Hyperoside Nanomicelles Alleviate Atherosclerosis by Modulating the Lipid Profile and Intestinal Flora Structure in High-Fat-Diet-Fed Apolipoprotein-E-Deficient Mice.

Atherosclerosis (AS) is a serious threat to human health and the main pathological basis of cardiovascular disease. Hyperoside (Hyp), a flavonoid found mainly in traditional Chinese herbs, can exert antitumor, anti-inflammatory, antioxidant, and cardiovascular-protective effects. Herein, we prepared hybrid nanomicelles (HFT) comprising Hyp loaded into pluronic F-127 and polyethylene glycol 1000 vitamin E succinate and assessed their effects on AS. To establish an AS model, apolipoprotein-E-deficient (ApoE-/-) mice were fed a high-fat diet. We then analyzed the effects of HFT on AS-induced changes in aortic tissues and metabolic markers, simultaneously assessing changes in gut flora community structure. In mice with AS, HFT significantly reduced the aortic plaque area; decreased levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, inflammatory factors, and inducible nitric oxide synthase (NOS); increased high-density lipoprotein cholesterol, endothelial NOS, superoxide dismutase, catalase, and glutathione levels; and promoted the proliferation of beneficial gut bacteria. HFT could regulate intestinal flora structure and lipid metabolism and inhibit inflammatory responses. These beneficial effects may be mediated by inhibiting nuclear factor kappa B signal activation, reducing inflammatory factor expression and improving gut microflora structure and dyslipidemia. The present study provides an empirical basis for the development and clinical application of new dosage forms of Hyp.

Serum untargeted lipidomics by UHPLC-ESI-HRMS aids the biomarker discovery of colorectal adenoma.

BACKGROUND: Colorectal adenoma (CA) is an important precancerous lesion and early screening target of colorectal cancer (CRC). Lipids with numerous physiological functions are proved to be involved in the development of CRC. However, there is no lipidomic study with large-scale serum samples on diagnostic biomarkers for CA. METHODS: The serum lipidomics of CA patients (n = 50) and normal control (NR) (n = 50) was performed by ultra high performance liquid chromatography-high resolution mass spectrometry with electrospray ionization (UHPLC-ESI-HRMS). Univariate and multivariate statistical analyses were utilized to screen the differential lipids between groups, and combining the constituent ratio analysis and diagnostic efficiency evaluation by receiver operating characteristic (ROC) curve disclosed the potential mechanism and biomarkers for CA. RESULTS: There were obvious differences in serum lipid profiles between CA and NR groups. Totally, 79 differential lipids were selected by criterion of P < 0.05 and fold change > 1.5 or < 0.67. Triacylglycerols (TAGs) and phosphatidylcholines (PCs) were the major differential lipids with ratio > 60%, indicating these two lipid metabolic pathways showed evident disequilibrium, which could contribute to CA formation. Of them, 12 differential lipids had good diagnostic ability as candidate biomarkers for CA (AUC ≥ 0.900) by ROC analysis. CONCLUSIONS: To our knowledge, this is the first attempt to profile serum lipidomics and explore lipid biomarkers of CA to help early screening of CRC. 12 differential lipids are obtained to act as potential diagnostic markers of CA. PCs and fatty acids were the main dysregulated biomarkers for CA in serum.

Untargeted lipidomics reveals specific lipid abnormalities in Sjögren's syndrome.

OBJECTIVE: The relationship between serum lipid variations in SS and healthy controls was investigated to identify potential predictive lipid biomarkers. METHODS: Serum samples from 230 SS patients and 240 healthy controls were collected. The samples were analysed by ultrahigh-performance liquid chromatography coupled with Q Exactive™ spectrometry. Potential lipid biomarkers were screened through orthogonal projection to latent structures discriminant analysis and further evaluated by receiver operating characteristic analysis. RESULTS: A panel of three metabolites [phosphatidylcholine (18:0/22:5), triglyceride (16:0/18:0/18:1) and acylcarnitine (12:0)] was identified as a specific biomarker of SS. The receiver operating characteristic analysis showed that the panel had a sensitivity of 84.3% with a specificity of 74.8% in discriminating patients with SS from healthy controls. CONCLUSION: Our approach successfully identified serum biomarkers associated with SS patients. The potential lipid biomarkers indicated that SS metabolic disturbance might be associated with oxidized lipids, fatty acid oxidation and energy metabolism.

Analysis of HETEs in human whole blood by chiral UHPLC-ECAPCI/HRMS.

The biosynthesis of eicosanoids occurs enzymatically via lipoxygenases, cyclooxygenases, and cytochrome P450, or through nonenzymatic free radical reactions. The enzymatic routes are highly enantiospecific. Chiral separation and high-sensitivity detection methods are required to differentiate and quantify enantioselective HETEs in complex biological fluids. We report here a targeted chiral lipidomics analysis of human blood using ultra-HPLC-electron capture (EC) atmospheric pressure chemical ionization/high-resolution MS. Monitoring the high-resolution ions formed by the fragmentation of pentafluorobenzyl derivatives of oxidized lipids during the dissociative EC, followed by in-trap fragmentation, increased sensitivity by an order of magnitude when compared with the unit resolution MS. The 12(S)-HETE, 12(S)-hydroxy-(5Z,8E,10E)-heptadecatrienoic acid [12(S)-HHT], and 15(S)-HETE were the major hydroxylated nonesterified chiral lipids in serum. Stimulation of whole blood with zymosan and lipopolysaccharide (LPS) resulted in stimulus- and time-dependent effects. An acute exposure to zymosan induced ∼80% of the chiral plasma lipids, including 12(S)-HHT, 5(S)-HETE, 15(R)-HETE, and 15(S)-HETE, while a maximum response to LPS was achieved after a long-term stimulation. The reported method allows for a rapid quantification with high sensitivity and specificity of enantiospecific responses to in vitro stimulation or coagulation of human blood.

Linoelaidic acid gavage has more severe consequences on triglycerides accumulation, inflammation and intestinal microbiota in mice than elaidic acid.

This work aims to study the effects of oral gavage (0.2 mg/g body weight) of elaidic acid (C18:1-9 t, EA) and linoelaidic acid (C18:2-9 t,12 t, LEA) on lipid metabolism, inflammation and gut homeostasis of mice. Results showed that both EA and LEA gavage significantly increased LDL-c, TC and oxidative stress levels in the liver and serum and may stimulate liver inflammation via NF-κB and MAPK signaling pathway. Compared with EA, LEA gavage significantly promoted TAG accumulation and inflammatory signaling. Serum lipidomics revealed that LEA intake significantly increased the concentration of ∼50 TAGs, while EA gavage primarily caused significant decreases in several SMs. 16S rRNA demonstrated that LEA ingestion markedly changed fecal microbiota by enriching Lactobacillus (phylum Firmicutes), however, EA treatment did not affect it. Overall, LEA gavage has more severe consequences on TAG accumulation, inflammation and microbial structure than EA, highlighting that the number of trans double bonds affects these processes.

UHPLC-HRMS-based serum untargeted lipidomics: Phosphatidylcholines and sphingomyelins are the main disturbed lipid markers to distinguish colorectal advanced adenoma from cancer.

Colorectal advanced adenoma (CAA) is a key precancerous lesion of colorectal cancer (CRC), and early diagnosis can lessen CRC morbidity and mortality. Although abnormal lipid metabolism is associated with the development of CRC, there are no studies on the biomarkers and mechanism of lipid metabolism linked to CAA carcinogenesis. Hence, we performed a lipidomics study of serum samples from 46 CAA, and 50 CRC patients by the ultra high-performance liquid chromatography tandem high resolution mass spectrometry (UHPLC-HRMS) in both electrospray ionization (ESI) modes. Differential lipids were selected by univariate and multivariate statistics analysis, and their diagnostic performance was evaluated using a receiver operating characteristic curve (ROC) analysis. Combining P < 0.05 and variable importance in projection (VIP) > 1, 59 differential lipids were obtained totally. Ten of them showed good discriminant ability for CAA and CRC (AUC > 0.900). Especially, the lipid panel consisting of PC 44:5, PC 35:6e, and SM d40:3 showed the highest selection frequency and outperformed (AUC = 0.952). Additionally, phosphatidylcholine (PC) and sphingomyelin (SM) were the main differential and high-performance lipids. In short, this is the first study to explore the biomarkers and mechanism for CAA-CRC sequence with large-scale serum lipidomics. The findings should provide valuable reference and new clues for the development of diagnostic and therapeutic strategies of CRC.

Serum Untargeted UHPLC-HRMS-Based Lipidomics to Discover the Potential Biomarker of Colorectal Advanced Adenoma.

BACKGROUND: As a key precancerous lesion, colorectal advanced adenoma (CAA) is closely related to the occurrence and development of colorectal cancer (CRC). Effective identification of CAA-related biomarkers can prevent CRC morbidity and mortality. Lipids, as an important endogenous substance, have been proved to be involved in the occurrence and development of CRC. Lipidomics is an advanced technique that studies lipid metabolism and biomarkers of diseases. However, there are no lipidomics studies based on large serum samples to explore diagnostic biomarkers for CAA. METHODS: An integrated serum lipid profile from 50 normal (NR) and 46 CAA subjects was performed using ultra-high performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS). Lipidomic data were acquired for negative and positive ionization modes, respectively. Differential lipids were selected by univariate and multivariate statistics analyses. A receiver operator characteristic curve (ROC) analysis was conducted to evaluate the diagnostic performance of differential lipids. RESULTS: A total of 53 differential lipids were obtained by combining univariate and multivariate statistical analyses (P < 0.05 and VIP > 1). In addition, 12 differential lipids showed good diagnostic performance (AUC > 0.90) for the discrimination of NR and CAA by receiver operating characteristic curve (ROC) analysis. Of them, the performance of PC 44:5 and PC 35:6e presented the outstanding performance (AUC = 1.00, (95% CI, 1.00-1.00)). Moreover, triglyceride (TAG) had the highest proportion (37.74%) as the major dysregulated lipids in the CAA. CONCLUSION: This is the first study that profiled serum lipidomics and explored lipid biomarkers with good diagnostic ability of CAA to contribute to the early prevention of CRC. Twelve differential lipids that effectively discriminate between NR and CAA serve as the potential diagnostic markers of CAA. An obvious perturbation of TAG metabolism could be involved in the CAA formation.

Lipidomic Analysis Reveals Serum Alteration of Plasmalogens in Patients Infected With ZIKA Virus.

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the Flavivirus genus of the Flaviviridae family. Since the large outbreaks in French Polynesia in 2013-2014 and in Brazil in 2015, ZIKV has been considered a new public health threat. Similar to other related flavivirus, ZIKV is associated with mild and self-limiting symptoms such as rash, pruritus, prostration, headache, arthralgia, myalgia, conjunctivitis, lower back pain and, when present, a short-term low grade fever. In addition, ZIKV has been implicated in neurological complications such as neonatal microcephaly and Guillain-Barré syndrome in adults. Herein, serum lipidomic analysis was used to identify possible alterations in lipid metabolism triggered by ZIKV infection. Patients who presented virus-like symptoms such as fever, arthralgia, headache, exanthema, myalgia and pruritus were selected as the control group. Our study reveals increased levels of several phosphatidylethanolamine (PE) lipid species in the serum of ZIKV patients, the majority of them plasmenyl-phosphatidylethanolamine (pPE) (or plasmalogens) linked to polyunsaturated fatty acids. Constituting up to 20% of total phospholipids in humans, plasmalogens linked to polyunsaturated fatty acids are particularly enriched in neural membranes of the brain. The biosynthesis of plasmalogens requires functional peroxisomes, which are important sites for viral replication, including ZIKV. Thus, increased levels of plasmalogens in serum of ZIKV infected subjects suggest a link between ZIKV life cycle and peroxisomes. Our data provide important insights into specific host cellular lipids that are likely associated with ZIKV replication and may serve as platform for antiviral strategy against ZIKV.