Cytokines may cause an acquired growth hormone (GH) resistance in patients with inflammatory diseases. Anabolic effects of GH are mediated through activation of STAT5 transcription factors. We have reported that TNF-alpha suppresses hepatic GH receptor (GHR) gene expression, whereas the cytokine-inducible SH2-containing protein 1 (Cis)/suppressors of cytokine signaling (Socs) genes are upregulated by TNF-alpha and IL-6 and inhibit GH activation of STAT5. However, the relative importance of these mechanisms in inflammatory GH resistance was not known. We hypothesized that IL-6 would prevent GH activation of STAT5 and that this would involve Cis/Socs protein upregulation. GH +/- LPS was administered to TNF receptor 1 (TNFR1) or IL-6 null mice and wild-type (WT) controls. STAT5, STAT3, GHR, Socs 1-3, and Cis phosphorylation and abundance were assessed by using immunoblots, EMSA, and/or real time RT-PCR. TNF-alpha and IL-6 abundance were assessed by using ELISA. GH activated STAT5 in WT and TNFR1 or IL-6 null mice. LPS pretreatment prevented STAT5 activation in WT and TNFR1 null mice; however, STAT5 activation was preserved in IL-6 null mice. GHR abundance did not change with LPS administration. Inhibition of STAT5 activation by LPS was temporally associated with phosphorylation of STAT3 and upregulation of Cis and Socs-3 protein in WT and TNFR1 null mice; STAT3, Cis, and Socs-3 were not induced in IL-6 null mice. IL-6 inhibits hepatic GH signaling by upregulating Cis and Socs-3, which may involve activation of STAT3. Therapies that block IL-6 may enhance GH signaling in inflammatory diseases.
Objective: To evaluate associations between early pregnancy 25-hydroxyvitamin D (25[OH]D) concentrations and antepartum depression and anxiety symptoms and potential modifiers thereof. Materials and Methods: In a pregnancy cohort (N = 498), we examined cross-sectional associations of early pregnancy (mean = 15.4 weeks gestation) serum 25[OH]D concentrations and depression and anxiety symptoms. Symptoms were measured using Depression, Anxiety, and Stress Scales (DASS-21) and Patient Health Questionnaire Depression Module (PHQ-9) instruments. Regression models were fit and effect modification by prepregnancy body mass index and leisure-time physical activity (LTPA) were assessed using interaction terms and stratified analyses. ( < 28.9 ng/mL) had 1.11 higher PHQ-9 scores than those in the highest quartile ( ‡ 39.5 ng/mL, p < 0.05). However, associations were attenuated and statistically insignificant in fully adjusted models. Inverse associations of 25[OH]D with depression symptoms were significant among participants who reported no LTPA, but not among women who reported any LTPA (interaction p = 0.018). Conclusions: Our study provides modest evidence for inverse cross-sectional associations of early pregnancy maternal vitamin D concentrations with antepartum depression symptoms. We also observed that these associations may be modified by physical activity.
We determined the prevalence and risk factors of gender-based violence among 1,330 female college students in Awassa, Ethiopia. Participants completed a self-administered questionnaire that collected information on experience with gender-based violence during three time periods (lifetime, since enrolling in college, and current academic year). The lifetime prevalence of gender-based violence was 59.9%; 46.1% of participants reported experiencing gender-based violence since enrolling in college, and the prevalence was 40.3% during the current academic year. Protestant religious affiliation, childhood rural residence, alcohol consumption, combined alcohol and khat (a natural stimulant) consumption, and witnessing domestic violence as a child were risk factors of lifetime experience with gender-based violence. Counseling for women who have experienced violence and awareness-raising programs aimed at preventing gender-based violence are needed in colleges.
Background While associations of vitamin D deficiency with Type 2 diabetes have been well demonstrated, investigations of vitamin D and risk of gestational diabetes mellitus (GDM) reported inconsistent findings. We examined associations of vitamin D status with GDM. Methods In a nested case-cohort study (135 GDM cases and 517 non-GDM controls), we measured maternal serum Vit-D status (total 25[OH]D and 25[OH]D3) in early pregnancy (16 weeks on average) using liquid chromatography-tandem mass spectroscopy. GDM was diagnosed according to the ADA guidelines. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CI) using logistic regression models. Results GDM cases had lower mean total 25[OH]D (27.3 vs. 29.3ng/ml) and 25[OH]D3 (23.9 vs. 26.7ng/ml) concentrations compared with women who did not develop GDM (both P-values<0.05). Overall, 25[OH]D3 concentrations, but not total 25[OH]D concentrations, were significantly associated with GDM risk. A 5ng/ml increase in 25[OH]D3 concentration was associated with a 14% decrease in GDM risk (P-value=0.02). Women in the lowest quartile for 25[OH]D3 concentration had a 2-fold (95%CI 1.15-3.58) higher risk of GDM compared with women in the highest quartile (P-value for trend<0.05). Conclusions Early pregnancy vitamin D status, particularly 25[OH]D3, is inversely associated with GDM risk.
Little epidemiologic research has focused on the mental health effects of gender-based violence among sub-Saharan African women. The objective of this study was to assess risk of depression and depressive symptoms among 1,102 female undergraduate students who were victims of gender-based violence. Students who reported experience of any gender-based violence were nearly twice as likely to be classified as having moderate depression during the academic year (OR = 1.98, 95% CI = 1.39-2.82) as compared with nonabused students. Compared with nonabused students, those who had experienced both physical and sexual abuse were 4 times more likely to report either moderately severe (OR = 4.32, 95% CI = 2.00-9.31) or severe depressive symptoms (OR = 4.19, 95% CI = 1.01-17.43). Our findings, consistent with previous studies, support the thesis that women's mental health status is adversely affected by exposure to gender-based violence.
Our results support the hypothesis that maternal iron deficiency anemia is associated with an increased risk of abruptio placentae.
Human placental (hPLAP) and germ cell (PLAP-like) alkaline phosphatases are polymorphic and heat-stable enzymes. This study was designed to develop specific immunoassays for quantifying hPLAP and PLAP-like enzyme activity (EA) in sera of cancer patients, pregnant women, or smokers. Polyclonal sheep anti-hPLAP antibodies were purified by affinity chromatography with whole hPLAP protein (ICA-PLAP assay) or a synthetic peptide (aa 57–71) of hPLAP (ICA-PEP assay); the working range was 0.1–11 U/L and cutoff value was 0.2 U/L EA for nonsmokers. The intra- and interassay coefficients of variation were 3.7%–6.5% (ICA-PLAP assay) and 9.0%–9.9% (ICA-PEP assay). An insignificant cross-reactivity was noted for high levels of unheated intestinal alkaline phosphatase in ICA-PEP assay. A positive correlation between the regression of tumor size and EA was noted in a child with embryonal carcinoma. It can be concluded that ICA-PEP assay is more specific than ICA-PLAP, which is still useful to detect other PLAP/PLAP-like phenotypes.
Parathyroid hormone (PTH) functions in part by regulating osteoblast cytokine expression. We recently demonstrated that PTH induced a rapid and transient increase in interleukin-6 (IL-6) mRNA expression in rat bones in vivo. To determine the molecular basis of this effect, we analyzed the human IL-6 promoter fused (-1,179 to +9) with the chloramphenicol acetyltransferase (CAT) reporter gene in stable transfections into human osteoblast-like osteosarcoma SaOS-2 cells. We compared the effects of PTH on IL-6 expression with adenylate cyclase activator forskolin, PKC activator phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, interleukin-1 alpha (IL-1 alpha), prostaglandin E-2 (PGE-2), RS-66271 (a parathyroid hormone-related peptide analog), and platelet-derived growth factor-BB (PDGF-BB). Analyses of cell clones showed that IL-6 promoter expression was extremely low in the unstimulated state. Exposure to PTH (0.001-100 nM) for 12 h stimulated CAT expression in a dose-dependent manner (200-500% of control). Treatment with IL-1 alpha was more potent than PTH in inducing transcription of the IL-6 promoter (900-1,000%). Activation of the cAMP-PKA pathway by treatment with forskolin induced a comparable level of induction with PTH. Together, the effects of PTH and forskolin were additive. RS-66271, previously shown to have PTH-like effects, induced a comparable level of IL-6 promoter expression. When examined together, PTH+RS-66271 effects were comparable to PTH effects alone. Exposure to PGE-2, PMA, PDGF-BB, or A23187 for 12 h did not significantly alter IL-6 promoter expression. These results demonstrate PTH, forskolin, the PTHrP analog RS-66271, and IL-1 alpha stimulate IL-6 expression by stimulating gene transcription. The response to forskolin suggests that the messenger system mediated by PKA is sufficient to induce IL-6 expression.
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