Halbergmcleod9264

The high-content screening assay showed that cell oxidative stress, mitochondrial damage, endoplasmic reticulum stress, and the concentration of calcium ions increased, and neutral lipid metabolism was changed notably in HepaRG cells. Induced apoptosis by PAs was indicated by cell cycle arrest in the G2/M phase, disrupting the mitochondrial membrane potential. Overall, our study revealed structure-dependent cytotoxicity and apoptosis after PA exposure, suggesting that the prediction results of in silico have certain reference values for compound toxicity. A 1,2-membered cyclic diester seems to be a more potent apoptosis inducer than other PAs.Hepatocellular carcinoma (HCC) is a leading cause of death, resulting in over 700 thousand deaths annually worldwide. Chemotherapy is the primary therapeutic strategy for patients with late-stage HCC. Heteronemin is a marine natural product isolated from Hippospongia sp. that has been found to protect against carcinogenesis in cholangiocarcinoma, prostate cancer, and acute myeloid leukemia. In this study, heteronemin was found to inhibit the proliferation of the HCC cell lines HA22T and HA59T and induce apoptosis via the caspase pathway. Heteronemin treatment also induced the formation of reactive oxygen species (ROS), which are associated with heteronemin-induced cell death, and to trigger ROS removal by mitochondrial SOD2 rather than cytosolic SOD1. The mitogen-activated protein kinase (MAPK) signaling pathway was associated with ROS-induced cell death, and heteronemin downregulated the expression of ERK, a MAPK that is associated with cell proliferation. Inhibitors of JNK and p38, which are MAPKs associated with apoptosis, restored heteronemin-induced cell death. In addition, heteronemin treatment reduced the expression of GPX4, a protein that inhibits ferroptosis, which is a novel form of nonapoptotic programmed cell death. Ferroptosis inhibitor treatment also restored heteronemin-induced cell death. Thus, with appropriate structural modification, heteronemin can act as a potent therapeutic against HCC.Recent studies have claimed that iron overload was correlated with the risk of hepatocellular carcinoma (HCC), and our previous studies have also demonstrated that dandelion polysaccharide (DP) suppressed HCC cell line proliferation via causing cell cycle arrest and inhibiting the PI3K/AKT/mTOR pathway, but the effect of DP on metabolism is still not very clear. Here, we aim to clarify the effects of DP on iron metabolism and the underlying mechanism. In this study, we found that DP could reduce iron burden in hepatoma cells and grafted tumors. Hepcidin is a central regulator in iron metabolism. We confirmed that the expression of hepcidin in HCC tumor tissues was significantly higher than that in the adjacent nontumor tissues. The expression of hepcidin was downregulated in the liver of mouse model treatment with DP, as well as in hepatoma cells. Moreover, RNA sequencing and western blot data revealed that DP inhibited the IL-6-activated JAK-STAT signaling pathway. In summary, our results revealed that DP might be a new potential drug candidate for the regulation of iron burden and the treatment of HCC.

Astragaloside IV shows neuroprotective activity, but its mechanism remains unclear. To investigate whether astragaloside IV protects from endoplasmic reticulum stress (ERS), we focus on the regulation of glycogen synthase kinase-3

(GSK-3

) and mitochondrial permeability transition pore (mPTP) by astragaloside IV in neuronal cell PC12.

PC12 cells treated with different concentrations of ERS inductor 2-deoxyglucose (2-DG) (25-500 

M) showed a significant increase of glucose-regulated protein 78 (GRP 78) and GRP 94 expressions and a decrease of tetramethylrhodamine ethyl ester (TMRE) fluorescence intensity and mitochondrial membrane potential (∆

m), with the peak effect seen at 50 

M, indicating that 2-DG induces ERS and the mPTP opening. Similarly, 50 

M of astragaloside IV increased the GSK-3

phosphorylation at Ser9 most significantly. Next, we examined the neuroprotection of astragaloside IV by dividing the PC12 cells into control group, 2-DG treatment group, astragaloside IV plus 2-DG treatment data suggested that astragaloside IV protects PC12 cells from ERS by inactivation of GSK-3

and preventing the mPTP opening. The GRP 78, GRP 94, IRE1, and PERK signaling pathways but not ATF6 are responsible for GSK-3

inactivation and neuroprotection by astragaloside IV.

Our data suggested that astragaloside IV protects PC12 cells from ERS by inactivation of GSK-3β and preventing the mPTP opening. The GRP 78, GRP 94, IRE1, and PERK signaling pathways but not ATF6 are responsible for GSK-3β inactivation and neuroprotection by astragaloside IV.Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths worldwide and a major global public health problem. With the rapid development of the economy, the incidence of CRC has increased linearly. Accumulating evidence indicates that changes in the gut microenvironment, such as undesirable changes in the microbiota composition, provide favorable conditions for intestinal inflammation and shaping the tumor growth environment, whereas administration of certain probiotics can reverse this situation to a certain extent. This review summarizes the roles of probiotics in the regulation of CRC, such as enhancing the immune barrier, regulating the intestinal immune state, inhibiting pathogenic enzyme activity, regulating CRC cell proliferation and apoptosis, regulating redox homeostasis, and reprograming intestinal microbial composition. Abundant studies have provided a theoretical foundation for the roles of probiotics in CRC prevention and treatment, but their mechanisms of action remain to be investigated, and further clinical trials are warranted for the application of probiotics in the target population.Age-related macular degeneration (AMD) is a major cause of visual impairment and blindness among the elderly. AMD is characterized by retinal pigment epithelial (RPE) cell dysfunction. However, the pathogenesis of AMD is still unclear, and there is currently no effective treatment. Accumulated evidence indicates that oxidative stress and autophagy play a crucial role in the development of AMD. check details H2S is an antioxidant that can directly remove intracellular superoxide anions and hydrogen peroxide. The purpose of this study is to investigate the antioxidative effect of H2S in RPE cells and its role in autophagy. The results show that exogenous H2S (NaHS) pretreatment effectively reduces H2O2-induced oxidative stress, oxidative damage, apoptosis, and inflammation in ARPE-19 cells. NaHS pretreatment also decreased autophagy levels raised by H2O2, increased cell viability, and ameliorated cell morphological damage. Interestingly, the suppression of autophagy by its inhibitor 3-MA showed an increase of cell viability, amelioration of morphology, and a decrease of apoptosis.