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Total 1197 results found since Jan 2013.

Dual-targeting RNA nanoparticles for efficient delivery of polymeric siRNA to cancer cells.
Abstract A new dual-targeting polymeric siRNA nanoparticle (Dual-PSNP) was developed via multiple processes: rolling circle transcription, condensation, electrostatic deposition, and click chemistry. The Dual-PSNP showed significantly improved cancer-specific intracellular delivery, gene knockdown efficacy, and apoptosis-mediated cytotoxicity through additive receptor-mediated interactions of the two ligands. PMID: 32463029 [PubMed - as supplied by publisher]
Source: Chemical Communications - May 27, 2020 Category: Chemistry Authors: Kim T, Hyun HN, Heo R, Nam K, Yang K, Kim YM, Lee YS, An JY, Park JH, Choi KY, Roh YH Tags: Chem Commun (Camb) Source Type: research

ASAP Emerging siRNA Design Principles and Consequences for Biotransformation and Disposition in Drug Development
Journal of Medicinal ChemistryDOI: 10.1021/acs.jmedchem.9b01839
Source: Journal of Medicinal Chemistry - May 26, 2020 Category: Chemistry Authors: Sara C. Humphreys* †, Mai B. Thayer†, Jabbar Campbell‡, Wen Li Kelly Chen§, Dan Adams§, Julie M. Lade†, and Brooke M. Rock† Source Type: research

Identification and validation of metformin protects against PM2.5-induced macrophages cytotoxicity by targeting toll like receptor pathway.
Abstract Fine particle matter (PM2.5) has been extensively reported to contribute to the pathogenesis of pulmonary diseases. Recently, metformin has been reported to attenuate PM2.5 associated respiratory and cardiovascular injury, but the underling mechanism has not been discovered. Here, we performed comprehensively bioinformatics analysis and fully validation experiment to investigate the protection role of metformin and underling mechanism with RNAseq profile in GEO database. A combination of various bioinformatics tools including edgeR, principal component analysis (PCA), K-Means clustering, Gene Set Enrichme...
Source: Chemosphere - May 25, 2020 Category: Chemistry Authors: Shi Y, Batibawa JW, Maiga M, Sun B, Li Y, Duan J, Sun Z Tags: Chemosphere Source Type: research

Mycosporine-like amino acids stimulate hyaluronan secretion by up-regulating hyaluronan synthase 2 via activation of the p38/MSK1/CREB/c-Fos/AP-1 axis Signal Transduction
Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that critically supports the physicochemical and mechanical properties of the skin. Here, we demonstrate that mycosporine-like amino acids (MAAs), which typically function as UV-absorbing compounds, can stimulate HA secretion from normal human fibroblasts. MAA-stimulated HA secretion was associated with significantly increased and decreased levels of mRNAs encoding HA synthase 2 (HAS2) and the HA-binding protein involved in HA depolymerization (designated HYBID), respectively. Using immunoblotting, we found that MAAs at 10 and at 25 μg/ml stimulate the phosphory...
Source: Journal of Biological Chemistry - May 21, 2020 Category: Chemistry Authors: Shuko Terazawa, Masahiko Nakano, Akio Yamamoto, Genji Imokawa Tags: Signal Transduction Source Type: research

The gene for the lysosomal protein LAMP3 is a direct target of the transcription factor ATF4 Gene Regulation
Autophagy and lysosomal activities play a key role in the cell by initiating and carrying out the degradation of misfolded proteins. Transcription factor EB (TFEB) functions as a master controller of lysosomal biogenesis and function during lysosomal stress, controlling most but, importantly, not all lysosomal genes. Here, we sought to better understand the regulation of lysosomal genes whose expression does not appear to be controlled by TFEB. Sixteen of these genes were screened for transactivation in response to diverse cellular insults. mRNA levels for lysosomal-associated membrane protein 3 (LAMP3), a gene that is hig...
Source: Journal of Biological Chemistry - May 21, 2020 Category: Chemistry Authors: Thomas D. Burton, Anthony O. Fedele, Jianling Xie, Lauren Y. Sandeman, Christopher G. Proud Tags: Gene Regulation Source Type: research

Engineering Magnetosomes with Chimeric Membrane and Hyaluronidase for Efficient Delivery of HIF-1 siRNA into Deep Hypoxic Tumors
Publication date: Available online 16 May 2020Source: Chemical Engineering JournalAuthor(s): Chengliang Lyu, Guihong Lu, Weier Bao, Feng Li, Shuang Wang, Fan Zhang, Xiaoyong Gao, Hidehiro Kamiya, Guanghui Ma, Wei Wei
Source: Chemical Engineering Journal - May 18, 2020 Category: Chemistry Source Type: research

Arachidonate 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid contribute to stromal aging-induced progression of pancreatic cancer Molecular Bases of Disease
In this study, we investigated whether the chronological aging of normal human fibroblasts (NHFs), a previously underappreciated area in pancreatic cancer research, influences the progression and therapeutic outcomes of PDAC. Results from experiments with murine xenografts and 2D and 3D co-cultures of NHFs and PDAC cells revealed that older NHFs stimulate proliferation of and confer resistance to radiation therapy of PDAC. MS-based metabolite analysis indicated that older NHFs have significantly increased arachidonic acid 12-lipoxygenase (ALOX12) expression and elevated levels of its mitogenic metabolite, 12-(S)-hydroxy-5,...
Source: Journal of Biological Chemistry - May 14, 2020 Category: Chemistry Authors: Ehab H. Sarsour, Jyung Mean Son, Amanda L. Kalen, Wusheng Xiao, Juan Du, Matthew S. Alexander, Brianne R. O'Leary, Joseph J. Cullen, Prabhat C. Goswami Tags: Cell Biology Source Type: research

Perturbation of phosphoglycerate kinase 1 (PGK1) only marginally affects glycolysis in cancer cells Metabolism
Phosphoglycerate kinase 1 (PGK1) plays important roles in glycolysis, yet its forward reaction kinetics are unknown, and its role especially in regulating cancer cell glycolysis is unclear. Here, we developed an enzyme assay to measure the kinetic parameters of the PGK1-catalyzed forward reaction. The Km values for 1,3-bisphosphoglyceric acid (1,3-BPG, the forward reaction substrate) were 4.36 μm (yeast PGK1) and 6.86 μm (human PKG1). The Km values for 3-phosphoglycerate (3-PG, the reverse reaction substrate and a serine precursor) were 146 μm (yeast PGK1) and 186 μm (human PGK1). The Vmax of the forward reaction was a...
Source: Journal of Biological Chemistry - May 7, 2020 Category: Chemistry Authors: Chengmeng Jin, Xiaobing Zhu, Hao Wu, Yuqi Wang, Xun Hu Tags: Metabolism Source Type: research

A kinesin adapter directly mediates dendritic mRNA localization during neural development in mice Neurobiology
Motor protein-based active transport is essential for mRNA localization and local translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased yeast two–hybrid screen for interactions between murine RNA-binding proteins (RBPs) and motor proteins, here we identified protein interaction with APP tail-1 (PAT1) as a potential direct adapter between zipcode-binding protein 1 (ZBP1, a β-actin RBP) and the kinesin-I motor complex. The amino acid sequence of mouse PAT1 is similar to that of the kinesin light chain (KLC), and we found that PAT1 binds to KLC directly...
Source: Journal of Biological Chemistry - May 7, 2020 Category: Chemistry Authors: Hao Wu, Jing Zhou, Tianhui Zhu, Ivan Cohen, Jason Dictenberg Tags: Cell Biology Source Type: research

ADAM10 and ADAM17 proteases mediate proinflammatory cytokine-induced and constitutive cleavage of endomucin from the endothelial surface Membrane Biology
In this study, using adenovirus-mediated overexpression of a tagged EMCN in human umbilical vein ECs, we found that treatment with tumor necrosis factor α (TNF-α) or the strong oxidant pervanadate leads to loss of cell-surface EMCN and increases the levels of the C-terminal fragment of EMCN 3- to 4-fold. Furthermore, treatment with the broad-spectrum matrix metalloproteinase inhibitor batimastat (BB94) or inhibition of ADAM metallopeptidase domain 10 (ADAM10) and ADAM17 with two small-molecule inhibitors, GW280264X and GI254023X, or with siRNA significantly reduced basal and TNFα-induced cell-surface EMCN cleavage. Rele...
Source: Journal of Biological Chemistry - May 7, 2020 Category: Chemistry Authors: Jinling Yang, Michelle E. LeBlanc, Issahy Cano, Kahira L. Saez-Torres, Magali Saint-Geniez, Yin-Shan Ng, Patricia A. D'Amore Tags: Glycobiology and Extracellular Matrices Source Type: research

ASAP Binding Dynamics of siRNA with Selected Lipopeptides: A Computer-Aided Study of the Effect of Lipopeptides ’ Functional Groups and Stereoisomerism
Journal of Chemical Theory and ComputationDOI: 10.1021/acs.jctc.9b01261
Source: Journal of Chemical Theory and Computation - May 6, 2020 Category: Chemistry Authors: Evangelia Pantatosaki* † and George K. Papadopoulos*†‡ Source Type: research

Dual targeting RNA nanoparticles for efficient delivery of polymeric siRNA to cancer cells
Chem. Commun., 2020, Accepted Manuscript DOI: 10.1039/D0CC01848A, CommunicationTaehyung Kim, Hana Hyun, Roun Heo, Keonwook Nam, Kyungjik Yang, Young Min Kim, Yoon Suk Lee, Jae Yoon An, Jae Hyung Park, KI YOUNG CHOI, Young Hoon Roh A new dual-targeting polymeric siRNA nanoparticle (Dual-PSNP) was developed via multiple processes; rolling circle transcription, condensation, electrostatic deposition, and click chemistry. The Dual-PSNP showed significantly improved cancer specific intracellular delivery,... The content of this RSS Feed (c) The Royal Society of Chemistry
Source: RSC - Chem. Commun. latest articles - April 25, 2020 Category: Chemistry Authors: Taehyung Kim Source Type: research

The mitochondrial protein PGAM5 suppresses energy consumption in brown adipocytes by repressing expression of uncoupling protein 1 Metabolism
Accumulating evidence suggests that brown adipose tissue (BAT) is a potential therapeutic target for managing obesity and related diseases. PGAM family member 5, mitochondrial serine/threonine protein phosphatase (PGAM5), is a protein phosphatase that resides in the mitochondria and regulates many biological processes, including cell death, mitophagy, and immune responses. Because BAT is a mitochondria-rich tissue, we have hypothesized that PGAM5 has a physiological function in BAT. We previously reported that PGAM5-knockout (KO) mice are resistant to severe metabolic stress. Importantly, lipid accumulation is suppressed i...
Source: Journal of Biological Chemistry - April 23, 2020 Category: Chemistry Authors: Sho Sugawara, Yusuke Kanamaru, Shiori Sekine, Lila Maekawa, Akinori Takahashi, Tadashi Yamamoto, Kengo Watanabe, Takao Fujisawa, Kazuki Hattori, Hidenori Ichijo Tags: Cell Biology Source Type: research

Molecules, Vol. 25, Pages 1994: Nanoparticle-Mediated Gene Silencing for Sensitization of Lung Cancer to Cisplatin Therapy
M. Merkel Platinum-based chemotherapy remains a mainstay treatment for the management of advanced non-small cell lung cancer. A key cellular factor that contributes to sensitivity to platinums is the 5′-3′ structure-specific endonuclease excision repair cross-complementation group 1 (ERCC1)/ xeroderma pigmentosum group F (XPF). ERCC1/XPF is critical for the repair of platinum-induced DNA damage and has been the subject of intense research efforts to identify small molecule inhibitors of its nuclease activity for the purpose of enhancing patient response to platinum-based chemotherapy. As an ...
Source: Molecules - April 23, 2020 Category: Chemistry Authors: Daniel P. Feldmann Joshua Heyza Christoph M. Zimmermann Steve M. Patrick Olivia M. Merkel Tags: Brief Report Source Type: research

Correction: A dual druggable genome-wide siRNA and compound library screening approach identifies modulators of parkin recruitment to mitochondria. Additions and Corrections
VOLUME 295 (2020) PAGES 3285–3300An incorrect graph was used in Fig. 5C. This error has now been corrected. Additionally, some of the statistics reported in the legend and text referring to Fig. 5C were incorrect. The F statistics for Fig. 5C should state Fken(3,16) = 7.454, p
Source: Journal of Biological Chemistry - April 23, 2020 Category: Chemistry Authors: Helen L. Scott, Nicola Buckner, Francesc Fernandez-Albert, Elisa Pedone, Lorena Postiglione, Gongyu Shi, Nicholas Allen, Liang-Fong Wong, Lorenzo Magini, Lucia Marucci, Gregory A. O'Sullivan, Sarah Cole, Justin Powell, Peter Maycox, James B. Uney Tags: Additions and Corrections Source Type: research