A comprehensive molecular analysis of cannabidiol: From solid state to antioxidant potential

Computational and Theoretical Chemistry, Год журнала: 2024, Номер unknown, С. 114890 - 114890

Опубликована: Сен. 1, 2024

Язык: Английский

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Dietary restriction and ageing: Recent evolutionary perspectives

Mechanisms of Ageing and Development, Год журнала: 2022, Номер 208, С. 111741 - 111741

Опубликована: Сен. 24, 2022

Язык: Английский

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Potential implications of natural compounds on aging and metabolic regulation

Ageing Research Reviews, Год журнала: 2024, Номер 101, С. 102475 - 102475

Опубликована: Авг. 31, 2024

Язык: Английский

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27-Hydroxylation of oncosterone by CYP27A1 switches its activity from pro-tumor to anti-tumor

Journal of Lipid Research, Год журнала: 2023, Номер 64(12), С. 100479 - 100479

Опубликована: Ноя. 20, 2023

Oncosterone (6-oxo-cholestane-3β,5α-diol; OCDO) is an oncometabolite and a tumor promoter on estrogen receptor alpha-positive breast cancer (ER(+) BC) triple-negative cancers (TN BC). OCDO oxysterol formed in three steps from cholesterol: 1) oxygen addition at the double bond to give α- or β- isomers of 5,6-epoxycholestanols (5,6-EC), 2) hydrolyses epoxide ring 5,6-ECs cholestane-3β,5α,6β-triol (CT), 3) oxidation C6 hydroxyl CT OCDO. On other hand, cholesterol can be hydroxylated by CYP27A1 ultimate methyl carbon its side chain 27-hydroxycholesterol ((25R)-Cholest-5-ene-3beta,26-diol, 27HC), which for ER(+) BC. It currently unknown whether precursors position C27 CYP27A1, as impact such modification proliferation TN BC cells. We investigated, herein, 27H-5,6-ECs ((25R)-5,6-epoxycholestan-3β,26-diol), 27H-CT ((25R)-cholestane-3β,5α,6β,26-tetrol) 27H-OCDO ((25R)-cholestane-6-oxo-3β,5α,26-triol) exist metabolites produced cells expressing CYP27A1. report, first time, that these compounds humans. pharmacological genetic evidence responsible their production. Importantly, we found 27-hydroxy-OCDO (27H-OCDO) inhibits cell blocks 27-HC-induced cells, showing this metabolic conversion commutes proliferative properties into antiproliferative ones. These data suggest unprecedented role control carcinogenesis inhibiting activities oncosterone 27-HC.

Язык: Английский

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Therapeutic Applications of Oxysterols and Derivatives in Age-Related Diseases, Infectious and Inflammatory Diseases, and Cancers

Advances in experimental medicine and biology, Год журнала: 2023, Номер unknown, С. 379 - 400

Опубликована: Дек. 1, 2023

Язык: Английский

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In Vitro Evaluation of the Effects of 7-Ketocholesterol and 7β-Hydroxycholesterol on the Peroxisomal Status: Prevention of Peroxisomal Damages and Concept of Pexotherapy

Advances in experimental medicine and biology, Год журнала: 2023, Номер unknown, С. 437 - 452

Опубликована: Дек. 1, 2023

Язык: Английский

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Altered Brain Cholesterol Machinery in a Down Syndrome Mouse Model: A Possible Common Feature with Alzheimer’s Disease

Antioxidants, Год журнала: 2024, Номер 13(4), С. 435 - 435

Опубликована: Апрель 3, 2024

Down syndrome (DS) is a complex chromosomal disorder considered as genetically determined form of Alzheimer’s disease (AD). Maintenance brain cholesterol homeostasis essential for functioning and development, its dysregulation associated with AD neuroinflammation oxidative damage. Brain imbalances also likely occur in DS, concurring the precocious AD-like neurodegeneration. In this pilot study, we analyzed, Ts2Cje (Ts2) mouse model expression genes encoding key enzymes involved metabolism levels main precursors products (i.e., oxysterols). The results showed, Ts2 mice compared to euploid mice, downregulation transcription 3-hydroxy-3-methylglutaryl-CoA reductase 24-dehydrocholesterol reductase, latter originally recognized an indicator AD, consequent reduction total levels. Moreover, responsible oxidation amounts resulting oxysterols were modified brains, autoxidation increased, suggesting exacerbation cerebral stress. We observed enhanced inflammatory response underlined by upregulation α-interferon interleukin-6, two cytokines whose synthesis increased brains patients. Overall, these suggest that DS share cycle derangements altered oxysterol levels, which may contribute events both diseases.

Язык: Английский

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Quantitative Determination of a Series of Oxysterols by an Optimized LC-MS/MS Analysis in Different Tissue Types

International Journal of Molecular Sciences, Год журнала: 2024, Номер 26(1), С. 77 - 77

Опубликована: Дек. 25, 2024

Oxysterols, as metabolites of cholesterol, play a key role in cholesterol homeostasis, autophagosome formation, and regulation immune responses. Disorders oxysterol metabolism are closely related to the pathogenesis neurodegenerative diseases. To systematically investigate profound molecular regulatory mechanisms diseases, it is necessary quantify oxysterols their central peripheral biospecimens simultaneously accurately. However, there lot unsolved problems with existing methods, such hindrance applying single method different biological specimens or challenge simultaneous quantification due differential groups on ends side chains. Herein, according physicochemical properties structure oxysterols, an optimized liquid chromatography-tandem mass spectrometry for was established by optimizing sample preparation process, chromatographic conditions, mobile phase pH, solvent selection. Seven were detected this method, including 27-hydroxycholesterol, 7α-hydroxycholesterol, 7α,27-dihydroxycholesterol, 7-dehydrocholesterol, 7α-hydroxy-3-oxo-4-cholestenoic acid, 3-hydroxy-5-cholestenoic 24(S)-hydroxycholesterol. Non-derivatization extraction methyl tert-butyl ether used biospecimens, followed separation phenyl hexyl column. By repeated validation, exhibited satisfactory linearity, precision, recovery, sensitivity, repeatability, stability, successfully applied detection plasma, cerebral cortex, liver mouse. In summary, our enables concurrent analysis various presenting broad range applicability.

Язык: Английский

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A diet supplemented with cholic acid elevates blood pressure accompanied by albuminuria in rats

Bioscience Biotechnology and Biochemistry, Год журнала: 2023, Номер 87(4), С. 434 - 441

Опубликована: Янв. 9, 2023

A diet supplemented with cholic acid (CA), the primary 12α-hydroxylated bile acid, can induce hepatic lipid accumulation in rats without obesity. This study examined effects of a CA-supplemented on blood pressure (BP). After acclimation, WKAH/HkmSlc (3 weeks old) were divided into two groups and fed control AIN-93-based or (0.5 g CA/kg) for 13 weeks. The CA increased systolic diastolic BP as well concentrations rats. No changes found sodium concentration. Urinary albumin concentration CA-fed An increase was observed expression ATP-binding cassette subfamily B member 1B that correlated BPs urinary accompanied by an portal taurocholic These results suggest acids are involved albuminuria via alteration function.

Язык: Английский

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Chemical synthesis and biochemical properties of cholestane-5α,6β-diol-3-sulfonate: A non-hydrolysable analogue of cholestane-5α,6β-diol-3β-sulfate

The Journal of Steroid Biochemistry and Molecular Biology, Год журнала: 2023, Номер 234, С. 106396 - 106396

Опубликована: Сен. 6, 2023

Язык: Английский

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