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https://www.readbyqxmd.com/read/29775559/mechanosensitivity-of-mitochondr-ial-large-conductance-calcium-activated-potassium-channels
#1
Agnieszka Walewska, Bogusz Kulawiak, Adam Szewczyk, Piotr Koprowski
Potassium channels have been discovered in the inner mitochondrial membrane of various cells. These channels can regulate the mitochondrial membrane potential, the matrix volume, respiration and reactive species generation. Therefore, it is believed that their activation is cytoprotective in various tissues. In our study, the single-channel activity of a large-conductance calcium-activated potassium channel (mitoBKCa ) was measured by the patch-clamp technique on mitoplasts derived from mitochondria isolated from human glioma U-87 MG cells...
May 15, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29775412/inhibitor-of-lysyl-oxidase-improves-cardiac-function-and-the-collagen-mmp-profile-in-response-to-volume-overload
#2
Elia C El Hajj, Milad C El Hajj, Van K Ninh, Jason D Gardner
The cardiac extracellular matrix is a complex architectural network that serves many functions including providing structural and biochemical support to surrounding cells, and regulating intercellular signaling pathways. Cardiac function is directly affected by extracellular matrix (ECM) composition, and alterations of the ECM contribute to progression of heart failure. Initially, collagen deposition is an adaptive response that aims to preserve tissue integrity and maintain normal ventricular function. However, the synergistic effects of the pro-inflammatory and pro-fibrotic responses induce a vicious cycle which causes excess activation of myofibroblasts, significantly increasing collagen deposition and accumulation in the matrix...
May 18, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29774075/plectin-targeted-liposomes-enhance-the-therapeutic-efficacy-of-a-parp-inhibitor-in-the-treatment-of-ovarian-cancer
#3
Siva Sai Krishna Dasa, Galina Diakova, Ryo Suzuki, Anne M Mills, Michael F Gutknecht, Alexander L Klibanov, Jill K Slack-Davis, Kimberly A Kelly
Advances in genomics and proteomics drive precision medicine by providing actionable genetic alterations and molecularly targeted therapies, respectively. While genomic analysis and medicinal chemistry have advanced patient stratification with treatments tailored to the genetic profile of a patient's tumor, proteomic targeting has the potential to enhance the therapeutic index of drugs like poly(ADP-ribose) polymerase (PARP) inhibitors. PARP inhibitors in breast and ovarian cancer patients with BRCA1/2 mutations have shown promise...
2018: Theranostics
https://www.readbyqxmd.com/read/29772274/pharmacodynamic-and-pharmacokinetic-characteristics-of-ymr-65-a-tubulin-inhibitor-in-tumor-bearing-mice
#4
Ali Fan, Jiali Wei, Mengru Yang, Qing Zhang, Yaliang Zhang, Qingwang Liu, Ning Li, Di Zhao, Yang Lu, Junxiu Li, Jie Zhao, Shuhua Deng, Bingjie Zhang, Hailiang Zhu, Xijing Chen
YMR-65, 5-(5-bromo-1-methyl-1H-indol-3-yl)-3-(3-methoxyphenyl)-4, 5-dihydro-1H-pyrazole-1-carboxamide, is a potential tubulin inhibitor exhibiting good anticancer activity. In our study, we illustrated the biological activities in HepG2 cells and the pharmacodynamic and pharmacokinetic profiles were evaluated in murine H22 hepatoma-bearing mice. Molecular docking assay and colchicine competition assay indicated that YMR-65 could bind tightly to the colchicine binding site of tubulin. Further investigation demonstrated that YMR-65 arrested cells in the G2/M phase of cell cycle and induced apoptosis in HepG2 cells...
May 14, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29771445/tirofiban-combined-with-rt-pa-intraarterial-thrombolysis-improves-the-recanalization-rate-of-acute-middle-cerebral-artery-occlusion-in-rabbits
#5
Y-J Yu, W Xiong
OBJECTIVE: To investigate the curative effect of tirofiban combined with recombinant tissue-plasminogen activator (rt-PA) selective intra-arterial thrombolysis on acute middle cerebral artery occlusion (MCAO). MATERIALS AND METHODS: A total of 60 adult male Japanese white rabbits weighing 2.5-3.0 kg were selected, and the acute cerebral infarction model was established via autologous thromboembolism of middle cerebral artery. Rabbits were randomly divided into 4 groups: tirofiban group (Ti group, 5 μg/kg, n=15), rt-PA group (rt-PA group, 2 mg/kg, n=15), tirofiban + rt-PA group (Ti + rt-PA group, 3 μg/kg Ti + 1 mg/kg rt-PA, n=15), and control group (Co group, n=15)...
May 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29771437/works-on-heart-how-about-brain-effect-of-hyperkalemia-on-focal-cerebral-ischemia-reperfusion-injury-in-rats
#6
T Qin, N Li, X-F Tan, J-H Zheng, R Tao, M-H Chen
OBJECTIVE: To investigate the effects of hyperkalemia on the brain after I/R in h transient middle cerebral artery occlusion (tMCAO) model. MATERIALS AND METHODS: A total of 120 adult male SD rats were randomly assigned to four groups: (1) hyperkalemia 80 µg/g (HK80) group; (2) hyperkalemia 40 µg/g (HK40) group; (3) normal saline (NS) group; (4) sham (SH) group. The concentration of serum K+ was elevated in HK80 and HK40 groups. The transient middle cerebral artery occlusion (tMCAO) model was used to assess the effect of hyperkalemia on the brain after I/R...
May 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29769037/a-method-for-estimating-relative-changes-in-the-synaptic-density-in-drosophila-central-nervous-system
#7
Dipti Rai, Swagata Dey, Krishanu Ray
BACKGROUND: Synapse density is an essential indicator of development and functioning of the central nervous system. It is estimated indirectly through the accumulation of pre and postsynaptic proteins in tissue sections. 3D reconstruction of the electron microscopic images in serial sections is one of the most definitive means of estimating the formation of active synapses in the brain. It is tedious and highly skill-dependent. Confocal imaging of whole mounts or thick sections of the brain provides a natural alternative for rapid gross estimation of the synapse density in large areas...
May 16, 2018: BMC Neuroscience
https://www.readbyqxmd.com/read/29766758/anti-inflammatory-peptide-attenuates-edema-and-promotes-bmp-2-induced-bone-formation-in-spine-fusion
#8
Juliane D Glaeser, Khosrowdad Salehi, Linda Kanim, Dmitriy Sheyn, Zachary NaPier, Phillip Behrens, Leslie Garcia, Jason M Cuéllar, Hyun W Bae
Recombinant human bone morphogenic protein-2 (BMP-2) loaded absorbable collagen sponges (ACS) have been successfully used to enhance bone formation and to induce spinal fusion in humans. However, side effects, such as soft-tissue edema and inflammation, have been reported. NEMO binding domain peptide (NBD) inhibits activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a central regulator of immune response. In this study, we investigated NBD's potential to reduce BMP-2-induced soft-tissue inflammation without affecting BMP-2-mediated spinal fusion in rat...
May 16, 2018: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29766029/seizure-suppressant-and-neuroprotective-effects-of-encapsulated-bdnf-producing-cells-in-a-rat-model-of-temporal-lobe-epilepsy
#9
Chiara Falcicchia, Giovanna Paolone, Dwaine F Emerich, Francesca Lovisari, William J Bell, Tracie Fradet, Lars U Wahlberg, Michele Simonato
Brain-derived neurotrophic factor (BDNF) may represent a therapeutic for chronic epilepsy, but evaluating its potential is complicated by difficulties in its delivery to the brain. Here, we describe the effects on epileptic seizures of encapsulated cell biodelivery (ECB) devices filled with genetically modified human cells engineered to release BDNF. These devices, implanted into the hippocampus of pilocarpine-treated rats, highly decreased the frequency of spontaneous seizures by more than 80%. These benefits were associated with improved cognitive performance, as epileptic rats treated with BDNF performed significantly better on a novel object recognition test...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29764626/25-hydroxvitamin-d-concentrations-are-not-lower-in-children-with-bronchial-asthma-atopic-dermatitis-obesity-or-attention-deficient-hyperactivity-disorder-than-in-healthy-children
#10
Thomas Reinehr, Christian Langrock, Eckard Hamelmann, Thomas Lücke, Cordula Koerner-Rettberg, Martin Holtmann, Tanja Legenbauer, Stephanie Gest, Mirjam Frank, Börge Schmidt, Katharina Radkowski, Karl-Heinz Jöckel
Vitamin D (vitD) is involved in immune regulation, and its receptor has been identified in several tissues including lung, adipose tissue, brain, and skin. Based on these observations, it has been suggested that vitD has an essential role not only in bone metabolism but also in other diseases such as atopic dermatitis (AD), bronchial asthma (BA), attention-deficit/hyperactivity disorder (ADHD), and obesity because the affected tissues express vitD receptors. Furthermore, obesity, AD, and BA are regarded as inflammatory diseases...
April 2018: Nutrition Research
https://www.readbyqxmd.com/read/29764580/-effect-of-rhubarb-on-neonatal-rats-with-bronchopulmonary-dysplasia-induced-by-hyperoxia
#11
Ling-Ling Yin, Zhen-Zhi Ye, Li-Jun Tang, Liang Guo, Wei-Min Huang
OBJECTIVE: To study the effect of rhubarb on neonatal rats with bronchopulmonary dysplasia (BPD) induced by hyperoxia. METHODS: A total of 64 rats (postnatal day 4) were randomly divided into four groups: air control, rhubarb control, hyperoxia model, and hyperoxia+rhubarb (n=16 each). The rats in the hyperoxia model and hyperoxia+rhubarb groups were exposed to hyperoxia (60% O2) to establish a BPD model. The rats in the rhubarb control and hyperoxia+rhubarb groups were given rhubarb extract suspension (600 mg/kg) by gavage daily...
May 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29761540/apixaban-decreases-brain-thrombin-activity-in-a-male-mouse-model-of-acute-ischemic-stroke
#12
Doron Bushi, Joab Chapman, Anton Wohl, Efrat Shavit Stein, Ekaterina Feingold, David Tanne
Factor Xa (FXa) plays a critical role in the coagulation cascade by generation of thrombin. During focal ischemia thrombin levels increase in the brain tissue and cause neural damage. This study examined the hypothesis that administration of the FXa inhibitor, apixaban, following focal ischemic stroke may have therapeutic potential by decreasing brain thrombin activity and infarct volume. Male mice were divided into a treated groups that received different doses of apixaban (2, 20, 100 mg/kg administered I...
May 14, 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29751734/apocarotenoids-emerging-roles-in-mammals
#13
Earl H Harrison, Loredana Quadro
Apocarotenoids are cleavage products of C40 isoprenoid pigments, named carotenoids, synthesized exclusively by plants and microorganisms. The colors of flowers and fruits and the photosynthetic process are examples of the biological properties conferred by carotenoids to these organisms. Mammals do not synthesize carotenoids but obtain them from foods of plant origin. Apocarotenoids are generated upon enzymatic and nonenzymatic cleavage of the parent compounds both in plants and in the tissues of mammals that have ingested carotenoid-containing foods...
May 11, 2018: Annual Review of Nutrition
https://www.readbyqxmd.com/read/29748235/p-glycoprotein-abcb1-inhibits-the-influx-and-increases-the-efflux-of-11-c-metoclopramide-across-the-blood-brain-barrier-a-pet-study-on-non-human-primates
#14
Sylvain Auvity, Fabien Caillé, Solène Marie, Catriona Wimberley, Martin Bauer, Oliver Langer, Irène Buvat, Sébastien Goutal, Nicolas Tournier
Rationale : PET imaging using radiolabeled high-affinity substrates of P-glycoprotein (ABCB1) has convincingly revealed the role of this major efflux transporter in limiting the influx of its substrates from blood into the brain across the blood-brain barrier (BBB). Many drugs, such as metoclopramide, are weak ABCB1 substrates and distribute into the brain even when ABCB1 is fully functional. In this study, we used kinetic modeling and validated simplified methods to highlight and quantify the impact of ABCB1 on the BBB influx and efflux of 11 C-metoclopramide, as a model weak ABCB1 substrate, in non-human primates...
May 10, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29747060/acoustic-stimulation-on-the-round-window-for-active-middle-ear-implants
#15
Kiwoong Seong, Kyuyup Lee, Sunil Puria, Jin-Ho Cho
Many clinical reports have discussed the effectiveness of stimulating the ear's round window (RW) with a tool to mitigate conductive and mixed hearing loss. The RW is one of the two openings from the middle ear into the inner ear. Various methods have been proposed to construct a highly efficient, easily implanted, and reliable RW transducer. Devices, however, such as floating mass transducers, have difficulty establishing proper contact without some degree of bone incision around the RW. Additionally, vibration energy may not be fully transmitted to the cochlea, but instead will be spread through the soft tissue around the transducer...
May 2, 2018: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/29740308/cyclosporin-a-mediated-activation-of-endogenous-neural-precursor-cells-promotes-cognitive-recovery-in-a-mouse-model-of-stroke
#16
Labeeba Nusrat, Jessica M Livingston-Thomas, Vaakiny Raguthevan, Kelsey Adams, Ilan Vonderwalde, Dale Corbett, Cindi M Morshead
Cognitive dysfunction following stroke significantly impacts quality of life and functional independance; yet, despite the prevalence and negative impact of cognitive deficits, post-stroke interventions almost exclusively target motor impairments. As a result, current treatment options are limited in their ability to promote post-stroke cognitive recovery. Cyclosporin A (CsA) has been previously shown to improve post-stroke functional recovery of sensorimotor deficits. Interestingly, CsA is a commonly used immunosuppressant and also acts directly on endogenous neural precursor cells (NPCs) in the neurogenic regions of the brain (the periventricular region and the dentate gyrus)...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29735438/-erythropoietin-accelerates-the-proliferation-of-glioma-cells-via-activating-akt-pathway
#17
Zi-Li Liu, Zhao-Hua Tang, Gang Huo, Fei-Lan Chen, Wen-Tao Wang, Wen-Xin Zeng, Hong Chen, Xin Li, Chen Chen
OBJECTIVE: To determine whether erythropoietin (EPO) promotes rapid proliferation of glioma through Akt pathway. METHODS: We detected the expression of EPO in human glioma tissues using immunohistochemistry. A nude mouse model bearing human glioma U87 cell xenograft was established and given intraperitoneal injection of EPO or saline every other day, and the tumor growth was observed. In the in vitro experiment, U87 cells were treated with PBS (control), EPO, or EPO with Akt inhibitor, and the expression of p-Akt and cyclin D1 was detected using Western blotting; the cell proliferation rate was determined using cell counting kit-8 and clone formation assay, and the cell cycle changes were analyzed with flow cytometry...
April 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/29729483/energy-response-of-diamond-sensor-to-beta-radiation
#18
Modeste Tchakoua Tchouaso, Haruetai Kasiwattanawut, Mark A Prelas
This paper demonstrates the ability of diamond sensors to respond to beta radiation. A Chemical Vapor Deposition (CVD) single crystal diamond was used in this work. The diamond crystal has a dimension of 4.5×4.5 by 0.5 mm thick. Metal contacts were fabricated on both sides of the diamond using titanium and palladium metals with thicknesses of 50 nm and 150 nm, respectively. The energy response of the diamond sensor was experimentally measured using three beta isotopes that cover the entire range of beta energy: 147 Pm, a weak beta radiation with a maximum energy of 0...
April 26, 2018: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/29728596/microrna-143-modulates-the-expression-of-natriuretic-peptide-receptor-3-in-cardiac-cells
#19
Juan Wang, Kai Sing Tong, Lee Lee Wong, Oi-Wah Liew, Divya Raghuram, Arthur Mark Richards, Yei-Tsung Chen
Natriuretic Peptide Receptor 3 (NPR3), the clearance receptor for extracellular bio-active natriuretic peptides (NPs), plays important roles in the homeostasis of body fluid volume and vascular tone. Using luciferase reporter and antagomir-based silencing assays, we demonstrated that the expression of NPR3 could be modulated by microRNA-143 (miR-143-3p), a microRNA species with up-regulated circulating concentrations in clinical heart failure. The regulatory effect of miR-143 on NPR3 expression was further evidenced by the reciprocal relationship between miR-143 and NPR3 levels observed in hypoxia-treated human cardiac cells and in left ventricular tissue from rats undergoing experimental myocardial infarction...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29727504/noninvasive-pk11195-pet-image-analysis-techniques-can-detect-abnormal-cerebral-microglial-activation-in-parkinson-s-disease
#20
Yeona Kang, P David Mozley, Ajay Verma, David Schlyer, Claire Henchcliffe, Susan A Gauthier, Ping C Chiao, Bin He, Anastasia Nikolopoulou, Jean Logan, Jenna M Sullivan, Kane O Pryor, Jacob Hesterman, Paresh J Kothari, Shankar Vallabhajosula
BACKGROUND AND PURPOSE: Neuroinflammation has been implicated in the pathophysiology of Parkinson's disease (PD), which might be influenced by successful neuroprotective drugs. The uptake of [11 C](R)-PK11195 (PK) is often considered to be a proxy for neuroinflammation, and can be quantified using the Logan graphical method with an image-derived blood input function, or the Logan reference tissue model using automated reference region extraction. The purposes of this study were (1) to assess whether these noninvasive image analysis methods can discriminate between patients with PD and healthy volunteers (HVs), and (2) to establish the effect size that would be required to distinguish true drug-induced changes from system variance in longitudinal trials...
May 4, 2018: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
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