COVID-19 vaccine hesitancy: Considerations for reluctance and improving vaccine uptake.

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic during the fall of 2019 led to the rapid development of vaccines aimed at curbing viral infection, spread, and its potential eradication. A recent trend is an overall increase in vaccine hesitancy, leading to the World Health Organization citing this as a problem which needs to be addressed. With the development and approval of vaccines for COVID-19, this trend has quickened, leading to potential negative ramifications in the ability controlling COVID-19 spread. Here we describe reported examples in overall vaccine hesitancy prior to the emergence of COVID-19, as well as summarizing recent reports on vaccine hesitancy related to COVID-19 vaccines. Gaining a better understanding of the reasons individuals have, as well as potential methods for decreasing hesitancy in the future, will hopefully lead to a greater percentage of vaccinated individuals and aid in ending the current pandemic.

The Interface between Cell Signaling Pathways and Pregnane X Receptor.

Highly expressed in the enterohepatic system, pregnane X receptor (PXR, NR1I2) is a well-characterized nuclear receptor (NR) that regulates the expression of genes in the liver and intestines that encode key drug metabolizing enzymes and drug transporter proteins in mammals. The net effect of PXR activation is to increase metabolism and clear drugs and xenobiotics from the body, producing a protective effect and mediating clinically significant drug interaction in patients on combination therapy. The complete understanding of PXR biology is thus important for the development of safe and effective therapeutic strategies. Furthermore, PXR activation is now known to specifically transrepress the inflammatory- and nutrient-signaling pathways of gene expression, thereby providing a mechanism for linking these signaling pathways together with enzymatic drug biotransformation pathways in the liver and intestines. Recent research efforts highlight numerous post-translational modifications (PTMs) which significantly influence the biological function of PXR. However, this thrust of research is still in its infancy. In the context of gene-environment interactions, we present a review of the recent literature that implicates PXR PTMs in regulating its clinically relevant biology. We also provide a discussion of how these PTMs likely interface with each other to respond to extracellular cues to appropriately modify PXR activity.