Every year, close to two million people world-wide are diagnosed with and die of lung cancer. Most patients present with advanced-stage cancer with limited curative options and poor prognosis. ...Diagnosis of lung cancer at an early stage provides the best chance for a cure. Low- dose CT screening of the chest in the high-risk population is the current standard of care for early detection of lung cancer. However, CT screening is invasive due to radiation exposure and carries the risk of unnecessary biopsies in non-cancerous tumors. In this pilot study, we present metabolic alterations observed in sputum and breath condensate of the
same
population of early- stage non-small cell lung cancer (NSCLC) patients cancer before and after surgical resection (SR), which could serve as noninvasive diagnostic tool. Exhaled breath condensate (EBC) (n=35) and sputum (n=15) were collected from early-stage non-small cell lung cancer (NSCLC) patients before and after SR. Median number of days for EBC and sputum collection before and after SR were 7 and 42; and 7 and 36 respectively Nuclear magnetic resonance (NMR) and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) were used to analyze the metabolic profile of the collected samples. A total of 26 metabolites with significant alteration post SR were identified, of which 14 (54%) were lipids and 12 constituted nine different chemical metabolite classes. Eighteen metabolites (69%) were significantly upregulated and 8 (31%) were downregulated. Median fold change for all the up- and downregulated metabolites (LC-QTOF-MS) were 10 and 8, respectively. Median fold change (MFC) in concentration of all the up- and downregulated metabolites (NMR) were 0.04 and 0.27, respectively. Furthermore, glucose (median fold change, 0.01, p=0.037), adenosine monophosphate (13 log fold, p=0.0037) and N1, N12- diacetylspermine (8 log fold p=0.011) sputum levels were significantly increased post-SR. These identified sputa and EBC indices of altered metabolism could serve as basis for further exploration of biomarkers for early detection of lung cancer, treatment response, and targets for drug discovery. Validation of these promising results by larger clinical studies is warranted.
Pulse consumption has been associated with reduced postprandial glucose response (PPGR) and improved satiety. The objective of this study was (i) to investigate the effects of fortifying white pan ...bread with split yellow pea (
L.) flour on PPGR and appetite-related sensations, and (ii) to determine whether Revtech heat processing of pea flour alters the postprandial effects. A randomized controlled crossover trial was performed with 24 healthy adults. Participants consumed 50 g available carbohydrate from bread containing 20% pea flour that was untreated (USYP), Revtech processed at 140 °C with no steam (RT0%), Revtech processed at 140 °C with 10% steam (RT10%), or a control bread with 100% white wheat flour (100%W). Blood samples were analyzed for glucose and plasma insulin at 0, 15, 30, 45, 60, 90, and 120 min post-meal. Appetite sensations and product acceptability were measured using visual analogue and 9-point hedonic scales. Results showed no significant difference in the postprandial glucose and insulin responses of different bread treatments. However, pea-containing variants resulted in 18% higher fullness and 16-18% lower hunger, desire to eat, and prospective food consumption ratings compared to 100% W. No differences in the aroma, flavor, color, and overall acceptability of different bread products were observed. This trial supports using pea flour as a value-added ingredient to improve the short-term appetite-related sensations of white pan bread without affecting the overall acceptability.
Metabolic alterations in malignant cells play a vital role in tumor initiation, proliferation, and metastasis. Biofluids from patients with non–small cell lung cancer (NSCLC) harbor metabolic ...biomarkers with potential clinical applications. In this study, we assessed the changes in the metabolic profile of patients with early-stage NSCLC using mass spectrometry and nuclear magnetic resonance spectroscopy before and after surgical resection. A single cohort of 35 patients provided a total of 29 and 32 pairs of urine and serum samples, respectively, pre-and post-surgery. We identified a profile of 48 metabolites that were significantly different pre- and post-surgery: 17 in urine and 31 in serum. A higher proportion of metabolites were upregulated than downregulated post-surgery (p < 0.01); however, the median fold change (FC) was higher for downregulated than upregulated metabolites (p < 0.05). Purines/pyrimidines and proteins had a larger dysregulation than other classes of metabolites (p < 0.05 for each class). Several of the dysregulated metabolites have been previously associated with cancer, including leucyl proline, asymmetric dimethylarginine, isopentenyladenine, fumaric acid (all downregulated post-surgery), as well as N6-methyladenosine and several deoxycholic acid moieties, which were upregulated post-surgery. This study establishes metabolomic analysis of biofluids as a path to non-invasive diagnostics, screening, and monitoring in NSCLC.
Purpose
Vitamin B
6
status in the body is affected by several factors including dietary supply of the antivitamin B
6
factor, 1-amino
d
-proline (1ADP), which is present in flaxseed. Owing to the ...prevalence of moderate B
6
deficiency in the general population, a co-occurrence of 1ADP may lead to a further deterioration of B
6
status. To this end, we applied a nontargeted metabolomics approach to identify potential plasma lipophilic biomarkers of deleterious effect of 1ADP on moderately vitamin B
6
-deficient rats using a high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry.
Methods
Twenty-four rats were fed with a semi-purified diet containing pyridoxine·HCl (PN·HCl) either 7 mg/kg diet (optimal B
6
) or 0.7 mg/kg diet (moderate B
6
). The rats were divided into four treatments (
n
= 6), and one treatment in each B
6
diet group was also fed ad libitum with 10 mg/kg diet of synthetic 1ADP. After 5 weeks of study, plasma was collected from the rats and lipophilic metabolites were extracted using acetonitrile as a solvent for analysis.
Results
Ten potential plasma lipophilic biomarkers were identified out of >2500 detected entities, which showed significant differences between the treatments. Plasma glycocholic acid, glycoursodeoxycholic acid, murocholic acid,
N
-docosahexaenoyl GABA,
N
-arachidonoyl GABA, lumula, nandrolone and orthothymotinic acid concentrations were significantly elevated, while plasma cystamine and 3-methyleneoxindole concentrations were significantly reduced as a result of either low B
6
status or 1ADP or their interaction.
Conclusion
Changes in these metabolites revealed a potential defect in pathways linked with the biosynthesis and metabolism of bile acid components,
N
-acyl amino acids, analgesic androgens, anti-inflammatory and neuroprotective molecules. We also noted that the changes in these biomarkers can be alleviated by the application of adequate vitamin B
6
.
The ‘no-reflow’ phenomenon (NRP) after primary percutaneous coronary intervention (PCI) is a serious complication among acute ST-segment elevation myocardial infarction (STEMI) patients. Herein, a ...comprehensive lipidomics approach was used to quantify over 300 distinct molecular species in circulating plasma from 126 patients with STEMI before and after primary PCI. Our analysis showed that three lipid classes: phosphatidylcholine (PC), alkylphosphatidylcholine (PC(O)), and sphingomyelin (SM), were significantly elevated (p < 0.05) in no-reflow patients before primary PCI. The levels of individual fatty acids and total fatty acid levels were significantly lower (p < 0.05) in no-reflow subjects after PCI. The grouping of patients based on ECG ST-segment resolution (STR) also demonstrated the same trend, confirming the possible role of these differential lipids in the setting of no-reflow. Sphingomyelin species, SM 41:1 and SM 41:2, was invariably positively correlated with corrected TIMI frame count (CTFC) at pre-PCI and post-PCI. The plasma levels of SM 42:1 exhibited an inverse association (p < 0.05) consistently with tumor necrosis factor-alpha (TNF-α) at pre-PCI and post-PCI. In conclusion, we identified plasma lipid profiles that distinguish individuals at risk of no-reflow and provided novel insights into how dyslipidemia may contribute to NRP after primary PCI.
•Chicken skin peptides reduced plasma angiotensin converting enzyme levels in SHR.•Metabolomics profile revealed distinct urinary and plasma metabolites of hypertension.•SHR urinary uric acid level ...was down-regulated by the peptide treatment.•SHR urinary N2-acetyl-L-ornithine was down-regulated in the treated groups.•Urinary buthionine sulfoximine (a prooxidant) was reduced in the treated SHR.
Plasma and urine metabolomics profiles of spontaneously hypertensive rats (SHRs) fed with chicken skin protein hydrolysates (CSPHs) were investigated to establish possible biomarkers of blood pressure regulation. SHR and wistar Kyoto (WKY) rats were randomised into groups that received casein-only (control), CSPHs (0.5 or 1%) or chicken skin meal (CSM 1%) diets for six weeks. Results showed that the diets significantly (P < 0.05) lowered systolic blood pressure (SBP) of SHRs (−36, −31 and −26 mmHg for CSPH 1%, CSPH 0.5% and CSM 1%, respectively) but not WKY. This correlated with decreased plasma angiotensin converting enzyme levels but not with superoxide dismutase activity. Partial least square discrimination analysis of detected metabolites in urine and plasma of rats showed significant changes in levels of symmetric dimethylarginine, N2-acetyl-L-ornithine, buthionine sulfoximine, uric acid, α-tocopherol succinate, L-isoleucine, creatinine, and phospholipids. CSPHs could therefore be used as ingredients in developing nutraceuticals and functional foods for hypertension management.
Background Metabolomics is a potential means for biofluid-based lung cancer detection. We conducted a non-targeted, data-driven assessment of plasma from early-stage non-small cell lung cancer ...(ES-NSCLC) cases versus cancer-free controls (CFC) to explore and identify the classes of metabolites for further targeted metabolomics biomarker development. Methods Plasma from 250 ES-NSCLC cases and 250 CFCs underwent ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) in positive and negative electrospray ionization (ESI) modes. Molecular feature extraction, formula generation, and find-by-ion tools annotated metabolic entities. Analysis was restricted to endogenous metabolites present in greater than or equal to 80% of samples. Unsupervised hierarchical cluster analysis identified clusters of metabolites. The metabolites with the strongest correlation with the principal component of each cluster were included in logistic regression modeling to assess discriminatory performance with and without adjustment for clinical covariates. Results A total of 1900 UHPLC-QTOF-MS assessments identified 1667 and 2032 endogenous metabolites in the ESI-positive and ESI-negative modes, respectively. After data filtration, 676 metabolites remained, and 12 clusters of metabolites were identified from each ESI mode. Multivariable logistic regression using the representative metabolite from each cluster revealed effective classification of cases from controls with overall diagnostic accuracy of 91% (ESI positive) and 94% (ESI negative). Metabolites of interest identified for further targeted analysis include the following: 1b, 3a, 12a-trihydroxy-5b-cholanoic acid, pyridoxamine 5'-phosphate, sphinganine 1-phosphate, gamma-CEHC, 20-carboxy-leukotriene B4, isodesmosine, and 18-hydroxycortisol. Conclusions Plasma-based metabolomic detection of early-stage NSCLC appears feasible. Further metabolomics studies targeting phospholipid, steroid, and fatty acid metabolism are warranted to further develop noninvasive metabolomics-based detection of early-stage NSCLC. Keywords: Early-stage non-small cell lung cancer, Plasma metabolomics, Early detection, Non-targeted metabolomics
Abstract Objectives Dietary modifications including healthy eating constitute one of the first line strategies for prevention and treatment of cardiovascular disease (CVD) risk factors including high ...cholesterol and atherosclerosis. The purpose of the present study was to investigate the potential cardiovascular benefits of wild rice in male and female LDL–receptor–deficient (LDLr-KO) mice. Methods Wild rice was used to create a semi-synthetic diet containing approximately 60% of total energy from carbohydrate. Two other experimental diets were similar in macronutrient composition, but containing either white rice or commercial carbohydrate sources. All diets were supplemented with 0.06% (w/w) dietary cholesterol. The mice were divided into six experimental groups and fed with these diets over 24 weeks. Results Consumption of wild rice significantly reduced the size and severity of atherosclerotic lesions in the aortic roots of male and female mice by 71 and 61% respectively, compared to the control group of the same gender. This effect was associated with significant reductions of plasma cholesterol levels by 15 and 40%, low density lipoprotein (LDL) levels by 12 and 42%, and very low density lipoprotein (VLDL) levels by 35 and 75% respectively, in male and female mice compared to the control group of the same gender. Increased fecal cholesterol excretion of up to 34% was also noted, compared to the control group of the same gender. However, the antiatherogenic effect of wild rice was not associated with increased superoxide dismutase (SOD) and catalase (CAT) activities. Conclusion Current data suggest that cholesterol-lowering effects of wild rice may be the main factor for the prevention of atherogenesis in LDLr-KO mice. Additional studies are needed to understand the mechanism of action.
•The study was carried out over an extended period (1 year).•The participants were patients with cardiovascular disease.•Several types of foods and flavourings were used in real-life setting.•30 g of ...milled flaxseed in each food, not commercially available.•Identified acceptability of flaxseed in different foods.
Dietary supplementation with milled flaxseed has provided significant health-related benefits to patients with cardiovascular disease (the FlaxPAD Trial). The purpose of this study was to examine which foods that contained flaxseed were best accepted over the one year duration of daily supplementation. Milled flaxseed (30 g) or a placebo (30 g of milled wheat) was incorporated into muffins, bagels, snack bars (all in different flavours), buns, tea biscuits and pasta or distributed in bags to sprinkle into their food of choice. Patients were free to choose each day the type of food product that they would consume. Over the course of one year, bagels were consumed > muffins > bars > sprinkles > biscuits > pasta > buns. The trends and quantities chosen were the same for flax and placebo foods. More flavourful varieties were generally better accepted. In conclusion, functional foods containing milled flaxseed will be ingested by a patient population over extended periods similar to placebo foods.
AbstractBackgroundLung cancer is a major cause of global morbidity and mortality. Current low dose CT screening is invasive and its role remains contentious. There are no known biomarkers to monitor ...treatment response, detect disease recurrence and patient selection for adjuvant treatment after curative surgical resection. Hence there is an urgent need to explore non-conventional and noninvasive tools to develop novel biomarkers to improve the outcome of this lethal cancer. MethodsThis is an ongoing exploratory and translational study involving collection of bio fluids from 50 patients with early stage non-small cell lung cancer before and after surgical resection. The primary Objective is to identify cancer specific metabolome in body fluids - sputum, exhaled breath condensate, blood and urine of the patients with early stage non-small. cell lung cancer (NSCLC) using Magnetic Resonance Spectroscopy (MRS) and Mass Spectroscopy (MS). ConclusionThe trajectory of change in metabolic profile of body fluids before and after surgical resection may have potential clinical applications in lung cancer screening, as biomarkers for disease recurrence and exploration of novel targets for therapeutic intervention.
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