Like all coronaviruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is surrounded by a lipid envelope hosting spike and other critical proteins. However, little is known about the biology of coronavirus membranes, their regulation by inflammation/disease, nor how they could be harnessed to dampen infection. Here, we show using lipidomics that four cultured SARS-CoV-2 strains (England2 (Wuhan), Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2)) contain highly conserved phospholipid (PL)/cholesterol-rich membranes. PL that drive blood clotting and support infectivity (phosphatidylserine (PS) and phosphatidylethanolamine (PE)) were 70-80% external-facing, particularly for Alpha and Beta strains. Interleukin-4 (IL-4) caused a 10-fold increase in secreted virions with dramatically-altered phospholipid fatty acyl saturation. In contrast, envelopes were not impacted by IL-6 (with/without its soluble receptor IL-6Ra) or dexamethasone-treatment of host cells. SARS-CoV-2 membranes isolated from patients were remarkably conserved and cholesterol enriched. Several pro-coagulant oxidized phospholipid damage-associated molecular patterns (DAMPs) and oxylipins generated by lipoxygenases (LOX), were detected in clinical viruses. Furthermore, using gene silencing, we found that 15-LOX2 was required for replication of coronaviruses MERS-CoV and HCoV-229E in macrophages, indicating a shared requirement for LOX products. In summary, the coronavirus envelope contains numerous bioactive lipids with known impacts on inflammation and thrombosis, as well supporting replication, and is altered by disease-relevant host inflammatory factors. This confirms the envelope as a target for therapeutic strategies via direct modulation of host innate immunity.

Urban ecosystems are subjected to multiple anthropogenic stresses, which impact aquatic communities. Artificial light at night (ALAN) for instance can significantly alter the composition of algal communities as well as the photosynthetic cycles of autotrophic organisms, possibly leading to cellular oxidative stress. The combined effects of ALAN and chemical contamination could increase oxidative impacts in aquatic primary producers, although such combined effects remain insufficiently explored. To address this knowledge gap, a one-month experimental approach was implemented under controlled conditions to elucidate effects of ALAN and dodecylbenzyldimethylammonium chloride (DDBAC) on aquatic biofilms. DDBAC is a biocide commonly used in virucidal products, and is found in urban aquatic ecosystems. The bioaccumulation of DDBAC in biofilms exposed or not to ALAN was analyzed. The responses of taxonomic composition, photosynthetic activity, and fatty acid composition of biofilms were examined. The results indicate that ALAN negatively affects photosynthetic yield and chlorophyll production of biofilms. Additionally, exposure to DDBAC at environmental concentrations induces lipid peroxidation, with an increase of oxylipins. This experimental study provides first insights on the consequences of ALAN and DDBAC for aquatic ecosystems. It also opens avenues for the identification of new biomarkers that could be used to monitor urban pollution impacts in natural environments.
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.

Introduction: Inflammation is a defensive response of the body and the pathological basis of many diseases. However, excessive inflammation and chronic inflammation impair the homeostasis of the organism. Arachidonic acid (AA) has a close relationship with inflammation and is the main mediator of the pro-inflammatory response. Based on the prodrug principle, the new pharmaceutical compound aspirin eugenol ester (AEE) was designed and synthesized. However, the effects of AEE on key enzymes, metabolites and inflammatory signaling pathways in the AA metabolic network have not been reported. Methods: In this study, the anti-inflammation effects of AEE were first investigated in mice and RAW264.7 cells in LPS induced inflammation model. Then, the changes of the key enzymes and AA metabolites were explored by RT-PCR and targeted metabolomics. Moreover, the regulatory effects on NF-kB and MAPKS signaling pathways were explored by Western Blotting. Results: Results indicated that AEE significantly reduced the number of leukocyte and increased the lymphocyte percentage. AEE decreased the expression levels of IL-1β, IL-6, IL-8 and TNF-α both in vivo and in vitro. In the liver of mice, AEE downregulated the levels of AA, prostaglandin D2 (PGD2) and upregulated 12- hydroxyeicosatetraenoic acid (12-HETE). However, the changes of PGE2, PGF2α, 6-keto-prostaglandin F1α (6-KETO-PGF1α), 9-hydroxy-octadecenoic acid (9- HODE), 13-HODE, 15-HETE, docosahexaenoic acid (DHA) and thromboxane B2 (TXB2) were not significant. Additionally, it was found that AEE decreased the relative mRNA expression levels of p65 and p38 and the ratio of p-p65/p65. Discussion: It was concluded that AEE might inhibit the LPS-induced inflammatory response through the regulation of AA metabolism. This study provides the theoretical foundation for the development of AEE as a medicinal anti-inflammatory drug.
Copyright © 2023 Liu, Tao, Shen, Liu, Yang, Ma and Li.

Low-density lipoprotein (LDL) contributes to atherogenesis and cardiovascular disease through interactions with peripheral blood cells, especially platelets. However, mechanisms by which LDL affects platelet activation and atherothrombosis, and how to best therapeutically target and safely prevent such responses remain unclear. Here, we investigate how oxidized low-density lipoprotein (oxLDL) enhances glycoprotein VI (GPVI)-mediated platelet hemostatic and procoagulant responses, and how traditional and emerging antiplatelet therapies affect oxLDL-enhanced platelet procoagulant activity ex vivo. Human platelets were treated with oxLDL and the GPVI-specific agonist, crosslinked collagen-related peptide, and assayed for hemostatic and procoagulant responses in the presence of inhibitors of purinergic receptors (P2YR), cyclooxygenase (COX), and tyrosine kinases. Ex vivo, oxLDL enhanced GPVI-mediated platelet dense granule secretion, α-granule secretion, integrin activation, thromboxane generation and aggregation, as well as procoagulant phosphatidylserine exposure and fibrin generation. Studies of washed human platelets, as well as platelets from mouse and nonhuman primate models of hyperlipidemia, further determined that P2YR antagonists (eg, ticagrelor) and Bruton tyrosine kinase inhibitors (eg, ibrutinib) reduced oxLDL-mediated platelet responses and procoagulant activity, whereas COX inhibitors (eg, aspirin) had no significant effect. Together, our results demonstrate that oxLDL enhances GPVI-mediated platelet procoagulant activity in a manner that may be more effectively reduced by P2YR antagonists and tyrosine kinase inhibitors compared with COX inhibitors.
Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.

The Apolipoprotein-E4 allele (APOE) is the strongest genetic risk factor for sporadic Alzheimer’s disease but its role in disease pathogenesis is incompletely understood. The APOE gene encodes Apolipoprotein E (ApoE). Astrocytes are the main source of ApoE in the central nervous system (CNS) and are essential for homeostasis in health and disease. In response to CNS insult, a coordinated multicellular inflammatory response is triggered causing reactive astrogliosis with changes in astrocytic gene expression, cellular structure and function. Human embryonic stem-cells with the ‘neutral’ APOE33 genotype were edited using CRISPR Cas-9 gene-editing to create isogenic APOE lines with an APOE44 genotype. Quiescent astrocytes were differentiated then stimulated with TNF-α, IL1α and C1q inducing an astrogliotic A1 phenotype. Several potentially pathological APOE44 -related phenotypes were identified in both quiescent cells and reactive A1 astrocytes including significantly decreased phagocytosis, impaired glutamate and a defective immunomodulatory response. In quiescent APOE44 astrocytes there was significantly decreased secretion of IL6, IL8 and several oxylipins. In A1 astrocytes there was a pro-inflammatory phenotype in APOE44 astrocytes with increases in GRO, ENA78, IL6 and IL8, a decrease in IL10 as well as significant differences in oxylipin expression. As TNF-α induced signaling in astrocytes is driven by Nuclear factor kappa B (NF-κB) proteins of this pathway were measured. Significantly higher levels of the p50, p65 and IκBα sub-units were found in both quiescent and A1 APOE44 astrocytes. This suggests that perturbation of NF-κB signaling may contribute to the damaging APOE44 cell phenotypes observed providing a new direction for targeted disease therapeutics.