Metabolomics for Clinical Biomarker Discovery and Therapeutic Target Identification

Molecules, Journal Year: 2024, Volume and Issue: 29(10), P. 2198 - 2198

Published: May 8, 2024

As links between genotype and phenotype, small-molecule metabolites are attractive biomarkers for disease diagnosis, prognosis, classification, drug screening treatment, insight into understanding pathology identifying potential targets. Metabolomics technology is crucial discovering targets of involved in phenotype. Mass spectrometry-based metabolomics has implemented applications various fields including target discovery, explanation mechanisms compound screening. It used to analyze the physiological or pathological states organism by investigating changes endogenous associated metabolism from complex metabolic pathways biological samples. The present review provides a critical update high-throughput functional techniques diverse applications, recommends use mass metabolite signatures that provide valuable insights We also recommend using as powerful tool patterns, efficacy evaluation herbal medicine.

Language: Английский

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α-Ketoglutarate alleviates osteoarthritis by inhibiting ferroptosis via the ETV4/SLC7A11/GPX4 signaling pathway

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: June 14, 2024

Abstract Osteoarthritis (OA) is the most common degenerative joint disorder that causes disability in aged individuals, caused by functional and structural alterations of knee joint. To investigate whether metabolic drivers might be harnessed to promote cartilage repair, a liquid chromatography–mass spectrometry (LC–MS) untargeted metabolomics approach was carried out screen serum biomarkers osteoarthritic rats. Based on correlation analyses, α-ketoglutarate (α-KG) has been demonstrated have antioxidant anti-inflammatory properties various diseases. These make α-KG prime candidate for further investigation OA. Experimental results indicate significantly inhibited H 2 O -induced cell matrix degradation apoptosis, reduced levels reactive oxygen species (ROS) malondialdehyde (MDA), increased superoxide dismutase (SOD) glutathione (GSH)/glutathione disulfide (GSSG) levels, upregulated expression ETV4, SLC7A11 GPX4. Further mechanistic studies observed α-KG, like Ferrostatin-1 (Fer-1), effectively alleviated Erastin-induced apoptosis ECM degradation. Fer-1 SLC7A11, GPX4 at mRNA protein decreased ferrous ion (Fe 2+ ) accumulation, preserved mitochondrial membrane potential (MMP) ATDC5 cells. In vivo, treatment ferroptosis OA rats activating ETV4/SLC7A11/GPX4 pathway. Thus, these findings inhibits via signaling pathway, thereby alleviating observations suggest exhibits therapeutic prevention OA, having clinical applications future.

Language: Английский

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Advances in Mass Spectrometry-Based Blood Metabolomics Profiling for Non-Cancer Diseases: A Comprehensive Review

Metabolites, Journal Year: 2024, Volume and Issue: 14(1), P. 54 - 54

Published: Jan. 14, 2024

Blood metabolomics profiling using mass spectrometry has emerged as a powerful approach for investigating non-cancer diseases and understanding their underlying metabolic alterations. Blood, readily accessible physiological fluid, contains diverse repertoire of metabolites derived from various systems. Mass offers universal precise analytical platform the comprehensive analysis blood metabolites, encompassing proteins, lipids, peptides, glycans, immunoglobulins. In this review, we present an overview research landscape in spectrometry-based profiling. While field is primarily focused on cancer, review specifically highlights studies related to diseases, aiming bring attention valuable that often remains overshadowed. Employing natural language processing methods, processed 507 articles provide insights into application metabolomic specific The encompasses wide range with emphasis cardiovascular disease, reproductive diabetes, inflammation, immunodeficiency states. By analyzing samples, researchers gain perturbations associated these potentially leading identification novel biomarkers development personalized therapeutic approaches. Furthermore, approaches utilized research, including GC-MS, LC-MS, others discussing advantages limitations. To enhance scope, propose recent supporting applicability GC×GC-MS metabolomics-based studies. This addition will contribute more exhaustive available techniques. Integration clinical practice holds promise improving disease diagnosis, treatment monitoring, patient outcomes. unraveling complex alterations healthcare professionals can pave way precision medicine interventions. Continuous advancements technology data methods further potential facilitating its translation laboratory routine application.

Language: Английский

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Metabolomics in diabetic nephropathy: Unveiling novel biomarkers for diagnosis (Review)

Molecular Medicine Reports, Journal Year: 2024, Volume and Issue: 30(3)

Published: July 3, 2024

Diabetic nephropathy (DN) also known as diabetic kidney disease, is a major microvascular complication of diabetes and leading cause end‑stage renal disease (ESRD), which affects the morbidity mortality patients with diabetes. Despite advancements in care, current diagnostic methods, such determination albuminuria estimated glomerular filtration rate, are limited sensitivity specificity, often only identifying damage after considerable morphological changes. The present review discusses potential metabolomics an approach for early detection management DN. Metabolomics study metabolites, small molecules produced by cellular processes, may provide more sensitive specific tool compared traditional methods. For purposes this review, systematic search was conducted on PubMed Google Scholar recent human studies published between 2011 2023 that used diagnosis has demonstrated metabolic biomarkers to ability detect broad spectrum metabolites high specificity allow earlier better DN, potentially reducing progression ESRD. Furthermore, pathway analysis assesses pathophysiological mechanisms underlying On whole, By providing in‑depth understanding alterations associated could significantly improve detection, enable timely interventions reduce healthcare burdens condition.

Language: Английский

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Progress and perspectives of metabolic biomarkers in blood sample for diabetic microvascular complications

Metabolomics, Journal Year: 2025, Volume and Issue: 21(2)

Published: March 31, 2025

Language: Английский

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Metabolomic profiles in serum and urine uncover novel biomarkers in children with nephrotic syndrome

European Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 53(7)

Published: March 1, 2023

Nephrotic syndrome is common in children and adults worldwide, steroid-sensitive nephrotic (SSNS) accounts for 80%. Aberrant metabolism involvement early SSNS sparsely studied, its pathogenesis remains unclear. Therefore, the goal of this study was to investigate changes initiated patients-related metabolites through serum urine metabolomics discover novel potential metabolic pathways.Serum samples (27 56 controls) (17 24 were collected. Meanwhile, non-targeted analyses performed by ultra-high-performance liquid chromatography-quadrupole time flight-mass spectrometry (UHPLC-QTOF-MS) determine SSNS. We applied causal inference model, DoWhy assess effects several selected metabolites. An ultraperformance chromatography-tandem mass (UPLC-MS/MS) used validate hits (D-mannitol, dulcitol, D-sorbitol, XMP, NADPH, NAD, bilirubin, α-KG-like) 41 43 controls. In addition, pathways explored.Compared urine, analysis more clearly discriminated at 194 differential five obtained group. Eight identified establishing diagnostic model SSNS, four variables had a positive effect. After validation targeted MS, except others have similar trends like untargeted analysis.With further quantitative analysis, we found seven may be new biomarkers risk prediction diagnosis

Language: Английский

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Metabolomic Investigation of Blood and Urinary Amino Acids and Derivatives in Patients with Type 2 Diabetes Mellitus and Early Diabetic Kidney Disease

Biomedicines, Journal Year: 2023, Volume and Issue: 11(6), P. 1527 - 1527

Published: May 25, 2023

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease; however, few biomarkers its early identification are available. The aim study was to assess new in stages DKD type 2 diabetes mellitus (DM) patients. This cross-sectional pilot performed an integrated metabolomic profiling blood and urine 90 patients with DM, classified into three subgroups according albuminuria stage from P1 P3 (30 normo-, 30 micro-, macroalbuminuric) 20 healthy controls using high-performance liquid chromatography mass spectrometry (UPLC-QTOF-ESI* MS). From a large cohort separated identified molecules, 33 39 amino acids derivatives serum urine, respectively, were selected for statistical analysis Metaboanalyst 5.0. online software. multivariate univariate algorithms confirmed relevance some as that responsible discrimination between Serum molecules such tiglylglycine, methoxytryptophan, serotonin sulfate, 5-hydroxy lysine, taurine, kynurenic acid, tyrosine found be more significant group C P1-P2-P3. In o-phosphothreonine, aspartic uric among most relevant metabolites group, well these potential may indicate their involvement 2DM progression, reflecting injury at specific sites along nephron, even DKD.

Language: Английский

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Gut microbiota microbial metabolites in diabetic nephropathy patients: far to go

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: May 8, 2024

Diabetic nephropathy (DN) is one of the main complications diabetes and a major cause end-stage renal disease, which has severe impact on quality life patients. Strict control blood sugar pressure, including use renin–angiotensin–aldosterone system inhibitors, can delay progression diabetic but cannot prevent it from eventually developing into disease. In recent years, many studies have shown close relationship between gut microbiota imbalance occurrence development DN. This review discusses latest research findings correlation microbial metabolites in DN, manifestations DN patients, application diagnosis their role disease progression, so on, to elucidate prevention provide theoretical basis methods for clinical treatment.

Language: Английский

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Biomarker Profiling by Targeted Metabolomic Analysis of Plasma and Urine Samples in Type 2 Diabetes Mellitus Patients and Early Diabetic Kidney Disease

Published: July 1, 2024

The incidence of diabetes mellitus (DM) continues to rise worldwide and one the most serious microvascular complications is diabetic kidney disease (DKD), which leading cause end-stage renal disease. Current bi-omarkers such as urinary albumin excretion rate have limitation for early detection DKD. In our study we used ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques quantify previously analyzed metabolites, tryptophan, kynurenic acid, taurine, l-acetylcarnitine, glycine, tiglylglycine. We performed targeted analy-sis metabolites from urine serum samples, collected 110 subjects. Of these, 90 patients type 2 DM (T2DM) were divided according albumin/creatinine ratio (UACR) into normoalbuminuria 300 mg/g groups, respectively, while 20 subjects rep-resented by healthy controls. Through various validation methods, identified several potential biomarkers, l-tryptophan in tiglylglycine, tau-rine urine.

Language: Английский

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The effect of high-intensity interval training on type 2 diabetic muscle: A metabolomics-based study

Heliyon, Journal Year: 2024, Volume and Issue: 10(15), P. e34917 - e34917

Published: July 20, 2024

BackgroundThis study aimed to investigate the effect of eight weeks high-intensity interval training (HIIT) on muscle metabolism in rats with type 2 diabetes (T2D) using metabolomics approaches.Methods20 male Wistar at age 8 weeks-were assigned four groups five, each group randomly: control (CTL), (DB), HIIT (EX), and + (DBX). T2D was induced by two months a high-fat diet plus single dose streptozotocin (35 mg/kg). Rats EX DBX performed (running 80–100 % Vmax, 4–10 intervals). NMR spectroscopy used determine changes metabolome profile after training.ResultsChanges metabolite abundance following exercise revealed distinct clustering multivariate analysis. The essential between DB CTL were arginine metabolism, purine phosphate pathway, amino sugar glutathione aminoacyl-tRNA biosynthesis. However, Arginine biosynthesis, pyrimidine alanine, aspartate, glutamate altered groups.ConclusionThese results suggest that could reverse metabolic rat muscles, contributing reduced FBG HOMA-IR levels.

Language: Английский

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