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https://www.selleckchem.com/products/zn-c3.html In the multi-step differentiation protocol used to generate pancreatic endocrine cells from human pluripotent stem cells, the induction of NGN3+ endocrine precursors from the PDX1+/NKX6.1+ pancreatic endoderm is crucial for efficient endocrine cell production. Here, we demonstrate that transient, not prolonged FOXO1 inhibition results in enhanced NGN3+ endocrine precursors and hormone-producing cell production. FOXO1 inhibition does not directly induce NGN3 expression but stimulates PDX1+/NKX6.1+ cell proliferation. NOTCH activity, whose suppression is important for Ngn3 expression, is not suppressed but Wnt signaling is stimulated by FOXO1 inhibition. Reversely, Wnt inhibition suppresses the effects of FOXO1 inhibitor. These findings indicate that FOXO1 and Wnt are involved in regulating the proliferation of PDX1+/NKX6.1+ pancreatic endoderm that gives rise to NGN3+ endocrine precursors. BACKGROUND Hypertensive pregnancy disorders (HPD) are associated with dysfunction of the autonomic nervous system. Cardiac autonomic functions can be assessed by heart rate variability (HRV) measurements. OBJECTIVE To study whether HRV detects differences in the function of the autonomic nervous system between pregnant women with HPD compared to normotensive pregnant women and between women with a history of a pregnancy complicated by HPD compared to women with a history of an uncomplicated pregnancy. METHODS A systematic search was performed in Medline, EMBASE, and CENTRAL to identify studies comparing HRV between pregnant women with HPD or women with a history of HPD to women with (a history of) normotensive pregnancies. RESULTS The search identified 523 articles of which 24 were included in this review, including 850 women with (a history of) HPD and 1205 normotensive controls. The included studies showed a large heterogenicity. A decrease in overall HRV was found in preeclampsia (PE), compared to normotensive pregnant controls. A

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