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https://www.readbyqxmd.com/read/29150004/dynamics-of-indel-profiles-induced-by-various-crispr-cas9-delivery-methods
#1
Michael Kosicki, Sandeep S Rajan, Flaminia C Lorenzetti, Hans H Wandall, Yoshiki Narimatsu, Emmanouil Metzakopian, Eric P Bennett
The introduction of CRISPR/Cas9 gene editing in mammalian cells is a scientific breakthrough, which has greatly affected basic research and gene therapy. The simplicity and general access to CRISPR/Cas9 reagents has in an unprecedented manner "democratized" gene targeting in biomedical research, enabling genetic engineering of any gene in any cell, tissue, organ, and organism. The ability for fast, precise, and efficient profiling of the double-stranded break induced insertions and deletions (indels), mediated by any of the available programmable nucleases, is paramount to any given gene targeting approach...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29149911/the-analysis-of-novel-microrna-mimic-sequences-in-cancer-cells-reveals-lack-of-specificity-in-stem-loop-rt-qpcr-based-microrna-detection
#2
Patrick Winata, Marissa Williams, Eileen McGowan, Najah Nassif, Nico van Zandwijk, Glen Reid
OBJECTIVE: MicroRNAs are frequently downregulated in cancer, and restoring expression has tumour suppressive activity in tumour cells. Our recent phase I clinical trial investigated microRNA-based therapy in patients with malignant pleural mesothelioma. Treatment with TargomiRs, microRNA mimics with novel sequence packaged in EGFR antibody-targeted bacterial minicells, revealed clear signs of clinical activity. In order to detect delivery of microRNA mimics to tumour cells in future clinical trials, we tested hydrolysis probe-based assays specific for the sequence of the novel mimics in transfected mesothelioma cell lines using RT-qPCR...
November 17, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29149878/assessing-the-delivery-of-alcohol-screening-and-brief-intervention-in-sexual-health-clinics-in-the-north-east-of-england
#3
C Sullivan, N Martin, C White, D Newbury-Birch
BACKGROUND: Risky drinking is associated with risky sexual experiences, however the relationship between alcohol and sex is complex. The aim of the study was to assess the feasibility of delivering alcohol screening and brief interventions in genitourinary medicine (GUM) clinics. The objectives were to; understand the levels of alcohol use amongst patients; report on the number of alcohol interventions delivered; and to analyse the relationship between alcohol use with demographic data as well as diagnosed sexually transmitted infections (STIs) to see if there were any associations...
November 17, 2017: BMC Public Health
https://www.readbyqxmd.com/read/29149824/gene-therapy-and-retinal-diseases
#4
Claudio Campa, Carla Enrica Gallenga, Elena Bolletta, Paolo Perri
Background Gene therapy represents the therapeutic delivery of nucleic acid polymers into a patient's cells with the aim of treating an underlying disease. Over the past 2 decades this new therapy has made substantial progress owing to better understanding of the pathobiologic basis of various diseases coupled with growth of gene transfer biotechnologies. The eye, in particular, represents a suitable target for such therapy due to the immune privilege provided by the blood-ocular barrier, the ability to directly visualize, access and locally treat the cells and the minimal amount of vector needed given the size of this organ...
November 16, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/29149775/lentiviral-vectors-and-adeno-associated-virus-vectors-useful-tools-for-gene-transfer-in-pain-research
#5
REVIEW
Zheng Chen-Xi, Wang Sheng-Ming, Bai Yun-Hu, Luo Ting-Ting, Wang Jia-Qi, Dai Chun-Qiu, Guo Bao-Lin, Luo Shi-Cheng, Wang Dong-Hui, Yang Yan-Ling, Wang Ya-Yun
Pain, especially chronic pain, has always been a heated point in both basic and clinical researches since it puts heavy burdens on both individuals and the whole society. A better understanding of the role of biological molecules and various ionic channels involved in pain can shed light on the mechanism under pain and advocate the development of pain management. Using viral vectors to transfer specific genes at targeted sites is a promising method for both research and clinical applications. Lentiviral vectors and adeno-associated virus (AAV) vectors which allow stable and long-term expression of transgene in non-dividing cells are widely applied in pain research...
November 17, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/29149315/a-cross-sectional-study-of-malaria-endemicity-and-health-system-readiness-to-deliver-services-in-kenya-namibia-and-senegal
#6
Elizabeth H Lee, Cara H Olsen, Tracey Koehlmoos, Penny Masuoka, Ann Stewart, Jason W Bennett, James Mancuso
Despite good progress towards elimination, malaria continues to contribute substantially to the sub-Saharan African disease burden. Sustaining previous gains requires continued readiness to deliver malaria services in response to actual disease burden, which in turn contributes to health systems strengthening. This study investigates a health system innovation. We examined whether malaria prevalence, or endemicity, is a driver of health facility readiness to deliver malaria services. To estimate this association, we geo-linked cross-sectional facility survey data to endemicity data for Kenya, Namibia and Senegal...
November 1, 2017: Health Policy and Planning
https://www.readbyqxmd.com/read/29149176/a-simple-way-for-targeted-delivery-of-an-antibiotic-in-vitro-evaluation-of-a-nanoclay-based-composite
#7
Leslie Valdés, Irela Pérez, Louis Charles de Ménorval, Ernesto Altshuler, Jon Otto Fossum, Aramis Rivera
The sodium-modified form of fluorohectorite nanoclay (NaFh) is introduced as a potential drug carrier, demonstrating its ability for the controlled release of the broad-spectrum antibiotic Ciprofloxacin through in vitro tests. The new clay-drug composite is designed to target the local infections in the large intestine, where it delivers most of the incorporated drug thanks to its pH-sensitive behavior. The composite has been conceived to avoid the use of coating technology and to decrease the side-effects commonly associated to the burst-release of the ciprofloxacin at the stomach level...
2017: PloS One
https://www.readbyqxmd.com/read/29148802/ppb-peptide-mediated-sirna-loaded-stable-nucleic-acid-lipid-nanoparticles-on-targeting-therapy-of-hepatic-fibrosis
#8
Zongxiang Jia, Yan Gong, Yufang Pi, Xueying Liu, Lipeng Gao, Liqing Kang, Jing Wang, Fan Yang, Jie Tang, Weiyue Lu, Qinghua Li, Wei Zhang, Zhiqiang Yan, Lei Yu
Hepatic fibrosis is a necessary process in the development of liver diseases such as hepatic cirrhosis and its complications, which has become a serious threat to human health. Currently, antifibrotic drug treatment is ineffective, and one of the reasons should be the lack of liver targeting ability. In this report, polypeptide pPB modified stable nucleic acid lipid nanoparticles (pPB-SNALP) were prepared to selectively deliver siRNAs against heat shock protein 47 (HSP47) to liver for targeted therapy of hepatic fibrosis...
November 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29148732/photocontrolled-release-of-doxorubicin-conjugated-through-a-thioacetal-photocage-in-folate-targeted-nanodelivery-systems
#9
Pamela T Wong, Shengzhuang Tang, Jayme Cannon, Dexin Chen, Rachel Sun, Jennifer Lee, James Phan, Ke Tao, Kang Sun, Biqiong Chen, James R Baker, Seok Ki Choi
Despite their proven ability for precise and targeted release, nanoplatform systems for photocontrolled delivery often face formidable synthetic challenges, in part, due to the paucity of advanced linker strategies. Here we report on a novel linker strategy using a thioacetal ortho-nitrobenzaldehyde (TNB) cage, demonstrating its application for delivery of doxorubicin (Dox) in two nanoscale systems. This photocleavable linker, TNB(OH), which presents two identical arms, each terminated with a hydroxyl functionality, was prepared in a single step from 6-nitroverataldehyde...
November 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29148707/versatile-supermolecular-inclusion-complex-based-on-host-guest-interaction-for-targeted-gene-delivery
#10
Yunxia Sun, Jingyi Zhu, Wen-Xiu Qiu, Qi Lei, Si Chen, Xian-Zheng Zhang
A facile and targeted gene delivery system was prepared by conjugating β-cyclodextrin modified polyethylenimine (PEI-CD) and adamantyl peptide (AdGRGDS) based on host-guest interaction. With the rational design between PEI-CD and AdGRGDS, PEI-CD/AdGRGDS gene delivery system showed excellent DNA binding capability, and exhibited good ability to compact DNA into uniform spherical nanoparticles. In vitro luciferase assay showed that gene expression transfected by PEI-CD/AdGRGDS was stronger than that by PEI-CD in HeLa cells, whereas, gene expression transfected by PEI-CD/AdGRGDS and PEI-CD was similar to each other in COS7 cells...
November 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29148700/selective-ph-responsive-core-sheath-nanofiber-membranes-for-chem-bio-med-applications-targeted-delivery-of-functional-molecules
#11
Daewoo Han, Andrew J Steckl
Core-sheath fibers using different Eudragit materials were successfully produced and their controlled multi-pH responses have been demonstrated. Coaxial fibers made of Eudragit L 100 (EL100) core and Eudragit S 100 (ES100) sheath provide protection and/or controlled release of core material at pH 6 by adjusting the sheath thickness (controlled by the flow rate of source polymer solution). Thickest sheath (~ 250 nm) provides the least core release ~ 1.25 %/hr, while the thinnest sheath (~ 140 nm) provides much quicker release ~ 16...
November 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29148575/effects-of-spot-parameters-in-pencil-beam-scanning-treatment-planning
#12
Aafke Christine Kraan, Nicolas Depauw, Ben Clasie, Marina Giunta, Tom Madden, Hanne M Kooy
BACKGROUND: Spot size σ (in-air at isocenter), inter-spot spacing d, and spot charge q influence dose delivery efficiency and plan quality in Intensity Modulated Proton Therapy (IMPT) treatment planning. The choice and range of parameters varies among different manufacturers. The goal of this work is to demonstrate the influence of the spot parameters on dose quality and delivery in IMPT treatment plans, to show their interdependence, and to make practitioners aware of the spot parameter values for a certain facility...
November 17, 2017: Medical Physics
https://www.readbyqxmd.com/read/29148565/tobacco-cessation-interventions-for-young-people
#13
REVIEW
Thomas R Fanshawe, William Halliwell, Nicola Lindson, Paul Aveyard, Jonathan Livingstone-Banks, Jamie Hartmann-Boyce
BACKGROUND: Most tobacco control programmes for adolescents are based around prevention of uptake, but teenage smoking is still common. It is unclear if interventions that are effective for adults can also help adolescents to quit. This is the update of a Cochrane Review first published in 2006. OBJECTIVES: To evaluate the effectiveness of strategies that help young people to stop smoking tobacco. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialized Register in June 2017...
November 17, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29147931/horses-for-courses-moving-india-towards-universal-health-coverage-through-targeted-policy-design
#14
Dayashankar Maurya, Altaf Virani, S Rajasulochana
The debate on how India's health system should move towards universal health coverage was (meant to be) put to rest by the recent National Health Policy 2017. However, the new policy is silent about tackling bottlenecks mentioned in the said policy proposal. It aims to provide universal access to free primary care by strengthening the public system, and to secondary and tertiary care through strategic purchasing from the private sector, to overcome deficiencies in public provisioning in the short run. Yet, in doing so, it ignores critical factors needed to replicate successful models of public healthcare delivery from certain states that it hopes to emulate...
November 16, 2017: Applied Health Economics and Health Policy
https://www.readbyqxmd.com/read/29147885/proceedings-of-the-2017-isev-symposium-on-hiv-neurohiv-drug-abuse-evs
#15
Guoku Hu, Sowmya Yelamanchili, Fatah Kashanchi, Norman Haughey, Vincent C Bond, Kenneth W Witwer, Lynn Pulliam, Shilpa Buch
Despite the success of combination antiretroviral therapy (cART), there is increased prevalence of HIV-associated neurocognitive disorders (HAND) in HIV-1-infected individuals on cART, which poses a major health care challenge. Adding further complexity to this long-term antiretroviral use is the comorbidity with drugs of abuse such as morphine, cocaine, and methamphetamine, which can in turn, exacerbate neurologic and cognitive deficits associated with HAND. Furthermore, HIV proteins, such as the transactivator of transcription (Tat) and the envelope protein (gp120), as well as antiretrovirals themselves can also contribute to the progression of neurodegeneration underlying HAND...
November 16, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/29147695/synthesis-of-an-ethyleneimine-tetrahedral-dna-nanostructure-complex-and-its-potential-application-as-a-multi-functional-delivery-vehicle
#16
Taoran Tian, Tao Zhang, Tengfei Zhou, Shiyu Lin, Sirong Shi, Yunfeng Lin
Nowadays, DNA nanostructures are extensively researched for their biocompatibility, editable functionality, and structural stability. Tetrahedral DNA nanostructures (TDNs), widely known for their membrane permeability, are regarded as potential candidates for drug delivery. However, the stability and membrane permeability of TDNs call for further enhancement if in vivo usage is ascribed. To overcome the drawbacks of TDNs, ethylene imine (PEI, 25 kDa, branched)-a classic cationic polymer in the field of gene delivery-was applied...
November 17, 2017: Nanoscale
https://www.readbyqxmd.com/read/29147629/trial-watch-immune-checkpoint-blockers-for-cancer-therapy
#17
REVIEW
Claire Vanpouille-Box, Claire Lhuillier, Lucillia Bezu, Fernando Aranda, Takahiro Yamazaki, Oliver Kepp, Jitka Fucikova, Radek Spisek, Sandra Demaria, Silvia C Formenti, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Immune checkpoint blockers (ICBs) are literally revolutionizing the clinical management of an ever more diversified panel of oncological indications. Although considerable attention persists around the inhibition of cytotoxic T lymphocyte-associated protein 4 (CTLA4) and programmed cell death 1 (PDCD1, best known as PD-1) signaling, several other co-inhibitory T-cell receptors are being evaluated as potential targets for the development of novel ICBs. Moreover, substantial efforts are being devoted to the identification of biomarkers that reliably predict the likelihood of each patient to obtain clinical benefits from ICBs in the absence of severe toxicity...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147508/chiral-nanoprobes-for-targeting-and-long-term-imaging-of-the-golgi-apparatus
#18
Rong Sheng Li, Peng Fei Gao, Hong Zhi Zhang, Lin Ling Zheng, Chun Mei Li, Jian Wang, Yuan Fang Li, Feng Liu, Na Li, Cheng Zhi Huang
The Golgi apparatus is an essential subcellular organelle. Targeting and monitoring the Golgi change at the single-cell level over a long time scale are critical but are challenges that have not yet been tackled. Inspired by the precise Golgi positioning ability of galactosyltransferase and protein kinase D, due to their cysteine residues, we developed a method for long-term Golgi imaging. Fluorescent molecules, carbon quantum dots (CQDs) and silica nanoparticles could target the Golgi when they are modified with l-cysteine...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29147499/nano-microvehicles-for-efficient-delivery-and-bio-sensing-at-the-cellular-level
#19
S Campuzano, B Esteban-Fernández de Ávila, P Yáñez-Sedeño, J M Pingarrón, J Wang
A perspective review of recent strategies involving the use of nano/microvehicles to address the key challenges associated with delivery and (bio)sensing at the cellular level is presented. The main types and characteristics of the different nano/microvehicles used for these cellular applications are discussed, including fabrication pathways, propulsion (catalytic, magnetic, acoustic or biological) and navigation strategies, and relevant parameters affecting their propulsion performance and sensing and delivery capabilities...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29147075/pediatric-ocular-nanomedicines-challenges-and-opportunities
#20
Natasha D Sheybani, Hu Yang
The eye is a highly complex, yet readily accessible organ within the human body. As such, the eye is an appealing candidate target for a vast array of drug therapies. Despite advances in ocular drug therapy research, the focus on pediatric ocular drug delivery continues to be highly underrepresented due to the limited number of degenerative ocular diseases with childhood onset. In this review, we explore more deeply the reasons underlying the disparity between ocular therapies available for children and for adults by highlighting diseases that most commonly afflict children (with focus on the anterior eye) and existing prognoses, recent developments in ocular drug delivery systems and nanomedicines for children, and barriers to use for pediatric patients...
September 2017: Chinese Chemical Letters Zhongguo Hua Xue Kuai Bao
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