المؤلفون: Zilong Ren, Lin Ma, Min Zhang, Xiafan Xu, Chunlan Du

المصدر: ACS Omega
ACS Omega, Vol 6, Iss 16, Pp 10859-10865 (2021)

مصطلحات موضوعية: chemistry.chemical_classification, Conformational change, Circular dichroism, biology, Chemistry, General Chemical Engineering, technology, industry, and agriculture, Substrate (chemistry), General Chemistry, macromolecular substances, Cofactor, Article, Hydrophobic effect, chemistry.chemical_compound, Enzyme, Sodium pyruvate, Lactate dehydrogenase, biology.protein, Biophysics, QD1-999

الوصف: For a better understanding on the interaction between polyethyleneimine (PEI) and proteins, spectroscopic studies including UV-vis absorption, resonance Rayleigh scattering, fluorescence, and circular dichroism were conducted to reveal the conformational change of rabbit muscle lactate dehydrogenase (rmLDH) and related to the bioactivity of the enzyme. Regardless of the electrostatic repulsion, PEI could bind on the surface of rmLDH, a basic protein, via hydrogen binding of the dense amine groups and hydrophobic interaction of methyl groups. The competitive binding by PEI led to a reduction of the binding efficiency of rmLDH toward β-nicotinamide adenine dinucleotide, the coenzyme, and sodium pyruvate, the substrate. However, the complex formation with PEI induced a less ordered conformation and an enhanced surface hydrophobicity of rmLDH, facilitating the turnover of the enzyme and generally resulting in an increased activity. PEI of higher molecular weight was more efficient to induce alteration in the conformation and catalytic activity of the enzyme.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce97445409c87cbd05630bb1c6db950bTest
http://europepmc.org/articles/PMC8153759Test

المؤلفون: Rui Tong, Zeqing Huang, Jianli Hao, Weiqing Zhang

المصدر: ACS Omega
ACS Omega, Vol 6, Iss 8, Pp 5471-5478 (2021)

مصطلحات موضوعية: chemistry.chemical_classification, Reactive oxygen species, General Chemical Engineering, General Chemistry, Glutathione, Pharmacology, medicine.disease_cause, Article, chemistry.chemical_compound, Chemistry, chemistry, Lactate dehydrogenase, medicine, Febuxostat, Interleukin 8, Propofol, Cytotoxicity, QD1-999, Oxidative stress, medicine.drug

الوصف: Background and purpose: A high risk of brain injury has been reported with the usage of general anesthetics such as propofol in infants. Experimental data indicated that oxidative stress and inflammation are involved in the neurotoxicity induced by propofol. Febuxostat is a novel anti-gout agent recently reported to exert an anti-inflammatory effect. The present study aims to investigate the protective property of febuxostat against the cytotoxicity of propofol in brain endothelial cells as well as the underlying preliminary mechanism. Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was utilized to screen the optimized incubation concentration of febuxostat. bEnd.3 brain endothelial cells were stimulated with 2% propofol in the presence or absence of febuxostat (10, 20 μM) for 24 h. The lactate dehydrogenase (LDH) release assay was conducted to detect cytotoxicity. The reactive oxygen species (ROS) levels were evaluated using dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining, and the concentration of reduced glutathione (GSH) was determined using a commercial kit. The expressions of TNF-α, IL-6, IL-12, CXCL-1, PDPN, CXCL8, VCAM-1, and E-selectin were determined using a quantitative real-time polymerase chain reaction (qRT-PCR) and an enzyme-linked immunosorbent assay (ELISA). Western blot and qRT-PCR were utilized to determine the expressions of COX-2 and KLF6. The production of PGE2 was evaluated by ELISA. Results: First, increased LDH release induced by propofol was significantly suppressed by febuxostat. The oxidative stress (elevated ROS levels and decreased GSH level) induced by propofol was alleviated by febuxostat. Second, the upregulated inflammatory factors (TNF-α, IL-6, and IL-12), pro-inflammatory chemokines (CXCL-1, PDPN, and CXCL8), adhesion molecules (VCAM-1 and E-selectin), and inflammatory mediators (COX-2 and PGE2) induced by propofol were greatly downregulated by febuxostat. Lastly, the expression of KLF6 was significantly suppressed by propofol but greatly elevated by febuxostat. Conclusion: Febuxostat prevented the cytotoxicity of propofol in brain endothelial cells by alleviating oxidative stress and inflammatory response through KLF6.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ed8577683c40b8d652fbb9770cf48b0bTest
http://europepmc.org/articles/PMC7931401Test

المؤلفون: John Knight, Alexandre Caron, Jayakumar Surendradoss, Oliver Chong, David A. Powell, Joyce Wu, Valerie Dumais, Aaron H. Graff, Samuel Gaudreault, Ding Jinyue, Renata Oballa, Andrew T. King, Tim Tang, Rajesh Gumpena, Jennifer H Cox, W. Todd Lowther, Marc-Olivier Boily

المصدر: ACS Med Chem Lett

مصطلحات موضوعية: Drug, education.field_of_study, Chemistry, media_common.quotation_subject, Lactate dehydrogenase A, Organic Chemistry, Endogeny, medicine.disease, Biochemistry, In vitro, Oxalate, Primary hyperoxaluria, chemistry.chemical_compound, In vivo, Drug Discovery, medicine, education, IC50, media_common

الوصف: [Image: see text] Both glycolate oxidase (GO) and lactate dehydrogenase A (LDHA) influence the endogenous synthesis of oxalate and are clinically validated targets for treatment of primary hyperoxaluria (PH). We investigated whether dual inhibition of GO and LDHA may provide advantage over single agents in treating PH. Utilizing a structure-based drug design (SBDD) approach, we developed a series of novel, potent, dual GO/LDHA inhibitors. X-ray crystal structures of compound 15 bound to individual GO and LDHA proteins validated our SBDD strategy. Dual inhibitor 7 demonstrated an IC(50) of 88 nM for oxalate reduction in an Agxt-knockdown mouse hepatocyte assay. Limited by poor liver exposure, this series of dual inhibitors failed to demonstrate significant PD modulation in an in vivo mouse model. This work highlights the challenges in optimizing in vivo liver exposures for diacid containing compounds and limited benefit seen with dual GO/LDHA inhibitors over single agents alone in an in vitro setting.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7d2657ef881efc3975d21c823aaea40eTest
https://europepmc.org/articles/PMC8274068Test/

المؤلفون: Kimichi Suzuki, Satoshi Maeda, Keiji Morokuma

المصدر: ACS Omega, Vol 4, Iss 1, Pp 1178-1184 (2019)
ACS Omega

مصطلحات موضوعية: Quantitative Biology::Biomolecules, Chemistry, General Chemical Engineering, Substrate (chemistry), L-Lactate dehydrogenase, Dehydrogenase, General Chemistry, Energy minimization, Molecular mechanics, Chemical reaction, Article, Quantitative Biology::Subcellular Processes, lcsh:Chemistry, Crystallography, lcsh:QD1-999, Structural transition, Reaction path

الوصف: The mechanism of l-lactate generation from pyruvate by l-lactate dehydrogenase (LDH) from the rabbit muscle was studied theoretically by the multistructural microiteration (MSM) method combined with the quantum mechanics/molecular mechanics (QM/MM)–ONIOM method, where the MSM method describes the MM environment as a weighted average of multiple different structures that are fully relaxed during geometry optimization or a reaction path calculation for the QM part. The results showed that the substrate binding and product states were stabilized only in the open-loop conformation of LDH and the reaction occurred in the closed-loop conformation. In other words, before and after the chemical reaction, a large-scale structural transition from the open-loop conformation to the closed-loop conformation and vice versa occurred. The closed-loop conformation stabilized the transition state of the reaction. In contrast, the open-loop conformation stabilized the substrate binding and final states. In other words, the closed- to open-loop transition at the substrate binding state urges capture of the substrate molecule, the subsequent open- to closed-loop transition promotes the product generation, and the final closed- to open-loop transition at the final state prevents the reverse reaction going back to the substrate binding state. It is thus suggested that the exchange of stability between the closed- and open-loop conformations at different states promotes the catalytic cycle.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a931a9d51514e60a2993faaf6943f2a9Test
https://doaj.org/article/3bf1283163c3417a9f153ff53d025f1dTest

المؤلفون: S.A. Angermayr, Klaas J. Hellingwerf

المساهمون: Molecular Microbial Physiology (SILS, FNWI)

المصدر: The journal of Physical Chemistry. B, 117(38), 11169-11175. American Chemical Society

مصطلحات موضوعية: Cyanobacteria, Photobioreactor, Biomass, Photosynthesis, Bioplastic, chemistry.chemical_compound, Bacterial Proteins, Lactococcus, Materials Chemistry, Lactic Acid, Physical and Theoretical Chemistry, Promoter Regions, Genetic, chemistry.chemical_classification, L-Lactate Dehydrogenase, biology, Carbon Dioxide, biology.organism_classification, Surfaces, Coatings and Films, Lactic acid, Enzyme, chemistry, Biofuel, Biofuels, Biochemical engineering

الوصف: Oxygenic photosynthesis will have a key role in a sustainable future. It is therefore significant that this process can be engineered in organisms such as cyanobacteria to construct cell factories that catalyze the (sun)light-driven conversion of CO2 and water into products like ethanol, butanol, or other biofuels or lactic acid, a bioplastic precursor, and oxygen as a byproduct. It is of key importance to optimize such cell factories to maximal efficiency. This holds for their light-harvesting capabilities under, for example, circadian illumination in large-scale photobioreactors. However, this also holds for the "dark" reactions of photosynthesis, that is, the conversion of CO2, NADPH, and ATP into a product. Here, we present an analysis, based on metabolic control theory, to estimate the optimal capacity for product formation with which such cyanobacterial cell factories have to be equipped. Engineered l-lactic acid producing Synechocystis sp. PCC6803 strains are used to identify the relation between production rate and enzymatic capacity. The analysis shows that the engineered cell factories for l-lactic acid are fully limited by the metabolic capacity of the product-forming pathway. We attribute this to the fact that currently available promoter systems in cyanobacteria lack the genetic capacity to a provide sufficient expression in single-gene doses.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2505ce6de24156c1a8c96f0ab78f06b0Test
https://hdl.handle.net/11245/1.395894Test

المؤلفون: Patrick Kestemont, Martine Raes, Jennifer Dorts, Marc Dieu, Frédéric Silvestre

المصدر: Journal of Proteome Research. 10(2):470-478

مصطلحات موضوعية: Gill, Fish Proteins, Gills, Male, Proteomics, Proteome, Biochemistry, chemistry.chemical_compound, Tandem Mass Spectrometry, Lactate dehydrogenase, Cytochrome c oxidase, Citrate synthase, Animals, Gobio, Electrophoresis, Gel, Two-Dimensional, chemistry.chemical_classification, biology, Dose-Response Relationship, Drug, Fishes, General Chemistry, Environmental exposure, Environmental Exposure, biology.organism_classification, Molecular biology, Enzyme, chemistry, Liver, Toxicity, biology.protein, Female, Sentinel Surveillance, Metabolic Networks and Pathways, Cadmium, Chromatography, Liquid

الوصف: The present study aimed at evaluating the toxicity of short-term cadmium (Cd) exposure in the European bullhead Cottus gobio, a candidate sentinel species. Several enzymatic activity assays (citrate synthase, cytochrome c oxidase, and lactate dehydrogenase) were carried out in liver and gills of fish exposed to 0.01, 0.05, 0.25, and 1 mg Cd/L for 4 days. Exposure to high Cd concentrations significantly altered the activity of these enzymes either in liver and/or in gills. Second, 2D-DIGE technique was used to identify proteins differentially expressed in tissues of fish exposed to either 0.01 or 1 mg Cd/L. Fifty-four hepatic protein spots and 37 branchial protein spots displayed significant changes in abundance in response to Cd exposure. A total of 26 and 12 different proteins were identified using nano LC-MS/MS in liver and gills, respectively. The identified differentially expressed proteins can be categorized into diverse functional classes, related to metabolic process, general stress response, protein fate, and cell structure for instance. This work provides new insights into the biochemical and molecular events in Cd-induced toxicity in fish and suggests that further studies on the identified proteins could provide crucial information to better understand the mechanisms of Cd toxicity in fish.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1061818ad3a1fe146665fee2bb3ca0f1Test
https://researchportal.unamur.be/en/publications/69837c68-297d-4c70-bfe8-c4feac2ca2e2Test

المؤلفون: Joshua J. Stapleton, Stacey L. Dean, Christine D. Keating

المصدر: Langmuir

مصطلحات موضوعية: Silicon, Silicon dioxide, Surface Properties, Inorganic chemistry, Nanowire, Nanoparticle, chemistry.chemical_element, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Urethane, Article, chemistry.chemical_compound, Adsorption, Electrochemistry, Chromates, Animals, Nanotechnology, heterocyclic compounds, General Materials Science, Organic Chemicals, Spectroscopy, Silanes, L-Lactate Dehydrogenase, Nanowires, Spectrum Analysis, Imidazoles, Surfaces and Interfaces, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Silicon Dioxide, 0104 chemical sciences, chemistry, Chemical engineering, Metals, Immunoglobulin G, Alkoxide, Functional group, Nanoparticles, 0210 nano-technology

الوصف: Organically modified silica coatings were prepared on metal nanowires using a variety of silicon alkoxides with different functional groups (i.e., carboxyl groups, polyethylene oxide, cyano, dihydroimidazole, and hexyl linkers). Organically modified silicas were deposited onto the surface of 6-μm-long, ∼300-nm-wide, cylindrical metal nanowires in suspension by the hydrolysis and polycondensation of silicon alkoxides. Syntheses were performed at several ratios of tetraethoxysilane to an organically modified silicon alkoxide to incorporate desired functional groups into thin organosilica shells on the nanowires. These coatings were characterized using transmission electron microscopy, X-ray photoelectron spectroscopy, and infrared spectroscopy. All of the organically modified silicas prepared here were sufficiently porous to allow the removal of the metal nanowire cores by acid etching to form organically modified silica nanotubes. Additional functionality provided to the modified silicas as compared to unmodified silica prepared using only tetraethoxysilane precursors was demonstrated by chromate adsorption on imidazole-containing silicas and resistance to protein adsorption on polyethyleneoxide-containing silicas. Organically modified silica coatings on nanowires and other nano- and microparticles have potential application in fields such as biosensing or nanoscale therapeutics due to the enhanced properties of the silica coatings, for example, the prevention of biofouling.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6b6bc4822bee837204e06dbfb6ccac9bTest
http://europepmc.org/articles/PMC2938830Test

المؤلفون: Khuloud T. Al-Jamal, Alberto Bianco, Sophie Lanone, Maurizio Prato, Cyrill Bussy, Jorge Boczkowski, Kostas Kostarelos

المساهمون: Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Bussy, Cyrill, Al Jamal, Khuloud T., Boczkowski, Jorge, Lanone, Sophie, Prato, Maurizio, Bianco, Alberto, Kostarelos, Kostas

المصدر: ACS Nano
ACS Nano, American Chemical Society, 2015, 9 (8), pp.7815-7830. ⟨10.1021/acsnano.5b02358⟩

مصطلحات موضوعية: implant, Cell, General Physics and Astronomy, Gene Expression, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Engineering (all), Drug Delivery Systems, Cytotoxic T cell, General Materials Science, Cytotoxicity, nanomaterials, CD11b Antigen, Microglia, biology, General Engineering, brain, carbon nanotubes, nanotoxicology, Materials Science (all), Physics and Astronomy (all), chemistry, toxicity, Cell biology, Frontal Lobe, secretion, medicine.anatomical_structure, Integrin alpha M, Organ Specificity, nanomaterial, Intracellular, Chimie/Chimie thérapeutique, drug effects, metabolism, Materials science, Cell Survival, Central nervous system, Primary Cell Culture, Nanotechnology, Nitric Oxide, cytology, Fetus, Glial Fibrillary Acidic Protein, medicine, Animals, carbon nanotube, Brain Chemistry, L-Lactate Dehydrogenase, Nanotubes, Carbon, genetics, Coculture Techniques, Corpus Striatum, CD11c Antigen, Rats, nervous system, Nanotoxicology, Astrocytes, Culture Media, Conditioned, biology.protein, pharmacology, Biomarkers

الوصف: Surface tunability and their ability to translocate plasma membranes make chemically functionalized carbon nanotubes (f-CNTs) promising intracellular delivery systems for therapeutic or diagnostic purposes in the central nervous system (CNS). The present study aimed to determine the biological impact of different types of multiwalled CNTs (MWNTs) on primary neuronal and glial cell populations isolated from fetal rat frontal cortex (FCO) and striatum (ST). Neurons from both brain regions were generally not affected by exposure to MWNTs as determined by a modified LDH assay. In contrast, the viability of mixed glia was reduced in ST-derived mixed glial cultures, but not in FCO-derived ones. Cytotoxicity was independent of MWNT type or dose, suggesting an inherent sensitivity to CNTs. Characterization of the cell populations in mixed glial cultures prior to nanotube exposure showed higher number of CD11b/c positive cells in the ST-derived mixed glial cultures. After exposure to MWNTs, CNT were uptaken more effectively by CD11b/c positive cells (microglia), compared to GFAP positive cells (astrocytes). When exposed to conditioned media from microglia enriched cultures exposed to MWNTs, ST-derived glial cultures secreted more NO than FCO-derived cells. These results suggested that the more significant cytotoxic response obtained from ST-derived mixed glia cultures was related to the higher number of microglial cells in this brain region. Our findings emphasize the role that resident macrophages of the CNS play in response to nanomaterials and the need to thoroughly investigate the brain region-specific effects toward designing implantable devices or delivery systems to the CNS. journal article research support, non-u.s. gov't 2015 Aug 25 2015 06 26 imported

وصف الملف: STAMPA

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1761bb582a10a756e89028f4adad6d91Test

المؤلفون: María Vallet-Regí, Alejandro Baeza, María Rocío Villegas

المصدر: E-Prints Complutense. Archivo Institucional de la UCM
instname
E-Prints Complutense: Archivo Institucional de la UCM
Universidad Complutense de Madrid

مصطلحات موضوعية: Proteases, Materials science, Cell Survival, Polymers, Metal Nanoparticles, Bone Neoplasms, Nanotechnology, Nanocapsules, Drug Delivery Systems, Microscopy, Electron, Transmission, Cell Line, Tumor, Neoplasms, medicine, Animals, Humans, General Materials Science, Collagenases, Drug Carriers, Osteosarcoma, Materiales, L-Lactate Dehydrogenase, Proteolytic enzymes, Hydrogen-Ion Concentration, Mesoporous silica, Silicon Dioxide, Química inorgánica, Enzymes, Extracellular Matrix, Rats, Cross-Linking Reagents, Nanomedicine, Microscopy, Fluorescence, Drug delivery, Collagenase, Biophysics, Nanoparticles, Collagen, Nanocarriers, medicine.drug

الوصف: Poor penetration of drug delivery nanocarriers within dense extracellular matrices constitutes one of the main liabilities of current nanomedicines. The conjugation of proteolytic enzymes on the nanoparticle surface constitutes an attractive alternative. However, the scarce resistance of these enzymes against the action of proteases or other aggressive agents present in the bloodstream strongly limits their application. Herein, a novel nanodevice able to transport proteolytic enzymes coated with an engineered pH-responsive polymeric is presented. This degradable coat protects the housed enzymes against proteolytic attack at the same time that it triggers their release under mild acidic conditions, usually present in many tumoral tissues. These enzyme nanocapsules have been attached on the surface of mesoporous silica nanoparticles, as nanocarrier model, showing a significatively higher penetration of the nanoparticles within 3D collagen matrices which housed human osteosarcoma cells (HOS). This strategy can improve the therapeutic efficacy of the current nanomedicines, allowing a more homogeneous and deeper distribution of the therapeutic nanosystems in cancerous tissues.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5733859ce5e6ea66d09d83c0ee1c4117Test

المؤلفون: M. Isabel Escribano, Oscar Goñi, Irene Romero, Carmen Merodio, Carlos Fernandez-Caballero, M. Teresa Sanchez-Ballesta

المصدر: Digital.CSIC. Repositorio Institucional del CSIC
instname

مصطلحات موضوعية: Antifungal, medicine.drug_class, Molecular Sequence Data, Class I chitinase, Gene Expression, Berry, Biology, Cryoprotective Agents, Freezing, Gene expression, Botany, Escherichia coli, medicine, Vitis, Amino Acid Sequence, Vitis vinifera, Plant Proteins, L-Lactate Dehydrogenase, Chitinases, Table grape, General Chemistry, Recombinant Proteins, Fungicides, Industrial, Fruit, Chitinase, biology.protein, sense organs, General Agricultural and Biological Sciences, Sequence Alignment

الوصف: Gene expression of a class I chitinase (Vcchit1b) in the skin of table grapes was analyzed as a molecular marker for changes induced at low temperature and also to study the effect of high CO2 levels modulating transcript levels at 0 °C. An active recombinant VcCHIT1b was overexpressed in Escherichia coli, and as the protein was produced as insoluble inclusion bodies, it was solubilized and refolded. The purified recombinant chitinase showed an optimum pH of 6.0 and a temperature of 50 °C, retaining activity at 0 and -10 °C. Purified chitinase exerted in vitro antifungal activity against Botrytis cinerea. Furthermore, recombinant chitinase was able to cryoprotect lactate dehydrogenase against freeze/thaw inactivation. However, the recombinant VcCHIT1b did not show any antifreeze activity when the thermal hysteresis activity was measured using differential scanning calorimetry. © 2009 American Chemical Society.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::463463300d239747c50b8be011456292Test
http://hdl.handle.net/10261/77736Test