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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Arachidonic acid metabolism in health and disease

MedComm, Journal Year: 2023, Volume and Issue: 4(5)

Published: Sept. 20, 2023

Arachidonic acid (AA), an n-6 essential fatty acid, is a major component of mammalian cells and can be released by phospholipase A2. Accumulating evidence indicates that AA plays biochemical roles, as it the direct precursor bioactive lipid metabolites eicosanoids such prostaglandins, leukotrienes, epoxyeicosatrienoic obtained from three distinct enzymatic metabolic pathways: cyclooxygenase pathway, lipoxygenase cytochrome P450 pathway. metabolism involved not only in cell differentiation, tissue development, organ function but also progression diseases, hepatic fibrosis, neurodegeneration, obesity, diabetes, cancers. These are generally considered proinflammatory molecules, they trigger oxidative stress stimulate immune response. Therefore, interventions pathways effective ways to manage inflammatory-related diseases clinic. Currently, inhibitors targeting enzymes related important area drug discovery. Moreover, many advances have been made clinical studies combination with chemotherapy immunotherapy. Herein, we review discovery focus on relation health diseases. Furthermore, summarized, potential applications discussed.

Language: Английский

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ACSL4-Mediated Ferroptosis and Its Potential Role in Central Nervous System Diseases and Injuries

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 10021 - 10021

Published: June 12, 2023

As an iron-dependent regulated form of cell death, ferroptosis is characterized by lipid peroxidation and has been implicated in the occurrence development various diseases, including nervous system diseases injuries. Ferroptosis become a potential target for intervention these or injuries relevant preclinical models. member Acyl-CoA synthetase long-chain family (ACSLs) that can convert saturated unsaturated fatty acids, Acyl—CoA familymember4 (ACSL4) involved regulation arachidonic acid eicosapentaenoic acid, thus leading to ferroptosis. The underlying molecular mechanisms ACSL4-mediated will promote additional treatment strategies injury conditions. Our review article provides current view ferroptosis, mainly structure function ACSL4, as well role ACSL4 We also summarize latest research progress central further proving ACSL4-medicated important

Language: Английский

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Gut microbiota and microbiota-derived metabolites promotes endometriosis

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Jan. 25, 2023

Endometriosis is a pathological condition of the female reproductive tract characterized by existence endometrium-like tissue at ectopic sites, affecting 10% women between age 15 and 49 in USA. However, currently there no reliable non-invasive method to detect presence endometriosis without surgery many find hormonal therapy as ineffective avoiding recurrences. There lack knowledge on etiology factors that contribute development endometriosis. A growing body recent evidence suggests an association gut microbiota pathophysiology. direct impact microbiota-derived metabolites disease progression largely unknown. To understand causal role endometriosis, we have implemented novel model using antibiotic-induced microbiota-depleted (MD) mice investigate progression. Interestingly, found MD showed reduced endometriotic lesion growth and, transplantation oral gavage feces from with rescued growth. Additionally, germ-free donor mice, indicated uterine dispensable for mice. Furthermore, modulates immune cell populations peritoneum lesions-bearing Finally, signature were significantly altered one metabolite, quinic acid promoted survival epithelial cells vitro vivo, suggesting disease-promoting potential metabolites. In summary, these data suggest metabolome possibly through adaptations. Of translational significance, findings will aid designing diagnostics stool

Language: Английский

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The imperative of arachidonic acid in early human development

Progress in Lipid Research, Journal Year: 2023, Volume and Issue: 91, P. 101222 - 101222

Published: Feb. 4, 2023

We are presenting new evidence on essential fatty acids (EFA) in prenatal human development. have demonstrated, for the first time, detailed process of active selection some by placenta (biomagnification) and rejection others (bioreduction) how this strategy is supreme importance understanding biology reproduction. The biomagnification dominated arachidonic acid (ArA) its allies: di-homo-gamma-linolenic (DGLA), adrenic ω6 docosapentaenoic acid. Stearic similarly bio-magnified which likely to provide sn-1 position membrane synthesis. In contrast there a bioreduction oleic, linoleic all ω3 precursors docosahexaenoic (DHA), including eicosapentaenoic (EPA). Although DHA biomagnified, amplification from mother fetus small compared ArA. report dominant compartmentalisation ArA fetal plasma, cell membranes red cells, mono-nuclear endothelium placenta. conclude that allies, play paramount role development products conception. It plausible inadequate provision may be relevant neuro-vascular complications prematurity neurodevelopmental disorders associated with premature birth. present ArA's universal an identical acid-based observed contrasting cultures. dominance post-natal nutritional milk makes compelling case re-evaluation role, especially reproductive biology.

Language: Английский

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Camel milk peptides alleviate hyperglycemia by regulating gut microbiota and metabolites in type 2 diabetic mice

Food Research International, Journal Year: 2023, Volume and Issue: 173, P. 113278 - 113278

Published: July 13, 2023

Language: Английский

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Mitochondrial Dysfunction in PCOS: Insights into Reproductive Organ Pathophysiology

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13123 - 13123

Published: Aug. 23, 2023

Polycystic ovary syndrome (PCOS) is a complex, but relatively common endocrine disorder associated with chronic anovulation, hyperandrogenism, and micro-polycystic ovaries. In addition to reduced fertility, people PCOS have higher risk of obesity, insulin resistance, metabolic disease, all comorbidities that are mitochondrial dysfunction. This review summarizes human animal data report dysfunction dysregulation in better understand how mitochondria impact reproductive organ pathophysiology. in-depth considers the elements regulating quantity quality, from biogenesis under transcriptional regulation both nuclear genome ultrastructural functional complexes regulate cellular metabolism reactive oxygen species production, as well dynamics subcellular interactions key quality control. When any these functions disrupted, energetic equilibrium within cell changes, processes can fail, death occur. If this process ongoing, it affects tissue function, causing disease. The objective consolidate classify broad number studies various organs, including (oocytes granulosa cells), uterus, placenta, circulation, A secondary uncover potential role transgenerational transmission disorders.

Language: Английский

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Polycystic ovary syndrome and its management: In view of oxidative stress

BioMolecular Concepts, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 1, 2024

In the past two decades, oxidative stress (OS) has drawn a lot of interest due to revelation that individuals with many persistent disorders including diabetes, polycystic ovarian syndrome (PCOS), cardiovascular, and other often have aberrant oxidation statuses. OS close interplay PCOS features such as insulin resistance, hyperandrogenism, chronic inflammation; there is belief might contribute development PCOS. currently recognized not only one most prevalent endocrine but also significant contributor female infertility, affecting considerable proportion women globally. Therefore, understanding relationship between crucial therapeutic preventive strategies for Moreover, mechanistic study intracellular reactive oxygen species/ nitrogen species formation its possible interaction women's reproductive health required, which includes complex enzymatic non-enzymatic antioxidant systems. Apart from that, our current review regulation pathogenesis OS. A change in lifestyle, physical activity, various supplements boost levels, particularly vitamins, usage medicinal herbs, thought be best way combat this occurrence improve pathophysiologic conditions associated

Language: Английский

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Advances in free fatty acid profiles in gestational diabetes mellitus

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 19, 2024

Abstract The morbidity of gestational diabetes mellitus (GDM) is increasing and associated with adverse perinatal outcomes long-term maternal infant health. exact mechanism underlying changes in plasma free fatty acid (FFA) profiles patients GDM unknown. However, it believed that diet lipid metabolism may play a role. Fatty acids contain many specific FFAs, the type FFA has different impacts on physiological processes; hence, determining FFAs individual essential. Alterations concentration or profile facilitate insulin resistance. Additionally, some show potential to predict early pregnancy are strongly growth development fetus occurrence macrosomia. Here, we aimed review women discuss relationship incidence outcomes.

Language: Английский

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Fatty acids and their metabolites (resolvins) are altered in women with gestational diabetes mellitus (GDM)

Food & Function, Journal Year: 2024, Volume and Issue: 15(6), P. 3023 - 3035

Published: Jan. 1, 2024

The maternal fatty acid status plays a key role in influencing pregnancy outcomes. Omega-3 acids are the precursors for E-series (RvE) and D-series resolvins (RvD) possess anti-inflammatory properties. Pregnancy complications like gestational diabetes mellitus (GDM) associated with excess inflammation. This study reports levels of across gestation GDM non-GDM women, placental acids, their association status. Pregnant women were recruited at 11-14 (V1) weeks followed 18-22 (V2) 26-28 (V3) delivery (V4). A total 209 who diagnosed as 207 included this study. Fatty estimated using gas chromatography. protein (RvE1, RvE2, RvD1 RvD2) measured ELISA kits. Total PUFAs, eicosapentaenoic (EPA), omega-6 linoleic (LA) arachidonic (AA) lower, while saturated (SFA) alpha-linolenic (ALA) higher weeks. Placental AA was lower (p < 0.05) GDM. RvE1, RvD2 0.001 all) group. delta 5 desaturase index positively associated, erythrocyte omega-3 negatively RvE2 LA ALA 0.05, both), respectively. Our findings suggest that influences pro-resolving mediators which may lead to increased inflammation

Language: Английский

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