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https://www.readbyqxmd.com/read/29775742/ryanodine-receptor-ca-2-release-channel-post-translational-modification-central-player-in-cardiac-and-skeletal-muscle-disease
#1
Amanda Denniss, Angela F Dulhunty, Nicole A Beard
Calcium release from internal stores is a quintessential event in excitation-contraction coupling in cardiac and skeletal muscle. The ryanodine receptor Ca2+ release channel is embedded in the internal sarcoplasmic reticulum Ca2+ store, which releases Ca2+ into the cytoplasm, enabling contraction. Ryanodine receptors form the hub of a macromolecular complex extending from the extracellular space to the sarcoplasmic reticulum lumen. Ryanodine receptor activity is influenced by the integrated effects of associated co-proteins, ions, and post-translational phosphor and redox modifications...
May 15, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29774078/targeting-intracellular-mmps-efficiently-inhibits-tumor-metastasis-and-angiogenesis
#2
Yaqi Lv, Xiangmei Zhao, Lidan Zhu, Sijia Li, Qingqing Xiao, Wei He, Lifang Yin
Treatment for metastatic cancer is a great challenge throughout the world. Commonly, directed inhibition of extracellular matrix metalloproteinases (MMPs) secreted by cancer cells can reduce metastasis. Here, a novel nanoplatform (HPMC NPs) assembled from hyaluronic acid (HA)-paclitaxel (PTX) prodrug and marimastat (MATT)/β-casein (CN) complexes was established to cure a 4T1 metastatic cancer model via targeting CD44 and intracellular, rather than extracellular, MMPs. Methods: HPMC NPs were prepared by assembling the complexes and prodrug under ultrasonic treatment, which the interaction between them was evaluated by förster resonance energy transfer, circular dichroism and fluorescence spectra...
2018: Theranostics
https://www.readbyqxmd.com/read/29774023/ferritin-h-deficiency-in-myeloid-compartments-dysregulates-host-energy-metabolism-and-increases-susceptibility-to-mycobacterium-tuberculosis-infection
#3
Vineel P Reddy, Krishna C Chinta, Vikram Saini, Joel N Glasgow, Travis D Hull, Amie Traylor, Fernanda Rey-Stolle, Miguel P Soares, Rajhmun Madansein, Md Aejazur Rahman, Coral Barbas, Kievershen Nargan, Threnesan Naidoo, Pratistadevi K Ramdial, James F George, Anupam Agarwal, Adrie J C Steyn
Iron is an essential factor for the growth and virulence of Mycobacterium tuberculosis ( Mtb) . However, little is known about the mechanisms by which the host controls iron availability during infection. Since ferritin heavy chain (FtH) is a major intracellular source of reserve iron in the host, we hypothesized that the lack of FtH would cause dysregulated iron homeostasis to exacerbate TB disease. Therefore, we used knockout mice lacking FtH in myeloid-derived cell populations to study Mtb disease progression...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29773170/iron-and-innate-antimicrobial-immunity-depriving-the-pathogen-defending-the-host
#4
REVIEW
Manfred Nairz, Stefanie Dichtl, Andrea Schroll, David Haschka, Piotr Tymoszuk, Igor Theurl, Günter Weiss
The acute-phase response is triggered by the presence of infectious agents and danger signals which indicate hazards for the integrity of the mammalian body. One central feature of this response is the sequestration of iron into storage compartments including macrophages. This limits the availability of this essential nutrient for circulating pathogens, a host defence strategy known as 'nutritional immunity'. Iron metabolism and the immune response are intimately linked. In infections, the availability of iron affects both the efficacy of antimicrobial immune pathways and pathogen proliferation...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29772703/alpha-mangostin-improves-insulin-secretion-and-protects-ins-1-cells-from-streptozotocin-induced-damage
#5
Dahae Lee, Young-Mi Kim, Kiwon Jung, Young-Won Chin, Ki Sung Kang
Alpha (α)-mangostin, a yellow crystalline powder with a xanthone core structure, is isolated from mangosteen ( Garcinia mangostana ), which is a tropical fruit of great nutritional value. The aim of the present study was to investigate the anti-diabetic effects of α-mangostin and to elucidate the molecular mechanisms underlying its effect on pancreatic beta (β)-cell dysfunction. To assess the effects of α-mangostin on insulin production, rat pancreatic INS-1 cells were treated with non-toxic doses of α-mangostin (1⁻10 μM) and its impact on insulin signaling was examined by Western blotting...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29771149/preparation-and-evaluation-of-tumour-microenvironment-response-multistage-nanoparticles-for-epirubicin-delivery-and-deep-tumour-penetration
#6
Jialing Dai, Shangcong Han, Fang Ju, Mei Han, Lisa Xu, Ruoyu Zhang, Yong Sun
Poor tumour penetration became a major challenge for the use of nanoparticles in anticancer therapy. To further enhance the tumour penetration efficiency, we developed a tumour-microenvironment-responsive multistage drug delivery system which was formed layer by layer via electrostatic interaction with cationic drug-loaded nanoparticles, hyaluronidase (HAase) and iRGD-modified gelatin (G-iRGD). The drug-loaded nanoparticles were formed by self-assembling mPEG-PDPA-PG and encapsulation with epirubicin (EPI)...
May 17, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29770299/regenerative-medicine-therapy-for-single-ventricle-congenital-heart-disease
#7
REVIEW
Chetan Ambastha, Gregory J Bittle, David Morales, Nathaniel Parchment, Progyaparamita Saha, Rachana Mishra, Sudhish Sharma, Alexander Vasilenko, Muthukumar Gunasekaran, Manal T Al-Suqi, Deqiang Li, Peixin Yang, Sunjay Kaushal
One of the most complex forms of congenital heart disease (CHD) involving single ventricle physiology is hypoplastic left heart syndrome (HLHS), characterized by underdevelopment of the left ventricle (LV), mitral and aortic valves, and narrowing of the ascending aorta. The underdeveloped LV is incapable of providing long-term systemic flow, and if left untreated, the condition is fatal. Current treatment for this condition consists of three consecutive staged palliative operations: the first is conducted within the first few weeks of birth, the second between 4 to 6 months, and the third and final surgery within the first 4 years...
April 2018: Translational Pediatrics
https://www.readbyqxmd.com/read/29769446/ubiquitination-and-deubiquitination-emerge-as-players-in-idiopathic-pulmonary-fibrosis-pathogenesis-and-treatment
#8
REVIEW
Shuang Li, Jing Zhao, Dong Shang, Daniel J Kass, Yutong Zhao
Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disease that is associated with aberrant activation of TGF-β, myofibroblast differentiation, and abnormal extracellular matrix (ECM) production. Proper regulation of protein stability is important for maintenance of intracellular protein homeostasis and signaling. Ubiquitin E3 ligases mediate protein ubiquitination, and deubiquitinating enzymes (DUBs) reverse the process. The role of ubiquitin E3 ligases and DUBs in the pathogenesis of IPF is relatively unexplored...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29769426/effect-of-the-intracellular-calcium-concentration-chelator-bapta-acetoxy-methylester-on-action-potential-duration-in-canine-ventricular-myocytes
#9
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/29769329/isolation-of-state-dependent-monoclonal-antibodies-against-the-12-transmembrane-domain-glucose-transporter-4-using-virus-like-particles
#10
David F Tucker, Jonathan T Sullivan, Kimberly-Anne Mattia, Christine R Fisher, Trevor Barnes, Manu N Mabila, Rona Wilf, Chidananda Sulli, Meghan Pitts, Riley J Payne, Moniquetta Hall, Duncan Huston-Paterson, Xiaoxiang Deng, Edgar Davidson, Sharon H Willis, Benjamin J Doranz, Ross Chambers, Joseph B Rucker
The insulin-responsive 12-transmembrane transporter GLUT4 changes conformation between an inward-open state and an outward-open state to actively facilitate cellular glucose uptake. Because of the difficulties of generating conformational mAbs against complex and highly conserved membrane proteins, no reliable tools exist to measure GLUT4 at the cell surface, follow its trafficking, or detect the conformational state of the protein. Here we report the isolation and characterization of conformational mAbs that recognize the extracellular and intracellular domains of GLUT4, including mAbs that are specific for the inward-open and outward-open states of GLUT4...
May 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29768491/plasmodium-falciparum-dipeptidyl-aminopeptidase-3-activity-is-important-for-efficient-erythrocyte-invasion-by-the-malaria-parasite
#11
Christine Lehmann, Michele Ser Ying Tan, Laura E de Vries, Ilaria Russo, Mateo Isidrio Sanchez, Daniel E Goldberg, Edgar Deu
Parasite egress from infected erythrocytes and invasion of new red blood cells are essential processes for the exponential asexual replication of the malaria parasite. These two tightly coordinated events take place in less than a minute and are in part regulated and mediated by proteases. Dipeptidyl aminopeptidases (DPAPs) are papain-fold cysteine proteases that cleave dipeptides from the N-terminus of protein substrates. DPAP3 was previously suggested to play an essential role in parasite egress. However, little is known about its enzymatic activity, intracellular localization, or biological function...
May 16, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29768045/mfe-hi-adipose-tissue-macrophages-compensate-for-tissue-iron-pertubations-in-mice
#12
Merla J Hubler, Keith M Erikson, Arion J Kennedy, Alyssa H Hasty
Resident adipose tissue macrophages (ATMs) play multiple roles to maintain tissue homeostasis, such as removing excess FFAs and regulation of extracellular matrix. The phagocytic nature and oxidative resiliency of macrophages not only allows them to function as innate immune cells but also to respond to specific tissue needs, such as iron homeostasis. MFehi ATMs are a subtype of resident ATMs that we recently identified to have twice the intracellular iron content as other ATMs and elevated expression of iron handling genes...
May 16, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29767993/multi-metallic-microparticles-increase-the-potency-of-rifampicin-against-intracellular-mycobacterium-tuberculosis
#13
Timothy Ellis, Michele Chiappi, Andres Garcia-Trenco, Maryam Al-Ejji, Srijata Sarkar, Theoni K Georgiou, Milo Sebastian Peter Shaffer, Teresa D Tetley, Stephan Schwander, Mary P Ryan, Alexandra E Porter
Mycobacterium tuberculosis (M.tb) has the extraordinary ability to adapt to the administration of antibiotics through the development of resistance mechanisms. By rapidly exporting drugs from within the cytosol, these pathogenic bacteria diminish antibiotic potency and drive the presentation of drug tolerant tuberculosis (TB). The membrane integrity of M.tb is pivotal in retaining these drug-resistant traits. Silver (Ag) and zinc oxide (ZnO) nanoparticles (NPs) are established antimicrobial agents that effectively compromise membrane stability, giving rise to increased bacterial permeability to antibiotics...
May 16, 2018: ACS Nano
https://www.readbyqxmd.com/read/29766792/gabaa-receptors-various-stoichiometrics-of-subunit-arrangement-in-%C3%AE-1%C3%AE-3-and-%C3%AE-1%C3%AE-3%C3%AE%C2%B5-receptors
#14
Ahmad Tarmizi Che Has, Mary Chebib
GABAA receptors (GABAARs) are members of the Cys-loop ligand-gated ion channel (LGIC) superfamily, which includes nicotinic acetylcholine, glycine, and serotonin (5HT3) receptors [1,2,3,4]. LGICs typically mediate fast synaptic transmission via the movement of ions through channels gated by neurotransmitters, such as acetylcholine for nicotinic receptors and GABA for GABAARs [5]. The term Cys-loop receptors originates from the presence of a conserved disulphide bond (or bridge) which holds together two cysteine amino acids of the loop that forms from the structure of polypeptides in the extracellular domain of the receptor's subunit [6]...
May 15, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29766408/association-between-circulating-levels-of-heat-shock-protein-27-and-aggressive-periodontitis
#15
Frank Kaiser, Nikos Donos, Brian Henderson, Rajesh Alagarswamy, George Pelekos, David Boniface, Luigi Nibali
Heat-shock protein (Hsp) 27 is a major intracellular molecular chaperone and controller of intracellular responses to inflammatory signals. In the extracellular space, recombinant Hsp27 has been described to exert anti-inflammatory activities. The aim of this study was to assess the association between circulating levels of Hsp27 and different types of periodontitis. Pro- and anti-inflammatory cytokines and the stress proteins Hsp27 and Hsp60 with proposed anti- and pro-inflammatory properties, respectively, were measured by two-site ELISA in the serum of patients with aggressive periodontitis (AgP, n = 30), chronic periodontitis (CP, n = 29) and periodontally healthy controls (H, n = 28)...
May 15, 2018: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/29765991/immune-response-and-evasion-mechanisms-of-plasmodium-falciparum-parasites
#16
REVIEW
Esmael Besufikad Belachew
Malaria causes approximately 212 million cases and 429 thousand deaths annually. Plasmodium falciparum is responsible for the vast majority of deaths (99%) than others. The virulence of P. falciparum is mostly associated with immune response-evading ability. It has different mechanisms to evade both Anopheles mosquito and human host immune responses. Immune-evading mechanisms in mosquito depend mainly on the Pfs47 gene that inhibits Janus kinase-mediated activation. Host complement factor also protects human complement immune attack of extracellular gametes in Anopheles mosquito midgut...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29765356/soluble-and-cell-cell-mediated-drivers-of-proteasome-inhibitor-resistance-in-multiple-myeloma
#17
REVIEW
Mariah L Farrell, Michaela R Reagan
It is becoming clear that myeloma cell-induced disruption of the highly organized bone marrow components (both cellular and extracellular) results in destruction of the marrow and support for multiple myeloma (MM) cell proliferation, survival, migration, and drug resistance. Since the first phase I clinical trial on bortezomib was published 15 years ago, proteasome inhibitors (PIs) have become increasingly common for treatment of MM and are currently an essential part of any anti-myeloma combination therapy...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29765331/high-ph-sensitive-store-operated-ca-2-entry-mediated-by-ca-2-release-activated-ca-2-channels-in-rat-odontoblasts
#18
Maki Kimura, Koichi Nishi, Asuka Higashikawa, Sadao Ohyama, Kaoru Sakurai, Masakazu Tazaki, Yoshiyuki Shibukawa
Odontoblasts play a crucial role in dentin formation and sensory transduction following the application of stimuli to the dentin surface. Various exogenous and endogenous stimuli elicit an increase in the intracellular free calcium concentration ([Ca2+ ]i ) in odontoblasts, which is mediated by Ca2+ release from intracellular Ca2+ stores and/or Ca2+ influx from the extracellular medium. In a previous study, we demonstrated that the depletion of Ca2+ stores in odontoblasts activated store-operated Ca2+ entry (SOCE), a Ca2+ influx pathway...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29765007/from-intra-to-extracellular-vesicles-extracellular-vesicles-in-developmental-signalling
#19
REVIEW
Ana-Citlali Gradilla, Eléanor Simon, Gustavo Aguilar, Isabel Guerrero
Signalling from cell-to-cell is fundamental for determining differentiation and patterning. This communication can occur between adjacent and distant cells. Extracellular vesicles (EVs) are membrane-based structures thought to facilitate the long-distance movement of signalling molecules. EVs have recently been found to allow the transport of two major developmental signalling pathways: Hedgehog and Wnt. These signalling molecules undergo crucial post-translational lipid modifications, which anchor them to membranes and impede their free release into the extracellular space...
May 15, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/29764923/extracellular-vesicles-lipids-as-key-components-of-their-biogenesis-and-functions
#20
Michel Record, Sandrine Silvente-Poirot, Marc Poirot, Michael J O Wakelam
Intercellular communication has been known for decades to involve either direct contact between cells or to operate by spreading molecules such as cytokines, growth factors, or lipid mediators. Through the last decade we have begun to appreciate the increasing importance of intercellular communication mediated by extracellular vesicles released by viable cells either from plasma membrane shedding microvesicles, also named microparticles), or from an intracellular compartment (exosomes). Exosomes and microvesicles circulate in all biological fluids and can trigger biological responses at distance...
May 15, 2018: Journal of Lipid Research
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