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Simon Bordage, Thanh-Nhat Pham, Andy Zedet, Anne-Sophie Gugglielmetti, Maude Nappey, Céline Demougeot, Corine Girard-Thernier
Polyphenols are plant secondary metabolites which possess many positive effects on human health. Although these beneficial effects could be mediated through an increase in nitric oxide synthase activity, little is known regarding the inhibitory effect of polyphenols on mammal arginase, an enzyme which competes with nitric oxide synthase for their common substrate, L-arginine. The aim of the present study was to determine the potential of a series of polyphenols as mammalian arginase inhibitors and to identify some structure-activity relationships...
October 24, 2016: Planta Medica
S K Bedada, R Appani, P K Boga
Carbamazepine (CBZ) is a widely used antiepileptic drug with narrow therapeutic window and it may be prone to drug interactions. The purpose of present study was to investigate the effect of PIP on metabolism and pharmacokinetics of CBZ in healthy volunteers. An open-label, 2 period, sequential study was conducted in 12 healthy volunteers. PIP 20 mg was administered once daily for 10 days during treatment phase. A single dose of CBZ 200 mg was administered during control and after treatment phases under fasting conditions...
October 24, 2016: Drug Research
Kaihang Wang, Julius Fredens, Simon F Brunner, Samuel H Kim, Tiongsun Chia, Jason W Chin
Synthetic recoding of genomes, to remove targeted sense codons, may facilitate the encoded cellular synthesis of unnatural polymers by orthogonal translation systems. However, our limited understanding of allowed synonymous codon substitutions, and the absence of methods that enable the stepwise replacement of the Escherichia coli genome with long synthetic DNA and provide feedback on allowed and disallowed design features in synthetic genomes, have restricted progress towards this goal. Here we endow E. coli with a system for efficient, programmable replacement of genomic DNA with long (>100-kb) synthetic DNA, through the in vivo excision of double-stranded DNA from an episomal replicon by CRISPR/Cas9, coupled to lambda-red-mediated recombination and simultaneous positive and negative selection...
October 24, 2016: Nature
Jingjing Wu, Mingzhi Zhang, Delong Liu
The Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has been approved for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Acquired resistance to ibrutinib due to BTK C481S mutation has been reported. Mutations in PLCγ2 can also mediate resistance to ibrutinib. Untoward effects due to off-target effects are also disadvantages of ibrutinib. More selective and potent BTK inhibitors (ACP-196, ONO/GS-4059, BGB-3111, CC-292) are being investigated. This review summarized the preclinical research and clinical data of ONO/GS-4059...
October 20, 2016: Oncotarget
Jinfeng Kong, Juan Du, Yunling Wang, Mingzi Yang, Jianchao Gao, Xiaofan Wei, Weigang Fang, Jun Zhan, Hongquan Zhang
Kindlin-1, an integrin-interacting protein, has been implicated in TGF-β/Smad3 signaling. However, the molecular mechanism underlying Kindlin-1 regulation of TGF-β/Smad3 signaling remains elusive. Here, we reported that Kindlin-1 is an important mediator of TGF-β/Smad3 signaling by showing that Kindlin-1 physically interacts with TGF-β receptor I (TβRI), Smad anchor for receptor activation (SARA) and Smad3. Kindlin-1 is required for the interaction of Smad3 with TβRI, Smad3 phosphorylation, nuclear translocation, and finally the activation of TGF-β/Smad3 signaling pathway...
October 20, 2016: Oncotarget
Yuanfei Zhou, Tingxing Song, Jie Peng, Zheng Zhou, Hongkui Wei, Rui Zhou, Siwen Jiang, Jian Peng
Sirtuin 1 (SIRT1) regulates adipocyte and osteoblast differentiation. However, the underlying mechanism should be investigated. This study revealed that SIRT1 acts as a crucial repressor of adipogenesis. RNA-interference-mediated SIRT1 knockdown or genetic ablation enhances adipogenic potential, whereas SIRT1 overexpression inhibits adipogenesis in mesenchymal stem cells (MSCs). SIRT1 also deacetylates the histones of sFRP1, sFRP2, and Dact1 promoters; inhibits the mRNA expression of sFRP1, sFRP2, and Dact1; activates Wnt signaling pathways; and suppresses adipogenesis...
October 20, 2016: Oncotarget
Lourdes Mateos-Hernández, Margarita Villar, Ernesto Doncel-Pérez, Marco Trevisan-Herraz, Ángel García-Forcada, Francisco Romero Ganuza, Jesús Vázquez, José de la Fuente
Guillain-Barré syndrome (GBS) is an autoimmune-mediated peripheral neuropathy of unknown cause. However, about a quarter of GBS patients have suffered a recent bacterial or viral infection, and axonal forms of the disease are especially common in these patients. Proteomics is a good methodological approach for the discovery of disease biomarkers. Until recently, most proteomics studies of GBS and other neurodegenerative diseases have focused on the analysis of the cerebrospinal fluid (CSF). However, serum represents an attractive alternative to CSF because it is easier to sample and has potential for biomarker discovery...
October 20, 2016: Oncotarget
Kun-Ling Tsai, Ching-Hsia Hung, Shih-Hung Chan, Jhih-Yuan Shih, Yung-Hsin Cheng, Yi-Ju Tsai, Huei-Chen Lin, Pei-Ming Chu
Atherosclerosis is considered to be a form of chronic inflammation and a disorder of lipid metabolism. Oxidative transformations in the lipid and apolipoprotein B (Apo B) constituent of low density lipoprotein drive the initial step in atherogenesis due to macrophage scavenger receptors identify oxidized LDL (oxLDL) but non-oxidized LDL. The human vascular endothelial cells fact a critical role in vasodilation, provides a nonadhesive surface for circulation, reduces vascular smooth muscle proliferation, inflammation, thrombus formation and platelet aggregation...
October 20, 2016: Oncotarget
Alexandre Chlenski, Marija Dobratic, Helen R Salwen, Mark Applebaum, Lisa J Guerrero, Ryan Miller, Gillian DeWane, Elena Solomaha, Jeremy D Marks, Susan L Cohn
SPARC is a matrix protein that mediates interactions between cells and the microenvironment. In cancer, SPARC may either promote or inhibit tumor growth depending upon the tumor type. In neuroblastoma, SPARC is expressed in the stromal Schwannian cells and functions as a tumor suppressor. Here, we developed a novel in vivo model of stroma-rich neuroblastoma using non-tumorigenic SHEP cells with modulated levels of SPARC, mixed with tumorigenic KCNR cells. Tumors with stroma-derived SPARC displayed suppressed growth, inhibited angiogenesis and increased lipid accumulation...
October 20, 2016: Oncotarget
Edson Costa E Silva, Sheyla Viana Omonte, Alessandro Gomides Veiga Martins, Hércules Henrique Onibene de Castro, Hayder Egg Gomes, Élton Gonçalves Zenóbio, Peterson Antônio Dutra de Oliveira, Martinho Campolina Rebello Horta, Paulo Eduardo Alencar Souza
OBJECTIVE: The aim of this study was to evaluate the effect of hyaluronic acid (HA) in the structure and degradation patterns of BioGide(®) and OsseoGuard™ collagen membranes. HA mediates inflammation and acts in cell migration, adhesion, and differentiation, benefitting tissue remodeling and vascularization. These are desirable effects in guided regeneration procedures, but it is still unknown whether HA alters the barrier properties of absorbable membranes. DESIGN: Bone defects were created in the calvaria of rats, which were treated with HA gel 1% (HA group) or simply filled with blood clot (control group), and covered with BioGide(®) or OsseoGuard™...
October 17, 2016: Archives of Oral Biology
Jing Liu, Dujuan Zhao, Wenxiu He, Huiyuan Zhang, Zhonghao Li, Yuxia Luan
The anti-leukemia effect of cytarabine (Ara-C) is severely restricted by its high hydrophilic properties and rapid plasma degradation. Herein, a novel amphiphilic small molecular prodrug of Ara-C was developed by coupling a short aliphatic chain, hexanoic acid (HA) to 4-NH2 of the parent drug. Based on the amphiphilic nature, the resulting bioconjugate (HA-Ara) could spontaneously self-assemble into stable spherical nanoassemblies (NAs) with an extremely high drug loading (∼71wt%). Moreover, folate receptor (FR)-targeting NAs with high grafting efficient folic acid - bovine serum albumin (FA-BSA) conjugate immobilized on the surface (NAs/FA-BSA) was prepared...
October 19, 2016: Journal of Colloid and Interface Science
Annie Lévesque, Aimee N C Campbell, Martina Pavlicova, Mei-Chen Hu, Robrina Walker, Erin A McClure, Udi E Ghitza, Genie Bailey, Maxine Stitzer, Edward V Nunes
OBJECTIVE: Coping strategies are a predictor of abstinence among patients with substance use disorders. However, little is known regarding the role of coping strategies in the effectiveness of the Community Reinforcement Approach (CRA). Using data from a 12week randomized control trial assessing the effectiveness of the Therapeutic Education System (TES), an internet-delivered version of the CRA combined with contingency management, we tested the role of coping strategies as a mediator of treatment effectiveness...
September 30, 2016: Addictive Behaviors
K Anand, C Tiloke, A Phulukdaree, B Ranjan, A Chuturgoon, S Singh, R M Gengan
The biosynthesis of nanostructured biopalladium nanoparticles (PdNPs) from an aqueous solution of crystalline palladium acetate is reported. For the synthesised PdNPs in solution, an agroforest biomass waste petal of Moringa oleifera derived bis-phthalate was used as natural reducing and biocapping agents. Continuous absorption in the UV region and subsequent brown colour change confirmed the formation of PdNPs. A strong surface plasmon peak for PdNPs occurred at 460nm. PdNPs were characterized by SEM with EDX, FTIR, TEM and DLS...
September 29, 2016: Journal of Photochemistry and Photobiology. B, Biology
Jun Shi, Huiping Deng, Huichao Pan, Yinjie Xu, Min Zhang
Epigallocatechin-3-gallate (EGCG) has been shown to possess anti-inflammatory effects. Microcystin-LR (MC-LR) is a potent toxin and our past research suggested that it also mediated human umbilical vein endothelial cell (HUVEC) injury. The aim of this study was to investigate the effects of EGCG on MC-LR-induced oxidative stress and inflammatory responses in HUVECs. HUVECs were stimulated with MC-LR in the presence or absence of EGCG. MC-LR (40 μM) significantly increased cell death and decreased cell viability, migration, and tube formation, whereas EGCG (50 μM) inhibited these effects...
October 21, 2016: Chemosphere
Ranjit Singh, Ranju Bansal
Neuroinflammatory mechanisms mediated by activated glial and cytokines (TNF-α, IL-1β) might contribute neuronal degeneration leading to Alzheimer's (AD) and Parkinson's disease (PD). Lipopolysaccharide (LPS) is an inflammogen derived from the cell wall of Gram-negative bacteria, which promotes neuroinflammation and subsequent neurodegeneration. Dehydroepiandrosterone (DHEA) and testosterone have been reported as neuroprotective steroids useful for the treatment of various neurodegenerative disorders. In the present study, several 16-arylidene steroidal derivatives have been evaluated as neuroprotective agents in LPS-treated animal models...
October 24, 2016: ACS Chemical Neuroscience
Dong-Hyun Choi, Seong-Ho Kang, Heesang Song
Platelets are essential for progression of atherosclerotic lesions, plaque destabilization, and thrombosis. They secrete and express many substances that are crucial mediators of coagulation, inflammation, and atherosclerosis. Mean platelet volume (MPV) is a precise measure of platelet size, and is routinely reported during complete blood count analysis. Emerging evidence supports the use of MPV as a biomarker predicting the risk of ischemic stroke in patients with atrial fibrillation, and as a guide for prescription of anticoagulation and rhythm-control therapy...
October 24, 2016: Korean Journal of Internal Medicine
Sabrina J Merat, Richard Molenkamp, Koen Wagner, Sylvie M Koekkoek, Dorien van de Berg, Etsuko Yasuda, Martino Böhne, Yvonne B Claassen, Bart P Grady, Maria Prins, Arjen Q Bakker, Menno D de Jong, Hergen Spits, Janke Schinkel, Tim Beaumont
Hepatitis C virus (HCV) is world-wide a major cause of liver related morbidity and mortality. No vaccine is available to prevent HCV infection. To design an effective vaccine, understanding immunity against HCV is necessary. The memory B cell repertoire was characterized from an intravenous drug user who spontaneously cleared HCV infection 25 years ago. CD27+IgG+ memory B cells were immortalized using BCL6 and Bcl-xL. These immortalized B cells were used to study antibody-mediated immunity against the HCV E1E2 glycoproteins...
2016: PloS One
Akimasa Someya, Takako Ikegami, Koji Sakamoto, Isao Nagaoka
Osteoarthritis (OA) is one of the major joint diseases, and the synovial inflammation is involved in the pathogenesis and progression of OA. Glucosamine (GlcN) is widely used as a dietary supplement for OA, and is expected to exert the antiinflammatory action in OA. However, the detailed mechanism for the antiinflammatory action of GlcN remains poorly understood. In this study, to elucidate the molecular mechanism involved in the GlcN-medicated regulation of synovial cell activation, we comprehensively analyzed the effect of GlcN on the gene expression using a human synovial cell line MH7A by DNA microarray...
2016: PloS One
Thomas F Giustino, Paul J Fitzgerald, Stephen Maren
The medial prefrontal cortex (mPFC) plays a crucial role in emotional learning and memory in rodents and humans. While many studies suggest a differential role for the prelimbic (PL) and infralimbic (IL) subdivisions of mPFC, few have considered the relationship between neural activity in these two brain regions recorded simultaneously in behaving animals. Importantly, how concurrent PL and IL activity relate to conditioned freezing behavior is largely unknown. Here we used single-unit recordings targeting PL and IL in awake, behaving rats during the acquisition and expression of conditioned fear...
2016: PloS One
Simon R Knight, Leanne Metcalfe, Katriona O'Donoghue, Simon T Ball, Angela Beale, William Beale, Rachel Hilton, Keith Hodkinson, Graham W Lipkin, Fiona Loud, Lorna P Marson, Peter J Morris
BACKGROUND: It has been suggested that the research priorities of those funding and performing research in transplantation may differ from those of end service users such as patients, carers and healthcare professionals involved in day-to-day care. The Kidney Transplant Priority Setting Partnership (PSP) was established with the aim of involving all stakeholders in prioritising future research in the field. METHODS: The PSP methodology is as outlined by the James Lind Alliance...
2016: PloS One
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