Materials and Methods: All groups of hFOB 1.19 cells were induced with 12.5 μg/ml of BPA except the control (Ctrl) group. Meanwhile, treated groups received phytoestrogens; Daidzein (Dz), Genistein (Gt), Equol (Eq) and 17β-oestradiol (Est) in different concentrations for 24 hr duration.
Results: We found that the protein expression of non-classical oestrogen-related receptor (ERRG) was highly expressed in BPA group, whereas classical oestrogen receptor alpha (ERα) and oestrogen receptor beta (ERβ) were relatively increased with phytoestrogens treatment under BPA exposure. The dense actin cytoskeletal filaments were also observed. qRT-PCR showed up-regulation of mitogen-activated protein kinase 3 (MAPK3) and G protein-coupled receptor 30 (GPR30) expressions; significant down-regulation of ERRG and up-regulation of ERα and ERβ were observed in phytoestrogens-treated cells, which was supported by the increased expressions of oestrogen receptor 1 (ESR1) and oestrogen receptor 2 (ESR2).
Conclusion: Phytoestrogens improved the deteriorative effect of BPA via down-regulation of ERRG in hFOB 1.19 cells. This study showed that the efficacy of consumption of phytoestrogens in rendering them as potential therapeutic strategy in combating the adverse bone effects of BPA.
MATERIALS & METHODS: This is a case-control study consisting of 47 MDD patients and 47 healthy controls. MDD patients were treated with antidepressant drugs according to their physician's choice. The severity of MDD was assessed using Beck Depression Inventory (BDI) and Montgomery-Asberg Depression Rating Scale (MADRS) at the time of recruitment. Healthy controls completed the Depression Anxiety Scoring System (DASS21) questionnaire to ensure they were in good mental health without history of MDD. The percentage and absolute count of CD4+ CD25+ Tregs and CD4+ CD25+ FOXP3+ Tregs were identified by multiparameter flow cytometry.
RESULTS: The percentage and absolute count of CD4+ CD25+ Treg cells were significantly higher in MDD patients than in healthy controls (P<0.001, in both cases). Likewise, the percentage and absolute count of CD4+ CD25+ FOXP3+ Treg cells were also significantly higher in MDD patients compared to healthy controls (P=0.003 and P=0.002, respectively). However, there was no significant correlation between the percentage and absolute count of CD4+ CD25+ Treg and CD4+ CD25+ FOXP3+ Treg cells with BDI or MADRS score.
CONCLUSIONS: Our results suggest that antidepressant treatments contributed to an upregulation of Tregs in MDD patients.
RESULTS: Key biological processes linked to upregulated genes (n = 214) included 'response to endoplasmic reticulum stress' and 'lipid metabolism', and processes representing downregulated genes (n = 357) included 'DNA-conformation change' and 'cellular lipid metabolism'.
CONCLUSIONS: Exposure of C. elegans to Pf-fraction 5 induces significant changes in the transcriptome. Gene ontology analysis suggests that Pf-fraction 5 induces endoplasmic reticulum and mitochondrial stress, and the changes in gene expression are either a direct or indirect consequence of this. Further work is required to assess specific responses to sub-fractions of Pf-fraction 5 in time-course experiments in C. elegans, to define the chemical(s) with potent anthelmintic properties, to attempt to unravel their mode(s) of action and to assess their selectivity against nematodes.
METHODS AND RESULTS: We investigated steady-state messenger RNA levels of 84 histone-modifying enzymes and related regulators in colony-stimulating factor-1 differentiated primary human macrophages using quantitative polymerase chain reaction. IFN-γ or IL-4 treatment for 6-48 h changed 11 mRNAs significantly. IFN-γ increased CIITA, KDM6B, and NCOA1, and IL-4 also increased KDM6B by 6 h. However, either cytokine decreased AURKB, ESCO2, SETD6, SUV39H1, and WHSC1, whereas IFN-γ alone decreased KAT2A, PRMT7, and SMYD3 mRNAs only after 18 h, which coincided with decreased cell proliferation. Rendering macrophages quiescent by growth factor starvation or adenovirus-mediated overexpression of p27(kip1) inhibited expression of AURKB, ESCO2, SUV39H1, and WHSC1, and mRNA levels were restored by overexpressing the S-phase transcription factor E2F1, implying their expression, at least partly, depended on proliferation. However, CIITA, KDM6B, NCOA1, KAT2A, PRMT7, SETD6, and SMYD3 were regulated independently of effects on proliferation. Silencing KDM6B, the only transcriptional activator upregulated by both IFN-γ and IL-4, pharmacologically or with short hairpin RNA, blunted a subset of responses to each cytokine.
CONCLUSION: These findings demonstrate that IFN-γ or IL-4 can regulate the expression of histone acetyl transferases and histone methyl transferases independently of effects on proliferation and that upregulation of the histone demethylase, KDM6B, assists phenotypic polarization by both cytokines.