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https://www.readbyqxmd.com/read/28449094/hepatic-tm6sf2-overexpression-affects-cellular-apob-trafficking-plasma-lipid-levels-hepatic-steatosis-and-atherosclerosis
#1
Nicole Ehrhardt, Michael E Doche, Shuang Chen, Hui Z Mao, Meghan T Walsh, Candy Bedoya, Maha Guindi, Weidong Xiong, Joseph Ignatius Irudayam, Jahangir Iqbal, Sebastien Fuchs, Samuel W French, M Mahmood Hussain, Moshe Arditi, Vaithilingaraja Arumugaswami, Miklós Péterfy
The human TM6SF2 gene has been implicated in plasma lipoprotein metabolism, alcoholic and non-alcoholic fatty liver disease and myocardial infarction in multiple genome-wide association studies. To investigate the role of Tm6sf2 in metabolic homeostasis, we generated mice with elevated expression using adeno-associated virus (AAV)-mediated gene delivery. Hepatic overexpression of mouse Tm6sf2 resulted in phenotypes previously observed in Tm6sf2-deficient mice including reduced plasma lipid levels, diminished hepatic TG secretion and increased hepatosteatosis...
April 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28448623/development-of-the-cutaneous-microbiome-in-the-preterm-infant-a-prospective-longitudinal-study
#2
Mohan Pammi, Jacqueline L O'Brien, Nadim J Ajami, Matthew C Wong, James Versalovic, Joseph F Petrosino
BACKGROUND: Neonatal sepsis in preterm infants is often due to organisms that colonize the skin including Staphylococcus spp. and Candida spp. Development and maturation of the skin microbiome in the neonatal period, especially in preterm infants, may be critical in preventing colonization with pathogens and subsequent progression to neonatal sepsis. Development of the skin microbiome in preterm infants or its determinants in the first 4 weeks of life has not been evaluated. METHODS: We evaluated the skin microbiome from three body sites, antecubital fossa, forehead and gluteal region, in a prospective cohort of 15 preterm (birth weight < 1500 g and < 32 weeks of gestation) and 15 term neonates...
2017: PloS One
https://www.readbyqxmd.com/read/28448606/a-feeding-protocol-for-delivery-of-agents-to-assess-development-in-varroa-mites
#3
Ana R Cabrera, Paul D Shirk, Peter E A Teal
A novel feeding protocol for delivery of bio-active agents to Varroa mites was developed by providing mites with honey bee larva hemolymph supplemented with cultured insect cells and selected materials delivered on a fibrous cotton substrate. Mites were starved, fed on treated hemolymph to deliver selected agents and then returned to bee larvae. Transcript levels of two reference genes, actin and glyceraldehyde 3-phosphate dehydrogenase (GAPDH), as well as for nine selected genes involved in reproductive processes showed that the starvation and feeding protocol periods did not pose a high level of stress to the mites as transcript levels remained comparable between phoretic mites and those completing the protocol...
2017: PloS One
https://www.readbyqxmd.com/read/28448022/development-of-an-economical-dna-delivery-system-by-acufection-and-its-application-to-skin-research
#4
Yu-Jei Lin, Tsung-Lin Lee, Chia-Chi Ku
Dysregulation of immune response in skin is associated with numerous human skin disorders. Direct transfer of immune-related genes into skin tissue is a fascinating approach to investigate immune modulation of cutaneous inflammation in mouse models of human diseases. Here we present a cost-effective protocol that delivered naked DNA in mouse skin and leads to transgene expression. The method is coined "acufection", denoting acupuncture-mediated DNA transfection. To perform acufection, mouse skin was first infused with DNA in phosphate-buffered saline (PBS) and then pricked lightly with a bundle of acupuncture needles to facilitate the absorption of DNA and transfection into cells...
April 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447884/do-micrornas-play-a-role-in-the-activity-of-plant-based-vaccines
#5
Sergio Rosales-Mendoza, Jorge A Salazar-González
An important trend in vaccinology is the development of oral vaccines based on genetically modified plants. Areas covered: Several studies have suggested that dietary microRNAs from plants and other organisms are bioavailable upon oral ingestion exerting biological events in the host such as the modulation of gene expression in several cell types. Since oral plant-based vaccines rely on whole cells as vaccine delivery vehicles, miRNAs could play a role in the immunogenic activity of this type of vaccine. In the present report, this hypothesis is discussed under the light of recent evidence on the immunomodulatory activity exerted by miRNAs using in vitro and in vivo evaluations...
April 27, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28447859/transgene-expression-in-dogs-after-liver-directed-hydrodynamic-delivery-of-i-sleeping-beauty-i-transposons-using-balloon-catheters
#6
Kendra Anne Hyland, Elena L Aronovich, Erik R Olson, Jason B Bell, Myra Urness Rusten, Roland Gunther, David W Hunter, Perry B Hackett, R Scott McIvor
The <i>Sleeping Beauty</i> transposon system has been extensively tested for integration of reporter and therapeutic genes <i>in vitro</i> and <i>in vivo</i> in mice. Dogs were used as a large animal model for human therapy and minimally invasive infusion of DNA solutions. DNA solutions were delivered into the entire liver or the left side of the liver using balloon catheters for temporary occlusion of venous outflow. A peak intravascular pressure between 80 and 140 mmHg supported sufficient DNA delivery in dog liver for detection of secretable reporter proteins...
April 27, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28447465/transferrin-dressed-virus-like-ternary-nanoparticles-with-aggregation-induced-emission-for-targeted-delivery-and-rapid-cytosolic-release-of-sirna
#7
Tingbin Zhang, Weisheng Guo, Chunqiu Zhang, Jing Yu, Jing Xu, Shuyi Li, Jian-Hua Tian, Paul C Wang, Jinfeng Xing, Xing-Jie Liang
Viruses have evolved to be outstandingly efficient at gene delivery, but their use as vectors is limited by safety risks. Inspired by the structure of viruses, we constructed a virus-mimicking vector (denoted as TR4@siRNA@Tf NCs) with virus-like architecture and infection properties. Composed of a hydrophilic peptide, an AIEgen and a lipophilic tail, TR4 imitates the viral capsid and endows the vector with aggregation-induced emission (AIE) properties as well as efficient siRNA compaction. The outer glycoprotein transferrin (Tf) mimics the viral envelope protein, and endows the vector with reduced cytotoxicity as well as enhanced targeting capability...
April 27, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28447455/efficiency-and-safety-of-%C3%AE-cd-d3-7-as-an-sirna-carrier-for-decreasing-mmp-9-expression-and-improving-wound-healing-in-diabetic-rats
#8
Na Li, Hengcong Luo, Meng Ren, Li-Ming Zhang, Wei Wang, Cheng Lin Pan, Liqun Yang, Guojuan Lao, Junjie Deng, Kaijin Mai, Kan Sun, Chuan Yang, Li Yan
Over-expression of MMP-9 is critical for diabetic chronic wounds involved in the refractory wound healing process. We aimed to develop a strategy through RNAi to decrease MMP-9 expression and improving diabetic wound healing. We had explored β-CD-(D3)7 as a gene carrier to take siRNA effectively interfere with MMP-9 expression. It has been proved that β-CD-(D3)7 could be used as an effective siRNA delivery system. In this study we want to know exactly about the efficiency and safety of β-CD-(D3)7/MMP-9 siRNA for improving wound healing in diabetic rats...
April 27, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28446728/inhibition-of-hsf1-suppresses-the-growth-of-hepatocarcinoma-cell-lines-in-vitro-and-akt-driven-hepatocarcinogenesis-in-mice
#9
Antonio Cigliano, Chunmei Wang, Maria G Pilo, Marta Szydlowska, Stefania Brozzetti, Gavinella Latte, Giovanni M Pes, Rosa M Pascale, Maria A Seddaiu, Gianpaolo Vidili, Silvia Ribback, Frank Dombrowski, Matthias Evert, Xin Chen, Diego F Calvisi
Upregulation of the heat shock transcription factor 1 (HSF1) has been described as a frequent event in many cancer types, but its oncogenic role in hepatocellular carcinoma (HCC) remains poorly delineated. In the present study, we assessed the function(s) of HSF1 in hepatocarcinogenesis via in vitro and in vivo approaches. In particular, we determined the importance of HSF1 on v-Akt murine thymoma viral oncogene homolog (AKT)-induced liver cancer development in mice. We found that knockdown of HSF1 activity via specific siRNA triggered growth restraint by suppressing cell proliferation and inducing massive cell apoptosis in human HCC cell lines...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28446340/peptide-dendrimer-lipid-conjugates-as-dna-and-sirna-transfection-reagents-role-of-charge-distribution-across-generations
#10
Marc Heitz, Albert Kwok, Gabriela A Eggimann, Florian Hollfelder, Tamis Darbre, Jean-Louis Reymond
Transfection reagents are used to deliver DNA and siRNA into cells to achieve genetic manipulations, and may ultimately enable nonviral gene therapy. Progress in transfection reagents is limited by the fact that such reagents cannot be easily optimized due to their polymeric nature and/or difficult synthesis. We have developed a new class of well-defined and easily modifiable transfection reagents in the form of peptide dendrimers. These dendrimers self-assemble with DNA or siRNA and lipofectin to form nanoparticles which efficiently enter mammalian cells and liberate their nucleic acid cargo...
April 26, 2017: Chimia
https://www.readbyqxmd.com/read/28445988/specific-up-regulation-of-p21-by-a-small-active-rna-sequence-suppresses-human-colorectal-cancer-growth
#11
Lu-Lu Wang, Hui-Hui Guo, Yun Zhan, Chen-Lin Feng, Shuai Huang, Yan-Xing Han, Wen-Sheng Zheng, Jian-Dong Jiang
The double stranded small active RNA (saRNA)- p21-saRNA-322 inhibits tumor growth by stimulating the p21 gene expression. We focused our research of p21-saRNA-322 on colorectal cancer because 1) p21 down-regulation is a signature abnormality of the cancer, and 2) colorectal cancer might be a suitable target for in situ p21-saRNA-322 delivery. The goal of the present study is to learn the activity of p21-saRNA-322 in colorectal cancer. Three human colorectal cancer cell lines, HCT-116, HCT-116 (p53-/-) and HT-29 were transfected with the p21-saRNA-322...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445664/beyond-genes-and-molecules-a-precision-delivery-initiative-for-precision-medicine
#12
Ravi B Parikh, J Sanford Schwartz, Amol S Navathe
In 2015, President Barack Obama launched the Precision Medicine Initiative (PMI), aimed at enabling "a new era of medicine through research, technology, and policies that empower patients, researchers, and providers to work together toward development of individualized care." He requested $215..
April 27, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28445365/improvement-of-flap-necrosis-in-a-rat-random-skin-flap-model-by-in-vivo-electroporation-mediated-hgf-gene-transfer
#13
S Morteza Seyed Jafari, Maziar Shafighi, Helmut Beltraminelli, Thomas Geiser, Robert E Hunger, Amiq Gazdhar
BACKGROUND: Despite great understanding of underlying mechanisms for flap necrosis and advances in surgical techniques, flap necrosis remains a critical issue. In the present study, the authors investigated the efficacy of electroporation-mediated hepatocyte growth factor (HGF) gene delivery to random dorsal skin flaps (McFarlane) to accelerate wound healing and reduce flap necrosis. METHODS: Fifteen male Wistar rats (290 to 320 g) were divided randomly into three groups...
May 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28445136/selective-eradication-of-cancer-cells-by-delivery-of-adenovirus-based-toxins
#14
Shiran Shapira, Assaf Shapira, Diana Kazanov, Gil Hevroni, Sarah Kraus, Nadir Arber
BACKGROUND AND OBJECTIVE: KRAS mutation is an early event in colorectal cancer carcinogenesis. We previously reported that a recombinant adenovirus, carrying a pro-apoptotic gene (PUMA) under the regulation of Ets/AP1 (RAS-responsive elements) suppressed the growth of cancer cells harboring hyperactive KRAS. We propose to exploit the hyperactive RAS pathway, rather than to inhibit it as was previously tried and failed repeatedly. We aim to improve efficacy by substituting PUMA with a more potent toxin, the bacterial MazF-MazE toxin-antitoxin system, under a very tight regulation...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444967/co-delivery-of-microrna-21-antisense-oligonucleotides-and-gemcitabine-using-nanomedicine-for-pancreatic-cancer-therapy
#15
Yaqing Li, Yinting Chen, Jiajia Li, Zuoquan Zhang, Chumei Huang, Guoda Lian, Kege Yang, Shaojie Chen, Ying Lin, Lingyun Wang, Kaihong Huang, Linjuan Zeng
Tumor metastasis occurs naturally in pancreatic cancer, and the efficacy of chemotherapy is usually poor. Precision medicine, combining down-regulation of target genes with chemotherapy drugs, is expected to improve the therapeutic effects. Therefore, we developed a combined therapy of microRNA-21 antisense oligonucleotides (ASO-miR-21) and Gemcitabine (Gem) using a targeted co-delivery nanoparticle (NP) carrier and investigated the synergistic inhibitory effects on pancreatic cancer cells metastasis and growth...
April 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28443896/an-msn-peg-ip-drug-delivery-system-and-il13r%C3%AE-2-as-targeted-therapy-for-glioma
#16
Jinlong Shi, Shiqiang Hou, Jianfei Huang, Shanshan Wang, Wei Huan, Chuanjun Huang, Xiaojiang Liu, Rui Jiang, Wenbo Qian, Jingjing Lu, Xiubing Wang, Wei Shi, Rongqin Huang, Jian Chen
A combination of gene therapy and chemotherapy has recently received interest as a targeted therapy for glioma. A mesoporous silica nanoparticle (MSN)-based vehicle coated with IL13Rα2-targeted peptide (IP) using polyethylene glycol (PEG), MSN-PEG-IP (MPI), was constructed and confirmed as a potential glioma-targeted drug delivery system in vitro. In this work, tissue microarray (TMA) results revealed that IL13Rα2 was over-expressed in human glioma tissues and that high expression of IL13Rα2 in patients was associated with poor survival...
April 26, 2017: Nanoscale
https://www.readbyqxmd.com/read/28443125/viral-vectors-for-plant-genome-engineering
#17
REVIEW
Syed Shan-E-Ali Zaidi, Shahid Mansoor
Recent advances in genome engineering (GE) has made it possible to precisely alter DNA sequences in plant cells, providing specifically engineered plants with traits of interest. Gene targeting efficiency depends on the delivery-method of both sequence-specific nucleases and repair templates, to plant cells. Typically, this is achieved using Agrobacterium mediated transformation or particle bombardment, both of which transform only a subset of cells in treated tissues. The alternate in planta approaches, stably integrating nuclease-encoding cassettes and repair templates into the plant genome, are time consuming, expensive and require extra regulations...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28442998/glial-cell-line-derived-neurotrophic-factor-gene-delivery-in-parkinson-s-disease-a-delicate-balance-between-neuroprotection-trophic-effects-and-unwanted-compensatory-mechanisms
#18
REVIEW
Liliane Tenenbaum, Marie Humbert-Claude
Glial cell line-derived neurotrophic factor (GDNF) and Neurturin (NRTN) bind to a receptor complex consisting of a member of the GDNF family receptor (GFR)-α and the Ret tyrosine kinase. Both factors were shown to protect nigro-striatal dopaminergic neurons and reduce motor symptoms when applied terminally in toxin-induced Parkinson's disease (PD) models. However, clinical trials based on intraputaminal GDNF protein administration or recombinant adeno-associated virus (rAAV)-mediated NRTN gene delivery have been disappointing...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28442450/implementing-an-internet-delivered-skin-cancer-genetic-testing-intervention-to-improve-sun-protection-behavior-in-a-diverse-population-protocol-for-a-randomized-controlled-trial
#19
Jennifer L Hay, Marianne Berwick, Kate Zielaskowski, Kirsten Am White, Vivian M Rodríguez, Erika Robers, Dolores D Guest, Andrew Sussman, Yvonne Talamantes, Matthew R Schwartz, Jennie Greb, Jessica Bigney, Kimberly A Kaphingst, Keith Hunley, David B Buller
BACKGROUND: Limited translational genomic research currently exists to guide the availability, comprehension, and appropriate use of personalized genomics in diverse general population subgroups. Melanoma skin cancers are preventable, curable, common in the general population, and disproportionately increasing in Hispanics. OBJECTIVE: Variants in the melanocortin-1 receptor (MC1R) gene are present in approximately 50% of the population, are major factors in determining sun sensitivity, and confer a 2-to-3-fold increase in melanoma risk in the general population, even in populations with darker skin...
April 25, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28442415/retro-inverso-d-peptide-modified-ha-rhb-pdna-core-shell-ternary-nanoparticles-for-the-dual-targeted-delivery-of-short-hairpin-rna-encoding-plasmids
#20
Jijin Gu, Xinyi Chen, Xiaoling Fang, Xianyi Sha
The active targeting of gene carriers is a powerful strategy for improving tumour-specific delivery and therapy. Although numerous L-peptide ligands play significant roles in the active targeting of nanomedicine, retro-inverso D-peptides have been explored as targeting ligands due to their superior stability and bioactivity in vivo. In this study, retro-inverso D-peptide (RIF7)-modified hyaluronic acid (HA)/bioreducible hyperbranched poly(amido amine) (RHB)/plasmid DNA (pDNA) ternary nanoparticles were successfully developed using the layer-by-layer method for the CD44-positive tumour-specific delivery of short hairpin RNA-encoding pDNA through the synergistic reaction of the Anxa1 (tumour vasculature) and CD44 (tumour cell-surface) receptors, which mediated the dual targeting...
April 22, 2017: Acta Biomaterialia
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