Anticancer mechanisms on pyroptosis induced by Oridonin: New potential targeted therapeutic strategies.

Pyroptosis is a type of inflammatory cell death that is triggered by the formation of pores on the cell membrane by gasdermin (GSDM) family proteins. This process activates inflammasomes and leads to the maturation and release of proinflammatory cytokines such as interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). Pyroptosis, a form of programmed cell death, has been found to be associated with various biomolecules such as caspases, granzymes, non-coding RNA (lncRNA), reactive oxygen species (ROS), and NOD-like receptor protein 3 (NLRP3). These biomolecules have been shown to play a dual role in cancer by affecting cell proliferation, metastasis, and the tumor microenvironment (TME), resulting in both tumor promotion and anti-tumor effects. Recent studies have found that Oridonin (Ori) has anti-tumor effects by regulating pyroptosis through various pathways. Ori can inhibit pyroptosis by inhibiting caspase-1, which is responsible for activating pyroptosis of the canonical pathway. Additionally, Ori can inhibit pyroptosis by inhibiting NLRP3, which is responsible for activating pyroptosis of the noncanonical pathway. Interestingly, Ori can also activate pyroptosis by activating caspase-3 and caspase-8, which are responsible for activating pyroptosis of the emerging pathway; Ori has been found to be effective in inhibiting pyroptosis by blocking the action of perforin, which is responsible for facilitating the entry of granzyme into cells and activating pyroptosis. Additionally, Ori plays a crucial role in regulating pyroptosis by promoting the accumulation of ROS while inhibiting the ncRNA and NLRP3 pathways. It is worth noting that all of these pathways ultimately regulate pyroptosis by influencing the cleavage of GSDM, which is a key factor in the process. These studies concludes that Ori has extensive anti-cancer effects that are related to its potential regulatory function on pyroptosis. The paper summarizes several potential ways in which Ori participates in the regulation of pyroptosis, providing a reference for further study on the relationship between Ori, pyroptosis, and cancer.

The neuroprotective effects of phosphocreatine on Amyloid Beta 25-35-induced differentiated neuronal cell death through inhibition of AKT /GSK-3ß /Tau/APP /CDK5 pathways in vivo and vitro.

Alzheimer (AD) is a degenerative disease that can lead memory loss and behavioral dysfunction. Aß protein and phosphorylation of Tau protein are related to the onset of AD. However, at present, its treatment and drugs are limited. The purpose of our study is to evaluate whether phosphocreatine (PCr) could protect neuronal injury induced by Aß protein in vivo and in vitro through AKT/GSK-3ß/Tau/APP/CDK5 pathways. Differentiated PC-12 cells were cultured with Aß25-35 for 24 h, while the mice were injected with D-Galactose for eight weeks, both of them were pretreated with PCr for 2 h. The results showed PCr could obviously induce cells and hippocampus apoptosis using DAPI and TUNEL. PCr decreased the levels of intercellular reactive oxygen species (ROS) and malondialdehyde (MDA), and increased the activities of superoxide dismutase (SOD). Besides, the apoptosis pathway was detected using Western blot, showing that PCr could significantly reduce caspase-3, caspase-9, Bcl-2/Bax expression in vivo and in vitro. At the same time, PCr could decreased Ca2+ and apoptosis by Flow Cytometry in PC-12 cells. We observed that the morphological alteration of hippocampus injury was mitigated with the pretreatment of PCr. Furthermore, PCr pretreatment could decrease Aß25-35-induced PC-12 cells apoptosis with APP cDNA transfection, which up-regulated AKT/GSK-3ß/CDK5 pathways and induced Tau phosphorylation. In summary, PCr could reduce Aß25-35 toxicity to protect neuronal cells via AKT/GSK-3ß/CDK5 pathways.

Se Regulates the Contractile Ability of Uterine Smooth Musclevia Selenoprotein N, Selenoprotein T, and Selenoprotein Win Mice.

Selenium (Se) is an essential micronutrient that maintains normal physiological functions in humans and animals. Se plays a vital role in regulating smooth muscle contractions, and selenoprotein N (SelN), selenoprotein T (SelT), and selenoprotein W (SelW) are closely related to the release of Ca2+. The present study analyzed the effects and mechanisms of SelN, SelT, and SelW in uterine smooth muscle contractions in a mouse model fed Se. The mRNA and protein levels in the uterine smooth muscle of mice were detected by qPCR, Western blot, and immunohistochemical analysis. The results showed that Se played an indispensable role in uterine smooth muscle contractions. Increased Se concentration in food increased the release of Ca2+ to a certain extent, causing CaM expression, MLCK expression, and MLC phosphorylation, which can lead to uterine smooth muscle contractions. In contrast, Se deficiency reduced the release of Ca2+ to a certain degree, thereby reducing the contractile ability of uterine smooth muscle. In this study, genes related to SelN, SelT, and SelW expression in uterine smooth muscle cells were investigated. The results showed that the Se concentration had an effect on the expression of SelN, SelT, and SelW in uterine smooth muscle cells. Se influences the release of Ca2+ through SelN, SelT, and SelW, which changes the expression of MLCK and then affects uterine smooth muscle contractions. The three selenoproteins SelN, SelT, and SelW play a very important role in uterine smooth muscle contractions, and the absence of any of these proteins affects the contractility of the uterus.