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.

Background: Gall bladder cancer (GBC) is the most common biliary tract malignancy and is often diagnosed at advanced stages, partly due to the absence of reliable biomarkers and limited understanding of its biology in African populations. This study aimed to characterize the metabolomic and lipoprotein profiles of GBC patients of Black African ancestry. Methods: NMR spectroscopy was used to profile the serum samples. Group comparisons used Wilcoxon tests, correlations used Spearman’s rank test, unsupervised analysis was carried out using the KODAMA algorithm, partial least squares modeling estimated free cholesterol (FC) to cholesterol ester (CE) ratios, while multivariate logistic regression evaluated independent predictors. Results: GBC patients showed altered ethanol levels and dysregulated lipoproteins, including increased IDL-C, IDL-TG, and LDL-TG, and decreased HDL-C, HDL-P, and medium HDL-P. Total and conjugated bilirubin strongly correlated with lipoproteins. Unsupervised analysis revealed a GBC subgroup with abnormal lipoprotein profiles and elevated FC/CE ratios, suggesting cholestasis-related LpX formation. Elevated asparagine, reduced ethanol, and an inflammatory metabolic signature characterized the GBC fingerprint. Ethanol and bilirubin emerged as independent predictors of GBC. Conclusions: GBC patients exhibit distinct metabolomic and lipoprotein alterations that may underlie disease progression and serve as potential biomarkers. These findings enhance understanding of GBC pathophysiology in African populations and may inform future diagnostic strategies.

Background Gall bladder cancer (GBC) is the most prevalent cancer of the biliary tract with a poor prognosis. Most of the patients are diagnosed at an advanced stage. This is due to a lack of reliable biomarkers and an understanding of the tumour biology in our patient population. This study aims to demonstrate the metabolomic and lipoprotein profiles associated with GBC patients of African ancestry. Methods: An untargeted metabolomics analysis was conducted on serum obtained from consenting individuals (41 GBC and 29 Benign Biliary Pathology (BBP)). Statisti-cal analysis was conducted in R (v 4.3.2), and Wilcoxon tests were used to compare the groups. Spearman’s rank test was used for correlation analyses. Unsupervised analysis of the groups was carried out using the KODAMA algorithm. Results: GBC patients showed a significant alteration of the metabolite ethanol as well as lipoproteins such as IDL-C, IDL-TG, LDL-TG, compared to BBP patients. In contrast, decreased levels of HDL-C, HDL-P, medium HDL-P were observed in GBC patients. Both Total and conjugated bilirubin levels showed a strong correlation with lipopro-teins. Furthermore, the altered free cholesterol to cholesterol ester ratio was demon-strated to be linked to abnormal lipid metabolism. Conclusion: This study demonstrated alterations in key lipoproteins and metabolites in the patient population. These alterations may play a role in disease progression and potentially serve as novel biomarkers for the disease.

Oral supplementation with the amino acid arginine, the precursor of the vasodilator nitric oxide (NO), is associated with a reduction in blood pressure (BP). However, it is uncertain whether a decreased plasma arginine concentration predicts increases in BP. We assessed the relationship between fasting plasma arginine or other amino acid concentrations and 24 hour ambulatory BP in 75 nevertreated participants recruited from the Johannesburg area, 55 of whom were male. Plasma amino acid concentrations were measured with high performance liquid chromatography-mass-spectrometry. Plasma arginine concentrations were not inversely correlated with ambulatory BP. However, plasma arginine concentrations were increased in 36 participants with a mean daytime systolic BP >140 mm Hg (61 ± 17 μmol/L) as compared to the remaining participants (54 ± 15 μmol/L, p‹0.05). Moreover, plasma arginine concentrations were positively correlated with 24-hour diastolic BP (r=0.26, p‹0.05). In males with a BMI‹30kg/m2, plasma arginine concentrations were positively correlated with both night diastolic (r=0.46, p‹0.005) and systolic (r=0.42, p‹0.005) BP. In a multivariate model with adjustments for age gender, body mass index, and other amino acid concentrations, plasma arginine concentrations were independently and positively associated with night diastolic BP (p‹0.05). In conclusion plasma arginine concentrations are positively associated with ambulatory BP in a group of participants of African descent in South Africa. These data do not support the notion that deficiencies of arginine, the amino acid substrate for NO, are related to increases in BP in groups of African ancestry living in South Africa. However, as with other ethnic groups, the positive relationship between plasma arginine concentrations and BP suggests a reduced capacity to utilise the amino acid substrate for NO synthesis.