Search results for "knockdown"
showing 10 items of 178 documents
The
2016
ABSTRACT Members of the Junctophilin (JPH) protein family have emerged as key actors in all excitable cells, with crucial implications for human pathophysiology. In mammals, this family consists of four members (JPH1-JPH4) that are differentially expressed throughout excitable cells. The analysis of knockout mice lacking JPH subtypes has demonstrated their essential contribution to physiological functions in skeletal and cardiac muscles and in neurons. Moreover, mutations in the human JPH2 gene are associated with hypertrophic and dilated cardiomyopathies; mutations in JPH3 are responsible for the neurodegenerative Huntington's disease-like-2 (HDL2), whereas JPH1 acts as a genetic modifier …
PO-182 The upregulation of EPDR1 is related to tumour invasiveness in a cohort of localised colorectal cancer patients
2018
Introduction Colorectal cancer (CRC) represents a relevant public health problem. Despite new therapeutic advances, prognosis of patients diagnosed with advanced disease is still poor. The identification of new markers involved in the mechanisms of invasiveness represents a priority in order to better understand cancer development and generate new therapeutic targets. We describe here the possible role of EPDR1, a gene not yet well characterised, which encodes a protein related to ependymins, a family of piscine transmembrane proteins involved in cell adhesion. To evaluate the role of EPDR1, a translational investigation was planned to explore the consequences of the upregulation of EPDR1 i…
Cellular Uptake of siRNA-Loaded Nanocarriers to Knockdown PD-L1: Strategies to Improve T-cell Functions
2020
T-cells are a type of lymphocyte (a subtype of white blood cells) that play a central role in cell-mediated immunity. Currently, adoptive T-cell immunotherapy is being developed to destroy cancer cells. In this therapy, T-cells are harvested from a patient&rsquo
Drosophila DJ-1 mutants are sensitive to oxidative stress and show reduced lifespan and motor deficits.
2007
Parkinson's disease (PD) is a progressive movement disorder caused by the selective and massive loss of dopaminergic neurons (DA) in the substantia nigra pars compacta (SNc). DJ-1 loss-of-function mutations are involved in inherited early-onset PD forms and result in dysfunction of the oxidative stress response. In mice models, DJ-1 loss provokes sensitivity to oxidative insults but does not produce neurodegeneration. Similar results have been found when analyzing Drosophila mutants for the DJ-1 orthologous genes, DJ-1alpha and DJ-1beta. Here, we report the analysis of two new mutations for the Drosophila DJ-1 genes. Both ubiquitous induction of DJ-1alpha knockdown by RNAi and loss of funct…
Differential Gene Expression of Medullary Thyroid Carcinoma Reveals Specific Markers Associated with Genetic Conditions
2013
Maliszewska, Agnieszka et al.
Inhibiting proliferation in KB cancer cells by RNA interference-mediated knockdown of nicotinamide N-methyltransferase expression.
2011
The enzyme Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide and other pyridines, playing a pivotal role in the biotransformation and detoxification of many drugs and xenobiotic compounds. Several tumours have been associated with abnormal NNMT expression, however its role in tumour development remains largely unknown. In this study we investigated expression levels of Nicotinamide N-methyltransferase in a cancer cell line and we evaluated the effect of shRNA-mediated silencing of NNMT on cell proliferation. Cancer cells were examined for NNMT expression by semiquantitative RT-PCR and Western blot analysis. A HPLC-based catalytic assay was performed to asses…
α-Mannosyl-Functionalized Cationic Nanohydrogel Particles for Targeted Gene Knockdown in Immunosuppressive Macrophages
2019
Immunosuppressive M2 macrophages govern the immunophathogenic micromilieu in many severe diseases including cancer or fibrosis, thus, their re-polarization through RNA interference is a promising concept to support combinatorial therapies. For targeted siRNA delivery, however, safe and stable carriers are required that manage cell specific transport to M2 macrophages. Here, siRNA-loaded cationic nanogels are reported with α-mannosyl decorated surfaces that target and modify M2 macrophages selectively. Via amphiphilic precursor block copolymers bearing one single α-mannosyl moiety at their chain end mannosylated cationic nanohydrogel particles (ManNP) were obtained of 20 nm diameter determin…
Size-dependent knockdown potential of siRNA-loaded cationic nanohydrogel particles.
2014
To overcome the poor pharmacokinetic conditions of short double-stranded RNA molecules in RNA interference therapies, cationic nanohydrogel particles can be considered as alternative safe and stable carriers for oligonucleotide delivery. For understanding key parameters during this process, two different types of well-defined cationic nanohydrogel particles were synthesized, which provided nearly identical physicochemical properties with regards to their material composition and resulting siRNA loading characteristics. Yet, according to the manufacturing process using amphiphilic reactive ester block copolymers of pentafluorophenyl methacrylate (PFPMA) and tri(ethylene glycol)methyl ether m…
SiRNA-mediated in vivo gene knockdown by acid-degradable cationic nanohydrogel particles
2017
Cationic nanohydrogel particles have become an attractive tool for systemic siRNA delivery, but improvement of their in vivo tolerance is desirable, especially to prevent potential long term side effects by tissue and cellular accumulation. Here, we designed novel ketal cross-linked cationic nanohydrogel particles that were assessed for reduced tissue accumulation and robust siRNA delivery in vitro and in vivo. An oligo-amine cross-linker equipped with a ketal moiety in its core was synthesized and applied to nanohydrogel cross-linking of self-assembled reactive ester block copolymers in DMSO. The resulting acid-sensitive cationic nanoparticles spontaneously disassembled over time in acidic…
HSP70, the Key to Account for Erythroid Tropism of Diamond-Blackfan Anemia?
2015
Abstract Diamond-Blackfan anemia (DBA) was the first ribosomopathy identified and is characterized by a moderate to severe, usually macrocytic aregenerative anemia associated with congenital malformations in 50% of the DBA cases. This congenital rare erythroblastopenia is due to a blockade in erythroid differentiation between the BFU-e and CFU-e stages. The link between a haploinsufficiency in a ribosomal protein (RP) gene that now encompass 15 different RP genes and the erythroid defect is still to be fully defined. Recently, mutations in TSR2 and GATA1 genes have been identified in a few DBA families. The GATA1 gene encodes for the major transcription factor critical for erythropoiesis an…