A STUDY OF VITEX TRIFOLIA AND ITS ACTIVE COMPONENTS FOR POTENTIAL ANTI-INFLAMMATORY AND ANTI-MALARIAL ACTIVITIES

Ph.DDOCTOR OF PHILOSOPHY (FOS

The Utility of Amino Acid Metabolites in the Diagnosis of Major Depressive Disorder and Correlations with Depression Severity

Major depressive disorder (MDD) is a highly prevalent and disabling condition with a high disease burden. There are currently no validated biomarkers for the diagnosis and treatment of MDD. This study assessed serum amino acid metabolite changes between MDD patients and healthy controls (HCs) and their association with disease severity and diagnostic utility. In total, 70 MDD patients and 70 HCs matched in age, gender, and ethnicity were recruited for the study. For amino acid profiling, serum samples were analysed and quantified by liquid chromatography-mass spectrometry (LC-MS). Receiver-operating characteristic (ROC) curves were used to classify putative candidate biomarkers. MDD patients had significantly higher serum levels of glutamic acid, aspartic acid and glycine but lower levels of 3-Hydroxykynurenine; glutamic acid and phenylalanine levels also correlated with depression severity. Combining these four metabolites allowed for accurate discrimination of MDD patients and HCs, with 65.7% of depressed patients and 62.9% of HCs correctly classified. Glutamic acid, aspartic acid, glycine and 3-Hydroxykynurenine may serve as potential diagnostic biomarkers, whereas glutamic acid and phenylalanine may be markers for depression severity. To elucidate the association between these indicators and clinical features, it is necessary to conduct additional studies with larger sample sizes that involve a spectrum of depressive symptomatology

Integration of the cortical haemodynamic response measured by functional near-infrared spectroscopy and amino acid analysis to aid in the diagnosis of major depressive disorder

10.3390/diagnostics11111978Diagnostics1111197

Datasheet1_Characteristics of pulmonary artery strain assessed by cardiovascular magnetic resonance imaging and associations with metabolomic pathways in human ageing.docx

BackgroundPulmonary artery (PA) strain is associated with structural and functional alterations of the vessel and is an independent predictor of cardiovascular events. The relationship of PA strain to metabolomics in participants without cardiovascular disease is unknown.MethodsIn the current study, community-based older adults, without known cardiovascular disease, underwent simultaneous cine cardiovascular magnetic resonance (CMR) imaging, clinical examination, and serum sampling. PA global longitudinal strain (GLS) analysis was performed by tracking the change in distance from the PA bifurcation to the pulmonary annular centroid, using standard cine CMR images. Circulating metabolites were measured by cross-sectional targeted metabolomics analysis.ResultsAmong n = 170 adults (mean age 71 ± 6.3 years old; 79 women), mean values of PA GLS were 16.2 ± 4.4%. PA GLS was significantly associated with age (β = −0.13, P = 0.017), heart rate (β = −0.08, P = 0.001), dyslipidemia (β = −2.37, P = 0.005), and cardiovascular risk factors (β = −2.49, P = 0.001). Alanine (β = −0.007, P = 0.01) and proline (β = −0.0009, P = 0.042) were significantly associated with PA GLS after adjustment for clinical risk factors. Medium and long-chain acylcarnitines were significantly associated with PA GLS (C12, P = 0.027; C12-OH/C10-DC, P = 0.018; C14:2, P = 0.036; C14:1, P = 0.006; C14, P = 0.006; C14-OH/C12-DC, P = 0.027; C16:3, P = 0.019; C16:2, P = 0.006; C16:1, P = 0.001; C16:2-OH, P = 0.016; C16:1-OH/C14:1-DC, P = 0.028; C18:1-OH/C16:1-DC, P = 0.032).ConclusionBy conventional CMR, PA GLS was associated with aging and vascular risk factors among a contemporary cohort of older adults. Metabolic pathways involved in PA stiffness may include gluconeogenesis, collagen synthesis, and fatty acid oxidation.</p

Characteristics of pulmonary artery strain assessed by cardiovascular magnetic resonance imaging and associations with metabolomic pathways in human ageing

BackgroundPulmonary artery (PA) strain is associated with structural and functional alterations of the vessel and is an independent predictor of cardiovascular events. The relationship of PA strain to metabolomics in participants without cardiovascular disease is unknown.MethodsIn the current study, community-based older adults, without known cardiovascular disease, underwent simultaneous cine cardiovascular magnetic resonance (CMR) imaging, clinical examination, and serum sampling. PA global longitudinal strain (GLS) analysis was performed by tracking the change in distance from the PA bifurcation to the pulmonary annular centroid, using standard cine CMR images. Circulating metabolites were measured by cross-sectional targeted metabolomics analysis.ResultsAmong n = 170 adults (mean age 71 ± 6.3 years old; 79 women), mean values of PA GLS were 16.2 ± 4.4%. PA GLS was significantly associated with age (β = −0.13, P = 0.017), heart rate (β = −0.08, P = 0.001), dyslipidemia (β = −2.37, P = 0.005), and cardiovascular risk factors (β = −2.49, P = 0.001). Alanine (β = −0.007, P = 0.01) and proline (β = −0.0009, P = 0.042) were significantly associated with PA GLS after adjustment for clinical risk factors. Medium and long-chain acylcarnitines were significantly associated with PA GLS (C12, P = 0.027; C12-OH/C10-DC, P = 0.018; C14:2, P = 0.036; C14:1, P = 0.006; C14, P = 0.006; C14-OH/C12-DC, P = 0.027; C16:3, P = 0.019; C16:2, P = 0.006; C16:1, P = 0.001; C16:2-OH, P = 0.016; C16:1-OH/C14:1-DC, P = 0.028; C18:1-OH/C16:1-DC, P = 0.032).ConclusionBy conventional CMR, PA GLS was associated with aging and vascular risk factors among a contemporary cohort of older adults. Metabolic pathways involved in PA stiffness may include gluconeogenesis, collagen synthesis, and fatty acid oxidation

Plasma tryptophan- kynurenine pathway metabolites and risk for progression to end stage kidney disease in patients with type 2 diabetes

Objective: We sought to study the associations between plasma metabolites in tryptophan-kynurenine pathway and the risk of progression to end stage kidney disease (ESKD) in patients with type 2 diabetes. Design and Methods: Plasma tryptophan, kynurenine, 3-hydroxykynurenine, kynurenic acid and xanthurenic acid concentrations were measured in discovery (N=1915) and replication (N=346) cohorts. External validation was performed in Chronic Renal Insufficiency Cohort (CRIC) participants with diabetes (N=1312). The primary outcome was a composite of incident ESKD (progression to eGFR < 15 ml/min/1.73m2, sustained dialysis or renal death). The secondary outcome was annual eGFR decline. Results: In discovery cohort, tryptophan was inversely associated with risk for ESKD and kynurenine-to-tryptophan ratio (KTR) was positively associated with risk for ESKD after adjustment for clinical risk factors including baseline eGFR and albuminuria (adjusted HR [95% CI], 0.62 [0.51-0.75] and 1.48 [1.20-1.84], per one SD). High levels of kynurenic acid and xanthurenic acid were associated with low risks of ESKD (0.74 [0.60-0.91] and 0.74 [0.60-0.91]). Consistently, high levels of tryptophan, kynurenic acid and xanthurenic acid were independently associated with a slower eGFR decline whilst a high KTR was predictive of a faster eGFR decline. Similar outcomes were obtained in replication cohort. Furthermore, the inverse association between kynurenic acid and risk of ESKD was externally validated in CRIC participants with diabetes (adjusted HR 0.78 [0.65-0.93]). Conclusion: Accelerated catabolism of tryptophan in kynurenine pathway may be involved in progressive loss of kidney function. However, shunting the kynurenine pathway toward kynurenic acid branch may potentially slow renal progression.</p