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Lung cancer is a leading cause of cancer‐related deaths worldwide. Recent studies have identified pyroptosis, a type of programmed cell death, as a critical process in the development and progression of lung cancer. In this study, we investigated the effect of EEBR, a new compound synthesized by our team, on pyroptosis in non‐small cell lung cancer cells (NSCLC) and the underlying molecular mechanisms. Our results demonstrated that EEBR significantly reduced the proliferation and metastasis of NSCLC cells in vitro. Moreover, EEBR‐induced pyroptosis in NSCLC cells, as evidenced by cell membrane rupture, the release of cytokines such as interleukin‐18 and interleukin‐1 beta and the promotion of Gasdermin D cleavage in a Caspase‐1‐dependent manner. Furthermore, EEBR promoted the nuclear translocation of NF‐κB and upregulated the protein level of NLRP3. Subsequent studies revealed that EEBR‐induced pyroptosis was suppressed by the inhibition of NF‐κB. Finally, EEBR effectively suppressed the growth of lung cancer xenograft tumours by promoting NSCLC pyroptosis in animal models. Taken together, our findings suggest that EEBR induces Caspase‐1‐dependent pyroptosis through the NF‐κB/NLRP3 signalling cascade in NSCLC, highlighting its potential as a candidate drug for NSCLC treatment. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the effects of platelet‐rich plasma on gingipain‐caused changes in cell morphology and apoptosis of osteoblasts. Mouse osteoblasts MC3T3‐E1 cells were treated with gingipain extracts from Porphyromonas gingivalis in the presence or absence of platelet‐rich plasma. Apoptosis was detected with terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling staining. F‐actin was determined by phalloidin‐fluorescent staining and observed under confocal microscopy. Western blot analysis was used to detect integrin β1, F‐actin, and G‐actin protein expressions. A knocking down approach was used to determine the role of integrin β1. The platelet‐rich plasma protected osteoblasts from gingipain‐induced apoptosis in a dose‐dependent manner, accompanied by upregulation of integrin β1. Platelet‐rich plasma reversed the loss of F‐actin integrity and decrease of F‐actin/G‐actin ratio in osteoblasts in the presence of gingipains. By contrast, the effects of platelet‐rich plasma were abrogated by knockdown of integrin β1. The platelet‐rich plasma failed to reduce cell apoptosis and reorganize the cytoskeleton after knockdown of integrin β1. In conclusion, platelet‐rich plasma inhibits gingipain‐induced osteoblast apoptosis and actin cytoskeleton disruption by upregulating integrin β1 expression. [ABSTRACT FROM AUTHOR]

Previous studies have shown that arctigenin is a promising chemopreventive or therapeutic agent against various cancers. However, less is known about anticancer activity of 3'-desmethylarctigenin (3'-DMAG), which is a biotransformed product from arctigenin or arctin. In this study, we compared the anticancer activity of 3'-DMAG with its parent compound arctigenin and demonstrated that 3'-DMAG exerted a more potent inhibitory effect on HepG2 cells than arctigenin. Mechanistically, reactive oxygen species generation played an apical role in 3'-DMAG-induced G2/M cell cycle arrest and apoptosis in HepG2 cells. Furthermore, the Chk2-Cdc25c-Cdc2-cyclin B1 cascade was found to contribute to the cell cycle arrest, whereas the activation of mitochondrial pathway was involved in the cell apoptosis by 3'-DMAG. Additionally, a mouse xenograft hepatocellular carcinoma model was used to evaluate the antitumor effect of 3'-DMAG in vivo, and the results indicated that 3'-DMAG treatment significantly inhibited tumor growth without apparent toxicity. Taken together, 3'-DMAG is highly effective against liver cancer both in vitro and in vivo. The findings of the present study suggest that this compound deserves to be further investigated for its potential anticancer activity. [ABSTRACT FROM AUTHOR]

Background: Gingipains are cysteine proteases produced by Porphyromonas gingivalis, the predominant pathogen in chronic periodontitis. The present study aims to examine the role of gingipains in promoting apoptosis in osteoblasts.Methods: Human calvarial osteoblasts and osteoblast MC3T3-E1 cells were treated with 8.348 U/L gingipains. Flow cytometry analysis and terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling staining were used to detect cell apoptosis. Protein expression was examined by Western blotting, and gene expression was detected by real-time polymerase chain reaction. Small interfering (si)RNA transfection was used to knock down BH3-interacting domain death agonist (Bid) expression.Results: Treatment with 8.348 U/L gingipains from 4 to 72 hours increased apoptosis, accompanied by elevated cleaved caspase-3 levels. Notably, gingipain-induced apoptosis was associated with increase of Bid and its truncated form, tBid, as well as p53. Transfection with Bid siRNA resulted in suppression of gingipain-induced apoptosis. The p53 inhibitor, Pifithrin-α, blocked the gingipain-induced Bid. The ability of gingipains to stimulate p53 and Bid expression was mimicked by PD-0325901 and MK-2206, the specific extracellular signal-regulated protein kinases (ERK) and protein kinase B (PKB) inhibitors, respectively. Furthermore, treatment with gingipains reduced phospho-ERK and phospho-PKB levels, an effect correlated to gingipain-induced increase in p53 and tBid expression.Conclusion: The present findings suggest that Bid plays an essential role in gingipain-induced osteoblast apoptosis, which is dependent on inhibition of ERK and PKB phosphorylation, followed by the activation of p53. [ABSTRACT FROM AUTHOR]

Introduction: The effects of edaravone against pentylenetetrazole (PTZ)‐induced epilepsy in male albino rats were investigated. Edaravone is a well‐known commercial drug used in the treatment of strokes and amyotrophic lateral sclerosis (ALS). Antioxidant and free radical scavenging activities of edaravone have been reported in patients with ALS. Methods: In this study, the experimental groups were as follows: sham, control, 5 mg/kg edaravone, and 10 mg/kg edaravone. Behavioral assessment, determination of biochemical markers, apoptosis, nitric oxide (NO), and mRNA and protein expression of cyclooxygenase‐II (COX‐II) were carried out. Seizure incidence, including generalized tonic–clonic seizure (GTCS) and minimal clonic seizure (MCS), was directly associated with PTZ administration in rats. Results: Edaravone supplementation substantially increased MCS and GTCS latency in rats, and biochemical markers were significantly altered in the brain tissue of PTZ‐treated rats. Edaravone treatment normalized altered biochemical markers compared with the untreated control. Apoptosis and NO levels were significantly reduced by more than 50% compared to their respective controls. COX‐II mRNA was increased by 130% in PTZ‐treated rats, while edaravone supplementation reduced mRNA and protein expression of COX‐II by more than 20% and 40%, respectively. Immunohistochemistry indicated that COX‐II protein expression was reduced by 13.2% and 33.7% following supplementation with 5 and 10 mg/kg edaravone, respectively. Conclusion: Taken together, our results suggest that edaravone functions by downregulating the levels of COX‐II and NO and is a potential candidate for the treatment of PTZ‐induced epilepsy. Edaravone supplementation significantly normalized altered lipid peroxidation and antioxidant biochemical markers. Apoptosis and NO levels were reduced compared to their respective controls. mRNA and protein expression of COX‐II was substantially reduced following edaravone supplementation. Taken together, our results suggest that edaravone is a potential candidate for the treatment of PTZ‐induced epilepsy and functions by downregulating the levels of COX‐II and NO. [ABSTRACT FROM AUTHOR]