Influences of lead-based perovskite nanoparticles exposure on early development of human retina

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 26, 2025

Lead-based perovskite nanoparticles (Pb-PNPs) are widely utilized in the photovoltaic industry. However, due to their poor stability and high water solubility, lead often gets released into environment, which can negatively impact development of central nervous system (CNS). As an extension CNS, effects mechanisms Pb-PNPs on human retinal have remained elusive. We aimed investigate development. Human embryonic stem cell-derived three-dimensional floating organoids (hEROs) were established simulate early Using immunofluorescence staining, biological-transmission electron microscopy analysis, inductively coupled plasma-mass spectrometry, two-dimensional element distribution detection, RNA sequencing, we evaluated compared toxicity CsPbBr3 (a representative substance Pb-PNPs) Pb(AC)2 investigated toxicity-reducing SiO2 encapsulation. Our findings revealed that exposure resulted a concentration-dependent decrease area thickness neural retina hEROs. Additionally, hindered cell proliferation promoted apoptosis while suppressing ganglion differentiation, alteration further led disruption structure. By contrast, hEROs was slightly less toxic than Pb(AC)2. Mechanistically, activated endoplasmic reticulum stress, by up-regulating Caspase-3 inhibited down-regulating Pax6. Interestingly, after coating with silica, it exhibited lower toxicities alleviating stress. Overall, our study provides evidence Pb-PNPs-induced developmental retina, explores potential nanoparticles' toxicity, suggests feasible strategy reduce toxicity.

Язык: Английский

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Flotillin- 1 ameliorates experimental diabetic retinopathy by inhibiting ferroptosis in blood-retinal barrier

Journal of Molecular Medicine, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

Язык: Английский

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Retinal light damage: From mechanisms to protective strategies

Survey of Ophthalmology, Год журнала: 2024, Номер 69(6), С. 905 - 915

Опубликована: Июль 23, 2024

Highlights•Light damage is considered to be an important pathogenic factor leading retinal degenerative diseases.•The mechanisms of light include the disruption REDOX balance and Ca2+ homeostasis, pyroptosis, endoplasmic reticulum stress, cell autophagy inflammatory release.•The strategy protection promising.AbstractVisible serves as a crucial medium for vision formation.;however, prolonged or excessive exposure recognized significant etiological contributing diseases. The retina, with its unique structure adaptability, relies on homeostasis cellular functions maintain visual health. Under normal conditions, retina can mount adaptive responses various insults, including light-induced damage. Unfortunately, intense triggers cascade pathological alterations in photoreceptor cells, pigment epithelial ganglion glial cells. These encompass intracellular Ca²⁺ autophagy, release cytokines, culminating irreversible We first delineate through 4 main avenues: mitochondria function, inflammation. Subsequently, we discuss protective strategies against damage, aiming guide research toward prevention treatment conditions.

Язык: Английский

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Precise subcellular organelle-targeted analyses of the hepatotoxicity of rhubarb

Acupuncture and Herbal Medicine, Год журнала: 2024, Номер 4(2), С. 243 - 256

Опубликована: Апрель 25, 2024

Objective: Drug-induced liver injury (DILI) is the leading cause of acute failure and poses a significant challenge to human health. Rhubarb ( Rheum officinale Baill . DaHuang) has been clinically used for its heat-clearing diuresis-promoting effects. However, toxic effects on different organelles in require further validation. Methods: We analyzed potential targets affecting hepatotoxicity rhubarb damage relationship with five major organelles, including microsomes, mitochondria, endoplasmic reticulum (ER), Golgi apparatus (GA), lysosomes through Integrated Traditional Chinese Medicine (ITCM)/HERB databases network pharmacology. isolated purified incubated them fractions monomers an adenosine triphosphate (ATP) culture system examined structural functional changes using particle size analysis molecular biological experiments investigate whether affects rupture liver. Results: By combining virtual predictions experimental verification, our research confirmed that emodin from anthraquinone rhubarb, catechin tannins palmitic acid organic acids caused most representative organelles. Among all monomeric compounds, microsome, ER, lysosome; induced microsome GA damage; microsomes liver, suggesting components may exert multi-organelle injury. Conclusions: Our findings revealed varying degrees damaging which turn cellular life activities by impairing organelle morphology function. This study provides theoretical basis technical support refined rhubarb.

Язык: Английский

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Pigment epithelium-derived factor exerts neuroprotection in oxygen-induced retinopathy by targeting endoplasmic reticulum stress and oxidative stress

Experimental Eye Research, Год журнала: 2024, Номер 249, С. 110147 - 110147

Опубликована: Ноя. 5, 2024

Язык: Английский

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Blue Light Damages Retinal Ganglion Cells Via Endoplasmic Reticulum Stress and Autophagy in Chickens

Investigative Ophthalmology & Visual Science, Год журнала: 2025, Номер 66(1), С. 3 - 3

Опубликована: Янв. 2, 2025

Purpose: Because chickens have excellent light perception properties, this study focused on investigating whether monochromatic can cause photodamage in chicken retinal ganglion cells (RGCs). Methods: Post-hatching day were exposed to four different light-emitting diode environments for five weeks, respectively, blue (480 nm), green (560 red (660 or white (6000 K). The mechanisms through which influences the structure of retina analyzed by detecting morphological retina, gene and protein expression levels, ultrastructure optic nerve. Results: Blue exposure weeks significantly impacted thickness inner reticular layer, synaptic function, number RGCs retina. Moreover, neurodegenerative disease characteristics, such as a reduction dendritic branches presence myelin lesions, also been observed RGCs. activation kinase RNA-like ER kinase-mediated unfolded response, along with abnormal degradation autophagy substrate P62, accompanies these pathological processes. Additionally, our findings indicate that photosensitivity OPN4 is linked endoplasmic reticulum stress RGCs, may elucidate why experience damage exclusively under exposure. Conclusions: autophagy, especially Our enhances understanding underlying emphasizes risk low-illuminance environments.

Язык: Английский

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A One Stone Three Birds Paradigm of Photon‐Driven Pyroptosis Dye for Amplifying Tumor Immunotherapy

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Abstract Activating the pyroptosis pathway of tumor cells by photodynamic therapy (PDT) for immunogenic cell death (ICD) is considered a valid strategy in pursuit antitumor immunotherapy, but it remains huge challenge due to lack reliable design guidelines. Moreover, often overlooked that conventional PDT can exacerbate development immunosuppressive microenvironment, which apparently unfavorable clinical immunotherapy. The endoplasmic reticulum's (ER) pivotal role cellular homeostasis and its emerging link have galvanized interest ER‐centric imaging therapeutics. Herein, using targeted group‐assisted (TAGS), an intriguing cyclooxygenase‐2‐targeted conjugate, Indo‐Cy , strategically created, exploits enzyme's overabundance tumoral ER, especially under proinflammatory hypoxic conditions. This with highly precise ER imaging, embodies trifunctional strategy: i) innovating electron transfer mechanism, converting hemicyanine moiety into oxygen‐independent type I photosensitizer, thereby navigating around hypoxia constraints traditional PDT; ii) executing ER‐targeted PDT, amplifying caspase‐1/GSDMD‐mediated ICD; 3) attenuating pathways inhibiting cyclooxygenase‐2 downstream factors, including HIF‐1α, PGE2, VEGF. 's multimodal approach potently induces vivo bolsters immunity, underscoring dyes' potential as versatile oncotherapeutics.

Язык: Английский

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Neuronal CDK5RAP3 deficiency leads to encephalo-dysplasia via upregulation of N-glycosylases and glycogen deposition

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Апрель 6, 2025

Abstract CDK5RAP3 is a binding protein of CDK5 activating proteins and also one the key co-factors E3 enzyme in UFMylation system. Several reports have implicated involvement other components system neuronal development multiple psychiatric disorders. However, precise role neurons remains elusive. In this study, we generated neuron-specific knockout mice (CDK5RAP F/F : Nestin-Cre). conditional (CDK5RAP3 CKO) exhibited severe encephalo-dysplasia slower developmental trajectory compared to wild-type (WT) succumbed postnatal demise by day 14. Transcriptome sequencing unveiled that deficiency affects synapse formation, transmembrane trafficking physiological programs brain. Morphological analysis demonstrated leads increased SLC17A6 N-glycosylase (RPN1 ALG2) expression, while causing endoplasmic reticulum (ER) stress. vitro experiments utilizing ROSA26-ERT2Cre MEFs were conducted elucidate similar mechanism following deletion. Both vivo vitro, significantly expression N-glycosylases ALG2), as well total amount glycoproteins. may potentially maintain balance enhancing degradation RPN1 ALG2 through proteolytic pathways autophagy. This study underscores indispensable sheds new light on drug discovery endeavors targeting early brain abnormalities.

Язык: Английский

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Magnesium-assisted hydrogen improves isoproterenol-induced heart failure

Medical Gas Research, Год журнала: 2025, Номер 15(4), С. 459 - 470

Опубликована: Апрель 29, 2025

Heart failure (HF) is a leading cause of mortality among patients with cardiovascular disease and often associated myocardial apoptosis endoplasmic reticulum stress (ERS). While hydrogen has demonstrated potential in reducing oxidative ERS, recent evidence suggests that magnesium may aid release within the body, further enhancing these protective effects. This study aimed to investigate cardioprotective effects ERS through rat model isoproterenol (ISO)-induced HF. Magnesium was administered orally ISO-induced HF rats, which improved cardiac function, reduced fibrosis hypertrophy, lowered plasma levels creatine kinase-MB, troponin-I, N-terminal B-type natriuretic peptide precursor rats. It also inhibited cardiomyocyte by upregulating B-cell lymphoma-2, downregulating Bcl-2-associated X protein, suppressing markers (glucose-related protein 78, activating transcription factor 4, C/EBP-homologous protein). elevated blood, plasma, tissue, as well artificial gastric juice pure water, where lasted for at least four hours. Additionally, complementary vitro experiments were conducted using H9C2 injury models, hydrogen-rich culture medium intervention. Hydrogen-rich survival proliferation ISO-treated cells, cell surface area, apoptosis, downregulated pathway proteins. However, negated tunicamycin (an inducer ERS) cells. In conclusion, exerts significant cardioprotection mitigating

Язык: Английский

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Endoplasmic Reticulum Stress Drives Neuroinflammation Through Lipocalin 2 Upregulation in Retinal Microglia After Optic Nerve Injury

Investigative Ophthalmology & Visual Science, Год журнала: 2025, Номер 66(5), С. 12 - 12

Опубликована: Май 6, 2025

This study aims to explore how lipocalin 2 (LCN2) connects endoplasmic reticulum (ER) stress and inflammation in optic nerve injury (ONI) identify potential therapeutic strategies. An crush (ONC) mouse model was used investigate the role of ER LCN2 ONI. Immunofluorescence, quantitative PCR, Western blot analyses were performed assess markers, LCN2, inflammation-related genes, retinal ganglion cell (RGC) survival, with or without treatment 4PBA (an inhibitor) TUN activator) both ONC BV2 cells. Lcn2 knockdown achieved using small interfering RNA cells adeno-associated virus (AAV)-mediated gene silencing vivo underlying signaling pathways. markers (GRP78, ATF4, CHOP) expression increased retinas, accompanied by microglial activation RGC loss. Inhibition effectively decreased expression, attenuated activation, survival post-ONC. Intravitreal injection recombinant induced a proinflammatory phenotype microglia exacerbated neurotoxicity. AAV-mediated mitigated reduced neuroinflammation, provided neuroprotection, surpassing treatment. In vitro studies further confirmed that significantly inflammatory response inhibiting NLRP3 inflammasome via TLR4/NF-κB pathway. elucidates critical linking ONI, offering promising target. outperforms broad inhibition, providing novel strategy for treating injuries.

Язык: Английский

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