Natural and Semisynthetic Immunomodulatory Luakuliide Labdane Diterpenoids.

Spectroscopy-guided isolation of extracts of the Tongan marine sponge cf. (Lamarck, 1814) has resulted in the reisolation of the labdane diterpenoid luakuliide A () and one new congener, luakulialactam A (). In addition to establishing the absolute configuration of , synthetic modifications to the luakuliide framework at key positions has created a set of six derivatives (-) which were used to interrogate a structure-activity relationship relating to the immunomodulatory effects of luakuliide A.

Nalfurafine promotes myelination in vitro and facilitates recovery from cuprizone + rapamycin-induced demyelination in mice.

The kappa opioid receptor has been identified as a promising therapeutic target for promoting remyelination. In the current study, we evaluated the ability of nalfurafine to promote oligodendrocyte progenitor cell (OPC) differentiation and myelination in vitro, and its efficacy in an extended, cuprizone-induced demyelination model. Primary mouse (C57BL/6J) OPC-containing cultures were treated with nalfurafine (0.

CPHEN-017: Comprehensive phenotyping of neutrophil extracellular traps (NETs) on peripheral human neutrophils.

With the recent discovery of their ability to produce neutrophil extracellular traps (NETs), neutrophils are increasingly appreciated as active participants in infection and inflammation. NETs are characterized as large, web-like networks of DNA and proteins extruded from neutrophils, and there is considerable interest in how these structures drive disease in humans. Advancing research in this field is contingent on developing novel tools for quantifying NETosis.

Synthesis and Detection of BODIPY-, Biotin-, and F- Labeled Single-Entity Dendritic Heparan Sulfate Mimetics.

Heparin and heparan sulfate (HS) are naturally occurring mammalian glycosaminoglycans, and their synthetic and semi-synthetic mimetics have attracted significant interest as potential therapeutics. However, understanding the mechanism of action by which HS, heparin, and HS mimetics have a biological effect is difficult due to their highly charged nature, broad protein interactomes, and variable structures. To address this, a library of novel single-entity dendritic mimetics conjugated to BODIPY, Fluorine-19 ( F), and biotin was synthesized for imaging and localization studies.

Enhanced and complementary benefits of a nalfurafine and fingolimod combination to treat immune-driven demyelination.

Objectives: Multiple sclerosis (MS) is a neurodegenerative disease characterised by inflammation and damage to myelin sheaths. While all current disease-modifying treatments (DMTs) are very effective at reducing relapses, they do not slow the progression of the disease, and there is little evidence that these treatments are able to repair or remyelinate damaged axons. Recent evidence suggests that activating kappa opioid receptors (KORs) has a beneficial effect on the progression of MS, and this study investigates the effects of KOR agonists treatment in combination with two current DMTs.