Psoriasis is a severe disease associated with the disturbance of metabolism and inflammation, but the molecular mechanisms underlying these aspects of psoriasis pathology are poorly understood. Here, we report that glutaminase 1–mediated (GLS1-mediated) glutaminolysis was aberrantly activated in patients with psoriasis and in psoriasis-like mouse models, which promoted Th17 and γδ T17 (IL-17A–producing γδ T) cell differentiation through enhancement of histone H3 acetylation of the Il17a promoter, thereby contributing to the immune imbalance and development of psoriasis. We further demonstrate that mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) protease was constitutively active in psoriatic CD4⁺ and γδ T cells, thereby supporting GLS1 expression by stabilizing c-Jun, which directly binds to the GLS1 promoter region. Blocking the activity of either GLS1 or MALT1 protease resolved Th17 and γδ T17 cell differentiation and epidermal hyperplasia in the psoriasis-like mouse models. Finally, IL-17A enhanced GLS1 expression via the MALT1/cJun pathway in keratinocytes, resulting in hyperproliferation of and chemokine production by keratinocytes. Our findings identify the role of the MALT1/cJun/GLS1/glutaminolysis/H3 acetylation/T17 axis in psoriasis pathogenesis and reveal potential therapeutic targets for this disease.

We aimed to investigate the protective effect of Lycium barbarum polysaccharides (LBPs) against oxidative stress–induced apoptosis and senescence in human lens epithelial cells. To study apoptosis, SRA01/04 cells, a human lens epithelial cell lines, were exposed to 200 µM hydrogen peroxide (H₂O₂) for 24 h with or without pretreatment with LBPs. Cell viability was measured using a Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis, intracellular reactive oxygen species (ROS), and the loss of mitochondria membrane potential (Δψm) were detected by flow cytometric analyses. Expression levels of Bcl-2 and Bax proteins were measured by western blot analysis. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were quantized using commercial enzymatic kits according to the manufacturer's instructions. To study senescence, SRA01/04 cells were pre-incubated with LBPs and all cells were then exposed to 100 µM H₂O₂ for 96 h. Cellular senescence was assessed by morphologic examination and senescence-associated β-galactosidase (SA-β-gal) staining. LBPs significantly reduced H₂O₂-induced cell apoptosis, the generation of ROS, the loss of Δψm, and the levels of MDA. LBPs also inhibited H₂O₂-induced downregulated Bcl-2 and upregulated Bax proteins and increased the levels of SOD and GSH enzyme activity. Moreover, LBPs significantly attenuated H₂O₂-induced cellular senescence. These findings suggested that LBPs protect human lens epithelial cells from H₂O₂-induced apoptosis by modulating the generation of ROS, loss of Δψm, Bcl-2 family, and antioxidant enzyme activity and attenuating cellular senescence.

The accumulation of excessive reactive oxygen species can exacerbate any injury of retinal tissue because free radicals can trigger lipid peroxidation, protein damage and DNA fragmentation. Increased oxidative stress is associated with the common pathological process of many eye diseases, such as glaucoma, diabetic retinopathy and ischemic optic neuropathy. Many studies have demonstrated that Lycium barbarum polysaccharides (LBP) protects against oxidative injury in numerous cells and tissues. For the model of hypoxia we used cultured retinal ganglion cells and induced hypoxia by incubating with 200 µM cobalt chloride (CoCl ₂ ) for 24 hours. To investigate the protective effect of LBP and its mechanism of action against oxidative stress injury, the retinal tissue was pretreated with 0.5 mg/mL LBP for 24 hours. The results of flow cytometric analysis showed LBP could effectively reduce the CoCl ₂ -induced retinal ganglion cell apoptosis, inhibited the generation of reactive oxygen species and the reduction of mitochondrial membrane potential. These findings suggested that LBP could protect retinal ganglion cells from CoCl ₂ -induced apoptosis by reducing mitochondrial membrane potential and reactive oxygen species.

Retinal neovascularization (RNV) is a common pathological feature in many kinds of fundus oculi diseases. Sometimes RNV can even lead to severe vision loss. Oxidative injury is one of the main predisposing factors for RNV occurrence and development. The specific mechanism may be closely related to the special structural tissues of the retina. Retinal astrocytes (RACs) are mesenchymal cells located in the retinal neuroepithelial layer. RACs have an intimate anatomical relationship with microvascular endothelial cells. They have a variety of functions, but little is known about the mechanisms by which RACs regulate the function of endothelial cells. The molecules secreted by RACs, such as exosomes, have recently received a lot of attention and may provide potential clues to address the RAC‐mediated modulation of endothelial cells. In this study, we aimed to preliminarily explore the mechanisms of how RAC exosomes generated under oxidative stress are involved in the regulation of endothelial function. Our results showed that the apoptosis and autophagy levels in RACs were positively correlated with the oxidative stress level, and the exosomes generated from RACs under normal and oxidative stress conditions had different effects on the proliferation and migration of endothelial cells. However, the effect of RACs on endothelial cell function could be markedly reversed by the autophagy inhibitor 3‐methyladenine or the exosome inhibitor GW4869. Therefore, oxidative stress can lead to increased autophagy in RACs and can further promote RACs to regulate endothelial cell function by releasing exosomes.

Purpose: Fusarium Solani is the principal pathogen associated with fungal keratitis. As a sensitive drug to F. Solani, natamycin (NAT) was limited by the poor penetration and low bioavailability in clinical application. The aim of this study was to develop a new type of tri-block polymer nanoparticle-gel complex ([email protected]@NAT) for delivering NAT and evaluate its physicochemical properties, antifungal activity, safety, penetrability, adhesion, and efficacy in treating fungal keratitis. Methods: [email protected] was prepared and characterized with a nano-particle size analyzer, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). The minimum inhibitory concentration (MIC), cytotoxicity, penetrability of NAT (Natacyn^® 5% ophthalmic suspension; Alcon) and [email protected] with different concentrations were assessed. The eye surface retention time, ocular irritation, and curative effect of the NAT ophthalmic suspension and [email protected]@NAT on a rabbit fungal keratitis model were evaluated. Results: [email protected] had a particle size of 150 nm, a positive surface charge, and a sustained-release effect. The MIC for F. Solani was 2 μg/mL. A cytotoxicity test and ocular irritation test showed that [email protected] and [email protected]@NAT had good biocompatibility and no obvious irritation for rabbit corneas. Penetration experiments confirmed that [email protected] can successfully enter corneal epithelial cells and through the cornea to enter the anterior chamber. Compared with NAT ophthalmic suspension, [email protected]@NAT had stronger cornea permeation at the same concentration. The therapeutic effect and precorneal retention ability of the NAT ophthalmic suspension and [email protected]@NAT on the fungal keratitis rabbit model were compared. [email protected]@NAT achieved a better therapeutic effect at a lower drug concentration, and its eye surface retention time was significantly longer than that of the NAT ophthalmic suspension. Conclusion: [email protected]@NAT was shown to be a safe and effective nanodrug delivery system for NAT. It has great potential to improve the cure rate of fungal keratitis, reduce the administration frequency during the treatment process, and improve patient compliance. Graphical Abstract:

To report a case of a carotid-cavernous fistula (CCF) that occurred after a motor vehicle accident and review the uniqueness of this case and the main confusing points for the diagnosis of such cases. A 22-year-old man complained of left eyelid swelling, eye redness, visual decrease and occasional headache after motor vehicle accident 4 months prior during which he experienced a head injury. He was initially thought to have glaucoma, but he was finally diagnosed with a right CCF based on magnetic resonance imaging (MRI) and digital subtraction angiography (DSA). Timely embolization surgery resulted in obvious relief of the ocular symptoms and an improved prognosis. This is the first reported case of a post-traumatic unilateral CCF with contralateral symptoms in direct CCF, it is very infrequent and deserves our attention. We should maintain high suspicion of CCF and confirm the diagnosis by DSA when managing such patients to prevent serious consequences. Early diagnosis and treatment can improve the prognosis of patients.