Molecular lipid species in urinary exosomes as potential prostate cancer biomarkers

BackgroundExosomes have recently appeared as a novel source of noninvasive cancer biomarkers, since these nanovesicles contain molecules from cancer cells and can be detected in biofluids. We have here investigated the potential use of lipids in urinary exosomes as prostate cancer biomarkers.MethodsA high-throughput mass spectrometry quantitative lipidomic analysis was performed to reveal the lipid composition of urinary exosomes in prostate cancer patients and healthy controls.ResultsControl samples were first analysed to characterise the lipidome of urinary exosomes and test the reproducibility of the method. In total, 107 lipid species were quantified in urinary exosomes. Several differences, for example, in cholesterol and phosphatidylcholine, were found between urinary exosomes and exosomes derived from cell lines, thus showing the importance of in vivo studies for biomarker analysis. The 36 most abundant lipid species in urinary exosomes were then quantified in 15 prostate cancer patients and 13 healthy controls. Interestingly, the levels of nine lipids species were found to be significantly different when the two groups were compared. The highest significance was shown for phosphatidylserine (PS) 18:1/18:1 and lactosylceramide (d18:1/16:0), the latter also showed the highest patient-to-control ratio. Furthermore, combinations of these lipid species and PS 18:0-18:2 distinguished the two groups with 93% sensitivity and 100% specificity. Finally, in agreement with the reported dysregulation of sphingolipid metabolism in cancer cells, alteration in specific sphingolipid lipid classes were observed.ConclusionThis study shows for the first time the potential use of exosomal lipid species in urine as prostate cancer biomarkers.     

呼吸系统疾病相关脂类及脂质组学研究进展

脂质不仅是细胞重要的信号分子,还参与调节诸多重要的生命活动,包括物质运输、结构支持、能量转换、细胞发育、分化和凋亡等。脂质组学是代谢组学的一门新兴分支学科。通过比较不同生理状态下脂质代谢网络的变化,进而识别代谢调控中关键的生物标志物,最终揭示脂质在各种生命活动中的作用机制。大量研究表明,脂类代谢异常与呼吸系统疾病的发生发展有着密切联系,脂质组学能揭示与呼吸系统疾病相关的脂类变化,找到异常的代谢通路,识别脂类生物标志物,对疾病的早期诊断、病情发展和治疗靶点的发现等方面展现出广泛的应用前景。本文对近几年的文献进行归纳总结,介绍了结构脂质和信号脂质在支气管肺炎、哮喘、急性肺损伤、肺纤维化等呼吸系统疾病中的研究进展和应用前景。其中,结构脂质重点介绍了磷脂酰胆碱、磷脂酰甘油、鞘脂类,信号脂质主要包括类花生酸类如前列腺素类、凝血恶烷类、白三烯类、脂氧素、羟基二十碳四烯酸、异前列烷等。目前,脂质组学发展迅速,分析技术的发展也将进一步推动脂质的研究及其在临床中的应用。     

Targeted lipidomics: Discovery of new fatty acyl amides

The discovery of endogenous fatty acyl amides such as N-arachidonoyl ethanolamide (anandamide), N-oleoyl ethanolamide (OEA), and N-arachidonoyl dopamine (NADA) as important signaling molecules in the central and peripheral nervous system has led us to pursue other unidentified signaling molecules. Until recently, technical challenges, particularly those associated with lipid purification and chemical analysis, have hindered the identification of low abundance signaling lipids. Improvements in chromatography and mass spectrometry (MS) such as miniaturization of high-performance liquid chromatography components, hybridization of multistage mass spectrometers and time-of-flight technology, the development of electrospray ionization (ESI) and of information-dependent acquisition, now permit rapid identification of novel, low abundance, signaling lipids.     

脂质组学在中药研究中的应用

脂质组学是对生物体中脂质的种类、功能和代谢途径进行系统性研究的一门新兴学科，通过比较不同生理或病理状态下脂质代谢网络的变化，发现疾病或药物的生物标志物和分子机制。脂质组学作为系统生物学的重要组成部分，与中医药的整体观及系统理论相契合，是促进中医药现代化研究的有力工具。主要对脂质组学技术进行简述，总结近年来脂质组学技术在中药药效、作用机制和毒性研究中的应用概况，并结合其他学科在中药药性理论和中药质量控制研究中的应用成果，为拓展脂质组学在中药研究中的应用思路，推动中医药传统理论与现代科学技术的有机融合提供参考。     

Effects of Aging on Human Meibum

PurposeThe purpose of this study was to determine if aging affects meibum lipid composition in non-meibomian gland dysfunction (MGD)/non-dry eye (DE) population. Aging has been repeatedly linked to pathological changes in various tissues and organs, including the onset of MGD and DE, in a number of clinical and population-wide surveys. Both conditions have been associated with abnormal meibum secretion and composition, among other factors. However, the chemical basis for such a connection has not been established yet.MethodsTo identify and characterize possible changes in the meibum and meibogenesis with aging, lipidomic analyses of meibum samples collected from human subjects of two age groups – young (29 ± 5 years, n = 21) and elderly (68 ± 7 years, n = 29) – with similar male to female ratios in each group were conducted. Intact lipid species from major lipid groups of meibum (such as wax esters, cholesteryl esters, free cholesterol, triacylglycerols, etc.) were compared using lipidome-wide untargeted (such as Principal Component Analysis) and targeted (such as Orthogonal Projections to Latent Structures Discriminant Analysis) approaches, along with focused analyses of specific lipid species in liquid-chromatography mass spectrometry (LC-MS) and tandem mass spectrometry (MS-MS) experiments.ResultsExtremely high similarities of meibum lipids in the two age groups were observed, with only minor changes in the individual lipid species. The magnitude of the intergroup variability for tested lipid species was comparable to the intragroup variability for the same meibum components. No statistically significant differences in the lipid esterification, elongation, and unsaturation patterns were observed.ConclusionsChronological aging itself seems to have only minor effect on meibogenesis in healthy, non-MGD/non-DE subjects.     

Comparative lipidomics and proteomics analysis of platelet lipid rafts using different detergents

Lipid rafts play a pivotal role in physiological functions of platelets. Their isolation using nonionic mild detergents is considered as the gold standard method, but there is no consensual detergent for lipid raft studies. We aimed to investigate which detergent is the most suitable for lipid raft isolation from platelet membrane, based on lipidomics and proteomics analysis.

Platelets were obtained from healthy donors. Twelve sucrose fractions were extracted by three different detergents, namely Brij 35, Lubrol WX, and Triton X100, at 0.05% and 1%. After lipidomics analysis and determination of fractions enriched in cholesterol (Ch) and sphingomyelin (SM), proteomics analysis was performed.

Lipid rafts were mainly observed in 1–4 fractions, and non-rafts were distributed on 5–12 fractions. Considering the concentration of Ch and SM, Lubrol WX 1% and Triton X100 1% were more suitable detergents as they were able to isolate lipid raft fractions that were more enriched than non-raft fractions. By proteomics analysis, overall, 822 proteins were identified in platelet membrane. Lipid raft fractions isolated with Lubrol WX 0.05% and Triton X100 1% contained mainly plasma membrane proteins. However, only Lubrol WX 0.05 and 1% and Triton X100 1% were able to extract non-denaturing proteins with more than 10 transmembrane domains.

Our results suggest that Triton X100 1% is the most suitable detergent for global lipid and protein studies on platelet plasma membrane. However, the detergent should be adapted if investigation of an association between specific proteins and lipid rafts is planned.     

非靶向脂质组学在子痫前期预测中的应用

目的采用非靶向脂质组学寻找能早期预测子痫前期的生物标志物。方法选取子痫前期高危孕妇,根据后期是否发生子痫前期分为子痫前期组(33例)和无子痫前期组(对照组,33例)。采用超高效液相色谱(UPLC)-飞行时间质谱(TOF)联用技术对所有对象的血清样本进行脂质组学检测。采用差异倍数、非参数Wilcoxon秩和检验、主成分分析(PCA)和偏最小二乘判别(PLS-DA)筛选生物标志物,并对定性的生物标志物进行代谢通路和富集分析。采用受试者工作特征(ROC)曲线评价筛选出的代谢物对子痫前期的诊断价值。结果共筛选出42种生物标志物,其中甘氨胆酸、二十二碳五烯酸和磷脂酰肌醇(PI)(16:1(9Z)/16:0)水平在子痫前期组中明显升高,胆固醇酯(CE)[22:4(7Z,10Z,13Z,16Z)]、二酰甘油(DG)[18:0/20:1(11Z)/0:0]水平明显降低。含2种以上生物标志物的代谢通路分别为鞘脂类代谢途径、甘油磷脂代谢途径和初级胆汁酸生物合成途径,主要参与α-亚麻酸和亚麻酸代谢、缩醛磷脂合成、长链饱和脂肪酸的线粒体β氧化、鞘脂代谢及胆汁酸生物合成。ROC曲线分析结果显示,CE[22:4(7Z,10Z,13Z,16Z)]、DG[18:0/20:1(11Z)/0:0]、二十二碳五烯酸、PI[16:1(9Z)/16:0]及甘氨胆酸诊断子痫前期的曲线下面积分别为0.723、0.715、0.678、0.669和0.660。结论非靶向脂质组学筛选出的生物标志物能有效区分子痫前期患者和无子痫前期孕妇。甘油磷脂代谢、初级胆汁酸代谢、α-亚麻酸和亚麻酸代谢、胆碱代谢与子痫前期发病有关。     

Wound healing grafts: Omega‐3 fatty acid lipid content differentiates the lipid profiles of acellular Atlantic cod skin from traditional dermal substitutes

Acellular fish skin (ACS) has emerged as a dermal substitute used to promote wound healing with decreased scar formation and pain relief that may be due to polyunsaturated fatty acid (PUFA) content. However, the PUFA content of ACS is still unknown. The aim of this study was to compare the total fatty acids and lipid profiles of ACS to two bovine‐based grafts and standard of care human cadaver skin (HCS). Furthermore, there was also the goal to assess the capability of ACS lipid content to enhance wound healing. The fatty acid analysis was performed with GC–FID, and an LC–MS untargeted method was developed in order to the analyse the lipid profiles of the grafts was. The enhancement of wound healing by the ACS extract was investigated in vitro on HaCat cells. Our results showed that ACS had the highest content of PUFA (27.0 ± 1.43% of their total fatty acids), followed by HCS (20.6 ± 3.9%). The two grafts of bovine origin presented insignificant PUFA amounts. The majority of the PUFAs found in ACS were omega‐3, and in HCS, they were omega‐6. The untargeted lipidomics analysis demonstrated that ACS grafts were characterized by phosphatidylcholine containing either 20:5 or 22:6 omega‐3 PUFA. The ACS lipid extract increased the HaCat cells migration and enhanced wound closure 4 hr earlier versus control. Our study demonstrated that ACS has a lipid profile that is distinct from other wound healing grafts, that PUFAs are maintained in ACS post‐processing as phosphatidylcholine, and that ACS lipid content influences wound healing properties.     

Can oral health and oral‐derived biospecimens predict progression of dementia?

Growing evidence indicates that oral health and brain health are interconnected. Declining cognition and dementia coincide with lack of self‐preservation, including oral hygiene. The oral microbiota plays an important role in maintaining oral health. Emerging evidence suggests a link between oral dysbiosis and cognitive decline in patients with Alzheimer's disease. This review showcases the recent advances connecting oral health and cognitive function during aging and the potential utility of oral‐derived biospecimens to inform on brain health. Collectively, experimental findings indicate that the connection between oral health and cognition cannot be underestimated; moreover, oral biospecimens are abundant and readily obtainable without invasive procedures, which may help inform on cognitive health.