Objective

Inflammation may influence gestational hyperglycemia, but to date, the data from observational studies is largely limited to results from the third trimester of pregnancy. Our objective was to evaluate first trimester adipocytokine levels. We sought to determine whether first trimester adiponectin and tumor necrosis factor-alpha (TNF)-alpha concentrations were independently associated and predictive of maternal glucose tolerance, as measured by the 1-hour glucose challenge test (GCT), after adjustment for maternal lifestyle behaviors and body mass index (BMI).

Material and methods

Prospective study of pregnant women (n=211) enrolled in the Parity, Inflammation, and Diabetes Study. Nonfasting serum levels of adiponectin and TNF-r2 were measured at 8-14 weeks of pregnancy. GCT results were abstracted from electronic prenatal records. Multiple linear regression models were developed to determine the association of adiponectin and TNF-r2 levels with response to the GCT, adjusting for demographics, pregravid dietary intake and physical activity, first trimester BMI, and gestational weight gain.

Results

At baseline, higher adiponectin concentrations were inversely and statistically significantly associated with maternal response to the GCT [regression coefficient (β) -0.68; 95% confidence interval (CI): -1.29, -0.06). Adjustment for lifestyle factors did not alter the association of adiponectin with the GCT (β -0.74; 95% CI: -1.43, -0.05). After adjustment for first trimester BMI, the association of adiponectin was attenuated and no longer significant (β -0.46; 95% CI: -1.15, 0.24). TNF-r2 levels were not associated with the GCT (β -0.003; 95% CI: -0.011, 0.005).

Conclusions

First trimester adiponectin levels are not predictive of the 1-hour GCT response, but may be a marker for the effect of maternal BMI on glucose response to the GCT.

Castration-resistance prostate cancer (CRPC), also known as hormone-refractory prostate cancer (HRPC), requires immediate attention since it is not only resistant to androgen ablation, chemo- and radiotherapy, but also highly metastatic. Increasing evidence suggests that enrichment of neuroendocrine (NE) cells is associated with CRPC. Here, combined RNA-seq and ChIP-seq analysis reveals that REST is involved in epithelial-mesenchymal transition (EMT) and stemness acquisition in NE differentiated prostate cancer (PCa) cells via direct transcriptional repression of Twist1 and CD44. Specifically we show that short-term knockdown of REST induces NE differentiation of LNCaP cells. Long-term REST knockdown enhanced the expression of Twist1 and CD44, cell migration and sphere formation. Overexpression of REST in hormone-refractory CWR22Rv1 PCa cells significantly reduces Twist1 and CD44 expression, cell migration and sphere formation. Collectively, our study uncovers REST in regulating EMT and stemness properties of NE PCa cells and suggests that REST is a potential therapeutic target for CRPC.