Circadian Influences on Brain Lipid Metabolism and Neurodegenerative Diseases DOI Creative Commons
Yusuf Hussain, Mehraj U Din Dar, Xiaoyue Pan

et al.

Metabolites, Journal Year: 2024, Volume and Issue: 14(12), P. 723 - 723

Published: Dec. 22, 2024

Circadian rhythms are intrinsic, 24 h cycles that regulate key physiological, mental, and behavioral processes, including sleep–wake cycles, hormone secretion, metabolism. These controlled by the brain’s suprachiasmatic nucleus, which synchronizes with environmental signals, such as light temperature, consequently maintains alignment day–night cycle. Molecular feedback loops, driven core circadian “clock genes”, Clock, Bmal1, Per, Cry, essential for rhythmic gene expression; disruptions in these loops associated various health issues. Dysregulated lipid metabolism brain has been implicated pathogenesis of neurological disorders contributing to oxidative stress, neuroinflammation, synaptic dysfunction, observed conditions Alzheimer’s Parkinson’s diseases. Disruptions expression have shown perturb regulatory mechanisms brain, thereby triggering neuroinflammatory responses damage. This review synthesizes current insights into interconnections between metabolism, a focus on their roles disease. It further examines how desynchronization genes affects explores potential through disrupted signaling might contribute pathophysiology neurodegenerative disorders.

Language: Английский

Reducing LDL-Cholesterol to Very Low Levels: Sailing Between Established Benefits and Potential Risks DOI
Stefania Angela Di Fusco, Massimo Volpe, Federico Nardi

et al.

High Blood Pressure & Cardiovascular Prevention, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Language: Английский

Citations

0
Bootstrap inference and machine learning reveal core differential plasma metabolic connectome signatures in major depressive disorder DOI

Hongxin Pan,

Yuyang Sha,

Xiaobing Zhai

et al.

Journal of Affective Disorders, Journal Year: 2025, Volume and Issue: 378, P. 281 - 292

Published: March 3, 2025

Language: Английский

Citations

0
Targeting PCSK9 beyond the liver: evidence from experimental and clinical studies DOI
Lorenzo Da Dalt, Andrea Baragetti, Giuseppe Danilo Norata

et al.

Expert Opinion on Therapeutic Targets, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

PCSK9 has been widely studied as a target for lipid-lowering its inhibition increases LDL-R recycling on the surface of hepatocytes, which promotes catabolism LDL particles.PCSK9 can be synthesized in extra-hepatic tissues, including brain, pancreas, heart, and immune cells. This is interest to understand whether effects observed when genetically inhibited by naturally occurring mutations are also recapitulated pharmacology. Genetics studies reported an increased risk developing new-onset diabetes, ectopic adiposity reduced immune-inflammatory responses with deficiency. However, these aspects were not clinical trials data from real world medicine monoclonal antibodies (mAbs) gene silencing approaches targeting PCSK9. It possible that biological adaptations lifelong, case genetic studies, could explain discrepancy obtained testing pharmacological Also, mAbs have use 12 years, thus probably, this time window, reduction circulating up 80-90% does lead changes other than impressive LDL-C CVD events.

Language: Английский

Citations

0
Triglycerides, high-density lipoprotein and cognitive function in middle-aged and older adults: a cross-sectional analysis DOI
Luyao Xie, Huanhuan Luo, Yajie Zhao

et al.

Biogerontology, Journal Year: 2025, Volume and Issue: 26(2)

Published: March 22, 2025

Language: Английский

Citations

0
Müller cells trophism and pathology as the next therapeutic targets for retinal diseases. DOI Creative Commons
Alessandro Arrigo, Ottavio Cremona, Emanuela Aragona

et al.

Progress in Retinal and Eye Research, Journal Year: 2025, Volume and Issue: unknown, P. 101357 - 101357

Published: April 1, 2025

Language: Английский

Citations

0
The Prognostic Value of the Naples Prognostic Score in Depression: Association with Prevalence and Mortality DOI
Jinkou Zhao, Yang Luo, Xiaofang Li

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 9, 2025

Abstract Background Depressive disorder is a widespread mental health condition, distinguished by symptoms such as persistent low mood, loss of interest, diminished energy, and changes in sleep appetite. The Naples Prognostic Score (NPS), which combines biomarkers related to inflammation nutritional status, has been shown have prognostic value several diseases. This study used data from the National Health Nutrition Examination Survey (NHANES), was carried out between 2007 2018, examine link NPS, depression prevalence, mortality people with depression. Methods cross-sectional analysis involved 29,655 participants, 2,688 individuals diagnosed depression, 2,190 participants followed for outcomes. Patient Questionnaire-9 (PHQ-9) measure blood albumin, total cholesterol, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte (LMR) were calculate NPS. relationship NPS examined using weighted logistic regression, while depressed patients evaluated Cox proportional hazards models, controlled clinical demographic variables. Results An increased likelihood (OR = 1.32, 95% CI: 1.09–1.60, p < 0.01) higher risk death all causes (HR 4.54, 2.24–9.21, 0.01), heart disease 8.39, 2.85–24.71, malignant neoplasms 5.10, 1.21–21.41, 0.03), diabetes 5.66, 1.44–22.24, hypertension 6.68, 1.69–26.40, significantly correlated scores. Conclusion highlights relevance predicting both prevalence its associated risk. offers valuable tool early stratification can support development personalized management strategies potentially improving their long-term

Language: Английский

Citations

0
Apolipoprotein E (APOE) and Alzheimer’s disease risk in a Ugandan population: A pilot case-control study DOI Creative Commons
Kamada Lwere, Haruna Muwonge,

Hakim Sendagire

et al.

Medicine, Journal Year: 2025, Volume and Issue: 104(19), P. e42407 - e42407

Published: May 9, 2025

Alzheimer’s disease (AD) is a neurodegenerative disorder that characterized by cognitive decline and progressive functional impairment. The Apolipoprotein E (APOE) gene, particularly its ε2, ε3, ε4 alleles, plays crucial role in lipid metabolism, has been implicated AD pathogenesis. Although the APOE status associated with an increased risk of AD, impact varies across populations. This study investigated prevalence association between alleles Ugandan cohort. case-control was conducted Uganda, included 87 participants (45 patients 42 healthy controls). Cognitive assessment performed using Montreal Assessment (MoCA) clinical diagnoses were based on ICD-11 DSM-5 criteria. Venous blood collected for genotyping polymerase chain reaction. Statistical analyses, including logistic regression generalized additive models (GAMs), used to assess after adjusting age, education, sex. 45 controls. group significantly older than controls (79.6 vs 73.0 years; P = .0006). allele common both (42.2%) control groups (44.0%), which higher 1000 Genomes African ancestry data. No significant found genotype or dosage sex, education. However, probability increases among carriers lower educational levels. While predicted adults, no statistically relationship observed These findings support need larger population-specific studies explore APOE’s sub-Saharan Africa.

Language: Английский

Citations

0
Multi-Targeting Valproic Acid Conjugates as Potent Agents Against Inflammation and Hyperlipidemia DOI Creative Commons

Panagiotis Theodosis‐Nobelos,

Eleni A. Rekka

Molecules, Journal Year: 2025, Volume and Issue: 30(11), P. 2339 - 2339

Published: May 27, 2025

Novel derivatives of valproic acid with biologically active moieties, such as thiomorpholine, 4-aminopyridine, serine methyl ester, trolox and the cinnamic derivative [(E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid], were synthesized at satisfactory yields. The conjugation these moieties was based on rationale design evaluation compounds selected structural characteristics, aiming multiple targets. These reduced acute inflammation considerably and, in most cases, more than several highly used, well-known, non-steroidal anti-inflammatory drugs. They also offered inhibition soybean lipoxygenase, some them (compounds 5 6) possessed radical scavenging lipid peroxidation attenuating effects. Their antioxidant capacity times higher that established trolox. All tested decreased plasma markers tyloxapol-induced hyperlipidemia rats. Compound 2 resulted 71.1%, 52.8% 79.1% decrease total cholesterol, triglycerides LDL-cholesterol, respectively, 150 μmol/kg (i.p.). effect LDL cholesterol is comparable or equal to simvastatin, a hypocholesterolemic 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitor, however, additionally great triglyceride-decreasing compared simvastatin. Thus, may be valuable addition multi-functional agents acting against various degenerative disorders implicate derangement.

Language: Английский

Citations

0
How active cholesterol coordinates cell cholesterol homeostasis: Test of a hypothesis DOI Creative Commons

Yvonne Lange,

Theodore L. Steck

Progress in Lipid Research, Journal Year: 2024, Volume and Issue: 96, P. 101304 - 101304

Published: Nov. 1, 2024

How do cells coordinate the diverse elements that regulate their cholesterol homeostasis? Our model postulates membrane forms simple complexes with bilayer phospholipids. The phospholipids in plasma are of high affinity; consequently, they fully complexed sterol. This sets resting level cholesterol. Cholesterol excess stoichiometric equivalence point these has chemical activity; we refer to it as active It equilibrates low affinity intracellular membranes where serves a negative feedback signal manifold regulatory proteins rein ongoing accretion. We tested review literature regarding fourteen homeostatic enterocytes. provided strong albeit indirect support for following hypothesis. Active inhibits uptake and biosynthesis by suppressing both expression activity gene products activated SREBP-2; namely, HMGCR, LDLR NPC1L1. also reduces free cell serving substrate its esterification ACAT synthesis side-chain oxysterols, 27-hydroxycholesterol particular. oxysterols drive depletion promoting destruction HMGCR stimulating sterol well activation LXR. latter fosters multiple proteins, including four transporters which is likely substrate. By nulling cholesterol, maintains cellular at physiologic set point.

Language: Английский

Citations

2
Innovative Peptide-Based Plasmonic Optical Biosensor for the Determination of Cholesterol DOI Creative Commons

Ana Lia Bernardo,

Anne Parra,

Virginia Cebrián

et al.

Biosensors, Journal Year: 2024, Volume and Issue: 14(11), P. 551 - 551

Published: Nov. 13, 2024

Plasmonic-based biosensors have gained prominence as potent optical biosensing platforms in both scientific and medical research, attributable to their enhanced sensitivity precision detecting biomolecular chemical interactions. However, the detection of low molecular weight analytes with high specificity remains a complex unresolved issue, posing significant limitations for advancement clinical diagnostic tools device technologies. Notably, abnormal cholesterol levels are well-established indicator various pathological conditions; yet, quantitative free form is complicated by its small size, pronounced hydrophobicity, necessity mediator molecules achieve efficient sensing. In present study, novel strategy quantification was developed, leveraging plasmonic readout conjunction highly specific cholesterol-binding peptide (C-pept) biorecognition element, anchored on functionalized silica substrate. The resulting biosensor exhibited an exceptionally limit 21.95 µM demonstrated linear response 10–200 range. This peptide-integrated sensor introduces one-step competitive method quantification, positioning itself sensitive modality implementation within AVAC platform, which operates using reflective dark-field microscopy.

Language: Английский

Citations

2