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https://www.readbyqxmd.com/read/28335495/brain-derived-neurotrophic-factor-loaded-ps80-pbca-nanocarrier-for-in-vitro-neural-differentiation-of-mouse-induced-pluripotent-stem-cells
#1
Chiu-Yen Chung, Martin Hsiu-Chu Lin, I-Neng Lee, Tsong-Hai Lee, Ming-Hsueh Lee, Jen-Tsung Yang
Brain derived neurotrophic factor (BDNF) can induce neural differentiation in stem cells and has the potential for repair of the nervous system. In this study, a polysorbate 80-coated polybutylcyanoacrylate nanocarrier (PS80 PBCA NC) was constructed to deliver plasmid DNAs (pDNAs) containing BDNF gene attached to a hypoxia-responsive element (HRE-cmvBDNF). The hypoxia-sensing mechanism of BDNF expression and inductiveness of the nano-formulation on mouse induced pluripotent stem cells (iPSCs) to differentiate into neurons following hypoxia was tested in vitro with immunofluorescent staining and Western blotting...
March 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28335277/receptor-meditated-endocytosis-by-hyaluronic-acid-superparamagnetic-nanovetor-for-targeting-of-cd44-overexpressing-tumor-cells
#2
Kwang Sik Yu, Meng Meng Lin, Hyun-Ju Lee, Ki-Sik Tae, Bo-Sun Kang, Je Hun Lee, Nam Seob Lee, Young Gil Jeong, Seung-Yun Han, Do Kyung Kim
The present report proposes a more rational hyaluronic acid (HA) conjugation protocol that can be used to modify the surface of the superparamagnetic iron oxide nanoparticles (SPIONs) by covalently binding the targeting molecules (HA) with glutamic acid as a molecular linker on peripheral surface of SPIONs. The synthesis of HA-Glutamic Acid (GA)@SPIONs was included oxidization of nanoparticle's surface with H₂O₂ followed by activation of hydroxyl group and reacting glutamic acid as an intermediate molecule demonstrating transfection of lung cancer cells...
August 18, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28335269/galactosylated-liposomes-for-targeted-co-delivery-of-doxorubicin-vimentin-sirna-to-hepatocellular-carcinoma
#3
Hea Ry Oh, Hyun-Young Jo, James S Park, Dong-Eun Kim, Je-Yoel Cho, Pyung-Hwan Kim, Keun-Sik Kim
The combination of therapeutic nucleic acids and chemotherapeutic drugs has shown great promise for cancer therapy. In this study, asialoglycoprotein receptors (ASGPR) targeting-ligand-based liposomes were tested to determine whether they can co-deliver vimentin siRNA and doxorubicin to hepatocellular carcinoma (HCC) selectively. To achieve this goal, we developed an ASGPR receptor targeted co-delivery system called gal-doxorubicin/vimentin siRNA liposome (Gal-DOX/siRNA-L). The Gal-DOX/siRNA-L was created via electrostatic interaction of galactose linked-cationic liposomal doxorubicin (Gal-DOX-L) on vimentin siRNA...
July 30, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28335020/znhit3-is-defective-in-peho-syndrome-a-severe-encephalopathy-with-cerebellar-granule-neuron-loss
#4
Anna-Kaisa Anttonen, Anni Laari, Maria Kousi, Yawei J Yang, Tiina Jääskeläinen, Mirja Somer, Eija Siintola, Eveliina Jakkula, Mikko Muona, Saara Tegelberg, Tuula Lönnqvist, Helena Pihko, Leena Valanne, Anders Paetau, Melody P Lun, Johanna Hästbacka, Outi Kopra, Tarja Joensuu, Nicholas Katsanis, Maria K Lehtinen, Jorma J Palvimo, Anna-Elina Lehesjoki
Progressive encephalopathy with oedema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an early childhood onset, severe autosomal recessive encephalopathy characterized by extreme cerebellar atrophy due to almost total granule neuron loss. By combining homozygosity mapping in Finnish families with Sanger sequencing of positional candidate genes and with exome sequencing a homozygous missense substitution of leucine for serine at codon 31 in ZNHIT3 was identified as the primary cause of PEHO syndrome. ZNHIT3 encodes a nuclear zinc finger protein previously implicated in transcriptional regulation and in small nucleolar ribonucleoprotein particle assembly and thus possibly to pre-ribosomal RNA processing...
March 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28335006/a-platform-for-functional-assessment-of-large-variant-libraries-in-mammalian-cells
#5
Kenneth A Matreyek, Jason J Stephany, Douglas M Fowler
Sequencing-based, massively parallel genetic assays have revolutionized our ability to quantify the relationship between many genotypes and a phenotype of interest. Unfortunately, variant library expression platforms in mammalian cells are far from ideal, hindering the study of human gene variants in their physiologically relevant cellular contexts. Here, we describe a platform for phenotyping variant libraries in transfectable mammalian cell lines in two steps. First, a landing pad cell line with a genomically integrated, Tet-inducible cassette containing a Bxb1 recombination site is created...
March 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334721/microrna-9-inhibits-nlrp3-inflammasome-activation-in-human-atherosclerosis-inflammation-cell-models-through-the-jak1-stat-signaling-pathway
#6
Yue Wang, Zhihua Han, Yuqi Fan, Junfeng Zhang, Kan Chen, Lin Gao, Huasu Zeng, Jiatian Cao, Changqian Wang
BACKGROUND/AIMS: MicroRNA-9 (miR-9) is involved in inflammatory reaction in atherosclerosis; however, its function and regulatory mechanisms remain unclear. We aimed to uncover the exact roles of miR-9 and downstream signaling pathways using in vitro human atherosclerosis models. METHODS: We used oxidized low-density lipoprotein (oxLDL)-stimulated human THP-1 derived macrophages, oxLDL-stimulated human primary peripheral blood monocytes and lipopolysaccharides (LPS) or Alum-stimulated human THP-1 derived macrophages as in vitro atherosclerosis inflammation models...
March 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28334537/multivalency-effect-of-tat-peptide-functionalized-nanoparticle-in-cellular-endocytosis-and-subcellular-trafficking
#7
Nikhil R Jana, Chumki Dalal
Although trans-activating transcription (TAT)-peptide functionalized nanoparticle/polymer/liposome is widely used for cellular transfection applications, the multivalency (number of attached peptide per particle) effect on cell uptake mechanism and subcellular targeting performance is largely unexplored. Here we show that multivalency of nanoparticle controls the cellular interaction, cellular entry/exit mechanism and subcellular targeting performance. We have synthesized TAT peptide functionalized quantum dot (QD) of 30-35 nm hydrodynamic diameter with varied multivalency from 10 to 75 (e...
March 23, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28334039/l-arginine-attenuates-interleukin-1%C3%AE-il-1%C3%AE-induced-nuclear-factor-kappa-beta-nf-%C3%AE%C2%BAb-activation-in-caco-2-cells
#8
Qinghe Meng, Mitchell Cooney, Natesh Yepuri, Robert N Cooney
BACKGROUND: Specific nutrients like L-arginine (L-Arg) ameliorate intestinal inflammation, however the exact mechanisms of this effect are unclear. We hypothesized the anti-inflammatory effects of L-Arg require active transport and metabolism by inducible nitric oxide synthase (iNOS) to generate nitric oxide (NO). To test this hypothesis we examined the effects of L-Arg, L-Arg transport activity, NO production and iNOS inhibitor on IL-1β-mediated NF-κB-activation in Caco-2 cells. METHODS: Caco-2 cells were cultured, transfected with a NF-κB promoter luciferase vector, incubated ± L-Arg, ± IL-1β and luciferase activity was measured...
2017: PloS One
https://www.readbyqxmd.com/read/28333279/inhibition-of-pim1-kinase-attenuates-inflammation-induced-pro-labour-mediators-in-human-fetal-membranes-in-vitro
#9
Ratana Lim, Gillian Barker, Martha Lappas
STUDY QUESTION: Does proviral integration site for Moloney murine leukemic virus (PIM)1 kinase play a role in regulating the inflammatory processes of human labour and delivery? SUMMARY ANSWER: PIM1 kinase plays a critical role in fetal membranes in regulating pro-inflammatory and pro-labour mediators. WHAT IS KNOWN ALREADY: Infection and inflammation have strong causal links to preterm delivery by stimulating pro-inflammatory cytokines and collagen degrading enzymes, which can lead to rupture of membranes...
March 9, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28333152/radiation-inducible-mir-770-5p-sensitizes-tumors-to-radiation-through-direct-targeting-of-pdz-binding-kinase
#10
Hyung Chul Lee, Nam-Gu Her, Donghee Kang, Seung Hee Jung, Jinwook Shin, Minyoung Lee, In Hwa Bae, Young-Nyun Kim, Heon Joo Park, Young-Gyu Ko, Jae-Seon Lee
Radiotherapy represents the most effective non-surgical modality in cancer treatment. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression, and are involved in many biological processes and diseases. To identify miRNAs that influence the radiation response, we performed miRNA array analysis using MCF7 cells at 2, 8, and 24 h post irradiation. We demonstrated that miR-770-5p is a novel radiation-inducible miRNA. When miR-770-5p was overexpressed, relative cell number was reduced due to increased apoptosis in MCF7 and A549 cells...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28332309/effects-of-mir-145-5p-through-nras-on-the-cell-proliferation-apoptosis-migration-and-invasion-in-melanoma-by-inhibiting-mapk-and-pi3k-akt-pathways
#11
Sha Liu, Guozhen Gao, Dexiong Yan, Xiangjun Chen, Xingwei Yao, Shuzhong Guo, Guirong Li, Yu Zhao
We aimed to detect the effects of miR-145-5p on the cell proliferation, apoptosis, migration, and invasion in NRAS-mutant, BRAF-mutant, and wild-type melanoma cells, in order to figure out the potential mechanisms and provide a novel therapeutic target of melanoma. RT-qPCR and western blot were used to detect the expression of miR-145-5p and NRAS in melanoma tumor tissues and cells, respectively. Luciferase assay was performed to determine whether miR-145-5p directly targeted NRAS. After transfecting miR-145-5p mimics, miR-145-5p inhibitors, NRAS cDNA and NRAS siRNA into CHL-1, VMM917 and SK-mel-28 cells, functional assays were used to detect the proliferation, apoptosis, invasion and migration, including MTT, flow cytometry, Transwell and wound healing assays...
March 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28332237/tumor-necrosis-factor-alpha-inhibits-differentiation-of-myogenic-cells-in-human-urethral-rhabdosphincter
#12
Mayuka Shinohara, Yasuhiro Sumino, Fuminori Sato, Tohru Kiyono, Naohiro Hashimoto, Hiromitsu Mimata
OBJECTIVES: To examine the inhibitory effects of tumor necrosis factor-α on myogenic differentiation of human urethral rhabdosphincter cells. METHODS: A rhabdosphincter sample was obtained from a patient who underwent total cystectomy. To expand the lifespan of the primary cultured cells, rhabdosphincter myogenic cells were immortalized with mutated cyclin-dependent kinase 4, cyclin D1 and telomerase. The differential potential of the cells was investigated. The transfected human rhabdosphincter cells were induced for myogenic differentiation with recombinant human tumor necrosis factor-α and/or the tumor necrosis factor-α antagonist etanercept at different concentrations, and activation of signaling pathways was monitored...
March 22, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28332001/ncam1-is-the-target-of-mirna-572-validation-in-the-human-oligodendroglial-cell-line
#13
Roberta Mancuso, Simone Agostini, Ivana Marventano, Ambra Hernis, Marina Saresella, Mario Clerici
The neural cell adhesion molecule 1 (NCAM1) is a fundamental protein in cell-cell interaction and in cellular developmental processes, and its dysregulation is involved in a number of diseases including multiple sclerosis. Studies in rats suggest that the modulation of NCAM1 expression is regulated by miRNA-572, but no data are available confirming such interaction in the human system. We analyzed whether this is the case using a human oligodendroglial cell line (MO3.13). MO3.13 cells were transfected with miRNA-572 mimic and inhibitor separately; NCAM1 mRNA and protein expression levels were analyzed at different time points after transfection...
March 22, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28331100/microrna-434-3p-regulates-age-related-apoptosis-through-eif5a1-in-the-skeletal-muscle
#14
Patricia S Pardo, Ameena Hajira, Aladin M Boriek, Junaith S Mohamed
Sarcopenia is caused by increased activation of catabolic pathways, including apoptosis. However, the mechanism underlying sarcopenia is not well understood. We report that aging alters miRNA expression profile as evidenced by miRNA microarray and real-time PCR. Our data show that miR-434-3p is highly downregulated miRNA in skeletal muscles of the aging mouse and provided the first evidence that miR-434 is a novel regulator of apoptosis. Myocytes transfected with miR-434-3p mimic prevents apoptosis induced by various apoptotic stimuli, and that inhibitory role of miR-434-3p was abolished by its antagomir, suggesting a role for miR-434-3p in apoptosis...
March 22, 2017: Aging
https://www.readbyqxmd.com/read/28331063/microrna-148b-regulates-megalin-expression-and-is-associated-with-receptor-downregulation-in-mice-with-unilateral-ureteral-obstruction
#15
Lu Wen, Pia K Andersen, Dina Mu Husum, Rikke Norregaard, Zhanzheng Zhao, Zhangsuo Liu, Henrik Birn
Megalin is a multiligand, endocytic receptor important for the normal, proximal tubule reabsorption of filtered proteins, hormones, enzymes, essential nutrients, and nephrotoxins. Megalin dysfunction has been associated with acute as well as chronic kidney diseases. Tubular proteinuria has been observed following unilateral ureteral obstruction (UUO) suggesting megalin dysfunction; however, the pathophysiological mechanism has not been resolved. In order to identify potential regulators of megalin expression, we examined renal microRNAs (miRNAs) expression and observed an upregulation of microRNA-148b (miR-148b) in obstructed mouse kidneys 7 days after UUO which was associated with a significant reduction in proximal tubule megalin expression and accumulation of megalin ligands...
March 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28330877/k-channel-modulatory-subunits-kchip-and-dpp-participate-in-kv4-mediated-mechanical-pain-control
#16
Yen-Ling Kuo, Jen-Kun Cheng, Wen-Hsien Hou, Yu-Cheng Chang, Po-Hao Du, Jhao-Jun Jian, Ruey-Horng Rau, Jung-Hui Yang, Cheng-Chang Lien, Meei-Ling Tsaur
The K(+) channel pore-forming subunit Kv4.3 is expressed in a subset of non-peptidergic nociceptors within the dorsal root ganglion (DRG), and knockdown of Kv4.3 selectively induces mechanical hypersensitivity, a major symptom of neuropathic pain. K(+) channel modulatory subunits KChIP1, KChIP2 and DPP10 are coexpressed in Kv4.3(+) DRG neurons, but whether they participate in Kv4.3-mediated pain control is unknown. Here, we show the existence of a Kv4.3/KChIP1/KChIP2/DPP10 complex (abbreviated as the Kv4 complex) in the endoplasmic reticulum and cell surface of DRG neurons...
March 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28330858/prolactin-up-regulates-female-predominant-cyp-gene-expressions-and-down-regulates-male-predominant-gene-expressions-in-mice-liver
#17
Yuya Sato, Yoshikatsu Kaneko, Takamasa Cho, Kei Goto, Tadashi Otsuka, Suguru Yamamoto, Shin Goto, Hiroki Maruyama, Ichiei Narita
Prolactin is a polypeptide hormone with over 300 separate biological activities and its serum level is increased during pregnancy and lactation. It has been described that pregnancy and lactation affect drug and steroid metabolism in mice and humans. Several studies reported that pregnancy or lactation influences liver cytochrome P450 (Cyp) expression and its activity, affecting the biosynthesis of steroids and xenobiotics through growth hormone or sex hormones; however, the role of prolactin as the regulator of liver Cyp expression has not been elucidated so far...
March 22, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28330769/difference-in-the-core-shell-dynamics-of-polyethyleneimine-and-poly-l-lysine-dna-polyplexes
#18
Elina Vuorimaa-Laukkanen, Ekaterina S Lisitsyna, Tiia-Maaria Ketola, Emmanuelle Morin-Pickardat, Huamin Liang, Martina Hanzlíková, Marjo Yliperttula
Electrostatic polymer-DNA complexes (polyplexes) have been widely investigated for DNA delivery, and remarkable differences in transfection efficacy have been seen among the materials. For example, polyethyleneimine (PEI) mediates DNA transfection more effectively than poly(l-lysine) (PLL). Biophysical properties of the polyplexes may explain their different properties in gene delivery. We investigated the structural dynamics in DNA polyplexes, especially the material exchange between the core and shell regions of the PEI and PLL polyplexes...
March 18, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28330734/enhanced-cellular-uptake-and-gene-silencing-activity-of-sirna-using-temperature-responsive-polymer-modified-liposome
#19
Jian Wang, Eri Ayano, Yoshie Maitani, Hideko Kanazawa
Short interfering RNA (siRNA) delivery systems using nanoparticle carriers have been limited by inefficient intracellular delivery. One drawback is the poor cellular uptake of siRNA/particle complexes through the plasma membrane and release of the nucleic acids into the cytosol. In this study, to develop the temperature-responsive liposome as a novel carrier for siRNA delivery, we prepared lipoplexes and assessed cellular uptake of siRNA and gene silencing activity of target genes, compared with those of a commercial transfection reagent, Lipofectamine RNAiMAX, and non-modified or PEGylated liposomes...
March 19, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28330493/loss-of-mmp-8-in-ductal-carcinoma-in-situ-dcis-associated-myoepithelial-cells-contributes-to-tumour-promotion-through-altered-adhesive-and-proteolytic-function
#20
Muge Sarper, Michael D Allen, Jenny Gomm, Linda Haywood, Julie Decock, Sally Thirkettle, Ahsen Ustaoglu, Shah-Jalal Sarker, John Marshall, Dylan R Edwards, J Louise Jones
BACKGROUND: Normal myoepithelial cells (MECs) play an important tumour-suppressor role in the breast but display an altered phenotype in ductal carcinoma in situ (DCIS), gaining tumour-promoter functions. Matrix metalloproteinase-8 (MMP-8) is expressed by normal MECs but is lost in DCIS. This study investigated the function of MMP-8 in MECs and the impact of its loss in DCIS. METHODS: Primary normal and DCIS-associated MECs, and normal (N-1089) and DCIS-modified myoepithelial (β6-1089) cell lines, were used to assess MMP-8 expression and function...
March 23, 2017: Breast Cancer Research: BCR
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