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https://www.readbyqxmd.com/read/30120653/tolfenamic-acid-attenuates-3-nitropropionic-acid-induced-biochemical-alteration-in-mice
#1
Peng Liu, Yinjie Li, Danyang Liu, Xuefei Ji, Tianyan Chi, Lin Li, Libo Zou
Tolfenamic acid (TA), a nonsteroidal anti-inflammatory drug, shows neuroprotective effects and alleviates cognitive deficits in transgenic mouse models of Alzheimer's disease. However, whether TA can prevent the biochemical alterations induced by intraperitoneal injection of 3-nitropropionic acid (3-NP) in mice is still unknown. In this study, the striatal lesion area was measured by 2,3,5-triphenyltetrazolium chloride staining. Glutamate, SDH and ATP levels were tested using colorimetric assay kits. The neuroinflammatory cytokine levels were tested by ELISA kits...
August 17, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/30118564/thylakoids-proteome-modulation-in-pea-plants-grown-at-different-irradiances-a-quantitative-proteomic-profiling-in-a-non-model-organism-aided-by-transcriptomic-data-integration
#2
Pascal Albanese, Marcello Manfredi, Angela Re, Emilio Marengo, Guido Saracco, Cristina Pagliano
Plant thylakoid membranes contain hundreds of proteins closely interplaying to cope with ever-changing environmental conditions. We investigated how Pisum sativum L. (pea) grown at different irradiances optimizes light-use efficiency through the differential accumulation of thylakoid proteins. Thylakoid membranes from plants grown under low (LL), moderate (ML) and high (HL) light intensity were characterized by combining chlorophyll fluorescence measurements with quantitative label-free proteomic analysis. Protein sequences retrieved from available transcriptomic data considerably improved the thylakoid proteome profiling, increasing the quantifiable proteins from 63 to 194...
August 17, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/30116313/effects-of-mulberry-leaf-on-experimental-hyperlipidemia-rats-induced-by-high-fat-diet
#3
Jianbo Huang, Yangpeng Wang, Chao Ying, Lei Liu, Zhaohuan Lou
Hypercholesterolemia is a major risk factor for cardiovascular disease. Mulberry leaf (ML) is a Traditional Chinese Medicine used to treat hyperlipidemia in clinical settings. The aim of the present study was to identify the potential effect and possible target of ML in anti-hypercholesterolemia. Male Sprague-Dawley rats were fed with a high-fat diet and treated with ML for 5 weeks. Blood lipid levels, total cholesterol (TC) and total bile acid (TBA) in the liver and feces were measured to assess the effects of ML on hypercholesterolemia...
August 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/30114704/pci29732-a-bruton-s-tyrosine-kinase-inhibitor-enhanced-the-efficacy-of-conventional-chemotherapeutic-agents-in-abcg2-overexpressing-cancer-cells
#4
Chunlei Ge, Fang Wang, Chaochu Cui, Xiaodong Su, Kenneth Kin Wah To, Xiaokun Wang, Hui Zhang, Xin Song, Liwu Fu
BACKGROUND/AIMS: Multidrug resistance (MDR) induced by the ABC transporter subfamily B member 1 (ABCB1) and subfamilyG member 2 (ABCG2) limits successful cancer chemotherapy and no commercially available MDR modulator is used in the clinic. In the current study, we aimed to investigate the effects of PCI29732 on the enhancement of chemotherapeutic agents. METHODS: Cell cytotoxicity and reversal effect were measured with MTT assay. Additionally, flow cytometry was employed to detect the accumulation and efflux of the drugs...
August 16, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/30113397/the-gcs-sgk1-atp-signaling-pathway-in-spinal-astrocytes-underlied-presurgical-anxiety-induced-postsurgical-hyperalgesia
#5
ZuoXia Zhang, Hao Wu, Yue Liu, XiaoPing Gu, Wei Zhang, ZhengLiang Ma
BACKGROUND: Patients undergoing surgery often feel anxious. Accumulating evidence indicated that presurgical anxiety was related to the more severe postsurgical pain. An animal model was established that exposed Sprague-Dawley rats to a single-prolonged stress (SPS) procedure to induce presurgical anxiety-like behaviors. The experiment revealed that presurgical anxiety not only aggravated but also prolonged postsurgical pain. However, the underlying mechanisms were unknown. METHODS: The rats in group C + Cort, group I + Cort, group A + Cort, and group AI + Cort were injected with corticosterone...
August 14, 2018: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/30112929/overcoming-drug-resistant-lung-cancer-by-paclitaxel-loaded-hyaluronic-acid-coated-liposomes-targeted-to-mitochondria
#6
Yongfeng Tian, Hua Zhang, Yanmei Qin, Dong Li, Yang Liu, Hao Wang, Li Gan
As a major cause for the inefficiency of cancer chemotherapy, multidrug resistance (MDR) has become a major barrier to cancer treatment. Mitochondrion-orientated transportation of smart liposomes has been developed as a promising strategy to deliver anticancer drugs directly to tumor sites and actively target the mitochondria, so that drugs can interfere with mitochondrial function and facilitate cell apoptosis, overcoming MDR. Herein, we report a novel dual-functional paclitaxel (PTX) liposome system possessing both CD44 targeting and mitochondrial targeting properties to enhance drug accumulation in mitochondria and trigger apoptosis of drug-resistant cancer cells...
August 16, 2018: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/30109929/r-domain-phosphorylation-by-protein-kinase-a-stimulates-dissociation-of-unhydrolyzed-atp-from-the-first-nucleotide-binding-site-of-the-cystic-fibrosis-transmembrane-conductance-regulator
#7
Luba A Aleksandrov, Jonathan F Fay, John R Riordan
The cystic fibrosis transmembrane conductance regulator (CFTR) is an asymmetric ATP-binding cassette transporter in which ATP hydrolysis occurs only at the second of the two composite nucleotide-binding sites whereas there are noncanonical substitutions of key catalytic residues in the first site. Therefore, in widely accepted models of CFTR function, ATP is depicted as remaining bound at the first site while it is hydrolyzed at the second site. However, the long lifetime of ATP at nucleotide-binding domain 1 (NBD1) had been measured under conditions where the channel had not been activated by phosphorylation...
August 15, 2018: Biochemistry
https://www.readbyqxmd.com/read/30108166/the-persistence-inducing-toxin-hokb-forms-dynamic-pores-that-cause-atp-leakage
#8
Dorien Wilmaerts, Mariam Bayoumi, Liselot Dewachter, Wouter Knapen, Jacek T Mika, Johan Hofkens, Peter Dedecker, Giovanni Maglia, Natalie Verstraeten, Jan Michiels
Bacterial populations harbor a small fraction of cells that display transient multidrug tolerance. These so-called persister cells are extremely difficult to eradicate and contribute to the recalcitrance of chronic infections. Several signaling pathways leading to persistence have been identified. However, it is poorly understood how the effectors of these pathways function at the molecular level. In a previous study, we reported that the conserved GTPase Obg induces persistence in Escherichia coli via transcriptional upregulation of the toxin HokB...
August 14, 2018: MBio
https://www.readbyqxmd.com/read/30107029/cftr-potentiation-by-vx-770-involves-stabilization-of-the-pre-hydrolytic-o-1-state
#9
Emily Langron, Stella Prins, Paola Vergani
BACKGROUND AND PURPOSE: Cystic fibrosis (CF) is a debilitating hereditary disease caused by mutations in the CFTR gene, which encodes an anion channel. WT-CFTR gating is a non-equilibrium process. After ATP binding, CFTR enters a stable open state (O1 ). ATP hydrolysis leads it to a short-lived post-hydrolytic open state (O2 ), from which channels close. Here we use mutations to probe the mechanism of VX-770, the first compound directly targeting the CFTR protein approved for treatment of CF...
August 14, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/30106622/cardiac-branched-chain-amino-acid-oxidation-is-reduced-during-insulin-resistance-in-the-heart
#10
Natasha Fillmore, Cory S Wagg, Liyan Zhang, Arata Fukushima, Gary D Lopaschuk
Recent studies have proposed that elevated branched-chain amino acids (BCAAs) may induce insulin resistance (IR) in muscle secondary to increased BCAA oxidation inhibiting glucose oxidation (GO) and fatty acid oxidation (FAO). However, BCAA oxidation rates have not been assessed in muscle IR and cardiac FAO rates are elevated in obesity-associated IR. We examined cardiac BCAA oxidation in mice fed a high fat diet (HFD) to induce IR to better understand the role of cardiac BCAA oxidation in cardiac IR. BCAA oxidation, GO, FAO, and glycolysis were measured in isolated working hearts from mice fed a low fat diet (LFD) or HFD for 10 wk...
August 14, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/30105015/c-reactive-protein-stimulates-nicotinic-acetylcholine-receptors-to-control-atp-mediated-monocytic-inflammasome-activation
#11
Katrin Richter, Sabrina Sagawe, Andreas Hecker, Mira Küllmar, Ingolf Askevold, Jelena Damm, Sarah Heldmann, Michael Pöhlmann, Sophie Ruhrmann, Michael Sander, Klaus-Dieter Schlüter, Sigrid Wilker, Inke R König, Wolfgang Kummer, Winfried Padberg, Arik J Hone, J Michael McIntosh, Anna Teresa Zakrzewicz, Christian Koch, Veronika Grau
Blood levels of the acute phase reactant C-reactive protein (CRP) are frequently measured as a clinical marker for inflammation, but the biological functions of CRP are still controversial. CRP is a phosphocholine (PC)-binding pentraxin, mainly produced in the liver in response to elevated levels of interleukin-1β (IL-1β) and of the IL-1β-dependent cytokine IL-6. While both cytokines play important roles in host defense, excessive systemic IL-1β levels can cause life-threatening diseases such as trauma-associated systemic inflammation...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30104552/effects-of-rhizome-extract-of-dioscorea-batatas-and-its-active-compound-allantoin-on-the-regulation-of-myoblast-differentiation-and-mitochondrial-biogenesis-in-c2c12-myotubes
#12
Junnan Ma, Seok Yong Kang, Xianglong Meng, An Na Kang, Jong Hun Park, Yong-Ki Park, Hyo Won Jung
With the aging process, a loss of skeletal muscle mass and dysfunction related to metabolic syndrome is observed in older people. Yams are commonly use in functional foods and medications with various effects. The present study was conducted to investigate the effects of rhizome extract of Dioscorea batatas (Dioscoreae Rhizoma, Chinese yam) and its bioactive compound, allantoin, on myoblast differentiation and mitochondrial biogenesis in skeletal muscle cells. Yams were extracted in water and allantoin was analyzed by high performance liquid chromatography (HPLC)...
August 13, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/30104387/deciphering-the-super-relaxed-state-of-human-%C3%AE-cardiac-myosin-and-the-mode-of-action-of-mavacamten-from-myosin-molecules-to-muscle-fibers
#13
Robert L Anderson, Darshan V Trivedi, Saswata S Sarkar, Marcus Henze, Weikang Ma, Henry Gong, Christopher S Rogers, Joshua M Gorham, Fiona L Wong, Makenna M Morck, Jonathan G Seidman, Kathleen M Ruppel, Thomas C Irving, Roger Cooke, Eric M Green, James A Spudich
Mutations in β-cardiac myosin, the predominant motor protein for human heart contraction, can alter power output and cause cardiomyopathy. However, measurements of the intrinsic force, velocity, and ATPase activity of myosin have not provided a consistent mechanism to link mutations to muscle pathology. An alternative model posits that mutations in myosin affect the stability of a sequestered, super relaxed state (SRX) of the protein with very slow ATP hydrolysis and thereby change the number of myosin heads accessible to actin...
August 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30100910/human-plasmablast-migration-toward-cxcl12-requires-glucose-oxidation-by-enhanced-pyruvate-dehydrogenase-activity-via-akt
#14
Hyo-Kyung Pak, Bora Nam, Yoon Kyoung Lee, Yong-Woo Kim, Jin Roh, Jaekyoung Son, Yoo-Sam Chung, Jongseon Choe, Chan-Sik Park
Migration of human plasmablast to the bone marrow is essential for the final differentiation of plasma cells and maintenance of effective humoral immunity. This migration is controlled by CXCL12/CXCR4-mediated activation of the protein kinase AKT. Herein, we show that the CXCL12-induced migration of human plasmablasts is dependent on glucose oxidation. Glucose depletion markedly inhibited plasmablast migration by 67%, and the glucose analog 2-deoxyglucose (2-DG) reduced the migration by 53%; conversely, glutamine depletion did not reduce the migration...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30099658/elevated-hydrostatic-pressure-stimulates-atp-release-which-mediates-activation-of-the-nlrp3-inflammasome-via-p2x-4-in-rat-urothelial-cells
#15
Cody L Dunton, J Todd Purves, Francis M Hughes, Huixia Jin, Jiro Nagatomi
Partial bladder outlet obstruction (pBOO) is a prevalent urological condition commonly accompanied by increased intravesical pressure, inflammation, and fibrosis. Studies have demonstrated that pBOO results in increased NLRP3 inflammasome and caspase-1 activation and that ATP is released from urothelial cells in response to elevated pressure. In the present study, we investigated the role of elevated pressure in triggering caspase-1 activation via purinergic receptors activation in urothelial cells. Rat urothelial cell line, MYP3 cells, was subjected to hydrostatic pressures of 15 cmH2 O for 60 min, or 40 cmH2 O for 1 min to simulate elevated storage and voiding pressure conditions, respectively...
August 11, 2018: International Urology and Nephrology
https://www.readbyqxmd.com/read/30098482/pyrazinyl-ureas-revisited-1-3-benzyloxy-pyrazin-2-yl-3-3-4-dichlorophenyl-urea-a-new-blocker-of-a%C3%AE-induced-mptp-opening-for-alzheimer-s-disease
#16
Ahmed Elkamhawy, Jung-Eun Park, Ahmed H E Hassan, Ae Nim Pae, Jiyoun Lee, Sora Paik, Beoung-Geon Park, Eun Joo Roh
Herein, we report synthesis and evaluation of new twenty-eight pyrazinyl ureas against β amyloid (Aβ)-induced opening of mitochondrial permeability transition pore (mPTP) using JC-1 assay which measures the change of mitochondrial membrane potential (ΔΨm). The neuroprotective effect of seventeen compounds against Aβ-induced mPTP opening was superior to that of the standard Cyclosporin A (CsA). Among them, 1-(3-(benzyloxy)pyrazin-2-yl)-3-(3,4-dichlorophenyl)urea (5) effectively maintained mitochondrial function and cell viabilities on ATP assay and MTT assay...
July 31, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30098371/potential-effects-of-metformin-in-dna-ber-system-based-on-oxidative-status-in-type-2-diabetes
#17
Irem Dogan Turacli, Tuba Candar, Emine Berrin Yuksel, Sebnem Kalay, Ali Kemal Oguz, Selda Demirtas
Metformin is used to reduce hyperglycemia that induces energetic stress and leads to reduction in gluconeogenesis. Also, metformin inhibits complex I in oxidative phosphorylation, thereby decreasing cellular ATP levels. Activation of AMPK by the reduced ATP levels can induce inhibition of reactive oxygen species (ROS) production and activate p53-mediated DNA repair. DNA polymerase-β and XRCC1 function to repair DNA damages in the BER (base excision repair) system. In type 2 diabetes patients, metformin can enhance AMPK activation therefore suppress oxidative stress...
August 8, 2018: Biochimie
https://www.readbyqxmd.com/read/30097643/targeting-nucleotide-binding-domain-of-multidrug-resistance-associated-protein-1-mrp1-for-the-reversal-of-multi-drug-resistance-in-cancer
#18
Divya Dhasmana, Ashutosh Singh, Rohit Shukla, Timir Tripathi, Neha Garg
Multidrug resistance (MDR) is the major cause, by which cancer cells expel the drugs out, developing a challenge against the current chemotherapeutic drugs regime. This mechanism is attributed to the over expression of ABC transporters like MRP1 on the surface of cells. Since nucleotide binding domains (NBD) of ABC transporters are the site of ATP binding and hydrolysis, thereby in this study we have targeted NBD1 of MRP1using molecular docking and molecular dynamic simulations (MDS). The compounds present in the FDA approved library were docked against NBD1 of the human multidrug resistance associated protein 1 (PDB ID: 2CBZ)...
August 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30097494/quantifying-intracellular-rates-of-glycolytic-and-oxidative-atp-production-and-consumption-using-extracellular-flux-measurements
#19
Shona A Mookerjee, Akos A Gerencser, David G Nicholls, Martin D Brand
No abstract text is available yet for this article.
August 10, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30096366/the-utility-of-heparg-cells-for-bioenergetic-investigation-and-detection-of-drug-induced-mitochondrial-toxicity
#20
Laleh Kamalian, Oisin Douglas, Carol Jolly, Jan Snoeys, Damir Simic, Mario Monshouwer, Dominic P Williams, B Kevin Park, Amy E Chadwick
The importance of mitochondrial toxicity in drug-induced liver injury is well established. The bioenergetic phenotype of the HepaRG cell line was defined in order to assess their suitability as a model of mitochondrial hepatotoxicity. Bioenergetic phenotyping categorised the HepaRG cells as less metabolically active when measured beside the more energetic HepG2 cells. However, inhibition of mitochondrial ATP synthase induced an increase in glycolytic activity of both HepaRG and HepG2 cells suggesting an active Crabtree Effect in both cell lines...
August 7, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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