Estrogen and progesterone are the main pregnancy hormones produced by the placenta. It is well understood that estrogen stimulates angiogenesis in the uterus during the reproductive cycle. Although the estrogen and progesterone signaling pathways are assumed to be associated with placental vascularization and preeclampsia, expression of estrogen receptors (ESRs) and progesterone receptor (PGR) in the placenta have not been well studied. The present study examined the expression patterns of steroid hormone receptors in placentas. Human placenta samples were collected and divided into normal and preeclampsia groups. Results revealed that expression levels of ESR1 were reduced, whereas ESR2 and PGR were elevated in preeclamptic placentas. To generate an in vitro preeclampsia environment, human placenta‑derived BeWo cells were incubated under hypoxic conditions, or treated with catechol‑O‑methyl transferase inhibitor (COMT‑in) or L‑NG‑nitroarginine methyl ester (L‑NAME). Expression levels of ESR1, ESR2 and PGR in hypoxic cells demonstrated similar regulation as those in placentas from women with preeclampsia. Although COMT‑in and L‑NAME did not significantly regulate the expression levels of the receptors, COMT‑in translocated ESR2 and PGR from the nucleus to the cytoplasm, indicating that these receptors were inactivated. These results suggested that ESRs and PGR are associated with symptoms of preeclampsia in the placenta. The expression of ESR1 was reduced in preeclamptic placenta and hypoxic BeWo cells. In addition, the activation of ESR2 and PGR was blocked in placenta cells subjected to COMT‑in treatment. The reduced ESR1 expression and inactivation of ESR2 and PGR proteins may affect the physiological complications of preeclampsia in the placenta.

The growth of 3D nanostructures on conducting substrates through a controlled hydrolysis process of titanium isopropoxide at low‐pH and higher‐pressure is reported. SEM analysis shows the formation of 300–500 nm nanorods, which are symmetrically arranged with an average size of 8–15 µm and 2–3 µm height clusters to form nanoflower‐like structures. 3D nanostructured TiO2 grown on conducting substrates shows efficient in vitro transdifferentiation of human hepatic progenitor cells (hHPCs) into insulin producing cells (T‐iPCs). The physiological functions of transdifferentiated hHPCs confirm the activation of pancreatic transcription factors, which triggers insulin exocytosis during hyperglycemic challenge. The T‐iPCs on TiO2 chips show upregulated expression of master regulator Pdx‐1, β‐cell specific marker Nkx‐6.1, and more importantly C‐peptide similar to human pancreatic β‐cells during hyperglycemic challenge. Intraperitoneally transplanted cellularized TiO2 implants show prompt recovery in blood insulin level and glucose homeostasis in streptozotocin‐induced C57BL6 mice in a glucose regulated manner without immunosuppressant. These implants provide long‐term survival and function of T‐iPCs without eliciting significant immunological reactions and fibrotic tissue/extracellular matrix deposition in vivo, which could be a better technology for developing effective therapeutic options for the management of hyperglycemia.