BIOPHYSICS, Год журнала: 2024, Номер 69(3), С. 359 - 369
Опубликована: Июнь 1, 2024
Язык: Английский
Translational Medicine of Aging, Год журнала: 2023, Номер 7, С. 52 - 65
Опубликована: Янв. 1, 2023
The underlying molecular mechanisms associated with sporadic Alzheimer's disease (AD), a progressive neurodegenerative disease, are not yet fully understood. Adult neurons post-mitotic cells that may need to survive for as long the lifespan of organism itself, they exposed DNA damaging stimuli and depend on repair their survival. It is reasonable hypothesize inadequate damaged could eventually contribute neuronal synaptic loss characteristic AD. Recent work related somatic mutations in neurons, damage response (DDR), role mitochondria, cell cycle regulation has highlighted multifactorial nature Over past two decades, most clinical trials AD treatment have targeted formation amyloid-β (Aβ) oligomers clearance Aβ plaques. However, no new drug managing had been approved since 2003 -until Aducanumab was 2021 Lecanemab 2023. As far we aware, there currently very few progress directly targeting enhancing repair, rescuing failing or regulating apoptosis primary mechanism action. This manuscript reviews recent developments regarding how excessive defective potentiate main purpose review towards developing effective therapeutic interventions can improve outcomes patients.
Язык: Английский
Процитировано
4
Опубликована: Апрель 9, 2024
Despite the advances in stent design, coating drugs, polymers, use of intravascular imaging, special devices (such as lithotripsy, ultra-high-pressure non-compliant balloons, and drug-coated balloons), improved operator skills techniques, problem in-stent restenosis (ISR) thrombosis (ST) remains a challenge for interventional cardiologists. Atherosclerotic lesions, ISR, ST, are systemic metabolic chronic inflammatory illnesses with local manifestation coronary vessels. Therefore, we propose managing these systemically through plant-based diet (PBD) intervention. We explain how PBD intervention can help mitigate atherosclerosis, ST. Thus, overcome biological epigenetic problems ISR ST similarly to reversing atherosclerosis. Our team is pioneering implementation cardiology patients who have undergone So far, results been very promising. hope that future, many research studies will be performed investigate further role decreasing incidence
Язык: Английский
Процитировано
1
Medical Oncology, Год журнала: 2024, Номер 41(5)
Опубликована: Апрель 11, 2024
Язык: Английский
Процитировано
1
Biomolecules, Год журнала: 2024, Номер 14(11), С. 1398 - 1398
Опубликована: Ноя. 2, 2024
The natural polyphenol resveratrol is a biologically active compound that interacts with DNA and affects the activity of some nuclear enzymes. Its effect on interaction between nucleosomes poly(ADP-ribose) polymerase-1 (PARP1) catalytic PARP1 was studied using Western blotting, spectrophotometry, electrophoretic mobility shift assay, single particle Förster resonance energy transfer microscopy. Resveratrol inhibited at micro- sub-micromolar concentrations, but inhibitory decreased higher concentrations due to aggregation polyphenol. inhibition by accompanied its binding enzyme center subsequent decrease in affinity nucleosomal DNA. Concurrent talazoparib substrate pocket PARP1, which occurs presence resveratrol, restores nucleosomes, suggesting sites overlap. data suggest can be classified as inhibitor PARP1.
Язык: Английский
Процитировано
1
Infection and Drug Resistance, Год журнала: 2023, Номер Volume 16, С. 4201 - 4212
Опубликована: Июнь 1, 2023
Background: At present, the treatment and prevention of Pasteurella multocida infections in pigs mainly rely on antibiotics vaccines, but inflammatory injury cannot be eliminated. The compound 18β-glycyrrhetinic acid (GA), a pentacyclic triterpenoid extracted from Glycyrrhiza glabra L . root (liquorice) with chemical structure similar to that steroidal hormones, has become research focus because its anti-inflammatory, antiulcer, antimicrobial, antioxidant, immunomodulatory, hepatoprotective neuroprotective effects, potential for vascular endothelial by P. not been evaluated. This study aimed investigate effects mechanisms GA intervention infections. Materials Methods: Putative targets were identified using network pharmacological screening molecular docking simulation. cell viability PIEC cells was investigated via CCK-8 assay. mechanism transfection western blot. Results: Through simulation, this found PARP1 may core target exert anti-inflammatory effects. Mechanistically, alleviates -induced inflammation PARP1-mediated NF-κB HMGB1 signalling suppression. Conclusion: These findings, first time, demonstrate therapeutic relationship among GA, injury, providing candidate drug, explanation treating caused infection. Keywords: pharmacology, PARP1, infection
Язык: Английский
Процитировано
3
Current Neuropharmacology, Год журнала: 2023, Номер 21(12), С. 2409 - 2423
Опубликована: Март 22, 2023
Abstract: Schizophrenia is a chronic and progressive disorder characterized by cognitive, emotional, behavioral abnormalities associated with neuronal development synaptic plasticity alterations. Genetic epigenetic in cortical parvalbumin-positive GABAergic interneurons consequent alterations glutamate-mediated excitatory neurotransmission during early neurodevelopment underlie schizophrenia manifestation progression. Also, pregnancy or phases of postnatal life are vulnerability inflammatory processes, which at the basis brain pathology higher risk comorbidities, including cardiovascular diseases metabolic syndrome. In addition, patients adopt an unhealthy lifestyle poor nutrition, leading to premature death. Here, I explored role functional nutrition as integrated intervention for long-term management schizophrenia. Several natural bioactive compounds plant-based whole foods, flavonoids, phytonutrients, vitamins, fatty acids, minerals, modulate functioning targeting neuroinflammation improving cognitive decline. Although further clinical studies needed, diet rich might be effective synergism standard treatments improve symptoms reduce comorbidities.
Язык: Английский
Процитировано
3
Protein Expression and Purification, Год журнала: 2023, Номер 211, С. 106336 - 106336
Опубликована: Июль 5, 2023
Язык: Английский
Процитировано
2
Cells, Год журнала: 2022, Номер 11(21), С. 3343 - 3343
Опубликована: Окт. 23, 2022
Inhibitors (PARPi) of poly(ADP-ribose-)polymerase-1 (PARP1) are used in antitumor therapy; their cytotoxicity correlates with the efficiency PARP1 trapping cell chromatin. Previous studies have demonstrated PARPi-induced on DNA, although details mechanism remain controversial. Here, interactions PARP1-nucleosome complexes PARPi, olaparib (Ola), talazoparib (Tala), and veliparib (Veli) were studied. PARPi trap nucleosomes without affecting structure complexes. The increases order Tala>Ola>>Veli, recapitulating relative efficiencies cells, but different from potency to inhibit catalytic activity PARP1. level inhibition auto-PARylation, which otherwise promotes dissociation Tala Ola (but not Veli) additionally modulated by enhanced binding nucleosomes. occurs a loss histones leads restoration intact nucleosomal DNA. data suggest that chromatin can considerably affect action.
Язык: Английский
Процитировано
4
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 3895 - 3895
Опубликована: Март 31, 2024
This study investigates the toxic effect of harmful materials, unfiltered by placenta, on neonatal umbilical cord (UC) vessels, focusing stress-induced adaptations in transcriptional and translational processes. It aims to analyze changes pathways related mRNA condensate formation, regulation, DNA damage response under maternal smoking-induced stress. UC vessels from neonates born smoking (Sm) nonsmoking mothers (Ctr) were examined. Immunofluorescence staining confocal microscopy assessed localization key markers, including Transcription Complex Subunit 1 (CNOT1) largest subunit RNA polymerase II enzyme (RPB1). Additionally, markers response, such as Poly(ADP-ribose) polymerase-1, evaluated. In Sm samples, dissolution CNOT1 granules was observed, potentially aiding stalled translation enhancing transcription via RPB1 assembly translocation. Control showed predominant cytoplasmic localization. Despite adaptive responses, endothelial cells exhibited significant damage, indicated like polymerase-1. Ex vivo metal treatment control mirrored sample alterations, emphasizing marker roles cell survival exposure. Maternal induces specific molecular affecting pathways. Understanding these intricate mechanisms could inform interventions improve health outcomes mitigate adverse effects exposure during pregnancy.
Язык: Английский
Процитировано
0
Cardiology Open Access, Год журнала: 2024, Номер 9(1), С. 01 - 15
Опубликована: Апрель 29, 2024
Despite the advances in stent design, coating drugs, polymers, use of intravascular imaging, special devices (such as lithotripsy, ultra-high-pressure non-compliant balloons, and drug-coated balloons), improved operator skills techniques, problem in-stent restenosis (ISR) thrombosis (ST) remains a challenge for interventional cardiologists. Atherosclerotic lesions, ISR, ST, are systemic metabolic chronic inflammatory illnesses with local manifestation coronary vessels. Therefore, we propose managing these systemically through plant-based diet (PBD) intervention. We explain how PBD intervention can help mitigate atherosclerosis, ST. Thus, overcome biological epigenetic problems ISR ST similarly to reversing atherosclerosis. Our team is pioneering implementation cardiology patients who have undergone So far, results been very promising. hope that future, many research studies will be performed investigate further role decreasing incidence
Язык: Английский
Процитировано
0