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https://www.readbyqxmd.com/read/29458203/precision-pharmacology-for-alzheimer-s-disease
#1
REVIEW
Harald Hampel, Andrea Vergallo, Lisi Flores Aguilar, Norbert Benda, Karl Broich, A Claudio Cuello, Jeffrey Cummings, Bruno Dubois, Howard J Federoff, Massimo Fiandaca, Remy Genthon, Marion Haberkamp, Eric Karran, Mark Mapstone, George Perry, Lon S Schneider, Lindsay A Welikovitch, Janet Woodcock, Filippo Baldacci, Simone Lista
The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses...
February 16, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29458169/inhibition-of-microsomal-prostaglandin-e-synthase-1-facilitates-liver-repair-after-hepatic-injury-in-mice
#2
Nobuyuki Nishizawa, Yoshiya Ito, Koji Eshima, Hirotoki Ohkubo, Ken Kojo, Tomoyoshi Inoue, Joan Raouf, Per-Johan Jakobsson, Satoshi Uematsu, Shizuo Akira, Shuh Narumiya, Masahiko Watanabe, Masataka Majima
BACKGROUND & AIMS: Liver repair following hepatic ischemia/reperfusion (I/R) injury is crucial to survival. This study aims to examine the role of endogenous prostaglandin E2 (PGE2 ) produced by inducible microsomal PGE synthase-1 (mPGES-1), a terminal enzyme of PGE2 generation, in liver injury and repair following hepatic I/R. METHODS: mPGES-1 deficient (mPGES-1-/- ) mice or their wild counterparts (WT) were subjected to partial hepatic ischemia followed by reperfusion...
February 16, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29458129/honeysuckle-encoded-microrna2911-inhibits-enterovirus-71-replication-via-targeting-vp1-gene
#3
Xihan Li, Ying Huang, Menghuai Sun, Hong Ji, Hui Dou, Jia Hu, Yanfeng Yan, Xu Wang, Leiyao Chen
Enterovirus 71 (EV71) is the primary pathogen of hand-foot-and-mouth disease (HFMD) in children and virus infections are associated with severe neurological dysfunctions and even death. MIR2911 is a honeysuckle-encoded atypical microRNA with extremely stability. Here, we report that MIR2911 directly inhibits EV71 replication by targeting the VP1 gene. Bioinformatics prediction and luciferase reporter assay showed that MIR2911 could target the VP1 gene of EV71. Transfection experiments using synthetic MIR2911 and extracted RNA from HS decoction shown that each of these preparations was capable of inhibiting EV71 VP1 protein expression; however, these preparations did not impact EV71 mutants in which the MIR2911-binding sites were mutated...
February 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29458052/regulation-of-proliferation-and-functioning-of-transplanted-cells-by-using-herpes-simplex-virus-thymidine-kinase-gene-in-mice
#4
Mari Tsujimura, Kosuke Kusamori, Chihiro Oda, Airi Miyazaki, Hidemasa Katsumi, Toshiyasu Sakane, Makiya Nishikawa, Akira Yamamoto
Though cell transplantation is becoming an attractive therapeutic method, uncontrolled cell proliferation or overexpression of cellular functions could cause adverse effects. These unfavorable outcomes could be avoided by regulating the proliferation or functioning of transplanted cells. In this study, we used a combination of the herpes simplex virus thymidine kinase (HSVtk) gene, a suicide gene, and ganciclovir (GCV) to control the proliferation and functioning of insulin-secreting cells after transplantation in diabetic mice...
February 16, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29458007/a-genomically-characterized-collection-of-high-grade-serous-ovarian-cancer-xenografts-for-preclinical-testing
#5
Paulina Cybulska, Jocelyn M Stewart, Azin Sayad, Carl Virtanen, Patricia A Shaw, Blaise Clarke, Natalie Stickle, Marcus Q Bernardini, Benjamin G Neel
High-grade serous ovarian cancer (HGSC) is the leading cause of morbidity and mortality from gynecologic malignancy. Overall survival remains low, due to the nearly ubiquitous emergence of platinum-resistance and the paucity of effective next-line treatments. Current cell culture-based models show limited similarity to HGSC and are therefore unreliable predictive models for pre-clinical evaluation of investigational drugs. This deficiency could help explain the low overall rate of successful drug development and the decades of largely unchanged approaches to HGSC treatment...
February 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29457968/in-vitro-and-in-vivo-effects-of-mk2206-and-chloroquine-combination-therapy-on-endometriosis-autophagy-may-be-required-for-regrowth-of-endometriosis
#6
Sachiko Matsuzaki, Jean-Luc Pouly, Michel Canis
BACKGROUND AND PURPOSE: A high recurrence rate after medical treatment is a major clinical problem for patients with endometriosis. In the present study, we evaluated the in vitro effects of combined treatment with MK2206 (an AKT inhibitor) + chloroquine on cell growth and regrowth of endometriotic stromal cells, and the in vivo effects on endometriotic implants in a mouse xenograft model of endometriosis. EXPERIMENTAL APPROACH: We evaluated the effects of autophagy inhibition by knockdown of the ATG13, Beclin-1, and ATG12 genes and pharmacologic agents (chloroquine, bafilomycin A1, or 3-methyalanine) individually and in combination with MK2206 on cell growth and/or cell regrowth of endometriotic stromal cells in vitro...
February 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29457878/genetic-determinants-of-heart-failure-facts-and-numbers
#7
EDITORIAL
Frauke S Czepluch, Bernd Wollnik, Gerd Hasenfuß
The relevance of gene mutations leading to heart diseases and hence heart failure has become evident. The risk for and the course of heart failure depends on genomic variants and mutations underlying the so-called genetic predisposition. Genetic contribution to heart failure is highly heterogenous and complex. For any patient with a likely inherited heart failure syndrome, genetic counselling is recommended and important. In the last few years, novel sequencing technologies (named next-generation sequencing - NGS) have dramatically improved the availability of molecular testing, the efficiency of genetic analyses, and moreover reduced the cost for genetic testing...
February 19, 2018: ESC Heart Failure
https://www.readbyqxmd.com/read/29457830/mirna-124-3p-neuropilin-1-nrp-1-axis-plays-an-important-role-in-mediating-glioblastoma-growth-and-angiogenesis
#8
Guilong Zhang, Lukui Chen, Ahsan Ali Khan, Bingqian Li, Bin Gu, Fan Lin, Xinhui Su, Jianghua Yan
Glioblastoma Multiforme (GBM) is the most lethal brain malignancy which involves multi-gene abnormality. Unfortunately, effective therapy against GBM is still lacking. Previously, we found that NRP-1 and its downstream NRP-1/GIPC1 pathway played an important role in GBM. In this study, we further investigated the upstream signaling of NRP-1 to understand how it is regulated. Firstly, we identified that hsa-miR-124-3p was miRNA differentially expressed in GBM and in normal brain tissues by high-throughput sequencing...
February 19, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29457277/polymorphisms-of-cyp27b1-are-associated-with-ifn-efficacy-in-hbeag-positive-patients
#9
Yingying Wu, Yongbin Zeng, Wennan Wu, Jinpiao Lin, Qishui Ou
BACKGROUND: Host single nucleotide polymorphisms were associated with antiviral therapy in CHB patients. The CYP27B1 gene, encoding 25(OH)D3 -1α hydroxylase, might activate 25(OH)D3 to 1,25(OH)2 D3 in kidney resulted in influencing the efficacy of interferon (IFN). The aim of the study was to investigate the association between CYP27B1 polymorphisms and the response to IFN in HBeAg-positive patients. METHODS: Eighty-seven HBeAg-positive CHB patients infected with HBV genotype B or C were included in the study...
February 18, 2018: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/29457276/abrus-agglutinin-stimulates-bmp-2-dependent-differentiation-through-autophagic-degradation-of-%C3%AE-catenin-in-colon-cancer-stem-cells
#10
Prashanta Kumar Panda, Prajna Paramita Naik, Prakash P Praharaj, Biswa Ranjan Meher, Piyush Kumar Gupta, Rama S Verma, Tapas K Maiti, Muthu K Shanmugam, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Gautam Sethi, Rajesh Agarwal, Sujit K Bhutia
Eradicating cancer stem cells (CSCs) in colorectal cancer (CRC) through differentiation therapy is a promising approach for cancer treatment. Our retrospective tumor-specimen analysis elucidated alteration in the expression of bone morphogenetic protein 2 (BMP-2) and β-catenin during the colon cancer progression, indicating that their possible intervention through "forced differentiation" in colon cancer remission. We reveal that Abrus agglutinin (AGG) induces the colon CSCs differentiation, enhancing sensitive to the anticancer therapeutics...
February 19, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29456889/a-bibliometric-analysis-in-gene-research-of-myocardial-infarction-from-2001-to-2015
#11
Huaqiang Zhou, Wulin Tan, Zeting Qiu, Yiyan Song, Shaowei Gao
Objectives: We aimed to evaluate the global scientific output of gene research of myocardial infarction and explore their hotspots and frontiers from 2001 to 2015, using bibliometric methods. Methods: Articles about the gene research of myocardial infarction between 2001 and 2015 were retrieved from the Web of Science Core Collection (WoSCC). We used the bibliometric method and Citespace V to analyze publication years, journals, countries, institutions, research areas, authors, research hotspots, and trends...
2018: PeerJ
https://www.readbyqxmd.com/read/29456886/heterogenic-transplantation-of-bone-marrow-derived-rhesus-macaque-mesenchymal-stem-cells-ameliorates-liver-fibrosis-induced-by-carbon-tetrachloride-in-mouse
#12
Xufeng Fu, Bin Jiang, Bingrong Zheng, Yaping Yan, Junfeng Wang, Yanchao Duan, Shanshan Li, Li Yan, Hong Wang, Bingbing Chen, Xiongbo Sang, Weizhi Ji, Ren-He Xu, Wei Si
Liver fibrosis is a disease that causes high morbidity and has become a major health problem. Liver fibrosis can lead to the end stage of liver diseases (livercirrhosisand hepatocellularcarcinoma). Currently, liver transplantation is the only effective treatment for end-stage liver disease. However, the shortage of organ donors, high cost of medical surgery, immunological rejection and transplantation complications severely hamper liver transplantation therapy. Mesenchymal stem cells (MSCs) have been regarded as promising cells for clinical applications in stem cell therapy in the treatment of liver diseases due to their unique multipotent differentiation capacity, immunoregulation and paracrine effects...
2018: PeerJ
https://www.readbyqxmd.com/read/29456854/novel-braf-mutation-in-melanoma-a-case-report
#13
Serena Trubini, Alessandro Ubiali, Carlo Terenzio Paties, Luigi Cavanna
In melanoma, a number of specific genetic and genomic aberrations have been identified to be important in tumorigenesis. In particular, the mutant B-Raf proto-oncogene, Serine/Threonine kinase (BRAF) gene is the target of tailored therapy with kinase inhibitor molecules. Identification of the array of mutations in patients with melanoma will be useful in determining a genetic profile of the tumor with potential implications for treatment decisions. A rare aminoacidic insertion in codon 599 of the BRAF gene (c...
March 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29456821/resveratrol-decreases-apoptosis-and-nlrp3-complex-expressions-in-experimental-varicocele-rat-model
#14
Elnaz Hajipour, Farideh Jalali Mashayekhi, Ghasem Mosayebi, Maryam Baazm, Adib Zendedel
Objectives: Varicocele is an abnormal dilation in the testicular vein, which can cause hypoxia, reactive oxygen species accumulation, elevation in testicular temperature, and promote apoptosis and increase proinflammatory cytokine production. According to the varicocele pathophysiology, it is possible that a group of cytosolic receptors called nucleotide oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes also involve in varicocele pathogenesis...
February 2018: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29456764/integrative-analysis-of-the-epigenetic-basis-of-muscle-invasive-urothelial-carcinoma
#15
Thomas Sanford, Maxwell V Meng, Reema Railkar, Piyush K Agarwal, Sima P Porten
Background: Elucidation of epigenetic alterations in bladder cancer will lead to further understanding of the biology of the disease and hopefully improved therapies. Our aim was to perform an integrative epigenetic analysis of invasive urothelial carcinoma of the bladder to identify the epigenetic abnormalities involved in the development and progression of this cancer. Methods: Pre-processed methylation data and RNA-seq data were downloaded from The Cancer Genome Atlas (TCGA) and processed using the R package TCGA-Assembler...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29456730/the-regulation-and-function-of-microrna-377-rassf8-signaling-axis-in-gastric-cancer
#16
Xiaobo Bo, Yusheng Chen, Weizhong Sheng, Yuda Gong, Haiyu Wang, Weidong Gao, Bo Zhang
Gastric cancer is a major cause of cancer-associated mortality worldwide. The aberrant expression of microRNA (miRNA) is involved in tumorigenesis. Ras proteins transfer information from the extracellular environment to internal cellular compartments and are essential in numerous signal transduction pathways. To investigate the regulation, function and clinical significance of the miRNA377/Ras association domain family (RASSF) 8 signaling axis in gastric cancer, reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, cell counting kit-8, western blotting, and Transwell assays were used...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29456677/concurrent-eosinophilia-and-igg4-related-disease-in-a-child-a-case-report-and-review-of-the-literature
#17
Can Chen, Kuang Chen, Xilian Huang, Kaile Wang, Shenxian Qian
The current study presents the case of a 9-year-old Chinese boy who presented with eosinophilia and elevated serum levels of immunoglobulin G4 (IgG4). A bone marrow puncture identified an elevated eosinophil rate of 23% (normal range, <5%), which indicated eosinophilia. However, gene analysis, fluorescent in situ hybridization and other examinations, including bone marrow aspiration, blood routine, auto-antibody tests and parasitic and allergens screening, contradicted a diagnosis of secondary or clonal eosinophilia...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456535/liver-x-receptor-agonist-therapy-prevents-diffuse-alveolar-hemorrhage-in-murine-lupus-by-repolarizing-macrophages
#18
Shuhong Han, Haoyang Zhuang, Stepan Shumyak, Jingfan Wu, Chao Xie, Hui Li, Li-Jun Yang, Westley H Reeves
The generation of CD138+ phagocytic macrophages with an alternative (M2) phenotype that clear apoptotic cells from tissues is defective in lupus. Liver X receptor-alpha (LXRα) is an oxysterol-regulated transcription factor that promotes reverse cholesterol transport and alternative (M2) macrophage activation. Conversely, hypoxia-inducible factor 1-α (HIF1α) promotes classical (M1) macrophage activation. The objective of this study was to see if lupus can be treated by enhancing the generation of M2-like macrophages using LXR agonists...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29456531/first-occurrence-of-plasmablastic-lymphoma-in-adenosine-deaminase-deficient-severe-combined-immunodeficiency-disease-patient-and-review-of-the-literature
#19
Maddalena Migliavacca, Andrea Assanelli, Maurilio Ponzoni, Roberta Pajno, Federica Barzaghi, Fabio Giglio, Francesca Ferrua, Marta Frittoli, Immacolata Brigida, Francesca Dionisio, Roberto Nicoletti, Miriam Casiraghi, Maria Grazia Roncarolo, Claudio Doglioni, Jacopo Peccatori, Fabio Ciceri, Maria Pia Cicalese, Alessandro Aiuti
Adenosine deaminase-deficient severe combined immunodeficiency disease (ADA-SCID) is a primary immune deficiency characterized by mutations in the ADA gene resulting in accumulation of toxic compounds affecting multiple districts. Hematopoietic stem cell transplantation (HSCT) from a matched donor and hematopoietic stem cell gene therapy are the preferred options for definitive treatment. Enzyme replacement therapy (ERT) is used to manage the disease in the short term, while a decreased efficacy is reported in the medium-long term...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29456457/effect-of-ovarian-cancer-ascites-on-skov-3-cells-proteome-new-proteins-associated-with-aggressive-phenotype-in-epithelial-ovarian-cancer
#20
Alfredo Toledo-Leyva, Julio César Villegas-Pineda, Sergio Encarnación-Guevara, Dolores Gallardo-Rincón, Patricia Talamás-Rohana
Background: Epithelial ovarian cancer is the second most lethal gynecological cancer worldwide. Ascites can be found in all clinical stages, however in advanced disease stages IIIC and IV it is more frequent and could be massive, associated with worse prognosis. Due to the above, it was our interest to understanding how the ascites of ovarian cancer patients induces the mechanisms by which the cells present in it acquire a more aggressive phenotype and to know new proteins associated to this process...
2018: Proteome Science
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