Mouse Bone Marrow-Derived Mesenchymal Stem Cells Alleviate Perinatal Brain Injury Via a CD8 T Cell Mechanism in a Model of Intrauterine Inflammation.

The objective of this study was to determine if mouse bone marrow-derived mesenchymal stem cells (BMMSCs) ameliorate preterm birth and perinatal brain injury induced by intrauterine inflammation (IUI). A mouse model of IUI-induced perinatal brain injury at embryonic (E) day 17 was utilized. BMMSCs were derived from GFP-transgenic mice and phenotypically confirmed to be CD44, Sca-1, CD45, CD34, CD11b, and CD11c by flow cytometry and sorted by fluorescence-activated cell sorting (FACS).

Magnesium sulfate inhibits inflammation through P2X7 receptors in human umbilical vein endothelial cells.

Background: Magnesium sulfate (MgSO) is utilized for fetal neuroprotection in preterm birth but its mechanism of action is still poorly understood. P2X7 receptor (P2X7R) is required for secretion of IL-1β, and can be blocked by divalent cations such as magnesium (Mg) and its own antagonist, Brilliant Blue G (BBG). We sought to determine whether during inflammation MgSO can block endothelial IL-1β secretion, using an in-vitro model.

Maternal inflammation leads to different mTORC1 activity varied by anatomic locations in mouse placenta†.

Maternal inflammation (MI) is associated with many adverse perinatal outcomes. The placenta plays a vital role in mediating maternal-fetal resource allocation. Studies have shown that MI contributes to placental dysfunction, which then leads to adverse birth outcomes and high health risks throughout childhood.

Exposure to systemic and intrauterine inflammation leads to decreased pup survival via different placental mechanisms.

Problem: Exposure to systemic maternal inflammation (i.e., maternal sepsis, influenza, human immunodeficiency virus, or pyelonephritis) and intrauterine (IU) inflammation (i.

Melatonin for prevention of placental malperfusion and fetal compromise associated with intrauterine inflammation-induced oxidative stress in a mouse model.

Melatonin has been shown to reduce oxidative stress and mitigate hypercoagulability. We hypothesized that maternally administered melatonin may reduce placental oxidative stress and hypercoagulability associated with exposure to intrauterine inflammation (IUI) and consequently improve fetoplacental blood flow and fetal sequelae. Mice were randomized to the following groups: control (C), melatonin (M), lipopolysaccharide (LPS; a model of IUI) (L), and LPS with melatonin (ML).

Administration of melatonin for prevention of preterm birth and fetal brain injury associated with premature birth in a mouse model.

Problem: Maternal inflammation leads to preterm birth and perinatal brain injury. Melatonin, through its anti-inflammatory effects, has been shown to be protective against inflammation-induced perinatal adverse effects. However, the immunomodulatory effects of melatonin on preterm birth and prematurity-related morbidity remain unknown.

IL-1 receptor antagonist therapy mitigates placental dysfunction and perinatal injury following Zika virus infection.

Zika virus (ZIKV) infection during pregnancy causes significant adverse sequelae in the developing fetus, and results in long-term structural and neurologic defects. Most preventive and therapeutic efforts have focused on the development of vaccines, antivirals, and antibodies. The placental immunologic response to ZIKV, however, has been largely overlooked as a target for therapeutic intervention.

Placental malperfusion in response to intrauterine inflammation and its connection to fetal sequelae.

Exposure to intrauterine inflammation (IUI) is associated with short- and long-term adverse perinatal outcomes. However, little data exist on utilizing placenta to prognosticate fetal injury in this scenario. Our study aimed to utilize imaging modalities to evaluate mechanisms contributing to placental injury following IUI exposure and correlated it to concomitant fetal brain injury.

Maternal Supplementation of Low Dose Fluoride Alleviates Adverse Perinatal Outcomes Following Exposure to Intrauterine Inflammation.

Maternal periodontal disease has been linked to adverse pregnancy sequelae, including preterm birth (PTB); yet, root planing and scaling in pregnancy has not been associated with improved perinatal outcomes. Fluoride, a cariostatic agent, has been added to drinking water and dental products to prevent caries and improve dental health. The objective of this study was to explore the effects of fluoride supplementation using a mouse model of preterm birth and perinatal sequalae.

Increased placental T cell trafficking results in adverse neurobehavioral outcomes in offspring exposed to sub-chronic maternal inflammation.

Interleukin-1 beta (IL-1β) is a cytokine mediator of perinatal brain injury. The effect of sub-chronic systemic IL-1β exposure in perinatal and offspring outcomes is unclear. The aim of this study was to examine the effects of maternal IL-1β exposure on pregnancy and offspring outcomes.

Maternal CD8 T-cell depletion alleviates intrauterine inflammation-induced perinatal brain injury.

We investigated the mechanisms by which CD8 T-cell trafficking in placenta contributes to perinatal brain injury by studying effects of maternal CD8 T-cell depletion (DEP) in a mouse model of intrauterine inflammation (IUI). Maternal CD8 T cells were depleted with anti-CD8 antibodies. IUI was induced with lipopolysaccharide (LPS).

Paclitaxel is necessary for improved survival in epithelial ovarian cancers with homologous recombination gene mutations.

Purpose: To investigate the impact of somatic mutations in homologous recombination (HR) genes on the chemotherapeutic response and survival of patients with epithelial ovarian cancer (EOC).

Experimental Design: We performed targeted massively parallel sequencing of tumor DNA from 158 patients with EOC. We associated adjuvant chemotherapy and clinical outcome with mutations in selected genes, focusing on those encoding HR proteins.

Identifying the serotonin transporter signal in Western blot studies of the neurotoxic potential of MDMA and related drugs.

A number of published studies have questioned the serotonin neurotoxic potential of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") and related drugs (fenfluramine, p-chloroamphetamine) based upon results from Western blot studies using a custom synthesized serotonin transporter (SERT) antibody that found no reduction in the abundance of a 50kDa protein after substituted amphetamine treatment. The purpose of this study was to collect Western blot data using the same SERT antibody used in those studies, but with positive and negative controls to identify the SERT protein signal. A 63-68 kDa band that had the regional distribution expected of rat brain SERT, was decreased by 5,7-DHT, and was absent in SERT KO animals was identified as the SERT protein.

Heating induces aggregation and decreases detection of serotonin transporter protein on western blots.

In recent years, there has been growing interest in the use of Western blot analysis to monitor changes in the abundance of the serotonin transporter (SERT) protein. In the Western blot procedure, heat denaturation is a common, early step. We now report that heating samples to 90 degrees C decreases the abundance of the SERT protein band and causes dispersion of a majority of the SERT signal to a high molecular weight smear.

Loss of serotonin transporter protein after MDMA and other ring-substituted amphetamines.

We studied in vivo expression of the serotonin transporter (SERT) protein after 3,4-methylenedioxymethamphetamine (MDMA), p-chloroamphetamine (PCA), or fenfluramine (FEN) treatments, and compared the effects of substituted amphetamines to those of 5,7-dihydroxytryptamine (5,7-DHT), an established serotonin (5-HT) neurotoxin. All drug treatments produced lasting reductions in 5-HT, 5-HIAA, and [(3)H]paroxetine binding, but no significant change in the density of a 70 kDa band initially thought to correspond to the SERT protein. Additional Western blot studies, however, showed that the 70 kDa band did not correspond to the SERT protein, and that a diffuse band at 63-68 kDa, one that had the anticipated regional brain distribution of SERT protein (midbrain>striatum>neocortex>cerebellum), was reduced after 5,7-DHT and was absent in SERT-null animals, was decreased after MDMA, PCA, or FEN treatments.