Purpose: To investigate the aqueous proteomics and metabolomics in low-energy and high-energy femtosecond laser-assisted cataract surgery (FLACS).
Methods: In this prospective observational study, 72 patients were randomized to 3 groups: low-energy FLACS, high-energy FLACS, and conventional phacoemulsification (controls). Aqueous was collected after femtosecond laser treatment or at the beginning of surgery (controls).
Objective: Bariatric surgery effectively treats non-alcoholic fatty liver disease (NAFLD). The glutamate-serine-glycine (GSG) index has emerged as a non-invasive diagnostic marker for NAFLD, but its ability to monitor treatment response remains unclear. This study investigates the GSG index's ability to monitor NAFLD's response to bariatric surgery.
View Article and Find Full Text PDFThis study compared the effectiveness of capillary dried blood spots (DBS) versus venous DBS in detecting metabolic changes related to drug-resistant epilepsy (DRE). DBS samples were collected from 142 epilepsy patients (58 drug-resistant, 84 drug-responsive) via venipuncture or fingerstick capillary sampling. Metabolomic analysis using gas chromatography-mass spectrometry compared DBS metabolite profiles between the two groups.
View Article and Find Full Text PDFBackground: EZH2, well-known for its canonical methyltransferase activity in transcriptional repression in many cancers including glioblastoma (GBM), has an understudied non-canonical function critical for sustained tumor growth. Recent GBM consortial efforts reveal complex molecular heterogeneity for which therapeutic vulnerabilities correlated with subtype stratification remain relatively unexplored. Current enzymatic EZH2 inhibitors (EZH2inh) targeting its canonical SET domain show limited efficacy and lack durable response, suggesting that underlying differences in the non-canonical pathway may yield new knowledge.
View Article and Find Full Text PDFBackground: Ceramides have recently been identified as novel biomarkers associated with diabetes mellitus (DM) and major adverse cardiac and cerebrovascular events (MACCE). This study aims to explore their utility in diagnosing microvascular disease.
Methods: This study prospectively enrolled 309 patients from 2018 to 2020 into three groups: healthy controls (Group 1, N = 51), DM patients without acute myocardial infarction (AMI) (Group 2, N = 150), and DM patients with AMI (Group 3, N = 108).
Aim: (i) To characterize Enterococcus faecalis biofilm formation pathways by semi-targeted metabolomics and targeted nitrogen panel analysis of strong (Ef63) and weak (Ef 64) biofilm forming E. faecalis clinical isolates and (ii) to validate the identified metabolic markers using targeted inhibitors.
Methodology: Previous proteomics profiling of E.
Background: We previously reported changes in the serum metabolome associated with impaired myocardial relaxation in an asymptomatic older community cohort. In this prospective parallel-group randomized control pilot trial, we subjected community adults without cardiovascular disease to exercise intervention and evaluated the effects on serum metabolomics.
Methods: Between February 2019 to November 2019, thirty (83% females) middle-aged adults (53 ± 4 years) were randomized with sex stratification to either twelve weeks of moderate-intensity exercise training (Intervention) (n = 15) or Control (n = 15).
Context: Metabolites in tricarboxylic acid (TCA) pathway have pleiotropic functions.
Objective: To study the association between urine TCA cycle metabolites and the risk for chronic kidney disease (CKD) progression in individuals with type 2 diabetes.
Design, Setting And Participants: A prospective study in a discovery (n = 1826) and a validation (n = 1235) cohort of type 2 diabetes in a regional hospital and a primary care facility.
Aging-induced aortic stiffness has been associated with altered fatty acid metabolism. We studied aortic stiffness using cardiac magnetic resonance (CMR)-assessed ventriculo-arterial coupling (VAC) and novel aortic (AO) global longitudinal strain (GLS) combined with targeted metabolomic profiling. Among community older adults without cardiovascular disease, VAC was calculated as aortic pulse wave velocity (PWV), a marker of arterial stiffness, divided by left ventricular (LV) GLS.
View Article and Find Full Text PDFBackground: Pulmonary 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.
Methods: In the current study, community-based older adults, without known cardiovascular disease, underwent simultaneous cine cardiovascular magnetic resonance (CMR) imaging, clinical examination, and serum sampling.
Diabetic nephropathy (DN) is characterized by abnormal kidney energy metabolism, but its causes and contributions to DN pathogenesis are not clear. To examine this issue, we carried out targeted metabolomics profiling in a mouse model of DN that develops kidney disease resembling the human disorder. We found a distinct profile of increased lactate levels and impaired energy metabolism in kidneys of mice with DN, and treatment with an angiotensin-receptor blocker (ARB) reduced albuminuria, attenuated kidney pathology and corrected many metabolic abnormalities, restoring levels of lactate toward normal while increasing kidney ATP content.
View Article and Find Full Text PDFObjective: We sought to study the associations between plasma metabolites in the tryptophan-kynurenine pathway and the risk of progression to end-stage kidney disease (ESKD) in patients with type 2 diabetes.
Research Design And Methods: Plasma tryptophan, kynurenine, 3-hydroxykynurenine, kynurenic acid, and xanthurenic acid concentrations were measured in discovery (n = 1,915) and replication (n = 346) cohorts. External validation was performed in Chronic Renal Insufficiency Cohort (CRIC) participants with diabetes (n = 1,312).
Non-alcoholic steatohepatitis (NASH) is a condition characterized by inflammation and hepatic injury/fibrosis caused by the accumulation of ectopic fats in the liver. Recent advances in lipidomics have allowed the identification and characterization of lipid species and have revealed signature patterns of various diseases. Here, we describe a lipidomics workflow to assess the lipid profiles of liver homogenates taken from a NASH mouse model.
View Article and Find Full Text PDFBackground: Leukodystrophies are a heterogeneous group of disorders affecting the white matter of the central nervous system, with or without affecting the peripheral nervous system. Biallelic variants in DEGS1 , coding for desaturase 1 (Des1) protein, were recently reported to be associated with hypomyelinating leukodystrophy (HLD), a subclass of leukodystrophies where the formation of the myelin sheath is affected.
Methods: Genomic sequencing was performed on our index patient with severe developmental delay, severe failure to thrive, dystonia, seizures, and hypomyelination on brain imaging.
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.
View Article and Find Full Text PDFAlzheimer's disease (AD) is a neurodegenerative disorder that affects millions of people worldwide. Growing evidence suggests that the gut microbiome (GM) plays a pivotal role in the pathogenesis of AD through the microbiota-gut-brain axis (MGB). Alterations in GM composition and diversity have been observed in both animal models and in human patients with AD.
View Article and Find Full Text PDFFasting increases susceptibility to acute myocardial ischaemia/reperfusion injury (IRI) but the mechanisms are unknown. Here, we investigate the role of the mitochondrial NAD-dependent deacetylase, Sirtuin-3 (SIRT3), which has been shown to influence fatty acid oxidation and cardiac outcomes, as a potential mediator of this effect. Fasting was shown to shift metabolism from glucose towards fatty acid oxidation.
View Article and Find Full Text PDFThe immediate and delayed metabolic changes in rats treated with valproate (VPA), a drug used for the treatment of epilepsy, were profiled. An established approach using dried blood spots (DBS) as sample matrices for gas chromatography/mass spectrometry-based metabolomics profiling was modified using double solvents in the extraction of analytes. With the modified method, some of the previously undetectable metabolites were recovered and subtle differences in the metabolic changes upon exposure to a single dose of VPA between males and female rats were identified.
View Article and Find Full Text PDFBackground: Cosmetics manufacturers are focused on cosmetic delivery systems into the skin, but the level of diffusion of the systems in the skin tissues is not well understood. The current methods, such as Franz diffusion, assess analyte diffusion in the whole skin or artificial membranes, which has limitations for understanding skin delivery systems.
Aims: Our study aimed to create a transdermal delivery method which is based on dermal-epidermal separation of human skin, allowing us to assess each layer of skin separately for its efficacy.
Background: Health-related quality of life (HRQoL) measures are predictors of adverse health outcomes in older adults. Studies have demonstrated cross-sectional associations between HRQoL measures and blood-based biochemical markers. Acylcarnitines (ACs) are a class of metabolites generated in the mitochondria and are predictive of multiple geriatric syndromes.
View Article and Find Full Text PDFNonalcoholic steatohepatitis (NASH) is characterized by hepatic steatosis, lobular inflammation, and fibrosis. Thyroid hormone (TH) reduces steatosis; however, the therapeutic effect of TH on NASH-associated inflammation and fibrosis is not known. This study examined the therapeutic effect of TH on hepatic inflammation and fibrosis during NASH and investigated THs molecular actions on autophagy and mitochondrial biogenesis.
View Article and Find Full Text PDFAims: Little is known about pathophysiology of sarcopenia in diabetes. We aimed to study amino acid profile associated with skeletal muscle mass loss longitudinally in Type 2 Diabetes Mellitus (T2DM).
Methods: This is a prospective study of 1140 patients aged 56.
Background: Major depressive disorder (MDD) is a debilitating condition with a high disease burden and medical comorbidities. There are currently few to no validated biomarkers to guide the diagnosis and treatment of MDD. In the present study, we evaluated the differences between MDD patients and healthy controls (HCs) in terms of cortical haemodynamic responses during a verbal fluency test (VFT) using functional near-infrared spectroscopy (fNIRS) and serum amino acid profiles, and ascertained if these parameters were correlated with clinical characteristics.
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