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https://www.readbyqxmd.com/read/29666981/an-early-life-mucosal-insult-temporarily-decreases-acute-oxazolone-induced-inflammation-in-mice
#1
Katja M Bendtsen, Peter Tougaard, Axel K Hansen
Inflammatory priming of immune cells in early life may optimize the response to a subsequent inflammatory challenge later in life. To prime the immune cells in the gut in vivo through a short inflammatory insult, we administered a low dose of dextran sulfate sodium (DSS) to 5-weeks-old BALB/c mice in the drinking water. We hypothesized that DSS-primed mice would show decreased inflammation and difference in immunological profiling, when subjected to presensitizing and oxazolone-induced colitis by rectal instillation at 9 weeks compared to non-DSS-primed control mice...
April 18, 2018: Inflammation
https://www.readbyqxmd.com/read/29661024/surface-engineered-lipid-nanoparticle-mediated-site-specific-drug-delivery-system-for-the-treatment-of-inflammatory-bowel-disease
#2
Gurpreet Kaur Sinhmar, Neel N Shah, Shruti U Rawal, Nimitt V Chokshi, Hiren N Khatri, Bhoomika M Patel, Mayur M Patel
The major challenge for the treatment of inflammatory bowel disease (IBD) is the incompetence to deliver the drug molecule selectively at the site of inflammation. Taking this into consideration, we proposed development of mannosylated nanostructured lipid carrier system (Mn-NLCs) for active targeting and site-specific delivery of budesonide to the inflamed tissues. The developed Mn-NLCs were characterized for particle size and size distribution, zeta potential, %entrapment efficiency, FTIR and TEM analysis...
April 16, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29648818/imidazole-alkaloids-and-their-zinc-complexes-from-the-calcareous-marine-sponge-leucetta-chagosensis
#3
Wei-Zhuo Tang, Zhong-Zhen Yang, Wei Wu, Jie Tang, Fan Sun, Shu-Ping Wang, Chun-Wei Cheng, Fan Yang, Hou-Wen Lin
Five new imidazole derivatives (1-5), together with eight related known alkaloids, were isolated from a calcareous marine sponge, Leucetta chagosensis, collected from the South China Sea. Their structures were fully characterized by spectroscopic methods. Structurally, 1 possesses an unusual skeleton featuring imidazole and oxazolone rings linked via a nitrogen atom, whereas 2 bears an intriguing guanylurea-substituted imidazole ring. Compounds 4 and 5 were identified as zinc complexes; they represent the metal complex analogues of naamidine J (6) and pyronaamidine (7), respectively...
April 12, 2018: Journal of Natural Products
https://www.readbyqxmd.com/read/29603634/current-status-of-o-heterocycles-a-synthetic-and-medicinal-overview
#4
Pankaj Kumar Singh, Om Silakari
O-heterocycles have been explored since long in the field of medicinal chemistry but they have not yet been given their due significance and are usually shunned out in comparison to N-heterocycles. Designing of bioactive molecules for almost every pathophysiological condition is primarily focused on designing novel N-heterocycles. The basic reasons for this bias are the ease of synthesis and possible mimicking of physiological molecules by N-heterocycles. But considering only this criteria never provides any breakthrough molecule for any disease condition, rather risk of toxicity/side effects are increased with such molecules...
March 30, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29567715/the-biosynthesis-of-methanobactin
#5
Grace E Kenney, Laura M K Dassama, Maria-Eirini Pandelia, Anthony S Gizzi, Ryan J Martinie, Peng Gao, Caroline J DeHart, Luis F Schachner, Owen S Skinner, Soo Y Ro, Xiao Zhu, Monica Sadek, Paul M Thomas, Steven C Almo, J Martin Bollinger, Carsten Krebs, Neil L Kelleher, Amy C Rosenzweig
Metal homeostasis poses a major challenge to microbes, which must acquire scarce elements for core metabolic processes. Methanobactin, an extensively modified copper-chelating peptide, was one of the earliest natural products shown to enable microbial acquisition of a metal other than iron. We describe the core biosynthetic machinery responsible for the characteristic posttranslational modifications that grant methanobactin its specificity and affinity for copper. A heterodimer comprising MbnB, a DUF692 family iron enzyme, and MbnC, a protein from a previously unknown family, performs a dioxygen-dependent four-electron oxidation of the precursor peptide (MbnA) to install an oxazolone and an adjacent thioamide, the characteristic methanobactin bidentate copper ligands...
March 23, 2018: Science
https://www.readbyqxmd.com/read/29400411/design-synthesis-and-biological-evaluation-of-novel-1-2-diaryl-4-substituted-benzylidene-5-4h-imidazolone-derivatives-as-cytotoxic-agents-and-cox-2-lox-inhibitors
#6
Phoebe F Lamie, John N Philoppes, Lucie Rárová
A new series of 1,2-diaryl-4-substituted-benzylidene-5(4H)-imidazolone derivatives 4a-l was synthesized. Their structures were confirmed by different spectroscopic techniques (IR, 1 H NMR, DEPT-Q NMR, and mass spectroscopy) and elemental analyses. Their cytotoxic activities in vitro were evaluated against breast, ovarian, and liver cancer cell lines and also normal human skin fibroblasts. Cyclooxygenase (COX)-1, COX-2 and lipoxygenase (LOX) inhibitory activities were measured. The synthesized compounds showed selectivity toward COX-2 rather than COX-1, and the IC50 values (0...
February 5, 2018: Archiv der Pharmazie
https://www.readbyqxmd.com/read/29395580/a-lamellar-body-mimetic-system-for-the-treatment-of-oxazolone-induced-atopic-dermatitis-in-hairless-mice
#7
Verónica Moner, Estibalitz Fernández, Ana Cristina Calpena, Adriana Garcia-Herrera, Mercedes Cócera, Olga López
BACKGROUND: Atopic dermatitis is a common skin disease characterized by a Th2 cell-dominant inflammatory infiltrate, elevated serum IgE levels and impaired epidermal barrier function. It is associated to abnormal epidermal lamellar body secretion, producing alteration in lipid composition and extracellular lamellar membrane organization. OBJECTIVES: The oxazolone-induced atopic dermatitis in hairless mice was used to evaluate in vivo the effect of the application of a lipid system that mimics the morphology, structure and composition of epidermal lamellar bodies...
January 30, 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29392979/characterization-of-acetylated-histidine-b1-ion-structure-a-competition-between-oxazolone-and-side-chain-imidazole-moiety
#8
Kranthikumar Yadav, J Laxmikanth Rao, R Srinivas, R Nagaraj, M V Jagannadham
The detection of post-translational modifications of proteins is an important comprehensive research area. Over the years, proteomic studies involving protein acetylation have attracted a great deal of attention. In the present study, we have focussed on the acetylation of histidine and the intrinsic stability of b1-ion of oxazolone ring and/or with side chain imidazole bicyclic product. The formation of oxazolone structure may occur when an amino moiety undergoes acetylation reaction and when it is present in the vicinity of the side chain imidazole moiety...
January 1, 2018: European Journal of Mass Spectrometry
https://www.readbyqxmd.com/read/29386485/juniperus-chinensis-fruits-attenuate-oxazolone-and-2-4-dinitrochlorobenzene-induced-atopic-dermatitis-symptoms-in-mice
#9
Jonghwan Jegal, No-June Park, Sang-A Park, Sim-Kyu Bong, Hyun Jegal, Su-Nam Kim, Min Hye Yang
Juniperus chinensis, commonly Chinese juniper, has been used for treating inflammatory diseases. This study aimed to investigate anti-atopic dermatitis (AD) effects of standardized J. chinensis fruits extract on murine oxazolone- and 2,4-dinitrochlorobenzene (DNCB)-induced models of AD. Ear swelling, epidermis thickening, and eosinophils infiltration in the oxazolone-mediated dermatitis of BALB/c mice were significantly reduced upon topical application of J. chinensis fruits 95% EtOH extract (JCE). Besides, transdermal administration of JCE to SKH-1 hairless mice inhibited the development of DNCB-induced AD-like skin lesions by suppressing transepidermal water loss and improving skin hydration...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29365216/insight-into-metal-removal-from-peptides-that-sequester-copper-for-methane-oxidation
#10
Arnaud Basle, Abdelnasser El Ghazouani, Jaeick Lee, Christopher Dennison
Methanobactins (Mbns) are modified peptides that sequester copper (Cu) methanotrophs use to oxidize methane. Limited structural information is available for this class of natural products, as is an understanding of how cells utilize Mbn-bound Cu. The crystal structure of Methylosinus sporium NR3K Cu(I)-Mbn provides further information about the structural diversity of Mbns and the first insight into their Cu-release mechanism. Nitrogen ligands from oxazolone and pyrazinedione rings chelate Cu(I) along with adjacent thioamides...
January 24, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29363669/histamine-drives-severity-of-innate-inflammation-via-histamine-4-receptor-in-murine-experimental-colitis
#11
J B Wechsler, A Szabo, C L Hsu, R A Krier-Burris, H A Schroeder, M Y Wang, R G Carter, T E Velez, L M Aguiniga, J B Brown, M L Miller, B K Wershil, T A Barrett, P J Bryce
Ulcerative colitis (UC) patients exhibit elevated histamine, but how histamine exacerbates disease is unclear as targeting histamine 1 receptor (H1R) or H2R is clinically ineffective. We hypothesized that histamine functioned instead through the other colon-expressed histamine receptor, H4R. In humans, UC patient biopsies exhibited increased H4R RNA and protein expression over control tissue, and immunohistochemistry showed that H4R was in proximity to immunopathogenic myeloperoxidase-positive neutrophils. To characterize this association further, we employed both the oxazolone (Ox)- and dextran sulfate sodium (DSS)-induced experimental colitis mouse models and also found upregulated H4R expression...
January 24, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29353040/eupatilin-an-activator-of-ppar%C3%AE-inhibits-the-development-of-oxazolone-induced-atopic-dermatitis-symptoms-in-balb-c-mice
#12
Yujung Jung, Jin-Chul Kim, No-June Park, Sim-Kyu Bong, Sullim Lee, Hyun Jegal, Li Tai Jin, Sang Moo Kim, Yong Kee Kim, Su-Nam Kim
Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is the main lipophilic flavonoid obtained from the Artemisia species. Eupatilin has been reported to have anti-apoptotic, anti-oxidative and anti-inflammatory activities. Previously, we found that eupatilin increases transcriptional activity and expression of peroxisome proliferator-activated receptor α (PPARα) in a keratinocyte cell line and acts as an agonist of PPARα. PPARα agonists ameliorate atopic dermatitis (AD) and restore the skin barrier function...
February 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29330048/b-cell-activation-in-the-cecal-patches-during-the-development-of-an-experimental-colitis-model
#13
Taro Watabe, Takashi Nagaishi, Naoya Tsugawa, Yudai Kojima, Nisha Jose, Akinori Hosoya, Michio Onizawa, Yasuhiro Nemoto, Shigeru Oshima, Tetsuya Nakamura, Hajime Karasuyama, Takahiro Adachi, Mamoru Watanabe
Although previous studies have suggested that appendix seems to be involved in the colitis, the role of this in the pathogenesis remains unclear. In this study, we assessed the importance of appendiceal lymphoid follicles, specifically the cecal patches (CP) in mice, using an experimental colitis model. Treatment with oxazolone resulted in ulcerations particularly at CP with follicular expansion as well as colitis. The colitis was attenuated by either appendectomy or the absence of mature B cells. We therefore established an intravital imaging system accompanied by the fluorescence resonance energy transfer technology to analyze the dynamic immune response of CP B cells...
February 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29329002/integration-of-multi-scale-molecular-modeling-approaches-with-experiments-for-the-in-silico-guided-design-and-discovery-of-novel-herg-neutral-antihypertensive-oxazalone-and-imidazolone-derivatives-and-analysis-of-their-potential-restrictive-effects-on-cell
#14
Serdar Durdagi, Busecan Aksoydan, Ismail Erol, Isik Kantarcioglu, Yavuz Ergun, Gulay Bulut, Melih Acar, Timucin Avsar, George Liapakis, Vlasios Karageorgos, Ramin E Salmas, Barış Sergi, Sara Alkhatib, Gizem Turan, Berfu Nur Yigit, Kutay Cantasir, Bahar Kurt, Turker Kilic
AT1 antagonists is the most recent drug class of molecules against hypertension and they mediate their actions through blocking detrimental effects of angiotensin II (A-II) when acts on type I (AT1) A-II receptor. The effects of AT1 antagonists are not limited to cardiovascular diseases. AT1 receptor blockers may be used as potential anti-cancer agents - due to the inhibition of cell proliferation stimulated by A-II. Therefore, AT1 receptors and the A-II biosynthesis mechanisms are targets for the development of new synthetic drugs and therapeutic treatment of various cardiovascular and other diseases...
February 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29281784/determining-linear-free-energy-relationships-in-peptide-fragmentation-using-derivatization-and-targeted-mass-spectrometry
#15
Yuanyuan Shen, Reza Nemati, Lei Wang, Xudong Yao
The sequence complexity of a proteome is utilized with rational chemical derivatization to establish the linear free energy relationship (LFER) in order to investigate the collision-induced dissociation (CID) of peptides. The derivatization produces groups of peptides that have varying designer residues of aliphatic amino acids at the N-terminus but stay invariable for the rest of sequences, which are naturally occurring and uncontrolled. Collisional fragmentation of the derivatized peptides is advantageously monitored by liquid-chromatography multiple-reaction-monitoring mass spectrometry...
February 6, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29258854/ameliorative-effects-of-juniperus-rigida-fruit-on-oxazolone-and-2-4-dinitrochlorobenzene-induced-atopic-dermatitis-in-mice
#16
Sullim Lee, No-June Park, Sim-Kyu Bong, Jonghwan Jegal, Sang-A Park, Su-Nam Kim, Min Hye Yang
ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Juniperus rigida have been used in Korean traditional medicine for the treatment of inflammatory diseases in humans such as rheumatoid arthritis. AIM OF THE STUDY: This study aimed to investigate the anti-atopic properties of J. rigida fruit in in vivo murine atopic dermatitis (AD) models. METHODS AND RESULTS: BALB/c mouse ears ad SKH-1 hairless mice stimulated with oxazolone (4 weeks) and DNCB (3 weeks), respectively, were treated with the 1% Juniperus rigida fruit EtOH extract (JFE)...
March 25, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29236214/neural-network-modeling-of-ache-inhibition-by-new-carbazole-bearing-oxazolones
#17
Levent Cavas, Gamze Topcam, Cevher Gundogdu-Hizliates, Yavuz Ergun
Acetylcholine esterase (AChE) is one of the targeted enzymes in the therapy of important neurodegenerative diseases such as Alzheimer's disease. Many studies on carbazole- and oxazolone-based compounds have been conducted in the last decade due to the importance of these compounds. New carbazole-bearing oxazolones were synthesized from several carbazole aldehydes and p-nitrobenzoyl glycine as AChE inhibitors by the Erlenmeyer reaction in the present study. The inhibitory effects of three carbazole-bearing oxazolone derivatives on AChE were studied in vitro and the experimental results were modeled using artificial neural network (ANN)...
December 13, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/29225517/intestinally-restricted-janus-kinase-inhibition-a-potential-approach-to-maximize-the-therapeutic-index-in-inflammatory-bowel-disease-therapy
#18
David T Beattie, M Teresa Pulido-Rios, Fei Shen, Melissa Ho, Eva Situ, Pam R Tsuruda, Patrick Brassil, Melanie Kleinschek, Sharath Hegde
Background: An unmet need remains for safe and effective treatments to induce and maintain remission in inflammatory bowel disease (IBD) patients. The Janus kinase (JAK) inhibitor, tofacitinib, has demonstrated robust efficacy in ulcerative colitis patients although, like other systemic immunosuppressants, there may be safety concerns associated with its use. This preclinical study evaluated whether modulating intestinal inflammation via local JAK inhibition can provide efficacy without systemic immunosuppression...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/29206209/dioscorea-quinqueloba-ameliorates-oxazolone-and-2-4-dinitrochlorobenzene-induced-atopic-dermatitis-symptoms-in-murine-models
#19
Jonghwan Jegal, No-June Park, Sim-Kyu Bong, Hyun Jegal, Su-Nam Kim, Min Hye Yang
Dioscorea quinqueloba has been used for food substances, as well as in herbal medicines for allergic diseases such as asthma. This study aimed to investigate the anti-atopic dermatitis (AD) effects of the total extract of D. quinqueloba rhizomes and active fractionson murine oxazolone- and 2,4-dinitrochlorobenzene-induced models of AD. Specific AD symptoms, such as erythema, ear swelling, and epidermis thickening, were significantly reduced in the oxazolone-mediated AD BALB/c mice upon topical application of D...
December 5, 2017: Nutrients
https://www.readbyqxmd.com/read/29205369/regulatory-b-cells-induced-by-ultraviolet-b-through-toll-like-receptor-4-signalling-contribute-to-the-suppression-of-contact-hypersensitivity-responses-in-mice
#20
Xiaoming Liu, Haiyan Huang, Hongbin Gao, Xia Wu, Wei Zhang, Bo Yu, Xia Dou
BACKGROUND: Ultraviolet (UV) B irradiation is known to suppress contact hypersensitivity (CHS) responses in mouse models by suppressing immune responses. However, the cellular mechanisms responsible for UVB-induced systemic suppression remain unclear. Regulatory B cells have been reported to play an inhibitory role during CHS. It is presently unknown whether regulatory B cells contribute to the effect of UVB phototherapy. OBJECTIVE: To investigate the inductive effect of UVB on regulatory B cells and the underlying mechanisms by using a CHS mouse model...
February 2018: Contact Dermatitis
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