Shuangmei Liu

Myocardial ischemia (MI) often leads to sympathetic overexcitation, though the underlying mechanisms are not fully understood. This work was to elucidate the role of P2Y6 receptors in the superior cervical ganglion (SCG) in mediating sympathetic hyperactivity after MI. In vivo, a rat model of MI was established by mild ligation of the left anterior descending coronary artery. These rats exhibited ST-segment elevation, elevated blood pressure, increased heart rate, enhanced sympathetic nerve discharge, raised serum norepinephrine levels, and structural damage to myocardial tissue. These changes were accompanied by P2Y6 expression upregulation in the SCG and NF-κB signalling activation, as indicated by increased levels of p65, phospho-p65, IL-1β, and TNF-α. P2Y6 knockdown with shRNA significantly alleviated these pathological manifestations. In vitro, oxygen-glucose deprivation in PC12 cells similarly upregulated P2Y6 expression and activated NF-κB signalling. The P2Y6 agonist UDP further enhanced, while the antagonist MRS2578 suppressed, the expression of p65, phospho-p65, IL-1β, and TNF-α. Moreover, the NF-κB inhibitor PTD-P65-P1 abolished UDP-induced IL-1β release. In conclusion, P2Y6 receptors in the SCG contribute to MI-related sympathetic overactivity via NF-κB-mediated inflammatory signalling, highlighting P2Y6 as a potential therapeutic target for autonomic dysregulation after myocardial ischemia.

Diabetic neuropathy (DN) is a common complication of diabetes, affecting over 50% of patients, leading to significant pain and a burden. Currently, there are no effective treatments available. Cell death is considered a key factor in promoting the progression of DN. This article reviews how cell death is initiated in DN, emphasizing the critical roles of oxidative stress, mitochondrial dysfunction, inflammation, endoplasmic reticulum stress, and autophagy. Additionally, we thoroughly summarize the mechanisms of cell death that may be involved in the pathogenesis of DN, including apoptosis, autophagy, pyroptosis, and ferroptosis, among others, as well as potential therapeutic targets offered by these death mechanisms. This provides potential pathways for the prevention and treatment of diabetic neuropathy in the future.

Notch signaling is an evolutionarily conserved pathway, which involves in various cell life activities. Other studies and our report showed that the Notch signaling plays very important role in follicle development in mammalian ovaries. In luteal cells, Notch ligand, delta-like ligand 4, is involved in normal luteal vasculature. In this study, murine luteal cells were cultured in vitro and treated with Notch signaling inhibitors, L-658,458 and N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycinet-butyl ester (DAPT). We found that L-658,458 and DAPT treatment decrease basal and human chorionic gonadotropin (hCG)-stimulated progesterone secretion. On the contrary, overexpression of intracellular domain of Notch3 increased basal and hCG-stimulated progesterone secretion. Further studies demonstrated that Notch signaling regulated the expression of steroidogenic acute regulatory protein and CYP11A, 2 key enzymes for progesterone synthesis. In conclusion, Notch signaling plays important role in regulating progesterone secretion in murine luteal cells.