Taken together, this highlights pilocarpine through the activation of muscarinic receptors appear to afford significant protection against retinal neurons damage and optic nerve degeneration at clinically relevant concentrations. These data also further support muscarinic receptors as potential therapeutic neuroprotective targets in glaucoma.

The present study aimed to evaluate the effect of fluoride (F) on spermatogenesis in male rats. F at 50 and 100 mg/L was administered for 70 days, after which the testicular and epididymis tissues were collected to observe the histopathological structure under a light microscope. The ultrastructure of the testis and sperm was also examined via transmission electron microscopy. The apoptosis of spermatogenic cells was measured through terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of proliferation factors, namely, proliferating cell nuclear antigen (PCNA) and Ki-67, in the testicular and epididymis tissues, were assayed through immunohistochemistry. F at 50 and 100 mg/L significantly damaged the structure of the testis and epididymis, and the testis and sperm ultrastructure exhibited various changes, including mitochondrial swelling and vacuolization, and apsilated and raised sperm membrane. F treatment significantly increased spermatogenic cell apoptosis in the testis. PCNA (P < 0.01) and Ki-67 (P < 0.01) also presented positive expression in the testis. By comparison, no significant changes occurred in the epididymis. In summary, excessive F intake results in spermatogenesis dysfunction by damaging the testicular structure and inducing spermatogenic cell apoptosis in male rats. The positive expression level of PCNA and Ki-67 was a good response to spermatogenesis dysfunction.

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Hypoxia-induced retinal ganglion cell (RGC) death has been proposed to be the critical event in the pathophysiology of glaucoma. Therefore, delaying or halting RGC degeneration, known as neuroprotection, is a novel and promising approach with potential clinical applications for treating glaucoma. In this study, we investigate hypoxia-induced cell death of RGCs and the underlying mechanisms of N-acetylcysteine (NAC) as a neuroprotectant. To establish a model for chemical hypoxia-induced cell death, RGC-5 cells were treated with the hypoxia mimetic cobalt chloride (CoCl2). Following CoCl2 exposure, significant levels of apoptotic and autophagic cell death were observed in RGC-5 cells, evidenced by lysosome dysfunction and autophagosome formation. Pretreating RGC-5 cells with NAC significantly counteracted the autophagic cell death. NAC-mediated neuroprotection was attributed to the direct scavenging of reactive oxygen species and was mediated by targeting the hypoxia-inducible factor-1α pathway via the BNIP3 and PI3K/Akt/mTOR pathways. These results provide insights into the degeneration of RGCs and present a potential clinical application for NAC as a neuroprotectant.

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Histone deacetylase (HDAC) 2 plays a vital role in modifying histones to mediate inflammatory responses, while HDAC2 itself is commonly regulated by post-translational modifications. Small ubiquitin-related modifier (SUMO), as an important PTM factor, is involved in the regulation of multiple protein functions. Our previous studies have shown that carbocisteine (S-CMC) reversed cigarette smoke extract (CSE)-induced down-regulation of HDAC2 expression/activity in a thiol/GSH-dependent manner and enhanced sensitivity of steroid therapy. However, the mechanism by which S-CMC regulates HDAC2 is worth further exploring. Our study aimed to investigate the relationships between HDAC2 sumoylation and its deacetylase activity under oxidative stress and the molecular mechanism of S-CMC to regulate HDAC2 activity that mediates inflammatory responses in human bronchial epithelial cells. We found that modification of HDAC2 by SUMO1 and SUMO2/3 occurred in 16HBE cells under physiological conditions, and CSE induced SUMO1 modification of HDAC2 in a dose and time-dependent manner. K462 and K51 of HDAC2 were the two major modification sites of SUMO1, and the K51 site mediated deacetylation activity and function of HDAC2 on histone H4 that regulates IL-8 secretion. S-CMC inhibited CSE-induced SUMO1 modification of HDAC2 in the presence of thiol/GSH, increased HDAC activity, and decreased IL-8 expression. Our study may provide novel mechanistic explanation of S-CMC to ameliorate steroid sensitivity treatment in chronic obstructive pulmonary disease.