Nobiletin suppresses adipocyte differentiation of 3T3-L1 cells by an insulin and IBMX mixture induction.

BACKGROUND: Nobiletin is a citrus flavonoid which possesses the flavone structure with six methoxy groups. Although nobiletin has been reported to display anti-inflammatory, anti-tumor, and anti-diabetes activities, its effect on adipocyte differentiation remained unclear. In the present study, we investigated the effect of nobiletin on the differentiation of 3T3-L1 preadipocytes into adipocytes. METHODS: 3T3-L1 preadipocytes were treated with nobiletin under various differentiation conditions. The effect of nobiletin on adipocyte differentiation was evaluated by oil red O staining, real-time RT-PCR, and Western blotting. RESULTS: Nobiletin significantly suppressed the differentiation of 3T3-L1 preadipocytes into adipocytes, upon induction with insulin together with a cAMP elevator such as 3-isobutyl-1-methylxanthine (IBMX), by downregulating the expression of the gene encoding peroxisome proliferator-activated receptor (PPAR) γ2. In addition, nobiletin decreased the phosphorylation of cAMP-response element-binding protein (CREB) and strongly enhanced the phophorylation of signal transducer and activator of transcription (STAT) 5. GENERAL SIGNIFICANCE: Nobiletin has a suppressive effect on the differentiation of preadipocytes into adipocytes when cells were induced with a general differentiation cocktail such as insulin, IBMX, and dexamethasone.

Neural basis underlying the sense of coherence in medical professionals revealed by the fractional amplitude of low-frequency fluctuations.

Although mitigating burnout has long been a pressing issue in healthcare, recent global disasters, including the COVID-19 pandemic and wars, have exacerbated this problem. Medical professionals are frequently exposed to diverse job-induced distress; furthermore, the importance of people's sense of coherence (SOC) over work has been addressed to better deal with burnout. However, the neural mechanisms underlying SOC in medical professionals are not sufficiently investigated. In this study, the intrinsic fractional amplitude of low-frequency fluctuations (fALFF) were measured as an indicator of regional brain spontaneous activity using resting-state functional magnetic resonance imaging in registered nurses. The associations between participants' SOC levels and the fALFF values within brain regions were subsequently explored. The SOC scale scores were positively correlated with fALFF values in the right superior frontal gyrus (SFG) and the left inferior parietal lobule. Furthermore, the SOC levels of the participants mediated the link between their fALFF values in the right SFG and the depersonalization dimension of burnout. The results deepened the understanding of the counter role of SOC on burnout in medical professionals and may provide practical insights for developing efficient interventions.

Proteose peptone fraction of bovine milk depressed IgE production in vitro and in vivo.

Proteose peptone (PP) is a heat-stable and acid-soluble protein in milk whey. We reveal in this study the IgE production-suppressing activity of the PP fraction in bovine milk. The PP fraction suppressed IgE production by human myeloma cell line U266 cells by depressing the IgE mRNA expression. The suppressive activity of the PP fraction was facilitated by trypsin digestion. An oral administration of the PP fraction significantly decreased the levels of total and ovalbumin (OVA)-specific IgE in the serum collected from OVA-sensitized mice. However, the serum levels of other Ig classes in OVA-sensitized mice were not affected by the intake of the PP fraction. The PP fraction suppressed the mRNA expression level of IgE in mice splenocytes collected from OVA-sensitized mice. Moreover, the B cell population in the spleen was decreased, while the T cell population was increased by administering the PP fraction. These results suggest that the PP fraction modified the B/T cell balance.

Heavy oil fractions induce negative influences on mouse immune system.

It is well known that heavy oil such as pollutant caused serious influences on the marine ecosystem. We may suffer from various disorders in our body via intake of marine foods polluted with heavy oil. However the influences of heavy oil on our immune system have not yet been clarified. Here we show the effects of heavy oil extracts, water-soluble fraction (WSF), methanol-soluble fraction (MSF) and ethanol-soluble fraction (ESF), on immunoglobulin production of mouse splenocytes. All extracts increased IgA productivity of splenocytes. In oral administration, shrinkage of the immune organs such as spleen or thymus was observed in only WSF-administrated mice at least during 7 days. The amount of IgG production level in splenocytes cultured medium and sera were reduced by each extract administration. A flowcytometry method, to monitor splenocytes of WSF-administrated mice, has been set up using double staining with B and T cell-specific surface antibody. The results from cell population analysis indicated that B cells, including plasma cells producing antibody were reduced. The decrease in IgG level in sera was caused by reduction of plasma cells in spleen. Hence, it is suggested that reduction of Ig production was affected by the chemical compounds contained in WSF possibly such as polycyclic aromatic hydrocarbons (PAHs) through the estrogen receptor expressed in lymphocytes.