Ischemic stroke is a leading cause of death and disability worldwide, and autophagy may be involved in the pathological process of cerebral ischemia/reperfusion injury. Hydrogen sulfide (H₂S) is an endogenous gasotransmitter with protective effects against multiple diseases. Here, we tested the effect of H₂S on cerebral ischemia/reperfusion injury in rats. Sodium hydrosulfide (NaHS), an H₂S donor, improved neurological function and reduced the size of the infarcts induced by transient middle cerebral artery occlusion (MCAO) followed by reperfusion in rats. NaHS treatment reduced the lactate dehydrogenase (LDH) activity in the serum (a marker of cellular membrane integrity) and the expression of cleaved caspase‐3 (a marker for apoptosis) in the brains of MCAO rats. We also found that autophagy was overactivated in the brains of MCAO rats, as indicated by an increased ratio of LC3 II to I, decreased expression of p62, and transmission electron microscope detection. NaHS treatment significantly inhibited the autophagic activity in the brains of MCAO rats. Furthermore, PC12 cells were subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) to mimic MCAO in vitro. We found that NaHS treatment reduced cellular injury and suppressed overactivated autophagy induced by OGD/R in PC12 cells. An autophagy stimulator (rapamycin) eliminated the protective effect of NaHS against LDH release and caspase‐3 activity induced by OGD/R in PC12 cells. An autophagy inhibitor (3‐methyladenine, 3‐MA) also reduced the cellular injury induced by OGD/R in PC12 cells. In conclusion, the results indicate that overactivated autophagy accelerates cellular injury after MCAO in rats and that exogenous H₂S attenuates cerebral ischemia/reperfusion injury via suppressing overactivated autophagy in rats.

Bone cancer pain (BCP) is common in patients with advanced cancers when the tumors are metastasized to bone. The limited understanding of the complex pathogenesis of BCP leads to the poor effectiveness of clinical treatment. Previous studies have shown that astrocyte-specific connexin (Cx) 43, a forming protein of gap junction (GJ) and hemichannel, and N-methyl-D-aspartate receptors (NMDARs), especially the phosphorylated NMDAR 2B subunit (NR2B) phosphorylated NR2B (p-NR2B) subunit are involved in BCP. However, the relationship between Cx43 and p-NR2B in BCP remains unclear. In the present study, we investigated the expressions of Cx43, glial fibrillary acidic protein (GFAP, a marker of astrocytes), and p-NR2B in the spinal dorsal horn (SDH) in a mouse model of BCP established by intra-femural inoculation of Lewis lung carcinoma (LLC) cells via intrathecal (ith) injection of the GJ/hemichannel blocker carbenoxolone (CARB) and the NMDAR antagonist MK801, respectively. We found that the characters of BCP were mimicked by intra-femural inoculation of LLC cells in mice, and the expressions of Cx43, GFAP and p-NR2B in BCP mice were remarkably increased in a time-dependent manner from day 7 to day 21 after cell inoculation with a gradual aggravate in spontaneous pain and mechanical allodynia. Furthermore, Cx43 was predominantly expressed in the spinal astrocytes. Both CARB and MK801 inhibited the expressions of Cx43, GFAP and p-NR2B with attenuated pain hypersensitivity in BCP mice. In addition, Cx43 was co-localized with p-NR2B in the SDH, which further evidenced the presence of functional NR2B in the spinal astrocytes in BCP mice. Our findings demonstrate that inhibition of Cx43 and p-NR2B in spinal astrocytes could attenuate BCP in mice and Cx43 and p-NR2B in the astrocytes of the SDH may play an important role via their combination action in the development and maintenance of BCP in mice. These results may provide a potential therapeutic target in the prevention and/or treatment of BCP.

Comparison of the Performance of 24 Early Warning Scores with the Updated National Early Warning Score (NEWS2) for Predicting Unplanned Intensive Care Unit (ICU) Admission in Postoperative Brain Tumor Patients: A Retrospective Study at a Single Center - Article abstract #929168

Background: The paired-box gene 6 (PAX6) is an important transcription factor in the central nervous system, mainly regulating the development and differentiation of embryonic eyes and the nervous system. PAX6 expression is significantly decreased in glioma, and the expression levels are closely related to glioma development and prognosis. Therefore, it is important to study and elucidate the biological function of PAX6 in glioma to further our understanding of the occurrence and development of glioma. Methods: This study focused on the expression and regulation of PAX6 and hypoxia-inducing factor (HIF-1α) and investigated the molecular mechanism of ferroptosis regulated by PAX6 and HIF-1α. Firstly, immunohistochemistry, qPCR, Western blot, and other methods were used to detect PAX6 and HIF-1α expression in glioma tissues and cells, as well as the specific way in which PAX6 regulates HIF-1α. Then, some relative indicators of ferroptosis regulated by PAX6 in glioma were studied. Results: The results showed that PAX6 inhibited HIF-1α expression by regulating the levels of reactive oxygen species (ROS); overexpression of PAX6 promoted the expression of ROS and lipid peroxides (LPOs) in glioma cells and decreased the expression of intracellular antioxidant systems glutathione peroxidase 4 (GPX4) and glutathione (GSH). Conclusions: Downregulation of PAX6 plays an important role in regulating ferroptosis in glioma cells. Our research provides a reference basis for a deeper understanding of the role of PAX6 in ferroptosis of glioma.