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https://www.readbyqxmd.com/read/28505514/tlr4-supports-the-expansion-of-fasl-cd5-cd1d-hi-regulatory-b-cells-which-decreases-in-contact-hypersensitivity
#1
Keng Wang, Lei Tao, Jianbing Su, Yueyang Zhang, Binhua Zou, Yiyuan Wang, Min Zou, Nana Chen, Linsheng Lei, Xiaojuan Li
Certain B cells termed as "regulatory B cells" (Bregs) can suppress the ongoing immune responses and a splenic CD5(+)CD1d(hi) Breg subset identified earlier was shown to exert its regulatory functions through secretion of IL-10. Though FasL expression is an alternative mechanism of immune suppression used by B cells, little is known about the FasL expressing CD5(+)CD1d(hi) Bregs. In this study, we isolated splenocytes or splenic CD19(+) B cells and compared the efficiency of toll-like receptor(TLR)4 ligand (lipopolysaccharide) with TLR9 ligand (CpG), anti-CD40 and TLR9 ligand (CpG) plus anti-CD40 on the FasL expression of splenic CD5(+)CD1d(hi) Bregs by flow cytometry...
May 12, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28500957/design-synthesis-of-novel-oxazolone-triazinone-derivatives-and-their-biological-evaluation-as-cox-2-inhibitors
#2
Lamia W Mohamed, Osama M El-Badry, Afaf K El-Ansary, Ahmed Ismael
A new series of oxazolones and triazinones were designed and synthesized and evaluated against both COX-1 and COX-2 enzymes. Full structure elucidation of the new derivatives was performed using microanalyses, IR, 1H NMR, 13C NMR and mass spectra. Most of the derivatives showed good inhibitory activity against COX-2 enzyme specifically compounds IIIc, IIIe, IVd and IVg with IC50 values 0.024, 0.019, 0.011 and 0.014µM compared to celecoxib as reference drug with IC50 value of 0.05µM. Altogether, these results indicate that these derivatives can be effective anti-inflammatory agents...
April 24, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28482341/indigo-naturalis-ameliorates-oxazolone-induced-dermatitis-but-aggravates-colitis-by-changing-the-composition-of-gut-microflora
#3
Soichiro Adachi, Namiko Hoshi, Jun Inoue, Eiichiro Yasutomi, Takafumi Otsuka, Ramesh Dhakhwa, Zi Wang, Yuna Koo, Toshihiro Takamatsu, Yuriko Matsumura, Haruka Yamairi, Daisuke Watanabe, Makoto Ooi, Toshihito Tanahashi, Shin Nishiumi, Masaru Yoshida, Takeshi Azuma
BACKGROUND: Indigo naturalis (IND) is an herbal medicine that has been used as an anti-inflammatory agent to treat diseases including dermatitis and inflammatory bowel disease in China. However, the mechanism by which IND exerts its immunomodulatory effect is not well understood. METHODS: A murine model of dermatitis and inflammatory bowel disease, both induced by oxazolone (OXA), was treated with IND. The severity of dermatitis was evaluated based on ear thickness measurements and histological scoring...
May 9, 2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/28429299/participation-of-c-h-protons-in-the-dissociation-of-a-proton-deficient-dipeptide
#4
Damodar Koirala, Sabyasachy Mistry, Paul G Wenthold
The dissociation of anionic dipeptides Phe*Gly and GlyPhe*, where Phe* refers to sulfonated phenyl alanine, has been investigated by using ion trap mass spectrometry. The dipeptides undergo collision-induced dissociation (CID) to give the same products, indicating that they rearrange to a common structure before dissociation. The rearrangement does not occur with the dipeptide methyl esters. The structures of the b2 ions were investigated to determine the effect that having a remote, anionic site has on product formation...
April 20, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28424989/t-lymphocyte-derived-enkephalins-reduce-th1-th17-colitis-and-associated-pain-in-mice
#5
Lilian Basso, Laure Garnier, Arnaud Bessac, Jérôme Boué, Catherine Blanpied, Nicolas Cenac, Sophie Laffont, Gilles Dietrich
BACKGROUND: Endogenous opioids, including enkephalins, are fundamental regulators of pain. In inflammatory conditions, the local release of opioids by leukocytes at the inflammatory site inhibits nociceptor firing, thereby inducing analgesia. Accordingly, in chronic intestinal Th1/Th17-associated inflammation, enkephalins released by colitogenic CD4(+) T lymphocytes relieve inflammation-induced visceral pain. The present study aims to investigate whether mucosal T-cell-derived enkephalins also exhibit a potent anti-inflammatory activity as described for exogenous opioid drugs in Th1/Th17-associated colitis...
April 19, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28418286/external-application-of-nf-%C3%AE%C2%BAb-inhibitor-dhmeq-suppresses-development-of-atopic-dermatitis-like-lesions-induced-with-dncb-ox-in-balb-c-mice
#6
Xiaoxue Jiang, Yi Lan, Bing Wei, Cailing Dai, Yaru Gu, Jun Ma, Xiaoyan Liu, Kazuo Umezawa, Yuyang Zhang
CONTEXT: Dehydroxymethylepoxyquinomicin (DHMEQ) which is originally developed as an analog of antibiotic epoxyquinomicin C is a specific and potent inhibitor of NF-κB and has been shown to possess promising potential as an anti-inflammatory and anti-tumor agent. OBJECTIVE: This study examines DHMEQ's effect on therapeutic potential for atopic dermatitis (AD)-like lesions. MATERIALS AND METHODS: AD lesions were chronically induced by the repetitive and alternative application of 2,4-dinitrochlorobenzene (DNCB) and oxazolone (OX) on ears in BALB/c mice...
June 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28378889/the-prebiotic-c-terminal-elongation-of-peptides-can-be-initiated-by-n-carbamoyl-amino-acids
#7
Ninette Abou Mrad, Ghinwa Ajram, Jean-Christophe Rossi, Laurent Boiteau, Fabrice Duvernay, Robert Pascal, Gregoire Danger
The formation of peptides upon EDC promoted activation of N-carbamoylamino acids (CAA), was considered in the scope of our recent works on carbodiimide promoted C-terminus elongation of peptides in a prebiotic context. Thus EDC promoted activation of CAA derivatives of Tyr(Me) or Ala in dilute aqueous medium pH 5.5-6.5 in the presence of excess of AA, resulted in peptide formation via C-terminus activation / elongation. Kinetic results similar to those of EDC-mediated activation of N-acyl-AA lead us to postulate the formation of a 2-amino-5(4H)-oxazolone intermediate by cyclization of the activated CAA, in spite of the absence of epimerization occurred at CAA residues...
April 5, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28374317/infrared-multiple-photon-dissociation-action-spectroscopy-of-the-b2-ion-from-ppg-evidence-of-third-residue-affecting-b2-fragment-structure
#8
John C Poutsma, Jonathan Martens, Jos Oomens, Phillipe Maitre, Vincent Steinmetz, Matthew Bernier, Mengxuan Jia, Vicki Wysocki
Infrared multiple-photon dissociation (IRMPD) action spectroscopy was performed on the b2(+) fragment ion from the protonated PPG tripeptide. Comparison of the experimental infrared spectrum with computed spectra for both oxazolone and diketopiperazine structures indicates that the majority of the fragment ion population has an oxazolone structure with the remainder having a diketopiperazine structure. This result is in contrast with a recent study of the IRMPD action spectrum of the PP b2(+) fragment ion from PPP, which was found to be nearly 100% diketopiperazine (Martens et al...
April 3, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28357423/polyfluoroarylation-of-oxazolones-access-to-non-natural-fluorinated-amino-acids
#9
Kip A Teegardin, Jimmie D Weaver
Herein, conditions are provided for the formation and use of the oxazolone enolate for the nucleophilic substitution of highly fluorinated (hetero)arenes, which after unmasking yield highly fluorinated non-natural amino acids and derivatives. In addition, the properties and chemical behavior of this new class of amino acids are explored. The utility is demonstrated in the one pot synthesis of medicinally relevant 2-aminohydantoins.
March 30, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28342759/activation-of-epithelial-stat1-by-interleukin-28-controls-mucosal-healing-in-mice-with-colitis-and-is-increased-in-mucosa-of-patients-with-inflammatory-bowel-disease
#10
Mircea T Chiriac, Barbara Buchen, Alexandra Wandersee, Gheorghe Hundorfean, Claudia Günther, Yvonne Bourjau, Sean E Doyle, Benjamin Frey, Arif B Ekici, Christian Büttner, Benno Weigmann, Raja Atreya, Stefan Wirtz, Christoph Becker, Jürgen Siebler, Markus F Neurath
BACKGROUND & AIMS: We investigated the roles of interleukin 28A (also called IL28A or interferon lambda 2) in intestinal epithelial cell (IEC) activation, studying its effects in mouse models of inflammatory bowel diseases (IBD) and intestinal mucosal healing. METHODS: Colitis was induced in C57BL/6JCrl mice (controls), mice with intestinal epithelial cell-specific disruption of Stat1 (Stat1IEC-KO), mice with disruption of the interferon lambda receptor 1 gene (Il28ra-/-), and mice with disruption of the interferon regulatory factor 3 gene (Irf3-/-), with or without disruption of Irf7 (Irf7-/-)...
March 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28290578/pd-cu-catalyzed-tandem-head-to-tail-dimerization-cycloisomerization-of-terminal-ynamides-for-the-synthesis-of-5-vinyloxazolones
#11
Luning Tang, Hai Huang, Yang Xi, Guangke He, Hongjun Zhu
An attractive and novel methodology involving Pd/Cu-catalyzed tandem head-to-tail dimerization/cycloisomerization of terminal ynamides for the synthesis of 3,5-disubstituted oxazolones was developed. Under Pd(PPh3)2Cl2/CuI cooperative catalyzed reaction conditions, it provided efficient access to 5-vinyloxazolones with exceptional functional group tolerance and good chemoselectivity. The control experiments demonstrated that Pd(PPh3)2Cl2 serves a key role in the dimerization of terminal ynamides and shows low catalytic activity in the intramolecular cyclization...
March 14, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28290517/sensitivity-to-oxazolone-induced-dermatitis-is-transferable-with-gut-microbiota-in-mice
#12
Line Fisker Zachariassen, Lukasz Krych, Kåre Engkilde, Dennis Sandris Nielsen, Witold Kot, Camilla Hartmann Friis Hansen, Axel Kornerup Hansen
Atopic Dermatitis (AD) has been associated with gut microbiota (GM) dysbiosis in humans, indicating a causative role of GM in AD etiology. Furthermore, the GM strongly correlates to essential disease parameters in the well-known oxazolone-induced mouse model of AD. Here, we demonstrate that it is possible to transfer both a high-responding and a low-responding AD phenotype with GM from conventional mice to germ-free mice. The mice inoculated with the high-responding GM had significantly higher clinical score, increased ear thickness, and increased levels of IL-1β, TNFα, IL-4, IL-5, and IL-6 compared to the mice inoculated with the low-responding GM...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28286160/p2x7-receptor-promotes-intestinal-inflammation-in-chemically-induced-colitis-and-triggers-death-of-mucosal-regulatory-t-cells
#13
Vanessa R Figliuolo, Luiz Eduardo Baggio Savio, Hanaa Safya, Hayandra Nanini, Cláudio Bernardazzi, Alessandra Abalo, Heitor S P de Souza, Jean Kanellopoulos, Pierre Bobé, Cláudia M L M Coutinho, Robson Coutinho-Silva
P2X7 receptor activation contributes to inflammation development in different pathologies. We previously reported that the P2X7 receptor is over-expressed in the gut mucosa of patients with inflammatory bowel disease, and that P2X7 inhibition protects against chemically induced colitis. Here, we investigated in detail the role of the P2X7 receptor in inflammatory bowel disease development, by treating P2X7 knockout (KO) and WT mice with two different (and established) colitis inductors. P2X7 KO mice were protected against gut inflammation induced by 2,4,6-trinitrobenzenesulfonic acid or oxazolone, with no weight loss or gut histological alterations after treatment...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28222357/mangiferin-antagonizes-tnf-%C3%AE-mediated-inflammatory-reaction-and-protects-against-dermatitis-in-a-mice-model
#14
Yunpeng Zhao, Wenhan Wang, Xihai Wu, Xiaoqian Ma, Ruize Qu, Xiaomin Chen, Chenghao Liu, Yaoge Liu, Xiaokai Wang, Pengcheng Yan, Hao Zhang, Jingrui Pan, Weiwei Li
This study aimed to investigate whether mangiferin played a protective role in a well-established dermatitis mouse model and tumor necrosis factor alpha (TNF-α)-induced RAW264.7 macrophages. Contact dermatitis is an inflammatory skin disease in the clinic, while its underlying mechanism still remains to be elucidated. Mangiferin, 1,3,6,7-tetrahydroxyxanthone-C2-β-d-glucoside (C-glucosyl xanthone), a natural antioxidant that was reported to inhibit inflammatory reactions, has been recently proved to be a potential therapy for inflammation...
February 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28167257/tetradecanol-reduces-el-4-t-cell-growth-by-the-down-regulation-of-nf-%C3%AE%C2%BAb-mediated-il-2-secretion
#15
Jung Up Park, Bok Yun Kang, Hwa-Jeong Lee, Sunoh Kim, Donghyuck Bae, Jong-Hwan Park, Young Ran Kim
Tetradecanol is a straight-chain saturated fatty alcohol purified from Dendropanax morbifera leaves. We found that tetradecanol (30μM) reduced specifically the growth of T cells such as EL-4 T cell and isolated murine CD4(+) T cells. In this study, we investigated the effects of tetradecanol on the regulation of interlukin-2 (IL-2), a potent T cell growth factor. Tetradecanol significantly inhibited IL-2 secretion in EL-4 T cells activated with phorbol 12-myristate 13-acetate (PMA) plus ionomycin (Io) and also in isolated murine CD4(+) T cells activated with anti-CD3 and anti-CD28 antibodies...
March 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28158195/repeated-hapten-exposure-induces-persistent-tactile-sensitivity-in-mice-modeling-localized-provoked-vulvodynia
#16
Jasmine Landry, Tijana Martinov, Hanna Mengistu, Jyothi Dhanwada, Charles J Benck, Jaclyn Kline, Beebie Boo, Linnea Swanson, Elena Tonc, Randy Daughters, Brian T Fife, Devavani Chatterjea
BACKGROUND: Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology. Epidemiologic studies associate the risk of vulvodynia with a history of atopic disease. We used an established model of hapten-driven contact hypersensitivity to investigate the underlying mechanisms of allergy-provoked prolonged sensitivity to pressure. METHODS: We sensitized female ND4 Swiss mice to the hapten oxazolone on their flanks, and subsequently challenged them four days later with oxazolone or vehicle for ten consecutive days on the labia...
2017: PloS One
https://www.readbyqxmd.com/read/28153485/loop-f-of-the-%C3%AE-subunit-determines-the-pharmacologic-profile-of-novel-competitive-inhibitors-of-gabaa-receptors
#17
Balázs Mihalik, Adrienn Pálvölgyi, Ferenc Bogár, Katalin Megyeri, István Ling, József Barkóczy, Ferenc Bartha, Tamás A Martinek, István Gacsályi, Ferenc A Antoni
The neurotransmitter γ-amino butyric acid (GABA) has a fundamental role in CNS function and ionotropic (GABAA) receptors that mediate many of the actions of GABA are important therapeutic targets. This study reports the mechanism of action of novel GABAA antagonists based on a tricyclic oxazolo-2,3-benzodiazepine scaffold. These compounds are orthosteric antagonists of GABA on heteropentameric GABAA receptors of αxβ2γ2 configuration expressed in HEK293 cells. In silico modelling predicted that the test compounds docked in the GABA binding-pocket and would interact with amino-acid residues in the α- and β-subunit interface that are known to be important for the binding of GABA...
March 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28125560/o-012-il-36-signaling-controls-the-induced-regulatory-t-cell-th9-cell-balance-and-gut-inflammation
#18
Akihito Harusato, Hirohito Abo, Vu Ngo, Samuel Yi, Satoru Osuka, Jakob Kohlmeier, Jian-Dong Li, Andrew Gewirtz, Asma Nusrat, Timothy Denning
BACKGROUND: In the United States over 1.4 million people suffer from inflammatory bowel disease (IBD). Therefore, there is a pressing need for the development of novel molecular therapeutics targeting pro-inflammatory mediators. Recently a novel interleukin-1 family member, IL-36γ was shown to be up-regulated in patients with inflammatory bowel disease (IBD) and to play an important role in healing of acute intestinal damage in mice, however, the function of IL-36γ with regards to T helper (TH) cell differentiation during gut inflammation remains undefined...
February 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28116609/dendritic-core-multishell-nanocarriers-in-murine-models-of-healthy-and-atopic-skin
#19
Moritz Radbruch, Hannah Pischon, Anja Ostrowski, Pierre Volz, Robert Brodwolf, Falko Neumann, Michael Unbehauen, Burkhard Kleuser, Rainer Haag, Nan Ma, Ulrike Alexiev, Lars Mundhenk, Achim D Gruber
Dendritic hPG-amid-C18-mPEG core-multishell nanocarriers (CMS) represent a novel class of unimolecular micelles that hold great potential as drug transporters, e.g., to facilitate topical therapy in skin diseases. Atopic dermatitis is among the most common inflammatory skin disorders with complex barrier alterations which may affect the efficacy of topical treatment.Here, we tested the penetration behavior and identified target structures of unloaded CMS after topical administration in healthy mice and in mice with oxazolone-induced atopic dermatitis...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28068430/molecular-mimics-of-classic-p-glycoprotein-inhibitors-as-multidrug-resistance-suppressors-and-their-synergistic-effect-on-paclitaxel
#20
Moustafa E El-Araby, Abdelsattar M Omar, Maan T Khayat, Hanan A Assiri, Ahmed M Al-Abd
P-glycoprotein (Pgp) is a membrane bound efflux pump spread in a variety of tumor cells and considered as a main component of multidrug resistance (MDR) to chemotherapies. In this work, three groups of compounds (imidazolone, oxazolone and vinyl dipeptide derivatives) were synthesized aiming to develop a molecular framework that effectively suppresses MDR. When tested for their influence on Pgp activity, four compounds coded Cur1-01, Cur1-12V, Curox-1 and Curox-3 significantly decreased remaining ATP concentration indicating Pgp substrate site blocking...
2017: PloS One
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