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Yanyan Zheng, Li Zhu, Lulu Fan, Wenna Zhao, Jianlong Wang, Xianxiao Hao, Yunhui Zhu, Xiufang Hu, Yaofeng Yuan, Jingwei Shao, Wenfeng Wang
Emodin, a natural anthraquinone derivative isolated from Rheum palmatum L., has been demonstrated to exhibit good anti-cancer effect. In this study, a series of novel quaternary ammonium salts of emodin, anthraquinone and anthrone were synthesized and their anticancer activities were tested in vitro. The effects of emodin quaternary ammonium salts on cell viability, apoptosis, intracellular ROS, and mitochondrial membrane potential were investigated in A375, BGC-823, HepG2 and HELF cells. The results demonstrated that compound 4a induced morphological changes and decreased cell viability...
October 7, 2016: European Journal of Medicinal Chemistry
Jing Qiu, Min Wang, Jun Zhang, Qing Cai, Dan Lu, Yansong Li, Yushu Dong, Tianzhi Zhao, Huisheng Chen
Neuroinflammation remains the primary cause of morbidity and mortality in stroke-induced secondary brain injury. The NOD-like receptor pyrin 3 (NLRP3) inflammasome is involved in diverse inflammatory diseases, including cerebral ischemia, and is thus considered an effective therapeutic target. In the present study, we investigated the neuroprotection of Sinomenine (SINO), a potent natural anti-apoptotic and anti-inflammatory molecule, against cerebral ischemia in a mouse model of middle cerebral artery occlusion (MCAO) in vivo and in an oxygen glucose deprivation (OGD)-treated astrocytes/microglia model in vitro...
October 18, 2016: International Immunopharmacology
Pearl L H Mok, Sussie Antonsen, Carsten Bøcker Pedersen, Roger T Webb
BACKGROUND: Younger or older parental age has been linked with a range of adverse offspring endpoints. We investigated associations between parental age and nine adverse offspring outcomes in three correlated domains: (i) Premature death: suicide, unnatural death, natural death; (ii) Psychiatric morbidity: any mental illness, suicide attempt, substance misuse; (iii) Criminality: violent offending, imprisonment, driving whilst intoxicated. METHODS: Persons born in Denmark 1966-1996 were followed from their 15th until 40th birthday or December 2011 (N=1,793,681)...
October 2, 2016: Journal of Affective Disorders
Tom A Hummer, K Luan Phan, David W Kern, Martha K McClintock
Evidence suggests the putative human pheromone Δ4,16-androstadien-3-one (androstadienone), a natural component of human sweat, increases attention to emotional information when passively inhaled, even in minute amounts. However, the neural mechanisms underlying androstadienone's impact on the perception of emotional stimuli have not been clarified. To characterize how the compound modifies neural circuitry while attending to emotional information, 22 subjects (11 women) underwent two fMRI scanning sessions, one with an androstadienone solution and one with a carrier control solution alone on their upper lip...
September 29, 2016: Psychoneuroendocrinology
Kartik Ramakrishna, Kalpana Premkumar, Jayakanthan Kabeerdoss, K R John
BACKGROUND & AIM: Innate immune responses are important in susceptibility to pulmonary tuberculosis (TB). In order to test the hypothesis that Toll-like receptor (TLR) 2 function would be abnormal in patients with active pulmonary TB we compared the cytokine responses of peripheral blood mononuclear cells (PBMC) to innate immune ligands in a case-control study. METHODS: PBMC from 19 untreated pulmonary TB patients, 17 healthy controls, and 11 treated pulmonary TB patients, were cultured for 24h with TLR 2 ligand (PAM-CSK) and other TLR ligands (muramyl dipeptide, flagellin, lipopolysaccharide (LPS), CpG oligodeoxynucleotide (CpG-ODN))...
October 18, 2016: Cytokine
Bin Tang, Yanmei Huang, Hongqin Yang, Peixiao Tang, Hui Li
As a natural dietary polyphenol, 3,4,5-tri-O-caffeoylquinic acid (3,4,5-triCQA) exhibits numerous stronger pharmacological activities than that of its analogues. Studies on interaction between 3,4,5-triCQA and protein are very helpful for understanding the mechanism of these enhanced biological functions. In this study, (1)H saturation transfer difference NMR ((1)H STD-NMR) combined with multi-spectroscopy were used to probe the interaction of 3,4,5-triCQA with human serum albumin (HSA). Both qualitative and quantitative (1)H STD-NMR indicated that 3,4,5-triCQA can specifically bind to HSA at the favored Sudlow's site II with caffeoyl groups as the main recognizable moiety...
October 17, 2016: Journal of Photochemistry and Photobiology. B, Biology
Thomas J Lawton, Amy C Rosenzweig
Nature utilizes two groups of enzymes to catalyze methane conversions, methyl-coenzyme M reductases (MCRs) and methane monooxygenases (MMOs). These enzymes have been difficult to incorporate into industrial processes due to their complexity, poor stability, and lack of recombinant tractability. Despite these issues, new ways of preparing and stabilizing these enzymes have recently been discovered, and new mechanistic insight into how MCRs and MMOs break the C-H bond in nature's most inert hydrocarbon have been obtained...
October 18, 2016: Current Opinion in Chemical Biology
Anna Chung-Kwan Tse, Jing-Woei Li, Simon Yuan Wang, Ting-Fung Chan, Keng Po Lai, Rudolf Shiu-Sun Wu
Hypoxia is a global environmental concern and poses a significant threat to aquatic ecosystems, including the sustainability of natural fish populations. The deleterious effects of hypoxia on fish reproductive fitness, as mediated by disruption of sex hormones and gene expression along the Brain-Pituitary-Gonad axis, have been well documented. Recently, we further demonstrated that the observed disruption of steroidogenesis in the ovary of marine medaka Oryzias melastigma is mediated through microRNAs (miRNAs)...
October 8, 2016: Aquatic Toxicology
Amal A Sultan, Sanaa A El-Gizawy, Mohamed A Osman, Gamal M El Maghraby
Mixed micelles provide promising strategy for enhancing dissolution and permeability of drugs. However, their fluid nature limited the stability of the loaded drug and hindered the development of stable oral dosage form. Accordingly, the objective was to develop solid self dispersing mixed micelle forming systems (MMFS) for enhanced dissolution and intestinal permeability of hydrochlorothiazide. Pseudoternary phase diagrams were constructed using sodium cholate, lecithin with either poloxamer 407 or PEG 4000 to determine the composition of MMFS...
October 13, 2016: Colloids and Surfaces. B, Biointerfaces
Łukasz Jeleń, Adam Krzyżak, Thomas Fevens, Michał Jeleń
Grading of breast cancer malignancy is a key step in its diagnosis, which in turn helps to determine its prognosis and a course of treatment. In this paper, we consider the application of pattern recognition and image processing techniques to perform computer-assisted automatic breast cancer malignancy grading from cytological slides of fine needle aspiration biopsies. To determine a classification of the malignancy of the slide, a feature set is first determined from imagery of the slides. In this paper we investigated the nature of a wide set of features extracted from biopsy images to determine their discriminatory power and cross-correlation...
October 13, 2016: Computers in Biology and Medicine
Tian Hua, Kiran Vemuri, Mengchen Pu, Lu Qu, Gye Won Han, Yiran Wu, Suwen Zhao, Wenqing Shui, Shanshan Li, Anisha Korde, Robert B Laprairie, Edward L Stahl, Jo-Hao Ho, Nikolai Zvonok, Han Zhou, Irina Kufareva, Beili Wu, Qiang Zhao, Michael A Hanson, Laura M Bohn, Alexandros Makriyannis, Raymond C Stevens, Zhi-Jie Liu
Cannabinoid receptor 1 (CB1) is the principal target of Δ(9)-tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use. CB1 is activated by endocannabinoids and is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. Here, we present the 2.8 Å crystal structure of human CB1 in complex with AM6538, a stabilizing antagonist, synthesized and characterized for this structural study...
October 20, 2016: Cell
Yohann Nédélec, Joaquín Sanz, Golshid Baharian, Zachary A Szpiech, Alain Pacis, Anne Dumaine, Jean-Christophe Grenier, Andrew Freiman, Aaron J Sams, Steven Hebert, Ariane Pagé Sabourin, Francesca Luca, Ran Blekhman, Ryan D Hernandez, Roger Pique-Regi, Jenny Tung, Vania Yotova, Luis B Barreiro
Individuals from different populations vary considerably in their susceptibility to immune-related diseases. To understand how genetic variation and natural selection contribute to these differences, we tested for the effects of African versus European ancestry on the transcriptional response of primary macrophages to live bacterial pathogens. A total of 9.3% of macrophage-expressed genes show ancestry-associated differences in the gene regulatory response to infection, and African ancestry specifically predicts a stronger inflammatory response and reduced intracellular bacterial growth...
October 20, 2016: Cell
Hélène Quach, Maxime Rotival, Julien Pothlichet, Yong-Hwee Eddie Loh, Michael Dannemann, Nora Zidane, Guillaume Laval, Etienne Patin, Christine Harmant, Marie Lopez, Matthieu Deschamps, Nadia Naffakh, Darragh Duffy, Anja Coen, Geert Leroux-Roels, Frederic Clément, Anne Boland, Jean-François Deleuze, Janet Kelso, Matthew L Albert, Lluis Quintana-Murci
Humans differ in the outcome that follows exposure to life-threatening pathogens, yet the extent of population differences in immune responses and their genetic and evolutionary determinants remain undefined. Here, we characterized, using RNA sequencing, the transcriptional response of primary monocytes from Africans and Europeans to bacterial and viral stimuli-ligands activating Toll-like receptor pathways (TLR1/2, TLR4, and TLR7/8) and influenza virus-and mapped expression quantitative trait loci (eQTLs)...
October 20, 2016: Cell
Nathaniel J Robinson, William P Schiemann
Despite significant clinical advancements, cancer remains a leading cause of mortality throughout the world due largely to the process of metastasis and the dissemination of cancer cells from their primary tumor of origin to distant secondary sites. The clinical burden imposed by metastasis is further compounded by a paucity of information regarding the factors that mediate metastatic progression. Linear chromosomes are capped by structures known as telomeres, which dictate cellular lifespan in humans by shortening progressively during successive cell divisions...
October 18, 2016: Biochimica et Biophysica Acta
Shlomo Sasson
Activated peroxisome proliferator-activated receptor-δ (PPARδ) induces the expression of genes encoding enzymes that metabolize fatty acids and carbohydrate. Attempts to identify cellular activators of PPARδ produced large lists of various fatty acids and their metabolic derivatives; however, there is no consensus on specific and selective binding interactions of natural ligands with PPARδ. Most models on binding interactions within the ligand binding domain (LBD) of PPARδ have been derived from analyses of PPARδ-LBD crystals formed with synthetic low molecular weight ligands...
October 18, 2016: Biochimie
Richard A Manderville, Stacey D Wetmore
The formation of DNA adducts by the attack of intermediates derived from toxic substances at the C8 position of 2-deoxyguanosine (dG) is a common damaging event. Although the majority of studies on C8-dG adducts have focused on lesions containing a C8-N-C tether between the bulky moiety and the nucleobase, the formation of O-linked lesions with a similar tether topology and C-linked adducts involving direct C8-C connectivity have also been uncovered. Several studies have been done to try to better understand the structural impact and mutagenicity of O-linked and C-linked aryl C8-dG adducts, including lesions arising from unsubstituted and chloro substituted phenols, and the food mutagen ochratoxin A (OTA)...
October 21, 2016: Chemical Research in Toxicology
Michael Chalick, Oded Jacobi, Edward Pichinuk, Christian Garbar, Armand Bensussan, Alan Meeker, Ravit Ziv, Tania Zehavi, Nechama I Smorodinsky, John Hilkens, Franz-Georg Hanisch, Daniel B Rubinstein, Daniel H Wreschner
Translation of mRNA in alternate reading frames (ARF) is a naturally occurring process heretofore underappreciated as a generator of protein diversity. The MUC1 gene encodes MUC1-TM, a signal-transducing trans-membrane protein highly expressed in human malignancies. Here we show that an AUG codon downstream to the MUC1-TM initiation codon initiates an alternate reading frame thereby generating a novel protein, MUC1-ARF. MUC1-ARF, like its MUC1-TM 'parent' protein, contains a tandem repeat (VNTR) domain. However, the amino acid sequence of the MUC1-ARF tandem repeat as well as N- and C- sequences flanking it differ entirely from those of MUC1-TM...
2016: PloS One
Johan Kreuger, Paul O'Callaghan
Here we report on a technical difficulty we encountered while optimizing genotyping strategies to identify mice derived from Exoc3l2tm1a(KOMP)Wtsi embryonic stem cells obtained from the Knockout Mouse Project Repository. The Exoc3l2tm1a(KOMP)Wtsi construct encodes a "knockout-first" design with loxP sites that confer conditional potential (KO1st). We designed primers that targeted wild-type sequences flanking the most downstream element of the construct, an 80 base pair synthetic loxP region, which BLAST alignment analysis reveals is an element common to over 10,000 conditional gene-targeting mouse models...
2016: PloS One
Qian Lu, Jihong Wang, Junshu Jiang, Shengnan Wang, Qilan Jia, Yue Wang, Weiping Li, Qin Zhou, Li Lv, Qingwei Li
BACKGROUND: The RGD-toxin protein Lj-RGD3 is a naturally occurring 118 amino acid peptide that can be obtained from the salivary gland of the Lampetra japonica fish. This unique peptide contains 3 RGD (Arg-Gly-Asp) motifs in its primary structure. Lj-RGD3 is available in recombinant form (rLj-RGD3) and can be produced in large quantities using DNA recombination techniques. The pharmacology of the three RGD motif-containing peptides has not been studied. This study investigated the protective effects of rLj-RGD3, a novel polypeptide, against ischemia/reperfusion-induced damage to the brain caused by middle cerebral artery occlusion (MCAO) in a rat stroke model...
2016: PloS One
Sonia M Hernandez, Catharine N Welch, Valerie E Peters, Erin K Lipp, Shannon Curry, Michael J Yabsley, Susan Sanchez, Andrea Presotto, Peter Gerner-Smidt, Kelley B Hise, Elizabeth Hammond, Whitney M Kistler, Marguerite Madden, April L Conway, Tiffany Kwan, John J Maurer
Worldwide, Salmonella spp. is a significant cause of disease for both humans and wildlife, with wild birds adapted to urban environments having different opportunities for pathogen exposure, infection, and transmission compared to their natural conspecifics. Food provisioning by people may influence these factors, especially when high-density mixed species flocks aggregate. White Ibises (Eudocimus albus), an iconic Everglades species in decline in Florida, are becoming increasingly common in urbanized areas of south Florida where most are hand-fed...
2016: PloS One
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