Small molecule metabolites: discovery of biomarkers and therapeutic targets

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

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Endocrine-Disrupting Chemicals and Disease Endpoints

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5342 - 5342

Published: March 10, 2023

Endocrine-disrupting chemicals (EDCs) have significant impacts on biological systems, and been shown to interfere with physiological especially by disrupting the hormone balance. During last few decades, EDCs affect reproductive, neurological, metabolic development function even stimulate tumor growth. EDC exposure during can disrupt normal patterns alter susceptibility disease. Many endocrine-disrupting properties, including bisphenol A, organochlorines, polybrominated flame retardants, alkylphenols, phthalates. These compounds gradually elucidated as risk factors for many diseases, such neural, diseases cancers. Endocrine disruption has spread wildlife species that are connected food chains. Dietary uptake represents an important source of exposure. Although represent a public health concern, relationship specific mechanism between remain unclear. This review focuses disease-EDC disease endpoints associated endocrine better understanding EDCs-disease elucidates new prevention/treatment opportunities screening methods.

Language: Английский

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Impact of Chemical Endocrine Disruptors and Hormone Modulators on the Endocrine System

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(10), P. 5710 - 5710

Published: May 20, 2022

There is growing concern regarding the health and safety issues of endocrine-disrupting chemicals (EDCs). Long-term exposure to EDCs has alarming adverse effects through both hormone-direct hormone-indirect pathways. Non-chemical agents, including physical agents such as artificial light, radiation, temperature, stress exposure, are currently poorly investigated, even though they can seriously affect endocrine system, by modulation hormonal action. Several mechanisms have been suggested explain interference with activity. However, difficulty in quantifying low standardization studies, presence confounding factors do not allow establishment a causal relationship between disorders specific toxic agents. In this review, we focus on recent findings hormone system modulators thyroid, parathyroid glands, adrenal steroidogenesis, beta-cell function, male female reproductive function.

Language: Английский

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Metabolic diseases and healthy aging: identifying environmental and behavioral risk factors and promoting public health

Frontiers in Public Health, Journal Year: 2023, Volume and Issue: 11

Published: Oct. 13, 2023

Aging is a progressive and irreversible pathophysiological process that manifests as the decline in tissue cellular functions, along with significant increase risk of various aging-related diseases, including metabolic diseases. While advances modern medicine have significantly promoted human health extended lifespan, diseases such obesity type 2 diabetes among older adults pose major challenge to global public societies age. Therefore, understanding complex interaction between factors crucial for promoting well-being healthy aging. This review article explores environmental behavioral associated their impact on The environment, an obesogenic environment exposure toxins, strongly correlated rising prevalence its comorbidities. Behavioral factors, diet, physical activity, smoking, alcohol consumption, sleep patterns, influence throughout Public interventions targeting modifiable can effectively promote healthier lifestyles prevent Collaboration government agencies, healthcare providers community organizations essential implementing these creating supportive environments foster

Language: Английский

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High-Resolution Mass Spectrometry for Human Exposomics: Expanding Chemical Space Coverage

Environmental Science & Technology, Journal Year: 2024, Volume and Issue: 58(29), P. 12784 - 12822

Published: July 10, 2024

In the modern "omics" era, measurement of human exposome is a critical missing link between genetic drivers and disease outcomes. High-resolution mass spectrometry (HRMS), routinely used in proteomics metabolomics, has emerged as leading technology to broadly profile chemical exposure agents related biomolecules for accurate measurement, high sensitivity, rapid data acquisition, increased resolution space. Non-targeted approaches are increasingly accessible, supporting shift from conventional hypothesis-driven, quantitation-centric targeted analyses toward data-driven, hypothesis-generating exposome-wide profiling. However, HRMS-based exposomics encounters unique challenges. New analytical computational infrastructures needed expand analysis coverage through streamlined, scalable, harmonized workflows pipelines that permit longitudinal tracking, retrospective validation, multi-omics integration meaningful health-oriented inferences. this article, we survey literature on state-of-the-art technologies, review current informatic pipelines, provide an up-to-date reference exposomic chemists, toxicologists, epidemiologists, care providers, stakeholders health sciences medicine. We propose efforts benchmark fit-for-purpose platforms expanding space, including gas/liquid chromatography-HRMS (GC-HRMS LC-HRMS), discuss opportunities, challenges, strategies advance burgeoning field exposome.

Language: Английский

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Leveraging Administrative Health Databases to Address Health Challenges in Farming Populations: Scoping Review and Bibliometric Analysis (1975-2024)

JMIR Public Health and Surveillance, Journal Year: 2025, Volume and Issue: 11, P. e62939 - e62939

Published: Jan. 9, 2025

Background Although agricultural health has gained importance, to date, much of the existing research relies on traditional epidemiological approaches that often face limitations related sample size, geographic scope, temporal coverage, and range events examined. To address these challenges, a complementary approach involves leveraging reusing data beyond its original purpose. Administrative databases (AHDs) are increasingly reused in population-based digital public health, especially for populations such as farmers, who distinct environmental risks. Objective We aimed explore reuse AHDs addressing issues within farming by summarizing current landscape AHD-based identifying key areas interest, gaps, unmet needs. Methods conducted scoping review bibliometric analysis using PubMed Web Science. Building upon previous reviews research, we comprehensive literature search 72 terms population AHDs. identify hot spots, directions, used keyword frequency, co-occurrence, thematic mapping. also explored profile exposome mapping co-occurrences between factors outcomes. Results Between 1975 April 2024, 296 publications across 118 journals, predominantly from high-income countries, were identified. Nearly one-third associated with well-established cohorts, Agriculture Cancer Agricultural Health Study. The most frequently included disease registers (158/296, 53.4%), electronic records (124/296, 41.9%), insurance claims (106/296, 35.8%), (95/296, 32.1%), hospital discharge (41/296, 13.9%). Fifty (16.9%) studies involved >1 million participants. broad exposure proxies used, (254/296, 85.8%) relied proxies, which failed capture specifics tasks. Research remains underexplored, predominant focus specific external exposome, particularly pesticide exposure. A limited have been examined, primarily cancer, mortality, injuries. Conclusions increasing use holds major potential advance populations. However, substantial gaps persist, low-income regions among underrepresented subgroups, women, children, contingent workers. Emerging issues, including per- polyfluoroalkyl substances, biological agents, microbiome, microplastics, climate change, warrant further research. Major persist understanding various conditions, cardiovascular, reproductive, ocular, sleep-related, age-related, autoimmune diseases. Addressing overlooked is essential comprehending risks faced communities guiding policies. Within this context, promoting conjunction other sources (eg, mobile social data, wearables) artificial intelligence approaches, represents promising avenue future exploration.

Language: Английский

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Outdoor air pollution exposure and the risk of type 2 diabetes mellitus: A systematic umbrella review and meta-analysis

Environmental Research, Journal Year: 2025, Volume and Issue: unknown, P. 120885 - 120885

Published: Jan. 1, 2025

Language: Английский

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Time to Consider the “Exposome Hypothesis” in the Development of the Obesity Pandemic

Nutrients, Journal Year: 2022, Volume and Issue: 14(8), P. 1597 - 1597

Published: April 12, 2022

The obesity epidemic shows no signs of abatement. Genetics and overnutrition together with a dramatic decline in physical activity are the alleged main causes for this pandemic. While they undoubtedly represent contributors to problem, not able fully explain all cases current trends. In context, body knowledge related exposure as yet underappreciated obesogenic factors, which can be referred "exposome", merits detailed analysis. Contrarily genome, "exposome" is subject great dynamism variability, unfolds throughout individual's lifetime. development precise ways capturing full spectrum person extraordinarily demanding. Data derived from epidemiological studies linking excess weight elevated ambient temperatures, utero, intergenerational effects well epigenetics, microorganisms, microbiota, sleep curtailment, endocrine disruptors, among others, suggests possibility that may work alone or synergistically several alternative putative global epidemic. This narrative review reports available evidence on drivers Broadly based interventions needed better identify these at same time stimulating reflection potential relevance perpetuation

Language: Английский

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Environmental endocrine disruptor Bisphenol A induces metabolic derailment and obesity via upregulating IL-17A in adipocytes

Environment International, Journal Year: 2023, Volume and Issue: 172, P. 107759 - 107759

Published: Jan. 16, 2023

Bisphenol A (BPA), a ubiquitous environmental endocrine disruptor, has been extensively demonstrated to be associated with metabolic disorders, including obesity and type 2 diabetes mellitus. However, the underlying mechanism underpinning etiology of chronic disorders not sufficiently elucidated.This study is designed explore toxicological pathogenesis inflammation in BPA exposure during obesity.We investigated role IL-17A association from human cross-sectional animal models, genetically modified IL-17A-/- mice.Here, our work started case-control observation that was significantly risk (odds ratio = 4.72, 95%CI: 3.18 - 11.18, P < 0.01), disorder levels interleukin-17A (IL-17A) adipose (estimated changes β 0.46, 0.15 1.01, 0.01) bariatric surgery. Animal model fed high-fat diet (HFD) confirmed aggravated body weight gain insulin resistance, concurrent much heightened inflammatory responses tissue increase macrophage polarization towards M1 stage. Genetically ablated mice (IL-17A-/-) showed reversed response, improved homeostasis, along sensitivity both HFD group alone or more + group. Moreover, mediation analysis epidemiological investigation plasma attributed up 30.01% mediating associations between risk.This research paradigm provides strong evidence for elucidation moderating resistance obesity. Such findings reiterate obesogenic disruptor unveils potential mechanisms such effect.

Language: Английский

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The effect of endocrine-disrupting chemicals on placental development

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 21, 2023

Endocrine-disrupting chemicals (EDCs) or endocrine disruptors are substances that either naturally occurring artificial and released into the natural environment. Humans exposed to EDCs through ingestion, inhalation, skin contact. Many everyday household items, such as plastic bottles containers, liners of metal food cans, detergents, flame retardants, food, gadgets, cosmetics, pesticides, contain disruptors. Each hormone has a unique chemical makeup structural attributes. The way hormones connect receptors is described “lock key” mechanism, with each serving key (lock). This mechanism enabled by complementary shape their hormone, which allows activate receptors. exogenous compounds have negative impact on organisms’ health interacting functioning system. associated cancer, cardiovascular risk, behavioural disorders, autoimmune abnormalities, reproductive disorders. exposure in humans highly harmful during critical life stages. Nonetheless, effect placenta often underestimated. especially sensitive due its abundance In this review, we evaluated most recent data effects placental development function, including heavy metals, plasticizers, UV filters preservatives. under evaluation evidence from human biomonitoring found nature. Additionally, study indicates important knowledge gaps will direct future research topic.

Language: Английский

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