Alterations in Placental Inflammation-Related Gene Expression Partially Mediate the Effects of Prenatal Alcohol Consumption on Maternal Iron Homeostasis.

Prenatal alcohol exposure (PAE) is associated with alterations in maternal and infant iron homeostasis that are consistent with changes seen in the setting of inflammation. We hypothesized that PAE leads to alterations in the placental expression of genes related to iron metabolism and inflammation that play functional roles in the teratogenic effects of alcohol on iron homeostasis. A total of 126 heavy-drinking women (≥1 oz (30 mL) absolute alcohol/day (~1.67 standard drinks/day) or women reporting binge drinking (≥2 drinks/occasion)) and 80 control women (<0.5 oz AA per day, no binging) in Cape Town, South Africa were interviewed prenatally regarding demographics, and alcohol, smoking, and drug use around conception and during pregnancy. Prenatal/maternal and infant hemoglobin and ferritin were measured. Whole-transcriptome RNA sequencing analysis was performed on flash-frozen transplacental tissue samples. Gene sets related to iron metabolism (n = 398) and inflammation (n = 467) were constructed by searching the Molecular Signatures Database for related ontology terms. Principal component analysis (PCA) yielded 59 factors for each theme. In multivariable regression models, PAE was related to 2 iron metabolism PCA factors (PCs) and 5 inflammation PCs, among which 2 iron metabolism and 4 inflammation factors were related to at least 1 key maternal or infant iron outcome. In causal inference analyses based on marginal structural models and the product method, the alterations in the expression profile of genes with functions in immune cell regulation, cytokine activity, angiogenesis, hematopoiesis, and ubiquitous cell processes appeared to partially mediate the relation of prenatal drinking frequency (days/week) around conception to a lower maternal hemoglobin-to-log(ferritin) ratio (proportion mediation = 51.35%). These findings suggest that placental inflammation may be partly responsible for the differences in alcohol-related iron homeostasis patterns between pregnant and non-pregnant adults.

Engineering Citric Acid-Based Porous Scaffolds for Bone Regeneration.

Tissue engineering aims to develop scaffolds that are biocompatible and mimic the mechanical and biological properties of the target tissue as closely as possible. Here, we describe the fabrication and characterization of a biodegradable, elastomeric porous scaffold: poly(1,8-octanediol-co-citric acid) (POC) incorporated with nanoscale hydroxyapatite (HA). While this chapter focuses on the scaffold's potential for bone regeneration, POC can also be used in other tissue engineering applications requiring an elastomeric implant. Because of the relative ease with which POC can be synthesized, its mechanical properties can be tailored to mimic the structure and function of the target elastomeric tissue for enhanced tissue regeneration.

Peptide and antibody ligands for renal targeting: nanomedicine strategies for kidney disease.

The kidney is one of the body's main filtration organs, and hence, opportunity exists for designing nanomedicine that can naturally accumulate in the kidneys for renal diseases. In addition to traditional physiochemical properties for kidney accumulation, such as size and charge, synthesized nanoparticles can be conjugated with targeting ligands which further home the nanocarriers to cell types of interest. In this review, we highlight key studies that have shown success in utilizing peptide- or antibody-based ligands in nanoparticles to target the glomerulus, podocytes, or renal tubule cells in the kidney. In addition, other ligand candidates which have shown renal affinity, but have not yet been integrated into a nanoparticle are also presented. These studies can provide insight into the design of novel clinical solutions for improved detection, prevention, and treatment of renal diseases using nanomedicine efforts.