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https://www.readbyqxmd.com/read/29793215/in-silico-insight-into-voltage-gated-sodium-channel-1-7-inhibition-for-anti-pain-drug-discovery
#1
Mingxing Wang, Wei Li, Ying Wang, Yongbo Song, Jian Wang, Maosheng Cheng
Studies on human genetics have implicated the voltage-gated sodium channel Nav1.7 as an appealing target for the treatment of pain. In this study, we put forward a ligand-based pharmacophore for the first time, which was generated by a set of multiple chemical scaffolds including sulfonamide and non-sulfonamide derivatives and consisted of four chemical features: an aromatic ring, a hydrophobic group and two hydrogen acceptors. The active cavity was divided into three regions according to the properties of the amino acids surrounded and was used for the docking of 16 known active inhibitors...
May 18, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29793112/3d-printed-membrane-as-an-alternative-to-amniotic-membrane-for-ocular-surface-conjunctival-defect-reconstruction-an-in-vitro-in-vivo-study
#2
Shima Dehghani, Morteza Rasoulianboroujeni, Hamed Ghasemi, Saeed Heidari Keshel, Zohreh Nozarian, Mohammad Naser Hashemian, Mehran Zarei-Ghanavati, Golshan Latifi, Reza Ghaffari, Zhanfeng Cui, Hua Ye, Lobat Tayebi
BACKGROUND: The aim of this study was to evaluate the surgical handling and clinical applicability of a specific 3D-printed membrane design fabricated using a gelatin, elastin and sodium hyaluronate blend for conjunctival reconstruction and compare it with amniotic membrane (AM), which is normally used in such surgeries. METHODS: 3D printing technique was employed to fabricate the membrane based on gradient design. Prior to printing, rheometry was employed to optimize the ink composition...
May 11, 2018: Biomaterials
https://www.readbyqxmd.com/read/29792672/biosynthesis-of-lincosamide-antibiotics-reactions-associated-with-degradation-and-detoxification-pathways-play-a-constructive-role
#3
Daozhong Zhang, Zhijun Tang, Wen Liu
Natural products typically are small molecules produced by living organisms. These products possess a wide variety of biological activities and thus have historically played a critical role in medicinal chemistry and chemical biology either as chemotherapeutic agents or as useful tools. Natural products are not synthesized for use by human beings; rather, living organisms produce them in response to various biochemical processes and environmental concerns, both internal and external. These processes/concerns are often dynamic and thus motivate the diversification, optimization, and selection of small molecules in line with changes in biological function...
May 24, 2018: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29792669/self-assembling-glutamate-functionalized-cyclodextrin-molecular-tube-for-specific-enrichment-of-n-linked-glycopeptides
#4
Haijiao Zheng, Xiqian Li, Qiong Jia
Cyclodextrin molecular tube (CDMT), a new comer of cyclodextrin family, possesses large and hydrophilic outer area and stable structure. Its development and applications remain highly desired, especially in the field of separation and enrichment. Herein, we developed a CDMT-based enrichment platform focusing on the specific capture of glycopeptides. To enhance the hydrophilicity of CDMT, it was functionalized with glutamate (glu). The prepared gluCDMT exhibited large hydrophilic surface, high stability, and good acidic/alkalic resistance...
May 24, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29792383/donor-variation-and-optimization-of-human-mesenchymal-stem-cells-chondrogenesis-in-hyaluronic-acid
#5
Minwook Kim, Isaac E Erickson, Alice H Huang, Sean T Garrity, Robert L Mauck, David R Steinberg
Mesenchymal stem cells (MSCs) are an attractive cell type for cartilage repair that can undergo chondrogenesis in a variety of three dimensional (3D) scaffolds. Hyaluronic acid (HA) hydrogels provide a biologically relevant interface for cell encapsulation. While our previous studies have shown that MSC-laden HA constructs can mature in vitro to match native mechanical properties using cells from animal sources, clinical application will depend on the successful translation of these findings to human cells...
May 24, 2018: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29791858/a-multi-layered-quantitative-in-vivo-expression-atlas-of-the-podocyte-unravels-kidney-disease-candidate-genes
#6
Markus M Rinschen, Markus Gödel, Florian Grahammer, Stefan Zschiedrich, Martin Helmstädter, Oliver Kretz, Mostafa Zarei, Daniela A Braun, Sebastian Dittrich, Caroline Pahmeyer, Patricia Schroder, Carolin Teetzen, HeonYung Gee, Ghaleb Daouk, Martin Pohl, Elisa Kuhn, Bernhard Schermer, Victoria Küttner, Melanie Boerries, Hauke Busch, Mario Schiffer, Carsten Bergmann, Marcus Krüger, Friedhelm Hildebrandt, Joern Dengjel, Thomas Benzing, Tobias B Huber
Damage to and loss of glomerular podocytes has been identified as the culprit lesion in progressive kidney diseases. Here, we combine mass spectrometry-based proteomics with mRNA sequencing, bioinformatics, and hypothesis-driven studies to provide a comprehensive and quantitative map of mammalian podocytes that identifies unanticipated signaling pathways. Comparison of the in vivo datasets with proteomics data from podocyte cell cultures showed a limited value of available cell culture models. Moreover, in vivo stable isotope labeling by amino acids uncovered surprisingly rapid synthesis of mitochondrial proteins under steady-state conditions that was perturbed under autophagy-deficient, disease-susceptible conditions...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29790546/dietary-fibers-prebiotics-and-exopolysaccharides-produced-by-lactic-acid-bacteria-potential-health-benefits-with-special-regard-to-cholesterol-lowering-effects
#7
REVIEW
E Korcz, Z Kerényi, L Varga
The gastrointestinal (GIT) microbiota, which plays a crucial role in human health, is influenced by a number of factors including diet. Consumption of specific dietary ingredients, such as dietary fibers and prebiotics, is an avenue by which the microbiota can be positively modulated. These substances may also reduce serum cholesterol levels through various mechanisms. Interest has increased in methods of reducing blood cholesterol level, because dyslipidemia is recognized as a contributory risk factor for the development of cardiovascular diseases...
May 23, 2018: Food & Function
https://www.readbyqxmd.com/read/29788780/isoform-selectivity-of-harmine-conjugated-1-2-3-triazoles-against-human-monoamine-oxidase
#8
Saqlain Haider, Manal Alhusban, Narayan D Chaurasiya, Babu L Tekwani, Amar G Chittiboyina, Ikhlas A Khan
AIM: There is little information available on the monoamine oxidase isoform selectivity of N-alkyl harmine analogs, which exhibit a myriad of activities including monoamine oxidase isoform A (MAO-A), tyrosine-phosphorylation-regulated kinase (DYRK1A) and cytotoxicity to several select cancer cell lines. RESULTS: Compounds 3e and 4c exhibited an IC50 of 0.83 ± 0.03 and 0.43 ± 0.002 μM against MAO-A and an IC50 of 0.26 ± 0.04 and 0.36 ± 0.001 μM against MAO-B, respectively...
May 23, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29788485/enzymatic-synthesis-of-random-sequences-of-rna-and-rna-analogues-by-dna-polymerase-theta-mutants-for-the-generation-of-aptamer-libraries
#9
Irina Randrianjatovo-Gbalou, Sandrine Rosario, Odile Sismeiro, Hugo Varet, Rachel Legendre, Jean-Yves Coppée, Valérie Huteau, Sylvie Pochet, Marc Delarue
Nucleic acid aptamers, especially RNA, exhibit valuable advantages compared to protein therapeutics in terms of size, affinity and specificity. However, the synthesis of libraries of large random RNAs is still difficult and expensive. The engineering of polymerases able to directly generate these libraries has the potential to replace the chemical synthesis approach. Here, we start with a DNA polymerase that already displays a significant template-free nucleotidyltransferase activity, human DNA polymerase theta, and we mutate it based on the knowledge of its three-dimensional structure as well as previous mutational studies on members of the same polA family...
May 21, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29788433/metabolic-footprinting-of-fermented-milk-consumption-in-serum-of-healthy-men
#10
Grégory Pimentel, Kathryn J Burton, Ueli von Ah, Ueli Bütikofer, François P Pralong, Nathalie Vionnet, Reto Portmann, Guy Vergères
Background: Fermentation is a widely used method of natural food preservation that has consequences on the nutritional value of the transformed food. Fermented dairy products are increasingly investigated in view of their ability to exert health benefits beyond their nutritional qualities. Objective: To explore the mechanisms underpinning the health benefits of fermented dairy intake, the present study followed the effects of milk fermentation, from changes in the product metabolome to consequences on the human serum metabolome after its ingestion...
May 21, 2018: Journal of Nutrition
https://www.readbyqxmd.com/read/29788236/a-novel-adeno-associated-virus-capsid-with-enhanced-neurotropism-corrects-a-lysosomal-transmembrane-enzyme-deficiency
#11
Julie Tordo, Claire O'Leary, André S L M Antunes, Nuria Palomar, Patrick Aldrin-Kirk, Mark Basche, Antonette Bennett, Zelpha D'Souza, Hélène Gleitz, Annie Godwin, Rebecca J Holley, Helen Parker, Ai Yin Liao, Paul Rouse, Amir Saam Youshani, Larbi Dridi, Carla Martins, Thierry Levade, Kevin B Stacey, Daniel M Davis, Adam Dyer, Nathalie Clément, Tomas Björklund, Robin R Ali, Mavis Agbandje-McKenna, Ahad A Rahim, Alexey Pshezhetsky, Simon N Waddington, R Michael Linden, Brian W Bigger, Els Henckaerts
Recombinant adeno-associated viruses (AAVs) are popular in vivo gene transfer vehicles. However, vector doses needed to achieve therapeutic effect are high and some target tissues in the central nervous system remain difficult to transduce. Gene therapy trials using AAV for the treatment of neurological disorders have seldom led to demonstrated clinical efficacy. Important contributing factors are low transduction rates and inefficient distribution of the vector. To overcome these hurdles, a variety of capsid engineering methods have been utilized to generate capsids with improved transduction properties...
May 16, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29787755/vibsanin-a-sensitizes-human-acute-myeloid-leukemia-cells-to-tyrosine-kinase-inhibitor-induced-myeloid-differentiation-via-activation-of-pkc-and-upregulation-of-lyn
#12
Xing Shen, Shuang Xing, Lu Zhang, Fangmin Wang, Hongling Ou, Yajun Shan, He Xiao, Guolin Xiong, Xinru Wang, Qinshi Zhao, Yuwen Cong, Zuyin Yu
Differentiation therapies have been proposed to overcome the impaired cell differentiation in acute myeloid leukemia (AML). However, thus far the all-trans retinoic acid-based differentiation therapy has been the only successful modality in treating acute promyelocytic leukemia. Here, we showed that vibsanin A, a novel protein kinase C (PKC) activator, sensitized AML cells to tyrosine kinase inhibitor (TKI)-induced differentiation. Vibsanin A augmented the ability of TKIs to induce growth inhibition and G1 cell cycle arrest of AML cells...
May 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29787262/discovery-of-novel-pazopanib-based-hdac-and-vegfr-dual-inhibitors-targeting-cancer-epigenetics-and-angiogenesis-simultaneously
#13
Jie Zang, Xuewu Liang, Yongxue Huang, Yuping Jia, Xiaoyang Li, Wenfang Xu, C James Chou, Yingjie Zhang
Herein a novel series of pazopanib hybrids as polypharmacological antitumor agents were developed based on the crosstalk between histone deacetylases (HDACs) and vascular endothelial growth factor (VEGF) pathway. Among them, one ortho-aminoanilide 6d and one hydroxamic acid 13f exhibited considerable total HDACs and VEGFR-2 inhibitory activities. The HDAC inhibitory activities endowed 6d and 13f with potent antiproliferative activities, which was not observed in the approved VEGFR inhibitor pazopanib. Compounds 6d and 13f possessed comparable HDAC isoform selectivity profiles to the clinical class I HDAC inhibitor MS-275 and the approved pan-HDAC inhibitor SAHA, respectively...
May 22, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29785907/the-fatty-acid-composition-of-estonian-and-latvian-retail-milk-implications-for-human-nutrition-compared-with-a-designer-milk
#14
Merike Henno, Tiia Ariko, Tanel Kaart, Sirje Kuusik, Katri Ling, Marko Kass, Hanno Jaakson, Ragnar Leming, D Ian Givens, Vita Sterna, Meelis Ots
The study reported in this Research Communication compared retail milks' FA profiles from two neighbouring countries, estimated the potential contributions of these milks and a designer milk (achieved by changing the diet of the dairy cow) to the recommended human dietary intake of FA, and predicted (based on the milk FA profile) methane emission from dairy cows. Retail milks in Estonia and Latvia were purchased from supermarkets monthly for one year. To compare the FA composition of retail milk with designer milk with an increased PUFA content, the bulk milk FA profile from a separate field trial was used...
May 2018: Journal of Dairy Research
https://www.readbyqxmd.com/read/29785806/chemiluminescence-of-copper-nanoclusters-and-its-application-for-trihexyphenidyl-hydrochloride-detection
#15
Xiaoxia Chen, Junmei Zhang, Yue Li, Suqin Han
Chemiluminescence (CL) of copper nanoclusters (CuNCs) induced by cerium (IV) (Ce(IV)) or potassium permanganate (KMnO4 ) in acidic medium was observed. The potential application of CuNCs CL in analytical chemistry was also demonstrated using trihexyphenidyl hydrochloride (THP) as an example based on its enhancing CL intensity for the CuNCs-Ce(IV)/KMnO4 systems. The excited state of the CuNCs acted as a luminophore in the CuNCs-Ce(IV) system, while CuNCs played the role of reductant in the CuNCs-KMnO4 system...
May 21, 2018: Luminescence: the Journal of Biological and Chemical Luminescence
https://www.readbyqxmd.com/read/29785215/mycobacteriosis-and-tuberculosis-laboratory-diagnosis
#16
REVIEW
Davood Azadi, Tahereh Motallebirad, Kazem Ghaffari, Hasan Shojaei
Background: Tuberculosis is one of the most important infectious diseases that has claimed its victims throughout much of known human history. With Koch's discovery of the tubercle bacillus as the etiologic agent of the disease, his sanitary and hygienic measures, which were based on his discovery and the development of a vaccine against tuberculosis by Albert Calmette and Camille Guérin in 1921, an attenuated Mycobacterium bovis strain, bacilli Calmette-Guérin (BCG), and the discovery of the first antibiotic against tuberculosis, streptomycin by Selman Waksman in 1943, soon led to the opinion that appropriate control measures had become available for tuberculosis and it had been assumed that the disease could ultimately be eradicated...
2018: Open Microbiology Journal
https://www.readbyqxmd.com/read/29785042/inducible-high-efficiency-crispr-cas9-targeted-gene-editing-and-precision-base-editing-in-african-trypanosomes
#17
Eva Rico, Laura Jeacock, Julie Kovářová, David Horn
The Cas9 endonuclease can be programmed by guide RNA to introduce sequence-specific breaks in genomic DNA. Thus, Cas9-based approaches present a range of novel options for genome manipulation and precision editing. African trypanosomes are parasites that cause lethal human and animal diseases. They also serve as models for studies on eukaryotic biology, including 'divergent' biology. Genome modification, exploiting the native homologous recombination machinery, has been important for studies on trypanosomes but often requires multiple rounds of transfection using selectable markers that integrate at low efficiency...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29784367/one-step-synthesis-of-fluorescent-carbon-dots-for-sensitive-and-selective-detection-of-hyperin
#18
Lizhen Liu, Zhi Mi, Qin Hu, Caiqing Li, Xiaohua Li, Feng Feng
In this article, we presented a new rapid, sensitive and selective method for the determination of hyperin (Hyp) based on the fluorescence quenching of fluorescent carbon dots (CDs). The CDs were prepared by simply mixing an aqueous solution of citric acid with diphosphorus pentoxide. This one-step synthetic route is fast and simple with neither high temperature nor complicated synthesis steps is involved. When Hyp was added to CDs solution, the fluorescence intensity of the CDs significantly decreased. The CDs display high selectivity for Hyp over many potentially interfering substances...
August 15, 2018: Talanta
https://www.readbyqxmd.com/read/29784358/short-probe-based-duplex-specific-nuclease-signal-amplification-strategy-enables-imaging-of-endogenous-micrornas-in-living-cells-with-ultrahigh-specificity
#19
Yingjun Ma, Jun Chen, Danping Chen, Yuzhi Xu, Li Zhang, Zong Dai, Xiaoyong Zou
Specific nucleic acids amplification at a constant and mild temperature is important for imaging assay of endogenous microRNAs (miRNAs) in living cells. Duplex-specific nuclease (DSN) is attractive in one-step isothermal assay of miRNA; however, its intrinsic limitations of low amplification specificity and high reaction temperature greatly restrict the application scope. Herein, we present a short-probe-based DSN signal amplification (spDSNSA) strategy enabling analysis of miRNAs at body temperature with significantly high specificity...
August 15, 2018: Talanta
https://www.readbyqxmd.com/read/29784321/iridoid-blue-based-pigments-of-genipa-americana-l-rubiaceae-extract-influence-of-ph-and-temperature-on-color-stability-and-antioxidant-capacity-during-in-vitro-simulated-digestion
#20
Iramaia Angélica Neri-Numa, Celio Fernando Figueiredo Angolini, Juliano Lemos Bicas, Ana Lucia Tasca Gois Ruiz, Glaucia Maria Pastore
Iridoid blue-based pigments (IBBP) extract of Genipa americana L. represents a natural alternative additive for food applications and also exerts desirable biological effects on human health. In this study the iridoids present in the extract were identified, the influence of pH and temperature on color difference (ΔE) of IBBP was evaluated using a central composite design (CCD) and finally the antioxidant capacity was monitored before and after its in vitro digestion. Ten glucoside iridoids were detected and the main compounds identified were genipin, genipin 1-β-gentiobioside and geniposide...
October 15, 2018: Food Chemistry
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