ABSTRACT
Poly- and perfluoroalkyl substances (PFAS) are a family of chemicals that have been used in a wide range of commercial products. While their use is declining, the prevalence of PFAS, combined with their chemical longevity, ensures that detectable levels will remain in the environment for years to come. As such, there is a pressing need to understand how PFAS contaminants interact with other elements of the human exposome and the consequences of these interactions for human health. Using serum albumin as a model system, we show that proteins can bind PFAS contaminants and facilitate their incorporation into model pulmonary surfactant systems and lipid bilayers. Protein-mediated PFAS delivery significantly altered the structure and function of both model membrane systems, potentially contributing to respiratory dysfunction and airway diseases in vivo. These results provide valuable insights into the synergistic interaction between PFAS contaminants and other elements of the human exposome and their potential consequences for human health.
ABSTRACT
The implantation of a biomaterial quickly initiates a tissue repair program initially characterized by a neutrophil influx. During the acute inflammatory response, neutrophils release neutrophil extracellular traps (NETs) and secrete soluble signals to modulate the tissue environment. In this work, we evaluated chloroquine diphosphate, an antimalarial with immunomodulatory and antithrombotic effects, as an electrospun biomaterial additive to regulate neutrophil-mediated inflammation. Electrospinning of polydioxanone was optimized for rapid chloroquine elution within 1 h, and acute neutrophil-biomaterial interactions were evaluated in vitro with fresh human peripheral blood neutrophils at 3 and 6 h before quantifying the release of NETs and secretion of inflammatory and regenerative factors. Our results indicate that chloroquine suppresses NET release in a biomaterial surface area-dependent manner at the early time point, whereas it modulates signal secretion at both early and late time points. More specifically, chloroquine elution down-regulates interleukin 8 (IL-8) and matrix metalloproteinase nine secretion while up-regulating hepatocyte growth factor, vascular endothelial growth factor A, and IL-22 secretion, suggesting a potential shift toward a resolving neutrophil phenotype. Our novel repurposing of chloroquine as a biomaterial additive may therefore have synergistic, immunomodulatory effects that are advantageous for biomaterial-guided in situ tissue regeneration applications.
ABSTRACT
Ascidian metamorphosis is a critical life history stage for exploring chordate evolution and conserved chordate developmental signaling pathways. The vast majority of research on ascidian development has been focused on embryogenesis. Thus there is still little known about the development of ascidian post-larval structures, including differentiation of the chordate pharyngeal gill slits and endostyle along with the heart, blood cells and gut. In this paper, we present our research on metamorphosis in the solitary ascidian Boltenia villosa. Through careful analysis of phalloidin staining in young juveniles, we have discerned a highly coordinated series of developmental events underlying the differentiation of the gut and body wall musculature. Additionally, we have employed subtractive hybridizations to isolate genes that are differentially transcribed during Boltenia metamorphosis. Some of these genes are expressed throughout ascidian development and some appear to be uniquely expressed during metamorphosis. Here we characterize several transcripts with potential developmental functions and discuss their possible roles in the differentiation of adult structures during solitary ascidian metamorphosis.
