Tetrahedral Framework Nucleic Acid‐Based Delivery of DJ‐1‐saRNA Prevent Retinal Ischaemia–Reperfusion Injury via Inhibiting Ferroptosis

Cell Proliferation, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

ABSTRACT Retinal ischaemia/reperfusion injury (RI/RI) is the primary pathophysiological mechanism underlying retinal ischaemic diseases, potentially resulting in significant and irreversible visual impairment. Currently, there are no effective treatments available for RI/RI, oxidative stress a critical factor that contributes to associated damage. DJ‐1, an important endogenous antioxidant, has been proposed as promising therapeutic agent RI/RI owing its potential overexpression. In this study, tetrahedral frame nucleic acids (tFNAs) were utilised delivery vehicle DJ‐1 small activating RNA (saRNA), synthesis of novel nanocomposite (tFNAs‐DJ‐1‐saRNA). vitro experiments demonstrated tFNAs effectively delivered DJ‐1‐saRNA R28 cells, thus exerting repair effect on injury. vivo investigations revealed intravitreal injection tFNAs‐DJ‐1‐saRNA facilitated gene expression mitigated atrophy induced by RI/RI. Mechanistically, activated xCT/GPX4 pathway, thereby inhibiting ferroptosis, reducing ganglion cell damage protecting tissue. conclusion, study complex can ameliorate suggesting treatment diseases.

Язык: Английский

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Selective deletion of zinc transporter 3 in amacrine cells promotes retinal ganglion cell survival and optic nerve regeneration after injury

Neural Regeneration Research, Год журнала: 2023, Номер 18(12), С. 2773 - 2780

Опубликована: Апрель 10, 2023

Vision depends on accurate signal conduction from the retina to brain through optic nerve, an important part of central nervous system that consists bundles axons originating retinal ganglion cells. The mammalian system, cannot regenerate once it is injured, leading permanent vision loss. To date, there no clinical treatment can nerve and restore vision. Our previous study found mobile zinc (Zn2+) level increased rapidly after injury in retina, specifically vesicles inner plexiform layer. Furthermore, chelating Zn2+ significantly promoted axonal regeneration with a long-term effect. In this study, we conditionally knocked out transporter 3 (ZnT3) amacrine cells or construct two transgenic mouse lines (VGATCreZnT3fl/fl VGLUT2CreZnT3fl/fl, respectively). We obtained direct evidence response was also selective deletion ZnT3 cell survival crush injury, improved function, recovery. Sequencing analysis reginal revealed inhibiting release presynaptic affected transcription key genes related postsynaptic neurons, regulated synaptic connection between cells, fate These results suggest trigger transcriptomic changes neuronal growth thereby influencing plasticity networks. make theory zinc-dependent death more complete provide new insights into complex interactions

Язык: Английский

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Natural compounds efficacy in Ophthalmic Diseases: A new twist impacting ferroptosis

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 172, С. 116230 - 116230

Опубликована: Фев. 12, 2024

Ferroptosis, a distinct form of cell death, is characterized by the iron-mediated oxidation lipids and finely controlled multiple cellular metabolic pathways. These pathways encompass redox balance, iron regulation, mitochondrial function, as well amino acid, lipid, sugar metabolism. Additionally, various disease-related signaling also play role in regulation ferroptosis. In recent years, with introduction concept ferroptosis deepening research on its mechanism, closely related to biological conditions eye diseases, including organ development, aging, immunity, cancer. This article reviews development ferroptosis, mechanism latest progress ophthalmic diseases ocular within framework metabolism, active oxygen biology, biology. Key regulators mechanisms introduce important concepts major open questions field natural compounds. It hoped that future research, further breakthroughs will be made use promote treatment diseases. At same time, compounds may direction new drug for potential future. Open up way clinical ophthalmologists prevent

Язык: Английский

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Deferoxamine attenuates visual impairment in retinal ischemia‒reperfusion via inhibiting ferroptosis

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Ноя. 17, 2023

Retinal ischemia‒reperfusion (I/R) injury can cause significant damage to human retinal neurons, greatly compromising their functions. Existing interventions have been proven little effect. Ferroptosis is a newly discovered type of programmed cell death that has found be involved in the process multiple organs throughout body. Studies shown it also present injury. A rat model was constructed and treated with deferoxamine. In this study, we accumulation Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), consumption glutathione (GSH) via ELISA testing; increased expression transferrin; decreased ferritin, SLC7A11, GPX4 Western blotting (WB) real-time PCR testing. Structural signs ferroptosis (mitochondrial shrinkage) were observed across types, including ganglion cells (RGCs), photoreceptor cells, pigment epithelial cells. Changes visual function detected by F-VEP ERG. The results showed iron oxidative stress model, resulting tissue damage. Deferoxamine protects structural functional soundness retina inhibiting through simultaneous inhibition hemochromatosis, initiation transferrin, degradation ferritin activating antioxidant capacity System Xc-GSH-GPX4 pathway.

Язык: Английский

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Ulinastatin attenuated cardiac ischaemia/reperfusion injury by suppressing activation of the tissue kallikrein‐kinin system

British Journal of Pharmacology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 18, 2024

Abstract Background and Purpose Ulinastatin has beneficial effects in patients undergoing coronary artery bypass grafting (CABG) surgery due to its anti‐inflammatory properties, but the underlying mechanism remains unclear. Experimental Approach We used samples from CABG, a model of cardiac ischaemia–reperfusion injury (IRI) mice murine endothelial cell cultures investigate links between ulinastatin, kallikrein‐kinin system (KKS), dysfunction inflammation response ischaemia/reperfusion (IRI). These were assessed using clinical investigations, vitro vivo experiments RNA sequencing analysis. Key Results inhibited activity tissue kallikrein, key enzyme KKS, at 24 h after CABG surgery, which was verified our model. Under normal conditions, ulinastatin only kallikrein did not affect bradykinin (B 1 /B 2 ) receptors. protected against IRI, vitro, by suppressing activation down‐regulating B receptor‐related signalling pathways including ERK/ iNOS, resulted enhanced barrier function, mitigation oedema, decreased infarct size, improved function mortality. Inhibition knockdown , receptors prevented ERK translocation into nucleus, reducing reperfusion‐induced cells. Conclusions Implications Treatment with exerts protective influence on reperfusion system. Our findings highlight potential targeting /bradykinin alleviate dysfunction, thus improving IRI.

Язык: Английский

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The emerging role of neutrophil extracellular traps in endometritis

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Март 22, 2023

Endometritis is a kind of common obstetric disease in women, usually caused by various pathogenic bacteria. Neutrophil infiltration one the most important pathological features endometritis. Neutrophils can reach uterine cavity through endometrium, and make early response to infection pathogen. extracellular traps (NETs), meshwork chromatin fibers extruded neutrophils, have role entrapping microbial pathogens. It has been confirmed that NETs strong antibacterial effect play crucial roles occurrence development diseases. However, while killing bacteria, excessive formation may cause immune damage body. are present endometrium female domestic animals different physiological periods, especially post-mating, postpartum presence lesions, Meanwhile, its products might contribute reduction physical clearance persistent In brief, double-edged sword it endometritis, which be beneficial or harmful, specific mechanism needs further study. Here we provide an overview endometritis regulatory selenium on

Язык: Английский

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Tafluprost promotes axon regeneration after optic nerve crush via Zn2+-mTOR pathway

Neuropharmacology, Год журнала: 2023, Номер 242, С. 109746 - 109746

Опубликована: Окт. 12, 2023

Язык: Английский

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Melanin‐Like Nanomedicine Functions as a Novel RPE Ferroptosis Inhibitor to Ameliorate Retinal Degeneration and Visual Impairment in Dry Age‐Related Macular Degeneration

Advanced Healthcare Materials, Год журнала: 2024, Номер 13(30)

Опубликована: Авг. 11, 2024

Ferrous ion accumulation and lethal oxidative stress mediate irreversible retinal pigment epithelial (RPE) cell ferroptosis subsequent photoreceptor degeneration, a potential key pathogenic factor in the onset of dry age-related macular degeneration (dAMD), causing vision loss global elderly population. However, currently, no effective interventional treatment strategy exists clinical practice. Herein, lesion site-targeted melanin-like nanoparticles, named ConA-MelNPs, are designed as novel inhibitor for degenerative diseases. ConA-MelNPs possessed chelating iron characteristics, alleviating severe mitochondrial damage caused by protecting RPE cells from induced sodium iodate (NaIO

Язык: Английский

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In-vivo Raman microspectroscopy reveals differential nitrate concentration in different developmental zones in Arabidopsis roots

Plant Methods, Год журнала: 2024, Номер 20(1)

Опубликована: Дек. 18, 2024

Abstract Background Nitrate (NO 3 − ) is one of the two major forms inorganic nitrogen absorbed by plant roots, and tissue nitrate concentration in roots considered important for optimizing developmental programs. Technologies to quantify expression levels transporters assimilating enzymes at cellular level have improved drastically past decade. However, a technological gap remains detecting high spatial resolution. Using extraction-based methods, it challenging reliably estimate from small volume cells (i.e., with resolution), since targeting or specific group physically difficult. Alternatively, detection microelectrodes offers subcellular resolution cell specificity, but this method has some limitations on accessibility speed. Finally, optical biosensors very good ( in-vivo sensitivity (below 1 mM) cellular-level resolution, require transformation, limiting their applicability. In work, we apply Raman microspectroscopy high-dynamic range mapping different zones Arabidopsis thaliana in-situ . Results As proof concept, used content seedlings grown agar media concentrations. Our results revealed that root increases gradually meristematic zone (~ 250 µm cap) maturation mm under typical growth conditions Arabidopsis, trend not been previously reported. This was observed plants concentrations (0.5–10 mM). These were validated through destructive measurement concentration. Conclusions We present methodology based label-free within volumes Arabidopsis. Measurements are done without additional sample preparation. measurements changes lower higher tip mature tissue. Accumulation shows saturation behavior. The presented Raman-based approach allows non-destructive Raman-active compounds.

Язык: Английский

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Therapeutic potential of iron chelators in retinal vascular diseases

International Journal of Ophthalmology, Год журнала: 2023, Номер 16(11), С. 1899 - 1910

Опубликована: Окт. 25, 2023

Iron is one of the necessary metal elements in human body. There are numerous factors that control balance iron metabolism, and its storage transportation mechanisms intricate. As most energy-intensive tissues body, retina susceptible to imbalance. The occurrence overload leads generation a significant quantity reactive oxygen species. This will aggravate local oxidative stress inflammatory reactions even lead ferroptosis, eventually resulting retinal dysfunction. blood-retina-retinal barrier harmed by elevated inflammation, which characteristics vascular disorders. pathophysiology disorders may be significantly influenced iron. Recently, iron-chelating agents have been found antioxidative anti-inflammatory actions addition chelating. Therefore, neutralization considered new potentially useful therapeutic strategy. article reviews diseases discusses potential agents.

Язык: Английский

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