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https://www.readbyqxmd.com/read/28646812/oral-consumption-of-vitamin-k2-for-8-weeks-associated-with-increased-maximal-cardiac-output-during-exercise
#1
Brian K McFarlin, Andrea L Henning, Adam S Venable
Background • Vitamin K1 and K2 are not typically common in a Western diet because they are found in a variety of fermented foods. Vitamin K2 in particular has been demonstrated to restore mitochondrial function and has a key role in production of mitochondrial adenosine triphosphate. Thus, it is reasonable to speculate that dietary supplementation with vitamin K2 could increase the function of muscle with high mitochondrial content (ie, skeletal and cardiac muscle). Objective • The purpose of this study was to determine if 8 wk of dietary supplementation with Vitamin K2 could alter cardiovascular responses to a graded cycle ergometer test...
July 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28646582/comprehensive-mathematical-model-of-oxidative-phosphorylation-valid-for-physiological-up-to-pathological-conditions
#2
Margit Heiske, Thierry Letellier, Edda Klipp
We developed a mathematical model of oxidative phosphorylation (OXPHOS) that allows for a precise description of mitochondrial function with respect to the respiratory flux and the ATP production. The model reproduced flux-force relationships under various experimental conditions (state 3 and 4, uncoupling, shortage of respiratory substrate) as well as time courses, exhibiting correct P/O ratios. The model was able to reproduce experimental threshold curves for perturbations of the respiratory chain complexes, the F1 F0 -ATP synthase, the ADP/ATP carrier, the phosphate/OH carrier, and the proton leak...
June 24, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28646516/tofacitinib-restores-the-inhibition-of-reverse-cholesterol-transport-induced-by-inflammation-understanding-the-lipid-paradox-associated-with-rheumatoid-arthritis
#3
S Pérez-Baos, J I Barrasa, P Gratal, A Larrañaga-Vera, I Prieto-Potin, G Herrero-Beaumont, R Largo
BACKGROUND AND PURPOSE: Patients with active rheumatoid arthritis (RA) have increased cardiovascular mortality, paradoxically associated with reduced circulating lipid levels. The Janus kinase (Jak) inhibitor tofacitinib ameliorates systemic and joint inflammation in RA with a concomitant increase in serum lipids. We analyzed the effect of tofacitinib on the lipid profile of hyperlipidemic rabbits with chronic arthritis (CA) and on the regulation of reverse cholesterol transport (RCT) during chronic inflammation...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28646182/high-intensity-interval-training-improves-mitochondrial-function-and-suppresses-thrombin-generation-in-platelets-undergoing-hypoxic-stress
#4
Li-Hua Wu, Shao-Chiang Chang, Tieh-Cheng Fu, Ching-Hui Huang, Jong-Shyan Wang
This study elucidates how high-intensity interval training (HIT) and moderate-intensity continuous training (MCT) affect mitochondrial functionality and thrombin generation (TG) in platelets following hypoxic exercise (HE, 100 W under 12% O2 for 30 min). Forty-five healthy sedentary males were randomized to engage either HIT (3-minute intervals at 40% and 80%VO2max, n = 15) or MCT (sustained 60%VO2max, n = 15) for 30 minutes/day, 5 days/week for 6 weeks, or to a control group (CTL, n = 15) that did not received exercise intervention...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646166/atp-release-during-cell-swelling-activates-a-ca-2-dependent-cl-current-by-autocrine-mechanism-in-mouse-hippocampal-microglia
#5
E Murana, F Pagani, B Basilico, M Sundukova, L Batti, S Di Angelantonio, B Cortese, A Grimaldi, A Francioso, P Heppenstall, P Bregestovski, C Limatola, D Ragozzino
Microglia cells, resident immune cells of the brain, survey brain parenchyma by dynamically extending and retracting their processes. Cl(-) channels, activated in the cellular response to stretch/swelling, take part in several functions deeply connected with microglia physiology, including cell shape changes, proliferation, differentiation and migration. However, the molecular identity and functional properties of these Cl(-) channels are largely unknown. We investigated the properties of swelling-activated currents in microglial from acute hippocampal slices of Cx3cr1 (+/GFP) mice by whole-cell patch-clamp and imaging techniques...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646164/regulation-of-drosophila-lifespan-by-bellwether-promoter-alleles
#6
Júlia Frankenberg Garcia, Mary Anna Carbone, Trudy F C Mackay, Robert R H Anholt
Longevity varies among individuals, but how natural genetic variation contributes to variation in lifespan is poorly understood. Drosophila melanogaster presents an advantageous model system to explore the genetic underpinnings of longevity, since its generation time is brief and both the genetic background and rearing environment can be precisely controlled. The bellwether (blw) gene encodes the α subunit of mitochondrial ATP synthase. Since metabolic rate may influence lifespan, we investigated whether alternative haplotypes in the blw promoter affect lifespan when expressed in a co-isogenic background...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646135/active-translocation-of-a-semiflexible-polymer-assisted-by-an-atp-based-molecular-motor
#7
A Fiasconaro, J J Mazo, F Falo
In this work we study the assisted translocation of a polymer across a membrane nanopore, inside which a molecular motor exerts a force fuelled by the hydrolysis of ATP molecules. In our model the motor switches to its active state for a fixed amount of time, while it waits for an ATP molecule which triggers the motor, during an exponentially distributed time lapse. The polymer is modelled as a beads-springs chain with both excluded volume and bending contributions, and moves in a stochastic three dimensional environment modelled with a Langevin dynamics at a fixed temperature...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646020/mcam-mediates-chemoresistance-in-small-cell-lung-cancer-via-the-pi3k-akt-sox2-signaling-pathway
#8
Satyendra C Tripathi, Johannes F Fahrmann, Muge Celiktas, Mitzi Aguilar, Kieren D Marini, Mohit Kumar Jolly, Hiroyuki Katayama, Hong Wang, Eunice N Murage, Jennifer B Dennison, D Neil Watkins, Herbert Levine, Edwin J Ostrin, Ayumu Taguchi, Samir M Hanash
Despite favorable responses to initial therapy, small cell lung cancer (SCLC) relapse occurs within a year and exhibits resistance to multiple drugs. Due to limited accessibility of patient tissues for research purposes, SCLC-patient derived xenografts (PDX) have provided the best opportunity to address this limitation. Here we sought to identify novel mechanisms involved in SCLC chemoresistance. Through in-depth proteomic profiling, we identified MCAM as a markedly upregulated surface receptor in chemoresistant SCLC cell lines and in chemoresistant PDX compared to matched treatment-naïve tumors...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28645941/a-first-time-in-human-study-of-gsk2636771-a-phosphoinositide-3-kinase-beta-selective-inhibitor-in-patients-with-advanced-solid-tumors
#9
Joaquin Mateo, Gopinath Ganji, Charlotte Lemech, Howard A Burris, Sae-Won Han, Karen E Swales, Shaun Decordova, Maurice P DeYoung, Deborah A Smith, Shanker Kalyana-Sundaram, Jiuhua Wu, Monica Motwani, Rakesh Kumar, Jerry M Tolson, Sun Young Rha, Hyun Cheol Chung, Joseph Paul Eder, Sunil Sharma, Yung-Jue Bang, Jeffrey R Infante, Li Yan, Johann S de Bono, Hendrik-Tobias Arkenau
The phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT) pathway is commonly activated in several tumor types. Selective targeting of p110β could result in successful pathway inhibition while avoiding the on and off target effects of pan-PI3K inhibitors. GSK2636771 is a potent, orally bioavailable, adenosine triphosphate-competitive, selective inhibitor of PI3Kβ.<br /><br />Experimental Design: <p>We evaluated the safety, pharmacokinetics, pharmacodynamics and antitumor activity of GSK2636771 to define the recommended Phase II dose (RP2D)...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28645928/molecular-mechanisms-in-cardiomyopathy
#10
REVIEW
Keith Dadson, Ludger Hauck, Filio Billia
Cardiomyopathies represent a heterogeneous group of diseases that negatively affect heart function. Primary cardiomyopathies specifically target the myocardium, and may arise from genetic [hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), mitochondrial cardiomyopathy] or genetic and acquired [dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM)] etiology. Modern genomics has identified mutations that are common in these populations, while in vitro and in vivo experimentation with these mutations have provided invaluable insight into the molecular mechanisms native to these diseases...
July 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28645831/synthesis-and-biological-evaluation-of-jl-a7-derivatives-as-potent-abcb1-inhibitors
#11
Miaobo Pan, Jian Cui, Lei Jiao, Hesham Ghaleb, Chen Liao, Jiaqi Zhou, Mutta Kairuki, Haiyan Lin, Wenlong Huang, Hai Qian
Cancer chemotherapy failure is often due to the overexpression of ATP-binding cassette (ABC) transporters (particularly ABCB1), resulting in a variety of structurally and pharmacologically unrelated drugs efflux. The multidrug resistance (MDR) phenomenon could be reversed by ABCB1 inhibitors. Now, JL-A7 as the lead compound based on a triazol-N-ethyl-tetrahydroisoquinoline scaffold, 18 compounds were designed and synthesized. Substitution in para positions yielded high activities toward ABCB1. Moreover, compound 5 could effectively block the drug efflux function of ABCB1 and increase the accumulation of anti-cancer drugs to achieve effective treatment concentration in MDR cells...
June 13, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28645773/abc-protein-cgabcf2-is-required-for-asexual-and-sexual-development-appressorial-formation-and-plant-infection-in-colletotrichum-gloeosporioides
#12
Zongshan Zhou, Jianyuan Wu, Meiyu Wang, Junxiang Zhang
ATP-binding cassette (ABC) proteins are exclusively found in both prokaryotes and eukaryotes. In this study, we have characterized a gene from Glomerella leaf spot pathogen Colletotrichum gloeosporioides that encodes an ABC protein, whose function to date remains unknown. We designated this gene as CgABCF2. Deletion of CgABCF2 showed drastic reduction both growing rate and conidial production in C. gloeosporioides. The Δcgabcf2 mutant did not form the appressoria, lost the capability to infect apple and failed to form lesions on the wounded leaves and fruits...
June 20, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28645703/mapping-of-the-anterior-tibial-profile-to-identify-accurate-reference-points-for-sagittal-alignment-of-tibial-component-in-total-knee-arthroplasty
#13
Gianluca Cinotti, Ettore Caruso, Luigi Orsina, Giuseppe La Torre, Francesca Romana Ripani
BACKGROUND: Although standard instrumentation is the procedure most frequently used to implant a total knee arthroplasty (TKA), high rates of malalignment of tibial component are reported using this technique. Anatomical landmarks for sagittal alignment have been little investigated and the best reference axis which parallels the mechanical axis is yet to be established. HYPOTHESIS: Mapping the anterior tibial profile (ATP) may allow the identification of segmental zones of the ATP parallel to the mechanical axis which can be use to align the extramedullary rod...
June 20, 2017: Orthopaedics & Traumatology, Surgery & Research: OTSR
https://www.readbyqxmd.com/read/28645607/the-tca-cycle-as-a-bridge-between-oncometabolism-and-dna-transactions-in-cancer
#14
REVIEW
Fabio Ciccarone, Rolando Vegliante, Luca Di Leo, Maria Rosa Ciriolo
Cancer cells exploit metabolic rearrangements for sustaining their high proliferation rate and energy demand. The TCA cycle is a central metabolic hub necessary for ATP production and for providing precursors used in many biosynthetic pathways. Thus, dysregulation of the TCA cycle flux is frequently observed in cancer. The identification of mutations in several enzymes of the TCA cycle in human tumours demonstrated a direct connection between this metabolic pathway and cancer occurrence. Moreover, changes in the expression/activity of these enzymes were also shown to promote metabolic adaptation of cancer cells...
June 20, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28645576/mechanisms-of-hepatocellular-toxicity-associated-with-new-psychoactive-synthetic-cathinones
#15
Dino Luethi, Matthias E Liechti, Stephan Krähenbühl
Synthetic cathinones are a new class of psychostimulant substances. Rarely, they can cause liver injury but associated mechanisms are not completely elucidated. In order to increase our knowledge about mechanisms of hepatotoxicity, we investigated the effect of five frequently used cathinones on two human cell lines. Bupropion was included as structurally related drug used therapeutically. In HepG2 cells, bupropion, MDPV, mephedrone and naphyrone depleted the cellular ATP content at lower concentrations (0...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28645489/effects-of-hypnotic-bromovalerylurea-on-microglial-bv2-cells
#16
Shun Kawasaki, Naoki Abe, Fumito Ohtake, Afsana Islam, Mohammed Emamussalehin Choudhury, Ryo Utsunomiya, Satoshi Kikuchi, Tasuku Nishihara, Jun Kuwabara, Hajime Yano, Yuji Watanabe, Mayuki Aibiki, Toshihiro Yorozuya, Junya Tanaka
An old sedative and hypnotic bromovalerylurea (BU) has anti-inflammatory effects. BU suppressed nitric oxide (NO) release and proinflammatory cytokine expression by lipopolysaccharide (LPS)-treated BV2 cells, a murine microglial cell line. However, BU did not inhibit LPS-induced nuclear translocation of nuclear factor-κB and subsequent transcription. BU suppressed LPS-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1) and expression of interferon regulatory factor 1 (IRF1)...
June 8, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28645005/application-of-stem-cell-derived-neuronal-cells-to-evaluate-neurotoxic-chemotherapy
#17
Claudia Wing, Masaaki Komatsu, Shannon M Delaney, Matthew Krause, Heather E Wheeler, M Eileen Dolan
The generation of induced pluripotent stem cells (iPSCs) and differentiation to cells composing major organs has opened up the possibility for a new model system to study adverse toxicities associated with chemotherapy. Therefore, we used human iPSC-derived neurons to study peripheral neuropathy, one of the most common adverse effects of chemotherapy and cause for dose reduction. To determine the utility of these neurons in investigating the effects of neurotoxic chemotherapy, we measured morphological differences in neurite outgrowth, cell viability as determined by ATP levels and apoptosis through measures of caspase 3/7 activation following treatment with clinically relevant concentrations of platinating agents (cisplatin, oxaliplatin and carboplatin), taxanes (paclitaxel, docetaxel and nab-paclitaxel), a targeted proteasome inhibitor (bortezomib), an antiangiogenic compound (thalidomide), and 5-fluorouracil, a chemotherapeutic that does not cause neuropathy...
June 15, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28644992/surface-coating-modulated-toxic-responses-to-silver-nanoparticles-in-wolffia-globosa
#18
Xiaoyan Zou, Penghui Li, Jie Lou, Hongwu Zhang
With the omnipresence of silver nanoparticles (AgNPs) in our daily consumer products, their release has raised serious concerns. However, the biochemical mechanisms by which plants counteract the toxicity of nanoparticles are largely unknown. This study investigated the exposure of aquatic Wolffia globosa to ATP-nAg (AgNPs coated with adenosine triphosphate), cit-nAg (AgNPs coated with citrate), and Ag(+). Hill reaction activity was basically lost in W. globosa treated with 10mg/L ATP-nAg and Ag(+), while the activity was still maintained at 38...
June 15, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28644842/investigation-of-discriminant-metabolites-in-tamoxifen-resistant-and-choline-kinase-alpha-downregulated-breast-cancer-cells-using-1h-nuclear-magnetic-resonance-spectroscopy
#19
Hoe Suk Kim, Lianji Tian, Hyeonjin Kim, Woo Kyung Moon
Metabolites linked to changes in choline kinase-α (CK-α) expression and drug resistance, which contribute to survival and autophagy mechanisms, are attractive targets for breast cancer therapies. We previously reported that autophagy played a causative role in driving tamoxifen (TAM) resistance of breast cancer cells (BCCs) and was also promoted by CK-α knockdown, resulting in the survival of TAM-resistant BCCs. There is no comparative study yet about the metabolites resulting from BCCs with TAM-resistance and CK-α knockdown...
2017: PloS One
https://www.readbyqxmd.com/read/28644490/potentiating-role-of-copper-on-spatial-memory-deficit-induced-by-beta-amyloid-and-evaluation-of-mitochondrial-function-markers-in-the-hippocampus-of-rats
#20
Ladan Behzadfar, Mohammad Abdollahi, Omid Sabzevari, Rohollah Hosseini, Ahmad Salimi, Parvaneh Naserzadeh, Mohammad Sharifzadeh, Jalal Pourahmad
Mounting evidence suggests that copper, a crucial element in normal brain function, plays an important role in the etiology of Alzheimer's disease, which is known as a neurodegenerative mitochondrial disorder. However, the precise mechanisms of its effects on cognitive and mitochondrial functions through the CNS have not been thoroughly recognized yet. In this study, we aimed to investigate the long-term (3-week) effects of copper sulfate (50, 100 and 200 mg kg(-1) day(-1)) exposure on learning and memory as well as on mitochondrial function in the hippocampus of rats in the presence and absence of beta amyloid (1 μg μl(-1) per side) intrahippocampally (IH)...
June 23, 2017: Metallomics: Integrated Biometal Science
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