The hyaluronan-binding activity of aggrecan is important, but not essential, for its specific insertion into perineuronal nets.

Aggrecan (ACAN) is a large, secreted chondroitin sulfate proteoglycan that includes three globular regions named G1, G2, G3, and is decorated with multiple glycosaminoglycan attachments between its G2 and G3 domains. The N-terminal G1 region interacts with the glycosaminoglycan hyaluronan (HA), which is an essential component of the vertebrate extracellular matrix. In the central nervous system, ACAN is found in perineuronal nets (PNNs), honeycomb-like structures that are enriched on parvalbumin-positive neurons in specific neural circuits.

A Phase 1 Study to Evaluate the Pharmacokinetic Drug-Drug Interaction Between Islatravir and Methadone in Participants on Stable Methadone Therapy.

Islatravir is a nucleoside reverse transcriptase translocation inhibitor in development for the treatment of HIV-1. People living with HIV-1 receiving methadone maintenance therapy may benefit from islatravir. This study was designed to evaluate single-dose islatravir on steady-state methadone pharmacokinetics.

Effect of evolocumab in patients with chronic limb threatening ischemia (Evol-CLI study).

Background: Chronic limb-threatening ischemia (CLTI) is associated with increased risk of major adverse cardiac and limb events (MACLE). In patients with peripheral arterial disease (PAD), evolocumab is associated with decreased MACLE, improved maximal walking time, increased vascular flow-mediated dilation (FMD), and decreased carotid intima-media thickness (IMT). We investigated the additive effect of evolocumab in patients with CLTI on maximally tolerated lipid lowering therapy after an index revascularization for non-healing wounds.

Immune profile diversity is achieved with synthetic TLR4 agonists combined with the RG1-VLP vaccine in mice.

The TLR4 (Toll-like receptor 4)-activating agonist MPLA (monophosphoryl lipid A) is a key component of the adjuvant systems AS01 and AS04, utilized in marketed preventive vaccines for several infectious pathogens. As MPLA is a biologically-derived product containing a mixture of several lipid A congeners with a 4' phosphoryl group and varying numbers of acyl chains with distinct activities, extensive efforts to refine its production and immunogenicity are ongoing; notably, the development of the BECC (Bacterial Enzymatic Combinatorial Chemistry) system in which bacteria express lipid A-modifying enzymes to produce a panoply of lipid A congeners. In an effort to characterize the adjuvant activity of these lipid A congeners, we compared biologically-derived and synthetic versions of BECC470 and BECC438 for adjuvant activity in BALB/c mice vaccinated with the HPV (Human papilloma virus) VLP-based vaccine, RG1-VLP.