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https://read.qxmd.com/read/30742774/astrocytic-cystine-glutamate-antiporter-is-a-key-regulator-of-erythropoietin-expression-in-the-ischemic-retina
#1
Byung Joo Lee, Hyoung Oh Jun, Jin Hyoung Kim, Jeong Hun Kim
Ischemic retinopathies and optic neuropathies are important causes of vision loss. The neuroprotective effect of erythropoietin (EPO) in ischemic neuronal injury and the expression of EPO and its receptor in retinal tissue have been well documented. However, the exact regulatory mechanism of EPO expression in retinal ischemia still remains to be elucidated. In this study, we investigated the role of cystine/glutamate antiporter (system xc- ) in the regulation of astrocytic EPO expression by using both in vitro and in vivo models...
February 11, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30741871/comparison-of-physiological-and-perceptual-responses-to-upper-lower-and-whole-body-exercise-in-elite-cross-country-skiers
#2
Vidar Undebakke, Jonathan Berg, Arnt E Tjønna, Øyvind Sandbakk
Undebakke, V, Berg, J, Tjønna, AE, and Sandbakk, Ø. Comparison of physiological and perceptual responses to upper-, lower-, and whole-body exercise in elite cross-country skiers. J Strength Cond Res XX(X): 000-000, 2019-The primary purpose of the present study was to compare physiological and perceptual responses to maximal and submaximal exercise between upper-, lower-, and whole-body exercise modes in elite cross-country (XC) skiers. Twelve elite XC skiers performed 5-7 submaximal 5-minute stages and an incremental test to exhaustion using upper-body poling (UP), running (RUN), and diagonal skiing (DIA), randomized on 3 separate days...
February 6, 2019: Journal of Strength and Conditioning Research
https://read.qxmd.com/read/30738038/transport-of-cystine-across-xc-antiporter
#3
Maryam Ghasemitarei, Maksudbek Yusupov, Jamoliddin Razzokov, Babak Shokri, Annemie Bogaerts
Extracellular cystine (CYC) uptake by xC- antiporter is important for the cell viability. Especially in cancer cells, the upregulation of xC- activity is observed, which protects these cells from intracellular oxidative stress. Hence, inhibition of the CYC uptake may eventually lead to cancer cell death. Up to now, the molecular level mechanism of the CYC uptake by xC- antiporter has not been studied in detail. In this study, we applied several different simulation techniques to investigate the transport of CYC through xCT, the light subunit of the xC- antiporter, which is responsible for the CYC and glutamate translocation...
February 6, 2019: Archives of Biochemistry and Biophysics
https://read.qxmd.com/read/30719640/inhibition-of-becn1-suppresses-lipid-peroxidation-by-increasing-system-x-c-activity-in-early-brain-injury-after-subarachnoid-hemorrhage
#4
Yazhou Guo, Xiao Liu, Dezhong Liu, Kai Li, Changwei Wang, Yu Liu, Bing He, Pengfei Shi
Lipid peroxidation plays a crucial role in early brain injury (EBI) after subarachnoid hemorrhage (SAH), and cystine/glutamate antiporter system Xc - has been proved to be associated with glutathione (GSH) synthesis, which protects cells against oxidative damage. Antioxidant effect of system Xc - is mediated by Beclin 1 (BECN1). Therefore, this study aimed to determine whether administration of BECN1 small interfering RNA (siRNA) could attenuate EBI after SAH experiment, specifically through suppressing lipid peroxidation and increasing system Xc - activity...
February 4, 2019: Journal of Molecular Neuroscience: MN
https://read.qxmd.com/read/30684867/on-the-role-of-synthesized-hydroxylated-chalcones-as-dual-functional-amyloid-%C3%AE-aggregation-and-ferroptosis-inhibitors-for-potential-treatment-of-alzheimer-s-disease
#5
Lin Cong, Xiyu Dong, Yan Wang, Yulin Deng, Bo Li, Rongji Dai
In addition to amyloid cascade hypothesis, ferroptosis - a recently identified cell death pathway associated with the accumulation of lipid hydroperoxides - was hypothesized as one of the main forms of cell death in Alzheimer's disease. Herein, a series of hydroxylated chalcones were designed and synthesized as dual-functional inhibitors to inhibit amyloid-β peptide (Aβ) aggregation as well as ferroptosis simultaneously. Thioflavin-T assay indicated trihydroxy chalcones inhibited Aβ aggregation better. In human neuroblastoma SH-SY5Y cells, cytoprotective chalcones 14a-c with three hydroxyl substituents exhibited a significant neuroprotection against Aβ1-42 aggregation induced toxicity...
January 17, 2019: European Journal of Medicinal Chemistry
https://read.qxmd.com/read/30651275/measurement-of-tumor-antioxidant-capacity-and-prediction-of-chemotherapy-resistance-in-preclinical-models-of-ovarian-cancer-by-positron-emission-tomography
#6
Hannah E Greenwood, Patrick N McCormick, Thibault Gendron, Matthias Glaser, Raul Pereira, Oliver D K Maddocks, Kerstin Sander, Tong Zhang, Norman Koglin, Mark F Lythgoe, Erik Årstad, Daniel Hochhauser, Timothy H Witney
PURPOSE: Drug-resistance is a major obstacle for the effective treatment of patients with high grade serous ovarian cancer (HGSOC). Currently, there is no satisfactory way to identify HGSOC patients that are refractive to the standard of care. Here, we propose the system xc - radiotracer (4 S )-4-(3-[18 F]fluoropropyl)-L-glutamate ([18 F]FSPG) as a non-invasive method to measure upregulated antioxidant pathways present in drug resistant HGSOC. >Experimental Design:Using matched chemotherapy sensitive and resistant ovarian cancer cell lines, we assessed their antioxidant capacity and its relation to [18 F]FSPG uptake, both in cells and in animal models of human ovarian cancer...
January 16, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://read.qxmd.com/read/30635754/prospective-comparison-of-4s-4-3-18-f-fluoropropyl-l-glutamate-versus-18-f-fluorodeoxyglucose-pet-ct-for-detecting-metastases-from-pancreatic-ductal-adenocarcinoma-a-proof-of-concept-study
#7
Mei-Fang Cheng, Ya-Yao Huang, Bing-Ying Ho, Ting-Chun Kuo, Ling-Wei Hsin, Chyng-Yann Shiue, Hsun-Chuan Kuo, Yung-Ming Jeng, Rouh-Fang Yen, Yu-Wen Tien
PURPOSE: (4S)-4-(3-18 F-Fluoropropyl)-L-glutamate (FSPG) positron emission tomography (PET) reflects system xC - transporter (xCT) expression. FSPG PET has been used to detect brain, lung, breast and liver cancer with only modest success. There is no report on the use of FSPG PET in pancreatic ductal adenocarcinoma (PDAC), presumably because of normal xCT expression in the pancreas. Nonetheless, the tissue-specific expression of xCT in the pancreas suggests that FSPG PET may be ideal for identifying metastasized PDAC...
January 11, 2019: European Journal of Nuclear Medicine and Molecular Imaging
https://read.qxmd.com/read/30631447/memantine-protects-thalamocortical-hyper-glutamatergic-transmission-induced-by-nmda-receptor-antagonism-via-activation-of-system-xc
#8
Motohiro Okada, Kouji Fukuyama, Yasuhiro Kawano, Takashi Shiroyama, Yuto Ueda
Deficiencies in N-methyl-d-aspartate (NMDA)/glutamate receptor (NMDAR) signaling have been considered central to the cognitive impairments of schizophrenia; however, an NMDAR antagonist memantine (MEM) improves cognitive impairments of Alzheimer's disease and schizophrenia. These mechanisms of paradoxical clinical effects of NMDAR antagonists remain unclear. To explore the mechanisms by which MK801 and MEM affect thalamocortical transmission, we determined interactions between local administrations of MK801, MEM, system xc- (Sxc), and metabotropic glutamate receptors (mGluRs) on extracellular glutamate and GABA levels in the mediodorsal thalamic nucleus (MDTN) and medial prefrontal cortex (mPFC) using dual-probe microdialysis with ultra-high-pressure liquid chromatography...
February 2019: Pharmacology Research & Perspectives
https://read.qxmd.com/read/30605320/triplet-tuning-a-novel-family-of-non-empirical-exchange-correlation-functionals
#9
Zhou Lin, Troy Van Voorhis
In the framework of density functional theory (DFT), the lowest triplet excited state, T1 , can be evaluated using multiple formulations, the most straightforward of which are unrestricted DFT (UDFT) and time-dependent DFT (TDDFT). Assuming the exact exchange-correlation (XC) functional is applied, UDFT and TDDFT should provide identical energies for T1 ( ET ), which is also a constraint that we require our novel XC functionals to obey. However, this condition is not satisfied by most of the popular XC functionals, leading to inaccurate predictions of low-lying, spectroscopically and photochemically important excited states, such as T1 and the lowest singlet excited state (S1 )...
January 3, 2019: Journal of Chemical Theory and Computation
https://read.qxmd.com/read/30595058/the-effect-of-ratio-of-endoscope-sheath-diameter-on-intrapelvic-pressure-during-flexible-ureteroscopic-lasertripsy
#10
Li Fang, Guohai Xie, Zhong Zheng, Wanzhang Liu, Jiaqi Zhu, Ting Huang, Yunfei Lu, Yue Cheng
PURPOSE: To clarify appropriate combinations of Flexible ureteroscope(FURS) and Ureteral access sheath(UAS), that can maintain a low intrapelvic pressure(IPP) during FURS with lasertripsy. METHODS: Four kinds of FURSs (Polyscope, Olympus URF-P6, Stroz Flex-Xc, Olympus URF-V) and six size of UASs (11/13F×36cm, 11/13F×46cm, 12/14F×36cm, 12/14F×46cm, 13/15F×36cm, 13/15F×46cm) were tested. A novel gas-liquid-pressure-control system (GLPCS) was used to maintain a stable and adjustable irrigation pressure form 50-500cmH2O...
December 29, 2018: Journal of Endourology
https://read.qxmd.com/read/30558933/transtibial-amputee-gait-during-slope-walking-with-the-unity-suspension-system
#11
Hossein Gholizadeh, Edward D Lemaire, Emily H Sinitski
BACKGROUND: People with lower limb amputation may experience walking limitations on slopes because of missing musculoskeletal and neuromuscular systems. Elevated vacuum suspension could benefit transtibial amputee gait for slope walking, but research is lacking to inform clinical practice. METHODS: Twelve people with unilateral transtibial amputation were fitted with the Unity elevated vacuum suspension system (Össur) and Pro-Flex XC foot. 3D motion analysis was performed for 7° incline, 7° decline, and level walking within a CAREN-Extended system virtual Park environment...
September 2018: Gait & Posture
https://read.qxmd.com/read/30557027/combining-pair-density-functional-theory-and-variational-two-electron-reduced-density-matrix-methods
#12
Mohammad Mostafanejad, A Eugene DePrince
Complete active space self-consistent field (CASSCF) computations can be realized at polynomial cost via the variational optimization of the active-space two-electron reduced-density matrix (2-RDM). Like conventional approaches to CASSCF, variational 2-RDM (v2RDM)-driven CASSCF captures nondynamical electron correlation in the active space, but it lacks a description of the remaining dynamical correlation effects. Such effects can be modeled through a combination of v2RDM-CASSCF and on-top pair-density functional theory (PDFT)...
December 17, 2018: Journal of Chemical Theory and Computation
https://read.qxmd.com/read/30540556/comparative-biomechanical-evaluation-of-two-technologically-different-microprocessor-controlled-prosthetic-knee-joints-in-safety-relevant-daily-life-situations
#13
Malte Bellmann, Thomas Maximilian Köhler, Thomas Schmalz
Safety-relevant gait situations (walking on stairs and slopes, walking backwards, walking with small steps, simulated perturbations of swing phase extension) were investigated in a motion analysis laboratory with six unilateral transfemoral amputees using two different microprocessor-controlled prosthetic knee joints (Rheo Knee XC, C-Leg). A randomized crossover design was chosen. The study results imply that the performance and safety potential of a microprocessor-controlled knee joint can be associated with the individual control algorithms and the technological concepts that are implemented to generate motion resistances for controlling flexion and extension movements...
December 12, 2018: Biomedizinische Technik. Biomedical Engineering
https://read.qxmd.com/read/30440017/sex-based-differences-in-speed-sub-technique-selection-and-kinematic-patterns-during-low-and-high-intensity-training-for-classical-cross-country-skiing
#14
Guro Strøm Solli, Jan Kocbach, Trine M Seeberg, Johannes Tjønnås, Ole Marius Hoel Rindal, Pål Haugnes, Per Øyvind Torvik, Øyvind Sandbakk
OBJECTIVES: We investigated sex-based differences in speed, sub-technique selection, and kinematic patterns during low- (LIT) and high-intensity training (HIT) for classical cross-country (XC) skiing across varying terrain. METHODS: Six male and six female elite XC skiers with an approximately 15% differences in VO2max (men: 68.9±2.9 mL·min-1·kg-1, women: 60.1±3.3 mL·min-1·kg-1) were monitored using a multi-sensor system to collect time-synchronised data of heart rate, speed, and multiple tri-axial inertial measurements units while XC skiing on a 5-km competition track...
2018: PloS One
https://read.qxmd.com/read/30401715/assessment-of-tumor-redox-status-through-s-4-3-18f-fluoropropyl-l-glutamic-acid-positron-emission-tomography-imaging-of-system-xc-activity
#15
Patrick N McCormick, Hannah E Greenwood, Matthias Glaser, Oliver D K Maddocks, Thibault Gendron, Kerstin Sander, Gayatri Gowrishankar, Aileen Hoehne, Tong Zhang, Adam J Shuhendler, David Y Lewis, Mathias Berndt, Norman Koglin, Mark F Lythgoe, Sanjiv S Gambhir, Erik Årstad, Timothy H Witney
The cell's endogenous antioxidant system is vital to maintenance of redox homeostasis. Despite its central role in normal and pathophysiology, no non-invasive tools exist to measure this system in patients. The cystine/glutamate antiporter system xc- maintains the balance between intracellular reactive oxygen species and antioxidant production through the provision of cystine, a key precursor in glutathione biosynthesis. Here we show that tumor cell retention of a system xc--specific positron emission tomography radiotracer, (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG), decreases in proportion to levels of oxidative stress following treatment with a range of redox-active compounds...
November 6, 2018: Cancer Research
https://read.qxmd.com/read/30380864/embedded-cluster-density-approximation-for-exchange-correlation-energy-a-natural-extension-of-the-local-density-approximation
#16
Chen Huang
We develop a local correlation method in the framework of Kohn-Sham density functional theory (KS-DFT). The method is termed "embedded cluster density approximation" (ECDA) and is a logical extension of the local density approximation. In ECDA, an embedded cluster is defined for each atom based on the finite-temperature density functional embedding theory. The clusters' XC energy densities are calculated using high-level XC functionals. The system's XC energy is then constructed by patching these locally computed, high-level XC energy densities over the system in an atom-by-atom manner...
October 31, 2018: Journal of Chemical Theory and Computation
https://read.qxmd.com/read/30349141/lack-of-agreement-of-in-vivo-raw-bioimpedance-measurements-obtained-from-two-single-and-multi-frequency-bioelectrical-impedance-devices
#17
Analiza M Silva, Catarina N Matias, Catarina L Nunes, Diana A Santos, Elisabetta Marini, Henry C Lukaski, Luís B Sardinha
BACKGROUND: It is important for highly active individuals to accurately assess their hydration level. Bioelectrical impedance (BIA) can potentially meet these needs but its validity in active individuals is not well established. METHODS: We compared whole-body bioimpedance measurements obtained from multi-frequency bioelectrical impedance spectroscopy (BIS, Xitron 4200) at a 50 kHz frequency with those determined by a phase-sensitive single-frequency device (SF-BIA, BIA-101, RJL/Akern Systems) in two populations: active adults and elite athletes...
October 22, 2018: European Journal of Clinical Nutrition
https://read.qxmd.com/read/30316632/synthesis-and-evaluation-of-an-18-f-labeled-boramino-acid-analog-of-aminosuberic-acid-for-pet-imaging-of-the-antiporter-system-x-c
#18
Milena Čolović, Etienne Rousseau, Zhengxing Zhang, Joseph Lau, Chengcheng Zhang, Hsiou-Ting Kuo, Hua Yang, Paul Schaffer, François Bénard, Kuo-Shyan Lin
In this study, we synthesized 18 F-ASu-BF3 , a close boramino acid analog of 5-[18 F]fluoro-aminosuberic acid (18 F-ASu), via 18 F-19 F isotope exchange reaction and evaluated its potential for imaging with positron emission tomography (PET). 18 F-ASu-BF3 was stable in mouse plasma and taken up into PC3 prostate cancer cells via the system xC - amino acid transporter. The continuous use of isoflurane for anesthesia during dynamic imaging acquisition slowed down the excretion of 18 F-ASu-BF3 and enabled visualization of PC3 tumor xenografts in mice...
December 1, 2018: Bioorganic & Medicinal Chemistry Letters
https://read.qxmd.com/read/30300680/systemic-l-buthionine-s-r-sulfoximine-administration-modulates-glutathione-homeostasis-via-ngf-trka-and-mtor-signaling-in-the-cerebellum
#19
Carla Garza-Lombó, Pavel Petrosyan, Miguel Tapia-Rodríguez, Cesar Valdovinos-Flores, María E Gonsebatt
Glutathione (GSH) is an essential component of intracellular antioxidant systems that plays a primordial role in the protection of cells against oxidative stress, maintaining redox homeostasis and xenobiotic detoxification. GSH synthesis in the brain is limited by the availability of cysteine and glutamate. Cystine, the disulfide form of cysteine is transported into endothelial cells of the blood-brain barrier (BBB) and astrocytes via the system xc - , which is composed of xCT and the heavy chain of 4F2 cell surface antigen (4F2hc)...
October 6, 2018: Neurochemistry International
https://read.qxmd.com/read/30298963/egfr-promotes-glioma-progression-by-regulating-xct-and-glun2b-containing-nmda-receptor-signaling
#20
Kentaro Suina, Kenji Tsuchihashi, Juntaro Yamasaki, Shohei Kamenori, Subaru Shintani, Yuki Hirata, Shogo Okazaki, Oltea Sampetrean, Eishi Baba, Koichi Akashi, Yoichiro Mitsuishi, Fumiyuki Takahashi, Kazuhisa Takahashi, Hideyuki Saya, Osamu Nagano
Autocrine and paracrine factors, including glutamate and epidermal growth factor (EGF), are potent inducers of brain tumor cell invasion, a pathological hallmark of malignant gliomas. System xc(-) consists of xCT and CD98hc subunits and functions as a plasma membrane antiporter for the uptake of extracellular cystine in exchange for intracellular glutamate. We previously showed that the EGF receptor (EGFR) interacts with xCT and thereby promotes the activity of system xc(-) in a kinase-independent manner, resulting in enhanced glutamate release, in glioma cells...
October 9, 2018: Cancer Science
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