Inflammatory and glycolytic programs underpin a primed blood neutrophil state in patients with pneumonia DOI Creative Commons
Alex R. Schuurman, Joe M. Butler, Erik H.A. Michels

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(7), P. 107181 - 107181

Published: June 19, 2023

Neutrophils are potent immune cells with key antimicrobial functions. Previous in vitro work has shown that neutrophil effector functions mainly fueled by intracellular glycolysis. Little is known about the state of neutrophils still circulation patients during infection. Here, we combined flow cytometry, stimulation assays, transcriptomics, and metabolomics to investigate link between inflammatory metabolic pathways blood community-acquired pneumonia. Patients' neutrophils, relative from age- sex- matched controls, showed increased degranulation upon ex vivo stimulation, portrayed distinct upregulation transcriptional programs. This phenotype was accompanied a high-energy ATP content, transcriptomic glycolysis glycogenolysis. One month after hospital admission, these changes were largely normalized. These data elucidate molecular programs underpin balanced, yet primed

Language: Английский

Recent advances in machine learning applications in metabolic engineering DOI
Pradipta Patra,

Disha B.R.,

Pritam Kundu

et al.

Biotechnology Advances, Journal Year: 2022, Volume and Issue: 62, P. 108069 - 108069

Published: Nov. 25, 2022

Language: Английский

Citations

53

Unlocking the Mitochondria for Nanomedicine-based Treatments: Overcoming Biological Barriers, Improving Designs, and Selecting Verification Techniques DOI Creative Commons
Camilla Pegoraro,

Inés Domingo-Ortí,

Inmaculada Conejos‐Sánchez

et al.

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 207, P. 115195 - 115195

Published: Feb. 5, 2024

Enhanced targeting approaches will support the treatment of diseases associated with dysfunctional mitochondria, which play critical roles in energy generation and cell survival. Obstacles to mitochondria-specific include presence distinct biological barriers need pass through (or avoid) various internalization mechanisms. A range studies have reported design mitochondrially-targeted nanomedicines that navigate complex routes required influence mitochondrial function; nonetheless, a significant journey lies ahead before become suitable for clinical use. Moving swiftly forward require safety studies, vivo assays confirming effectiveness, methodologies validate mitochondria-targeted nanomedicines' subcellular location/activity. From nanomedicine standpoint, we describe involved (from administration arrival within mitochondria), features influencing rational design, techniques used identify/validate successful targeting. Overall, rationally-designed mitochondria-targeted-based hold great promise precise therapeutic delivery.

Language: Английский

Citations

11

Advances in Mass Spectrometry-Based Blood Metabolomics Profiling for Non-Cancer Diseases: A Comprehensive Review DOI Creative Commons
Ekaterina Demicheva, Vladislav Dordiuk, Fernando Polanco Espino

et al.

Metabolites, Journal Year: 2024, Volume and Issue: 14(1), P. 54 - 54

Published: Jan. 14, 2024

Blood metabolomics profiling using mass spectrometry has emerged as a powerful approach for investigating non-cancer diseases and understanding their underlying metabolic alterations. Blood, readily accessible physiological fluid, contains diverse repertoire of metabolites derived from various systems. Mass offers universal precise analytical platform the comprehensive analysis blood metabolites, encompassing proteins, lipids, peptides, glycans, immunoglobulins. In this review, we present an overview research landscape in spectrometry-based profiling. While field is primarily focused on cancer, review specifically highlights studies related to diseases, aiming bring attention valuable that often remains overshadowed. Employing natural language processing methods, processed 507 articles provide insights into application metabolomic specific The encompasses wide range with emphasis cardiovascular disease, reproductive diabetes, inflammation, immunodeficiency states. By analyzing samples, researchers gain perturbations associated these potentially leading identification novel biomarkers development personalized therapeutic approaches. Furthermore, approaches utilized research, including GC-MS, LC-MS, others discussing advantages limitations. To enhance scope, propose recent supporting applicability GC×GC-MS metabolomics-based studies. This addition will contribute more exhaustive available techniques. Integration clinical practice holds promise improving disease diagnosis, treatment monitoring, patient outcomes. unraveling complex alterations healthcare professionals can pave way precision medicine interventions. Continuous advancements technology data methods further potential facilitating its translation laboratory routine application.

Language: Английский

Citations

10

The detection of adulteration of olive oil with various vegetable oils – A case study using high-resolution 700 MHz NMR spectroscopy coupled with multivariate data analysis DOI
Hibah Alharbi, Jordan Kahfi,

Ayindrila Dutta

et al.

Food Control, Journal Year: 2024, Volume and Issue: 166, P. 110679 - 110679

Published: June 25, 2024

Language: Английский

Citations

10

Metformin’s Effects on Cognitive Function from a Biovariance Perspective: A Narrative Review DOI Open Access

Dimitrie Chele,

Carmen Adella Sîrbu,

Marian Mitrică

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1783 - 1783

Published: Feb. 19, 2025

This study examines the effects of metformin on brain functions focusing variability results reported in literature. While some studies suggest that may have neuroprotective diabetic patients, others report an insignificant impact cognitive function, or even a negative effect. We propose this inconsistency be due to intrinsic cellular-level among individuals, which we term "biovariance". Biovariance persists demographically homogeneous samples complex and stochastic biological processes. Additionally, metabolic actions metformin, including its influence neuroenergetics neuronal survival, produce different depending individual characteristics.

Language: Английский

Citations

1

Lactate-dependent transcriptional regulation controls mammalian eye morphogenesis DOI Creative Commons
Nozomu Takata, Jason Miska, Marc A. Morgan

et al.

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

Published: July 14, 2023

Abstract Mammalian retinal metabolism favors aerobic glycolysis. However, the role of glycolytic in morphogenesis remains unknown. We report that glycolysis is necessary for early stages development. Taking advantage an unbiased approach combines use eye organoids and single-cell RNA sequencing, we identify specific glucose transporters genes progenitors. Next, determine optic vesicle territory mouse embryos displays elevated levels activity. At functional level, show removal Glucose transporter 1 Lactate dehydrogenase A gene activity from developing progenitors arrests morphogenesis. Surprisingly, uncover lactate-mediated upregulation key eye-field transcription factors controlled by epigenetic modification histone H3 acetylation through deacetylase Our results unexpected bioenergetic independent lactate as a signaling molecule mammalian

Language: Английский

Citations

19

Gluconeogenesis Flux in Metabolic Disease DOI
Ankit Shah,

Fredric E. Wondisford

Annual Review of Nutrition, Journal Year: 2023, Volume and Issue: 43(1), P. 153 - 177

Published: Aug. 21, 2023

Gluconeogenesis is a critical biosynthetic process that helps maintain whole-body glucose homeostasis and becomes altered in certain medical diseases. We review gluconeogenic flux various diseases, including common metabolic disorders, hormonal imbalances, specific inborn genetic errors, cancer. discuss how the activity contributes to disease pathogenesis using data from experiments isotopic tracer spectroscopy methodologies. These vitro, animal, human studies provide insights into changes circulating levels of available gluconeogenesis substrates efficiency converting those by organs. highlight ongoing knowledge gaps, emerging research areas, suggest future investigations. A better understanding may ultimately identify novel targeted treatment strategies for such

Language: Английский

Citations

17

Review on computer-assisted biosynthetic capacities elucidation to assess metabolic interactions and communication within microbial communities DOI Creative Commons
Mahnoor Zulfiqar, Vinay Singh, Christoph Steinbeck

et al.

Critical Reviews in Microbiology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 40

Published: Jan. 25, 2024

Microbial communities thrive through interactions and communication, which are challenging to study as most microorganisms not cultivable. To address this challenge, researchers focus on the extracellular space where communication events occur. Exometabolomics interactome analysis provide insights into molecules involved in dynamics of their interactions. Advances sequencing technologies computational methods enable reconstruction taxonomic functional profiles microbial using high-throughput multi-omics data. Network-based approaches, including community flux balance analysis, aim model molecular within between communities. Despite these advances, challenges remain computer-assisted biosynthetic capacities elucidation, requiring continued innovation collaboration among diverse scientists. This review provides current state future directions elucidation studying

Language: Английский

Citations

6

Challenges and recent advances in quantitative mass spectrometry‐based metabolomics DOI Open Access

Nathan Ghafari,

Lekha Sleno

Analytical Science Advances, Journal Year: 2024, Volume and Issue: 5(5-6)

Published: June 1, 2024

Abstract The field of metabolomics has gained tremendous interest in recent years. Whether the goal is to discover biomarkers related certain pathologies or better understand impact a drug contaminant, numerous studies have demonstrated how crucial it variations metabolism. Detailed knowledge metabolic variabilities can lead more effective treatments, as well faster less invasive diagnostics. Exploratory approaches are often employed metabolomics, using relative quantitation look at perturbations between groups samples. Most been based on metabolite profiling quantitation, with very few an approach for absolute quantitation. Using accurate facilitates comparison different studies, enabling longitudinal studies. In this review, we discuss most widely used techniques quantitative mass spectrometry (MS). Various aspects will be addressed, such use external and/or internal standards, derivatization techniques, vivo isotopic labelling, MS imaging. principles, associated limitations and challenges, described each approach.

Language: Английский

Citations

6

Plant Life with and without Oxygen: A Metabolomics Approach DOI Open Access
Vladislav V. Yemelyanov, Roman K. Puzanskiy, Maria F. Shishova

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16222 - 16222

Published: Nov. 12, 2023

Oxygen deficiency is an environmental challenge which affects plant growth, the development and distribution in land aquatic ecosystems, as well crop yield losses worldwide. The capacity to exist conditions of or complete lack oxygen depends on a number anatomic, developmental molecular adaptations. leads inhibition aerobic respiration, causes energy starvation acceleration glycolysis passing into fermentations. We focus systemic metabolic alterations revealed with different approaches metabolomics. deprivation stimulates accumulation glucose, pyruvate lactate, indicating sugar metabolism, lactic fermentation, respectively. Among Krebs-cycle metabolites, only succinate level increases. Amino acids related glycolysis, including phosphoglycerate family (Ser Gly), shikimate (Phe, Tyr Trp) (Ala, Leu Val), are greatly elevated. Members Asp (Asn, Lys, Met, Thr Ile), Glu (Glu, Pro, Arg GABA), accumulate well. These metabolites important members signature plants, linking altered Krebs cycle allowing alternative pathways NAD(P)H reoxidation avoid excessive toxic fermentation products (lactate, acetaldehyde, ethanol). Reoxygenation induces downregulation levels major anaerobically induced amino acids, especially (GABA Glu) Ile). profiles during native hypoxia rather similar, consisting products, succinate, fumarate particularly Ala, Gly GABA. most intriguing fact that oxidative stress very much response but not reoxygenation.

Language: Английский

Citations

14