ABSTRACT
Atherosclerosis still represents a major driver of cardiovascular diseases worldwide. Together with accumulation of lipids in the plaque, inflammation is recognized as one of the key players in the formation and development of atherosclerotic plaque. Systemic anti-inflammatory treatments are successful in reducing the disease burden, but are correlated with severe side effects, underlining the need for targeted formulations. In this work, curcumin is chosen as the anti-inflammatory payload model and further loaded in lignin-based nanoparticles (NPs). The NPs are then coated with a tannic acid (TA)- Fe (III) complex and further cloaked with fragments derived from platelet cell membrane, yielding NPs with homogenous size. The two coatings increase the interaction between the NPs and cells, both endothelial and macrophages, in steady state or inflamed status. Furthermore, NPs are cytocompatible toward endothelial, smooth muscle and immune cells, while not inducing immune activation. The anti-inflammatory efficacy is demonstrated in endothelial cells by real-time quantitative polymerase chain reaction and ELISA assay where curcumin-loaded NPs decrease the expression of Nf-κb, TGF-ß1, IL-6, and IL-1ß in lipopolysaccharide-inflamed cells. Overall, due to the increase in the cell-NP interactions and the anti-inflammatory efficacy, these NPs represent potential candidates for the targeted anti-inflammatory treatment of atherosclerosis.
Subject(s)
Anti-Inflammatory Agents , Atherosclerosis , Blood Platelets , Curcumin , Nanoparticles , Curcumin/chemistry , Curcumin/pharmacology , Atherosclerosis/drug therapy , Humans , Nanoparticles/chemistry , Blood Platelets/metabolism , Blood Platelets/drug effects , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/administration & dosage , Animals , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Human Umbilical Vein Endothelial Cells , Tannins/chemistry , Tannins/pharmacology , RAW 264.7 Cells , Mice , Macrophages/drug effects , Macrophages/metabolismABSTRACT
The dynamics of the origins and spread of farming are globally debated in anthropology and archaeology. Lately, numerous aDNA studies have turned the tide in favour of migrations, leaving only a few cases in Neolithic Europe where hunter-gatherers might have adopted agriculture. It is thus widely accepted that agriculture was expanding to its northern extreme in Sweden c. 4000 BC by migrating Funnel Beaker Culture (FBC) farmers. This was followed by intense contacts with local hunter-gatherers, leading to the development of the Pitted Ware Culture (PWC), who nonetheless relied on maritime prey. Here, we present archaeobotanical remains from Sweden and the Åland archipelago (Finland) showing that PWC used free-threshing barley and hulled and free-threshing wheat from c. 3300 BC. We suggest that these hunter-gatherers adopted cultivation from FBC farmers and brought it to islands beyond the 60th parallel north. Based on directly dated grains, land areas suitable for cultivation, and absence of signs of exchange with FBC in Sweden, we argue that PWC cultivated crops in Åland. While we have isotopic and lipid-biomarker proof that their main subsistence was still hunting/fishing/gathering, we argue small-scale cereal use was intended for ritual feasts, when cereal products could have been consumed with pork.