Atherosclerosis (AS) is a chronic disorder of large arteries that is a major risk factors of high morbidity and mortality. Oxidative modification LDL is one of the important contributors to atherogenesis. Macrophages take up ox-LDL and convert into foam cells, which is the hallmark of AS. To advance the understanding of the metabolic perturbation involved in ox-LDL induced macrophage-derived foam cells and discover the potential biomarkers of early AS, a global metabolomics approach was applied based on UHPLC-QTOF/MS. Multivariate statistical analyses identified five metabolites (25-azacholesterol, anandamide, glycocholate, oleoyl ethanolamide, and 3-oxo-4, 6-choladienoate) for distinguishing foamy macrophages from controls. Among the six main metabolic pathways, the unsaturated fatty acid, especially arachidonic acid metabolism, contributed importantly to early AS. A new biomarker, anandamide (AEA), whose synthesis and metabolism in macrophages are disturbed by overloaded ox-LDL, results in metabolic obstruction. This study is the first to investigate the metabolic disturbance in macrophage-derived foam cells induced by ox-LDL and screen potential biomarkers and metabolic pathways associated with early AS. Our findings provide a new insight in the underlying pathophysiological mechanisms and also help to identify novel targets for the intervention of AS.
Succinate
dehydrogenase (SDH) is one of the most important molecular
targets for the development of new fungicides. Carboxamide fungicides
are a class of SDH inhibitors widely used to inhibit highly destructive
plant pathogens. Although cases of resistance have been found in fungal
pathogens due to the unrestricted use in recent years, there is still
demand for new compounds with improved fungicidal activity. Therefore,
a series of ester compounds were designed to investigate potential
novel antifungal molecules. First, the antifungal activity of different
benzyl alcohol compounds (A1–A21) was tested,
and a highly active fragment (3,5-dichlorobenzyl alcohol) was found.
Subsequently, various compounds were synthesized by esterification
between different acids and 3,5-dichlorobenzyl alcohol, among which
compound 5 exhibited remarkable antifungal activity against Botrytis cinerea and Rhizoctonia solani with EC50 values of 6.60 and 1.61 mg/L, respectively,
which were comparable to those of commercial fungicide boscalid (EC50 = 1.24 and 1.01 mg/L). In vivo testing
further demonstrated that compound 5 was effective in
suppressing B. cinerea (200 mg/L, 50.9%).
Moreover, SDH inhibition assays, fluorescence quenching analysis,
and determination of mitochondrial membrane potential revealed that
compound 5 has similar effects to boscalid. Furthermore,
the fungicidal activity of target compounds can be maintained by modifying
the amide bond to an ester bond. These results will provide basis
for the development of novel fungicides.
Emamectin benzoate (EMB) as one of the typical biological pesticides has a wide range of applications in agriculture. However, the immune toxic effects of EMB in human received limited attention. In our study, THP-1 macrophage as an in vitro model was used to evaluate immune functions exposed to EMB. We observed that EMB inhibited phagocytic activity and respiratory burst capacity of macrophages without inducing cellular toxicity, implying the potential immunosuppression.Besides, EMB disturbed the cytokines balance embodied in the increase of TNF-α, IL-1β, IL-6, CCL27, CXCL8 mRNA expression and the decrease of IL-4, IL-13, IL-10 mRNA expression. EMB could exhibit pro-inflammatory responses in macrophages and promote the conversion of macrophages to M1 phenotype. Moreover, NF-κB pathway involved in regulating immune function from KEGG pathway analysis. EMB exposure could activate the NF-κB pathway in THP-1 macrophages by exploring the critical proteins. This research provided insights on immunotoxicity evaluation and clarified EMB-induced immunotoxicity was related to NF-κB pathway activation.
Emamectin benzoate (EMB) is an insecticide extensively used in agricultural area.Assessing the toxic effects of EMB in mammals or humans and its endogenous metabolites alteration are the appropriate means of evaluating its risks to human health. In the study, THP-1 macrophage, a human immune model, was applied to
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