Small molecule metabolites: discovery of biomarkers and therapeutic targets

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Март 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.

Язык: Английский

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Aggregation-Induced Emission Luminogen: Role in Biopsy for Precision Medicine

Chemical Reviews, Год журнала: 2024, Номер 124(20), С. 11242 - 11347

Опубликована: Окт. 9, 2024

Biopsy, including tissue and liquid biopsy, offers comprehensive real-time physiological pathological information for disease detection, diagnosis, monitoring. Fluorescent probes are frequently selected to obtain adequate on processes in a rapid minimally invasive manner based their advantages biopsy. However, conventional fluorescent have been found show aggregation-caused quenching (ACQ) properties, impeding greater progresses this area. Since the discovery of aggregation-induced emission luminogen (AIEgen) promoted advancements molecular bionanomaterials owing unique high quantum yield (QY) signal-to-noise ratio (SNR),

Язык: Английский

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Diabetes in China: epidemiology, pathophysiology and multi-omics

Nature Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Янв. 14, 2025

Язык: Английский

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Multiplatform Metabolomics Reveals Novel Serum Metabolite Biomarkers in Diabetic Retinopathy Subjects

Advanced Science, Год журнала: 2020, Номер 7(22)

Опубликована: Окт. 1, 2020

Diabetic retinopathy (DR) is the main cause of vision loss or blindness in working age adults worldwide. The lack effective diagnostic biomarkers for DR leads to unsatisfactory curative treatments. To define potential metabolite diagnosis, a multiplatform-based metabolomics study performed. In this study, total 905 subjects with diabetes without (NDR) and at different clinical stages are recruited. Multiplatform methods used characterize serum metabolic profiles screen validate biomarkers. Based on criteria p < 0.05 false-discovery rate 0.05, 348 290 metabolites significantly associated pathogenesis early-stage DR, respectively. biomarker panel consisting 12-hydroxyeicosatetraenoic acid (12-HETE) 2-piperidone exhibited better performance than hemoglobin A1c (HbA1c) differentiating from diabetes, AUCs 0.946 versus 0.691 0.928 0.648 discovery validation sets, addition, showed higher sensitivity detection HbA1c. conclusion, comprehensively revealed dysregulation onset progression. defined can be DR.

Язык: Английский

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Reduction of choroidal neovascularization via cleavable VEGF antibodies conjugated to exosomes derived from regulatory T cells

Nature Biomedical Engineering, Год журнала: 2021, Номер 5(9), С. 968 - 982

Опубликована: Июль 26, 2021

Язык: Английский

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Design of Multi‐Shelled Hollow Cr₂O₃Spheres for Metabolic Fingerprinting

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(22), С. 12504 - 12512

Опубликована: Март 15, 2021

Abstract Schizophrenia (SZ) detection enables effective treatment to improve the clinical outcome, but objective and reliable SZ diagnostics are still limited. An ideal diagnosis of suited for robust screening must address throughput, low invasiveness, accuracy. Herein, we built a multi‐shelled hollow Cr 2 O 3 spheres (MHCSs) assisted laser desorption/ionization mass spectrometry (LDI MS) platform direct metabolic profiling biofluids towards diagnostics. The MHCSs displayed strong light absorption enhanced ionization microscale surface roughness with stability LDI metabolites. We profiled urine serum metabolites (≈1 μL) efficacy in seconds. discriminated patients (SZs) from healthy controls (HCs) highest area under curve (AUC) value 1.000 blind test. identified four compounds optimal diagnostic power as simplified metabolite panel demonstrated quantification clinic use. Our approach accelerates growth new platforms toward precision near future.

Язык: Английский

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Diabetic retinopathy: Involved cells, biomarkers, and treatments

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Авг. 9, 2022

Diabetic retinopathy (DR), a leading cause of vision loss and blindness worldwide, is caused by retinal neurovascular unit dysfunction, its cellular pathology involves at least nine kinds cells, including photoreceptors, horizontal bipolar amacrine ganglion glial cells (Müller astrocytes, microglia), endothelial pericytes, pigment epithelial cells. Its mechanism complicated inflammatory factor production, neovascularization, BRB impairment. However, the has not been completely elucidated. Drug treatment for DR gradually advancing recently. Research on potential drug targets relies upon clear information pathogenesis effective biomarkers. Therefore, we reviewed recent literature diagnostic prognostic biomarkers in terms blood, protein, clinical preclinical therapy (including synthesized molecules natural molecules). This review may provide theoretical basis further research.

Язык: Английский

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Multiplatform Untargeted Metabolomics

Magnetic Resonance in Chemistry, Год журнала: 2023, Номер 61(12), С. 628 - 653

Опубликована: Апрель 3, 2023

Metabolomics samples like human urine or serum contain upwards of a few thousand metabolites, but individual analytical techniques can only characterize hundred metabolites at best. The uncertainty in metabolite identification commonly encountered untargeted metabolomics adds to this low coverage problem. A multiplatform (multiple techniques) approach improve upon the number reliably detected and correctly assigned. This be further improved by applying synergistic sample preparation along with use combinatorial sequential non-destructive destructive techniques. Similarly, peak detection strategies that employ multiple probabilistic approaches have led better annotation decisions. Applying these also addresses issues reproducibility found single platform methods. Nevertheless, analysis large data sets from disparate presents unique challenges. While general processing workflow is similar across platforms, many software packages are fully capable types instrument. Traditional statistical methods such as principal component were not designed handle multiple, distinct sets. Instead, multivariate requires multiblock other model for understanding contribution instruments. review summarizes advantages, limitations, recent achievements metabolomics.

Язык: Английский

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Metabolites as Risk Factors for Diabetic Retinopathy in Patients With Type 2 Diabetes: A 12-Year Follow-up Study

The Journal of Clinical Endocrinology & Metabolism, Год журнала: 2023, Номер 109(1), С. 100 - 106

Опубликована: Авг. 10, 2023

Diabetic retinopathy (DR) is a specific microvascular complication in patients with diabetes and the leading cause of blindness. Recent advances omics, especially metabolomics, offer possibility identifying novel potential biomarkers for DR.The aim was to identify metabolites associated DR.We performed 12-year follow-up study including 1349 participants type 2 (1021 without DR, 328 DR) selected from METSIM cohort. Individuals who had before baseline were excluded (n = 63). The diagnosis based on fundus photography examination. We nontargeted metabolomics profiling metabolites.We found 17 significantly incident DR after adjustment confounding factors. Among amino acids, N-lactoyl isoleucine, valine, tyrosine, phenylalanine, N-(2-furoyl) glycine, 5-hydroxylysine an increased risk citrulline decreased DR. fatty acids N,N,N-trimethyl-5-aminovalerate myristoleate (14:1n5), palmitoleate (16:1n7), 5-dodecenoate (12:1n7) Sphingomyelin (d18:2/24:2), sphingolipid, Carboxylic acid maleate organic compounds 3-hydroxypyridine sulfate, 4-vinylphenol 4-ethylcatechol dimethyl sulfone DR.Our first large population-based longitudinal multiple several different metabolic pathways.

Язык: Английский

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Ethanolamine as a biomarker and biomarker-based therapy for diabetic retinopathy in glucose-well-controlled diabetic patients

Science Bulletin, Год журнала: 2024, Номер 69(12), С. 1920 - 1935

Опубликована: Янв. 2, 2024

Diabetic retinopathy (DR) is the leading cause of blindness among working-age population. Although controlling blood glucose levels effectively reduces incidence and development DR to less than 50%, there are currently no diagnostic biomarkers or effective treatments for in glucose-well-controlled diabetic patients (GW-DR). In this study, we established a prospective GW-DR cohort by strictly adhering glycemic control guidelines maintaining regular retinal examinations over median 2-year follow-up period. The discovery encompassed 71 individuals selected from pool 292 recruited at baseline, all whom consistently maintained hemoglobin A1c (HbA1c) below 7% without experiencing hypoglycemia. Within individuals, 21 subsequently experienced new-onset GW-DR, resulting an rate 29.6%. validation cohort, also observed significant 17.9%. Employing targeted metabolomics, investigated metabolic characteristics serum revealing association between lower ethanolamine risk. This was corroborated exhibiting superior performance distinguishing diabetes compared conventional risk factor HbA1c, with AUCs 0.954 versus 0.506 0.906 0.521 cohorts, respectively. Furthermore, streptozotocin (STZ)-induced rat model, attenuated inflammation, accompanied suppression microglial diacylglycerol (DAG)-dependent protein kinase C (PKC) pathway activation. conclusion, propose that potential biomarker represents viable biomarker-based therapeutic option GW-DR.

Язык: Английский

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