Associations of oxytocin with metabolic parameters in obese women of childbearing age

Introduction: The aim of this study was to compare plasma oxytocin levels in obese women of childbearing age with non-obese women of childbearing age, and to investigate the relationship between plasma oxytocin levels and metabolic parameters (including blood glucose, insulin resistance, blood lipid, and blood pressure). Material and methods: A total of 151 obese women of childbearing age and 160 non-obese women of childbearing age were enrolled in this study. Plasma oxytocin levels were measured by electrochemiluminescence immunoassays. Height, body weight, body mass index (BMI), fasting blood glucose (FBG), fasting insulin (FI), homeostasis model assessment for insulin resistance (HOMA-IR), total triglycerides (TG), total cholesterol (TC), low-density lipoprotein-C (LDL-C), high-density lipoprotein-C (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured in all subjects. Quantile regression analysis was used to analyse the associations of plasmaoxytocin levels with FBG, FI, HOMA-IR, TG, TC, LDL-C, HDL-C, SBP, and DBP. Results: In obese women of childbearing age, plasma oxytocin levels were lower compared with non-obese controls. After adjusting for age, quantile regression analysis showed that the plasma oxytocin levels were inversely associated with HOMA-IR at the quantile level between 0.27 and 0.79 (i.e. the HOMA-IR level of 2.11 and 3.07, respectively), the plasma oxytocin levels were inversely associated with TC after the quantile level of 0.21 (i.e. the TC level of 3.78 ), and the plasma oxytocin levels were inversely associated with LDL-C at all quantile levels of LDL-C. In addition, the plasma oxytocin levels showed a positive association with HDL-C at all quantile levels of HDL-C.No significant associations were found between the plasma oxytocin levels and FBG, FI, TG, SBP, and DBP. Conclusions: Oxytocin deficiency was common in obese women of childbearing age. Oxytocin showed negative correlation with HOMA-IR, TC, and LDL-C, while it showed positive association with HDL-C. Our findings suggest that oxytocin played an important role in inhibiting metabolic disorders associated with obesity in women of childbearing age.

Structures of heat shock factor trimers bound to DNA

Summary: Heat shock factor 1 (HSF1) and 2 (HSF2) play distinct but overlapping regulatory roles in maintaining cellular proteostasis or mediating cell differentiation and development. Upon activation, both HSFs trimerize and bind to heat shock elements (HSEs) present in the promoter region of target genes. Despite structural insights gained from recent studies, structures reflecting the physiological architecture of this transcriptional machinery remains to be determined. Here, we present co-crystal structures of human HSF1 and HSF2 trimers bound to DNA, which reveal a triangular arrangement of the three DNA-binding domains (DBDs) with protein-protein interactions largely mediated by the wing domain. Two structural properties, different flexibility of the wing domain and local DNA conformational changes induced by HSF binding, seem likely to contribute to the subtle differential specificity between HSF1 and HSF2. Besides, two more structures showing DBDs bound to “two-site” head-to-head HSEs were determined as additions to the published tail-to-tail dimer-binding structures

Bis(3-nitro­phen­yl) sulfone

The asymmetric unit of the title compound, C12H8N2O6S, an important diphenyl sulfone derivative, contains one half-mol­ecule; a mirror plane passes through the SO2 group. The dihedral angle between the two symmetry-related benzene rings is 40.10 (13)°. An intra­molecular C—H⋯O hydrogen bond results in the formation of a five-membered ring, which adopts an envelope conformation

TGF-beta 1 induces human alveolar epithelial to mesenchymal cell transition (EMT)

Background: Fibroblastic foci are characteristic features in lung parenchyma of patients with idiopathic pulmonary fibrosis (IPF). They comprise aggregates of mesenchymal cells which underlie sites of unresolved epithelial injury and are associated with progression of fibrosis. However, the cellular origins of these mesenchymal phenotypes remain unclear. We examined whether the potent fibrogenic cytokine TGF-β1 could induce epithelial mesenchymal transition (EMT) in the human alveolar epithelial cell line, A549, and investigated the signaling pathway of TGF-β1-mediated EMT. Methods: A549 cells were examined for evidence of EMT after treatment with TGF-β1. EMT was assessed by: morphology under phase-contrast microscopy; Western analysis of cell lysates for expression of mesenchymal phenotypic markers including fibronectin EDA (Fn-EDA), and expression of epithelial phenotypic markers including E-cadherin (E-cad). Markers of fibrogenesis, including collagens and connective tissue growth factor (CTGF) were also evaluated by measuring mRNA level using RT-PCR, and protein by immunofluorescence or Western blotting. Signaling pathways for EMT were characterized by Western analysis of cell lysates using monoclonal antibodies to detect phosphorylated Erk1/2 and Smad2 after TGF-β1 treatment in the presence or absence of MEK inhibitors. The role of Smad2 in TGF-β1-mediated EMT was investigated using siRNA. Results: The data showed that TGF-β1, but not TNF-α or IL-1β, induced A549 cells with an alveolar epithelial type II cell phenotype to undergo EMT in a time-and concentration-dependent manner. The process of EMT was accompanied by morphological alteration and expression of the fibroblast phenotypic markers Fn-EDA and vimentin, concomitant with a downregulation of the epithelial phenotype marker E-cad. Furthermore, cells that had undergone EMT showed enhanced expression of markers of fibrogenesis including collagens type I and III and CTGF. MMP-2 expression was also evidenced. TGF-β1-induced EMT occurred through phosphorylation of Smad2 and was inhibited by Smad2 gene silencing; MEK inhibitors failed to attenuate either EMT-associated Smad2 phosphorylation or the observed phenotypic changes. Conclusion: Our study shows that TGF-β1 induces A549 alveolar epithelial cells to undergo EMT via Smad2 activation. Our data support the concept of EMT in lung epithelial cells, and suggest the need for further studies to investigate the phenomenon

Macular pigment and serum zeaxanthin levels with Goji berry supplement in early age-related macular degeneration

AIM: To evaluate the efficacy of Goji berry supplementation on improving macular pigment, serum zeaxanthin levels and visual acuity in patients with early age-related macular degeneration (AMD). METHODS: A total of 114 patients (aged from 51 to 92y, mean age 69.53±8.41y) with early AMD were enrolled in our prospective, randomized controlled study. The included patients were assigned randomly to the Goji group (n=57) with 25 g of Goji berries supplementation per day for 90d and the control group (n=57) with their normal diet for 90d. Macular pigment optical density (MPOD) was measured using heterochromatic flicker photometry (HFP). The levels of serum lutein (L)/zeaxanthin (Z) were analyzed using high-performance liquid chromatography (HPLC). MPOD, serum L/Z levels and best corrected visual acuity (BCVA) were recorded at baseline and 90d. RESULTS: In the Goji group, there were no statistically significant differences in the serum L levels between the baseline (0.199±0.149 µmol/mL) and 90d (0.203±0.181 µmol/mL) (t=-0.186, P=0.850); however the serum Z levels were increased at 90d (0.101±0.087 µmol/mL) compared with those at the baseline (0.029±0.032 µmol/mL) (t=6.412, P<0.001). Patients treated with Goji berry for 90d showed an elevated MPOD (0.877±0.202 DU) from the baseline (0.731±0.205 DU) (t=-4.741, P=0.000). In contrast to the control group, the serum Z levels and MPOD were higher in the Goji group at 90d (both P<0.05). At 90d, patients with Goji berry supplementation had a relative decrease in BCVA (0.21±0.18 logMAR) compared with the baseline (0.27±0.20) (t=2.397, P=0.020). CONCLUSION: Overall, daily supplementation with Goji berry for 90d improves MPOD by increasing serum Z levels rather than serum L levels in early AMD patients. Goji berry may be an effective therapeutic intervention for preventing the progression of early AMD

The prebiotic effects of oats on blood lipids, gut microbiota, and short-chain fatty acids in mildly hypercholesterolemic subjects compared with rice: a randomized, controlled trial

20openInternationalInternational coauthor/editorPhytochemicals derived from oats are reported to possess a beneficial effect on modulating dyslipidemia, specifically on lowering total and LDL cholesterol. However, deeper insights into its mechanism remain unclear. In this randomized controlled study, we assigned 210 mildly hypercholesterolemic subjects from three study centers across China (Beijing, Nanjing, and Shanghai) to consume 80 g of oats or rice daily for 45 days. Plasma lipid profiles, short chain fatty acids (SCFAs), and fecal microbiota were measured. The results showed that total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) decreased significantly with both oats and rice intake after 30 and 45 days. The reduction in TC and non-HDL-C was greater in the participants consuming oats compared with rice at day 45 (p = 0.011 and 0.049, respectively). Oat consumption significantly increased the abundance of Akkermansia muciniphila and Roseburia, and the relative abundance of Dialister, Butyrivibrio, and Paraprevotella, and decreased unclassified f-Sutterellaceae. In the oat group, Bifidobacterium abundance was negatively correlated with LDL-C (p = 0.01, r = −0.31) and, TC and LDL-C were negatively correlated to Faecalibacterium prausnitzii (p = 0.02, r = −0.29; p = 0.03, r = −0.27, respectively). Enterobacteriaceae, Roseburia, and Faecalibacterium prausnitzii were positively correlated with plasma butyric acid and valeric acid concentrations and negatively correlated to isobutyric acid. HDL-C was negatively correlated with valeric acid (p = 0.02, r = −0.25) and total triglyceride (TG) was positively correlated to isovaleric acid (p = 0.03, r = 0.23). Taken together, oats consumption significantly reduced TC and LDL-C, and also mediated a prebiotic effect on gut microbiome. Akkermansia muciniphila, Roseburia, Bifidobacterium, and Faecalibacterium prausnitzii, and plasma SCFA correlated with oat-induced changes in plasma lipids, suggesting prebiotic activity of oats to modulate gut microbiome could contribute towards its cholesterol-lowering effect.openXu, Dengfeng; Feng, Meiyuan; Chu, YiFang; Wang, Shaokang; Shete, Varsha; Tuohy, Kieran M; Liu, Feng; Zhou, Xirui; Kamil, Alison; Pan, Da; Liu, Hechun; Yang, Xian; Yang, Chao; Zhu, Baoli; Lv, Na; Xiong, Qian; Wang, Xin; Sun, Jianqin; Sun, Guiju; Yang, YuexinXu, D.; Feng, M.; Chu, Y.; Wang, S.; Shete, V.; Tuohy, K.M.; Liu, F.; Zhou, X.; Kamil, A.; Pan, D.; Liu, H.; Yang, X.; Yang, C.; Zhu, B.; Lv, N.; Xiong, Q.; Wang, X.; Sun, J.; Sun, G.; Yang, Y

RNF216 Regulates the Migration of Immortalized GnRH Neurons by Suppressing Beclin1-Mediated Autophagy

RNF216, encoding an E3 ubiquitin ligase, has been identified as a causative gene for Gordon Holmes syndrome, characterized by ataxia, dementia, and hypogonadotropic hypogonadism. However, it is still elusive how deficiency in RNF216 leads to hypogonadotropic hypogonadism. In this study, by using GN11 immature GnRH neuronal cell line, we demonstrated an important role of RNF216 in the GnRH neuron migration. RNA interference of RNF216 inhibited GN11 cell migration, but had no effect on the proliferation of GN11 cells or GnRH expression. Knockdown of RNF216 increased the protein levels of its targets, Arc and Beclin1. RNAi of Beclin1, but not Arc, normalized the suppressive effect caused by RNF216 knockdown. As Beclin1 plays a critical role in the autophagy regulation, we further demonstrated that RNAi of RNF216 led to increase in autophagy, and autophagy inhibitor CQ and 3-MA rescued the GN11 cell migration deficit caused by RNF216 knockdown. We further demonstrated that pharmacological increase autophagy by rapamycin could suppress the GN11 cell migration. We thus have identified that RNF216 regulates the migration of GnRH neuron by suppressing Beclin1 mediated autophagy, and indicated a potential contribution of autophagy to the hypogonadotropic hypogonadism