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https://www.readbyqxmd.com/read/28918503/coq0-induced-mitochondrial-ptp-opening-triggers-apoptosis-via-ros-mediated-vdac1-upregulation-in-hl-60-leukemia-cells-and-suppresses-tumor-growth-in-athymic-nude-mice-xenografted-nude-mice
#1
You-Cheng Hseu, Varadharajan Thiyagarajan, Ting-Tsz Ou, Hsin-Ling Yang
Coenzyme Q (CoQ) analogs with variable numbers of isoprenoid units have been demonstrated as anticancer and antioxidant/pro-oxidant molecules. This study examined the in vitro and in vivo antitumor and apoptosis activities of CoQ0 (2,3-dimethoxy-5-methyl-1,4-benzoquinone, zero isoprenoid side-chains) through upregulation of the Voltage-dependent anion channel 1 (VDAC1) signaling pathway on human promyelocytic leukemia. CoQ0 (0-40 μg/mL) treatment significantly reduced HL-60 cell viability, and up-regulated mitochondrial VDAC1 expression...
September 16, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28918449/immunochemical-study-of-the-effect-of-f2glc-on-glycogen-synthase-translocation-and-glycogen-synthesis-in-isolated-rat-hepatocytes
#2
J M Fernández-Novell, M Díaz-Lobo
The compound 2-deoxy-2-fluoro-α-D-glucopyranosyl fluoride (F2Glc), which is a nonmetabolized superior glucose analogue, is a potent inhibitor of glycogen phosphorylase and pharmacological properties are reported. Glycogen phosphorylase (GP) and glycogen synthase (GS) are responsible of the degradation and synthesis, respectively, of glycogen which is a polymer of glucose units that provides a readily available source of energy in mammals. GP and GS are two key enzymes that modulate cellular glucose and glycogen levels; therefore, these proteins are suggested as potential targets for the treatment of diseases related to glycogen metabolism disorders...
September 16, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28918276/phytoremediation-of-soil-co-contaminated-with-cd-and-bde-209-using-hyperaccumulator-enhanced-by-am-fungi-and-surfactant
#3
Hui Li, Xing Li, Lei Xiang, Hai Ming Zhao, Yan Wen Li, Quan Ying Cai, Li Zhu, Ce Hui Mo, Ming Hung Wong
Pot experiments were conducted to investigate the uptake and translocation of both Cd and decabromodiphenyl ether (BDE-209) in Solanum nigrum, under the treatments of two arbuscular mycorrhizal fungi [AMF, Funneliformis mosseae (FM) and Rhizophagus intraradices (RI)] and surfactant β-cyclodextrin (β-CD). Results showed that S. nigrum treated with either FM or β-CD significantly elevated shoot biomass and Cd concentrations and contents in shoots. The concentrations of BDE-209 in shoots and the dissipation and debromination efficiencies of BDE-209 in soil were significantly enhanced in S...
September 14, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28918189/effects-of-temperature-and-peg-grafting-density-on-the-translocation-of-pegylated-nanoparticles-across-asymmetric-lipid-membrane
#4
Zuoheng Zhang, Xubo Lin, Ning Gu
Plasma membrane internalization of nanoparticles (NPs) is important for their biomedical applications such as drug-delivery carriers. On one hand, in order to improve their half-life in circulation, PEGylation has been widely used. However, it may hinder the NPs' membrane internalization ability. On the other hand, higher temperature could enhance the membrane permeability and may affect the NPs' ability to enter into or exit from cells. To make full use of their advantages, we systematically investigated the effects of temperature and PEG density on the translocation of PEGylated nanoparticles across the plasma asymmetric membrane of eukaryotic cells, using near-atom level coarse-grained molecular dynamics simulations...
September 6, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28918037/a-novel-pak1-atf2-mir-132-signaling-axis-is-involved-in-the-hematogenous-metastasis-of-gastric-cancer-cells
#5
Funan Liu, Zhenguo Cheng, Xiaodong Li, Yanshu Li, Hongyan Zhang, Jiabin Li, Furong Liu, Huimian Xu, Feng Li
We, along with others, have shown previously that P21-activated kinase 1 (Pak1) plays a pivotal role in gastric cancer progression and metastasis. However, whether Pak1 controls gastric cancer metastasis by regulating microRNAs (miRNAs) has never been explored. Here, we report a novel mechanism of Pak1 in tumor metastasis. A detailed examination revealed that Pak1 interacts with and phosphorylates the serine 62 residue of ATF2 and then blocks its translocation into the nucleus. We also confirmed that ATF2 binds to the promoter of miR-132 and tightly regulates its transcription, thus explaining the regulatory mechanism of miR-132 by Pak1...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918013/mir-135b-stimulates-osteosarcoma-recurrence-and-lung-metastasis-via-notch-and-wnt-%C3%AE-catenin-signaling
#6
Hua Jin, Song Luo, Yun Wang, Chang Liu, Zhenghao Piao, Meng Xu, Wei Guan, Qing Li, Hua Zou, Qun-You Tan, Zhen-Zhou Yang, Yan Wang, Dong Wang, Cheng-Xiong Xu
Cancer stem cells (CSCs) play an important role in osteosarcoma (OS) metastasis and recurrence, and both Wnt/β-catenin and Notch signaling are essential for the development of the biological traits of CSCs. However, the mechanism that underlies the simultaneous hyperactivation of both Wnt/β-catenin and Notch signaling in OS remains unclear. Here, we report that expression of miR-135b correlates with the overall and recurrence-free survival of OS patients, and that miR-135b has an activating effect on both Wnt/β-catenin and Notch signaling...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917548/volar-capsular-release-after-distal-radius%C3%A2-fractures
#7
Robin N Kamal, David S Ruch
PURPOSE: Loss of full wrist range of motion is common after treatment of distal radius fractures. Loss of wrist extension limiting functional activities, although uncommon, can occur after volar plating of distal radius fractures. Unlike other joints in which capsular release is a common form of treatment for stiffness, this has been approached with caution in the wrist owing to concerns for carpal instability. We tested the null hypothesis that hardware removal and open volar capsular release would not lead to improved upper extremity-specific patient-reported outcome (Disabilities of the Arm, Shoulder, and Hand [DASH] questionnaire)...
September 14, 2017: Journal of Hand Surgery
https://www.readbyqxmd.com/read/28917060/lipids-and-ions-traverse-the-membrane-by-the-same-physical-pathway-in-the-nhtmem16-scramblase
#8
Tao Jiang, Kuai Yu, H Criss Hartzell, Emad Tajkhorshid
From bacteria to mammals, different phospholipid species are segregated between the inner and outer leaflets of the plasma membrane by ATP-dependent lipid transporters. Disruption of this asymmetry by ATP-independent phospholipid scrambling is important in cellular signaling, but its mechanism remains incompletely understood. Using MD simulations coupled with experimental assays, we show that the surface hydrophilic transmembrane cavity exposed to the lipid bilayer on the fungal scramblase nhTMEM16 serves as the pathway for both lipid translocation and ion conduction across the membrane...
September 16, 2017: ELife
https://www.readbyqxmd.com/read/28917050/preparation-of-selenocysteine-containing-forms-of-human-selenok-and-selenos
#9
Zhengqi Zhang, Jun Liu, Sharon Rozovsky
Selenoprotein K (SELENOK) and Selenoprotein S (SELENOS) are the members of the endoplasmic-reticulum-associated degradation (ERAD) complex, which is responsible for translocating misfolded proteins from the endoplasmic reticulum (ER) to the cytosol for degradation. Besides its involvement in the ERAD, SELENOK was shown to bind and stabilize the palmitoyl transferase DHHC6, and thus contributes to palmitoylation. SELENOK and SELENOS reside in the ER membrane by the way of a single transmembrane helix. Both contain an intrinsically disordered region with a selenocysteine (Sec) located one or two residues away from the C-terminus...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28916545/serologic-evidence-of-gut-driven-systemic-inflammation-in-juvenile-idiopathic-arthritis
#10
Lampros Fotis, Nurmohammad Shaikh, Kevin W Baszis, Charles M Samson, Raffi Lev-Tzion, Anthony R French, Phillip I Tarr
OBJECTIVE: Accumulating evidence links juvenile idiopathic arthritis (JIA) to nonhost factors such as gut microbes. We hypothesize that children with new-onset JIA have increased intestinal bacterial translocation and circulating lipopolysaccharide (LPS). METHODS: We studied systemic treatment-naive patients with JIA [polyarticular JIA, n = 22, oligoarticular JIA, n = 31, and spondyloarthropathies (SpA), n = 16], patients with established inflammatory bowel disease-related arthritis (IBD-RA, n = 11), and 34 healthy controls...
September 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28916481/identification-of-2-4-dihydroxy-5-pyrimidinyl-imidothiocarbomate-as-a-novel-inhibitor-to-y-box-binding-protein-1-yb-1-and-its-therapeutic-actions-against-breast-cancer
#11
Vinoth Prasanna Gunasekaran, Kumari Nishi, Dakshinamurthy Sivakumar, Thirunavukkarasu Sivaraman, Ganeshan Mathan
In spite of advances in breast cancer treatment and early diagnosis, drug toxicity, cancer relapse, multidrug resistance and metastasis are the major impediment to the developments of efficient drugs. However, unique druggable targets of cancer cells distinct from the normal cells provide new rationale in cancer treatment. Previous reports clearly emphasize the differential expression and localization of Y box binding protein-1 (YB-1) between normal breast tissues and different stages of breast cancer. Y box binding protein-1 is DNA as well as RNA binding protein involved in transcription and translation regulation of various proteins involved in cancer progression, apoptosis, cell cycle, epithelial to mesenchymal transition (EMT) and drug resistance...
September 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28916473/down-regulation-of-nox2-activity-in-phagocytes-mediated-by-atm-kinase-dependent-phosphorylation
#12
Sylvain Beaumel, Antoine Picciocchi, Franck Debeurme, Corinne Vives, Anne-Marie Hesse, Myriam Ferro, Didier Grunwald, Heather Stieglitz, Pahk Thepchatri, Susan M E Smith, Franck Fieschi, Marie José Stasia
NADPH oxidases (NOX) have many biological roles, but their regulation to control production of potentially toxic ROS molecules remains unclear. A previously identified insertion sequence of 21 residues (called NIS) influences NOX activity, and its predicted flexibility makes it a good candidate for providing a dynamic switch controlling the NOX active site. We constructed NOX2 chimeras in which NIS had been deleted or exchanged with those from other NOXs (NIS1, 3 and 4). All contained functional heme and were expressed normally at the plasma membrane of differentiated PLB-985 cells...
September 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28916279/the-role-of-il-6-released-from-pulmonary-epithelial-cells-in-diesel-ufp-induced-endothelial-activation
#13
Rossella Bengalli, Eleonora Longhin, Sara Marchetti, Maria C Proverbio, Cristina Battaglia, Marina Camatini
Diesel exhaust particles (DEP) and their ultrafine fraction (UFP) are known to induce cardiovascular effects in exposed subjects. The mechanisms leading to these outcomes are still under investigation, but the activation of respiratory endothelium is likely to be involved. Particles translocation through the air-blood barrier and the release of mediators from the exposed epithelium have been suggested to participate in the process. Here we used a conditioned media in vitro model to investigate the role of epithelial-released mediators in the endothelial cells activation...
September 12, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28916191/%C3%AE-the-hydro-alcoholic-extracts-of-sardinian-wild-thistles-onopordum-spp-inhibit-tnf%C3%AE-induced-il-8-secretion-and-nf-%C3%AE%C2%BAb-pathway-in-human-gastric-epithelial-ags-cells
#14
Arianna Marengo, Marco Fumagalli, Cinzia Sanna, Andrea Maxia, Stefano Piazza, Cecilia Cagliero, Patrizia Rubiolo, Enrico Sangiovanni, Mario Dell'Agli
ETHNOPHARMACOLOGICAL RELEVANCE: Thistles species (Family: Compositae) are traditionally used in the Mediterranean area, particularly in Sardinia. They are usually gathered from the wild and used for both food and therapeutic purposes, including gastrointestinal disorders. AIM OF THE STUDY: This work aims to evaluate the anti-inflammatory activity of eight wild thistles from Sardinia, in an in vitro model of gastric inflammation, and to identify the major active compounds in the extracts...
September 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28915917/translocation-of-molecular-chaperones-to-the-titin-springs-is-common-in-skeletal-myopathy-patients-and-affects-sarcomere-function
#15
Andreas Unger, Lisa Beckendorf, Pierre Böhme, Rudolf Kley, Marion von Frieling-Salewsky, Hanns Lochmüller, Rolf Schröder, Dieter O Fürst, Matthias Vorgerd, Wolfgang A Linke
Myopathies encompass a wide variety of acquired and hereditary disorders. The pathomechanisms include structural and functional changes affecting, e.g., myofiber metabolism and contractile properties. In this study, we observed increased passive tension (PT) of skinned myofibers from patients with myofibrillar myopathy (MFM) caused by FLNC mutations (MFM-filaminopathy) and limb-girdle muscular dystrophy type-2A due to CAPN3 mutations (LGMD2A), compared to healthy control myofibers. Because the giant protein titin determines myofiber PT, we measured its molecular size and the titin-to-myosin ratio, but found no differences between myopathies and controls...
September 15, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28915816/cramp-deficiency-leads-to-a-pro-inflammatory-phenotype-and-impaired-phagocytosis-after-exposure-to-bacterial-meningitis-pathogens
#16
Eugenia Kress, Julika Merres, Lea-Jessica Albrecht, Sven Hammerschmidt, Thomas Pufe, Simone C Tauber, Lars-Ove Brandenburg
BACKGROUND: Antimicrobial peptides are important components of the host defence with a broad range of functions including direct antimicrobial activity and modulation of inflammation. Lack of cathelin-related antimicrobial peptide (CRAMP) was associated with higher mortality and bacterial burden and impaired neutrophil granulocyte infiltration in a model of pneumococcal meningitis. The present study was designed to characterize the effects of CRAMP deficiency on glial response and phagocytosis after exposure to bacterial stimuli...
September 16, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28915648/synergistic-suppression-of-t-8-21-positive-leukemia-cell-growth-by-combining-oridonin-and-mapk1-erk2-inhibitors
#17
Pavel Spirin, Timofey Lebedev, Natalia Orlova, Alexey Morozov, Nadezhda Poymenova, Sergey E Dmitriev, Anton Buzdin, Carol Stocking, Olga Kovalchuk, Vladimir Prassolov
One of the most common chromosomal translocations in acute myeloid leukemia is t(8;21)(q22;q22), which results in the appearance of abnormal transcripts encoding for the fusion protein RUNX1-ETO. Therefore, this oncoprotein is considered to be a pertinent and promising target for treating t(8;21) leukemia. Previously, we have shown that downregulation of RUNX1-ETO leads to activation of intracellular signaling pathways enhancing cell survival and determined that the protein ERK2 can mediate activation of most of these pathways...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915577/vorinostat-suppresses-hypoxia-signaling-by-modulating-nuclear-translocation-of-hypoxia-inducible-factor-1-alpha
#18
Chao Zhang, Chunzhang Yang, Michael J Feldman, Herui Wang, Ying Pang, Dominic M Maggio, Dongwang Zhu, Cody L Nesvick, Pauline Dmitriev, Petra Bullova, Prashant Chittiboina, Roscoe O Brady, Karel Pacak, Zhengping Zhuang
Histone deacetylase inhibitors (HDACis) are a potent class of tumor-suppressive agents traditionally believed to exert their effects through loosening tightly-wound chromatin resulting in de-inhibition of various tumor suppressive genes. Recent literature however has shown altered intratumoral hypoxia signaling with HDACi administration not attributable to changes in chromatin structure. We sought to determine the precise mechanism of HDACi-mediated hypoxia signaling attenuation using vorinostat (SAHA), an FDA-approved class I/IIb/IV HDACi...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915556/critical-roles-of-smyd2-mediated-%C3%AE-catenin-methylation-for-nuclear-translocation-and-activation-of-wnt-signaling
#19
Xiaolan Deng, Ryuji Hamamoto, Theodore Vougiouklakis, Rui Wang, Yuichiro Yoshioka, Takehiro Suzuki, Naoshi Dohmae, Yo Matsuo, Jae-Hyun Park, Yusuke Nakamura
Accumulation of β-catenin in the nucleus is a hallmark of activation of the Wnt/β-catenin signaling pathway, which drives development of a large proportion of human cancers. However, the mechanism of β-catenin nuclear translocation has not been well investigated. Here we report biological significance of SMYD2-mediated lysine 133 (K133) methylation of β-catenin on its nuclear translocation. Knockdown of SMYD2 attenuates the nuclear localization of β-catenin protein in human cancer cells. Consequently, transcriptional levels of well-known Wnt-signaling molecules, cMYC and CCND1, are significantly reduced...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915104/rift-valley-fever-phlebovirus-nss-protein-core-domain-structure-suggests-molecular-basis-for-nuclear-filaments
#20
Michal Barski, Benjamin Brennan, Ona K Miller, Jane A Potter, Swetha Vijayakrishnan, David Bhella, James H Naismith, Richard M Elliott, Ulrich Schwarz-Linek
Rift Valley fever phlebovirus (RVFV) is a clinically and economically important pathogen increasingly likely to cause widespread epidemics. RVFV virulence depends on the interferon antagonist non-structural protein (NSs), which remains poorly characterized. We identified a stable core domain of RVFV NSs (residues 83-248), and solved its crystal structure, a novel all-helical fold organized into highly ordered fibrils. A hallmark of RVFV pathology is NSs filament formation in infected cell nuclei. Recombinant virus encoding the NSs core domain induced intranuclear filaments, suggesting it contains all essential determinants for nuclear translocation and filament formation...
September 15, 2017: ELife
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