Continuous voriconazole lavage in managing moderate and severe fungal keratitis: a randomized controlled trial.

PURPOSE: To assess the effectiveness and safety of continuous lavage with 1% voriconazole (CL) for moderate and severe fungal keratitis. METHODS: Thirty-one patients were randomized to receive topical eye drops either alone (T) or combined with continuous 1% voriconazole lavage (CL-T). The primary outcome was the cure rate at 3 months. The secondary outcomes were the 6-day efficacy, 3-day infiltration size and depth, hypopyon height, central corneal thickness (CCT), epithelial defect size, and subject feelings and clinical signs assessment scores. RESULTS: At 3 months, the cure rate was comparable between the groups in patients with moderate fungal keratitis (66.7% vs. 62.5%, P = 0.60). However, among severe cases, 4 cases (44.4%) in the CL-T group healed successfully, while none in the T group; this difference was not significant (P = 0.08), although it was very close to 0.05. This may be related to the small sample size. After 6 days, the percentage of patients with "worsened" ulcers in the CL-T group was lower than that in the T group (0% vs. 31%, P = 0.043). The infiltration size, infiltration depth, and hypopyon height in the CL-T group were smaller than those in the T group after 3 days (all P < 0.05). There was no difference in CCT, epithelial defect size, subject feelings scores, or clinical signs scores between groups. CONCLUSION: These outcomes suggest that CL is an effective and safe adjuvant method for controlling the progression of moderate and severe fungal keratitis. TRIAL REGISTRATION NUMBER: ChiCTR2100050565.

PTB: Not just a polypyrimidine tract-binding protein.

Polypyrimidine tract-binding protein (PTB), as a member of the heterogeneous nuclear ribonucleoprotein family, functions by rapidly shuttling between the nucleus and the cytoplasm. PTB is involved in the alternative splicing of pre-messenger RNA (mRNA) and almost all steps of mRNA metabolism. PTB regulation is organ-specific; brain- or muscle-specific microRNAs and long noncoding RNAs partially contribute to regulating PTB, thereby modulating many physiological and pathological processes, such as embryonic development, cell development, spermatogenesis, and neuron growth and differentiation. Previous studies have shown that PTB knockout can inhibit tumorigenesis and development. The knockout of PTB in glial cells can be reprogrammed into functional neurons, which shows great promise in the field of nerve regeneration but is controversial.

Icaritin and icariin reduce p-Tau levels in a cell model of Alzheimer's disease by downregulating glycogen synthase kinase 3ß.

This study aimed to explore the neuroprotective effect of icariin/icaritin (ICA/ICT) and the role of ICA/ICT in the treatment of Alzheimer's disease (AD). ICA and ICT were used to treat okadaic acid (OA)-induced Tau hyperphosphorylation in SH-SY5Y cells. We detected the relative changes in Tau, p-Tau, protein phosphatase 2A (PP2A), and glycogen synthase kinase 3ß (GSK-3ß) by Western blotting and enzyme-linked immunosorbent assay. At 40 nmol/L OA, the cell viability of the SH-SY5Y cells was significantly changed. We used different concentrations of ICA and IC to treat AD model cells and found that the effect of 2.5 µmol/L ICA and 1 µmol/L ICT was best after 48 H of treatment. After SH-SY5Y cell induction, the p-Tau levels were increased (P < 0.05); after the ICA/ICT treatment, the p-Tau and GSK-3ß levels were decreased (P < 0.05), although PP2A expression did not change (P > 0.05). We found that ICA and ICT exert an effect on AD model cells by decreasing the levels of GSK-3ß and p-Tau. The therapeutic effect of ICT is slightly better than that of ICA. Although these drugs were effective in the cell model, more studies are required to determine whether they are promising for the treatment and prevention of AD.

In Vivo Confocal Microscopy Findings of a Rare Cryptococcus neoformans Keratitis.

PURPOSE: To report a rare case of fungal keratitis caused by Cryptococcus neoformans, highlighting its unique morphological features using in vivo confocal microscopy (IVCM). METHODS: This was a retrospective case report. A 66-year-old man presented with foreign body sensation and blurred vision in his left eye for over 10 months. RESULTS: His best-corrected visual acuity was 20/20. Slit-lamp examination revealed a gray-white lesion approximately 4-5 mm in the superficial layer of the central cornea without epithelial defects. The IVCM images revealed numerous round or round-like pathogens, each with a central highly reflective body surrounded by a dark ring, ranging in size from 5 to 30 µm, and to a maximum of 85 µm, observed in the corneal epithelium and superficial stroma. No obvious inflammatory cell infiltration was observed in the lesions or endothelium. C. neoformans infection was confirmed. The round pathogens completely disappeared after 8 weeks of treatment with topical amphotericin B and voriconazole eye drops. CONCLUSION: Fungal keratitis caused by C. neoformans is rare and easily overlooked due to atypical clinical signs and symptoms. This case reports the unique morphological features of C. neoformans in the cornea using IVCM for the first time, facilitating rapid, noninvasive auxiliary diagnosis of C. neoformans keratitis and treatment follow-up.

Ripa-56 protects retinal ganglion cells in glutamate-induced retinal excitotoxic model of glaucoma.

Glaucoma is a prevalent cause of blindness globally, characterized by the progressive degeneration of retinal ganglion cells (RGCs). Among various factors, glutamate excitotoxicity stands out as a significant contributor of RGCs loss in glaucoma. Our study focused on Ripa-56 and its protective effect against NMDA-induced retinal damage in mice, aiming to delve into the potential underlying mechanism. The R28 cells were categorized into four groups: glutamate (Glu), Glu + Ripa-56, Ripa-56 and Control group. After 24 h of treatment, cell death was assessed by PI / Hoechst staining. Mitochondrial membrane potential changes, apoptosis and reactive oxygen species (ROS) production were analyzed using flow cytometry. The alterations in the expression of RIP-1, p-MLKL, Bcl-2, BAX, Caspase-3, Gpx4 and SLC7A11 were examined using western blot analysis. C57BL/6j mice were randomly divided into NMDA, NMDA + Ripa-56, Ripa-56 and control groups. Histological changes in the retina were evaluated using hematoxylin and eosin (H&E) staining. RGCs survival and the protein expression changes of RIP-1, Caspase-3, Bcl-2, Gpx4 and SLC7A11 were observed using immunofluorescence. Ripa-56 exhibited a significant reduction in the levels of RIP-1, p-MLKL, Caspase-3, and BAX induced by glutamate, while promoting the expression of Bcl-2, Gpx-4, and SLC7A1 in the Ripa-56-treated group. In our study, using an NMDA-induced normal tension glaucoma mice model, we employed immunofluorescence and H&E staining to observe that Ripa-56 treatment effectively ameliorated retinal ganglion cell loss, mitigating the decrease in retinal ganglion cell layer and bipolar cell layer thickness caused by NMDA. In this study, we have observed that Ripa-56 possesses remarkable anti- necroptotic, anti-apoptotic and anti-ferroptosis properties. It demonstrates the ability to combat not only glutamate-induced excitotoxicity in R28 cells, but also NMDA-induced retinal excitotoxicity in mice. Therefore, Ripa-56 could be used as a potential retinal protective agent.

Comparison of clinical outcomes between cystotome-assisted prechop phacoemulsification surgery and femtosecond laser-assisted cataract surgery for hard nucleus cataracts.

BACKGROUND/OBJECTIVES: To compare the safety and efficacy of cystotome-assisted prechop phacoemulsification surgery (CAPPS) and femtosecond laser-assisted cataract surgery (FLACS) in patients with hard nucleus cataract. SUBJECTS/METHODS: Ninety-six eyes of 64 patients with grade IV hard nucleus cataract were assigned to 1 of the 2 groups (49 CAPPS and 47 FLACS). Follow-up visits were performed at 1 day, 1 week, 1 month, 3 months, 6 months, and 1 year, and the outcome measures comprised ultrasound power, effective phacoemulsification time (EPT), corrected distance visual acuity (CDVA), endothelial cell density (ECD), corneal endothelium cell loss rate (ECL), central corneal thickness (CCT), and intraoperative and postoperative complications. RESULTS: The ultrasound power and EPT were lower in the CAPPS group (p = 0.03 and <0.0001, respectively). Patients in both groups gained better CDVA postoperatively. The ECD value decreased at each follow-up visit and did not return to the preoperative level; FLACS resulted in greater endothelial cell loss compared to CAPPS. CCT increased immediately after the surgery and decreased thereafter. The mean CCT value returned to the preoperative level 3 months postoperatively in the CAPPS group, while in the FLACS group, CCT value took 6 months to return to the preoperative level. Miosis was more likely to occur in the FLACS group. CONCLUSIONS: Due to its efficacy and cost-effectiveness, CAPPS is worth promoting and applying to clinical work in the future.

Autophagy and senescence of rat retinal precursor cells under high glucose.

Backgrounds: Diabetic retinopathy (DR) is a common diabetic ocular disease characterized by retinal ganglion cell (RGC) changes. An abnormal environment, hyperglycemia, may progressively alter the structure and function of RGCs, which is a primary pathological feature of retinal neurodegeneration in DR. Accumulated studies confirmed autophagy and senescence play a vital role in DR; however, the underlying mechanisms need to be clarified. Methods: This study included the microarray expression profiling dataset GSE60436 from Gene Expression Omnibus (GEO) to conduct the bioinformatics analysis. The R software was used to identify autophagy-related genes (ARGs) that were differentially expressed in fibrovascular membranes (FVMs) and normal retinas. Co-expression and tissue-specific expression were elicited for the filtered genes. The genes were then analyzed by ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Set Enrichment Analysis (GSEA). R28 cells were cultured with high glucose, detected by reverse transcription-quantitative (RT-qPCR) and stained by apoptosis kit. Results: In the retina, 31 differentially expressed ARGs (24 up-regulated genes) were discovered and enriched. The enrichment results revealed that differentially expressed ARGs were significantly enriched in autophagy, apoptosis, aging, and neural function. Four hub genes (i.e., TP53, CASP1, CCL2, and CASP1) were significantly up-regulated. Upregulation of cellular autophagy and apoptosis level was detected in the hyperglycemia model in vitro. Conclusions: Our results provide evidence for the autophagy and cellular senescence mechanisms involved in retinal hyperglycemia injury, and the protective function of autophagy is limited. Further study may favour understanding the disease progression and neuroprotection of DR.

Protective activity of tert-butylhydroquinone against oxidative stress and apoptosis induced by glutamate agonizts in R28 cells and mice retina.

Glutamate excitotoxicity can cause cell damage and apoptosis and play an important role in a variety of retinal diseases. Tertiary-butylhydroquinone (tBHQ) is an approved food-grade phenolic antioxidant with antioxidant activity in a variety of cells and tissues. We observed the protective effect of tBHQ on glutamatergic agonist-induced retina and explored its possible mechanism of action through in vitro cell experiments. The results showed that tBHQ had protective effects on NMDA-induced mouse retinal excitotoxicity and glutamate-induced excitotoxicity in rat retinal precursor cells (R28 cells). tBHQ reversed glutamate-induced apoptosis, production of intracellular reactive oxygen species, and reduction of mitochondrial membrane potential. Western blot analysis showed that tBHQ could increase the expression of procaspase-3, Bcl-2, AIF precursor, CAT, SOD2, Nrf2, NQO1, HO-1 and NF-κB in glutamate-treated cells, and decrease the expression of AIF cleavage products. Furthermore, we discovered that tBHQ activated müller glial cells. Based on these results, tBHQ may have antioxidant and anti-apoptotic properties, thus serving as a potential retinal protective agent. Its anti-oxidative stress effect was attributed to up-regulation of Nrf2, and its anti-apoptotic effect was related to its up-regulation of Bcl-2 expression and inhibition of mitochondria-dependent apoptosis.

Chronic Stress Promotes Cancer Development.

Stress is an inevitable part of life. Chronic stress on account of reasons like adversity, depression, anxiety, or loneliness/social isolation can endanger human health. Recent studies have shown that chronic stress can induce tumorigenesis and promote cancer development. This review describes the latest progress of research on the molecular mechanisms by which chronic stress promotes cancer development. Primarily, chronic stress activates the classic neuroendocrine system [the hypothalamic-pituitary-adrenal (HPA) axis] and the sympathetic nervous system (SNS) and leads to a decline and dysfunction of the prefrontal cortex and the hippocampus under stress. Stress hormones produced during the activation of both the HPA axis and the SNS can promote tumorigenesis and cancer development through a variety of mechanisms. Chronic stress can also cause corresponding changes in the body's immune function and inflammatory response, which is significant because a long-term inflammatory response and the decline of the body's immune surveillance capabilities are implicated in tumorigenesis. Stress management is essential for both healthy people and cancer patients. Whether drugs that limit the signaling pathways downstream of the HPA axis or the SNS can suppress chronic stress-induced cancers or prolong patient survival deserves further study.