Small molecule metabolites: discovery of biomarkers and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 20, 2023

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks diseases. Metabolite signatures that have close proximity subject's phenotypic informative dimension, are useful for predicting diagnosis prognosis diseases as well monitoring treatments. The lack early biomarkers could poor serious outcomes. Therefore, noninvasive methods with high specificity selectivity desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool biomarker pathway analysis, revealing possible mechanisms human various deciphering therapeutic potentials. It help identify functional related variation delineate biochemical changes indicators pathological damage prior disease development. Recently, scientists established large number profiles reveal underlying networks target exploration in biomedicine. This review summarized analysis on potential value small-molecule candidate metabolites clinical events, may better diagnosis, prognosis, drug screening treatment. We also discuss challenges need be addressed fuel next wave breakthroughs.

Language: Английский

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Applications of multi‐omics analysis in human diseases

MedComm, Journal Year: 2023, Volume and Issue: 4(4)

Published: July 31, 2023

Multi-omics usually refers to the crossover application of multiple high-throughput screening technologies represented by genomics, transcriptomics, single-cell proteomics and metabolomics, spatial so on, which play a great role in promoting study human diseases. Most current reviews focus on describing development multi-omics technologies, data integration, particular disease; however, few them provide comprehensive systematic introduction multi-omics. This review outlines existing technical categories multi-omics, cautions for experimental design, focuses integrated analysis methods especially approach machine learning deep integration corresponding tools, medical researches (e.g., cancer, neurodegenerative diseases, aging, drug target discovery) as well open-source tools databases, finally, discusses challenges future directions precision medicine. With algorithms, important disease research, also provided detailed introduction. will guidance researchers, who are just entering into research.

Language: Английский

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The Potential of Metabolomics in Biomedical Applications

Metabolites, Journal Year: 2022, Volume and Issue: 12(2), P. 194 - 194

Published: Feb. 19, 2022

The metabolome offers a dynamic, comprehensive, and precise picture of the phenotype. Current high-throughput technologies have allowed discovery relevant metabolites that characterize wide variety human phenotypes with respect to health, disease, drug monitoring, even aging. Metabolomics, parallel genomics, has led biomarkers aided in understanding diversity molecular mechanisms, highlighting its application precision medicine. This review focuses on metabolomics can be applied improve as well trends impacts metabolic neurodegenerative diseases, cancer, longevity, exposome, liquid biopsy development, pharmacometabolomics. identification distinct metabolomic profiles will help improvement clinical strategies treat disease. In years come, become tool routinely diagnose monitor health aging, or development. Biomedical applications already foreseen progression such obesity diabetes, using branched-chain amino acids, acylcarnitines, certain phospholipids, genomics; these assess disease severity predict potential treatment. Future endeavors should focus determining applicability utility metabolomic-derived markers their appropriate implementation large-scale settings.

Language: Английский

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Ion Mobility Mass Spectrometry (IM-MS) for Structural Biology: Insights Gained by Measuring Mass, Charge, and Collision Cross Section

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(6), P. 2902 - 2949

Published: Feb. 24, 2023

The investigation of macromolecular biomolecules with ion mobility mass spectrometry (IM-MS) techniques has provided substantial insights into the field structural biology over past two decades. An IM-MS workflow applied to a given target analyte provides mass, charge, and conformation, all three these can be used discern information. While charge are determined in (MS), it is addition that enables separation isomeric isobaric ions direct elucidation which reaped huge benefits for biology. In this review, where we focus on analysis proteins their complexes, outline typical features an experiment from preparation samples, creation ions, different spectrometers. We describe interpretation data terms protein conformation how compared other sources use computational tools. benefit coupling activation via collisions gas or surfaces photons photoactivation detailed reference recent examples. And finally, afforded by experiments when study conformationally dynamic intrinsically disordered proteins.

Language: Английский

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Probiotics synergized with conventional regimen in managing Parkinson’s disease

npj Parkinson s Disease, Journal Year: 2022, Volume and Issue: 8(1)

Published: May 24, 2022

Parkinson's disease (PD) is mainly managed by pharmacological therapy (e.g., Benserazide and dopamine agonists). However, prolonged use of these drugs would gradually diminish their dopaminergic effect. Gut dysbiosis was observed in some patients with PD, suggesting close association between the gut microbiome PD. Probiotics modulate host's microbiota beneficially. A 3-month randomized, double-blind, placebo-controlled clinical trial conducted to investigate beneficial effect probiotic co-administration Eighty-two PD were recruited randomly divided into [n = 48; Bifidobacterium animalis subsp. lactis Probio-M8 (Probio-M8), Benserazide, agonists] placebo (n 34; placebo, agonists) groups. Finally, 45 29 from groups provided complete fecal serum samples for further omics analysis, respectively. The results showed that conferred added benefits improving sleep quality, alleviating anxiety, gastrointestinal symptoms. Metagenomic analysis that, after intervention, there significantly more species-level genome bins (SGBs) animalis, Ruminococcaceae, Lachnospira, while less Lactobacillus fermentum Klebsiella oxytoca group (P < 0.05). Interestingly, correlated positively scores UPDRS-III, HAMA, HAMD-17, negatively MMSE. feces hardness. Moreover, co-administering increased SGBs involved tryptophan degradation, gamma-aminobutyric acid, short-chain fatty acids, secondary bile acid biosynthesis, as well acetic levels Taken together, synergized conventional regimen strengthened efficacy managing accompanied modifications microbiome, microbial metabolic potential, metabolites.

Language: Английский

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Targeting dysregulated lipid metabolism for the treatment of Alzheimer's disease and Parkinson's disease: Current advancements and future prospects

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 196, P. 106505 - 106505

Published: April 19, 2024

Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features AD memory decline cognitive dysfunction, while PD mainly manifests as motor dysfunction such limb tremors, muscle rigidity abnormalities, slow gait. Abnormalities in cholesterol, sphingolipid, glycerophospholipid metabolism have been demonstrated to directly exacerbate progression by stimulating Aβ deposition tau protein tangles. Indirectly, abnormal lipids can increase burden on brain vasculature, induce insulin resistance, affect structure neuronal cell membranes. Abnormal lipid leads through inducing accumulation α-syn, mitochondria endoplasmic reticulum, ferroptosis. Great progress has made targeting abnormalities for treatment recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, monoclonal antibodies apolipoprotein E (ApoE). This review comprehensively summarizes involvement dysregulated pathogenesis PD, application Lipid Monitoring, emerging regulatory drug targets. A better understanding lipidological bases may pave way developing effective prevention methods neurodegenerative disorders.

Language: Английский

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Metabolomics and health: from nutritional crops and plant-based pharmaceuticals to profiling of human biofluids

Cellular and Molecular Life Sciences, Journal Year: 2021, Volume and Issue: 78(19-20), P. 6487 - 6503

Published: Aug. 19, 2021

During the past decade metabolomics has emerged as one of fastest developing branches "-omics" technologies. Metabolomics involves documentation, identification, and quantification metabolites through modern analytical platforms in various biological systems. Advanced tools, such gas chromatography-mass spectrometry (GC/MS), liquid spectroscopy (LC/MS), non-destructive nuclear magnetic resonance (NMR) spectroscopy, have facilitated metabolite profiling complex matrices. Metabolomics, along with transcriptomics, an influential role discovering connections between genetic regulation, phenotyping biomarkers identification. Comprehensive allows integration summarized data towards manipulation biosynthetic pathways, determination nutritional quality markers, improvement crop yield, selection desired metabolites/genes, their heritability breeding. Along that, is invaluable predicting activity medicinal plants, assisting bioactivity-guided fractionation process bioactive leads discovery, well serving a tool for control authentication commercial plant-derived natural products. Metabolomic analysis human biofluids implemented clinical practice to discriminate physiological pathological state humans, aid early disease biomarker discovery predict individual response drug therapy. Thus, could be utilized preserve health by improving crops accelerating diagnostics, or increasing therapeutic efficacy drugs via more personalized approach. Here, we attempt explore potential value comprising above-mentioned applications improvement, plants utilization, and, prognosis, diagnosis management diseases.

Language: Английский

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Therapeutic Delivery of Nanoscale Sulfur to Suppress Disease in Tomatoes: In Vitro Imaging and Orthogonal Mechanistic Investigation

ACS Nano, Journal Year: 2022, Volume and Issue: 16(7), P. 11204 - 11217

Published: July 6, 2022

Nanoscale sulfur can be a multifunctional agricultural amendment to enhance crop nutrition and suppress disease. Pristine (nS) stearic acid coated (cS) nanoparticles were added soil planted with tomatoes (Solanum lycopersicum) at 200 mg/L infested Fusarium oxysporum. Bulk sulfur, ionic sulfate, healthy controls included. Orthogonal end points measured in two greenhouse experiments, including agronomic photosynthetic parameters, disease severity/suppression, mechanistic biochemical molecular the time-dependent expression of 13 genes related S bioassimilation pathogenesis-response, metabolomic profiles. Disease reduced plant biomass by up 87%, but nS cS significantly as determined area-under-the-disease-progress curve 54 56%, respectively. An increase planta accumulation was evident, size-specific translocation ratios suggesting different uptake mechanisms. In vivo two-photon microscopy gene revealed nanoscale-specific elemental pathway within that is separate from traditional sulfate accumulation. These findings correlate well profiling, which exhibited increased resistance immunity metabolites only nanoscale treatment. The linked metabolomics data demonstrate time-sensitive physiological window where stimulation will effective. provide understandings nonmetal nanomaterial-based suppression advance sustainable nanoenabled strategies food production.

Language: Английский

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More than meets the eye in Parkinson’s disease and other synucleinopathies: from proteinopathy to lipidopathy

Acta Neuropathologica, Journal Year: 2023, Volume and Issue: 146(3), P. 369 - 385

Published: July 8, 2023

The accumulation of proteinaceous inclusions in the brain is a common feature among neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease (PD), and dementia with Lewy bodies (DLB). main neuropathological hallmark PD DLB are inclusions, known (LBs), enriched not only α-synuclein (aSyn), but also lipid species, organelles, membranes, even nucleic acids. Furthermore, several genetic risk factors for mutations genes involved metabolism, GBA1, VSP35, or PINK1. Thus, it surprising that mechanisms have been implicated PD, inflammation, altered intracellular vesicular trafficking, mitochondrial dysfunction, alterations protein degradation systems, may be directly indirectly connected through homeostasis. In this review, we highlight discuss recent evidence suggests biology important drivers which require renovated attention by neuropathologists. Particularly, address implication lipids aSyn spreading pathology, ER stress. Together, should broaden view proteinopathy lipidopathy.

Language: Английский

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Advances in mass spectrometry-based multi-scale metabolomic methodologies and their applications in biological and clinical investigations

Science Bulletin, Journal Year: 2023, Volume and Issue: 68(19), P. 2268 - 2284

Published: Aug. 29, 2023

Metabolomics is a nascent field of inquiry that emerged in the late 20th century. It encompasses comprehensive profiling metabolites across spectrum organisms, ranging from bacteria and cells to tissues. The rapid evolution analytical methods data analysis has greatly accelerated progress this dynamic discipline over recent decades. Sophisticated techniques such as liquid chromatograph mass spectrometry (MS), gas MS, capillary electrophoresis nuclear magnetic resonance serve cornerstone metabolomic analysis. Building upon these methods, plethora modifications combinations have propel advancement metabolomics. Despite progress, scrutinizing metabolism at single-cell or single-organelle level remains an arduous task Some most thrilling advancements, metabolic techniques, offer profound insights into intricate mechanisms within organelles. This allows for study heterogeneity its pivotal role multiple biological processes. made MS imaging enabled high-resolution situ tissue sections even individual cells. Spatial reconstruction enable direct representation distribution alteration three-dimensional space. application novel led significant breakthroughs clinical studies, including discovery pathways, determination cell fate differentiation, anti-aging intervention through modulating metabolism, metabolomics-based clinicopathologic analysis, surgical decision-making based on on-site intraoperative review presents overview both conventional innovative highlighting their applications groundbreaking studies.

Language: Английский

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