Association of metabolomics with PD-1 inhibitor plus chemotherapy outcomes in patients with advanced non-small-cell lung cancer DOI Creative Commons
Liang Zheng, Fang Hu, Lin Huang

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(4), P. e008190 - e008190

Published: April 1, 2024

Background Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a standard treatment for patients non-small cell lung cancer (NSCLC) lacking driver gene mutations. Reliable biomarkers are essential predicting outcomes. Emerging evidence from various cancers suggests that early assessment of serum metabolites could serve as valuable This study aims to identify linked outcomes in advanced NSCLC undergoing first-line or second-line therapy programmed death 1 (PD-1) plus chemotherapy. Method 200 receiving either PD-1 inhibitor chemotherapy, and 50 were enrolled this study. The combination divided into Discovery set (n=50) Validation (n=150). These sets further categorized respond non-respond groups based on progression-free survival PFS criteria (PFS≥12 PFS<12 months). Serum samples collected all before initiation untargeted metabolomics analysis, the goal identifying validating can predict efficacy immunotherapy Additionally, validated grouped high low categories their medians, relationship was analyzed using Cox regression models therapy. Results After impact accounted for, two significant differential identified both sets: N-(3-Indolylacetyl)-L-alanine methomyl (VIP>1 p<0.05). Notably, upregulation observed group poorer prognosis. In univariate analysis PFS, lower levels associated longer (HR=0.59, 95% CI, 0.41 0.84, p=0.003), prolonged also indicated by (HR=0.67, 0.47 0.96, p=0.029). multivariate analyses significantly (HR=0.60, 0.37 0.98, p=0.041). Conclusion Improved stage IIIB-IV mutations, who underwent combined Further exploration potential predictive value pretreatment detection peripheral blood is warranted. Statement ICIs established itself new care oncogenic alterations. Therefore, prognosis paramount importance. Currently, only biomarker ligand-1 (PD-L1), but its not absolute. Our patient prior may treatment. Compared detecting PD-L1 expression, advantage our it more convenient, dynamic, seems work synergistically expression.

Language: Английский

Small molecule metabolites: discovery of biomarkers and therapeutic targets DOI Creative Commons
Shi Qiu, Ying Cai, Hong Yao

et al.

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

Citations

382
Aggregation-Induced Emission Luminogen: Role in Biopsy for Precision Medicine DOI Creative Commons
Yanhong Duo, Lei Han, Yaoqiang Yang

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(20), P. 11242 - 11347

Published: Oct. 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),

Language: Английский

Citations

19
Diabetes in China: epidemiology, pathophysiology and multi-omics DOI
Weiping Jia, Juliana C.N. Chan, Tien Yin Wong

et al.

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Language: Английский

Citations

2
Multiplatform Metabolomics Reveals Novel Serum Metabolite Biomarkers in Diabetic Retinopathy Subjects DOI Creative Commons
Qiuhui Xuan, Yang Ouyang, Yanfeng Wang

et al.

Advanced Science, Journal Year: 2020, Volume and Issue: 7(22)

Published: Oct. 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.

Language: Английский

Citations

96
Reduction of choroidal neovascularization via cleavable VEGF antibodies conjugated to exosomes derived from regulatory T cells DOI
Ying Tian, Fan Zhang, Yefeng Qiu

et al.

Nature Biomedical Engineering, Journal Year: 2021, Volume and Issue: 5(9), P. 968 - 982

Published: July 26, 2021

Language: Английский

Citations

85
Design of Multi‐Shelled Hollow Cr2O3Spheres for Metabolic Fingerprinting DOI
Rongxin Li, Yongjie Zhou, Chao Liu

et al.

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(22), P. 12504 - 12512

Published: March 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.

Language: Английский

Citations

63
Diabetic retinopathy: Involved cells, biomarkers, and treatments DOI Creative Commons

Jiahui Ren,

Shuxia Zhang,

Yunfeng Pan

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 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.

Language: Английский

Citations

56
Multiplatform Untargeted Metabolomics DOI Creative Commons

Micah J. Jeppesen,

Robert Powers

Magnetic Resonance in Chemistry, Journal Year: 2023, Volume and Issue: 61(12), P. 628 - 653

Published: April 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.

Language: Английский

Citations

29
Metabolites as Risk Factors for Diabetic Retinopathy in Patients With Type 2 Diabetes: A 12-Year Follow-up Study DOI Creative Commons
Lilian Fernandes Silva,

Jenna Hokkanen,

Jagadish Vangipurapu

et al.

The Journal of Clinical Endocrinology & Metabolism, Journal Year: 2023, Volume and Issue: 109(1), P. 100 - 106

Published: Aug. 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.

Language: Английский

Citations

26
Ethanolamine as a biomarker and biomarker-based therapy for diabetic retinopathy in glucose-well-controlled diabetic patients DOI Creative Commons
Guangyi Hu, Liping Gu, Ruonan Wang

et al.

Science Bulletin, Journal Year: 2024, Volume and Issue: 69(12), P. 1920 - 1935

Published: Jan. 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.

Language: Английский

Citations

12