When cancer drug resistance meets metabolomics (bulk, single-cell and/or spatial): Progress, potential, and perspective DOI Creative Commons
Zhiqiang Zhang, Chaohui Bao, Jiang Lu

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 12

Published: Jan. 6, 2023

Resistance to drug treatment is a critical barrier in cancer therapy. There an unmet need explore hallmarks that can be targeted overcome this resistance for therapeutic gain. Over time, metabolic reprogramming has been recognised as one hallmark used prevent resistance. With the advent of metabolomics, targeting alterations cells and host patients represents emerging strategy overcoming Driven by technological methodological advances mass spectrometry imaging, spatial metabolomics involves profiling all metabolites (metabolomics) so information captured bona fide within sample. Spatial offers opportunity demonstrate drug-resistant tumor profile with heterogeneity, also poses data-mining challenge reveal meaningful insights from high-dimensional information. In review, we discuss latest progress, focus on currently available bulk, single-cell technologies their successful applications pre-clinical translational studies We provide summary mechanisms underlying different aspects; these include Warburg effect, altered amino acid/lipid/drug metabolism, generation stem cells, immunosuppressive metabolism. Furthermore, propose solutions describing how resistance; early detection during initiation, monitoring clinical response, novel anticancer target immunotherapy, emergence metabolomics. conclude perspectives omics approaches (integrating metabolomics) could further developed improve management patients.

Language: Английский

Using MetaboAnalyst 5.0 for LC–HRMS spectra processing, multi-omics integration and covariate adjustment of global metabolomics data DOI Open Access
Zhiqiang Pang,

Guangyan Zhou,

Jessica Ewald

et al.

Nature Protocols, Journal Year: 2022, Volume and Issue: 17(8), P. 1735 - 1761

Published: June 17, 2022

Language: Английский

Citations

1080
MUC1 Tissue Expression and Its Soluble Form CA15-3 Identify a Clear Cell Renal Cell Carcinoma with Distinct Metabolic Profile and Poor Clinical Outcome DOI Open Access
Giuseppe Lucarelli,

Monica Rutigliano,

Davide Loizzo

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 13968 - 13968

Published: Nov. 12, 2022

An altered metabolism is involved in the development of clear cell renal carcinoma (ccRCC). MUC1 overexpression has been found to be associated with advanced disease and poor prognosis. In this study, we evaluated metabolomic profile human ccRCC, according expression, integrated it transcriptomic data. Moreover, analyzed role sustaining ccRCC aggressiveness prognostic value its soluble form CA15-3. Integrated analysis showed that MUC1-expressing was characterized by metabolic reprogramming involving glucose lipid pathway. addition, primary cancer cells treated a small interfering RNA targeting (siMUC1) migrated proliferated at slower rate than untreated cells. After cisplatin treatment, death siMUC1 significantly greater Kaplan–Meier curves significant differences CSS PFS among groups patients high versus low levels multivariate analysis, CA15-3 an independent adverse factor for cancer-specific progression-free survival. conclusion, expressing particular reprogramming. The inhibition expression decreases motility viability improves susceptibility, suggesting pathway can regulate de novo chemotherapy resistance ccRCC.

Language: Английский

Citations

74
Causality of genetically determined metabolites and metabolic pathways on osteoarthritis: a two-sample mendelian randomization study DOI Creative Commons

Yifei Gu,

Qianmei Jin,

Jinquan Hu

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 31, 2023

Abstract Background Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases and leading cause pain disability in aged population. However, underlying biological mechanism has not been fully understood. This study aims to reveal causal effect circulation metabolites on OA susceptibility. Methods A two-sample Mendelian Randomization (MR) analysis was performed estimate causality GDMs OA. genome-wide association (GWAS) 486 used as exposure, whereas 8 different phenotypes, including any-site (All OA), knee and/or hip (knee/hip OA, spine finger thumb (hand were set outcomes. Inverse-variance weighted (IVW) for calculating estimates. weight mode, median, MR-egger, MR-PRESSO sensitive analysis. Furthermore, metabolic pathway via web-based Metaconflict 4.0. All statistical analyses R software. Results In this MR analysis, a total 235 causative associations between phenotypes observed. After false discovery rate (FDR) correction 9 robust 7 (e.g., arginine, kynurenine, isovalerylcarnitine) 5 finally identified. Additionally, eleven significant pathways 4 identified by Conclusion The finding our suggested that can be considered useful circulating biomarkers screening prevention clinical practice, also serve candidate molecules future exploration drug target selection.

Language: Английский

Citations

62
A comprehensive review of integrative pharmacology-based investigation: A paradigm shift in traditional Chinese medicine DOI Creative Commons
Haiyu Xu, Yanqiong Zhang, Ping Wang

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 11(6), P. 1379 - 1399

Published: March 21, 2021

Over the past decade, traditional Chinese medicine (TCM) has widely embraced systems biology and its various data integration approaches to promote modernization. Thus, integrative pharmacology-based (TCMIP) was proposed as a paradigm shift in TCM. This review focuses on presentation of this novel concept main research contents, methodologies applications TCMIP. First, TCMIP is an interdisciplinary science that can establish qualitative quantitative pharmacokinetics–pharmacodynamics (PK–PD) correlations through knowledge from multiple disciplines techniques different PK–PD processes vivo. Then, contents are introduced follows: chemical ADME/PK profiles TCM formulas; confirming three forms active substances action modes; establishing correlation; building correlations, etc. After that, we summarize existing resources, computational models experimental methods highlight urgent establishment mathematical modeling methods. Finally, further discuss for improvement quality control, clarification molecular mechanisms underlying actions TCMs discovery potential new drugs, especially TCM-related combination drug discovery.

Language: Английский

Citations

101
Targeted metabolomics identifies high performing diagnostic and prognostic biomarkers for COVID-19 DOI Creative Commons
Yamilé López‐Hernández, Joel Monárrez‐Espino,

Ana-Sofía Herrera-van Oostdam

et al.

Scientific Reports, Journal Year: 2021, Volume and Issue: 11(1)

Published: July 19, 2021

Research exploring the development and outcome of COVID-19 infections has led to need find better diagnostic prognostic biomarkers. This cross-sectional study used targeted metabolomics identify potential biomarkers that predicted course illness by assessing 110 endogenous plasma metabolites from individuals admitted a local hospital for diagnosis/treatment. Patients were classified into four groups (≈ 40 each) according standard polymerase chain reaction (PCR) testing disease course: PCR-/controls (i.e., non-COVID controls), PCR+/not-hospitalized, PCR+/hospitalized, PCR+/intubated. Blood samples collected within 2 days admission/PCR testing. Metabolite concentration data, demographic data clinical propose develop optimal regression models diagnosis prognosis COVID-19. The area under receiver operating characteristic curve (AUC; 95% CI) was assess each models' predictive value. A panel included kynurenine: tryptophan ratio, lysoPC C26:0, pyruvic acid discriminated controls PCR+/not-hospitalized (AUC = 0.947; CI 0.931-0.962). second consisting C10:2, butyric acid, distinguished PCR+/hospitalized PCR+/intubated 0.975; 0.968-0.983). Only C28:0 differentiated patients 0.770; 0.736-0.803). If additional studies with confirm value these biomarkers, such panels could eventually be use in medical practice.

Language: Английский

Citations

62
Replication stress triggered by nucleotide pool imbalance drives DNA damage and cGAS-STING pathway activation in NAFLD DOI Creative Commons
Romain Donné,

Maëva Saroul-Aïnama,

Pierre Cordier

et al.

Developmental Cell, Journal Year: 2022, Volume and Issue: 57(14), P. 1728 - 1741.e6

Published: June 28, 2022

Language: Английский

Citations

43
Porcine gut microbiota in mediating host metabolic adaptation to cold stress DOI Creative Commons
Yu Zhang,

Sun Lan,

Run Zhu

et al.

npj Biofilms and Microbiomes, Journal Year: 2022, Volume and Issue: 8(1)

Published: April 5, 2022

Abstract The gut microbiota plays a key role in host metabolic thermogenesis by activating UCP1 and increasing the browning process of white adipose tissue (WAT), especially cold environments. However, crosstalk between host, which lacks functional UCP1, making them susceptible to stress, has rarely been illustrated. We used male piglets as model evaluate response stress via (four groups: room temperature group, n = 5; group with antibiotics, 3). found that thermogenesis insulin resistance increased levels serum metabolites such glycocholic acid (GCA) glycochenodeoxycholate (GCDCA) altered compositions functions cecal under stress. was characterized Ruminococcaceae , Prevotellaceae Muribaculaceae subjected had expression genes related bile short-chain fatty (SCFA) metabolism their liver fat lipolysis fat. In addition, CLPS, PNLIPRP1, CPT1B, UCP3 were significantly use antibiotics showed weakened or strengthened tolerance phenotype, indicating important thermogenesis. Our results demonstrate microbiota-blood-liver axis may regulate during acclimation piglets.

Language: Английский

Citations

41
Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice DOI Creative Commons
Ayelet M Rosenberg, Manish Saggar, Anna S. Monzel

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 10, 2023

Abstract The brain and behavior are under energetic constraints, limited by mitochondrial energy transformation capacity. However, the mitochondria-behavior relationship has not been systematically studied at a brain-wide scale. Here we examined association between multiple features of respiratory chain capacity stress-related behaviors in male mice with diverse behavioral phenotypes. Miniaturized assays enzyme activities DNA (mtDNA) content were deployed on 571 samples across 17 areas, defining specific patterns mito-behavior associations. By applying multi-slice network analysis to our dataset, identified three large-scale networks areas shared signatures. A major composed cortico-striatal exhibited strongest correlations, accounting for up 50% animal-to-animal differences, suggesting that this mito-based is functionally significant. also overlapped regional gene expression structural connectivity, distinct molecular phenotype This work provides convergent multimodal evidence anchored activities, expression, animal distinct, behaviorally-relevant phenotypes exist mouse brain.

Language: Английский

Citations

32
Cooperative STAT3-NFkB signaling modulates mitochondrial dysfunction and metabolic profiling in hepatocellular carcinoma DOI
Sharmeen Ishteyaque, Gurvinder Singh,

Karan Singh Yadav

et al.

Metabolism, Journal Year: 2024, Volume and Issue: 152, P. 155771 - 155771

Published: Jan. 5, 2024

Language: Английский

Citations

10
Blood metabolomic and transcriptomic signatures stratify patient subgroups in multiple sclerosis according to disease severity DOI Creative Commons

Alexandra E. Oppong,

Leda Coelewij,

G S M Robertson

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(3), P. 109225 - 109225

Published: Feb. 15, 2024

There are no blood-based biomarkers distinguishing patients with relapsing-remitting (RRMS) from secondary progressive multiple sclerosis (SPMS) although evidence supports metabolomic changes according to MS disease severity. Here machine learning analysis of serum data stratified RRMS SPMS high accuracy and a putative score was developed that patient subsets. The top differentially expressed metabolites between versus included lipids fatty acids, enriched in pathways related cellular respiration, notably, elevated lactate glutamine (gluconeogenesis-related) acetoacetate bOHbutyrate (ketone bodies), reduced alanine pyruvate (glycolysis-related). Serum were recapitulated the whole blood transcriptome, whereby genes also respiration SPMS. final gene-metabolite interaction network demonstrated potential metabolic shift glycolysis toward increased gluconeogenesis ketogenesis SPMS, indicating stress which may trigger response subsequent neurodegeneration.

Language: Английский

Citations

10