Background: Atopic dermatitis (AD) is a chronic relapsing inflammation usually observed in patients with an individual or a familial history of atopic diseases, precipitated by environmental factors including mite antigens (Ag). However, the exact etiology of AD is unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is necessary. In this study, we developed a new animal model of AD induced by mite Ag in NC/Nga mice. Methods: We injected the extracts of mite Ag intradermally at the ventral side of the ear of SPF NC/Nga mice on days 0, 2, 4, 7, 9, 11, 14 and 16, and measured the clinical symptoms and the ear thickness. On day 18, we collected blood and submandibular lymph nodes (LN) of the immunized ear to perform a histochemical analysis, and to measure the plasma immunoglobulins and cytokines. Results: The NC/Nga mice immunized with mite Ag suffered from AD-like skin lesions including erythema followed by edema, excoriation and scaling. The histological and immunohistochemical examinations of the affected skin showed epidermal hyperplasia with hyperkeratosis, severe infiltration of CD4+ T lymphocytes, eosinophils and macrophages, and degranulation of mast cells. The total plasma IgE level was markedly elevated in mite Ag-treated mice. LN cells of mice immunized with mite Ag synthesized IgE in an Ag-dependent manner and secreted interleukin-4 (IL-4) and IL-5 but not interferon-γ. Conclusions: NC/Nga mice treated with mite Ag manifest clinical and immunological aspects similar to patients with AD, suggesting that this model is suitable for exploring the pathogenesis of human AD.

In experimental studies, tachykinins, especially substance P (SP), cause many of the pathophysiological features of neurogenic inflammation. It is unclear whether these peptides are involved in human airway inflammation in diseases such as asthma and chronic bronchitis. To elucidate the relation between neurogenic inflammation and airway inflammatory diseases, we examined the SP concentration in sputum after hypertonic saline inhalation challenge in patients with asthma, patients with chronic bronchitis, and normal volunteers. SP concentration was measured by radioimmunoassay. The sputum SP concentration was significantly higher in patients with asthma (mean +/- SEM, 17.7 +/- 2.4 fmol/ml; p < 0.01) and patients with chronic bronchitis (25.6 +/- 5.5 fmol/ml; p < 0.01) than in normal volunteers (1.1 +/- 0.4 fmol/ml). In patients with asthma, the SP concentration was significantly related to the eosinophil cell count in induced sputum. In all subjects, the SP concentration in induced sputum correlated with FEV1/FVC. These data suggest that neurogenic inflammation may be involved in the airway inflammatory process and subsequent airway narrowing not only in asthma but also in chronic bronchitis.

This study reports the isolation and characterisation of six new metabolites with ‘gracilin’-type carbon skeletons and of aplytandiene-3 from the Australian nudibranch Goniobranchus splendidus. The structure of gracilin G is revised, and the C-6 configuration deduced by comparison of calculated 3JC/H values with values measured using the EXSIDE pulse sequence. A lactone isolated from Goniobranchus daphne contains a rearranged spongionellin-type skeleton. Screening of selected metabolites revealed significant cytotoxicity against a HeLa S3 cell line by five of the new terpenes.

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While high-colibactin-producing Escherichia coli is thought to be associated with colorectal oncogenesis, this study is complicated part due to an inability to isolate colibactin adequately. Here, we created fluorescent probes activated by ClbP, the colibactin-maturing peptidase, to identify high-colibactin-producing strains. Our probe served as a valuable clinical diagnostic tool that allowed simple high-throughput diagnostic screening of clinical samples. Furthermore, the probe also allowed identification of high-colibactin producers that would help advance our understanding of colibactin biosynthesis.

We aimed to investigate metabolites associated with the 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) in patients with rheumatoid arthritis (RA) using capillary electrophoresis quadrupole time-of-flight mass spectrometry. Plasma and urine samples were collected from 32 patients with active RA (DAS28-ESR≥3.2) and 17 with inactive RA (DAS28-ESR<3.2). We found 15 metabolites in plasma and 20 metabolites in urine which showed a significant but weak positive or negative correlation with DAS28-ESR. When metabolites between active and inactive patients were compared, 9 metabolites in plasma and 15 in urine were found to be significantly different. Consequently, we selected 11 metabolites in plasma and urine as biomarker candidates which significantly correlated positively or negatively with DAS28-ESR, and significantly differed between active and inactive patients. When a multiple logistic regression model was built to discriminate active and inactive cohorts, three variables—histidine and guanidoacetic acid from plasma and hypotaurine from urine—generated a high area under the receiver operating characteristic (ROC) curve value (AUC = 0.8934). Thus, this metabolomics approach appeared to be useful for investigating biomarkers of RA. Combination of plasma and urine analysis may lead to more precise and reliable understanding of the disease condition. We also considered the pathophysiological significance of the found biomarker candidates.

Epoxides are highly useful synthons and biosynthons in the construction of complex natural products during total synthesis and biosynthesis, respectively. Among enzyme-catalyzed epoxide transformations, a notably missing reaction, compared to the synthetic toolbox, is cationic rearrangement that takes place under strong acids. This is a challenging transformation for enzyme catalysis, as stabilization of the carbocation intermediate upon epoxide cleavage is required. Here, we discovered two Brønsted acid enzymes that can catalyze two unprecedented epoxide transformations in biology. PenF from the penigequinolone pathway catalyzes a cationic epoxide rearrangement under physiological conditions to generate a quaternary carbon center, while AsqO from the aspoquinolone pathway catalyzes a 3-exo-tet cyclization to forge a cyclopropane-tetrahydrofuran ring system. The discovery of these new epoxide-modifying enzymes further highlights the versatility of epoxides in complexity generation during natural product biosynthesis.

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