Type: research

Exogenous MSCs ameliorate hypoxia/reoxygenation injury in renal tubular epithelial cells through JAK/STAT signaling pathway-mediated regulation of HMGB1.
This study was conducted to investigate the repair mechanism of hypoxia/reoxygenation injury (HRI) in renal tubular epithelial cells (HK-2) by exogenous mesenchymal stem cells (MSCs). The activation of the JAK/STAT pathway in HK-2 cells after HRI and treatment of MSCs, JAK inhibitor WP1066 and STAT inhibitor SOCS3 was investigated using Western blot analysis. HK-2 cells were transfected with siRNA STAT3 and analyzed for expression of STAT3, JAK2 and HMGB1 using fluorescence quantitative PCR and Western blot. Cell viability and apoptosis were analyzed using the MTT assay and flow cytometry. After HRI, the JAK/STAT pathway i...
Source: American Journal of Translational Research - June 2, 2017 Category: Research Tags: Am J Transl Res Source Type: research

Clinical pharmacology and clinical trials of ribonucleotide reductase inhibitors: is it a viable cancer therapy?
ConclusionsBased on the results of clinical trials, we conclude that RR inhibitors are viable treatment options, either as a monotherapy or as a combination in cancer chemotherapy. With the recent advances made in cancer biology, further development of RR inhibitors with improved efficacy and reduced toxicity is possible for treatment of variety of cancers.
Source: Journal of Cancer Research and Clinical Oncology - June 17, 2017 Category: Cancer & Oncology Source Type: research

RNAi-mediated ephrin-B2 silencing attenuates astroglial-fibrotic scar formation and improves spinal cord axon growth.
CONCLUSIONS: These results suggest that astroglial-fibrotic scar formation and particularly the expression of aggrecan and versican could be mitigated by ephrin-B2 specific siRNA, thus improving the microenvironment for spinal axon regeneration. PMID: 28834283 [PubMed - as supplied by publisher]
Source: CNS Neuroscience and Therapeutics - August 21, 2017 Category: Neuroscience Authors: Li Y, Chen Y, Tan L, Pan JY, Lin WW, Wu J, Hu W, Chen X, Wang XD Tags: CNS Neurosci Ther Source Type: research