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Radhe Shyam, Nicolas Charbonnel, Aurélie Job, Christelle Blavignac, Christiane Forestier, Claude Taillefumier, Sophie Faure
Amphipathic cationic peptoids (N-substituted glycine oligomers) represent a promising class of antimicrobial peptide mimics. The aim of this study is to explore the potential of the triazolium group as a cationic moiety and helix inducer to develop potent antimicrobial helical peptoids. We report here the first solid-phase synthesis of peptoid oligomers incorporating 1,2,3-triazolium-type side chains, and their evaluation against Escherichia coli, Enterococcus faecalis and Staphylococcus aureus. Several triazolium-based oligomers, even of short length, selectively kill bacteria over mammalian cells...
June 19, 2018: ChemMedChem
Kate L Wegener, Amy E McGrath, Nicholas E Dixon, Aaron J Oakley, Denis B Scanlon, Andrew D Abell, John Bruning
The human sliding clamp (PCNA) controls access to DNA for many proteins involved in DNA replication and repair. Proteins are recruited to the PCNA surface by means of a short, conserved peptide motif known as the PCNA-interacting protein box (PIP-box). Inhibitors of these essential protein-protein interactions may be useful as cancer therapeutics by disrupting DNA replication and repair in these highly proliferative cells. PIP-box peptide mimetics have been identified as a potentially rapid route to potent PCNA inhibitors...
June 19, 2018: Chemistry: a European Journal
Laurent Jacob, Florence Combes, Thomas Burger
We propose a new hypothesis test for the differential abundance of proteins in mass-spectrometry based relative quantification. An important feature of this type of high-throughput analyses is that it involves an enzymatic digestion of the sample proteins into peptides prior to identification and quantification. Due to numerous homology sequences, different proteins can lead to peptides with identical amino acid chains, so that their parent protein is ambiguous. These so-called shared peptides make the protein-level statistical analysis a challenge and are often not accounted for...
June 18, 2018: Biostatistics
Simon Bissonnette, Nathalie Saint-Pierre, Valerie Lamantia, Catherine Leroux, Viviane Provost, Yannick Cyr, Remi Rabasa-Lhoret, May Faraj
Background: To optimize the prevention of type 2 diabetes (T2D), high-risk obese subjects with the best metabolic recovery after a hypocaloric diet should be targeted. Apolipoprotein B lipoproteins (apoB lipoproteins) induce white adipose tissue (WAT) dysfunction, which in turn promotes postprandial hypertriglyceridemia, insulin resistance (IR), and hyperinsulinemia. Objective: The aim of this study was to explore whether high plasma apoB, or number of plasma apoB lipoproteins, identifies subjects who best ameliorate WAT dysfunction and related risk factors after a hypocaloric diet...
June 18, 2018: American Journal of Clinical Nutrition
Speranza Rubattu, Maria Cotugno, Maurizio Forte, Rosita Stanzione, Franca Bianchi, Michele Madonna, Simona Marchitti, Massimo Volpe
OBJECTIVES: The combination of AT1 blocker/neutroendopeptidase neprilysin inhibition (ARNi) represents an interesting approach to reduce cardiovascular risk in hypertension. We assessed the efficacy of ARNi, compared with angiotensin II type 1 receptor blockade alone, on blood pressure (BP) and on protection from target organ damage development in the stroke-prone spontaneously hypertensive rat (SHRSP). METHODS: In high-salt fed SHRSP, we assessed plasma and tissue natriuretic peptides, urinary volume, BP and body weight over a short-term treatment (6 weeks) with either ARNi (sacubitril/valsartan 68 mg/kg per day) or valsartan (30 mg/kg per day), protection from stroke and renal damage (as documented by proteinuria) over 4 months of treatment with either sacubitril/valsartan or valsartan; the ability of either treatment to reduce progression of cerebrovascular and renal damage after 2 weeks of high-salt diet...
June 18, 2018: Journal of Hypertension
Konstantinos Gerasimidis, Konstantina Zafeiropoulou, Mary Mackinder, Umer Z Ijaz, Hazel Duncan, Elaine Buchanan, Tracey Cardigan, Christine A Edwards, Paraic McGrogan, Richard K Russell
OBJECTIVES: Detection of faecal gluten immunogenic peptides (GIP) is a biomarker of recent gluten consumption. GIP levels can be used to monitor gluten intake and compliment clinical methods to evaluate compliance to gluten free diet (GFD). In this study, recent gluten intake was measured by GIP in CD children and compared to routine clinical measures to evaluate GFD compliance. METHODS: GIP was measured in 90 samples from 63 CD children (44 previously and 19 newly diagnosed with follow-up samples at 6 and 12 months on GFD)...
June 18, 2018: Journal of Pediatric Gastroenterology and Nutrition
Jonathan Bishop, Peter Reed, Paul Austin, Miriam Hurst, Rohan Ameratunga, Alyson Craigie, Jeannette McFarlane, Simon E Chin, Stephen M Mouat, Helen M Evans
OBJECTIVE: The 2012 European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guideline for diagnosis of celiac disease (CD) questioned the requirement for intestinal biopsy to confirm the diagnosis. The guideline recommends that, in symptomatic patients with consistent HLA subtypes, the diagnostic accuracy of strongly positive serology is sufficient to confirm the diagnosis. We prospectively assessed these guidelines in a "real-life" clinical setting...
June 18, 2018: Journal of Pediatric Gastroenterology and Nutrition
Talal M Al-Qaoud, Jon S Odorico, Robert R Redfield
PURPOSE OF REVIEW: Pancreas transplantation in type 2 diabetes mellitus (T2DM) candidates remains disproportionately lower than in type 1 diabetes mellitus (T1DM); however, outcomes in carefully selected patients mirrors that of T1DM. Despite the 2014 United Network for Organ Sharing (UNOS) eligibility criteria for simultaneous pancreas/kidney transplant (SPK) transplantation in T2DM patients, an expected increase in the number of transplants was not observed. RECENT FINDINGS: In an updated International Pancreas and Transplant Registry (IPTR) analysis, 1514 primary deceased donor pancreas transplants were performed in T2DM recipients [1995-2015, SPK 88%, pancreas after kidney (PAK) 9%, pancreas transplant alone (PTA) 3%]...
June 18, 2018: Current Opinion in Organ Transplantation
Honggang Huang, Tracy L Scheffler, David E Gerrard, Martin R Larsen, Rene Lametsch
Pigs with the Halothane (HAL) and/or Rendement Napole (RN) gene mutations demonstrate abnormal muscle energy metabolism patterns and produce meat with poor quality, classified as pale, soft and exudative (PSE) meat, but it is not well understood how HAL and RN mutations regulate glucose and energy metabolism in porcine muscle. In order to investigate the potential signaling pathways and phosphorylation events related to these mutations, muscle samples were collected from four genotypes of pigs: wildtype, RN, HAL and RN-HAL double mutations and subjected to quantitative proteomic and phosphoproteomic analysis using the TiO2 enrichment strategy...
June 19, 2018: Journal of Proteome Research
Mario Di Gioacchino, Luca Di Giampaolo, Alessia Gatta, Annalisa Flacco, Rocco Mangifesta, Qiao Niu, Claudia Petrarca
OBJECTIVES: The first essential aspect for the prevention of occupational allergy is related to the accurate allergen identification and characterization. At present many efforts are made to characterize the potential for a chemical to be a sensitizing agent. METHODS: 'Omics' show great promise to identify key cellular and molecular events relevant to development of an adverse outcome pathway for respiratory sensitizers. One approach that shows promise is based on the measurement of the peptide reactivity of chemicals; the potential to form stable associations with protein/peptide being a key requirement for the induction of sensitization...
November 2017: Giornale Italiano di Medicina del Lavoro Ed Ergonomia
Yuliya Y Mints, Gheorghe Doros, John L Berk, Lawreen H Connors, Frederick L Ruberg
AIMS: Wild-type transthyretin (ATTRwt) cardiac amyloidosis has emerged as an important cause of heart failure in the elderly. Atrial fibrillation (AF) commonly affects older adults with heart failure and is associated with reduced survival, but its role in ATTRwt is unclear. We sought to explore the clinical impact of AF in ATTRwt. METHODS AND RESULTS: Patients with biopsy-proven ATTRwt cardiac amyloidosis (n = 146) were retrospectively identified, and clinical, echocardiographic, and biochemical data were collected...
June 19, 2018: ESC Heart Failure
Ying Yang, Hui Fang, Gang Xu, Yanfeng Zhen, Yazhong Zhang, Jinli Tian, Dandan Zhang, Guyue Zhang, Jing Xu
Liraglutide is a type of glucagon‑like‑peptide 1 receptor agonist, which has been reported as a novel type of antidiabetic agent with numerous benefits, including cardiovascular and neuroprotective effects. To the best of our knowledge, few studies to date have reported the potential mechanism underlying the neuroprotective effects of liraglutide on rats with type 2 diabetes mellitus (T2DM). The present study aimed to investigate the neuroprotective actions of liraglutide in diabetic rats and to determine the mechanisms underlying these effects...
June 18, 2018: Molecular Medicine Reports
Michael W Mullowney, Ryan A McClure, Matthew T Robey, Neil L Kelleher, Regan J Thomson
Covering: up to 2018Thioester reductase domains catalyze two- and four-electron reductions to release natural products following assembly on nonribosomal peptide synthetases, polyketide synthases, and their hybrid biosynthetic complexes. This reductive off-loading of a natural product yields an aldehyde or alcohol, can initiate the formation of a macrocyclic imine, and contributes to important intermediates in a variety of biosyntheses, including those for polyketide alkaloids and pyrrolobenzodiazepines. Compounds that arise from reductase-terminated biosynthetic gene clusters are often reactive and exhibit biological activity...
June 19, 2018: Natural Product Reports
Lei Gu, Xue Li, Jing Jiang, Gang Guo, Haoxing Wu, Min Wu, Hongyan Zhu
Superparamagnetic iron oxide nanoparticles (SPIONs) have been developed as excellent magnetic resonance imaging (MRI) contrast agents for stem cell labeling and tracking due to their biocompatibility. In this study, we designed a self-assembled peptide amphiphile (PA) with potential use in tissue engineering and drug delivery applications. This PA was conjugated to the surfaces of SPIONs to label rat mesenchymal stem cells (MSCs), which enhanced their contrast and labeling efficiencies. Studies on the labeled cells showed that the peptide-SPIONs had improved internalization, efficiency and T2-weight relaxivity both in vivo and in vitro and were nontoxic to the MSCs...
June 19, 2018: Nanoscale
Mrittika Debnath, Jessica M Farace, Kristopher D Johnson, Irina Nesterova
Quantitative assessment of biomarkers is essential in numerous contexts from decision-making in clinical situations to food quality monitoring to interpretation of life-science research findings. How-ever, appropriate quantitation techniques are not as widely ad-dressed as detection methods. One of the major challenges in bi-omarker's quantitation is the need to have a calibration for correlat-ing a measured signal to a target amount. The step complicates the methodologies and makes them less sustainable. In this work we address the issue via a new strategy: relying on position of re-sponse profile rather than on an absolute signal value for assess-ment of a target's amount...
June 19, 2018: Analytical Chemistry
Pengying Liao, Xiongdiao Lan, Dankui Liao, LiXia Sun, Liqin Zhou, Jianhua Sun, Zhangfa Tong
Carapax Trionycis (the shell of the turtle Pelodiscus sinensis) was hydrolyzed by six different commercial proteases. The hydrolysate prepared from papain showed stronger inhibitory activity against angiotensin I-converting enzyme (ACE) than other extracts. Two noncompetitive ACE inhibitory peptides were purified successively by ultrafiltration, gel filtration chromatography, ion exchange column chromatography, and high-performance liquid chromatography (HPLC). The amino acid sequences of them were identified as KRER and LHMFK, with IC50 values of 324...
June 19, 2018: Journal of Agricultural and Food Chemistry
Fengjuan Liu, Jinji Liu, Zaimei Yuan, Yubo Qing, Honghui Li, Kaixiang Xu, Wanyun Zhu, Heng Zhao, Baoyu Jia, Weirong Pan, Jianxiong Guo, Xuezeng Zhang, Wenmin Cheng, Wei Wang, Hong-Ye Zhao, Hong-Jiang Wei
Pig-to-human organ transplantation has drawn attention in recent years due to the potential use of pigs as an alternative source of human donor organs. While GGTA1 knockout (GTKO) can protect xenografts from hyperacute rejection, complement-dependent cytotoxicity might still contribute to this type of rejection. To prolong the xenograft survival, we utilized a T2A-mediated pCMV-hCD55-T2A-hCD59-Neo vector and transfected the plasmid into GTKO Diannan miniature pig fetal fibroblasts. After G418 selection combined with single-cell cloning culture, four colonies were obtained, and three of these were successfully transfected with the hCD55 and hCD59...
June 18, 2018: Molecular Biotechnology
Yan Huo, Lei Kang, Xiaoxi Pang, Haoyuan Shen, Ping Yan, Chunli Zhang, Xuhe Liao, Xueqi Chen, Rongfu Wang
PURPOSE: Tc-99m- and I-131-labeled arginine-arginine-leucine (RRL) peptides have shown the feasibility of tumor imaging in our previous studies. However, there have been no reports using RRL peptide for positron emission tomography (PET) imaging. In this study, RRL was radiolabeled with Ga-68 under optimized reaction conditions to develop a better specific and effective tumor imaging agent. PROCEDURES: RRL was synthesized and conjugated to a bifunctional chelating agent (DOTA-NHS), then radiolabeled with Ga-68...
June 18, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Alexandre Chicheportiche, Faozi Artoul, Arnon Schwartz, Simona Grozinsky-Glasberg, Amichay Meirovitz, David J Gross, Jeremy Godefroy
BACKGROUND: Peptide receptor radionuclide therapy (PRRT) with [177 Lu]-DOTA-TATE is an effective treatment of neuroendocrine tumors (NETs). After each cycle of treatment, patient dosimetry evaluates the radiation dose to the risk organs, kidneys, and bone marrow, the most radiosensitive tissues. Absorbed doses are calculated from the radioactivity in the blood and from single photon emission computed tomography (SPECT) images corrected by computed tomography (CT) acquired after each course of treatment...
June 19, 2018: EJNMMI Physics
Ke Li, Wen-Jing Song, Xia Wu, Dan-Yang Gu, Pu Zang, Ping Gu, Bin Lu, Jia-Qing Shao
PURPOSE: Glucagon has been recognized as a pivotal factor implicated in the pathophysiology ofdiabetes. The purpose of this study is to investigate the dynamic secretion levels of serum glucagon (GLA) in patients with type 1 diabetes mellitus (T1DM) with different courses of disease, and to analyze its correlation with blood glucose fluctuation. METHODS: This observational study included 55 T1DM patients and divided into 3 groups according to the courses of disease...
June 18, 2018: Endocrine
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