Role of inflammatory lipid and fatty acid metabolic abnormalities induced by plastic additives exposure in childhood asthma

Lipid metabolism play an essential role in occurrence and development of asthma,and it can be disturbed by phthalate esters(PAEs)and organophosphate fame retardants(OPFRs).As a chronic infammatory respiratory disease,the occurrence risk of childhood asthma is increased by PAEs and OPFRs exposure,but it remains not entirely clear how PAEs and OPFRs contribute the onset and progress of the disease.We have profiled the serum levels of PAEs and OPFRs congeners by liquid chromatography coupled with mass spectrometry,and its relationships with the dysregulation of lipid metabolism in asthmatic,bronchitic(acute infammation)and healthy(non-infammation)children.Eight PAEs and nine OPFRs congeners were found in the serum of children(1–5 years old)from Shenzhen,and their total median levels were 615.16 ng/m L and 17.06 ng/m L,respectively.Moreover,the serum levels of mono-methyl phthalate(MMP),tri-propyl phosphate(TPP)and tri-n-butyl phosphate(TNBP)were significant higher in asthmatic children than in healthy and bronchitic children as control.Thirty-one characteristic lipids and fatty acids of asthma were screened by machine-learning random forest model based on serum lipidome data,and the alterations of infammatory characteristic lipids and fatty acids including palmitic acids,12,13-Di HODE,14,21-Di HDHA,prostaglandin D2 and Lyso PA(18:2)showed significant correlated with high serum levels of MMP,TPP and TNBP.These results imply PAEs and OPFRs promote the occurrence of childhood asthma via disrupting infammatory lipid and fatty acid metabolism,and provide a novel sight for better understanding the effects of plastic additives on childhood asthma.

Integrated proteomic profiling identifies amino acids selectively cytotoxic to pancreatic cancer cells

Pancreatic adenocarcinoma(PDAC)is one of the most deadly cancers,characterized by extremely limited therapeutic options and a poor prognosis,as it is often diagnosed during late disease stages.Innovative and selective treatments are urgently needed,since current therapies have limited efficacy and significant side effects.Through proteomics analysis of extracellular vesicles,we discovered an imbalanced distribution of amino acids secreted by PDAC tumor cells.Our findings revealed that PDAC cells preferentially excrete proteins with certain preferential amino acids,including isoleucine and histidine,via extracellular vesicles.These amino acids are associated with disease progression and can be targeted to elicit selective toxicity to PDAC tumor cells.Both in vitro and in vivo experiments demonstrated that supplementation with these specific amino acids effectively eradicated PDAC cells.Mechanistically,we also identified XRN1 as a potential target for these amino acids.The high selectivity of this treatment method allows for specific targeting of tumor metabolism with very low toxicity to normal tissues.Furthermore,we found this treatment approach is easy-to-administer and with sustained tumor-killing effects.Together,our findings reveal that exocytosed amino acids may serve as therapeutic targets for designing treatments of intractable PDAC and potentially offer alternative treatments for other types of cancers.