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Activity tolerance

Wubing He, Lihong Chen, Lin Zheng, Liuping Luo, Lingyun Gao
BACKGROUND: Dendritic cells (DCs) and regulatory T (Treg) cells are crucial for inducing immune tolerance. However, the suppressive function of infused Treg cells and immature DCs (imDCs) following solid organ transplantation remains unclear. METHODS: ImDCs derived from DA-donor rats and Treg cells isolated from spleens of Lewis rats were prepared. A heterotopic liver transplantation model was established to examine the immune tolerance effects of infusion of Treg-imDCs, imDCs and Treg cells individually...
October 17, 2016: Molecular Immunology
Wei Qiu, Biao Ren, Huanqin Dai, Lixin Zhang, Qiong Zhang, Xuedong Zhou, Yuqing Li
OBJECTIVE: The aim of this study was to determine the inhibitory effect of eight antifungal drugs on S. mutans growth, biofilm formation and virulence factors. METHODS: The actions of antifungal drugs on S. mutans were determined by recovery plates and survival kinetic curves. Biofilms were observed by scanning electron microscopy and the viable cells were recovered on BHI plates, meanwhile biofilms were stained by BacLight live/dead kit to investigate the biofilm viability...
October 13, 2016: Archives of Oral Biology
Kenji Sugawara, Kohei Honda, Yoshie Reien, Norihide Yokoi, Chihiro Seki, Harumi Takahashi, Kohtaro Minami, Ichiro Mori, Akio Matsumoto, Haruaki Nakaya, Susumu Seino
Insulin secretagogues are used for treatment of type 2 diabetes. We attempted to discover novel small molecules to stimulate insulin secretion by using in silico similarity search using sulfonylureas as query, followed by measurement of insulin secretion. Among 38 compounds selected by in silico similarity search, we found three diphenylsemicarbazides and one quinolone that stimulate insulin secretion. We focused on compound 8 (C8), which had the strongest insulin-secreting effect. Based on the structure-activity relationship of C8-derivatives, we identified diphenylthiosemicarbazide (DSC) 108 as the most potent secretagogue...
2016: PloS One
Rüdiger Hardeland
Dynamic aspects of melatonin's actions merit increasing future attention. This concerns particularly entirely different effects in senescent, weakened oscillators and in dysregulated oscillators of cancer cells that may be epigenetically blocked. This is especially obvious in the case of sirtuin 1 (SIRT1) which is upregulated by melatonin in aged tissues, but strongly downregulated in several cancer cells. These findings are not at all controversial, but are explained on the basis of divergent changes in weakened and dysregulated oscillators...
October 20, 2016: Journal of Pineal Research
José-Francisco Rocha, Éric Sicard, Nicolas Fauchoux, Amílcar Falcão, Ana Santos, Ana I Loureiro, Roberto Pinto, Maria João Bonifácio, Teresa Nunes, Luís Almeida, Patrício Soares-da-Silva
AIMS: To compare the levodopa/carbidopa (LC) and levodopa/benserazide (LB) pharmacokinetic profiles following repeated doses of opicapone (OPC) administered apart from levodopa. METHODS: Two randomized, double blind, sex-balanced, placebo-controlled studies in 4 groups of 12 or 18 healthy subjects each. In each group, enrolled subjects received a once-daily morning (5, 15 and 30 mg) or evening (5, 15 and 50 mg) administration of OPC or placebo for up to 28 days...
October 20, 2016: British Journal of Clinical Pharmacology
Jun Li, Jie Ao, Kai Li, Jie Zhang, Yanyan Li, Le Zhang, Yuyan Wei, Di Gong, Junping Gao, Weiwei Tan, Lugang Huang, Lunxu Liu, Ping Lin, Yuquan Wei
Multidrug resistance (MDR) is one of the most important contributors to the high mortality of cancer and remains a major concern. We previously found that zinc finger protein 32 (ZNF32), an important transcription factor associated with cancer in Homo sapiens, protects tumor cells against cell death induced by oxidative stress and other stimuli. We thus hypothesized that ZNF32 might enable the tolerance of cancer cells to anti-tumor drugs because higher ZNF32 expression has been found in cancer tissues and in drug-resistant lung adenocarcinoma (AC) cells...
October 20, 2016: Cell Death & Disease
Suchithra Padmajan Sasikala, Kai Huang, Baptiste Giroire, Prem Prabhakaran, Lucile Henry, Alain Pénicaud, Philippe Poulin, Cyril Aymonier
We report the exfoliation of graphite and simultaneous N doping of graphene by two methods; by supercritical ammonia treatment and by liquid phase exfoliation with NH4OH. While the supercritical ammonia allowed N doping at a level of 6.4 at.% in 2 h, the liquid phase exfoliation with NH4OH allowed N doping at a level of 2.7at.% in 6 h. The N doped graphene obtained via supercritical ammonia route were few layers (<5), showed large lateral flake size (~8µm), low defect density (ID/IG<0.6) in spite of their high level of N doping...
October 20, 2016: ACS Applied Materials & Interfaces
Chuanguang Yao, Hongxin Song, Ying Wan, Kefeng Ma, Chenyu Zheng, Hongda Cui, Peng Xin, Xubo Ji, Sheng-Yuan Deng
A porphyrin-based electro-photodynamic imaging system was fabricated for monitoring the concentration of oxygen. Distinct from the electrochemiluminescent (ECL) inability of numerous organic species in aqueous solutions, a strong and stable red irradiation at 634 nm could be stimulated electrochemically on zinc(II) meso-tetra(4-carboxyphenyl) porphine (ZnTCPP)/tetraoctylammonium bromide (TOAB) in the physiological condition. In terms of in situ electron paramagnetic resonance and ECL spectroscopies, the nature of ECL was thoroughly investigated, being exactly the chemiluminescence from singlet oxygen (1O2) produced during the successive electro-reduction of ZnTCPP...
October 20, 2016: ACS Applied Materials & Interfaces
Animesh Pardanani
: Disease overview:Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extra-cutaneous organs. DIAGNOSIS: The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V. Risk stratification: The 2008 World Health Organization (WHO) classification of SM has been shown to be prognostically relevant...
November 2016: American Journal of Hematology
Dirk Jan Stenvers, Rick van Dorp, Ewout Foppen, Jorge Mendoza, Anne-Loes Opperhuizen, Eric Fliers, Peter H Bisschop, Johanna H Meijer, Andries Kalsbeek, Tom Deboer
Exposure to light at night (LAN) is associated with insomnia in humans. Light provides the main input to the master clock in the hypothalamic suprachiasmatic nucleus (SCN) that coordinates the sleep-wake cycle. We aimed to develop a rodent model for the effects of LAN on sleep. Therefore, we exposed male Wistar rats to either a 12 h light (150-200lux):12 h dark (LD) schedule or a 12 h light (150-200 lux):12 h dim white light (5 lux) (LDim) schedule. LDim acutely decreased the amplitude of daily rhythms of REM and NREM sleep, with a further decrease over the following days...
October 20, 2016: Scientific Reports
J N Mahlangu, T A Andreeva, D E Macfarlane, C Walsh, N S Key
INTRODUCTION: Development of inhibitors to human FVIII (hFVIII) significantly complicates the control of bleeding events in patients with haemophilia A. AIM: This prospective, multicentre, open-label, non-comparative, Phase II study evaluated the haemostatic activity of a recombinant B-domain-deleted porcine FVIII (r-pFVIII), in the treatment of non-life/non-limb-threatening bleeding in individuals with haemophilia A and FVIII inhibitors. METHODS: Acute bleeding episodes in patients with pFVIII inhibitor titres <0...
October 20, 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
Julienne K Muenzner, Bernhard Biersack, Alexander Albrecht, Tobias Rehm, Ulrike Lacher, Wolfgang Milius, Angela Casini, Jing-Jing Zhang, Ingo Ott, Viktor Brabec, Olga Stuchlikova, Ion C Andronache, Detlef Schuppan, Leonard Kaps, Rainer Schobert
Four gold(I) carbene complexes featuring 4-ferrocenyl substituted imidazol-2-ylidene ligands were investigated for antiproliferative and antivascular properties. They were active against a panel of seven cancer cell lines, including multidrug-resistant ones, with low micromolar or nanomolar IC50 (72 h) values, according to their lipophilicity and cellular uptake. The delocalised lipophilic cationic complexes 8 and 10 acted by increasing the reactive oxygen species in two ways: via a genuine ferrocene effect and by inhibiting the thioredoxin reductase...
October 20, 2016: Chemistry: a European Journal
Ulrike Glaubitz, Xia Li, Sandra Schaedel, Alexander Erban, Ronan Sulpice, Joachim Kopka, Dirk K Hincha, Ellen Zuther
Transcript and metabolite profiling were performed on leaves from six rice cultivars under high night temperature (HNT) condition. Six genes were identified as central for HNT response encoding proteins involved in transcription regulation, signal transduction, protein-protein interactions, jasmonate response, and the biosynthesis of secondary metabolites. Sensitive cultivars showed specific changes in transcript abundance including abiotic stress responses, changes of cell wall related genes, of ABA signaling and secondary metabolism...
October 20, 2016: Plant, Cell & Environment
Jizhe Sun, Huimin Yu, Jie Chen, Hui Luo, Zhongyao Shen
Rhodococcus ruber TH was selected as a parent strain to engineer for biomanufacturing of ammonium acrylate; the characteristics of this strain included accelerated growth rate, high cell tolerance and natively overexpressed nitrile hydratase (NHase). Transcriptome analysis revealed that the transcription levels of the native NHase, amidase and nitrilase were extremely high, moderate and extremely low, respectively. Through NHase-amidase double-knockout and amidase single-knockout, the engineered strains R. ruber THdAdN and R...
October 19, 2016: Journal of Industrial Microbiology & Biotechnology
Alberto Campanaro, Raffaella Battaglia, Massimo Galbiati, Ari Sadanandom, Chiara Tonelli, Lucio Conti
SUMOylation and anther growth. During fertilization, stamen elongation needs to be synchronized with pistil growth. The phytohormone gibberellic acid (GA) promotes stamen growth by stimulating the degradation of growth repressing DELLA proteins. DELLA accumulation is negatively regulated by GAs through the ubiquitin-proteasome system. In Arabidopsis thaliana, a proportion of DELLAs is also conjugated to the small ubiquitin-like modifier (SUMO) protein, which stabilizes DELLAs. Increased DELLA levels occur in the SUMO protease-deficient OVERLY TOLERANT TO SALT 1 and 2 (ots1 ots2) double mutants, especially under salt stress conditions...
October 19, 2016: Plant Reproduction
Charles Lekhya Priya, K V Bhaskara Rao
BACKGROUND: α-glucosidase inhibitors controls postprandial hyperglycemia (PPHG) by lowering sharp rise in blood glucose levels after ingestion of carbohydrate rich meal in type 2 diabetic (T2D) individuals. Acalypha indica commonly known as Indian copper leaf is used in traditional medicinal system to treat various diseases. In our previous in-vitro investigation, methanolic extract of A. indica stems (AIS) proved to be an effective a-glucosidase inhibitor, antioxidant, and well tolerated in acute and subchronic toxicity studies in albino wistar rats...
July 2016: Pharmacognosy Magazine
Hidekazu Nishikii, Byung-Su Kim, Yasuhisa Yokoyama, Yan Chen, Jeanette Baker, Antonio Pierini, Maite Alvarez, Melissa Mavers, Kristina Maas-Bauer, Yuqiong Pan, Shigeru Chiba, Robert S Negrin
CD4(+)Foxp3(+) regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft versus host disease (GVHD) in murine models of allogeneic hematopoietic stem cell transplantation (HCT). We recently demonstrated that a single treatment of the agonistic antibody to DR3 (Death receptor 3, αDR3) to donor mice resulted in the expansion of donor derived Treg and prevented acute GVHD, although the precise role of DR3 signaling in GVHD has not been elucidated...
October 19, 2016: Blood
Yang Luo, Junling Li, Yan Wang, Xuezhi Hao, Fenglian Qu
BACKGROUND: Epidermal growth factor receptor (EGFR) is commonly overexpressed in lung squamous cell carcinoma and has been associated with impaired prognosis. The aim of this study was to observe the efficacy and safety of nimotuzumab, a anti-EGFR monoclonal antibody, combined with chemotherapy as second- or later-line in the treatment of advanced lung squamous cell carcinoma. METHODS: A retrospective analysis of clinical data was conducted in 13 patients with advanced lung squamous cell carcinoma, who were administered with nimotuzumab combined with chemotherapy as second-line or later-line treatment...
October 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
András Kotschy, Zoltán Szlavik, James Murray, James Davidson, Ana Leticia Maragno, Gaëtane Le Toumelin-Braizat, Maïa Chanrion, Gemma L Kelly, Jia-Nan Gong, Donia M Moujalled, Alain Bruno, Márton Csekei, Attila Paczal, Zoltán B Szabo, Szabolcs Sipos, Gábor Radics, Agnes Proszenyak, Balázs Balint, Levente Ondi, Gábor Blasko, Alan Robertson, Allan Surgenor, Pawel Dokurno, Ijen Chen, Natalia Matassova, Julia Smith, Christopher Pedder, Christopher Graham, Aurélie Studeny, Gaëlle Lysiak-Auvity, Anne-Marie Girard, Fabienne Gravé, David Segal, Chris D Riffkin, Giovanna Pomilio, Laura C A Galbraith, Brandon J Aubrey, Margs S Brennan, Marco J Herold, Catherine Chang, Ghislaine Guasconi, Nicolas Cauquil, Fabien Melchiore, Nolwen Guigal-Stephan, Brian Lockhart, Frédéric Colland, John A Hickman, Andrew W Roberts, David C S Huang, Andrew H Wei, Andreas Strasser, Guillaume Lessene, Olivier Geneste
Avoidance of apoptosis is critical for the development and sustained growth of tumours. The pro-survival protein myeloid cell leukemia 1 (MCL1) is overexpressed in many cancers, but the development of small molecules targeting this protein that are amenable for clinical testing has been challenging. Here we describe S63845, a small molecule that specifically binds with high affinity to the BH3-binding groove of MCL1. Our mechanistic studies demonstrate that S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukaemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway...
October 19, 2016: Nature
Michel J Massaad, Jia Zhou, Daisuke Tsuchimoto, Janet Chou, Haifa Jabara, Erin Janssen, Salomé Glauzy, Brennan G Olson, Henner Morbach, Toshiro K Ohsumi, Klaus Schmitz, Markianos Kyriacos, Jennifer Kane, Kumiko Torisu, Yusaku Nakabeppu, Luigi D Notarangelo, Eliane Chouery, Andre Megarbane, Peter B Kang, Eman Al-Idrissi, Hasan Aldhekri, Eric Meffre, Masayuki Mizui, George C Tsokos, John P Manis, Waleed Al-Herz, Susan S Wallace, Raif S Geha
Alterations in the apoptosis of immune cells have been associated with autoimmunity. Here, we have identified a homozygous missense mutation in the gene encoding the base excision repair enzyme Nei endonuclease VIII-like 3 (NEIL3) that abolished enzymatic activity in 3 siblings from a consanguineous family. The NEIL3 mutation was associated with fatal recurrent infections, severe autoimmunity, hypogammaglobulinemia, and impaired B cell function in these individuals. The same homozygous NEIL3 mutation was also identified in an asymptomatic individual who exhibited elevated levels of serum autoantibodies and defective peripheral B cell tolerance, but normal B cell function...
October 17, 2016: Journal of Clinical Investigation
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