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https://www.readbyqxmd.com/read/29777691/improving-electrical-properties-of-ipsc-cardiomyocytes-by-enhancing-cx43-expression
#1
Valentin Sottas, Carl-Mattheis Wahl, Mihnea C Trache, Michael Bartolf-Kopp, Sidney Cambridge, Markus Hecker, Nina D Ullrich
The therapeutic potential of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is limited by immature functional features including low impulse propagation and reduced cell excitability. Key players regulating electrical activity are voltage-gated Na+ channels (Nav 1.5) and gap junctions built from connexin-43 (Cx43). Here we tested the hypothesis that enhanced Cx43 expression increases intercellular coupling and influences excitability by modulating Nav 1.5. Using transgenic approaches, Cx43 and Nav 1...
May 16, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29776422/beating-the-odds-programming-proliferation-in-the-mammalian-heart
#2
Rajan Jain, Andrey Poleshko, Jonathan A Epstein
The heart is one of the least regenerative organs in the human body; adult cardiac myocytes divide at extremely low frequency. Therefore, meaningful induction of cardiac regeneration requires in-depth understanding of myocyte cell-cycle control. Recent insights into how myocytes can be coaxed into duplicating in vivo might inform emerging therapeutics.
May 18, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29776409/calcitriol-downregulates-fibroblast-growth-factor-receptor-1-through-histone-deacetylase-activation-in-hl-1-atrial-myocytes
#3
Ting-Wei Lee, Ting-I Lee, Yung-Kuo Lin, Yu-Hsun Kao, Yi-Jen Chen
BACKGROUND: Fibroblast growth factor (FGF)-2 plays a crucial role in the pathophysiology of cardiovascular diseases (CVDs). FGF-2 was reported to induce cardiac hypertrophy through activation of FGF receptor 1 (FGFR1). Multiple laboratory findings indicate that calcitriol may be a potential treatment for CVDs. In this study, we attempted to investigate whether calcitriol regulates FGFR1 expression to modulate the effects of FGF-2 signaling in cardiac myocytes and explored the potential regulatory mechanism...
May 18, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29775452/the-effects-of-a-pulsed-electromagnetic-field-on-the-proliferation-and-osteogenic-differentiation-of-human-adipose-derived-stem-cells
#4
Yukun Yin, Ping Chen, Qiang Yu, Yan Peng, ZeHao Zhu, Jing Tian
BACKGROUND A low frequency pulsed electromagnetic field (PEMF) has been confirmed to play an important role in promoting the osteogenic differentiation of human bone marrow stem cells (BMSCs). Adipose-derived stem cells (ASCs) possess some attractive characteristics for clinical application compared to BMSCs, such as abundant stem cells from lipoaspirates, faster growth, less discomfort and morbidity during surgery. ASCs can become adipocytes, osteoblasts, chondrocytes, myocytes, neurocytes, and other cell types...
May 18, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29774530/cardiomyocyte-programmed-necrosis-mitochondria-death-receptor-and-beyond
#5
REVIEW
Junxia Zhang, Dairu Liu, Mao Zhang, Yan Zhang
Excessive death of cardiac myocytes leads to multiple cardiac diseases, including myocardial infarction, arrhythmia, heart failure and sudden cardiac death. For the last several decades, most work on cell death has focused on apoptosis, which is generally considered as the only form of regulated cell death, whereas necrosis has been regarded to be an unregulated process. Recent findings reveal that necrosis also occurs in a regulated manner and that it is closely related to the physiology and pathophysiology of multiple organs, including the heart...
May 18, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29773756/mir126-5p-down-regulation-facilitates-axon-degeneration-and-nmj-disruption-via-a-non-cell-autonomous-mechanism-in-als
#6
Roy Maimon, Ariel Ionescu, Avichai Bonnie, Sahar Sweetat, Shane Wald-Altman, Shani Inbar, Tal Gradus, Davide Trotti, Miguel Weil, Oded Behar, Eran Perlson
Axon degeneration and disruption of neuromuscular junctions (NMJs) are key events in Amyotrophic Lateral Sclerosis (ALS) pathology. Although the disease's etiology is not fully understood, it is thought to involve a non-cell-autonomous mechanism and alterations in RNA metabolism. Here, we identified reduced levels of miR-126-5p in pre-symptomatic ALS male mice models, and an increase in its targets: axon destabilizing type-3 Semaphorins and their co-receptor Neuropilins. Utilizing compartmentalized in vitro co-cultures, we demonstrated that myocytes expressing diverse ALS-causing mutations promote axon degeneration and NMJ dysfunction, which were inhibited by applying Neuropilin1 (NRP1) blocking antibody...
May 17, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29772546/gpcr-autoantibodies-in-chronic-heart-failure
#7
Valerie Boivin-Jahns, Roland Jahns
Chronic heart failure (CHF) is a syndrome characterized by shortness of breath, fluid retention, and a progressive reduction in cardiac function. More than 60% of the cases are ischemic in origin (i.e., due to myo-cardial infarction) and about 30% are caused by non-ischemic myocardial damage (i.e., due to genetic or non-genetic causes like myocardial inflammation). Because of alterations in both cellular and humoral immunity patients with non-ischemic CHF often develop abnormal or misled immune responses, including cross-reacting antibodies and/or autoantibodies to various cardiac anti-gens...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29769426/effect-of-the-intracellular-calcium-concentration-chelator-bapta-acetoxy-methylester-on-action-potential-duration-in-canine-ventricular-myocytes
#8
B Horvath, N Szentandrassy, R Veress, D Baranyai, K Kistamas, J Almassy, A Toth, J Magyar, T Banyasz, P P Nanasi
Intracellular calcium concentration ([Ca2+ ]i ) is often buffered by using the cell-permeant acetoxy-methylester form of the Ca2+ chelator BAPTA (BAPTA-AM) under experimental conditions. This study was designed to investigate the time-dependent actions of extracellularly applied BAPTA-AM on action potential duration (APD) in cardiac cells. Action potentials were recorded from enzymatically isolated canine ventricular myocytes with conventional sharp microelectrodes. The effect of BAPTA-AM on the rapid delayed rectifier K+ current (IKr ) was studied using conventional voltage clamp and action potential voltage clamp techniques...
February 2018: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29769316/the-serine-threonine-protein-kinase-endoribonuclease-ire1%C3%AE-protects-the-heart-against-pressure-overload-induced-heart-failure
#9
DeAnna Steiger, Tomohiro Yokota, Jin Li, Shuxun Ren, Susumu Minamisawa, Yibin Wang
Heart failure is associated with induction of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). The serine/threonine protein kinase/endoribonuclease IRE1α is a key protein in ER stress signal transduction. IRE1α activity can induce both protective UPR and apoptotic downstream signaling events, but the specific role for IRE1α activity in the heart is unknown. A major aim of this study was to characterize the specific contribution of IRE1α in cardiac physiology and pathogenesis. We used both cultured myocytes and a transgenic mouse line with inducible and cardiomyocyte-specific IRE1α overexpression as experimental models to achieve targeted IRE1α activation...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29765066/loss-of-cenp-f-results-in-dilated-cardiomyopathy-with-severe-disruption-of-cardiac-myocyte-architecture
#10
Annabelle Manalo, Alison K Schroer, Aidan M Fenix, Zoe Shancer, John Coogan, Tanner Brolsma, Dylan T Burnette, W David Merryman, David M Bader
Centromere-binding protein F (CENP-F) is a very large and complex protein with many and varied binding partners including components of the microtubule network. Numerous CENP-F functions impacting diverse cellular behaviors have been identified. Importantly, emerging data have shown that CENP-F loss- or gain-of-function has critical effects on human development and disease. Still, it must be noted that data at the single cardiac myocyte level examining the impact of CENP-F loss-of-function on fundamental cellular behavior is missing...
May 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29760730/current-progress-and-challenges-for-skeletal-muscle-differentiation-from-human-pluripotent-stem-cells-using-transgene-free-approaches
#11
REVIEW
Nunnapas Jiwlawat, Eileen Lynch, Jeremy Jeffrey, Jonathan M Van Dyke, Masatoshi Suzuki
Neuromuscular diseases are caused by functional defects of skeletal muscles, directly via muscle pathology or indirectly via disruption of the nervous system. Extensive studies have been performed to improve the outcomes of therapies; however, effective treatment strategies have not been fully established for any major neuromuscular disease. Human pluripotent stem cells have a great capacity to differentiate into myogenic progenitors and skeletal myocytes for use in treating and modeling neuromuscular diseases...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29759937/identification-of-epigenetic-regulators-of-dux4-fl-for-targeted-therapy-of-facioscapulohumeral-muscular-dystrophy
#12
Charis L Himeda, Takako I Jones, Ching-Man Virbasius, Lihua Julie Zhu, Michael R Green, Peter L Jones
Facioscapulohumeral muscular dystrophy (FSHD) is caused by epigenetic de-repression of the disease locus, leading to pathogenic misexpression of the DUX4 gene in skeletal muscle. While the factors and pathways involved in normal repression of the FSHD locus in healthy cells have been well characterized, very little is known about those responsible for the aberrant activation of DUX4-fl in FSHD myocytes. Reasoning that DUX4-fl activators might represent useful targets for small molecule inhibition, we performed a highly targeted, candidate-based screen of epigenetic regulators in primary FSHD myocytes...
April 26, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29758700/memory-induced-nonlinear-dynamics-of-excitation-in-cardiac-diseases
#13
Julian Landaw, Zhilin Qu
Excitable cells, such as cardiac myocytes, exhibit short-term memory, i.e., the state of the cell depends on its history of excitation. Memory can originate from slow recovery of membrane ion channels or from accumulation of intracellular ion concentrations, such as calcium ion or sodium ion concentration accumulation. Here we examine the effects of memory on excitation dynamics in cardiac myocytes under two diseased conditions, early repolarization and reduced repolarization reserve, each with memory from two different sources: slow recovery of a potassium ion channel and slow accumulation of the intracellular calcium ion concentration...
April 2018: Physical Review. E
https://www.readbyqxmd.com/read/29758550/microrna-449a-inhibition-protects-h9c2-cells-against-hypoxia-reoxygenation-induced-injury-by-targeting-the-notch-1-signaling-pathway
#14
Jing Cheng, Qianfu Wu, Rong Lv, Li Huang, Banglong Xu, Xianbao Wang, Aihua Chen, Fei He
BACKGROUND/AIMS: The present study aimed to detect the expression of miR-449a and investigate the effect of miR-449a on cell injury in cardiomyocytes subjected to hypoxia/ reoxygenation (H/R) and its underlying mechanisms. METHODS: The expression of miR-449a was determined using reverse transcription-polymerase chain reaction in both neonatal rat ventricular myocytes and H9C2 cells. For gain-of-function and loss-of-function studies, H9C2 cells were transfected with either miR-449a mimics or miR-449a inhibitor...
May 7, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29757934/comparison-of-synthetic-media-designed-for-expansion-of-adipose-derived-mesenchymal-stromal-cells
#15
Michelle Lensch, Angela Muise, Lisa White, Michael Badowski, David Harris
Mesenchymal stromal cells (MSCs) are multipotent cells that can differentiate into various cell types, such as osteoblasts, myocytes, and adipocytes. This characteristic makes the cells a useful tool in developing new therapies for a number of common maladies and diseases. The utilization of animal-derived growth serum, such as fetal bovine serum (FBS), for the expansion of MSCs has traditionally been used for cell culture. However, in clinical applications, animal-derived products present limitations and safety concerns for the recipient, as exposure to animal (xeno-) antigens and infectious agents is possible...
May 14, 2018: Biomedicines
https://www.readbyqxmd.com/read/29757281/analyses-of-mitochondrial-calcium-influx-in-isolated-mitochondria-and-cultured-cells
#16
Joshua T Maxwell, Chin-Hsien Tsai, Tahmina A Mohiuddin, Jennifer Q Kwong
Ca2+ handling by mitochondria is a critical function regulating both physiological and pathophysiological processes in a broad spectrum of cells. The ability to accurately measure the influx and efflux of Ca2+ from mitochondria is important for determining the role of mitochondrial Ca2+ handling in these processes. In this report, we present two methods for the measurement of mitochondrial Ca2+ handling in both isolated mitochondria and cultured cells. We first detail a plate reader-based platform for measuring mitochondrial Ca2+ uptake using the Ca2+ sensitive dye calcium green-5N...
April 27, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29755362/the-interplay-of-rogue-and-clustered-ryanodine-receptors-regulates-ca-2-waves-in-cardiac-myocytes
#17
Xudong Chen, Yundi Feng, Yunlong Huo, Wenchang Tan
Ca2+ waves in cardiac myocytes can lead to arrhythmias owing to delayed after-depolarisations. Based on Ca2+ regulation from the junctional sarcoplasmic reticulum (JSR), a mathematical model was developed to investigate the interplay of clustered and rogue RyRs on Ca2+ waves. The model successfully reproduces Ca2+ waves in cardiac myocytes, which are in agreement with experimental results. A new wave propagation mode of "spark-diffusion-quark-spark" is put forward. It is found that rogue RyRs greatly increase the initiation of Ca2+ sparks, further contribute to the formation and propagation of Ca2+ waves when the free Ca2+ concentration in JSR lumen ([Ca2+ ]lumen ) is higher than a threshold value of 0...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29754923/enhanced-late-sodium-current-underlies-pro-arrhythmic-intracellular-sodium-and-calcium-dysregulation-in-murine-sodium-channelopathy
#18
Mathilde R Rivaud, Antonius Baartscheer, Arie O Verkerk, Leander Beekman, Sridharan Rajamani, Luiz Belardinelli, Connie R Bezzina, Carol Ann Remme
BACKGROUND: Long QT syndrome mutations in the SCN5A gene are associated with an enhanced late sodium current (INa,L ) which may lead to pro-arrhythmic action potential prolongation and intracellular calcium dysregulation. We here investigated the dynamic relation between INa,L , intracellular sodium ([Na+ ]i ) and calcium ([Ca2+ ]i ) homeostasis and pro-arrhythmic events in the setting of a SCN5A mutation. METHODS AND RESULTS: Wild-type (WT) and Scn5a1798insD/+ (MUT) mice (age 3-5 months) carrying the murine homolog of the SCN5A-1795insD mutation on two distinct genetic backgrounds (FVB/N and 129P2) were studied...
July 15, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29754437/reduced-fiber-size-capillary-supply-and-mitochondrial-activity-in-constitutional-thinness-skeletal-muscle
#19
Bogdan Galusca, Julien Verney, Emmanuelle Meugnier, Yiin Ling, Pascal Edouard, Leonard Feasson, Marion Ravelojaona, Hubert Vidal, Bruno Estour, Natacha Germain
AIM: Constitutional thinness (CT) is a rare condition of natural low bodyweight, with no psychological issues, no marker of undernutrition and a resistance to weight gain. This study evaluated the skeletal muscle phenotype of CT women by comparison to a normal BMI control group. METHODS: 10 CT women (BMI< 17.5 kg/m2) and 10 female controls (BMI: 18.5-25 kg/m2) underwent metabolic and hormonal assessment along with muscle biopsies to analyse the skeletal muscular fibers pattern, capillarity, enzymes activities and transcriptomics...
May 13, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29752569/widespread-expression-of-perilipin-5-in-normal-human-tissues-and-in-diseases-is-restricted-to-distinct-lipid-droplet-subpopulations
#20
Merita Hashani, Hagen Roland Witzel, Lena Maria Pawella, Judith Lehmann-Koch, Jens Schumacher, Gunhild Mechtersheimer, Martina Schnölzer, Peter Schirmacher, Wilfried Roth, Beate Katharina Straub
Diseases associated with the accumulation of lipid droplets are increasing in western countries. Lipid droplet biogenesis, structure and degradation are regulated by proteins of the perilipin family. Perilipin 5 has been shown to regulate basal lipolysis in oxidative tissues. We examine perilipin 5 in normal human tissues and in diseases using protein biochemical and microscopic techniques. Perilipin 5 was constitutively located at small lipid droplets in skeletal myocytes, cardiomyocytes and brown adipocytes...
May 11, 2018: Cell and Tissue Research
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