Cystathionine ß-Synthase Suppresses NLRP3 Inflammasome Activation via Redox Regulation in Microglia.

Aims: Cystathionine ß-synthase (CBS) is essential for homocysteine (Hcy) transsulfuration, yielding cysteine as a common precursor of hydrogen sulfide (H2S), glutathione (GSH), and other sulfur molecules, which produce neuroprotective effects in neurological conditions. We previously reported a disruption of microglial CBS/H2S signaling in a Parkinson's disease (PD) mouse model. Yet, it remains unclear whether CBS affects nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome activity and other pathologies in PD. Results: Microglial CBS expression decreased after lipopolysaccharide (LPS) stimulation. Elevated GSSG (the oxidized GSH) content and decreased H2S generation were found in the brains of microglial cbs conditional-knockout (cbscKO) mice, whereas serum and brain Hcy levels remained unaltered. Moreover, microglial cbscKO mice were susceptible to NLRP3 inflammasome activation and dopaminergic neuron losses caused by LPS injection into the substantia nigra, whereas cbs overexpression or activation produced opposite effects. In vitro studies showed that cbs overexpression or activation suppressed microglial NLRP3 inflammasome activation and interleukin (IL)-1ß secretion by reducing mitochondrial reactive oxygen species (mitoROS) level. Conversely, ablation of cbs enhanced NLRP3 expression and mitoROS generation and augmented microglial NLRP3 inflammasome activity in response to adenosine triphosphate challenge, which was blocked by the mitoROS scavenger. Innovation and Conclusion: The study demonstrated an elevated GSSG level and reduced H2S generation, which correlated with a susceptible status of microglia in the brain of cbscKO mice. Our findings reveal a critical role of CBS in restraining the microglial NLRP3 inflammasome by controlling redox homeostasis and highlight that activation or upregulation of CBS may become a potential strategy for PD treatment.

Effects on the Ocular Surface from Reading on Different Smartphone Screens: A Prospective Randomized Controlled Study.

The purpose of this study was to investigate the influence of smartphone reading on the ocular surface and to compare the various effects of different screens and light conditions on the ocular surface. One hundred nineteen volunteers were randomly divided into: light + organic light-emitting diode (OLED), light + electronic ink (eINK), dark + OLED, and dark + eINK. Ocular surface examinations, including noninvasive break-up time (NIBUT), noninvasive keratograph tear meniscus height (NIKTMH), ocular redness, fluorescein break-up time (FBUT), corneal fluorescein staining, meibomian gland assessment, Schirmer I Test, and blinking frequency, were performed before and after a reading task. Symptoms were evaluated using the Ocular Surface Disease Index (OSDI) and Computer Vision Syndrome Questionnaire (CVS-Q). NIBUT and FBUT were decreased statistically significantly after participants read on an OLED screen for 2 hours compared with the baseline in light and dark environments, whereas no statistically significant decrease was observed on an eINK screen. NIKTMH was statistically significantly decreased after reading on an OLED screen in light and dark settings, and the eINK screen had a lesser effect on NIKTMH. An obvious increase in the ocular redness, OSDI and CVS-Q scores was observed after reading on an OLED screen, whereas the eINK screen had a lesser effect on these indicators. Blink rate increased gradually in OLED subgroups during the reading task, whereas no statistically significant difference was observed in the eINK subgroups. Our research suggested that reading on an OLED screen can cause ocular surface disorder and obvious subjective discomfort, whereas reading on an eINK screen can minimize ocular surface disorder in both dark and light environments.

Acetylsalicylic Acid Promotes Corneal Epithelium Migration by Regulating Neutrophil Extracellular Traps in Alkali Burn.

Neutrophils are the first cells to migrate into the cornea in response to alkali burns, and excessive neutrophil infiltration is associated with inflammatory injury and a poorer prognosis. In an effort to understand the mechanisms underlying the inflammation mediated by neutrophils after alkali burns, we examined the role of alkali-activated neutrophils on human corneal epithelial cells (HCEs) proliferation and migration, as well as the effects of acetylsalicylic acid (ASA) and dexamethasone (DXM) on NETosis. We stimulated human neutrophils with sodium hydroxide (NaOH) and observed dose- and time-dependent neutrophil extracellular traps (NETs) formation. We also observed that ASA, but not DXM, significantly inhibited NaOH-induced NETosis. Furthermore, the activation of nuclear factor (NF)-κB, but not the production of reactive oxygen species, was involved in ASA-regulated NETosis. Moreover, NETs were found to be involved in alkali-activated neutrophils (ANs) induced neutrophil-HCE adhesion. ANs enhanced HCEs proliferation via phagocytosis. Meanwhile, ANs inhibited HCEs migration through the release of NETs, which was partially rescued by 5 mM ASA. In conclusion, ANs may interfere with HCEs proliferation and migration by phagocytosis and NETs formation, respectively. ASA may enhance HCEs migration by decreasing NETs formation through inhibition of NF-κB activation and could be a promising strategy for improving the prognosis of corneal alkali burns.

Clinical efficacy comparison of low-temperature plasma radiofrequency ablation and Nd:YAG laser in treating recurrent acquired nasolacrimal duct obstruction.

To evaluate the effectiveness and safety of low-temperature plasma radiofrequency ablation (coblation) and Nd:YAG laser in treating recurrent nasolacrimal duct obstruction. A prospective study was performed on patients who agreed to be treated with coblation or Nd:YAG laser for recurrent nasolacrimal duct obstruction after failed lacrimal Nd:YAG laser combined with silicone intubation. The visual analogue scale (VAS) pain grade was assessed at baseline, immediately, and 3 and 7 days after surgery. The degree of watering, lacrimal passage irrigation, and complications were also evaluated 1 week and 1, 3, and 6 months after surgery. Ninety-five patients who met the criteria for recurrent nasolacrimal duct obstruction from February 2018 to February 2019 were included in this study, with 46 patients receiving coblation and 49 patients Nd:YAG laser. The intraoperative and postoperative (3 days after surgery) VAS pain grades of the patients who received coblation were significantly lower than those who received Nd:YAG laser (P < 0.001). The number of patients in the coblation group who achieved complete clinical relief (no epiphora symptoms with fluent lacrimal passage irrigation) was significantly larger than that in the lacrimal Nd:YAG laser group at 1, 3, and 6 months after surgery (P = 0.033, P = 0.006, P = 0.003, respectively). During the follow-up period, there were no unexpected complications in either group. Compared with Nd:YAG laser, coblation performed well in alleviating pain and maintaining sustained disease relief and may therefore be an alternative to conventional laser or dacryocystorhinostomy surgery in the management of recurrent nasolacrimal duct obstruction.