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https://www.readbyqxmd.com/read/29138063/polyrotaxane-based-systemic-delivery-of-%C3%AE-cyclodextrins-for-potentiating-therapeutic-efficacy-in-a-mouse-model-of-niemann-pick-type-c-disease
#1
Atsushi Tamura, Nobuhiko Yui
Niemann-Pick type C (NPC) disease is a fatal metabolic disorder characterized by the lysosomal accumulation of cholesterol. Although 2-hydroxypropyl β-cyclodextrin (HP-β-CD) promotes the excretion of cholesterol and prolongs the life span in animal models of NPC disease, it requires extremely high dose. We developed acid-labile β-CD-based polyrotaxanes (PRXs) comprising multiple β-CDs threaded along a polymer chain capped with acid-cleavable stopper molecules for potentiating therapeutic efficacy of β-CD in NPC disease...
November 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29120644/acid-induced-intracellular-dissociation-of-%C3%AE-cyclodextrin-threaded-polyrotaxanes-directed-toward-attenuating-phototoxicity-of-bisretinoids-through-promoting-excretion
#2
Atsushi Tamura, Moe Ohashi, Kei Nishida, Nobuhiko Yui
In the retinal pigment epithelium of patients with age-related macular degeneration (AMD), excess N-retinylidene-N-retinylethanolamine (A2E), a dimer of all-trans-retinal, accumulats to induce inflammatory cytokine secretion and phototoxic effects. Therefore, the reduction of intracellular A2E is a promising approach for the prevention and treatment of AMD. In this study, acid-labile β-cyclodextrin (β-CD)-threaded polyrotaxanes (PRXs) were synthesized and investigated their effects on the removal of A2E accumulated in retinal pigment epithelium cells (ARPE-19) in comparison to nonlabile PRXs and 2-hydroxypropyl β-CD (HP-β-CD) were examined...
November 9, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29113450/physiological-significance-of-plant-peroxiredoxins-prxs-and-the-structure-related-and-multi-functional-biochemistry-of-prx1
#3
Eun Seon Lee, Chang Ho Kang, Joung Hun Park, Sang Yeol Lee
<b><i>Significance:</i></b> Sessile plants respond to oxidative stress caused by internal and external stimuli by producing diverse forms of enzymatic and non-enzymatic antioxidant molecules. Peroxiredoxins (Prxs) in plants, including the Prx1, Prx5, Prx6, and PrxQ isoforms, constitute a family of antioxidant enzymes and play important functions in cells. Each Prx localizes to a specific subcellular compartment and has a distinct function in the control of plant growth, development, cellular metabolism, and various aspects of defense signaling...
November 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29084196/multi-modality-neuromonitoring-in-severe-pediatric-traumatic-brain-injury-monitoring-pediatric-tbi
#4
REVIEW
Adam M H Young, Mathew R Guilfoyle, Joseph Donnelly, Peter Smielewski, Shruti Agarwal, Marek Czosnyka, Peter J Hutchinson
Each year, the annual hospitalization rates of traumatic brain injury (TBI) in children in the US are 57.7 per 100 K less than 5 years of age and 23.1 per 100 K in the 5-14 year age group. Despite this, little is known about the pathophysiology of TBI in children and how to manage it most effectively. Historically, TBI management has been guided by clinical examination. This has been assisted progressively by clinical imaging, intracranial pressure (ICP) monitoring and finally software that can calculate optimal brain physiology...
October 30, 2017: Pediatric Research
https://www.readbyqxmd.com/read/29067017/identification-of-2-cys-peroxiredoxin-bmtpx-2-as-antioxidant-active-molecule-from-babesia-microti
#5
Xunan Hai, Houshuang Zhang, Zhonghua Wang, Haiyan Gong, Jie Cao, Yongzhi Zhou, Jinlin Zhou
Peroxiredoxins (Prxs) are a family of antioxidant enzymes that reduce peroxides in the presence of thioredoxin, thioredoxin reductase, and nicotinamide adenine dinucleotide phosphate (NADPH) to resist oxidative stress. In this study, we identified and isolated a 2-Cys Prx designated as 'BmTPx-2' from Babesia microti, with a full-length cDNA of 826 bp and an open reading frame of 756 bp, which encodes a 251-amino acid protein. BLAST analysis demonstrated that BmTPx-2 shows the typical features of members of the 2-Cys Prx family, which includes harboring two conserved VCP motifs with Cys(101) and Cys(221) conserved cysteine residues...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29063384/peroxiredoxin-i-expression-in-epithelial-cells-of-buccal-mucosa-from-patients-exposed-to-panoramic-x-rays-influence-of-the-age
#6
Milena B Silva, Ana P D Demasi, Elizabeth F Martinez, Maristane L Goudinho, Joarlene M Soares, José L C Junqueira, Ney S Araujo
OBJECTIVES: The aim of this study was to evaluate peroxiredoxin I (Prx I) participation in the cellular antioxidant response to low-dose X-rays through the analysis of its expression in buccal mucosa cells from patients of different ages following panoramic dental radiography. MATERIALS AND METHODS: Of the 50 patients included in this study, oral mucosa cells from six adults were collected for the immunofluorescence cytological analysis. The other 44 patients, 11 patients aged below 20 years; 22 patients aged between 20 and 50 years; and 11 patients aged above 50 years, were submitted to panoramic dental radiography, and oral mucosa cells were collected for the gene expression analysis before and 1 hour after exposure...
October 23, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/29054661/coordinated-role-of-soluble-and-cell-wall-bound-phenols-is-a-key-feature-of-the-metabolic-adjustment-in-a-mining-woody-fleabane-dittrichia-viscosa-l-population-under-semi-arid-conditions
#7
Antonio López-Orenes, María C Bueso, Isabel M Párraga-Aguado, Antonio A Calderón, María A Ferrer
Environmental contamination by hazardous heavy metals/metalloids (metal(loid)s) is growing worldwide. To restrict the migration of toxic contaminants, the establishment of a self-sustainable plant cover is required. Plant growth in multi-polluted soils is a challenging issue not only by metal(loid) toxicities, but also by the co-occurrence of other stressors. Dittrichia viscosa is a pioneer Mediterranean species able to thrive in metal(loid)-enriched tailings in semi-arid areas. The aim of the present work was to examine the metabolic adjustments involved in the acclimation responses of this plant to conditions prevailing in mine-tailings during Mediterranean spring and summer...
October 17, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29050524/transcranial-doppler-systolic-flow-index-and-icp-derived-cerebrovascular-reactivity-indices-in-tbi
#8
Frederick Adam Zeiler, Danilo Cardim, Joseph Donnelly, David Menon, Marek Czosnyka, Peter Smieleweski
To explore relationships between transcranial Doppler (TCD) indices of cerebrovascular reactivity and those derived from intracranial pressure (ICP). GOALS: A. Confirm previously described co-variance patterns of TCD/ICP indices, and B. Describe thresholds for Sx (correlation between systolic flow velocity (FVs) and cerebral perfusion pressure (CPP)) associated with outcome. Retrospective cohort of traumatic brain injury (TBI) patients: with TCD and ICP monitoring, we calculated various continuous indices of cerebrovascular reactivity: A...
October 19, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29043544/icp-versus-laser-doppler-cerebrovascular-reactivity-indices-to-assess-brain-autoregulatory-capacity
#9
F A Zeiler, J Donnelly, D Cardim, D K Menon, P Smielewski, M Czosnyka
BACKGROUND: To explore the relationship between various autoregulatory indices in order to determine which approximate small vessel/microvascular (MV) autoregulatory capacity most accurately. METHODS: Utilizing a retrospective cohort of traumatic brain injury patients (N = 41) with: transcranial Doppler (TCD), intracranial pressure (ICP) and cortical laser Doppler flowmetry (LDF), we calculated various continuous indices of autoregulation and cerebrovascular responsiveness: A...
October 17, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/29026190/growth-hormone-secretagogues-hexarelin-and-jmv2894-protect-skeletal-muscle-from-mitochondrial-damages-in-a-rat-model-of-cisplatin-induced-cachexia
#10
Giuseppe Sirago, Elena Conte, Flavio Fracasso, Antonella Cormio, Jean-Alain Fehrentz, Jean Martinez, Clara Musicco, Giulia Maria Camerino, Adriano Fonzino, Laura Rizzi, Antonio Torsello, Angela Maria Serena Lezza, Antonella Liantonio, Palmiro Cantatore, Vito Pesce
Chemotherapy can cause cachexia, which consists of weight loss associated with muscle atrophy. The exact mechanisms underlying this skeletal muscle toxicity are largely unknown and co-therapies to attenuate chemotherapy-induced side effects are lacking. By using a rat model of cisplatin-induced cachexia, we here characterized the mitochondrial homeostasis in tibialis anterior cachectic muscle and evaluated the potential beneficial effects of the growth hormone secretagogues (GHS) hexarelin and JMV2894 in this setting...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28993802/glycemia-is-related-to-impaired-cerebrovascular-autoregulation-after-severe-pediatric-traumatic-brain-injury-a-retrospective-observational-study
#11
Adam M H Young, Hadie Adams, Joseph Donnelly, Mathew R Guilfoyle, Helen Fernandes, Mathew R Garnett, Marek Czosnyka, Peter Smielewski, Mark Plummer, Shruti Agrawal, Peter J Hutchinson
INTRODUCTION: A strong association exists between hyperglycemia and outcome in pediatric traumatic brain injury (TBI). Herein, we describe observations of serum markers of glucose metabolism in a cohort of pediatric TBI patients and how these variables are related to parameters of intracranial pathophysiology. METHODS: A retrospective analysis was performed on pediatric severe TBI patients admitted to Addenbrookes Hospital Paediatric Intensive Care Unit (PICU) between January 2001 and December 2013...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28981898/overexpression-of-truncated-human-disc1-induces-appearance-of-hindbrain-oligodendroglia-in-the-forebrain-during-development
#12
Pavel Katsel, Peter Fam, Weilun Tan, Sonia Khan, Chunxia Yang, Yan Jouroukhin, Sergei Rudchenko, Mikhail V Pletnikov, Vahram Haroutunian
Genetic, neuroimaging, and gene expression studies suggest a role for oligodendrocyte (OLG) dysfunction in schizophrenia (SZ). Disrupted-in-schizophrenia 1 (DISC1) is a risk gene for major psychiatric disorders, including SZ. Overexpression of mutant truncated (hDISC1), but not full-length sequence of human DISC1 in forebrain influenced OLG differentiation and proliferation of glial progenitors in the developing cerebral cortex concurrently with reduction of OLG progenitor markers in the hindbrain. We examined gene and protein expression of the molecular determinants of hindbrain OLG development and their interactions with DISC1 in mutant hDISC1 mice...
August 18, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28964866/molecular-structure-and-functional-characterization-of-the-peroxiredoxin-5-in-procambarus-clarkii-following-lps-and-poly-i-c-challenge
#13
Liang Wu, Yang Zhou, Muhammad Nadeem Abbas, Saima Kausar, Qi Chen, Cheng-Xi Jiang, Li-Shang Dai
Peroxiredoxin (Prx) family members play a critical role in host defense against oxidative stress, and are also involved in immune responses following microbial infection. In the present study, we firstly cloned the cDNA of Peroxiredoxin 5 from Procambarus clarkii (denoted as PcPrx5) and investigated its immune functions towards LPS and Poly I:C exposure. The PcPrx5 cDNA was composed of 564 bp and consisting of 187 amino acid residues which included Prx5-like subfamily domain, AHP1 domain and Redoxin domain...
September 28, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28902413/frequent-genes-in-rare-diseases-panel-based-next-generation-sequencing-to-disclose-causal-mutations-in-hereditary-neuropathies
#14
Maike F Dohrn, Nicola Glöckle, Lejla Mulahasanovic, Corina Heller, Julia Mohr, Christine Bauer, Erik Riesch, Andrea Becker, Florian Battke, Konstanze Hörtnagel, Thorsten Hornemann, Saranya Suriyanarayanan, Markus Blankenburg, Jörg B Schulz, Kristl G Claeys, Burkhard Gess, Istvan Katona, Andreas Ferbert, Debora Vittore, Alexander Grimm, Stefan Wolking, Ludger Schöls, Holger Lerche, G Christoph Korenke, Dirk Fischer, Bertold Schrank, Urania Kotzaeridou, Gerhard Kurlemann, Bianca Dräger, Anja Schirmacher, Peter Young, Beate Schlotter-Weigel, Saskia Biskup
Hereditary neuropathies comprise a wide variety of chronic diseases associated to more than 80 genes identified to date. We herein examined 612 index patients with either a Charcot-Marie-Tooth phenotype, hereditary sensory neuropathy, familial amyloid neuropathy, or small fiber neuropathy using a customized multigene panel based on the next generation sequencing technique. In 121 cases (19.8%), we identified at least one putative pathogenic mutation. Of these, 54.4% showed an autosomal dominant, 33.9% an autosomal recessive, and 11...
September 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28893373/peroxiredoxin-i-participates-in-the-protection-of-reactive-oxygen-species-mediated-cellular-senescence
#15
Young-Ho Park, Hyun-Sun Kim, Jong-Hee Lee, Seon-A Choi, Jin-Man Kim, Goo Taeg Oh, Sang Won Kang, Sun-Uk Kim, Dae-Yeul Yu
Peroxiredoxin I (Prx I) plays an important role as a reactive oxygen species (ROS) scavenger in protecting and maintaining cellular homeostasis; however, the underlying mechanisms are not well understood. Here, we identified a critical role of Prx I in protecting cells against ROS-mediated cellular senescence by suppression of p16INK4a expression. Compared to wild-type mouse embryonic fibroblasts (WT-MEFs), Prx I-/- MEFs exhibited senescence-associated phenotypes. Moreover, the aged Prx I-/- mice showed an increased number of cells with senescence associated-β-galactosidase (SA-β-gal) activity in a variety of tissues...
September 12, 2017: BMB Reports
https://www.readbyqxmd.com/read/28871418/time-spent-with-impaired-autoregulation-is-linked-with-outcome-in-severe-infant-paediatric-traumatic-brain-injury
#16
Konstantin Hockel, Jennifer Diedler, Felix Neunhoeffer, Ellen Heimberg, Carmen Nagel, Martin U Schuhmann
BACKGROUND: It could be shown in traumatic brain injury (TBI) in adults that the functional status of cerebrovascular autoregulation (AR), determined by the pressure reactivity index (PRx), correlates to and even predicts outcome. We investigated PRx, cerebral perfusion pressure (CPP) and intracranial pressure (ICP) and their correlation to outcome in severe infant and paediatric TBI. METHODS: Seventeen patients (range, 1 day to 14 years) with severe TBI (median GCS at presentation, 4) underwent long-term computerised ICP and mean arterial pressure (MAP) monitoring using dedicated software to determine CPP and PRx and optimal CPP (CPP level where PRx shows best autoregulation) continuously...
September 4, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/28866748/early-response-of-glutathione-and-thioredoxin-dependent-antioxidant-defense-systems-to-tl-i-and-tl-iii-mediated-oxidative-stress-in-adherent-pheochromocytoma-pc12adh-cells
#17
Lis C Puga Molina, Damiana M Salvatierra Fréchou, Sandra V Verstraeten
Thallium (Tl) is a toxic heavy metal that causes oxidative stress both in vitro and in vivo. In this work, we evaluated the production of oxygen (ROS)- and nitrogen (RNS)-reactive species in adherent PC12 (PC12adh) cells exposed for 0.5-6 h to Tl(I) or Tl(III) (10-100 µM). In this system, Tl(I) induced mostly H2O2 generation while Tl(III) induced H2O2 and ONOO(·-) generation. Both cations enhanced iNOS expression and activity, and decreased CuZnSOD expression but without affecting its activity. Tl(I) increased MnSOD expression and activity but Tl(III) decreased them...
September 2, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28821623/proteolytic-cleavage-by-the-inner-membrane-peptidase-imp-complex-or-oct1-peptidase-controls-the-localization-of-the-yeast-peroxiredoxin-prx1-to-distinct-mitochondrial-compartments
#18
Fernando Gomes, Flávio Romero Palma, Mario H Barros, Eduardo T Tsuchida, Helena G Turano, Thiago G P Alegria, Marilene Demasi, Luis E S Netto
Yeast Prx1 is a mitochondrial 1-Cys peroxiredoxin that catalyzes the reduction of endogenously generated H2O2 Prx1 is synthesized on cytosolic ribosomes as a preprotein with a cleavable N-terminal presequence that is the mitochondrial targeting signal, but the mechanisms underlying Prx1 distribution to distinct mitochondrial subcompartments are unknown. Here, we provide direct evidence of the following dual mitochondrial localization of Prx1: a soluble form in the intermembrane space and a form in the matrix weakly associated with the inner mitochondrial membrane...
October 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28819737/further-controversies-about-brain-tissue-oxygenation-pressure-reactivity-after-traumatic-brain-injury
#19
Morten Andresen, Joseph Donnelly, Marcel Aries, Marianne Juhler, David Menon, Pja Hutchinson, Peter Smielewski
BACKGROUND: Continuous monitoring of cerebral autoregulation is considered clinically useful due to its ability to warn against brain ischemic insults, which may translate to a relationship with adverse outcome. It is typically performed using the pressure reactivity index (PRx) based on mean arterial pressure and intracranial pressure. A new ORx index based on brain tissue oxygenation and cerebral perfusion pressure (CPP) has been proposed that similarly allows for evaluation of cerebrovascular reactivity...
August 17, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28776692/brassinosteroid-mediated-apoplastic-h2-o2-glutaredoxin-12-14-cascade-regulates-antioxidant-capacity-in-response-to-chilling-in-tomato
#20
Xiao-Jian Xia, Ping-Ping Fang, Xie Guo, Xiang-Jie Qian, Jie Zhou, Kai Shi, Yan-Hong Zhou, Jing-Quan Yu
Brassinosteroids (BRs) regulate plant development and stress response. Although much has been learned about their roles in plant development, the mechanisms by which BRs regulate plant stress tolerance remain unclear. Chilling is a major stress that adversely affects plant growth. Here, we report that BR positively regulates chilling tolerance in tomato. BR partial deficiency aggravated chilling-induced oxidized protein accumulation, membrane lipid peroxidation and decrease of maximum quantum efficiency of photosystem II (Fv/Fm)...
August 4, 2017: Plant, Cell & Environment
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