Experimental Eye Research, Год журнала: 2024, Номер 250, С. 110159 - 110159
Опубликована: Ноя. 20, 2024
Язык: Английский
Seminars in Cancer Biology, Год журнала: 2024, Номер 106-107, С. 123 - 142
Опубликована: Сен. 30, 2024
Язык: Английский
Процитировано
10
International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 2334 - 2334
Опубликована: Март 5, 2025
Oxidative stress-induced photoreceptor cell death is closely associated with the etiology of age-related macular degeneration (AMD), and sodium iodate (SI) has been widely used as an oxidant stimulus in AMD models to induce retinal pigment epithelium (RPE) death. However, mechanism underlying SI-induced remains controversial unclear. In this study, we elucidate that ferroptosis a critical form induced by SI photoreceptor-derived 661W cells. disrupts system Xc-, leading glutathione (GSH) depletion triggering lipid peroxidation, thereby promoting Additionally, enhances intracellular Fe2+ levels, which further facilitates reactive oxygen species (ROS) accumulation, making cells more susceptible ferroptosis. Exogenous GSH, well specific inhibitors such Fer-1 antioxidants like NAC, significantly attenuate These findings provide new insights into mechanisms key pathway
Язык: Английский
Процитировано
1
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Апрель 16, 2025
Abstract Cytosolic lipid droplets (LDs) regulate homeostasis, with abnormal LD dynamics linked to metabolic diseases like atherosclerosis. In macrophage foam cells, LDs undergo autophagic degradation via lipophagy, but the extent of this process in vascular smooth muscle cell (VSMC) cells remains unclear. To track lipophagy real time, we developed a Rosella-PLIN2 biosensor by tagging perilipin 2 (PLIN2) fluorescent pH-biosensor Rosella. We show that proatherogenic lipoproteins and autophagy activators stimulate human macrophages. Targeting an LC3 fusion protein or LD-autophagy tethering compounds (LD-ATTECs) selectively enhanced promoting clearance. atherosclerosis model, accurately tracked arterial revealing distinct PLIN2 expression patterns non-leukocyte cells. identified deficiency VSMC demonstrate enhancing promotes catabolism primary TREM2 + macrophages exhibited high content low flux, whereas - had flux. Our findings highlight cell-specific interplay between immunometabolism unveiling novel therapeutic avenues for Additionally, model provides powerful tool studying metabolism, offering new insights into homeostasis disease mechanisms.
Язык: Английский
Процитировано
1
Investigative Ophthalmology & Visual Science, Год журнала: 2024, Номер 65(10), С. 29 - 29
Опубликована: Авг. 21, 2024
Purpose: Dysregulated cholesterol metabolism is critical in the pathogenesis of AMD. Cellular senescence contributes to development numerous age-associated diseases. In this study, we investigated link between burden and cellular photoreceptors. Methods: Retinas from rod-specific ATP binding cassette subfamily A member 1 (Abca1) G (Abcg1) (Abca1/g1-rod/-rod) knockout mice fed with a high-fat diet were analyzed for signs senescence. Real-time quantitative PCR immunofluorescence used characterize profile retina cholesterol-treated photoreceptor cell line (661W). Inducible elimination p16(Ink4a)-positive senescent cells (INK-ATTAC) or administration senolytic drugs (dasatinib quercetin: D&Q) examine impact senolytics on AMD-like phenotypes Abca1/g1-rod/-rod retina. Results: Increased accumulation as measured by markers was found Exogenous also induced 661W cells. Selective Abca1/g1-rod/-rod;INK-ATTAC D&Q improved visual function, lipid retinal pigment epithelium, Bruch's membrane thickening. Conclusions: Cholesterol promotes Eliminating photoreceptors improves function model neurodegeneration, senotherapy offers novel therapeutic avenue further investigation.
Язык: Английский
Процитировано
3
Cell stem cell, Год журнала: 2024, Номер 31(11), С. 1574 - 1590.e11
Опубликована: Окт. 21, 2024
Senescent neural progenitor cells have been identified in brain lesions of people with progressive multiple sclerosis (PMS). However, their role disease pathobiology and contribution to the lesion environment remains unclear. By establishing directly induced stem/progenitor cell (iNSC) lines from PMS patient fibroblasts, we studied senescent phenotype vitro. Senescence was strongly associated inflammatory signaling, hypermetabolism, senescence-associated secretory (SASP). PMS-derived iNSCs displayed increased glucose-dependent fatty acid cholesterol synthesis, which resulted accumulation lipid droplets. A 3-hydroxy-3-methylglutaryl (HMG)-coenzyme (CoA) reductase (HMGCR)-mediated lipogenic state found induce a SASP via cholesterol-dependent transcription factors. iNSC neurotoxicity mature neurons, treatment HMGCR inhibitor simvastatin altered SASP, promoting cytoprotective qualities reducing neurotoxicity. Our findings suggest disease-associated, cholesterol-related, hypermetabolic that leads neurotoxic signaling is rescuable pharmacologically.
Язык: Английский
Процитировано
3
Investigative Ophthalmology & Visual Science, Год журнала: 2025, Номер 66(1), С. 47 - 47
Опубликована: Янв. 21, 2025
Ever since the US Food and Drug Administration (FDA) approved first vascular endothelial growth factor (VEGF) antagonist 2 decades ago, inhibitors of VEGF have revolutionized treatment a variety ocular disorders involving pathologic neovascularization retinal exudation. In this perspective, we evaluate current status anti-VEGF therapies real-world challenges encountered with maintaining therapeutic outcomes. Finally, describe novel VEGF-based combinatorial approaches that are in clinical development.
Язык: Английский
Процитировано
0
Frontiers in Immunology, Год журнала: 2025, Номер 16
Опубликована: Фев. 10, 2025
This study aimed to elucidate the transcriptomic signatures and dysregulated pathways associated with autoimmune response in Cd38 -/- mice compared wild-type (WT) within bm12 chronic graft-versus-host disease (cGVHD) lupus model. We conducted bulk RNA sequencing on peritoneal exudate cells (PECs) spleen (SPC) at two four weeks following adoptive cell transfer. also analyzed from healthy, untreated mice. These analyses revealed a sustained upregulation of transcriptional profile purinergic receptors ectonucleotidases cGVHD WT PECs, which displayed coordinated expression several type I interferon-stimulated genes (ISGs) key molecules involved cyclic GMP-AMP synthase-stimulator interferon (cGAS-STING) signaling pathway, hallmarks pathology. A second receptor profile, included P2rx7 P2rx4 , showed gene components NLRP3 inflammasome its potential activators. processes were transcriptionally less active PECs than PECs. have shown evidence distinct enrichment that define such as Ca 2+ ion homeostasis, division, phagosome, autophagy, senescence, cytokine/cytokine interactions, Th17 Th1/Th2 differentiation versus samples, reflected milder inflammatory elicited relative counterparts allogeneic challenge. Last, we an intense metabolic reprogramming toward oxidative phosphorylation SPC mice, may reflect increased cellular demand for oxygen consumption, contrast short-lived effect level. Overall, these findings support pro-inflammatory immunomodulatory role CD38 during development cGVHD-lupus disease.
Язык: Английский
Процитировано
0
Investigative Ophthalmology & Visual Science, Год журнала: 2025, Номер 66(4), С. 14 - 14
Опубликована: Апрель 7, 2025
Microglial activation plays a pivotal role in the pathogenesis of retinal degeneration, contributing to neuroinflammation within retina. Previous studies identified that nicotinamide riboside (NR) mitigated light-induced degeneration (LIRD) and inhibited microglial activation. The cGAS-STING signaling pathway has been recognized as key mediator inflammation response cellular stress tissue damage. This study further explores regulatory impact NR on STING-mediated pyroptosis degeneration. Balb/c mice were subjected bright light exposure induce Bioinformatics analysis was used identify upregulated genes pathways involved progression based mouse transcriptomes from LIRD model. Molecular biology techniques immunofluorescence staining assess expression pyroptosis-associated molecules. Retinal function, photoreceptor apoptosis inflammatory evaluated presence absence supplementation. Exposure resulted mitochondrial dysfunction release dsDNA, significantly triggering pyroptosis. In contrast, treatment preserved biosynthesis, STING reactive microglia, dampened pro-inflammatory response. Additionally, intraperitoneal administration inhibitor H151 reduced pyroptosis, while improving function promoting survival. These findings suggest confers neuroprotection by attenuating damaged DNA-triggered Targeting presents promising therapeutic avenue for
Язык: Английский
Процитировано
0
Journal of Ginseng Research, Год журнала: 2025, Номер unknown
Опубликована: Май 1, 2025
Язык: Английский
Процитировано
0
Cell Death and Disease, Год журнала: 2025, Номер 16(1)
Опубликована: Май 16, 2025
Sepsis is a life-threatening multiple organ dysfunction resulting from dysregulated host response to infection, and patients with sepsis always exhibit state of immune disorder characterized by both overwhelming inflammation immunosuppression. The aging system, namely "immunosenescence", has been reported be correlated high morbidity mortality in elderly sepsis. Initially, immunosenescence was considered as range age-related alterations the system. However, increasing evidence proven that persistent or even short-term inflammatory challenge during could trigger accelerated cells, which might further exacerbate cytokine storm promote shift towards Thus, premature found young individuals, aggravates disorders induces progression Furthermore, old patients, synergistic effects may cause immunosenescence-associated more significantly, severe worse prognosis. Therefore, it necessary explore potential therapeutic strategies targeting
Язык: Английский
Процитировано
0