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https://www.readbyqxmd.com/read/28435089/cobalt-chloride-induces-rhoa-rock-activation-and-remodeling-effect-in-h9c2-cardiomyoblasts-involvement-of-pi3k-akt-and-mapk-pathways
#1
Cheng-I Cheng, Yueh-Hong Lee, Po-Han Chen, Yu-Chun Lin, Ming-Huei Chou, Ying-Hsien Kao
Chronic heart failure is a serious complication of myocardial infarction, one of the major causes of death worldwide that often leads to adverse cardiac hypertrophy and poor prognosis. Hypoxia-induced cardiac tissue remodeling is considered an important underlying etiology. This study aimed to delineate the signaling profile of RhoA/ROCK, PI3K/Akt, and MAPK and their involvement in regulation of remodeling events in cultured H9c2 cardiomyoblast cells. In addition to its growth-suppressive effect, the hypoxia-mimetic chemical, cobalt chloride (CoCl2) significantly induced RhoA kinase activation as revealed by increased MBS phosphorylation and ROCK1/2 expression in H9c2 cells...
April 20, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28434949/maternal-immune-activation-during-pregnancy-in-rats-impairs-working-memory-capacity-of-the-offspring
#2
Brendan G Murray, Don A Davies, Joel J Molder, John G Howland
Maternal immune activation during pregnancy is an environmental risk factor for psychiatric illnesses such as schizophrenia in the offspring. Patients with schizophrenia display an array of cognitive symptoms, including impaired working memory capacity. Rodent models have been developed to understand the relationship between maternal immune activation and the cognitive symptoms of schizophrenia. The present experiment was designed to test whether maternal immune activation with the viral mimetic polyinosinic:polycytidylic acid (polyI:C) during pregnancy affects working memory capacity of the offspring...
April 18, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28434765/4-connected-azabicyclo-5-3-0-decane-smac-mimetics-zn-2-chelators-as-dual-action-antitumoral-agents
#3
Leonardo Manzoni, Alessandro Samela, Stefano Barbini, Silvia Cairati, Marta Penconi, Daniela Arosio, Daniele Lecis, Pierfausto Seneci
Putative dual action compounds (DACs 3a-d) based on azabicyclo[5.3.0]decane (ABD) Smac mimetic scaffolds linked to Zn(2+)-chelating 2,2'-dipicolylamine (DPA) through their 4 position are reported and characterized. Their synthesis, their target affinity (cIAP1 BIR3, Zn(2+)) in cell-free assays, their pro-apoptotic effects, and their cytotoxicity in tumor cells with varying sensitivity to Smac mimetics are described. A limited influence of Zn(2+) chelation on in vitro activity of DPA-substituted DACs 3a-d was sometimes perceivable, but did not lead to strong cellular synergistic effects...
April 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28433788/regulation-of-human-nucleus-pulposus-cells-by-peptide-coupled-substrates
#4
Devin T Bridgen, Bailey V Fearing, Liufang Jing, Johannah Sanchez-Adams, Megan C Cohan, Farshid Guilak, Jun Chen, Lori A Setton
Nucleus pulposus (NP) cells are derived from the notochord and differ from neighboring cells of the intervertebral disc in phenotypic marker expression and morphology. Adult human NP cells lose this phenotype and morphology with age in a pattern that contributes to progressive disc degeneration and pathology. Select laminin-mimetic peptide ligands and substrate stiffnesses were examined for their ability to regulate human NP cell phenotype and biosynthesis through the expression of NP-specific markers aggrecan, N-cadherin, collagen types I and II, and GLUT1...
April 19, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28433778/novel-lipid-mimetic-prodrugs-delivering-active-compounds-to-adipose-tissue
#5
Andrea Mattarei, Andrea Rossa, Veronica Bombardelli, Michele Azzolini, Martina La Spina, Cristina Paradisi, Mario Zoratti, Lucia Biasutto
Obesity and associated pathologies are a dramatically growing problem. New therapies to prevent and/or cure them are strongly needed. Adipose tissue is a logical target for pharmacological intervention, since it is now recognized to exert an important endocrine function, secreting a variety of adipokines affecting, for example, adiposity and insulin resistance. This proof of principle work focuses on the development of novel lipid-mimetic prodrugs reaching fat deposits by the same lymphatic absorption route followed by dietary triglycerides...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28431961/ionizing-radiation-induces-long-term-senescence-in-endothelial-cells-through-mitochondrial-respiratory-complex-ii-dysfunction-and-superoxide-generation
#6
Audrey Lafargue, Charlotte Degorre, Isabelle Corre, Marie-Clotilde Alves-Guerra, Marie-Hélène Gaugler, François Vallette, Claire Pecqueur, François Paris
Ionizing radiation causes oxidative stress, leading to acute and late cellular responses. We previously demonstrated that irradiation of non-proliferating endothelial cells, as observed in normal tissues, induces early apoptosis, which can be inhibited by pretreatment with Sphingosine-1-Phosphate. We now propose to better characterize the long-term radiation response of endothelial cells by studying the molecular pathways associated with senescence and its link with acute apoptosis. First, senescence was validated in irradiated quiescent microvascular HMVEC-L in a dose- and time-dependent manner by SA β-galactosidase staining, p16(Ink4a) and p21(Waf1) expression, pro-inflammatory IL-8 secretion and DNA damage response activation...
April 18, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28431006/regulation-of-oxidized-platelet-lipidome-implications-for-coronary-artery-disease
#7
Madhumita Chatterjee, Dominik Rath, Jörg Schlotterbeck, Johannes Rheinlaender, Britta Walker-Allgaier, Nada Alnaggar, Monika Zdanyte, Iris Müller, Oliver Borst, Tobias Geisler, Tilman E Schäffer, Michael Lämmerhofer, Meinrad Gawaz
Aims: Hyperlipidaemia enhances susceptibility to thrombosis, while platelet oxidixed LDL (oxLDL) binding in acute coronary syndrome (ACS) correlates with activation status. This study explores the platelet lipidome in symptomatic coronary artery disease (CAD) patients and the functional consequences of the chemokine CXCL12 and its receptors CXCR-4/-7 on lipid uptake in platelets. Methods and results: Platelet-oxLDL detected by flow cytometry was enhanced (P = 0...
April 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28430274/high-throughput-and-ultratrace-naked-eye-colorimetric-detection-of-au-3-based-on-the-gold-amalgam-stimulated-peroxidase-mimetic-activity-in-aqueous-solutions
#8
Shouting Zhang, Zhuoyue Zhang, Tiansheng Wang, Dongxu Zhang, Xuemei Li, Zhonghua Xue, Duoliang Shan, Xiaoquan Lu
Herein, we present a catalysis-based, label-free, and efficient strategy for a rapid, high-throughput, highly selective and ultrasensitive naked-eye colorimetric assay of Au(3+) in aqueous solutions, based on the gold amalgam-stimulated peroxidase mimetic activity.
April 21, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28430190/tuning-underwater-adhesion-with-cation-%C3%AF-interactions
#9
Matthew A Gebbie, Wei Wei, Alex M Schrader, Thomas R Cristiani, Howard A Dobbs, Matthew Idso, Bradley F Chmelka, J Herbert Waite, Jacob N Israelachvili
Cation-π interactions drive the self-assembly and cohesion of many biological molecules, including the adhesion proteins of several marine organisms. Although the origin of cation-π bonds in isolated pairs has been extensively studied, the energetics of cation-π-driven self-assembly in molecular films remains uncharted. Here we use nanoscale force measurements in combination with solid-state NMR spectroscopy to show that the cohesive properties of simple aromatic- and lysine-rich peptides rival those of the strong reversible intermolecular cohesion exhibited by adhesion proteins of marine mussel...
May 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28429734/neuroprotective-pentapeptide-cn-105-is-associated-with-reduced-sterile-inflammation-and-improved-functional-outcomes-in-a-traumatic-brain-injury-murine-model
#10
Daniel T Laskowitz, Haichen Wang, Tony Chen, David T Lubkin, Viviana Cantillana, Tian Ming Tu, Dawn Kernagis, Guanen Zhou, Gary Macy, Bradley J Kolls, Hana N Dawson
At present, there are no proven pharmacological treatments demonstrated to improve long term functional outcomes following traumatic brain injury(TBI). In the setting of non-penetrating TBI, sterile brain inflammatory responses are associated with the development of cerebral edema, intracranial hypertension, and secondary neuronal injury. There is increasing evidence that endogenous apolipoprotein E(apoE) modifies the neuroinflammatory response through its role in downregulating glial activation, however, the intact apoE holoprotein does not cross the blood-brain barrier due to its size...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428174/klotho-an-anti-aging-molecule-attenuates-oxidant-induced-alveolar-epithelial-cell-mtdna-damage-and-apoptosis
#11
Seok-Jo Kim, Paul Cheresh, Mesut Eren, Renea P Jablonski, Anjana Yeldandi, Karen M Ridge, Gr Scott Budinger, Dong-Hyun Kim, Myles S Wolf, Douglas Vaughan, David W Kamp
Alveolar epithelial cell (AEC) apoptosis and inadequate repair resulting from 'exaggerated' lung aging and mitochondrial dysfunction are critical determinants promoting lung fibrosis. α-Klotho, which is an anti-aging molecule that is expressed predominantly in the kidney and secreted in the blood, can protect lung epithelial cells against hyperoxia-induced apoptosis. We reasoned that Klotho protects AEC exposed to oxidative stress in part by maintaining mitochondrial DNA (mtDNA) integrity and mitigating apoptosis...
April 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28428153/development-of-polyol-responsive-antibody-mimetics-for-single-step-protein-purification
#12
Richard J Suderman, Daren A Rice, Shane D Gibson, Eric J Strick, David M Chao
The purification of functional proteins is a critical pre-requisite for many experimental assays. Immunoaffinity chromatography, one of the fastest and most efficient purification procedures available, is often limited by elution conditions that disrupt structure and destroy enzymatic activity. To address this limitation, we developed polyol-responsive antibody mimetics, termed nanoCLAMPs, based on a 16 kDa carbohydrate binding module domain from Clostridium perfringens hyaluronidase. nanoCLAMPs bind targets with nanomolar affinity and high selectivity yet release their targets when exposed to a neutral polyol-containing buffer, a composition others have shown to preserve quaternary structure and enzymatic activity...
April 17, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28427521/management-of-metastatic-castration-resistant-prostate-cancer-a-focus-on-radium-223-opinions-and-suggestions-from-an-expert-multidisciplinary-panel
#13
REVIEW
Sergio Baldari, Giuseppe Boni, Roberto Bortolus, Orazio Caffo, Giario Conti, Giuseppe De Vincentis, Fabio Monari, Giuseppe Procopio, Daniele Santini, Ettore Seregni, Riccardo Valdagni
Radium-223, a calcium mimetic bone-seeking radionuclide that selectively targets bone metastases with alpha particles, is approved for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases. In patients with mCRPC, treatment with radium-223 has been associated with survival benefit, regardless of prior docetaxel use, and also has a positive impact on symptomatic skeletal events and quality of life. Radium-223 is best suited for patients with symptomatic mCRPC and bone-predominant disease and no visceral metastases, and may lead to better outcomes when given early in the course of the disease...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427390/advanced-glycation-end-products-decreases-expression-of-endothelial-nitric-oxide-synthase-through-oxidative-stress-in-human-coronary-artery-endothelial-cells
#14
Xiaomei Ren, Liqun Ren, Qin Wei, Hua Shao, Long Chen, Naifeng Liu
BACKGROUND: Advanced glycation end-products (AGEs) are elevated under diabetic conditions and associated with insulin resistance, endothelial dysfunction and vascular inflammation in humans. It has been demonstrated that AGEs evoke oxidative and inflammatory reactions in endothelial cells through the interaction with a receptor for AGEs (RAGE). Here, we aimed to identify the cellular mechanisms by which AGEs exacerbate the endothelial dysfunction in human coronary artery endothelial cells (HCAECs)...
April 20, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28426935/manipulation-of-mg2-ca2-switch-on-the-development-of-bone-mimetic-hydroxyapatite
#15
Nancy C Andrés, Noelia L D'Elía, Juan M Ruso, Adrián Esteban Campelo, Virginia L Massheimer, Paula V Messina
Ionic substitution can affect essential physicochemical properties leading to a specific biological behavior upon implantation. Therefore it has been proposed as a tool to increase the biological efficiency of calcium phosphate based materials. In the following study we have evaluated the contribution of an important cation in nature, Mg2+, into the structure of previously studied biocompatible and biodegradable hydroxyapatite (HA) nano-rods and its subsequent effect on its chemical, morphology and bone mimetic articulation...
April 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28425157/geographic-variation-in-mimetic-precision-among-different-species-of-coral-snake-mimics
#16
Christopher K Akcali, David W Pfennig
Batesian mimicry is widespread, but whether and why different species of mimics vary geographically in resemblance to their model is unclear. We characterized geographic variation in mimetic precision among four Batesian mimics of coral snakes. Each mimic occurs where its model is abundant (i.e., in "deep sympatry"), rare (i.e., at the sympatry/allopatry boundary or "edge sympatry"), and absent (i.e., in allopatry). Geographic variation in mimetic precision was qualitatively different among these mimics. In one mimic, the most precise individuals occurred in edge sympatry; in another, they occurred in deep sympatry; in the third, they occurred in allopatry; and in the fourth, precise mimics were not concentrated anywhere throughout their range...
April 20, 2017: Journal of Evolutionary Biology
https://www.readbyqxmd.com/read/28424988/overcoming-chemotherapy-drug-resistance-by-targeting-inhibitors-of-apoptosis-proteins-iaps
#17
REVIEW
Rama Rathore, Jennifer E McCallum, Elizabeth Varghese, Ana-Maria Florea, Dietrich Büsselberg
Inhibitors of apoptosis (IAPs) are a family of proteins that play a significant role in the control of programmed cell death (PCD). PCD is essential to maintain healthy cell turnover within tissue but also to fight disease or infection. Uninhibited, IAPs can suppress apoptosis and promote cell cycle progression. Therefore, it is unsurprising that cancer cells demonstrate significantly elevated expression levels of IAPs, resulting in improved cell survival, enhanced tumor growth and subsequent metastasis. Therapies to target IAPs in cancer has garnered substantial scientific interest and as resistance to anti-cancer agents becomes more prevalent, targeting IAPs has become an increasingly attractive strategy to re-sensitize cancer cells to chemotherapies, antibody based-therapies and TRAIL therapy...
April 19, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28423568/sepia-ink-oligopeptide-induces-apoptosis-and-growth-inhibition-in-human-lung-cancer-cells
#18
Zhi Zhang, Lei Sun, Guoren Zhou, Peng Xie, Jinjun Ye
Sepia ink oligopeptide (SIO), as a tripeptide extracted from Sepia ink, could be used as an inducer of apoptosis in human prostate cancer cells. We designed a cyclo-mimetic peptide of SIO by introducing a disulfide bond to stabilize the native peptide into beta turn structure, and produced a peptide with higher cell permeability and stability. Through labeling an FITC to the N-terminus of the peptide, the cell permeability was examined. Stabilized peptide showed enhanced cellular uptake than linear tripeptide as indicated by flow cytometry and cell fluorescent imaging...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423052/inflammation-induced-fetal-growth-restriction-in-rats-is-associated-with-increased-placental-hif-1%C3%AE-accumulation
#19
Kevin P Robb, Tiziana Cotechini, Camille Allaire, Arissa Sperou, Charles H Graham
INTRODUCTION: Hypoxia-inducible factor 1-alpha (HIF-1α) is the oxygen-sensitive subunit of the transcription factor HIF-1, and its expression is increased in placentas from pregnancies complicated by pre-eclampsia (PE). Fetal growth restriction (FGR) and PE often share a common pathophysiology; however, it is unknown whether increased placental HIF-1α occurs in FGR. We previously demonstrated that aberrant maternal inflammation in rats resulted in altered utero-placental perfusion and FGR, both of which were prevented by administration of the nitric oxide mimetic glyceryl trinitrate (GTN)...
2017: PloS One
https://www.readbyqxmd.com/read/28422793/engineering-antibody-like-inhibitors-to-prevent-and-treat-hiv-1-infection
#20
Matthew R Gardner, Michael Farzan
PURPOSE OF REVIEW: Here we discuss recently developed HIV-1 entry inhibitors that can target multiple epitopes on the HIV-1 envelope glycoprotein (Env), with an emphasis on eCD4-Ig. Some of these inhibitors are more potent and broader than any single antibody characterized to date. We also discuss the use of recombinant adeno-associated virus (rAAV) vectors as a platform for long-term expression of these inhibitors. RECENT FINDINGS: Much of the exterior of HIV-1 Env can be targeted by broadly neutralizing antibodies (bNAbs)...
May 2017: Current Opinion in HIV and AIDS
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