Osthole induces G2/M arrest and apoptosis in lung cancer A549 cells by modulating PI3K/Akt pathway

<p>Abstract</p> <p>Background</p> <p>To explore the effects of Osthole on the proliferation, cell cycle and apoptosis of human lung cancer A549 cells.</p> <p>Methods</p> <p>Human lung cancer A549 cells were treated with Osthole at different concentrations. Cell proliferation was measured using the MTT assay. Cell cycle was evaluated using DNA flow cytometry analysis. Induction of apoptosis was determined by flow cytometry and fluorescent microscopy. The expressions of Cyclin B1, p-Cdc2, Bcl-2, Bax, t-Akt and p-Akt were evaluated by Western blotting.</p> <p>Results</p> <p>Osthole inhibited the growth of human lung cancer A549 cells by inducing G2/M arrest and apoptosis. Western blotting demonstrated that Osthole down-regulated the expressions of Cyclin B1, p-Cdc2 and Bcl-2 and up-regulated the expressions of Bax in A549 cells. Inhibition of PI3K/Akt signaling pathway was also observed after treating A549 cells with Osthole.</p> <p>Conclusions</p> <p>Our findings suggest that Osthole may have a therapeutic application in the treatment of human lung cancer.</p

The protection of glycyrrhetinic acid (GA) towards acetaminophen (APAP)-induced toxicity partially through fatty acids metabolic pathway

Background: Acetaminophen (APAP)-induced liver toxicity remains the key factor limiting the clinical application of APAP, and herbs are the important sources for isolation of compounds preventing APAP-induced toxicity. Aims: To investigate the protection mechanism of glycyrrhetinic acid towards APAP-induced liver damage using metabolomics method. Methods: APAP-induced liver toxicity model was made through intraperitoneal injection (i.p.) of APAP (400 mg/kg). Glycyrrhetinic acid was dissolved in corn oil, and intraperitoneal injection (i.p.) of glycyrrhetinic acid (500 mg/kg body weight) was performed for 20 days before the injection of APAP. UPLC-ESI-QTOF MS was employed to analyze the metabolomic profile of serum samples. Results: The pre-treatment of glycyrrhetinic acid significantly protected APAP-induced toxicity, indicated by the histology of liver, the activity of ALT and AST. Metabolomics showed that the level of palmtioylcarnitine and oleoylcarnitine significantly increased in serum of APAP-treated mice, and the pre-treatment with GA can prevent this elevation of these two fatty acid-carnitines. Conclusion: Reversing the metabolism pathway of fatty acid is an important mechanism for the protection of glycyrrhetinic acid towards acetaminophen-induced liver toxicity

Development and validation of a prognostic nomogram model in locally advanced NSCLC based on metabolic features of PET/CT and hematological inflammatory indicators

Abstract Background We combined the metabolic features of 18F-FDG-PET/CT and hematological inflammatory indicators to establish a predictive model of the outcomes of patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving concurrent chemoradiotherapy. Results A predictive nomogram was developed based on sex, CEA, systemic immune-inflammation index (SII), mean SUV (SUVmean), and total lesion glycolysis (TLG). The nomogram presents nice discrimination that yielded an AUC of 0.76 (95% confidence interval: 0.66–0.86) to predict 1-year PFS, with a sensitivity of 63.6%, a specificity of 83.3%, a positive predictive value of 83.7%, and a negative predictive value of 62.9% in the training set. The calibration curves and DCA suggested that the nomogram had good calibration and fit, as well as promising clinical effectiveness in the training set. In addition, survival analysis indicated that patients in the low-risk group had a significantly longer mPFS than those in the high-risk group (16.8 months versus 8.4 months, P < 0.001). Those results were supported by the results in the internal and external test sets. Conclusions The newly constructed predictive nomogram model presented promising discrimination, calibration, and clinical applicability and can be used as an individualized prognostic tool to facilitate precision treatment in clinical practice