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https://www.readbyqxmd.com/read/28432944/phototoxic-action-of-a-zinc-ii-phthalocyanine-encapsulated-into-poloxamine-polymeric-micelles-in-2d-and-3d-colon-carcinoma-cell-cultures
#1
Nicolás Chiarante, María C García Vior, Josefina Awruch, Julieta Marino, Leonor P Roguin
Photodynamic therapy is emerging as a hopeful method for the treatment of oncological diseases. In the search of novel therapeutic strategies for colorectal cancer, in this work we reported the photocytotoxic activity of a lipophilic zinc(II) phthalocyanine on a murine colon adenocarcinoma cell line (CT26 cells). The 2,9(10),16(17),23(24) tetrakis[(2-dimethylamino)ethylsulfanyl]phthalocyaninatozinc(II), named Pc9, was encapsulated into Tetronic® 1107 polymeric poloxamine micelles (T1107) and assayed in 2D and 3D cell cultures...
April 11, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28432355/basal-autophagy-prevents-autoactivation-or-enhancement-of-inflammatory-signals-by-targeting-monomeric-myd88
#2
Takeshi Into, Toshi Horie, Megumi Inomata, Jin Gohda, Jun-Ichiro Inoue, Yukitaka Murakami, Shumpei Niida
Autophagy, the processes of delivery of intracellular components to lysosomes, regulates induction of inflammation. Inducible macroautophagy degrades inflammasomes and dysfunctional mitochondria to downregulate inflammatory signals. Nonetheless, the effects of constitutive basal autophagy on inflammatory signals are largely unknown. Here, we report a previously unknown effect of basal autophagy. Lysosomal inhibition induced weak inflammatory signals in the absence of a cellular stimulus and in the presence of a nutrient supply, and their induction was impaired by MyD88 deficiency...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432021/the-er-phagosome-connection-in-the-era-of-membrane-contact-sites
#3
REVIEW
Paula Nunes-Hasler, Nicolas Demaurex
Phagocytosis is an essential mechanism through which innate immune cells ingest foreign material that is either destroyed or used to generate and present antigens and initiate adaptive immune responses. While a role for the ER during phagosome biogenesis has been recognized, whether fusion with ER cisternae or vesicular derivatives occurs has been the source of much contention. Membrane contact sites (MCS) are tight appositions between ER membranes and various organelles that coordinate multiple functions including localized signalling, lipid transfer and trafficking...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28431763/immune-response-of-the-short-neck-clam-paphia-malabarica-to-salinity-stress-using-flow-cytometry
#4
Deodatta S Gajbhiye, Lidita Khandeparker
Paphia malabarica is a predominant and commercially important bivalve in India, persistently challenged by wavering salinity in a monsoon-influenced estuary. To examine the organism's immunological response under such a condition we challenged P. malabarica with different salinities (0, 5, 15, 25 and 35) for varied periods using a two-way experimental approach (in vitro and in vivo). This is the first study to report the response of P. malabarica hemocytes to salinity stress from a monsoon-influenced estuary on the southwest coast of India...
April 11, 2017: Marine Environmental Research
https://www.readbyqxmd.com/read/28431555/reduction-of-pulmonary-toxicity-of-metal-oxide-nanoparticles-by-phosphonate-based-surface-passivation
#5
Xiaoming Cai, Anson Lee, Zhaoxia Ji, Cynthia Huang, Chong Hyun Chang, Xiang Wang, Yu-Pei Liao, Tian Xia, Ruibin Li
BACKGROUND: The wide application of engineered nanoparticles has induced increasing exposure to humans and environment, which led to substantial concerns on their biosafety. Some metal oxides (MOx) have shown severe toxicity in cells and animals, thus safe designs of MOx with reduced hazard potential are desired. Currently, there is a lack of a simple yet effective safe design approach for the toxic MOx. In this study, we determined the key physicochemical properties of MOx that lead to cytotoxicity and explored a safe design approach for toxic MOx by modifying their hazard properties...
April 21, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28431397/sensitization-of-tamoxifen-resistant-breast-cancer-cells-by-z-ligustilide-through-inhibiting-autophagy-and-accumulating-dna-damages
#6
Hongyi Qi, Zhuyun Jiang, Chengqiang Wang, Yi Yang, Li Li, Hui He, Zanyang Yu
Autophagy plays a pro-survival role in the tamoxifen-resistant breast cancer cells. Herein we found that autophagy was concomitantly induced in tamoxifen-resistant MCF-7 (MCF-7TR5) cells through the dissociation of Bcl-2 from Beclin 1 and subsequent enhancement of interaction among the ATG14-Beclin1-PI3KC3 complex. Moreover, higher level of DNA damage was observed in MCF-7TR5 cells with the decreased BRCA1 and RAD51 level and the increased Ku80 level. Interestingly, Nur77 was selectively degraded by autophagy, which causes the release of Ku80 from the Nur77-Ku80 complex, resulting in the increase of the DNA binding of Ku80 and DNA-PKcs...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431247/the-ubiquitin-ligase-chip-integrates-proteostasis-and-aging-by-regulation-of-insulin-receptor-turnover
#7
Riga Tawo, Wojciech Pokrzywa, Éva Kevei, Melek E Akyuz, Vishnu Balaji, Svenja Adrian, Jörg Höhfeld, Thorsten Hoppe
Aging is attended by a progressive decline in protein homeostasis (proteostasis), aggravating the risk for protein aggregation diseases. To understand the coordination between proteome imbalance and longevity, we addressed the mechanistic role of the quality-control ubiquitin ligase CHIP, which is a key regulator of proteostasis. We observed that CHIP deficiency leads to increased levels of the insulin receptor (INSR) and reduced lifespan of worms and flies. The membrane-bound INSR regulates the insulin and IGF1 signaling (IIS) pathway and thereby defines metabolism and aging...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28430987/rab32-subfamily-small-gtpases-pleiotropic-rabs-in-endosomal-trafficking
#8
Norihiko Ohbayashi, Mitsunori Fukuda, Yasunori Kanaho
Rab small GTPases, well-known regulators of membrane trafficking pathways in eukaryotic cells, comprise approximately 60 different members in mammals. During the past decade, our understanding of the functions of mammalian Rab32 subfamily members (Rab32 and Rab38) have deepened, especially on the biogenesis of lysosome-related organelles, such as melanosomes, and the protection mechanisms against several pathogenic microbial infections. Endosome-mediated membrane trafficking by Rab32 subfamily members plays pivotal roles in these events...
April 14, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28430167/induced-pluripotent-stem-cell-modeling-of-gaucher-s-disease-what-have-we-learned
#9
REVIEW
Dino Matias Santos, Gustavo Tiscornia
Gaucher's disease (GD) is the most frequently inherited lysosomal storage disease, presenting both visceral and neurologic symptoms. Mutations in acid β-glucocerebrosidase disrupt the sphingolipid catabolic pathway promoting glucosylceramide (GlcCer) accumulation in lysosomes. Current treatment options are enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). However, neither of these approaches is effective in treating the neurological aspect of the disease. The use of small pharmacological compounds that act as molecular chaperones is a promising approach that is still experimental...
April 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28429522/globotriaosylsphingosine-induces-oxidative-dna-damage-in-cultured-kidney-cells
#10
Giovana Brondani Biancini, Ana Moira Morás, Luiza Steffens Reinhardt, Franciele Faccio Busatto, Nathalia Denise de Moura Sperotto, Jenifer Saffi, Dinara Jaqueline Moura, Roberto Giugliani, Carmen Regla Vargas
Fabry disease (FD) is a lysosomal disorder caused by mutations leading to a deficient activity α-galactosidase A with progressive and systemic accumulation of its substrates. Substrates deposition is related to tissue damage in FD, but the underlying molecular mechanisms remain not completely understood. DNA damage has been associated with disease progression in chronic diseases and was recently described in high levels in Fabry patients. Once renal complications are major morbidity causes in FD, we investigated the effects of the latest biomarker for FD - globotriaosylsphingosine (lyso-Gb3) in a cultured renal lineage - human embryonic kidney cells (HEK-293 T) - on DNA damage...
June 2017: Nephrology
https://www.readbyqxmd.com/read/28429406/haplodeficiency-of-cathepsin-d-does-not-affect-cerebral-amyloidosis-and-autophagy-in-app-ps1-transgenic-mice
#11
Shaowu Cheng, Willayat Y Wani, David A Hottman, Angela Jeong, Dongfeng Cao, Kyle J LeBlanc, Paul Saftig, Jianhua Zhang, Ling Li
Autophagy and lysosomal function are important for protein homeostasis and their dysfunction have been associated with Alzheimer's disease (AD). Increased immunoreactivities of an important lysosomal protease, cathepsin D (Cat D), are evident in amyloid plaques and neurons in patients with AD. The current study tests the hypothesis that deleting one allele of the cathepsin D gene (Ctsd) impacts cerebral β-amyloidosis in APPsw/PS1dE9 (APP/PS1) double transgenic mice. Despite a significant 38% decrease of Cat D level in APP/PS1/Ctsd+/- compared to APP/PS1/Ctsd+/+ mice, no changes in steady state levels and deposition of Aβ were found in the brain...
April 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28428740/protein-quality-control-by-molecular-chaperones-in-neurodegeneration
#12
REVIEW
Aaron Ciechanover, Yong Tae Kwon
Protein homeostasis (proteostasis) requires the timely degradation of misfolded proteins and their aggregates by protein quality control (PQC), of which molecular chaperones are an essential component. Compared with other cell types, PQC in neurons is particularly challenging because they have a unique cellular structure with long extensions. Making it worse, neurons are postmitotic, i.e., cannot dilute toxic substances by division, and, thus, are highly sensitive to misfolded proteins, especially as they age...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28428710/cma-down-regulates-p53-expression-through-degradation-of-hmgb1-protein-to-inhibit-irradiation-triggered-apoptosis-in-hepatocellular-carcinoma
#13
Jing-Hua Wu, Jia-Pei Guo, Jun Shi, Hui Wang, Lei-Lei Li, Bin Guo, Dian-Xing Liu, Qing Cao, Zhi-Yong Yuan
AIM: To investigate the mechanism of chaperone-mediated autophagy (CMA)-induced resistance to irradiation-triggered apoptosis through regulation of the p53 protein in hepatocellular carcinoma (HCC). METHODS: Firstly, we detected expression of lysosome-associated membrane protein 2a (Lamp-2a), which is the key protein of CMA, by western blot in HepG2 and SMMC7721 cells after irradiation. We further used shRNA Lamp-2a HCC cells to verify the radioresistance induced by CMA...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28428354/multiplex-tandem-mass-spectrometry-enzymatic-activity-assay-for-newborn-screening-of-the-mucopolysaccharidoses-and-type-2-neuronal-ceroid-lipofuscinosis
#14
Yang Liu, Fan Yi, Arun Babu Kumar, Naveen Kumar Chennamaneni, Xinying Hong, C Ronald Scott, Michael H Gelb, Frantisek Turecek
BACKGROUND: We expanded the use of tandem mass spectrometry combined with liquid chromatography (LC-MS/MS) for multiplex newborn screening of seven lysosomal enzymes in dried blood spots (DBS). The new assays are for enzymes responsible for the mucopolysaccharidoses (MPS-I, -II, -IIIB, -IVA, -VI, and -VII) and type 2 neuronal ceroid lipofuscinosis (LINCL). METHODS: New substrates were prepared and char-acterized for tripeptidyl peptidase 1 (TPP1), α-N-acetylglucosaminidase (NAGLU), and lysosomal β-glucuronidase (GUSB)...
April 20, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28428217/microrna-33-regulates-macrophage-autophagy-in-atherosclerosis
#15
Mireille Ouimet, Hasini Ediriweera, Milessa Silva Afonso, Bhama Ramkhelawon, Ragunath Singaravelu, Xianghai Liao, Rachel C Bandler, Karishma Rahman, Edward A Fisher, Katey J Rayner, John P Pezacki, Ira Tabas, Kathryn J Moore
OBJECTIVE: Defective autophagy in macrophages leads to pathological processes that contribute to atherosclerosis, including impaired cholesterol metabolism and defective efferocytosis. Autophagy promotes the degradation of cytoplasmic components in lysosomes and plays a key role in the catabolism of stored lipids to maintain cellular homeostasis. microRNA-33 (miR-33) is a post-transcriptional regulator of genes involved in cholesterol homeostasis, yet the complete mechanisms by which miR-33 controls lipid metabolism are unknown...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28427998/nitric-oxide-regulated-proteolysis-of-human-cyp2b6-via-the-ubiquitin-proteasome-system
#16
Choon-Myung Lee, Shweta Tripathi, Edward T Morgan
We showed previously that rat cytochrome P450 CYP2B1 undergoes NO-dependent proteasomal degradation in response to inflammatory stimuli, and that the related human enzyme CYP2B6 is also down-regulated by NO in primary human hepatocytes. To investigate the mechanism of CYP2B6 down-regulation, we made several cell lines (HeLa and HuH7 cells) in which native CYP2B6 or CYP2B6 with a C-terminal V5 tag (CYP2B6V5) are expressed from a lentiviral vector with a cytomegalovirus promoter. Native CYP2B6 protein was rapidly down-regulated in HeLa cells within 3h of treatment with the NO donor (Z)-1-[2-(2-Aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, while its mRNA level was not down-regulated...
April 17, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28427951/uncovering-the-immune-responses-of-apis-mellifera-ligustica-larval-gut-to-ascosphaera-apis-infection-utilizing-transcriptome-sequencing
#17
Dafu Chen, Rui Guo, Xijian Xu, Cuiling Xiong, Qin Liang, Yanzhen Zheng, Qun Luo, Zhaonan Zhang, Zhijian Huang, Dhiraj Kumar, Weijun Xi, Xuan Zou, Min Liu
Honeybees are susceptible to a variety of diseases, including chalkbrood, which is capable of causing huge losses of both the number of bees and colony productivity. This research is designed to characterize the transcriptome profiles of Ascosphaera apis-treated and un-treated larval guts of Apis mellifera ligustica in an attempt to unravel the molecular mechanism underlying the immune responses of western honeybee larval guts to mycosis. In this study, 24, 296 and 2157 genes were observed to be differentially expressed in A...
April 18, 2017: Gene
https://www.readbyqxmd.com/read/28427936/molecular-dissection-of-caenorhabditis-elegans-atp-binding-cassette-transporter-protein-haf-4-to-investigate-its-subcellular-localization-and-dimerization
#18
Takahiro Tanji, Hirohisa Shiraishi, Kenji Nishikori, Reiko Aoyama, Kazuaki Ohashi, Masatomo Maeda, Ayako Ohashi-Kobayashi
Caenorhabditis elegans HAF-4 and HAF-9 are half-type ATP-binding cassette (ABC) transporter proteins, which are highly homologous to the human peptide transporter protein, transporter associated with antigen processing-like (TAPL, ABCB9). TAPL forms homodimers and localizes to lysosomes, whereas HAF-4 and HAF-9 form heterodimers and localize to intestine-specific non-acidified organelles. Both TAPL and HAF-4/HAF-9 are predicted to have four amino-terminal transmembrane helices [transmembrane domain 0 (TMD0)] additional to the six transmembrane helices that form the canonical core domain of ABC transporters with a cytosolic ABC region...
April 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28427477/plasma-chitotriosidase-activity-versus-ccl18-level-for-assessing-type-i-gaucher-disease-severity-protocol-for-a-systematic-review-with-meta-analysis-of-individual-participant-data
#19
Tatiana Raskovalova, Patrick B Deegan, Ruby Yang, Elena Pavlova, Jérome Stirnemann, José Labarère, Ari Zimran, Pramod K Mistry, Marc Berger
BACKGROUND: Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by deficiency in acid beta-glucosidase. GD exhibits a wide clinical spectrum of disease severity with an unpredictable natural course. Plasma chitotriosidase activity and CC chemokine ligand 18 (CCL18) have been exchangeably used for monitoring GD activity and response to enzyme replacement therapy in conjunction with clinical assessment. Yet, a large-scale head-to-head comparison of these two biomarkers is currently lacking...
April 20, 2017: Systematic Reviews
https://www.readbyqxmd.com/read/28426067/bioinspired-peptosomes-with-programmed-stimuli-responses-for-sequential-drug-release-and-high-performance-anticancer-therapy
#20
Yuan Li, Wei Li, Weier Bao, Bin Liu, Dan Li, Yumeng Jiang, Wei Wei, Fazheng Ren
Combination therapy with enhanced therapeutic and antimetastatic efficacy has become promising for cancer treatment. There is an urgent need to design a co-delivery system to sequentially release the drug pair at desired locations that can increase the intra-tumoral drug concentration and reduce the side effects. Inspired by virus architecture and function, herein, we developed a peptosome (PS)-based co-delivery system, PePm/PS/Curcumin (Cur), for the sequential release of the therapeutic peptide Pe and chemodrug Cur...
April 20, 2017: Nanoscale
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