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Background: Thymus and activation‐regulated chemokine (TARC/CCL17) has been implicated in the pathogenesis of canine atopic dermatitis (cAD). Serum TARC concentrations are a reliable biomarker for human atopic dermatitis; however, their potential as a biomarker for cAD has not been investigated. Hypothesis/Objectives: To investigate whether serum TARC concentrations correlate with disease severity and therapeutic responses for cAD. Animals: Thirty‐nine dogs with cAD and 42 healthy dogs were recruited. Methods and materials: Serum TARC concentrations in dogs with cAD and healthy dogs were measured by sandwich ELISA with anti‐canine TARC antibodies. The clinical severity of cAD was scored using the validated Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI‐04). Serum TARC concentrations were compared between dogs with cAD and healthy controls, and their relationship with CADESI‐04 was examined. Serum TARC concentrations also were measured in 20 dogs with cAD treated with prednisolone or oclacitinib for four weeks. Results: Serum TARC concentrations were significantly higher in dogs with cAD than in healthy dogs (P < 0.001). In dogs with cAD, serum TARC concentrations correlated with CADESI‐04 scores (ρ = 0.457, P < 0.01). Furthermore, serum TARC concentrations significantly decreased in treated dogs with the attenuation of clinical signs (P < 0.001). Changes in serum TARC concentrations before and after treatment correlated with those in CADESI‐04 scores (ρ = 0.746, P < 0.001). Conclusions and clinical relevance: Serum TARC concentrations have potential as a clinical and research tool for the objective evaluation of disease severity and therapeutic responses for cAD. [ABSTRACT FROM AUTHOR]

A potent inhibitor of a dual-specificity protein phosphatase, VHR (vaccinia H1 related), was isolated during a screening of microbial metabolites. This inhibitor was identified as 4-isoavenaciolide (4-iA), and was determined to irreversibly inhibit VHR phosphatase activity with a 50% inhibitory concentration of 1.2 μM. Detailed tandem mass spectrometry analyses of proteolysed fragments revealed that two molecules of 4-iA bound a molecule of VHR at the two different fragments: one containing the catalytic domain and the other containing the α6 helix positioned surface domain. As 4-iA possesses a reactive exo-methylene moiety, it is possible that 4-iA inhibits VHR through the direct binding to the cysteine residue in the catalytic site (Cys124). Furthermore, 4-iA inhibited dual-specificity protein phosphatases and tyrosine phosphatases, but did not inhibit serine/threonine phosphatases. These results suggest that 4-iA is a cysteine-targeting inhibitor of protein phosphatases with a common HCX5RS/T motif in the catalytic site. [Copyright &y& Elsevier]

In this article, the authors present chemical equations related to the synthesis of heterocycles-fused naphthoquinones via tandem addition-elimination/intramolecular cyclization and Sonogashira coupling reactions published in the journal "Chemical and Pharmaceutical Bulletin" in 2013.