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https://www.readbyqxmd.com/read/29684895/design-synthesis-and-biological-evaluation-of-novel-xanthine-oxidase-inhibitors-bearing-a-2-arylbenzo-b-furan-scaffold
#1
Hong-Jin Tang, Wei Li, Mei Zhou, Li-Ying Peng, Jin-Xin Wang, Jia-Huang Li, Jun Chen
Xanthine oxidase, which catalyzes the oxidative reaction of hypoxanthine and xanthine into uric acid, is a key enzyme to the pathogenesis of hyperuricemia and gout. In this study, for the purpose of discovering novel xanthine oxidase (XO) inhibitors, a series of 2-arylbenzo[b]furan derivatives (3a-3d, 4a-4o and 6a-6d) were designed and synthesized. All these compounds were evaluated their xanthine oxidase inhibitory and antioxidant activities by using in vitro enzymatic assay and cellular model. The results showed that a majority of the designed compounds exhibited potent xanthine oxidase inhibitory effects and antioxidant activities, and compound 4a emerged as the most potent xanthine oxidase inhibitor (IC50  = 4...
February 2, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29684754/increases-in-helminth-induced-il-21-protein-levels-disappear-upon-sample-freezing
#2
Anupama Ariyaratne, Edina K Szabo, Joel Bowron, Constance A M Finney
IL-21 is a much studied cytokine that has been implicated in the regulation of TH1, TH2, TH17 and regulatory immune responses; its signalling is a promising therapeutic target for autoimmune, inflammatory and infectious diseases. Despite its biological importance, measuring IL-21 reliably has proved difficult. ELISAs are commonly used to measure cytokines in various biological samples. However, results obtained are only as good as the quality of the sample. Here, we show that when using fresh samples, a significant increase in IL-21 was measured in the intestinal homogenate of mice infected with the intestinal worm Heligmosomoides polygyrus...
April 20, 2018: Cytokine
https://www.readbyqxmd.com/read/29684620/in-vivo-quantification-of-hydrogen-gas-concentration-in-bone-marrow-surrounding-magnesium-fracture-fixation-hardware-using-an-electrochemical-hydrogen-gas-sensor
#3
Daoli Zhao, Andrew Brown, Tingting Wang, Sayuri Yoshizawa, Charles Sfeir, William R Heineman
Magnesium (Mg) medical devices are currently being marketed for orthopedic applications and have a complex degradation process which includes the evolution of hydrogen gas (H2 ). The effect of H2 exposure on relevant cell types has not been studied; and the concentration surrounding degrading Mg devices has not been quantified to enable such mechanistic studies. A simple and effective method to measure the concentration of H2 in varying microenvironments surrounding Mg implants is the first step to understanding the biological impact of H2 on these cells...
April 20, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29684594/new-apetx-like-peptides-from-sea-anemone-heteractis-crispa-modulate-asic1a-channels
#4
Rimma Kalina, Irina Gladkikh, Pavel Dmitrenok, Oleg Chernikov, Sergey Koshelev, Aleksandra Kvetkina, Sergey Kozlov, Emma Kozlovskaya, Margarita Monastyrnaya
Sea anemones are an abundant source of various biologically active peptides. The hydrophobic 20% ethanol fraction of tropical sea anemone Heteractis crispa was shown to contain at least 159 peptide compounds including neurotoxins, proteinase and α-amylase inhibitors, as well as modulators of acid-sensing ion channels (ASICs). The three new peptides, π-AnmTX Hcr 1b-2, -3, and -4 (41 aa) (short names Hcr 1b-2, -3, -4), identified by a combination of reversed-phase liquid chromatography and mass spectrometry were found to belong to the class 1b sea anemone neurotoxins...
April 20, 2018: Peptides
https://www.readbyqxmd.com/read/29684553/fission-yeast-cells-overproducing-hset-kifc1-provides-a-useful-tool-for-identification-and-evaluation-of-human-kinesin-14-inhibitors
#5
Masashi Yukawa, Tomoaki Yamauchi, Naoaki Kurisawa, Shakil Ahmed, Ken-Ichi Kimura, Takashi Toda
Many human cancer cells contain more than two centrosomes, yet these cancer cells can form pseudo-bipolar spindles through the mechanism, called centrosome clustering, and survive, instead of committing lethal multipolar mitoses. Kinesin-14/HSET, a minus end-directed motor, plays a crucial role in centrosome clustering. Accordingly, HSET is deemed to be a promising chemotherapeutic target to selectively kill cancer cells. Recently, three HSET inhibitors (AZ82, CW069 and SR31527) have been reported, but their specificity and efficacy have not been evaluated rigorously...
April 20, 2018: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/29684467/vitamin-c-for-the-treatment-of-sepsis-the-scientific-rationale
#6
REVIEW
Paul E Marik
Most vertebrates can synthesize vitamin C with synthesis increasing during stress. Humans, however, have lost the ability to synthesize vitamin C. Vitamin C is an important anti-oxidant and an enzyme cofactor for many important biological reactions. Sepsis results in the overwhelming production of reactive oxygen species with widespread endothelial, cellular and mitochondrial injury leading to progressive organ failure. Sepsis is associated with an acute deficiency of vitamin C. In experimental sepsis models, intravenous vitamin C reduces organ injury and improves survival...
April 20, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29684420/novel-cancer-gene-variants-and-gene-fusions-of-triple-negative-breast-cancers-tnbcs-reveal-their-molecular-diversity-conserved-in-the-patient-derived-xenograft-pdx-model
#7
Jaeyun Jung, Kiwon Jang, Jung Min Ju, Eunji Lee, Jong Won Lee, Hee Jung Kim, Jisun Kim, Sae Byul Lee, Beom Seok Ko, Byung Ho Son, Hee Jin Lee, Gyungyup Gong, Sei Yeon Ahn, Jung Kyoon Choi, Shree Ram Singh, Suhwan Chang
Despite the improved 5-year survival rate of breast cancer, triple-negative breast cancer (TNBC) remains a challenge due to lack of effective targeted therapy and higher recurrence and metastasis than other subtypes. To identify novel druggable targets and to understand its unique biology, we tried to implement 24 patient-derived xenografts (PDXs) of TNBC. The overall success rate of PDX implantation was 45%, much higher than estrogen receptor (ER)-positive cases. Immunohistochemical analysis revealed conserved ER/PR/Her2 negativity (with two exceptions) between the original and PDX tumors...
April 20, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29684332/lipid-flip-flop-vs-lateral-diffusion-in-the-relaxation-of-hemifusion-diaphragms
#8
Jasmine M Gardner, Cameron F Abrams
Molecular dynamics simulations of a solvent-free coarse-grained lipid model are used to characterize the mechanisms by which lipid-bilayer hemifusion diaphragm (HD) intermediates relax, across a range of global compositions of negative intrinsic curvature (NIC) lipids and neutral-curvature lipids. At low concentrations of NIC lipids, rapid fission produces a double bilayer end state through a lateral diffusion-based mechanism enabled by spontaneous rim-pore defects. At moderately higher NIC lipid concentrations, rim pores are absent and stable leaflet three-junctions persist, revealing an HD relaxation mechanism entirely reliant on lipid flip-flop, and end states that are either stable fusion pores or stable HD's...
April 20, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29684118/spontaneous-endometriosis-in-cynomolgus-monkeys-as-a-clinically-relevant-experimental-model
#9
A Nishimoto-Kakiuchi, S Netsu, S Okabayashi, K Taniguchi, H Tanimura, A Kato, M Suzuki, T Sankai, R Konno
STUDY QUESTION: Does spontaneous endometriosis in cynomolgus monkeys have the characteristics required of a good experimental model? SUMMARY ANSWER: Spontaneous endometriosis in cynomolgus monkeys exhibited similar clinicopathological characteristics to the human disease and was useful as an experimental model. WHAT IS KNOWN ALREADY: The prevalence of endometriosis in autopsied cynomolgus monkeys (Macaca fascicularis) in a breeding colony was reported to be 28...
April 19, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29684098/binquasi-a-peak-detection-method-for-chip-sequencing-data-with-biological-replicates
#10
Emily Goren, Peng Liu, Chao Wang, Chong Wang
Motivation: ChIP-seq experiments that are aimed at detecting DNA-protein interactions require biological replication to draw inferential conclusions, however there is no current consensus on how to analyze ChIP-seq data with biological replicates. Very few methodologies exist for the joint analysis of replicated ChIP-seq data, with approaches ranging from combining the results of analyzing replicates individually to joint modeling of all replicates. Combining the results of individual replicates analyzed separately can lead to reduced peak classification performance compared to joint modeling...
April 19, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29684020/black-boxing-and-cause-effect-power
#11
William Marshall, Larissa Albantakis, Giulio Tononi
Reductionism assumes that causation in the physical world occurs at the micro level, excluding the emergence of macro-level causation. We challenge this reductionist assumption by employing a principled, well-defined measure of intrinsic cause-effect power-integrated information (Φ), and showing that, according to this measure, it is possible for a macro level to "beat" the micro level. Simple systems were evaluated for Φ across different spatial and temporal scales by systematically considering all possible black boxes...
April 23, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29684017/dissecting-the-null-model-for-biological-invasions-a-meta-analysis-of-the-propagule-pressure-effect
#12
Phillip Cassey, Steven Delean, Julie L Lockwood, Jason Sadowski, Tim M Blackburn
A consistent determinant of the establishment success of alien species appears to be the number of individuals that are introduced to found a population (propagule pressure), yet variation in the form of this relationship has been largely unexplored. Here, we present the first quantitative systematic review of this form, using Bayesian meta-analytical methods. The relationship between propagule pressure and establishment success has been evaluated for a broad range of taxa and life histories, including invertebrates, herbaceous plants and long-lived trees, and terrestrial and aquatic vertebrates...
April 23, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29684011/computational-mechanisms-underlying-cortical-responses-to-the-affordance-properties-of-visual-scenes
#13
Michael F Bonner, Russell A Epstein
Biologically inspired deep convolutional neural networks (CNNs), trained for computer vision tasks, have been found to predict cortical responses with remarkable accuracy. However, the internal operations of these models remain poorly understood, and the factors that account for their success are unknown. Here we develop a set of techniques for using CNNs to gain insights into the computational mechanisms underlying cortical responses. We focused on responses in the occipital place area (OPA), a scene-selective region of dorsal occipitoparietal cortex...
April 23, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29683839/obesity-impacts-swelling-of-ankle-and-foot-joints-in-early-rheumatoid-arthritis-patients
#14
Veena K Ranganath, Erin L Duffy, Vikram K Garg, Thasia Woodworth, Mihaela Taylor, Harold E Paulus, Roy D Altman, David A Elashoff
OBJECTIVE: The evaluation of disease activity in obese rheumatoid arthritis (RA) patients presents challenges particularly in the clinical assessment of swollen joints. This study examines the effect of obesity on the American College of Rheumatology (ACR) core set measures used in assessing RA disease activity with specific focus on the swollen joint count (SJC). METHODS: We examined a cross-sectional cohort of 323 early seropositive RA patients (symptom duration ≤15 months)...
April 16, 2018: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/29683466/anatomy-of-triply-periodic-network-assemblies-characterizing-skeletal-and-inter-domain-surface-geometry-of-block-copolymer-gyroids
#15
Ishan Prasad, Hiroshi Jinnai, Rong-Ming Ho, Edwin L Thomas, Gregory M Grason
Triply-periodic networks (TPNs), like the well-known gyroid and diamond network phases, abound in soft matter assemblies, from block copolymers (BCPs), lyotropic liquid crystals and surfactants to functional architectures in biology. While TPNs are, in reality, volume-filling patterns of spatially-varying molecular composition, physical and structural models most often reduce their structure to lower-dimensional geometric objects: the 2D interfaces between chemical domains; and the 1D skeletons that thread through inter-connected, tubular domains...
April 23, 2018: Soft Matter
https://www.readbyqxmd.com/read/29683462/polysome-profiling-in-leishmania-human-cells-and-mouse-testis
#16
Zemfira N Karamysheva, Elena B Tikhonova, Petar N Grozdanov, James C Huffman, Kristen R Baca, Alexander Karamyshev, R Brian Denison, Clinton C MacDonald, Kai Zhang, Andrey L Karamyshev
Proper protein expression at the right time and in the right amounts is the basis of normal cell function and survival in a fast-changing environment. For a long time, the gene expression studies were dominated by research on the transcriptional level. However, the steady-state levels of mRNAs do not correlate well with protein production, and the translatability of mRNAs varies greatly depending on the conditions. In some organisms, like the parasite Leishmania, the protein expression is regulated mostly at the translational level...
April 8, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29683343/allicin-inhibits-mouse-colorectal-tumorigenesis-through-suppressing-the-activation-of-stat3-signaling-pathway
#17
Xiang Li, Jiahui Ni, Yixin Tang, Xu Wang, Huanhuan Tang, Haidong Li, Sulin Zhang, Xiaoyan Shen
Allicin is the major biologically active compounds of freshly crushed garlic. It has been reported to inhibit the proliferation and promote the apoptosis of multiple colorectal cancer cells. However, the anti-colorectal cancer effect of Allicin has not been verified by in vivo studies. In the present study, we investigated the effect of Allicin on azoxymethane/dextran sodium sulfate (AOM/DSS) colorectal cancer mouse model and explore the underlying possible mechanism. Our result showed that Allicin could inhibit colonic tumorigenesis of AOM/DSS mice in vivo...
April 23, 2018: Natural Product Research
https://www.readbyqxmd.com/read/29683319/multiply-intercalator-substituted-cu-ii-cyclen-complexes-as-dna-condensers-and-dna-rna-synthesis-inhibitors
#18
Jan Hormann, Jaroslav Malina, Oliver Lemke, Max J Hülsey, Stefanie Wedepohl, Jan Potthoff, Claudia Schmidt, Ingo Ott, Bettina G Keller, Viktor Brabec, Nora Kulak
Many drugs that are applied in anticancer therapy such as the anthracycline doxorubicin contain DNA-intercalating 9,10-anthraquinone (AQ) moieties. When Cu(II) cyclen complexes were functionalized with up to three (2-anthraquinonyl)methyl substituents, they efficiently inhibited DNA and RNA synthesis resulting in high cytotoxicity (selective for cancer cells) accompanied by DNA condensation/aggregation phenomena. Molecular modeling suggests an unusual bisintercalation mode with only one base pair between the two AQ moieties and the metal complex as a linker...
April 23, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29683269/multiple-machine-learning-based-chemoinformatics-models-for-identification-of-histone-acetyl-transferase-inhibitors
#19
Shagun Krishna, Sushil Kumar, Deependra Kumar Singh, Amar Deep Lakra, Dibyendu Banerjee, Mohammad Imran Siddiqi
The histone acetyl transferase (HAT) are involved in acetylation of histones that lead to transcription activation in numerous gene regulatory mechanisms. There are very few GCN5 HAT inhibitors reported despite of their role in cancer progression. In this study, we have utilized in-silico virtual screening approaches based on various machine learning algorithm to identify potent inhibitors of GCN5 HAT from commercially available Maybridge library. We have generated predictive chemoinformatics models based on k-Nearest neighbour, naïve Bayesian, Random Forest and Support Vector Machine...
April 23, 2018: Molecular Informatics
https://www.readbyqxmd.com/read/29683102/solid-lipid-particles-as-drug-carriers-effects-of-particle-preparation-methods-and-lipid-excipients-on-particle-characteristics
#20
Cintia Kieffer Gamboa, Ranoda Samir, Chengyu Wu, Huiling Mu
BACKGROUND: Oral delivery of biopharmaceuticals is limited by the absorption barriers in the gastrointestinal tract (GIT) such as low permeability across the biological membranes and the enzymatic degradation by proteases. In this study, lipid based drug delivery systems were proposed to overcome these obstacles. OBJECTIVE: The aim of this study was to evaluate the effect of particle preparation methods and excipients on the characteristics of solid lipid microparticles (SLM) and solid lipid nanoparticles (SLN)...
April 20, 2018: Pharmaceutical Nanotechnology
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