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https://www.readbyqxmd.com/read/28335269/galactosylated-liposomes-for-targeted-co-delivery-of-doxorubicin-vimentin-sirna-to-hepatocellular-carcinoma
#1
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/28335259/lipid-nanovectors-to-deliver-rna-oligonucleotides-in-cancer
#2
REVIEW
Virginia Campani, Giuseppina Salzano, Sara Lusa, Giuseppe De Rosa
The growing knowledge on the mechanisms of gene silencing and gene regulation by non-coding RNAs (ncRNA), mainly small interfering RNA (siRNA) and microRNA (miRNA), is providing a significant boost to the development of new therapeutic strategies for the treatment of cancer. However, the design of RNA-based therapeutics is hampered by biopharmaceutical issues, thus requiring the use of suitable delivery strategies. In this regards, lipid nanovectors have been successfully investigated to deliver RNA in different forms of cancer...
July 9, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28335197/cationic-nanoparticles-assembled-from-natural-based-steroid-lipid-for-improved-intracellular-transport-of-sirna-and-pdna
#3
Ruilong Sheng, Xiaoqing Zhuang, Zhao Wang, Amin Cao, Kaili Lin, Julian X X Zhu
Developing new functional biomaterials from biocompatible natural-based resources for gene/drug delivery has attracted increasing attention in recent years. In this work, we prepared a series of cationic nanoparticles (Diosarg-DOPE NPs) by assembly of a natural steroid diosgenin-based cationic lipid (Diosarg) with commercially-available helper lipid 1,2-dioleoyl-sn-glycero-3-phosphorethanolamine (DOPE). These cationic Diosarg-DOPE NPs were able to efficiently bind siRNA and plasmid DNA (pDNA) via electrostatic interactions to form stable, nano-sized cationic lipid nanoparticles instead of lamellar vesicles in aqueous solution...
April 13, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28334969/a-single-mir390-targeting-event-is-sufficient-for-triggering-tas3-tasirna-biogenesis-in-arabidopsis
#4
Felipe Fenselau de Felippes, Antonin Marchais, Alexis Sarazin, Stefan Oberlin, Olivier Voinnet
In plants, tasiRNAs form a class of endogenous secondary siRNAs produced through the action of RNA-DEPENDENT-RNA-POLYMERASE-6 (RDR6) upon microRNA-mediated cleavage of non-coding TAS RNAs. In Arabidopsis thaliana, TAS1, TAS2 and TAS4 tasiRNA production proceeds via a single cleavage event mediated by 22nt-long or/and asymmetric miRNAs in an ARGONAUTE-1 (AGO1)-dependent manner. By contrast, tasiRNA production from TAS3 seems to follow the so-called 'two-hit' process, where dual targeting of TAS3, specifically mediated by the 21nt-long, symmetric miR390, initiates AGO7-dependent tasiRNA production...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334937/dynamically-and-epigenetically-coordinated-gata-ets-sox-transcription-factor-expression-is-indispensable-for-endothelial-cell-differentiation
#5
Yasuharu Kanki, Ryo Nakaki, Teppei Shimamura, Taichi Matsunaga, Kohei Yamamizu, Shiori Katayama, Jun-Ichi Suehiro, Tsuyoshi Osawa, Hiroyuki Aburatani, Tatsuhiko Kodama, Youichiro Wada, Jun K Yamashita, Takashi Minami
Although studies of the differentiation from mouse embryonic stem (ES) cells to vascular endothelial cells (ECs) provide an excellent model for investigating the molecular mechanisms underlying vascular development, temporal dynamics of gene expression and chromatin modifications have not been well studied. Herein, using transcriptomic and epigenomic analyses based on H3K4me3 and H3K27me3 modifications at a genome-wide scale, we analysed the EC differentiation steps from ES cells and crucial epigenetic modifications unique to ECs...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334846/dapl1-a-susceptibility-locus-for-age-related-macular-degeneration-acts-as-a-novel-suppressor-of-cell-proliferation-in-the-retinal-pigment-epithelium
#6
Xiaoyin Ma, Huirong Li, Yipin Wang, Jing Wang, Qinxiang Zheng, Jiajia Hua, Juan Yang, Li Pan, Fan Lu, Jia Qu, Ling Hou
The retinal pigment epithelium (RPE) forms a monolayer at the back of the vertebrate eye and is fundamental to retinal function and homoeostasis. During early development, RPE cells undergo rapid proliferation, but in the adult, they remain normally nonproliferative throughout life. Nevertheless, under pathological conditions such as in proliferative vitreoretinopathy or after retinal ablation, mature RPE cells can re-enter the cell cycle and form nodules or multiple cell layers. Here we show that Dapl1, whose human homolog represents a susceptibility locus for age-related macular degeneration (AMD), is highly up-regulated in quiescent but not proliferating RPE cells and that experimental overexpression of DAPL1 in proliferating RPE cells inhibits their proliferation...
February 22, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334721/microrna-9-inhibits-nlrp3-inflammasome-activation-in-human-atherosclerosis-inflammation-cell-models-through-the-jak1-stat-signaling-pathway
#7
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/28334226/loss-of-cannabinoid-cb-1-receptors-induces-cortical-migration-malformations-and-increases-seizure-susceptibility
#8
Javier Díaz-Alonso, Adán de Salas-Quiroga, Juan Paraíso-Luna, Daniel García-Rincón, Patricia P Garcez, Maddy Parsons, Clara Andradas, Cristina Sánchez, François Guillemot, Manuel Guzmán, Ismael Galve-Roperh
Neuronal migration is a fundamental process of brain development, and its disruption underlies devastating neurodevelopmental disorders. The transcriptional programs governing this process are relatively well characterized. However, how environmental cues instruct neuronal migration remains poorly understood. Here, we demonstrate that the cannabinoid CB 1 receptor is strictly required for appropriate pyramidal neuron migration in the developing cortex. Acute silencing of the CB 1 receptor alters neuronal morphology and impairs radial migration...
October 5, 2016: Cerebral Cortex
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
#9
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/28333280/hcg-activates-the-erk1-2-mitogen-activated-protein-kinase-pathway-in-human-endometrial-stromal-cells-transiently-increasing-the-progesterone-receptor-and-regulating-genes-associated-with-endometrial-receptivity
#10
Alejandro Tapia-Pizarro, Sebastián Archiles, Felipe Argandoña, Cecilia Valencia, Keyla Zavaleta, María Cecilia Johnson, Reinaldo González-Ramos, Luigi Devoto
STUDY QUESTION: How does hCG signal in human endometrial stromal cells (ESCs) and what is its role in regulating ESC function? SUMMARY ANSWER: CG signaling in ESCs activates the extracellular signal-regulated protein kinases 1 and 2 (Erk1/2) pathway through exchange protein activated by cAMP (Epac) and transiently increases progesterone receptor (PR) transcript and protein expression and its transcriptional function. WHAT IS KNOWN ALREADY: hCG is one of the earliest embryo-derived secreted signals in the endometrium, which abundantly expresses LH/hCG receptors...
March 14, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28333279/inhibition-of-pim1-kinase-attenuates-inflammation-induced-pro-labour-mediators-in-human-fetal-membranes-in-vitro
#11
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/28332829/impact-of-peg-chain-length-on-the-physical-properties-and-bioactivity-of-pegylated-chitosan-sirna-nanoparticles-in-vitro-and-in-vivo
#12
Chuanxu Yang, Shan Gao, Frederik Dagnaes-Hansen, Maria Jakobsen, Jørgen Kjems
PEGylation of cationic polyplexes is a promising approach to enhance the stability and reduce unspecific interaction with biological components. Herein, we systematically investigate the impact of PEGylation on physical and biological properties of chitosan/siRNA polyplexes. A series of chitosan-PEG copolymers (CS-PEG2k, CS-PEG5k and CS-PEG10k) were synthesized with similar PEG mass content but with different molecular weight. PEGylation with higher molecular weight and less grafting degree resulted in smaller and more compacted nanoparticles with relatively higher surface charge...
March 23, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28332452/editorial-new-trends-in-gene-therapy-multidisciplinary-approaches-to-sirnas-controlled-delivery
#13
EDITORIAL
Anna Angela Barba, Mario Grassi, Gabriele Grassi, Gaetano Lamberti
No abstract text is available yet for this article.
2017: Current Drug Delivery
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
#14
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/28331341/investigating-the-expression-effect-and-tumorigenic-pathway-of-padi2-in-tumors
#15
Wei Guo, Yabing Zheng, Bing Xu, Fang Ma, Chang Li, Xiaoqian Zhang, Yao Wang, Xiaotian Chang
BACKGROUND: Peptidylarginine deiminase (PAD) catalyzes the conversion of arginine residues to citrulline residues, termed citrullination. Recent studies have suggested that PAD isoform 2 (PADI2) plays an important role in tumors, although its tumorigenic effect and mechanism are largely unknown. MATERIALS AND METHODS: Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to investigate the expression level of PADI2 in various tumor tissues and patient blood samples, respectively...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28331074/osteopontin-inhibits-osteoblast-responsiveness-through-the-downregulation-of-focal-adhesion-kinase-mediated-by-the-induction-of-low-molecular-weight-protein-tyrosine-phosphatase
#16
Joji Kusuyama, Kenjiro Bandow, Tomokazu Ohnishi, Mitsuhiro Hisadome, Kaori Shima, Ichiro Semba, Tetsuya Matsuguchi
Osteopontin (OPN) is an osteogenic marker protein. Osteoblast functions are affected by inflammatory cytokines and pathological conditions. OPN is highly expressed in bone legions such as rheumatoid arthritis. However, local regulatory effects of OPN on osteoblasts remain ambiguous. Here, we examined how OPN influences osteoblast responses to mechanical stress and growth factors. Expression of NO synthase 1 (Nos1) and Nos2 was increased by low intensity pulsed ultrasound (LIPUS) in MC3T3-E1 cells and primary osteoblasts...
March 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28330951/hypoxia-induced-proliferation-of-hela-cells-depends-on-epidermal-growth-factor-receptor-mediated-arginase-ii-induction
#17
Bhuvana A Setty, Natasha Pillay Smiley, Caitlyn M Pool, Yi Jin, Yusen Liu, Leif D Nelin
Solid tumors can often be hypoxic in regions, and cancer cells can respond to hypoxia with an increase in proliferation and a decrease in apoptosis, leading to a net increase in viable cell numbers. We have recently found that in an osteosarcoma cell line, hypoxia-induced proliferation depends on arginase II induction. Epidermal growth factor receptor (EGFR) has been shown to mediate the hypoxia-induced cellular proliferation in some cancer cell lines. We hypothesized that hypoxia-induced proliferation of HeLa cells would depend on arginase II induction and that this induction of arginase II would occur through EGFR activation...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28330734/enhanced-cellular-uptake-and-gene-silencing-activity-of-sirna-using-temperature-responsive-polymer-modified-liposome
#18
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
#19
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
https://www.readbyqxmd.com/read/28330417/involvement-of-nox2-and-nox4-nadph-oxidases-in-early-brain-injury-after-subarachnoid-hemorrhage
#20
Li Zhang, Zhen Li, Dongxia Feng, Haitao Shen, Xiaodi Tian, Haiying Li, Zhong Wang, Gang Chen
Oxidative stress is responsible for a poor prognosis of subarachnoid hemorrhage (SAH) patients. Nox2 has been shown to participate in SAH-induced early brain injury (EBI). Nox4 is another major subtype of Nox family widely expressed in CNS. Here, we investigated the role of Nox4 and whether there was a synergistic effect of Nox2 and Nox4 in SAH-induced EBI. Clinical brain biopsies of four patients with traumatic brain injury and perihematomal brain tissue from six subjects with SAH were examined. Gp91ds-tat (a specific inhibitor of Nox2), GKT137831 (a specific inhibitor of Nox4), and apocynin (a non-specific Nox inhibitor) were used to test the role of Nox2 and Nox4...
March 22, 2017: Free Radical Research
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