Role of lipoprotein structure and dynamics in disease development: from atherosclerosis to Covid-19

Опубликована: Янв. 1, 2023

Lipoproteins play a crucial role in lipid metabolism, serving as carriers for lipids such cholesterol and triglycerides the bloodstream. Atherosclerosis is complex cardiovascular disease characterized by accumulation of cholesterol-rich plaques arterial walls, leading to narrowed hardened arteries. Recently, spike protein from SARS-CoV-2 virus, responsible COVID-19, has been subject research concerning its potential impact on metabolism association with disease. Understanding interaction between lipoproteins influence could have implications our knowledge health. In this research, we investigated ultrastructure HDL individuals different profiles well mature model nascent membranes. these differences will help create novel rHDL particles superior lipid-removing CVD-treating properties. Finally, cell membranes study imbalances metabolism. To achieve objectives, deposition, exchange removal were followed techniques Neutron reflection attenuated total Fourier transformation infrared spectroscopy while, was unravelled small-angle X-ray scattering.

Язык: Английский

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Antidepressant Drugs and COVID-19: A Review of Basic and Clinical Evidence

Journal of Clinical Medicine, Год журнала: 2022, Номер 11(14), С. 4038 - 4038

Опубликована: Июль 12, 2022

The COVID-19 pandemic has encouraged the repurposing of existing drugs as a shorter development strategy in order to support clinicians with this difficult therapeutic dilemma. There is evidence theory that some antidepressants can reduce concentrations different cytokines humans and animals and, recently, antiviral activity against SARS-CoV-2 been reported. aims narrative review are evaluate possible role treatment infection benefits risks patients taking for mental disorders infection. A was performed analyse current literature identify antidepressant medication patients. electronic search completed MEDLINE MedRxiv/BioRxiv published ClinicalTrials.gov ongoing clinical trials. results show from preclinical data observational studies about efficacy specific treating In addition, two phase II testing fluvoxamine showed positive deterioration hospitalization rate versus placebo. Seven trials fluvoxamine, fluoxetine, tramadol (as per its anti-inflammatory effect) still early phases. Although available limited, sum several provide basis evaluating use humans. Further investigations will be needed application.

Язык: Английский

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Association of Altered Plasma Lipidome with Disease Severity in COVID-19 Patients

Biomolecules, Год журнала: 2024, Номер 14(3), С. 296 - 296

Опубликована: Март 1, 2024

The severity of COVID-19 is linked to an imbalanced immune response. dysregulated metabolism small molecules and bioactive lipids has also been associated with disease severity. To promote understanding the biochemistry provide targets for intervention, we applied a range LC-MS platforms analyze over 100 plasma samples from patients varying detailed clinical information on inflammatory responses (>30 markers). This third publication in series, it reports results comprehensive lipidome profiling using targeted LC-MS/MS. We identified 1076 lipid features across 25 subclasses, including glycerophospholipids, sterols, glycerolipids, sphingolipids, among which 531 were dramatically changed intensive care unit (ICU) compared ward. Patients ICU showed 1.3–57-fold increases ceramides, (lyso-)glycerophospholipids, diglycerides, triglycerides, plasmagen phosphoethanolamines, 1.3–2-fold lower levels cyclic lysophosphatidic acid, sphingosine-1-phosphates, sphingomyelins, arachidonic acid-containing phospholipids, lactosylceramide, cholesterol esters Specifically, phosphatidylinositols (PIs) strong fatty acid saturation-dependent behavior, saturated (SFA)- monosaturated (MUFA)-derived PI decreasing polystaturated (PUFA)-derived increasing. found ~4000 significant Spearman correlations between multiple markers response |R| ≥ 0.35 FDR corrected Q < 0.05. Except lysophospholipids positively CD4 fraction T cells, cytokines IL-8 IL-18. In contrast, sphingosine-1-phosphates negatively correlated innate such as CRP IL-6. Further indications metabolic changes moderate demonstrated recovering ward those at start hospitalization, where 99 species altered (6 increased by 30–62%; 93 decreased 1.3–2.8-fold). Overall, these findings support expand early that involved COVID-19.

Язык: Английский

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Advancing Viral Defense: Unravelling the Potential of Host-Directed Antivirals Against SARS-CoV-2

Drugs and Drug Candidates, Год журнала: 2025, Номер 4(2), С. 13 - 13

Опубликована: Март 28, 2025

The COVID-19 pandemic, driven by the high transmissibility and immune evasion caused SARS-CoV-2 its variants (e.g., Alpha, Delta, Omicron), has led to massive casualties worldwide. As of November 2024, International Committee on Taxonomy Viruses (ICTV) identified 14,690 viral species across 3522 genera. increasing infectious resistance FDA EMA-approved antivirals, such as 300-fold efficacy reduction in Nirmatrelvir against 3CLpro, highlight need for mutation-stable likewise targeting essential host proteins like kinases, heat shock proteins, lipid metabolism immunological pathway etc. Unlike direct-acting HDAs reduce risk conserved replication. proposal repurposing current FDA-approved drugs host-directed antiviral (HDA) approach is not new, Ouabain, a sodium-potassium ATPase inhibitor herpes simplex virus (HSV) Verapamil, calcium channel blocker influenza A (IAV), name few. Given colossal potential HDA exterminate infection, it been increasingly studied SARS-CoV-2. This review aims unravel interaction between viruses human hosts their successfully proposed provide insight into an alternative treatment rampant mutation benefits, limitations, protein-targeted therapies prospects are also covered this review.

Язык: Английский

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Sphingolipid Metabolism-Related Genes as Diagnostic Markers in Pneumonia-Induced Sepsis: The AUG Model

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Апрель 28, 2025

Pneumonia-induced sepsis (PIS) is a life-threatening condition with high mortality rates, necessitating the identification of biomarkers and therapeutic targets. Sphingolipid, particularly ceramides, are pivotal in modulating immune responses determining cell fate. In this study, we identified novel gene signature related to sphingolipid metabolism, comprising ACER3, UGCG, GBA, which key enzymes involved synthesis metabolism ceramides. This signature, termed “AUG model”, demonstrated strong diagnostic performance modest prognostic efficacy across both training (GSE65682) validation (E-MTAB-1548 E-MTAB-5273) datasets. A clinical cohort 20 PIS patients, 31 pneumonia cases, 11 healthy controls further validated increased expression AUG genes at mRNA protein levels peripheral blood samples upon admission. Our comprehensive analysis bulk single-cell transcriptome datasets revealed that these implicated death pathways, including autophagy apoptosis. Additionally, cell-communication indicated enhanced macrophage migration inhibitory factor (MIF) signaling may be associated dysregulated potentially driving inflammatory cascade. study identifies predictive model for PIS, highlighting role metabolism-related disease progression suggesting potential targets management.

Язык: Английский

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