Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a characteristic dysregulated metabolism. Abnormal clinicopathological features linked to defective metabolic and inflammatory response ...pathways can induce PDAC development and progression. In this study, we investigated the metabolites and lipoproteins profiles of PDAC patients of African ancestry. Nuclear Magnetic Resonance (NMR) spectroscopy was conducted on serum obtained from consenting individuals (34 PDAC, 6 Chronic Pancreatitis, and 6 healthy participants). Seventy-five signals were quantified from each NMR spectrum. The Liposcale test was used for lipoprotein characterization. Spearman’s correlation and Kapan Meier tests were conducted for correlation and survival analyses, respectively. In our patient cohort, the results demonstrated that levels of metabolites involved in the glycolytic pathway increased with the tumour stage. Raised ethanol and 3-hydroxybutyrate were independently correlated with a shorter patient survival time, irrespective of tumour stage. Furthermore, increased levels of bilirubin resulted in an abnormal lipoprotein profile in PDAC patients. Additionally, we observed that the levels of a panel of metabolites (such as glucose and lactate) and lipoproteins correlated with those of inflammatory markers. Taken together, the metabolic phenotype can help distinguish PDAC severity and be used to predict patient survival and inform treatment intervention.
•Eight novel metabolites characterizing definite TBM.•2-Hydroxybutyrate, identified for the first time in CSF of TBM cases, linked to uncontrolled glucose metabolism.•TBM exhibit upregulated creatine ...metabolism, disrupted glutamate-glutamine cycle, elevated neuroprotective free carnitine.•Elevated proline linked to classic TBM-hallmark of elevated protein.•Collectively, our findings imply destabilization and increased permeability of the bloodbrain barrier in TBM.
To better characterize the cerebrospinal fluid (CSF) metabolic profile of tuberculous meningitis (TBM) cases using a South African paediatric cohort.
1H NMR metabolomics was used to analyse the CSF of a South African paediatric cohort. Univariate and multivariate statistical analyses were performed to compare a homogeneous control group with a well-defined TBM group.
Twenty metabolites were identified to discriminate TBM cases from controls. As expected, reduced glucose and elevated lactate were the dominating discriminators. A closer investigation of the CSF metabolic profile yielded 18 metabolites of statistical significance. Ten metabolites (acetate, alanine, choline, citrate, creatinine, isoleucine, lysine, myo-inositol, pyruvate and valine) overlapped with two other prior investigations. Eight metabolites (2-hydroxybutyrate, carnitine, creatine, creatine phosphate, glutamate, glutamine, guanidinoacetate and proline) were unique to our paediatric TBM cohort.
Through strict exclusion criteria, quality control checks and data filtering, eight unique CSF metabolites associated with TBM were identified for the first time and linked to: uncontrolled glucose metabolism, upregulated proline and creatine metabolism, detoxification and disrupted glutamate–glutamine cycle in the TBM samples. Associated with oxidative stress and chronic neuroinflammation, our findings collectively imply destabilization, and hence increased permeability, of the blood–brain barrier in the TBM cases.
Introduction
Technological advancements enabled the analyses of limited sample volumes on
1
H NMR. Manual spectral profiling of the data is, however, complex, and timely.
Objective
To evaluate the ...performance of BAYESIL for automated identification and quantification of
1
H NMR spectra of limited volume samples.
Method
Aliquots of a pooled African elephant serum sample were analyzed using standard and reduced volumes. Performance was evaluated on confidence scores, non-detects and laboratory CV.
Results
Of the 47 compounds detected, 28 had favorable performances. The approach could differentiate samples based on biological variation.
Conclusions
BAYESIL is valuable for limited sample
1
H NMR data analyses.
Technological advancements enabled the analyses of limited sample volumes on
H NMR. Manual spectral profiling of the data is, however, complex, and timely.
To evaluate the performance of BAYESIL for ...automated identification and quantification of
H NMR spectra of limited volume samples.
Aliquots of a pooled African elephant serum sample were analyzed using standard and reduced volumes. Performance was evaluated on confidence scores, non-detects and laboratory CV.
Of the 47 compounds detected, 28 had favorable performances. The approach could differentiate samples based on biological variation.
BAYESIL is valuable for limited sample
H NMR data analyses.
To better characterize the cerebrospinal fluid (CSF) metabolic profile of tuberculous meningitis (TBM) cases using a South African paediatric cohort.
H NMR metabolomics was used to analyse the CSF of ...a South African paediatric cohort. Univariate and multivariate statistical analyses were performed to compare a homogeneous control group with a well-defined TBM group.
Twenty metabolites were identified to discriminate TBM cases from controls. As expected, reduced glucose and elevated lactate were the dominating discriminators. A closer investigation of the CSF metabolic profile yielded 18 metabolites of statistical significance. Ten metabolites (acetate, alanine, choline, citrate, creatinine, isoleucine, lysine, myo-inositol, pyruvate and valine) overlapped with two other prior investigations. Eight metabolites (2-hydroxybutyrate, carnitine, creatine, creatine phosphate, glutamate, glutamine, guanidinoacetate and proline) were unique to our paediatric TBM cohort.
Through strict exclusion criteria, quality control checks and data filtering, eight unique CSF metabolites associated with TBM were identified for the first time and linked to: uncontrolled glucose metabolism, upregulated proline and creatine metabolism, detoxification and disrupted glutamate-glutamine cycle in the TBM samples. Associated with oxidative stress and chronic neuroinflammation, our findings collectively imply destabilization, and hence increased permeability, of the blood-brain barrier in the TBM cases.
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