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https://www.readbyqxmd.com/read/29775948/novel-3-phenylcoumarin-lipoic-acid-conjugates-as-multi-functional-agents-for-potential-treatment-of-alzheimer-s-disease
#1
Leili Jalili-Baleh, Hamid Nadri, Hamid Forootanfar, Alireza Samzadeh-Kermani, Tuba Tüylü Küçükkılınç, Beyza Ayazgok, Mahban Rahimifard, Maryam Baeeri, Mohsen Doostmohammadi, Loghman Firoozpour, Syed Nasir Abbas Bukhari, Mohammad Abdollahi, Mohammad Reza Ganjali, Saeed Emami, Mehdi Khoobi, Alireza Foroumadi
New series of triazole-containing 3-phenylcoumarin-lipoic acid conjugates were designed as multi-functional agents for treatment of Alzheimer's disease. The target compounds 4a-o were synthesized via the azide-alkyne cycloaddition reaction and their biological activities were primarily evaluated in terms of neuroprotection against H2 O2 -induced cell death in PC12 cells and AChE/BuChE inhibition. The promising compounds 4j and 4i containing four carbons spacer were selected for further biological evaluations...
May 2, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29775946/il-9-exhibits-elevated-expression-in-osteonecrosis-of-femoral-head-patients-and-promotes-cartilage-degradation-through-activation-of-jak-stat-signaling-in-vitro
#2
Wei Geng, Wen Zhang, Jinzhu Ma
Osteonecrosis of the femoral head (ONFH) often causes severe symptoms in young people and limits the mobility of the hip joint. Interleukin-9 (IL-9) is a multi-functional inflammatory factor that participates in lumbar disk herniation and arthritis and has been reported in many studies. However, the correlation between IL-9 and ONFH is unclear. The present study aimed to determine the role of IL-9 in the pathogenetic mechanism of osteonecrosis. To assess IL-9 expression in ONFH and femoral neck fracture patients, cartilage tissue was examined through western blot analysis and immunohistochemistry...
May 15, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29775812/virus-entry-and-its-inhibition-to-prevent-and-treat-hepatitis-b-and-hepatitis-d-virus-infections
#3
REVIEW
Thomas Tu, Stephan Urban
While chronic infection with the human hepatitis B virus (HBV) and hepatitis delta virus (HDV) inflict major health burdens worldwide, current therapies cannot cure patients. One possible novel approach is blocking virus entry to prevent the establishment of infection in naïve hepatocytes. As HBV and HDV use identical viral envelope proteins and the same entry mechanisms, such a strategy would target both viruses. Entry inhibitors (e.g. neutralizing antibodies) have been relegated to the limited role of prophylaxis...
May 15, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29775644/redox-signal-mediated-trpm2-promotes-ang-ii-induced-adipocyte-insulin-resistance-via-ca-2-dependent-camkii-jnk-cascade
#4
Min Gao, Yu Du, Jing-Wen Xie, Jing Xue, Yi-Ting Wang, Li Qin, Ming-Ming Ma, Yong-Bo Tang, Xiao-Yan Li
BACKGROUND AND OBJECTIVE: Redox-sensitive transient receptor potential melastatin 2 (TRPM2) is a Ca2+ -permeable, nonselective cation channel which plays a crucial role in various physiological processes. However, little is known whether TRPM2 is involved in adipocyte dysfunction during hypertension. In the present study, we determined the role of TRPM2 in angiotensin II (Ang II)-induced insulin resistance in adipocytes and the underlying mechanisms. METHODS: Ang II-induced adipocyte insulin resistant model was conducted...
May 15, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29775612/crystal-structure-of-wa352-provides-insight-into-cytoplasmic-male-sterility-in-rice
#5
Xiang Wang, Zeyuan Guan, Zhou Gong, Junjie Yan, Guangsheng Yang, Yao-Guang Liu, Ping Yin
Plant cytoplasmic male sterility (CMS) is an important phenomenon and is widely utilized in hybrid crop breeding. The Wild Abortive CMS (CMS-WA), a well-known CMS type, has been successfully applied in the commercial production of hybrid rice seeds for more than 40 years. The CMS-WA causal gene WA352 encodes a novel transmenbrane protein and the interacts with the mitochondrial copper chaperone COX11, triggering reactive oxygen species production and resulting in male sterility in CMS-WA lines. However, the structure of WA352 is currently unknown, and the structural mechanism whereby WA352 perturbs COX11 function to cause CMS remains largely unknown...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775610/monocarboxylate-transporters-in-breast-cancer-and-adipose-tissue-are-novel-biomarkers-and-potential-therapeutic-targets
#6
Zhiyu Li, Qi Wu, Si Sun, Juan Wu, Juanjuan Li, Yimin Zhang, Changhua Wang, Jingping Yuan, Shengrong Sun
Monocarboxylate transporters (MCTs) are transmembrane proteins that control the lactate metabolism and associated with poor prognosis in solid tumors including breast cancer (BC). This study aimed to evaluate the clinical and prognostic value of MCTs used by immunohistochemistry and quantum dots-based fluorescent imaging technique in BC and surrounding stroma with emphasis on the interaction between tumour and stroma. Moreover, the data from The Cancer Genome Atlas (TCGA) was analyzed to evaluate the association between MCTs mRNA expression and prognosis of breast cancer patients...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775600/variation-in-interleukin-6-receptor-gene-associates-with-risk-of-crohn-s-disease-and-ulcerative-colitis
#7
C A Parisinos, S Serghiou, M Katsoulis, M J George, R S Patel, H Hemingway, A D Hingorani
Interleukin 6 (IL6) is an inflammatory cytokine; signaling via its receptor (IL6R) is believed to contribute to development of inflammatory bowel diseases (IBD). The single nucleotide polymorphism rs2228145 in IL6R associates with increased levels of soluble IL6R (s-IL6R), as well as reduced IL6R signaling and risk of inflammatory disorders; its effects are similar to those of a therapeutic monoclonal antibody that blocks IL6R signaling. We used the effect of rs2228145 on s-IL6R level as an indirect marker to investigate whether reduced IL6R signaling associates with risk of ulcerative colitis (UC) or Crohn's disease (CD)...
May 15, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29775573/indole-3-carbinol-i3c-enhances-the-sensitivity-of-murine-breast-adenocarcinoma-cells-to-doxorubicin-dox-through-inhibition-of-nf-%C3%AE%C2%BA%C3%AE-blocking-angiogenesis-and-regulation-of-mitochondrial-apoptotic-pathway
#8
Subhadip Hajra, Arup Ranjan Patra, Abhishek Basu, Prosenjit Saha, Sudin Bhattacharya
Various epidemiological and preclinical studies have already established the cancer chemopreventive potential of naturally occurring glucosinolate breakdown product Indole-3-Carbinol (I3C) as well as its abilities to induce selective cell death towards malignant cell. Therefore, the objective of the present study is to improve the therapeutic efficacy and prevention of doxorubicin (DOX)-induced toxicity, by the concurrent use of Indole-3-Carbinol (I3C). In this study, I3C was administered (20 mg/kg b.w., p...
May 15, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29775572/gene-therapy-with-antisense-oligonucleotides-silencing-c-myc-reduces-neointima-formation-and-vessel-wall-thickness-in-a-mouse-model-of-vein-graft-disease
#9
Christina Maria Steger, Nikolaos Bonaros, Ralf Joachim Rieker, Johannes Bonatti, Thomas Schachner
Gene therapy for avoiding intimal hyperplasia of vein grafts after coronary artery bypass grafting is still discussed controversially. A promising application of gene therapy in vein grafts is the use of antisense oligonucleotides to block the expression of genes encoding cell cycle regulatory proteins in vascular smooth muscle cells. C-myc, either directly or by regulating the expression of other proteins, controls cell proliferation, apoptosis and cell survival, tissue remodeling, angiogenesis, cell metabolism, production of inflammatory and anti-inflammatory cytokines, and also participates in cell transformation...
May 15, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29775473/na-k-atpase-signaling-mediates-mir-29b-3p-regulation-and-cardiac-fibrosis-formation-in-mice-with-chronic-kidney-disease
#10
Christopher A Drummond, Xiaoming Fan, Steven T Haller, David J Kennedy, Jiang Liu, Jiang Tian
The Na/K-ATPase is an important membrane ion transporter and a signaling receptor that is essential for maintaining normal cell function. The current study examined the role of Na/K-ATPase signaling in regulating miR-29b-3p, an anti-fibrotic microRNA, in a mouse chronic kidney disease (CKD) model (5/6th partial nephrectomy or PNx). The results showed that CKD induced significant reduction of miR-29b-3p expression in the heart tissue by activation of Src and NFκB signaling in these animals. To demonstrate the role of Na/K-ATPase signaling, we also performed the PNx surgery on Na/K-ATPase α1 heterozygous (α1+/-) mice, which expresses ~40% less Na/K-ATPase α1 compared to their wild type littermates (WT) and exhibits deficiency in Na/K-ATPase signaling...
2018: PloS One
https://www.readbyqxmd.com/read/29775453/ts-hsp70-induces-protective-immunity-against-trichinella-spiralis-infection-in-mouse-by-activating-dendritic-cells-through-tlr2-and-tlr4
#11
Rui Zhang, Qing Sun, Yi Chen, Ximeng Sun, Yuan Gu, Zhang Zhao, Yuli Cheng, Limei Zhao, Jingjing Huang, Bin Zhan, Xinping Zhu
BACKGROUND: Trichinellosis is a serious food-borne parasitic zoonosis worldwide. In the effort to develop vaccine against Trichinella infection, we have identified Trichinella spiralis Heat shock protein 70 (Ts-Hsp70) elicits partial protective immunity against T. spiralis infection via activating dendritic cells (DCs) in our previous study. This study aims to investigate whether DCs were activated by Ts-Hsp70 through TLR2 and/or TLR4 pathways. METHODS AND FINDINGS: After blocking with anti-TLR2 and TLR4 antibodies, the binding of Ts-Hsp70 to DCs was significantly reduced...
May 18, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29775438/breakdown-of-water-super-permeation-in-electrically-insulating-graphene-oxide-films-role-of-dual-interlayer-spacing
#12
M K Kavitha, Tushar Sakorikar, Pramitha V, Manu Jaiswal
Conventional graphene oxide is characterized by low sp<sup>2</sup> content in a sp<sup>3</sup> rich matrix, which is responsible both for electrical insulation and water super-permeation. Upon reduction, electrical conduction is achieved at the expense of water permeation ability. Here, we demonstrate that charge conduction and water permeation can be simultaneously restricted in a functionalized form of graphene oxide. Gravimetric studies reveal that diffusion of water vapour through glassy polymer membranes is arrested by loading hydrophobic form of GO in the polymer matrix, even as such water inhibition cannot be realized by substantially increasing the thickness of the bare polymer...
May 18, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29775412/inhibitor-of-lysyl-oxidase-improves-cardiac-function-and-the-collagen-mmp-profile-in-response-to-volume-overload
#13
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/29775312/limits-of-directed-self-assembly-in-block-copolymers
#14
Karim Raafat Gadelrab, Yi Ding, Ricardo Pablo-Pedro, Hsieh Chen, Kevin W Gotrik, David G Tempel, Caroline A Ross, Alfredo Alexander-Katz
Understanding the conditions under which defects appear in self-assembling soft-matter systems is of great importance, for example, in the development of block-copolymer (BCP) nanolithography. Here, we explore the limits of directed self-assembly of BCPs by deliberately adding random imperfections in the template. Our results show that defects emerge due to local "shear-like" distortions of the polymer-template system, a new mechanism that is fundamentally different from canonical mechanisms of 2D melting...
May 18, 2018: Nano Letters
https://www.readbyqxmd.com/read/29775310/fragment-based-discovery-of-a-potent-orally-bioavailable-inhibitor-which-modulates-the-phosphorylation-and-catalytic-activity-of-erk1-2
#15
Tom D Heightman, Valerio Berdini, Hannah Braithwaite, Ildiko Maria Buck, Megan Cassidy, Juan Castro, Aurelie Courtin, James E H Day, Charlotte East, Lynsey Fazal, Brent Graham, Charlotte M Griffiths-Jones, John F Lyons, Vanessa Martins, Sandra Muench, Joanne M Munck, David Norton, Marc O'Reilly, Nick Palmer, Puja Pathuri, Michael Reader, David C Rees, Sharna J Rich, Caroline Richardson, Harpreet Saini, Neil T Thompson, Nicola G Wallis, Hugh Walton, Nicola E Wilsher, Alison J-A Woolford, Michael Cooke, David Cousin, Stuart Onions, Jonathan Shannon, John Watts, Christopher W Murray
Aberrant activation of the MAPK pathway drives cell proliferation in multiple cancers. Inhibitors of BRAF and MEK kinases are approved for the treatment of BRAF mutant melanoma, but resistance frequently emerges, often mediated by increased signalling through ERK1/2. Here we describe the fragment based generation of ERK1/2 inhibitors which block catalytic phosphorylation of downstream substrates such as RSK but also modulate phosphorylation of ERK1/2 by MEK without directly inhibiting MEK. X-ray crystallographic and biophysical fragment screening followed by structure-guided optimization and growth from the hinge into a pocket proximal to the C-α helix afforded highly potent ERK1/2 inhibitors with excellent kinome selectivity...
May 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29775286/multiple-architectures-and-mechanisms-of-latency-in-metallopeptidase-zymogens
#16
Joan L Arolas, Theodoros Goulas, Anna Cuppari, F Xavier Gomis-Rüth
Metallopeptidases cleave polypeptides bound in the active-site cleft of catalytic domains through a general base/acid mechanism. This involves a solvent molecule bound to a catalytic zinc and general regulation of the mechanism through zymogen-based latency. Sixty reported structures from 11 metallopeptidase families reveal that prosegments, mostly N-terminal of the catalytic domain, block the cleft regardless of their size. Prosegments may be peptides (5-14 residues), which are only structured within the zymogens, or large moieties (<227 residues) of one or two folded domains...
May 18, 2018: Chemical Reviews
https://www.readbyqxmd.com/read/29775222/abca1-inhibits-pdgf-induced-proliferation-and-migration-of-rat-airway-smooth-muscle-cell-through-blocking-tlr2-nf-%C3%AE%C2%BAb-nfatc1-signaling
#17
Wei Cheng, Kun Yan, Yanni Chen, Wen Zhang, Zongzheng Ji, Chengxue Dang
Airway remodeling is a key feature of asthma, characterized by abnormal proliferation and migration of airway smooth muscle cells (ASMCs). ABCA1, a member of the ATP-binding cassette family of active transporters, plays an essential role in the progression of lung diseases. However, the contributions of ABCA1 in ASMCs remain to be explored. The purpose of the present study was to investigate the functional role and potential molecular mechanism of ABCA1 in platelet derived growth factor (PDGF)-induced primary rat ASMC proliferation and migration...
May 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29775120/successful-improvement-of-pain-symptomatology-in-a-suspected-case-of-cramp-fasciculation-syndrome-via-interventional-pain-treatment
#18
Anita Gupta, Lucas First, Celeste A Swain
Peripheral nerve hyperexcitability (PNH) syndromes are a rare set of neuromuscular disorders that include cramp-fasciculation syndrome (CFS) and Isaacs syndrome (IS). Successful treatment of these diseases has been achieved with antiepileptic medications; however, chronic pain symptoms can persist. We provide a case report of a 25-year-old female who has suffered from painful severe muscle spasms and fasciculations since childhood. With CFS as our working diagnosis, a treatment regimen using interventional pain techniques, including sympathetic chain blocks, ketamine infusions, and trigger point injections, resulted in a significant decrease in the patient's chronic pain symptoms...
May 18, 2018: Journal of Pain & Palliative Care Pharmacotherapy
https://www.readbyqxmd.com/read/29774971/3d-dna-origami-crystals
#19
Tao Zhang, Caroline Hartl, Kilian Frank, Amelie Heuer-Jungemann, Stefan Fischer, Philipp C Nickels, Bert Nickel, Tim Liedl
3D crystals assembled entirely from DNA provide a route to design materials on a molecular level and to arrange guest particles in predefined lattices. This requires design schemes that provide high rigidity and sufficiently large open guest space. A DNA-origami-based "tensegrity triangle" structure that assembles into a 3D rhombohedral crystalline lattice with an open structure in which 90% of the volume is empty space is presented here. Site-specific placement of gold nanoparticles within the lattice demonstrates that these crystals are spacious enough to efficiently host 20 nm particles in a cavity size of 1...
May 18, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29774925/synthesis-of-n-dialkylamino-methyl-acrylamides-and-n-dialkylamino-methyl-methacrylamides-from-schiff-base-salts-useful-building-blocks-for-smart-polymers
#20
Abdullah Alzahrani, Styliana I Mirallai, Benjamin A Chalmers, Patrick McArdle, Fawaz Aldabbagh
The traditional thermal Mannich reaction is unsuitable for preparing polymerizable N-methylene amino substituted acrylamides and methacrylamides. Herein we provide a facile multi-gram high yield synthesis of these monomeric precursors to stimuli-responsive polymers by the addition of acrylamides and methacrylamides onto in situ generated or freshly isolated methylene Schiff base (iminium) salts. The X-ray crystal structure of the hydrated iminium salt, 1-(hydroxymethyl)azocan-1-ium chloride and monomer·HCl salt (N-[(azocan-1-yl)methyl]prop-2-enamide hydrochloride) is described...
May 18, 2018: Organic & Biomolecular Chemistry
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