The Cardiac Circadian Clock DOI Creative Commons
Martin E. Young

JACC Basic to Translational Science, Journal Year: 2023, Volume and Issue: 8(12), P. 1613 - 1628

Published: June 21, 2023

Virtually all aspects of physiology fluctuate with respect to the time day. This is beautifully exemplified by cardiovascular physiology, for which blood pressure and electrophysiology exhibit robust diurnal oscillations. At molecular/biochemical levels (eg, transcription, translation, signaling, metabolism), cardiovascular-relevant tissues (such as heart) are profoundly different during day vs night. Unfortunately, this in turn contributes toward 24-hour rhythms both risk adverse event onset arrhythmias, myocardial infarction) pathogenesis severity extent ischemic damage). Accumulating evidence indicates that cell-autonomous timekeeping mechanisms, termed circadian clocks, temporally govern biological processes known play critical roles function/dysfunction. In paper, a comprehensive review our current understanding cardiomyocyte clock health disease detailed. Unprecedented basic, translational, epidemiologic studies support need implement chronobiological considerations strategies designed prevention treatment disease.

Language: Английский

Toward building mass spectrometry-based metabolomics and lipidomics atlases for biological and clinical research DOI Creative Commons
Stanislava Rakusanova, Oliver Fiehn, Tomáš Čajka

et al.

TrAC Trends in Analytical Chemistry, Journal Year: 2022, Volume and Issue: 158, P. 116825 - 116825

Published: Nov. 17, 2022

Current metabolomics and lipidomics studies are limited in the number of examined matrices, breadth scope methods, reporting metabolites, data sharing. Here, we discuss concept atlases that characterize quantitative distribution relationships metabolites biological matrices serve as a resource for future studies. Combined sample extraction is recommended to screen metabolome lipidome comprehensively. A multiplatform mass spectrometry-based approach with methods each fraction should follow separate detect differing their physicochemical properties. Since many known detected through untargeted analysis, routine use multiple internal standards quantification advised. This provides semiquantitative delivers molar concentrations selected polar lipids. An interactive web tool query generate statistical models, visualize data, download results be developed access generated easily.

Language: Английский

Citations

40
Identification and validation of serum metabolite biomarkers for endometrial cancer diagnosis DOI Creative Commons
Wanshan Liu, Jinglan Ma, Juxiang Zhang

et al.

EMBO Molecular Medicine, Journal Year: 2024, Volume and Issue: 16(4), P. 988 - 1003

Published: Feb. 14, 2024

Abstract Endometrial cancer (EC) stands as the most prevalent gynecological tumor in women worldwide. Notably, differentiation diagnosis of abnormity detected by ultrasound findings (e.g., thickened endometrium or mass uterine cavity) is essential and remains challenging clinical practice. Herein, we identified a metabolic biomarker panel for EC using machine learning high-performance serum fingerprints (SMFs) validated biological function. We first recorded SMFs 191 204 Non-EC subjects via particle-enhanced laser desorption/ionization spectrometry (PELDI-MS). Then, achieved an area-under-the-curve (AUC) 0.957–0.968 through SMFs, outperforming antigen 125 (CA-125, AUC 0.610–0.684, p < 0.05). Finally, glutamine, glucose, cholesterol linoleate with 0.901–0.902 function vitro. Therefore, our work would facilitate development novel diagnostic biomarkers clinics.

Language: Английский

Citations

8
Time of exercise differentially impacts bone growth in mice DOI

Shaoling Yu,

Qingming Tang, Xiaofeng Lu

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(6), P. 1036 - 1052

Published: May 28, 2024

Language: Английский

Citations

8
Integral-Omics: Serial Extraction and Profiling of Metabolome, Lipidome, Genome, Transcriptome, Whole Proteome and Phosphoproteome Using Biopsy Tissue DOI
Wei Li, Jing Ping Sun, Rui Sun

et al.

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

The integrative multiomics characterization of minute amounts clinical tissue specimens has become increasingly important. Here, we present an approach called Integral-Omics, which enables sequential extraction metabolites, lipids, genomic DNA, total RNA, proteins, and phosphopeptides from a single biopsy-level specimen. We benchmarked this method with various samples, applied the workflow to perform profiling tissues six patients colorectal cancer, found that tumor exhibited suppressed ferroptosis pathways at levels. Together, study presents methodology metabolomics, lipidomics, genomics, transcriptomics, proteomics, phosphoproteomics using biopsy specimens.

Language: Английский

Citations

1
Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST DOI
Hans‐Georg Sprenger, Melanie J. Mittenbühler, Yizhi Sun

et al.

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

Published: Feb. 1, 2025

Language: Английский

Citations

1
NADPH and Mitochondrial Quality Control as Targets for a Circadian-Based Fasting and Exercise Therapy for the Treatment of Parkinson’s Disease DOI Creative Commons
William M. Curtis, William A. Seeds, Mark P. Mattson

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(15), P. 2416 - 2416

Published: Aug. 4, 2022

Dysfunctional mitochondrial quality control (MQC) is implicated in the pathogenesis of Parkinson’s disease (PD). The improper selection mitochondria for mitophagy increases reactive oxygen species (ROS) levels and lowers ATP levels. downstream effects include oxidative damage, failure to maintain proteostasis ion gradients, decreased NAD+ NADPH levels, resulting insufficient energy metabolism neurotransmitter synthesis. A ketosis-based metabolic therapy that (R)-3-hydroxybutyrate (BHB) may reverse dysfunctional MQC by partially replacing glucose as an source, stimulating mitophagy, decreasing inflammation. Fasting can potentially raise cytoplasmic increasing export ketone body-derived citrate flux through isocitrate dehydrogenase 1 (IDH1). essential cofactor nitric oxide synthase, synthesized diffuse into matrix react with electron transport chain-synthesized superoxide form peroxynitrite. Excessive peroxynitrite production cause opening permeability transition pore (mPTP) depolarize activate PINK1-dependent mitophagy. Both fasting exercise increase ketogenesis cellular NAD+/NADH ratio, both which are beneficial neuronal metabolism. In addition, engage adaptive stress response signaling pathways protect neurons against proteotoxic PD. Here, we discuss how intermittent from evening meal next-day lunch together morning exercise, when circadian most oxidized, NADP+/NADPH reduced, gene expression high, slow progression

Language: Английский

Citations

36
Tryptophan metabolism is a physiological integrator regulating circadian rhythms DOI Creative Commons
Paul Petrus, Marlene Cervantes, Muntaha Samad

et al.

Molecular Metabolism, Journal Year: 2022, Volume and Issue: 64, P. 101556 - 101556

Published: July 30, 2022

The circadian clock aligns physiology with the 24-hour rotation of Earth. Light and food are main environmental cues (zeitgebers) regulating rhythms in mammals. Yet, little is known about interaction between specific dietary components light coordinating homeostasis. Herein, we focused on role essential amino acids. Mice were fed diets depleted acids their behavioral monitored tryptophan was selected for downstream analyses. metabolism modulating homeostasis studied using isotope tracing as well transcriptomic- metabolomic- Dietary depletion alters mice. Furthermore, shown to be regulated a time- light- dependent manner. A multi-omics approach combinatory diet/light interventions demonstrated that modulates temporal regulation transcription programs by buffering photic cues. Specifically, metabolites regulate central functions suprachiasmatic nucleus core machinery liver. Tryptophan modulator integrating Our findings propose potential point pharmacologic intervention modulate phenotypes associated disrupted rhythms.

Language: Английский

Citations

30
Animal Models of Exercise From Rodents to Pythons DOI Open Access
Margaret H. Hastings, Jonathan J. Herrera, J. Sawalla Guseh

et al.

Circulation Research, Journal Year: 2022, Volume and Issue: 130(12), P. 1994 - 2014

Published: June 9, 2022

Acute and chronic animal models of exercise are commonly used in research. testing is used, often combination with genetic, pharmacological, or other manipulations, to study the impact these manipulations on cardiovascular response detect impairments improvements function that may not be evident at rest. Chronic conditioning cardiac phenotypic regular training as a platform for discovery novel pathways mediating benefits conferred by could exploited therapeutically. The well established, and, frequently, molecular mimic pathway changes induced recapitulate least some its benefits. This review discusses approaches assessing during an acute challenge rodents, practical conceptual considerations use common rodent models. case studying feeding Burmese python model exercise-like physiological adaptation also explored.

Language: Английский

Citations

28
Minimal upstream open reading frame of Per2 mediates phase fitness of the circadian clock to day/night physiological body temperature rhythm DOI Creative Commons
Takahito Miyake, Yuichi Inoue,

Xinyan Shao

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(3), P. 112157 - 112157

Published: March 1, 2023

Body temperature in homeothermic animals does not remain constant but displays a regular circadian fluctuation within physiological range (e.g., 35°C–38.5°C mice), constituting fundamental systemic signal to harmonize clock-regulated physiology. Here, we find the minimal upstream open reading frame (uORF) encoded by 5′ UTR of mammalian core clock gene Per2 and reveal its role as regulatory module for temperature-dependent entrainment. A shift affect transcription instead increases translation through uORF. Genetic ablation uORF inhibition phosphoinositide-3-kinase, lying protein synthesis, perturb entrainment cells simulated body cycles. At organismal level, mutant skin shows delayed wound healing, indicating that uORF-mediated modulation is crucial optimal tissue homeostasis. Combined with transcriptional regulation, may enhance fitness

Language: Английский

Citations

22
Daytime-restricted feeding enhances running endurance without prior exercise in mice DOI

Haoran Xin,

Rongfeng Huang,

Meiyu Zhou

et al.

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(7), P. 1236 - 1251

Published: June 26, 2023

Language: Английский

Citations

22