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https://www.readbyqxmd.com/read/29149721/biological-safety-and-tissue-distribution-of-16-mercaptohexadecyl-trimethylammonium-bromide-modified-cationic-gold-nanorods
#1
Monika Zarska, Michal Sramek, Filip Novotny, Filip Havel, Andrea Babelova, Blanka Mrazkova, Oldrich Benada, Milan Reinis, Ivan Stepanek, Kamil Musilek, Jiri Bartek, Monika Ursinyova, Ondrej Novak, Rastislav Dzijak, Kamil Kuca, Jan Proska, Zdenek Hodny
The exceptionally high cellular uptake of gold nanorods (GNRs) bearing cationic surfactants makes them a promising tool for biomedical applications. Given the known specific toxic and stress effects of some preparations of cationic nanoparticles, the purpose of this study was to evaluate, in an in vitro and in vivo in mouse, the potential harmful effects of GNRs coated with (16-mercaptohexadecyl)trimethylammonium bromide ((MTAB)GNRs). Interestingly, even after cellular accumulation of high amounts of (MTAB)GNRs sufficient for induction of photothermal effect, no genotoxicity (even after longer-term accumulation), induction of autophagy, destabilization of lysosomes (dominant organelles of their cellular destination), alterations of actin cytoskeleton, or in cell migration could be detected in vitro...
November 1, 2017: Biomaterials
https://www.readbyqxmd.com/read/29149631/prostaglandin-j2-promotes-o-glcnacylation-raising-app-processing-by-%C3%AE-and-%C3%AE-secretases-relevance-to-alzheimer-s-disease
#2
Teneka Jean-Louis, Patricia Rockwell, Maria E Figueiredo-Pereira
Regulation of the amyloid precursor protein (APP) processing by α- and β-secretases is of special interest to Alzheimer's disease (AD), as these proteases prevent or mediate amyloid beta formation, respectively. Neuroinflammation is also implicated in AD. Our data demonstrate that the endogenous mediator of inflammation prostaglandin J2 (PGJ2) promotes full-length APP (FL-APP) processing by α- and β-secretases. The decrease in FL-APP was independent of proteasomal, lysosomal, calpain, caspase, and γ-secretase activities...
November 14, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29149599/autophagosomal-content-profiling-reveals-an-lc3c-dependent-piecemeal-mitophagy-pathway
#3
François Le Guerroué, Franziska Eck, Jennifer Jung, Tatjana Starzetz, Michel Mittelbronn, Manuel Kaulich, Christian Behrends
Autophagy allows the degradation of cytosolic endogenous and exogenous material in the lysosome. Substrates are engulfed by double-membrane vesicles, coined autophagosomes, which subsequently fuse with lysosomes. Depending on the involvement of specific receptor proteins, autophagy occurs in a selective or nonselective manner. While this process is well understood at the level of bulky cargo such as mitochondria and bacteria, we know very little about individual proteins and protein complexes that are engulfed and degraded by autophagy...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149494/inhibiting-mt2-tfe3-dependent-autophagy-enhances-melatonin-induced-apoptosis-in-tongue-squamous-cell-carcinoma
#4
Tengfei Fan, Huifeng Pi, Min Li, Zhenhu Ren, Zhijing He, Feiya Zhu, Li Tian, Manyu Tu, Jia Xie, Mengyu Liu, Yuming Li, Miduo Tan, Gaoming Li, Weijia Qing, Russel J Reiter, Zhengping Yu, Hanjiang Wu, Zhou Zhou
Autophagy modulation is a potential therapeutic strategy for tongue squamous cell carcinoma (TSCC). Melatonin possesses significant anti-carcinogenic activity. However, whether melatonin induces autophagy and its roles in cell death in TSCC are unclear. Herein, we show that melatonin induced significant apoptosis in the TSCC cell line Cal27. Apart from the induction of apoptosis, we demonstrated that melatonin-induced autophagic flux in Cal27 cells as evidenced by the formation of GFP-LC3 puncta, and the upregulation of LC3-II and downregulation of SQSTM1/P62...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29148970/autophagic-cell-death-is-dependent-on-lysosomal-membrane-permeability-through-bax-and-bak
#5
Jason Karch, Tobias G Schips, Bryan D Maliken, Matthew J Brody, Michelle A Sargent, Onur Kanisciak, Jeffery D Molkentin
Cells deficient in the pro-death Bcl-2 family members Bax and Bak are known to be resistant to apoptotic cell death, and in a previous eLIFE paper, Karch et al., 2013 showed that these 2 effectors are also needed for mitochondrial-dependent cellular necrosis. Here we show that mouse embryonic fibroblasts deficient in Bax/Bak1 are resistant to the third major form of cell death associated with autophagy through a mechanism involving lysosome permeability. Indeed, specifically targeting Bax only to the lysosome restores autophagic cell death in Bax/Bak1 null cells...
November 17, 2017: ELife
https://www.readbyqxmd.com/read/29147695/synthesis-of-an-ethyleneimine-tetrahedral-dna-nanostructure-complex-and-its-potential-application-as-a-multi-functional-delivery-vehicle
#6
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/29147032/emptying-the-stores-lysosomal-diseases-and-therapeutic-strategies
#7
REVIEW
Frances M Platt
Lysosomal storage disorders (LSDs) - designated as 'orphan' diseases - are inborn errors of metabolism caused by defects in genes that encode proteins involved in various aspects of lysosomal homeostasis. For many years, LSDs were viewed as unattractive targets for the development of therapies owing to their low prevalence. However, the development and success of the first commercial biologic therapy for an LSD - enzyme replacement therapy for type 1 Gaucher disease - coupled with regulatory incentives rapidly catalysed commercial interest in therapeutically targeting LSDs...
November 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29146937/tfeb-regulates-lysosomal-positioning-by-modulating-tmem55b-expression-and-jip4-recruitment-to-lysosomes
#8
Rose Willett, José A Martina, James P Zewe, Rachel Wills, Gerald R V Hammond, Rosa Puertollano
Lysosomal distribution is linked to the role of lysosomes in many cellular functions, including autophagosome degradation, cholesterol homeostasis, antigen presentation, and cell invasion. Alterations in lysosomal positioning contribute to different human pathologies, such as cancer, neurodegeneration, and lysosomal storage diseases. Here we report the identification of a novel mechanism of lysosomal trafficking regulation. We found that the lysosomal transmembrane protein TMEM55B recruits JIP4 to the lysosomal surface, inducing dynein-dependent transport of lysosomes toward the microtubules minus-end...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146245/repurposing-cationic-amphiphilic-drugs-as-adjuvants-to-induce-lysosomal-sirna-escape-in-nanogel-transfected-cells
#9
Freya Joris, Lynn De Backer, Thijs Van de Vyver, Chiara Bastiancich, Stefaan C De Smedt, Koen Raemdonck
Cytosolic delivery remains a major bottleneck for siRNA therapeutics. To facilitate delivery, siRNAs are often enclosed in nanoparticles (NPs). However, upon endocytosis such NPs are mainly trafficked towards lysosomes. To avoid degradation, cytosolic release of siRNA should occur prior to fusion of endosomes with lysosomes, but current endosomal escape strategies remain inefficient. In contrast to this paradigm, we aim to exploit lysosomal accumulation by treating NP-transfected cells with low molecular weight drugs that release the siRNA from the lysosomes into the cytosol...
November 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29145436/scrambled-eggs-proteomic-portraits-and-novel-biomarkers-of-egg-quality-in-zebrafish-danio-rerio
#10
Ozlem Yilmaz, Amélie Patinote, Thao Vi Nguyen, Emmanuelle Com, Regis Lavigne, Charles Pineau, Craig V Sullivan, Julien Bobe
Egg quality is a complex biological trait and a major determinant of reproductive fitness in all animals. This study delivered the first proteomic portraits of egg quality in zebrafish, a leading biomedical model for early development. Egg batches of good and poor quality, evidenced by embryo survival for 24 h, were sampled immediately after spawning and used to create pooled or replicated sample sets whose protein extracts were subjected to different levels of fractionation before liquid chromatography and tandem mass spectrometry...
2017: PloS One
https://www.readbyqxmd.com/read/29144277/newborn-screening-for-spinal-muscular-atrophy-and-lysosomal-storage-disorders-takes-advantage-of-novel-therapies
#11
EDITORIAL
Hans C Andersson
No abstract text is available yet for this article.
November 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/29144122/the-ratio-of-polycation-and-serum-is-a-crucial-index-determining-the-rnai-efficiency-of-polyplex
#12
Weiqi Zhang, Xianghui Meng, Huike Liu, Lifei Xie, Jian Liu, Haiyan Xu
We report that the mass ratio of the polycation to serum in the medium determines the RNAi efficiency in vitro by using spermine-modified pullulan (Ps) and spermine-modified dextran (Ds) as polycation models. The high ratio of Ps to serum protein (Ps/Pr) mediated the formation of larger polyplex, which led to the promoted cellular uptake, enhanced lysosomal escape and elevated RNAi efficiency. In addition, the supplementary of free Ps also enhanced siRNA transfection due to the elevation of Ps/Pr. Similar results were obtained with Ds...
November 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29143438/protective-effects-of-coenzyme-q10-nanoparticles-on-dichlorvos-induced-hepatotoxicity-and-mitochondrial-lysosomal-injury
#13
Aziz Eftekhari, Elham Ahmadian, Aida Azami, Mohammad Johari-Ahar, Mohammad Ali Eghbal
Development of biocompatible antioxidant nanoparticles for xenobiotic-induced liver disease treatment by oral or parenteral administration is of great interest in medicine. In the current study, we demonstrate the protective effects of coenzyme Q10 nanoparticles (CoQ10-NPs) on hepatotoxicity induced by dichlorvos (DDVP) as an organophosphate. Although CoQ10 is an efficient antioxidant, its poor bioavailability has limited the applications of this useful agent. First, CoQ10-NPs were prepared then characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM)...
November 16, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29143201/newborn-screening-for-lysosomal-storage-disorders-by-tandem-mass-spectrometry-in-north-east-italy
#14
Alberto B Burlina, Giulia Polo, Leonardo Salviati, Giovanni Duro, Carmela Zizzo, Andrea Dardis, Bruno Bembi, Chiara Cazzorla, Laura Rubert, Roberta Zordan, Robert J Desnick, Alessandro P Burlina
BACKGROUND: Lysosomal storage diseases (LSDs) are inborn errors of metabolism resulting from 50 different inherited disorders. The increasing availability of treatments and the importance of early intervention have stimulated newborn screening (NBS) to diagnose LSDs and permit early intervention to prevent irreversible impairment or severe disability. We present our experience screening newborns in North East Italy to identify neonates with Mucopolysaccharidosis type I (MPS I) and Pompe, Fabry, and Gaucher diseases...
November 15, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29142103/an-intracellular-activation-of-smoothened-independent-of-hedgehog-stimulation-in-drosophila
#15
Kai Jiang, Yajuan Liu, Jie Zhang, Jianhang Jia
Smoothened (Smo), a GPCR family protein, plays a critical role in the reception and transduction of Hedgehog (Hh) signal. Smo is phosphorylated and activated on the cell surface, however, it is unknown whether Smo can be intracellularly activated. Here, we demonstrate that inactivation of the ESCRT-III causes dramatic accumulation of Smo, and subsequent activation of Hh signaling. In contrast, inactivation of ESCRTs 0-II induces mild Smo accumulation. We provide evidence that Kurtz (Krz), the Drosophila β-arrestin2, acts in parallel with the ESCRTs 0-II pathway to sort Smo to the multivesicular bodies and lysosome-mediated degradation...
November 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29142073/gga1-regulates-signal-dependent-sorting-of-bace1-to-recycling-endosomes-which-moderates-a%C3%AE-production
#16
Wei Hong Toh, Pei Zhi Cheryl Chia, Mohammed Iqbal Hossain, Paul A Gleeson
The diversion of the membrane-bound β-secretase BACE1 from the endo-lysosomal pathway to recycling endosomes represents an important transport step in the regulation of amyloid beta (Aβ) production. However, the mechanisms that regulate endosome sorting of BACE1 are poorly understood. Here we assessed the transport of BACE1 from early to recycling endosomes and have identified essential roles for the SNX4-mediated, signal independent pathway and for a novel signal-mediated pathway. The signal-mediated pathway is regulated by the phosphorylation of the acidic cluster-dileucine DISLL cytoplasmic tail motif of BACE1...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29141697/microarray-expression-profile-of-lncrnas-and-mrnas-in-the-placenta-of-non-diabetic-macrosomia
#17
G Y Song, Q Na, D Wang, C Qiao
Macrosomia, not only is closely associated with short-term, birth-related problems, but also has long-term consequences for the offspring. We investigated the expression of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the placenta of macrosomia births using a microarray profile. The data showed that 2929 lncRNAs and 4574 mRNAs were upregulated in the placenta of macrosomia births compared with the normal birth weight group (fold change ⩾2.0, P<0.05), and 2127 lncRNAs and 2511 mRNAs were downregulated (fold change ⩾2...
November 16, 2017: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/29141151/light-responsive-nanoparticles-for-highly-efficient-cytoplasmic-delivery-of-anticancer-agents
#18
Yangyun Wang, Yibin Deng, Huanhuan Luo, Aijun Zhu, Hengte Ke, Hong Yang, Huabing Chen
Stimuli-responsive nanostructures have shown great promise for intracellular delivery of anticancer compounds. A critical challenge remains in the exploration of stimuli-responsive nanoparticles for fast cytoplasmic delivery. Herein, near-infrared (NIR) light-responsive nanoparticles were rationally designed to generate highly efficient cytoplasmic delivery of anticancer agents for synergistic thermo-chemotherapy. The drug-loaded polymeric nanoparticles of selenium-inserted copolymer (I/D-Se-NPs) were rapidly dissociated in several minutes through reactive oxygen species (ROS)-mediated selenium oxidation upon NIR light exposure, and this irreversible dissociation of I/D-Se-NPs upon such a short irradiation promoted continuous drug release...
November 15, 2017: ACS Nano
https://www.readbyqxmd.com/read/29140794/targeted-elimination-of-senescent-ras-transformed-cells-by-suppression-of-mek-erk-pathway
#19
Elena Y Kochetkova, Galina I Blinova, Olga A Bystrova, Marina G Martynova, Valery A Pospelov, Tatiana V Pospelova
The Ras-Raf-MEK-ERK pathway plays a central role in tumorigenesis and is a target for anticancer therapy. The successful strategy based on the activation of cell death in Ras-expressing cells is associated with the suppression of kinases involved in Ras pathway. However, activation of cytoprotective autophagy overcomes antiproliferative effect of the inhibitors and develops drug resistance. We studied whether cellular senescence induced by HDAC inhibitor sodium butyrate in E1a+cHa-Ras-transformed rat embryo fibroblasts (ERas) and A549 human Ki-Ras mutated lung adenocarcinoma cells would enhance the tumor suppressor effect of MEK/ERK inhibition...
November 14, 2017: Aging
https://www.readbyqxmd.com/read/29140481/excessive-burden-of-lysosomal-storage-disorder-gene-variants-in-parkinson-s-disease
#20
Laurie A Robak, Iris E Jansen, Jeroen van Rooij, André G Uitterlinden, Robert Kraaij, Joseph Jankovic, Peter Heutink, Joshua M Shulman
Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. We examined whether a genetic burden of variants in other lysosomal storage disorder genes is more broadly associated with Parkinson's disease susceptibility. The sequence kernel association test was used to interrogate variant burden among 54 lysosomal storage disorder genes, leveraging whole exome sequencing data from 1156 Parkinson's disease cases and 1679 control subjects. We discovered a significant burden of rare, likely damaging lysosomal storage disorder gene variants in association with Parkinson's disease risk...
November 13, 2017: Brain: a Journal of Neurology
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