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.

p38 MAPK inhibitor SB202190 suppresses ferroptosis in the glutamate-induced retinal excitotoxicity glaucoma model.

JOURNAL/nrgr/04.03/01300535-202410000-00031/figure1/v/2024-02-06T055622Z/r/image-tiff Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogen-activated protein kinase (MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.

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.

Role of epigenetic regulation in glaucoma.

Glaucoma is the world's leading irreversible blinding eye disease. Lowering intraocular pressure is currently the only effective clinical treatment. However, there is a lack of long-acting IOP-lowering drugs, and some patients still experience retinal ganglion cell loss even with good intraocular pressure control. Currently, there is no effective method for neuroprotection and regeneration in clinical practice for glaucoma. In recent years, epigenetics has been widely researched and reported for its role in glaucoma's neuroprotection and regeneration. This article reviews the changes in histone modifications, DNA methylation, non-coding RNA, and m6A methylation in glaucoma, aiming to provide new perspectives for glaucoma management, protection of retinal ganglion cells, and axon regeneration by understanding epigenetic alterations.

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.

Analysis of Methods to Reduce Jogging Injuries from the Perspective of Risk Cognition.

Objectives: Injuries are common events that impair the function of joggers; it is important to take effective measures to reduce the incidence of jogging injuries to maximize its benefits. Methods: We collected questionnaires from 3468 Chinese exercisers using a stratified random sampling method. We analyzed these data using AMOS 22.0 (IBM) and SPSS 26.0 (IBM). Results: We constructed a relationship model of jogging risk cognition, jogging risk behaviors, and jogging injury incidence, and the indicators fit well. The path coefficient between jogging risk cognition and jogging risk behaviors of joggers was -0.64; the path coefficient between jogging risk behaviors and jogging injuries incidence was 0.44; and the path coefficient between jogging risk cognition and jogging injuries incidence was -0.23. Conclusions: The higher the level of jogging risk cognition of joggers, the lower their jogging risk behaviors, leading to a lower incidence of jogging injuries. Based on the generally low level of jogging risk cognition of joggers, the construction of a jogging risk cognitive education system that can be integrated into universities, middle schools and primary schools, as well as family, school and society, is conducive to comprehensively improve the level of jogging risk cognition of joggers.

Anti-scarring effect of sodium hyaluronate at filtration pathway after filtering surgery in rabbits.

AIM: To investigate the anti-scarring effect of sodium hyaluronate (HA) at filtration pathway after filtering surgery in a rabbit model. METHODS: Fifteen healthy adult New Zealand white rabbits were selected for trabeculectomy in both eyes. The right eyes were used as HA group with 0.1 mL HA injected into the anterior chamber at the end of the operation; the left eyes were used with 0.1 mL sodium lactate Ringer's solution (RS) injected into the anterior chamber as RS group. Intraocular pressure (IOP), filtering blebs morphology, inflammatory reaction and complications were observed at the 7, 60, and 90d after surgery. RESULTS: One day after surgery, the IOP of HA and RS groups were 12.75±1.92 and 10.50±1.59 mm Hg (P=0.005). At the 7th day postoperative, the filtering blebs of each group were functional type and TGF-ß expression was significantly difference in both groups (0.10±0.01 vs 0.14±0.02, P=0.024). After 60d of the operation, all filtering blebs were scarring and alpha-smooth muscle actin (α-SMA) expression was significantly difference in both groups (0.40±0.04 vs 0.35±0.02, P=0.032). α-SMA positive cells were mainly distributed in the junction of conjunctiva and sclera and around the blood vessels. The collagen volume fraction (CVF) of HA and RS group was (75.49±7.01)% and (79.93±5.35)% (P=0.044). On the 90th day after the operation, CVF was (82.57±5.19)% and (88.08±1.75)% in HA and RS groups (P=0.036). There was no α-SMA positive cell in HA group, while a few positive cells were observed in RS group (P=0.000). CONCLUSION: HA has effect of anti-scar and anti-inflammation on filtration pathway after filtering surgery within 3mo by inhibiting fibroblast proliferation and collagen deposition.

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.

Depicting Developing Trend and Core Knowledge of Primary Open-Angle Glaucoma: A Bibliometric and Visualized Analysis.

Objective: The prevalence of glaucoma is rising due to an increasing aging population. Because of its insidious and irreversible nature, glaucoma has gradually become the focus of attention. We assessed primary open angle glaucoma, the most common type of glaucoma, to study its present status, global trend, and state of clinical research. Methods: Publications from 2000 to 2021 in Web of Science database were retrieved and analyzed by bibliometrics. VOSviewer and Citespace were used for analysis. Results: A total of 6,401 publications were included in this review, and we found that the number of publications increased from 139 in 2000 to 563 in 2021. American researchers have published the most papers and had the highest h-index and the most citations, while the Journal of Glaucoma has published the most papers on this topic. Some key researchers, contributing institutions, their partnerships, and scientific masterpieces were identified. The publications we reviewed fall into seven categories: publications on intraocular pressure, normal tension glaucoma, risk factors, the trabecular meshwork, optical coherence tomography, surgery, and mutation. Clear study hotspots were described, which began with epidemiology and transitioned to pathogenesis and diagnosis and then to treatment. Conclusion: Studies on primary open angle glaucoma extend well beyond ophthalmology to biochemistry molecular biology, general internal medicine, pharmacology, pharmacy, science technology, and other areas. Interest, research and publications on primary open angle glaucoma are on the rise.

Particle number emissions from fully warmed gasoline vehicles at various ambient temperatures.

Road vehicles have become the primary source of fine particles in many large cities. Vehicle hot-start PN emissions at various ambient temperatures were studied previously. Still, these studies used the same rolling resistance setting at different ambient temperatures and the tests at various ambient temperatures have similar PN emissions. Vehicles get larger resistance at cold ambient temperatures, so this experimental setting (same resistance at various ambient temperatures) is beyond the natural conditions. To evaluate how ambient temperatures affect the PN emissions from fully warmed vehicles, two vehicles were tested at four ambient temperatures: -10 °C, 0 °C, 23 °C, and 40 °C. Vehicle resistance variations under different ambient temperatures were taken into consideration. The observed results proved that PN emission would significantly deteriorate under cold conditions even when the vehicles are thoroughly warmed. The PN emission factor at -10 °C could be six times higher than at 23 °C. The deteriorated PN emission is caused by enhanced fuel enrichment and GPF regeneration, and larger vehicle resistance under cold ambient temperatures is the underlying reason for the increased PN emission. For the first time, this study proved that PN emission from fully warmed vehicles would significantly deteriorate when the ambient temperature decreases. The results could be used for emission models, inventory, and regulations.

Jogging-related Risk Cognition and the Stimulation of Risky Behavior during Jogging.

Objectives: With the rapid increase in the number of Chinese joggers, the number of people incurring injuries from jogging also has increased. Evaluating the relationship between jogging-related risk cognition and risky behaviors while jogging will help improve jogging-related risk cognition among joggers. Methods: We collected questionnaires about jogging-related risky behaviors and risk cognition from 3468 Chinese exercisers using a stratified random sampling method. We analyzed these data with correlation and multi-linear regression analyses. Results: The regression coefficients between risk cognition related to jogging-related technical procedures and risky behavior, between risk cognition related to personal physical and mental conditions and risky behavior, between risk cognition related to jogging-related equipment factors and risky behavior, between risk cognition related to jogging-related environmental factors and risky behavior, and between risk cognition related to personal jogging competition-related factors and risky behavior were all negative and statistically significant (p < .05). Conclusions: The level of risk cognition related to jogging is negatively correlated with actual risky behavior during jogging, which indicates that the higher the level of jogging-related risk cognition, the fewer jogging-related risky behaviors occur.