Regulation of human trophoblast syncytialization by histone demethylase LSD1.

A successful pregnancy is critically dependent upon proper placental development and function. During human placentation, villous cytotrophoblast (CTB) progenitors differentiate to form syncytiotrophoblasts (SynTBs), which provide the exchange surface between the mother and fetus and secrete hormones to ensure proper progression of pregnancy. However, epigenetic mechanisms that regulate SynTB differentiation from CTB progenitors are incompletely understood.

Expression, Regulation, and Function of the Calmodulin Accessory Protein PCP4/PEP-19 in Myometrium.

Objective: Calmodulin (CaM) plays a key role in the orchestration of Ca signaling events, and its regulation is considered an important component of cellular homeostasis. The control of uterine smooth muscle function is largely dependent on the regulation of Ca and CaM signaling. The objective of this study was to investigate the expression, function, and regulation of CaM regulatory proteins in myometrium during pregnancy.

Regulation of human placental drug transporters in HCV infection and their influence on direct acting antiviral medications.

Introduction: The objectives of this study were to determine how HCV infection affects placental drug transporters, and to determine the role of drug transporters on the cellular accumulation of direct-acting antiviral drugs in human trophoblasts.

Methods: Eighty-four ABC and SLC transporter genes were first screened in normal and HCV infected pregnant women using PCR profiler array. The changes in expression were confirmed by qPCR and Western blot.

MicroRNA-205 promotes cell invasion by repressing TCF21 in human ovarian cancer.

Background: Ovarian cancer is the leading lethal, gynecological malignancy in the United States. No doubt, the continued morbidity and mortality of ovarian cancer reflects a poor understanding of invasive mechanisms. Recent studies reveal that ovarian cancers express aberrant microRNAs (miRNAs or miRs), some of which have oncogenic or tumor suppressor properties.

HIF-KDM3A-MMP12 regulatory circuit ensures trophoblast plasticity and placental adaptations to hypoxia.

The hemochorial placenta develops from the coordinated multilineage differentiation of trophoblast stem (TS) cells. An invasive trophoblast cell lineage remodels uterine spiral arteries, facilitating nutrient flow, failure of which is associated with pathological conditions such as preeclampsia, intrauterine growth restriction, and preterm birth. Hypoxia plays an instructive role in influencing trophoblast cell differentiation and regulating placental organization.

OVO-like 1 regulates progenitor cell fate in human trophoblast development.

Epithelial barrier integrity is dependent on progenitor cells that either divide to replenish themselves or differentiate into a specialized epithelium. This paradigm exists in human placenta, where cytotrophoblast cells either propagate or undergo a unique differentiation program: fusion into an overlying syncytiotrophoblast. Syncytiotrophoblast is the primary barrier regulating the exchange of nutrients and gases between maternal and fetal blood and is the principal site for synthesizing hormones vital for human pregnancy.

Effect of prostaglandin E2 on multidrug resistance transporters in human placental cells.

Prostaglandin (PG) E2, a major product of cyclooxygenase (COX)-2, acts as an immunomodulator at the maternal-fetal interface during pregnancy. It exerts biologic function through interaction with E-prostanoid (EP) receptors localized to the placenta. The activation of the COX-2/PGE2/EP signal pathway can alter the expression of the ATP-binding cassette (ABC) transporters, multidrug resistance protein 1 [P-glycoprotein (Pgp); gene: ABCB1], and breast cancer resistance protein (BCRP; gene: ABCG2), which function to extrude drugs and xenobiotics from cells.

Induction of xenobiotic receptors, transporters, and drug metabolizing enzymes by oxycodone.

Perturbations of the expression of transporters and drug-metabolizing enzymes (DMEs) by opioids can be the locus of deleterious drug-drug interactions (DDIs). Many transporters and DMEs are regulated by xenobiotic receptors [XRs; e.g.

Human effector/initiator gene sets that regulate myometrial contractility during term and preterm labor.

Objective: Distinct processes govern transition from quiescence to activation during term (TL) and preterm labor (PTL). We sought gene sets that are responsible for TL and PTL, along with the effector genes that are necessary for labor independent of gestation and underlying trigger.

Study Design: Expression was analyzed in term and preterm with or without labor (n=6 subjects/group).

Characterization of the transport, metabolism, and pharmacokinetics of the dopamine D3 receptor-selective fluorenyl- and 2-pyridylphenyl amides developed for treatment of psychostimulant abuse.

The recent discovery of novel high-affinity and selective dopamine D3 receptor (DA D3R) antagonists and partial agonists has provided tools with which to further elucidate the role DA D3R plays in substance abuse. The present study was conducted to evaluate the transport, metabolism, pharmacokinetics, and brain uptake of the DA D3R-selective fluorenyl amides, NGB 2904 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-9H-fluorene-2-carboxamide] fumarate) and JJC 4-077 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3-hydroxybutyl)-9H-fluorene-2-carboxamide hydrochloride], and the 2-pyridylphenyl amides, CJB 090 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-4-(pyridine-2-yl)benzamide hydrochloride] and PG 01037 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-trans-but-2-enyl)-4-(pyridine-2-yl)benzamide hydrochloride], all of which have been studied in animal models of psychostimulant abuse. Additional screening with a panel of human and rat Supersomes was performed for NGB 2904 and PG 01037.

Toxicokinetic study of recombinant human heparin-binding epidermal growth factor-like growth factor (rhHB-EGF) in female Sprague Dawley rats.

Purpose: To determine the toxicity and pharmacokinetics of recombinant heparin-binding epidermal growth factor-like growth factor in female Sprague Dawley rats following intra-bladder and intravenous administration.

Materials And Methods: rhHB-EGF was administered once daily for 6 or 27 days at doses of 3, 10, or 30 microg/kg. 125I-rhHB-EGF was administered on day 7 or 28 for pharmacokinetic analysis.

Identification of interactive gene networks: a novel approach in gene array profiling of myometrial events during guinea pig pregnancy.

Objective: The transition from myometrial quiescence to activation is poorly understood, and the analysis of array data is limited by the available data mining tools. We applied functional analysis and logical operations along regulatory gene networks to identify molecular processes and pathways underlying quiescence and activation.

Study Design: We analyzed some 18,400 transcripts and variants in guinea pig myometrium at stages corresponding to quiescence and activation, and compared them to the nonpregnant (control) counterpart using a functional mapping tool, MetaCore (GeneGo, St Joseph, MI) to identify novel gene networks composed of biological pathways during mid (MP) and late (LP) pregnancy.

The effects of isokinetic contraction velocity on concentric and eccentric strength of the biceps brachii.

The purpose of this investigation was to determine the influence of contraction velocity on the eccentric (ECC) and concentric (CON) torque production of the biceps brachii. After performing warm-up procedures, each male subject (n = 11) completed 3 sets of 5 maximal bilateral CON and ECC isokinetic contractions of the biceps at speeds of 90, 180, and 300 degrees x s(-1) on a Biodex System 3 dynamometer. The men received a 3-minute rest between sets and the order of exercises was randomized.

Recognition, co-internalization, and recycling of an avian riboflavin carrier protein in human placental trophoblasts.

Absorption of riboflavin (RF) across membrane barriers is essential to cellular oxidation reduction processes. Riboflavin carrier protein (RCP), a 37-kDa secretory protein, is proposed to play an important role in RF absorption, although information on the mammalian ortholog remains unclear. This study alludes to the existence of a mammalian RF carrier protein and further characterizes its carrier role and fate using avian RCP in human placental trophoblast (BeWo), another mammalian cell line, monkey kidney (COS-1), and the avian control, chicken hepatic (LMH/2A) cells.

Heat stress induces a biphasic thermoregulatory response in mice.

Previous animal models of heat stress have been compromised by methodologies, such as restraint and anesthesia, that have confounded our understanding of the core temperature (T(c)) responses elicited by heat stress. Using biotelemetry, we developed a heat stress model to examine T(c) responses in conscious, unrestrained C57BL/6J male mice. Before heat stress, mice were acclimated for >4 wk to an ambient temperature (T(a)) of 25 degrees C.