Unnatural Amino Acids: Strategies, Designs, and Applications in Medicinal Chemistry and Drug Discovery.

Peptides can operate as therapeutic agents that sit within a privileged space between small molecules and larger biologics. Despite examples of their potential to regulate receptors and modulate disease pathways, the development of peptides with drug-like properties remains a challenge. In the quest to optimize physicochemical parameters and improve target selectivity, unnatural amino acids (UAAs) have emerged as critical tools in peptide- and peptidomimetic-based drugs.

HLA class I antibody-activated endothelium promotes CD206+ M2-macrophage polarization and MMP9 secretion through TLR4 signaling and P-selectin in a model of antibody-mediated rejection and allograft vasculopathy.

HLA donor-specific antibodies (DSA) elicit alloimmune responses against the graft vasculature, leading to endothelial cell (EC) activation and monocyte infiltration during antibody-mediated rejection (AMR). AMR promotes chronic inflammation and remodeling, leading to thickening of the arterial intima termed transplant vasculopathy (TV) or cardiac allograft vasculopathy (CAV) in heart transplants. Intragraft-recipient macrophages serve as a diagnostic marker in AMR however, their polarization and function remain unclear.

Indole-based COX-2 inhibitors: A decade of advances in inflammation, cancer, and Alzheimer's therapy.

Cyclooxygenase-2 (COX-2), a key enzyme in the cyclooxygenase family, is pivotal in producing pro-inflammatory prostaglandins, driving chronic inflammation and related disorders. Targeting COX-2 with selective inhibitors can mitigate these conditions while avoiding the gastrointestinal and hepatotoxic/nephrotoxic side effects of traditional NSAIDs. However, the selectivity towards COX-2 inhibition has been associated with cardiovascular risks, necessitating the discovery of novel molecular scaffolds avoiding CVS side effects.

Trend Analysis of Industry-Sponsored Research Funding and Research Productivity in Orthopaedic Surgery Using the Open Payments Database.

Introduction Orthopedic surgery and industry work together in order to provide optimal patient care. The Open Payments Database (OPD), established in 2013, reports industry payments to physicians. This study analyzes the first five years of industry-sponsored research funding (ISRF) to orthopedic surgeons and examines research productivity's effect on ISRF.