Nobiletin decreases inflammatory symptoms and markers in murine colitis as well as fibrotic collagen deposition and expression. Thus, nobiletin could be a potential new agent in therapy of chronic colitis.

Objectives: Volatile organic compounds (VOCs) in the breathing air were found to be altered in schizophrenia patients compared to healthy participants. The aim of this study was to confirm these findings and to examine for the first time whether these VOCs are stable or change in concentration during the early treatment course. Moreover, it was investigated whether there is a correlation of the VOCs with the existing psychopathology of schizophrenia patients, i.e., whether the concentration of masses detected in the breath gas changes when the psychopathology of the participants changes. Methods: The breath of a total of 22 patients with schizophrenia disorder was examined regarding the concentration of VOCs using proton transfer reaction mass spectrometry. The measurements were carried out at baseline and after two weeks at three different time points, the first time immediately after waking up in the morning, after 30 min, and then after 60 min. Furthermore, 22 healthy participants were investigated once as a control group. Results: Using bootstrap mixed model analyses, significant concentration differences were found between schizophrenia patients and healthy control participants (m/z 19, 33, 42, 59, 60, 69, 74, 89, and 93). Moreover, concentration differences were detected between the sexes for masses m/z 42, 45, 57, 69, and 91. Mass m/z 67 and 95 showed significant temporal changes with decreasing concentration during awakening. Significant temporal change over two weeks of treatment could not be detected for any mass. Masses m/z 61, 71, 73, and 79 showed a significant relationship to the respective olanzapine equivalents. The length of hospital stay showed no significant relationship to the masses studied. Conclusion: Breath gas analysis is an easy-to-use method to detect differences in VOCs in the breath of schizophrenia patients with high temporal stability. m/z 60 corresponding to trimethylamine might be of potential interest because of its natural affinity to TAAR receptors, currently a novel therapeutic target under investigation. Overall, breath signatures seemed to stable over time in patients with schizophrenia. In the future, the development of a biomarker could potentially have an impact on the early detection of the disease, treatment, and, thus, patient outcome.

Background and objectivesWnt-inhibitor sclerostin has anti-anabolic effects on bone formation by negatively regulating osteoblast differentiation. Loss of sclerostin expression results in high bone mass and bone strength in patients with sclerosteosis and sclerostin knockout mice. Therefore, antibody-mediated inhibition of sclerostin is currently evaluated for the treatment of osteoporosis in humans. Since it has been shown that sclerostin is upregulated by TNFα, we studied its impacton inflammatory arthritis using RA mouse models such as the human TNF transgenic (hTNFtg) model, the G6PI-induced arthritis model and the K/BxN serum transfer-induced arthritis model.Materials and methodsSclerostin knockout (sost-/-) mice were crossed with hTNFtg mice to generate sost-/ -/hTNFtg. Mice with serum transfer-induced arthritis were generated by injection of arthritogenic serum collected from K/BxN mice in sost-/- and wild type (WT) mice. Arthritis was induced in DEREG mice by immunisation with recombinant glucose-6-phosphate isomerase (G6PI). To switch to the non-remitting G6PI-induced arthritis, Foxp3+ regulatory T-cells were depleted by diphtheria toxin. hTNFtg and G6PI-induced arthritis mice were treated with a neutralising antibody against human and murine sclerostin. Clinical disease severity, bone erosion, cartilage destruction and pannus formation were evaluated by histomorphometric, x-ray and micro-CT analysis. Sclerostin expression and p38 activation was assessed by immunohistochemistry, western-blot-analysisor RT-PCR. Knockdown of LRP5 and LRP6 was performed by transfection of fibroblast-like synoviocytes (FLS) with siRNA.ResultsThis study showed for the first time that TNFα induces sclerostin expressionin RA-FLS. Surprisingly, the lack of sclerostin and its antibody-mediated inhibition led to deterioration of RA-like disease in hTNFtgmice with enhanced pannus formation and joint destruction. Suggesting a specific role for sclerostin in TNFα signalling, inhibition of sclerostin also failed to improve clinical signs and joint destruction in the partially TNFα-dependent G6PI-induced arthritis, but ameliorated disease severity in K/BxN serum transfer-induced arthritis,in which TNFα plays only a minor role. FLS from sost-/- /hTNFtg mice displayed increased TNFα-mediated p38 activation, a key step in arthritis development. In turn, sclerostin effectively blocked TNFα-induced but not IL-1-induced activation of p38 with participation of the canonical Wnt receptor LRP6.ConclusionCollectively, these data demonstrated that sclerostin appears to have a protective function in TNF-mediated chronic inflammation.