Exploration of circulating metabolic signature of erythrodermic psoriasis based on LC-MS metabolomics.

Erythrodermic psoriasis (EP) is a rare and life-threatening disease, the pathogenesis of which remains to be largely unknown. Metabolomics analysis can provide global information on disease pathophysiology, candidate biomarkers, and potential intervention strategies. To gain a better understanding of the mechanisms of EP and explore the serum metabolic signature of EP, we conducted an untargeted metabolomics analysis from 20 EP patients and 20 healthy controls. Furthermore, targeted metabolomics for focused metabolites were identified in the serum samples of 30 EP patients and 30 psoriasis vulgaris (PsV) patients. In the untargeted analysis, a total of 2992 molecular features were extracted from each sample, and the peak intensity of each feature was obtained. Principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed significant difference between groups. After screening, 98 metabolites were found to be significantly dysregulated in EP, including 67 down-regulated and 31 up-regulated. EP patients had lower levels of L-tryptophan, L-isoleucine, retinol, lysophosphatidylcholine (LPC), and higher levels of betaine and uric acid. KEGG analysis showed differential metabolites were enriched in amino acid metabolism and glycerophospholipid metabolism. The targeted metabolomics showed lower L-tryptophan in EP than PsV with significant difference and L-tryptophan levels were negatively correlated with the PASI scores. The serum metabolic signature of EP was discovered. Amino acid and glycerophospholipid metabolism were dysregulated in EP. The metabolite differences provide clues for pathogenesis of EP and they may provide insights for therapeutic interventions.

Predicting effect of anti-PD-1/PD-L1 inhibitors therapy for hepatocellular carcinoma by detecting plasma metabolite based on UHPLC-MS.

Introduction: Anti-PD-1/PD-L1 inhibitors therapy has become a promising treatment for hepatocellular carcinoma (HCC), while the therapeutic efficacy varies significantly among effects for individual patients are significant difference. Unfortunately, specific predictive biomarkers indicating the degree of benefit for patients and thus guiding the selection of suitable candidates for immune therapy remain elusive.no specific predictive biomarkers are available indicating the degree of benefit for patients and thus screening the preferred population suitable for the immune therapy. Methods: Ultra-high-pressure liquid chromatography-mass spectrometry (UHPLC-MS) considered is an important method for analyzing biological samples, since it has the advantages of high rapid, high sensitivity, and high specificity. Ultra-high-pressure liquid chromatography-mass spectrometry (UHPLC-MS) has emerged as a pivotal method for analyzing biological samples due to its inherent advantages of rapidity, sensitivity, and specificity. In this study, potential metabolite biomarkers that can predict the therapeutic effect of HCC patients receiving immune therapy were identified by UHPLC-MS. Results: A partial least-squares discriminant analysis (PLS-DA) model was established using 14 glycerophospholipid metabolites mentioned above, and good prediction parameters (R2 = 0.823, Q2 = 0.615, prediction accuracy = 0.880 and p < 0.001) were obtained. The relative abundance of glycerophospholipid metabolite ions is closely related to the survival benefit of HCC patients who received immune therapy. Discussion: This study reveals that glycerophospholipid metabolites play a crucial role in predicting the efficacy of immune therapy for HCC.

Lipid Identification of Biomarkers in Esophageal Squamous Cell Carcinoma by Lipidomic Analysis.

Lipids participate in many important biological functions through energy storage, membrane structure stabilization, signal transduction, and molecular recognition. Previous studies have shown that patients with esophageal squamous cell carcinoma (ESCC) have abnormal lipid metabolism. However, studies characterizing lipid metabolism in ESCC patients through lipidomics are limited. Plasma lipid profiles of 65 ESCC patients and 42 healthy controls (HC) were characterized by lipidomics-based ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Single-factor and multi-factor statistical analysis were used to screen the differences in blood lipids between groups, and combined with component ratio analysis and receiver operating characteristic (ROC) curve diagnostic efficiency assessment, to reveal the potential mechanisms and biomarkers of ESCC. There were significant differences in lipid profiles between the ESCC and HC groups. Thirty-six differential lipids (11 up-regulated and 25 down-regulated) were selected based on the criteria of p < .05 and fold change > 1.3 or < 0.77. Glycerophospholipids were the major differential lipids, suggesting that these lipid metabolic pathways exhibit a significant imbalance that may contribute to the development of esophageal squamous cell carcinoma. Among them, the seven candidate biomarkers for esophageal squamous cell carcinoma with the highest diagnostic value are three phosphatidylserine (PS), three fatty acids (FA) and one phosphatidylcholine (PC).

Metabolomics Study of Whole-body Vibration on Lipid Metabolism of Skeletal Muscle in Aging Mice.

Ageing increases the occurrence and development of many diseases. Exercise is believed to be an effective way to improve ageing and skeletal muscle atrophy. However, many elderly people are unable to engage in active exercise. Whole-body vibration is a passive way of moving that is especially suitable for the elderly and people who find it inconvenient to exercise. Metabolomics is the systematic study of metabolic changes in small molecules. In this study, metabolomics studies were performed to investigate the regulatory effect of whole-body vibration on the skeletal muscles of ageing mice. After 12 weeks, we found that whole-body vibration had the most obvious effect on lipid metabolism pathways (such as linoleic acid, α-linolenic acid metabolism, glycerophospholipid metabolism pathways) in skeletal muscle of ageing mice. Through further research we found that whole-body vibration decreased the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol and very low-density lipoprotein in blood; decreased the lipid deposition in skeletal muscle; decreased the protein expression of monocyte chemoattractant protein-1 and interleukin-6; improved the protein levels of phosphorylated insulin receptor substrate-1, phosphate phosphoinositide 3-kinase and p-AKT; improved the protein levels of klotho; and decreased the protein expression of p53. These findings reveal that whole-body vibration might postpone senility by attenuating lipid deposition and reducing chronic inflammation and the insulin resistance of skeletal muscle.

Distinct lipid signatures are identified in the plasma of rats with chronic inflammation induced by estradiol benzoate and sex hormones.

INTRODUCTION: Prostatitis is likely to occur in younger or middle-aged men, while prostate cancer is likely to occur in older men. Although amino acids and lipids as biomarkers of prostate cancer have been examined using prostate cancer cell lines/tissues, no previous studies have evaluated amino acids or lipids as potential chronic prostatitis biomarkers. OBJECTIVES: The study's aim was to identify amino acids and lipids that could serve as potential biomarkers of chronic prostatitis. METHODS: We profiled the amino acids and lipids found in plasma from rats collected in a previous study. In brief, a total of 148 Sprague-Dawley rats (offspring) were dosed with estradiol benzoate (EB) on postnatal days (PNDs) 1, 3 and 5, and subsequently dosed with testosterone (T)/estradiol (E) tubes via subcutaneous implants from PND 90 to 200. Plasma was collected on PNDs 30, 90, 100, 145 and 200. Analysis was conducted with a Xevo TQ-S triple-quadrupole mass spectrometer using a Biocrates AbsoluteIDQ p180 kit. RESULTS: Plasma acylcarnitines [(C2, C16:1, C18, C18:1, C18:1-OH, and C18:2)], glycerophospholipids (lysophosphatidylcholine-acyl, -di-acyl, and -di-acyl acyl-alkyl) and sphingomyelins [SM (OH) C16:1, SM C18:0, SM C18:1, and SM C20:2] significantly increased on PND 145, when chronic inflammation was observed in the dorsolateral prostate of rats dosed with EB, T, and E. No statistical significances of amino acid levels were observed in the EB + T + E group on PND 145. CONCLUSION: Exposure to EB, T, and E altered lipid levels in rat plasma with chronic prostate inflammation. These findings suggest that the identified lipids may be predictive chronic prostatitis biomarkers. The results require confirmation through additional nonclinical and human studies.

Performance of PEth Compared With Other Alcohol Biomarkers in Subjects Presenting For Occupational and Pre-Employment Medical Examination.

AIMS: To compare the performance of short- and long-term alcohol biomarkers for the evaluation of alcohol drinking in employment-related health controls. METHODS: The 519 blood samples originated from 509 patients (80% men) presenting at occupational health units and medical centers at employment agencies for the evaluation of risky drinking. The laboratory investigation comprised the measurement of phosphatidylethanol (PEth 16:0/18:1), carbohydrate-deficient transferrin (CDT; % disialotransferrin), gamma-glutamyl transferase (GGT), mean corpuscular volume (MCV), ethanol and ethyl glucuronide (EtG). RESULTS: Many samples tested positive for acute (57%) and chronic (69%) alcohol biomarkers. PEth was the single most positive biomarker (64%; cut-off 0.05 µmol/l or 35 µg/l) and the only positive chronic biomarker in 100 cases. The highest PEth concentrations were seen in samples positive for all chronic biomarkers, followed by those also being CDT positive (cut-off 2.0%). All 126 CDT-positive samples were positive for PEth using the lower reporting limit (≥0.05 µmol/l) and for 114 cases (90%) also using the higher limit (≥0.30 µmol/l or 210 µg/l). In the CDT-positive cases, the PEth median concentration was 1.71 µmol/l, compared with 0.45 µmol/l for the CDT-negative cases (P < 0.0001). PEth and CDT values were correlated significantly (r = 0.63, P < 0.0001). Among the EtG-positive cases (≥1.0 ng/ml), 95% were also PEth positive, and all ethanol-positive cases (≥0.10 g/l) were also PEth positive. CONCLUSIONS: For optimal detection of drinking habits, using a combination of short- and long-term alcohol biomarkers provided best information. PEth was the single most positive alcohol biomarker, whereas GGT and MCV offered little additional value over PEth and CDT.

Alcohol and Bone Turnover Markers among People Living with HIV and Substance Use Disorder.

BACKGROUND: Although unhealthy alcohol use and low bone density are prevalent among people living with HIV (PLWH), it is not clear whether alcohol use is associated with bone turnover markers (BTMs), and if so, at what quantity and frequency. The study objective was to examine the association between alcohol and BTMs in PLWH with substance use disorder. METHODS: We studied a prospective cohort recruited from 2 HIV clinics who met criteria for DSM-IV substance dependence or reported ever injection drug use. Outcomes were BTM of (i) bone formation (serum procollagen type 1 N-terminal propeptide [P1NP]) and (ii) bone resorption (serum C-telopeptide type 1 collagen [CTx]). Alcohol consumption measures included (i) mean number of drinks/d (Timeline Follow-Back [TLFB]) (primary predictor), (ii) any alcohol use on ≥20 of the past 30 days, and phosphatidylethanol (PEth), a biomarker of recent alcohol consumption. Linear regression analysis examined associations between (i) each alcohol measure and each BTM and (ii) change in alcohol and change in BTM over 12 months. RESULTS: Among 198 participants, baseline characteristics were as follows: The median age was 50 years; 38% were female; 93% were prescribed antiretroviral medications; 13% had ≥20 drinking days/month; mean drinks/day was 1.93 (SD 3.89); change in mean drinks/day was -0.42 (SD 4.18); mean P1NP was 73.1 ng/ml (SD 34.5); and mean CTx was 0.36 ng/ml (SD 0.34). Higher drinks/day was significantly associated with lower P1NP (slope -1.09 ng/ml; 95% confidence interval [CI] -1.94, -0.23, per each additional drink). On average, those who drank on ≥ 20 days/month had lower P1NP (-15.45 ng/ml; 95% CI: -26.23, -4.67) than those who did not. Similarly, PEth level ≥ 8ng/ml was associated with lower P1NP. An increase in drinks/d was associated with a decrease in P1NP nonsignificantly (-1.14; 95% CI: -2.40, +0.12; p = 0.08, per each additional drink). No significant associations were detected between either alcohol measure and CTx. CONCLUSIONS: In this sample of PLWH with substance use disorder, greater alcohol consumption was associated with lower serum levels of bone formation markers.

Persistent Urinary Ethyl Sulfate in the Absence of Urinary Ethyl Glucuronide in a Patient with Alcohol Use Disorder Who Claimed Abstinence.

A 48-year-old nurse with an alcohol use disorder history was being monitored in a professional health program. She consistently produced low-to-moderate urinary ethyl sulfate (EtS) concentrations in the absence of detectable urinary ethyl glucuronide (EtG), blood phosphatidylethanol and breath alcohol. She denied intentional ethanol consumption. After prolonged monitoring in a drug treatment program, including a period in a controlled environment, we concluded that this individual's urinary EtS likely resulted from anatomical and microbial factors related to Roux-en-Y gastric bypass surgery, with possible contributions from hidden dietary sources of ethanol. We have no definitive explanation for the lack of urinary EtG.

Prevalence of alcohol use in late pregnancy.

BACKGROUND: Prenatal alcohol exposure (PAE) can result in detrimental developmental complications. The objective of this study was to estimate the most recent PAE prevalence data for the state of West Virginia (WV) and associated factors. METHOD: In all, 1830 newborn residual dried blood spots (DBS) in the WV Newborn Screening Repository were analyzed for phosphatidylethanol (PETH). Data were matched with Project WATCH data (94% match, N = 1729). RESULTS: The prevalence of late pregnancy PAE was 8.10% (95%CI: 6.81, 9.38) for all births, 7.61% (95%CI: 6.26, 8.97) for WV residents only, and ranged from 2.27 to 17.11% by region. The significant factors associated with PAE included smoking (OR: 2.03, 95% CI: 1.40, 2.94), preterm births (OR: 1.88; 95% CI: 1.23, 2.89), birth weight of ≤2000 g vs. >3000 g (OR: 2.62, 95%CI: 1.19, 5.79), no exclusive breastfeeding intention (OR: 1.45, 95% CI: 1.02, 2.04), and not exclusively breastfeeding before discharge (OR: 1.61; 95% CI: 1.09, 2.38). CONCLUSION: The prevalence of PAE is higher than previously shown for the state. Accurate and timely estimates are vital to inform public health workers, policymakers, researchers, and clinicians to develop and promote effective prevention strategies to lower PAE prevalence and provide targeted interventions and treatment services for infants affected by PAE.

Differentiating Types of Self-Reported Alcohol Abstinence.

We contrast three types of abstinence: quit after alcohol associated problems (Q-AP), quit for other reasons (Q-OR), and lifetime abstainer (LTA). We summarized the characteristics of people living with HIV (PLWH), and matched uninfected individuals, by levels of alcohol use and types of abstinence. We then identified factors that differentiate abstinence and determined whether the association with an alcohol biomarker or a genetic polymorphism is improved by differentiating abstinence. Among abstainers, 34% of PLWH and 38% of uninfected were Q-AP; 53% and 53% were Q-OR; and 12% and 10% were LTA. Logistic regression models found smoking, alcohol, cocaine, and hepatitis C increased odds of Q-AP, whereas smoking and marijuana decreased odds of LTA. Differentiating types of abstinence improved association. Q-APs and LTAs can be readily differentiated by an alcohol biomarker and genetic polymorphism. Differentiating type of abstinence may enhance understanding of alcohol health effects.

Serum lipidomics for exploring biomarkers of bortezomib therapy in patients with multiple myeloma.

Although the proteasome inhibitor bortezomib (BTZ) shows excellent efficacy in multiple myeloma (MM), a fraction of patients has a suboptimal or no response to this agent. In addition, BTZ-induced peripheral neuropathy (BiPN), a frequent side-effect of this therapy, limits its use in some patients. This study aimed to explore serum lipid biomarker candidates to predict the response to BTZ and the severity of BiPN. Fifty-nine serum samples were collected from patients with MM prior to receiving BTZ plus low-dose dexamethasone therapy. Serum levels of phospholipids, sphingolipids, neutral lipids, and polyunsaturated fatty acids and their oxidation products were measured by a comprehensive lipidomic study. Overall, 385 lipid metabolites were identified in patients' sera; lower levels of several glycerophospholipids, sphingolipids, and cholesteryl esters were associated with a poor treatment response. Metabolites related to platelet-activating factor biosynthesis and cholesterol metabolism appeared particularly relevant. Furthermore, several lysophosphatidylcholines, phosphatidylcholines, ceramides, neutral lipids, and oxidative fatty acids were significantly increased or decreased in patients with BiPN grades ranging from G0 to G3. Among these compounds, mediators reportedly inducing myelin breakdown and stimulating inflammatory responses were prominent. Although further study is necessary to validate these biomarker candidates, our results contribute to the development of predictive biomarkers for response to BTZ treatment, or ensuing severe BiPN, in patients with MM.

Deep Lipidomics and Molecular Imaging of Unsaturated Lipid Isomers: A Universal Strategy Initiated by mCPBA Epoxidation.

Cellular lipidome is highly regulated through lipogenesis, rendering diverse double-bond positional isomers (C═C isomer) of a given unsaturated lipid species. In recent years, there are increasing reports indicating the physiological roles of C═C isomer compositions associated with diseases, while the biochemistry has not been broadly investigated due to the challenge in characterizing lipid isomers inherent to conventional mass spectrometry-based lipidomics. To address this challenge, we reported a universal, user-friendly, derivatization-based strategy, MELDI (mCPBA Epoxidation for Lipid Double-bond Identification), which enables both large-scale identification and spatial mapping of biological C═C isomers using commercial mass spectrometers without any instrument modification. With the developed liquid-chromatography mass spectrometry (LC-MS) lipidomics workflow, we elucidated more than 100 isomers among monounsaturated and polyunsaturated fatty acids and glycerophospholipids in human serum, where uncommon isomers of low abundance were quantified for the first time. The capability of MELDI-LC-MS in lipidome analysis was further demonstrated using the differentiated 3T3-L1 adipocytes, providing an insight into the cellular lipid reprogramming upon stearoyl-coenzyme A desaturase 1 (SCD1) inhibition. Finally, we highlighted the versatility of MELDI coupled with ambient mass spectrometry imaging to spatially resolve cancer-associated alteration of lipid isomers in a metastatic mouse tissue section. Our results suggested that MELDI will contribute to current lipidomics pipelines with a deeper level of structural information, allowing us to investigate the underlying lipid biochemistry.

Hepatitis C virus (HCV) related liver fibrosis in people who inject drugs (PWID) at the Stockholm Needle Exchange - evaluated with liver elasticity.

Background and aims: Sharing of unsterile injection equipment among people who inject drugs (PWID) is the major transmission-route for hepatitis C (HCV). HCV is highly prevalent in PWID in the Stockholm needle exchange programme (NEP). The frequency of advanced liver fibrosis among the participants is, however, unknown. Methods: From December 2016 to April 2018, all participants with chronic hepatitis C infection (CHC) were offered liver fibrosis evaluation at the Stockholm NEP, including liver stiffness measurement (LSM), a medical history and expanded blood tests to evaluate APRI and FIB-4 scores. Results: A total of 2037 individuals were enrolled of whom 964 (47.3%) had CHC. LSM was performed in 203 (21.1%) of eligible participants of whom 85% had mild fibrosis (LSM ≤9.4 kPa) and 15% advanced fibrosis (LSM ≥9.5 kPa). APRI >1 and FIB-4 > 3.25 only identified 30% of participants with advanced fibrosis. However, all 31(100%) participants with advanced fibrosis were detected when APRI >1 was combined with an age of ≥40 years and an injection drug use (IDU) duration of ≥15 years. Conclusions: We found that the diagnostic work-up for advanced fibrosis can be simplified with this combination of easily available factors. This allows identification of PWID in need of immediate HCV treatment to prevent further disease progression. Furthermore, LSM can be avoided among PWID with mild fibrosis, identified by age <40 years combined with IDU duration of <15 years and APRI score <1. This strategy enhances the HCV care cascade where LSM is not easily available, and will thus facilitate HCV treatment initiation.

Alcohol Consumption in Obese Patients Before and After Gastric Bypass as Assessed with the Alcohol Marker Phosphatidylethanol (PEth).

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) causes more rapid and enhanced absorption of alcohol. RYGB patients have also been reported to use more inpatient care for alcohol-related disease than do patients after other bariatric procedures. The present study was designed to evaluate alcohol consumption level before and after gastric bypass using a sensitive and specific alcohol biomarker. MATERIALS AND METHODS: Two separate consecutive groups of patients and a group of healthy blood donors, as reference group, were included in the study. Alcohol intake was assessed using the alcohol marker phosphatidylethanol (PEth) at preoperative baseline and at 1 and 2 years postoperatively. In the first patient group (n = 133), neither surgeon nor patient was informed about the results of PEth testing. In the second group (n = 214), PEth results above 0.30 µmol/L were considered to indicate excessive alcohol consumption and led to preoperative alcohol counseling. The groups were followed for 2 and 1 year, respectively. RESULTS: PEth results were significantly lower in both patient groups at baseline as well as postoperatively compared with the reference group. In both patient groups, there was a significant increase in PEth values at postoperative follow-up compared to baseline. CONCLUSIONS: Several physiological changes postoperatively have to be considered when interpreting PEth results in obese patients with dramatic weight reductions. According to results for PEth, obese patients treated with bariatric surgery would seem to have lower alcohol consumption compared with the reference group. Although slightly increasing their PEth values postoperatively, the RYGB patients did not reach the PEth values of the reference group.

Identification of the lipid biomarkers from plasma in idiopathic pulmonary fibrosis by Lipidomics.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an irreversible interstitial pulmonary disease featured by high mortality, chronic and progressive course, and poor prognosis with unclear etiology. Currently, more studies have been focusing on identifying biomarkers to predict the progression of IPF, such as genes, proteins, and lipids. Lipids comprise diverse classes of molecules and play a critical role in cellular energy storage, structure, and signaling. The role of lipids in respiratory diseases, including cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD) has been investigated intensely in the recent years. The human serum lipid profiles in IPF patients however, have not been thoroughly understood and it will be very helpful if there are available molecular biomarkers, which can be used to monitor the disease progression or provide prognostic information for IPF disease. METHODS: In this study, we performed the ultraperformance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-QTOF/MS) to detect the lipid variation and identify biomarker in plasma of IPF patients. The plasma were from 22 IPF patients before received treatment and 18 controls. RESULTS: A total of 507 individual blood lipid species were determined with lipidomics from the 40 plasma samples including 20 types of fatty acid, 159 types of glycerolipids, 221 types of glycerophospholipids, 47 types of sphingolipids, 46 types of sterol lipids, 7 types of prenol lipids, 3 types of saccharolipids, and 4 types of polyketides. By comparing the variations in the lipid metabolite levels in IPF patients, a total of 62 unique lipids were identified by statistical analysis including 24 kinds of glycerophoslipids, 30 kinds of glycerolipids, 3 kinds of sterol lipids, 4 kinds of sphingolipids and 1 kind of fatty acids. Finally, 6 out of 62 discriminating lipids were selected as the potential biomarkers, which are able to differentiate between IPF disease and controls with ROC analysis. CONCLUSIONS: Our results provided vital information regarding lipid metabolism in IPF patients and more importantly, a few potentially promising biomarkers were firstly identified which may have a predictive role in monitoring and diagnosing IPF disease.

A plasma lipidomics strategy reveals perturbed lipid metabolic pathways and potential lipid biomarkers of human colorectal cancer.

To explore underlying molecular mechanisms and identify novel lipid biomarkers promising for colorectal cancer (CRC) diagnosis, a continuous-flow two dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (2D LC-QToF/MS) method was employed to comprehensively measure lipid species in human plasma of CRC patients and healthy controls. With a total of 427 annotated lipid species, we identified 64 lipid species with corrected p value less than 0.05 and fold change more than 1.5. These significantly altered lipid species were mainly involved in glycerolipids and glycerophospholipids metabolism and sphingolipids metabolism. After the diagnosis ability evaluation based on the receiver operating characteristic (ROC) curve, phosphatidylglycerol (34:0), sphingomyelin (42:2), ceramide (44:5), lysophosphatidylcholine (18:3), lysophosphatidylcholine (18:2), phosphatidylethanolamine (O-36:3), phosphatidylethanolamine (O-38:3) and sphingomyelin (38:8) were finally proposed as the potential biomarkers with the area under the curve (AUC) more than 0.900. These results suggest that this 2D LC-QToF/MS-based lipidomics profiling has great potential as a noninvasive diagnostic method in detecting CRC and hopefully provide new clues to understand its underlying mechanism.

Serum Phospholipid Fatty Acid Composition in Cystic Fibrosis Patients with and without Liver Cirrhosis.

BACKGROUND/AIMS: Cystic fibrosis (CF) liver disease is the third most frequent cause of death in CF patients. Although it alters fatty acid (FA) metabolism, data concerning the profile of FA in CF patients with liver cirrhosis is lacking. This study aimed to assess the FA composition of serum phospholipids in CF patients with and without liver cirrhosis. METHODS: The study comprised 25 CF patients with liver cirrhosis and 25 without it. We assessed Z-scores for body height and weight, lung function, exocrine pancreatic sufficiency and colonization with Pseudomonas aeruginosa. FAs' profile of serum glycerophospholipids was quantified by gas chromatography mass spectrometry. RESULTS: In CF patients with liver cirrhosis, the levels of C16:0 were higher and the amounts of C20:2n-6, C20:3n-6, C20:4n-6, and all the n-3 polyunsaturated FAs (PUFAs) (C18:3n-3, C20:5n-3, C22:5n-3, C22:6n-3) were lower than those in CF subjects without liver cirrhosis. The n-6/n-3, C20:4n-6/C18:2n-6, total n-6/C18:2n-6, C20:5n-3/C18:3n-3 and total n-3/C18:3n-3 ratios did not differ between the 2 groups. CONCLUSIONS: Liver cirrhosis may associate with profound abnormalities in the composition of serum glycerophospholipids FAs in CF patients. None of the analyzed clinical factors could explain the greater prevalence of low levels of PUFAs in this CF subgroup.

Associations between fatty acids and low-grade inflammation in children from the LISAplus birth cohort study.

BACKGROUND/OBJECTIVES: Assessing fatty acid (FA) composition in relation to inflammatory markers can shed light on the role of different FA and their metabolism in low-grade inflammation. Existing exploratory studies in children are scarce, and findings inconsistent. We hence aim to analyse associations of FA with common inflammatory markers, high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6), in 10-year-old children. SUBJECTS/METHODS: Complete data were available for 958 participants from the 10-year follow-up of the LISAplus (Influence of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood plus the Influence of Traffic Emissions and Genetics) birth cohort study. FA composition was assessed in serum glycerophospholipids. Hs-CRP and IL-6 were categorised into three levels. Associations of FA with inflammatory markers were assessed using multinomial logistic regression, adjusting for potential confounders. Additionally, sex-stratified analyses were carried out. RESULTS: FA exposures associated with significantly higher low-grade inflammation, as indicated by higher hs-CRP or IL-6 levels, included: palmitic acid (PA) (IL-6: P<0.001, 95% confidence interval: 1.30; 2.43), arachidonic acid (AA) (hs-CRP: P=0.002, 1.07; 1.31), n-6 highly unsaturated FA (HUFA) (hs-CRP: P=0.002, 1.06; 1.27), ratio of AA to linoleic acid (AA/LA) (hs-CRP: P<0.001, 1.16; 1.62) and total saturated FA (SFA) (IL-6: P<0.001, 1.77; 3.15). FA exposures associated with reduced levels of inflammatory markers included LA (hs-CRP: P=0.001, 0.84; 0.96; IL-6: P<0.001, 0.69; 0.90) and total polyunsaturated FA (PUFA) (IL-6: P<0.001, 0.57; 0.78). CONCLUSIONS: These findings suggest that higher SFA and minor n-6 HUFA, namely PA and AA, are associated with increased low-grade inflammation in children, whereas the major dietary n-6 PUFA and total PUFA are associated with reduced inflammation. Elevated desaturase activity, estimated by the ratio AA/LA, may be associated with higher inflammation, particularly in boys.

The association of the lipidomic profile with features of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) affects up to 18% of reproductive-aged women with reproductive and metabolic complications. While lipidomics can identify associations between lipid species and metabolic diseases, no research has examined the association of lipid species with the pathophysiological features of PCOS. The aim of this study was to examine the lipidomic profile in women with and without PCOS. This study was a cross-sectional study in 156 age-matched pre-menopausal women (18-45 years, BMI >20 kg/m2; n = 92 with PCOS, n = 64 without PCOS). Outcomes included the association between the plasma lipidomic profile (325 lipid species (24 classes) using liquid chromatography mass spectrometry) and PCOS, adiposity, homeostasis assessment of insulin resistance (HOMA), sex hormone-binding globulin (SHBG) and free androgen index (FAI). There were no associations of the lipidomic profile with PCOS or testosterone. HOMA was positively associated with 2 classes (dihydroceramide and triacylglycerol), SHBG was inversely associated with 2 classes (diacylglycerol and triacylglycerol), FAI was positively associated with 8 classes (ceramide, phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylinositol, diacylglycerol and triacylglycerol) and waist circumference was associated with 8 classes (4 positively (dihydroceramide, phosphatidylglycerol, diacylglycerol and triacylglycerol) and 4 inversely (trihexosylceramide, GM3 ganglioside, alkenylphosphatidylcholine and alkylphosphatidylethanolamine)). The lipidomic profile was primarily related to central adiposity and FAI in women with or without PCOS. This supports prior findings that adiposity is a key driver of dyslipidaemia in PCOS and highlights the need for weight management through lifestyle interventions.

Metabolomic study on the antihypertensive effect of S-1-propenylcysteine in spontaneously hypertensive rats using liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry.

Aged garlic extract (AGE) has been shown to improve hypertension in both clinical trials and experimental animal models. However, the active ingredient of AGE remains unknown. In the present study, we investigated the antihypertensive effects of AGE and its major constituents including S-1-propenylcysteine (S1PC) and S-allylcysteine (SAC) using spontaneously hypertensive rats (SHR) and found that S1PC is an active substance to lower blood pressure in SHR. In addition, the metabolomics approach was used to investigate the potential mechanism of the antihypertensive action of S1PC in SHR. Treatment with AGE (2g/kg body weight) or S1PC (6.5mg/kg body weight; equivalent to AGE 2g/kg body weight) significantly decreased the systolic blood pressure (SBP) of SHR after the repeated administration for 10 weeks, whereas treatment with SAC (7.9mg/kg body weight; equivalent to AGE 2g/kg body weight) did not decrease the SBP. After the treatment for 10 weeks, the plasma samples obtained from Wistar Kyoto (WKY) rats and SHR were analyzed by means of ultra high performance liquid chromatography coupled with high-resolution quadrupole-Orbitrap mass spectrometry. Multivariate statistical analysis of LC-MS data showed a clear difference in the metabolite profiles between WKY rats and SHR. The results indicated that 30 endogenous metabolites significantly contributed to the difference and 7 of 30 metabolites were changed by the S1PC treatment. Furthermore, regression analysis showed correlation between SBP and the plasma levels of betaine, tryptophan and 3 LysoPCs. This metabolomics approach suggested that S1PC could exert its antihypertensive effect by affecting glycine, serine and threonine metabolism, tryptophan metabolism and glycerophospholipid metabolism.