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https://www.readbyqxmd.com/read/29783098/design-and-synthesis-of-aminocoumarin-derivatives-as-dpp-iv-inhibitors-and-anticancer-agents
#1
Rina Soni, Shubhangi S Soman
DPP-IV "a moonlighting protein" has immerged as promising pathway to control Type 2 diabetes as well as found to play key role in earlier stages of cancer. Here we have reported design, synthesis and applications of aminocoumarin derivatives as DPP-IV inhibitors. Compounds have been synthesized and studied for their DPP-IV inhibition activity. Three compounds have shown moderate inhibition at 100 µM concentration. All compounds were also screened for their anticancer activity against A549 (Lung cancer cell line), MCF-7 (Breast cancer cell line) using MTT assay...
May 17, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29782985/facile-preparation-of-recombinant-spider-eggcase-silk-spheres-via-an-hfip-on-oil-approach
#2
Jianming Chen, Jinlian Hu, Peijun Zuo, Jingyu Shi, Mo Yang
Versatile spider silk proteins have been prepared by various methods in morphology of spheres for functional applications. Inspired from natural spinning process, a facile approach for the fabrication of silk spheres is described. Distinct from the traditional emulsification method, silk spheres were assembled as rapidly as 10 s by using the HFIP-on-Oil method without any surfactants and agitation used. Notably, a series of factors, such as evaporation rate of HFIP, polarity and molecular weight of oils play central roles on the final silk morphologies...
May 18, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29782984/design-and-development-of-novel-hyaluronate-modified-nanoparticles-for-combo-delivery-of-curcumin-and-alendronate-fabrication-characterization-and-cellular-and-molecular-evidence-of-enhanced-bone-regeneration
#3
Jinlei Dong, Hnin Ei Thu, Mohammed A S Abourehab, Zahid Hussain
Osteoporosis is a medical condition of fragile bones with an increased susceptibility to bone fracture. Despite having availability of a wide range of pharmacological agents, prevalence of this metabolic disorder is continuously escalating. Owing to excellent biomedical achievements of nanomedicines in the last few decades, we aimed combo delivery of bone anti-resorptive agent, alendronate (ALN), and bone density enhancing drug, curcumin (CUR), in the form of polymeric nanoparticles. To further optimize the therapeutic efficacy, the prepared ALN/CUR nanoparticles were decorated with hyaluronic acid which is a well-documented biomacromolecule having exceptional bone regenerating potential...
May 18, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29782976/ldiscu-is-a-2fe-2s-scaffold-protein-which-interacts-with-ldiscs-and-its-expression-is-modulated-by-fe-s-proteins-in-leishmania-donovani
#4
Krishn Pratap Singh, Shadab Anwar, Amir Zaidi, Kuljit Singh, Pradeep Das, Samudrala Gourinath, Vahab Ali
The pathogenicity of protozoan parasites is frequently attributed to their ability to circumvent the deleterious effects of ROS and Fe-S clusters are among their susceptible targets with paramount importance for parasite survival. The biogenesis of Fe-S clusters is orchestrated by ISC system; the sulfur donor IscS and scaffold protein IscU being its core components. However, among protozoan parasites including Leishmania, no information is available regarding biochemical aspect of IscU, its interaction partners and regulation...
May 18, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29782958/changes-in-behavioural-parameters-oxidative-stress-and-neurotrophins-in-the-brain-of-adult-offspring-induced-to-an-animal-model-of-schizophrenia-the-effects-of-fa-deficient-or-fa-supplemented-diet-during-the-neurodevelopmental-phase
#5
L Canever, T G Freire, G A Mastella, L Damázio, S Gomes, I Fachim, C Michels, G Carvalho, A K Godói, B R Peterle, F F Gava, S Valvassori Sda, J Budni, J Quevedo, A I Zugno
A deficiency of maternal folic acid (FA) can compromise the function and development of the brain, and may produce a susceptibility to diseases such as schizophrenia (SZ) in the later life of offspring. The aim of this study was to evaluate the effects of both FA deficient and FA supplemented diets during gestation and lactation on behavioural parameters, the markers of oxidative stress and neurotrophic factors in adult offspring which had been subjected to an animal model of SZ. Female mother rats (Dam's) were separated into experimental maternal groups, which began receiving a special diet (food) consisting of the AIN-93 diet, a control diet, or an FA deficient diet during the periods of pregnancy and lactation...
May 18, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29782939/global-deletion-of-tetraspanin-cd82-attenuates-bone-growth-and-enhances-bone-marrow-adipogenesis
#6
Alexis Bergsma, Sourik S Ganguly, Daniel Dick, Bart O Williams, Cindy K Miranti
CD82 is a widely expressed member of the tetraspanin family of transmembrane proteins known to control cell signaling, adhesion, and migration. Tetraspanin CD82 is induced over 9-fold during osteoclast differentiation in vitro; however, its role in bone homeostasis is unknown. A globally deleted CD82 mouse model was used to assess the bone phenotype. Based on microCT and 4-point bending tests, CD82-deficient bones are smaller in diameter and weaker, but display no changes in bone density. Histomorphometry shows a decrease in size, erosion perimeter, and number of osteoclasts in situ, with a corresponding increase in trabecular surface area, specifically in male mice...
May 18, 2018: Bone
https://www.readbyqxmd.com/read/29782895/detection-of-il-36y-via-non-invasive-tape-stripping-reliably-discriminates-psoriasis-from-atopic-eczema
#7
Anna Berekméri, Anne Latzko, Adewonuola Alase, Tom Macleod, Joseph S Ainscough, Philip Laws, Mark Goodfield, Andrew Wright, Philip Helliwell, Sara Edward, Gordon D Brown, Delyth M Reid, Joerg Wenzel, Martin Stacey, Miriam Wittmann
This report demonstrates that sampling and detection of IL-36γ protein by non-invasive tape stripping of skin lesion provides a highly sensitive and selective diagnostic for psoriatic inflammation.
May 18, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29782894/screening-of-the-mmv-and-gsk-open-access-chemical-boxes-using-a-viability-assay-developed-against-the-kinetoplastid-crithidia-fasciculata
#8
Wakisa Kipandula, Simon A Young, Stuart A MacNeill, Terry K Smith
Diseases caused by the pathogenic kinetoplastids continue to incapacitate and kill hundreds of thousands of people annually throughout the tropics and sub-tropics. Unfortunately, in the countries where these neglected diseases occur, financial obstacles to drug discovery and technical limitations associated with biochemical studies impede the development of new, safe, easy to administer and effective drugs. Here we report the development and optimisation of a Crithidia fasciculata resazurin viability assay, which is subsequently used for screening and identification of anti-crithidial compounds in the MMV and GSK open access chemical boxes...
May 18, 2018: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/29782833/insights-into-stabilizing-forces-in-amyloid-fibrils-of-differing-sizes-from-polarizable-molecular-dynamics-simulations
#9
Darcy S Davidson, Anne M Brown, Justin A Lemkul
Pathological aggregation of amyloid-forming proteins is a hallmark of a number of human diseases, including Alzheimer's, type 2 diabetes, Parkinson's, and more. Despite having very different primary amino acid sequences, these amyloid proteins form similar supramolecular, fibril structures that are highly resilient to physical and chemical denaturation. To better understand the structural stability of disease-related amyloids and to gain a greater understanding of factors that stabilize functional amyloid assemblies, insights into tertiary and quaternary interactions are needed...
May 18, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29782554/hijacking-of-multiple-phospholipid-biosynthetic-pathways-and-induction-of-membrane-biogenesis-by-a-picornaviral-3cd-protein
#10
Sravani Banerjee, David Aponte-Diaz, Calvin Yeager, Suresh D Sharma, Gang Ning, Hyung S Oh, Qingxia Han, Masato Umeda, Yuji Hara, Robert Y L Wang, Craig E Cameron
RNA viruses induce specialized membranous structures for use in genome replication. These structures are often referred to as replication organelles (ROs). ROs exhibit distinct lipid composition relative to other cellular membranes. In many picornaviruses, phosphatidylinositol-4-phosphate (PI4P) is a marker of the RO. Studies to date indicate that the viral 3A protein hijacks a PI4 kinase to induce PI4P by a mechanism unrelated to the cellular pathway, which requires Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1, GBF1, and ADP ribosylation factor 1, Arf1...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29782552/role-of-kinesins-in-directed-adenovirus-transport-and-cytoplasmic-exploration
#11
Jie Zhou, Julian Scherer, Julie Yi, Richard B Vallee
Many viruses, including adenovirus, exhibit bidirectional transport along microtubules following cell entry. Cytoplasmic dynein is responsible for microtubule minus end transport of adenovirus capsids after endosomal escape. However, the identity and roles of the opposing plus end-directed motor(s) remain unknown. We performed an RNAi screen of 38 kinesins, which implicated Kif5B (kinesin-1 family) and additional minor kinesins in adenovirus 5 (Ad5) capsid translocation. Kif5B RNAi markedly increased centrosome accumulation of incoming Ad5 capsids in human A549 pulmonary epithelial cells within the first 30 min post infection, an effect dramatically enhanced by blocking Ad5 nuclear pore targeting using leptomycin B...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29782551/structural-insights-on-the-efficient-catalysis-of-hydroperoxide-reduction-by-ohr-crystallographic-and-molecular-dynamics-approaches
#12
Erika Piccirillo, Thiago G P Alegria, Karen F Discola, José R R Cussiol, Renato M Domingos, Marcos A de Oliveira, Leandro de Rezende, Luis E S Netto, Antonia T-do Amaral
Organic hydroperoxide resistance (Ohr) enzymes are highly efficient Cys-based peroxidases that play central roles in bacterial response to fatty acid hydroperoxides and peroxynitrite, two oxidants that are generated during host-pathogen interactions. In the active site of Ohr proteins, the conserved Arg (Arg19 in Ohr from Xylella fastidiosa) and Glu (Glu51 in Ohr from Xylella fastidiosa) residues, among other factors, are involved in the extremely high reactivity of the peroxidatic Cys (Cp) toward hydroperoxides...
2018: PloS One
https://www.readbyqxmd.com/read/29782536/fungal-type-carbohydrate-binding-modules-from-the-coccolithophore-emiliania-huxleyi-show-binding-affinity-to-cellulose-and-chitin
#13
Bart J M Rooijakkers, Martina S Ikonen, Markus B Linder
Six fungal-type cellulose binding domains were found in the genome of the coccolithophore Emiliania huxleyi and cloned and expressed in Escherichia coli. Sequence comparison indicate high similarity to fungal cellulose binding domains, raising the question of why these domains exist in coccolithophores. The proteins were tested for binding with cellulose and chitin as ligands, which resulted in the identification of two functional carbohydrate binding modules: EHUX2 and EHUX4. Compared to benchmark fungal cellulose binding domain Cel7A-CBM1 from Trichoderma reesei, these proteins showed slightly lower binding to birch and bacterial cellulose, but were more efficient chitin binders...
2018: PloS One
https://www.readbyqxmd.com/read/29782498/endoplasmic-reticulum-plasma-membrane-contact-sites-integrate-sterol-and-phospholipid-regulation
#14
Evan Quon, Yves Y Sere, Neha Chauhan, Jesper Johansen, David P Sullivan, Jeremy S Dittman, William J Rice, Robin B Chan, Gilbert di Paolo, Christopher T Beh, Anant K Menon
Tether proteins attach the endoplasmic reticulum (ER) to other cellular membranes, thereby creating contact sites that are proposed to form platforms for regulating lipid homeostasis and facilitating non-vesicular lipid exchange. Sterols are synthesized in the ER and transported by non-vesicular mechanisms to the plasma membrane (PM), where they represent almost half of all PM lipids and contribute critically to the barrier function of the PM. To determine whether contact sites are important for both sterol exchange between the ER and PM and intermembrane regulation of lipid metabolism, we generated Δ-super-tether (Δ-s-tether) yeast cells that lack six previously identified tethering proteins (yeast extended synatotagmin [E-Syt], vesicle-associated membrane protein [VAMP]-associated protein [VAP], and TMEM16-anoctamin homologues) as well as the presumptive tether Ice2...
May 21, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29782496/development-of-a-toolkit-for-piggybac-mediated-integrative-transfection-of-the-human-filarial-parasite-brugia-malayi
#15
Canhui Liu, Amruta S Mhashilkar, Johan Chabanon, Shulin Xu, Sara Lustigman, John H Adams, Thomas R Unnasch
BACKGROUND: The human filarial parasites cause diseases that are among the most important causes of morbidity in the developing world. The elimination programs targeting these infections rely on a limited number of drugs, making the identification of new chemotherapeutic agents a high priority. The study of these parasites has lagged due to the lack of reverse genetic methods. METHODOLOGY/PRINCIPAL FINDINGS: We report a novel co-culture method that results in developmentally competent infective larvae of one of the human filarial parasites (Brugia malayi) and describe a method to efficiently transfect the larval stages of this parasite...
May 21, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29782350/effect-of-pyruvate-kinase-m2-regulating-aerobic-glycolysis-on-chemotherapy-resistance-of-estrogen-receptor-positive-breast-cancer
#16
Yuejun Qian, Lina Bi, Yingxu Yang, Dong Wang
This study aims to explore the effect and mechanism of pyruvate kinase M2 (PKM2) on chemotherapy resistance of estrogen receptor-positive breast cancer (ER BC) by regulating aerobic glycolysis. The expression of PKM2 in ER BC MCF-7 cells, T47D cells and MCF-7/ADR cells (which are subject to adriamycin/ADR induction) were determined by quantitative real-time PCR and western blot. MCF-7/ADR (M/A) cells were grouped into blank group (M/A), negative group (M/A+NC), low expression of PKM2 group (M/A+si-PKM2 group), overexpression of PKM2 group (M/A+PKM2 group) and glycolysis inhibition group (M/A+PKM2+2-DG group)...
May 18, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29782332/detection-of-high-risk-thrombophilia-with-an-automated-global-test-the-coagulation-inhibitor-potential-assay
#17
Barbara Réger, Hajna Losonczy, Ágnes Nagy, Ágnes Péterfalvi, Réka Mózes, László Pótó, Nelli Farkas, Gábor L Kovács, Attila Miseta, Alizadeh Hussain, Orsolya Tóth
: The diagnosis of thrombophilia is a cost-consuming and time-consuming process, as each defect should be separately investigated. The Coagulation Inhibitor Potential (CIP) assay is a promising new global test, sensitive for most of the hereditary thrombophilias, developed for manual methodology. We adapt the original method to an optical coagulation analyser. By this automation, the test will be easier, faster and more precise, and it also allows carrying out 18 measurements simultaneously. The CIP assay was performed in 126 healthy subjects and 193 patients with different types of hereditary thrombophilia conditions...
May 17, 2018: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/29782274/-dysfunctional-high-density-lipoproteins-role-in-atherogenesis-and-potential-targets-for-phospholipid-therapy
#18
T I Torchovskaya, V A Kudinov, T S Zakharova, S S Markin
In recent years the number of articles on damages of high-density lipoproteins (HDL) properties in patients with atherosclerosis has sharply increased. First, it concerns their ability to accept cholesterol (CH) from macrophages - the basis of antiatherogenic action of HDL. This ability was assessed ex vivo - by activity of cell cholesterol (CH) efflux to HDL or into patient's serum. In many works inverse relationship was shown between CH acceptor capacity of HDL and severity of atherosclerotic disease or frequency of its exacerbations during long-term observation, independent from HDL CH concentration...
March 2018: Kardiologiia
https://www.readbyqxmd.com/read/29782248/-hepcidin-and-its-relationship-with-inflammation-in-old-and-older-patients-with-anemia-of-chronic-disease-associated-with-chf
#19
N I Solomakhina, E S Nakhodnova, E P Gitel, Y N Belenkov
BACKGROUND: Reported levels of hepcidin, the major regulator of systemic iron homeostasis in CHF patients, are controversial. Relationship of hepcidin with inflammation markers, which are typically increased in CHF, is understudied; this issue is practically unstudied in old and older CHF patients. AIM: To study the role of hepcidin in development of anemia of chronic disease (ACD) and the association of hepcidin with inflammation in old and older CHF patients. MATERIALS AND METHODS: Ninety old and older patients with IHD were evaluated...
2018: Kardiologiia
https://www.readbyqxmd.com/read/29782207/the-benzodiazepine-anesthetic-midazolam-prevents-hyperglycemia-induced-microvascular-leakage-in-the-retinas-of-diabetic-mice
#20
Yeon-Ju Lee, Minsoo Kim, Jee-Yeon Lee, Se-Hui Jung, Hye-Yoon Jeon, Seung Ah Lee, Seongsik Kang, Eun-Taek Han, Won Sun Park, Seok-Ho Hong, Young-Myeong Kim, Kwon-Soo Ha
We investigated the beneficial effects of midazolam against vascular endothelial growth factor (VEGF)-induced vascular leakage and its molecular mechanism of action in human retinal endothelial cells (HRECs) and the retinas of diabetic mice. Midazolam inhibited VEGF-induced elevation of intracellular Ca2+ , generation of reactive oxygen species (ROS), and transglutaminase activation in HRECs; these effects were reversed by the GABA, type A (GABAA ) receptor antagonist flumazenil but not by the translocator protein antagonist PK11195...
May 21, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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