Sophocarpine inhibits the progression of glioblastoma via PTEN/PI3K/Akt signaling pathway.

Glioblastoma multiforme (GBM) is the most fatal primary brain tumor which lacks effective treatment drugs. Alkaloids are known as a class of potential anti-tumor agents. Sophocarpine, a tetracyclic quinazoline alkaloid derived from Sophora alopecuroides L., possesses several pharmacological effects including anti-tumor effects in some malignancies. However, the effect and mechanism of sophocarpine on GBM remains to be explored. In this study, based on in vitro experiments, we found that sophocarpine significantly inhibited the viability, proliferation and migration of GBM cells including U251 and C6 cells in a dose- and time-dependent manner. Besides, sophocarpine arrested GBM cell cycle in G0/G1 phase and induced their apoptosis. Subsequently, we found that sophocarpine upregulated the expression of PTEN, a GBM tumor suppressor, and downregulated PI3K/Akt signaling in GBM cells. Moreover, inactivating of PTEN with bpV(phen) trihydrate partially restored the anti-GBM effects of sophocarpine via PI3K/Akt signaling. Finally, sophocarpine significantly inhibited the growth of tumor both in subcutaneous and orthotopic U251 xenograft GBM model in nude mice via PTEN/PI3K/Akt axis. Taken together, these results suggested that sophocarpine impeded GBM progression via PTEN/PI3K/Akt axis both in vitro and in vivo, providing with a promising therapy for treating GBM.

The safety and efficacy of third- and fourth-generation cryoballoons for atrial fibrillation: a systematic review and meta-analysis.

Objectives: An increasing number of studies have shown that third (CB3)- and fourth-generation cryoballoons (CB4) have been used to treat various types of atrial fibrillation (AF), but previous research regarding the safety and efficacy of CB3 or CB4 ablation remains controversial. Therefore, a meta-analysis was performed to further evaluate the safety and efficacy of pulmonary vein isolation (PVI) using the CB3 and CB4 in the treatment of AF. Methods: We searched PubMed, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, and Clinicaltrials.gov up to December 2023 for qualified trials and data extraction according to inclusion and exclusion criteria. All analyses were carried out using Review Manager 5.3 software. Results: The meta-analysis included 13 observational studies consisting of 3,281 subjects and did not include a randomized controlled trial. Overall analyses indicated that the CB3 significantly reduced total procedure time [weighted mean difference (WMD) = -8.69 min, 95% confidence interval (CI) = -15.45 to -1.94 min, I2 = 93%], increased the PVI recording [relative risk (RR) = 1.24, 95% CI = 1.03-1.49, I2 = 90%], and increased the mean nadir temperature of overall PVs (WMD = 2.80°C, 95% CI = 1.08-4.51°C, I2 = 89%) compared with the CB2. Moreover, the CB4 significantly reduced the total procedure time (WMD = -14.50 min, 95% CI = -20.89 to -8.11 min, I2 = 95%), reduced the fluoroscopy time (WMD = -2.37 min, 95% CI = -4.28 to -0.46 min, I2 = 95%), increased the PVI recording (RR = 1.40, 95% CI = 1.15-1.71, I2 = 90%) compared with the CB2. Time-to-isolation, the success rate of PVI, AF recurrence, and complications in the CB3 and CB4 were not significantly different compared with the CB2. Conclusion: These findings demonstrated that the CB3 and CB4 tended to be more effective than the CB2 in the treatment of AF, with shorter procedure times, more PVI recording, and similar safety endpoints.

Angelicin impedes the progression of glioblastoma via inactivation of YAP signaling pathway.

Glioblastoma (GBM) is a human malignant tumor with low survival and high recurrence rate. Angelicin, an active furanocoumarin compound, has been reported to possess potential antitumor activity towards various malignancies. However, the effect of angelicin on GBM cells and its mechanism are still unclear. In this study, we found that angelicin inhibited the proliferation of GBM by inducing the cell cycle arrested in G1 phase and suppressed the migration of GBM cells in vitro. Mechanically, we found that angelicin downregulated the expression of YAP and decreased the nuclear localization of YAP, and suppressed the expression of ß-catenin. Furthermore, overexpression of YAP partially restored the inhibitory effect of angelicin on GBM cells in vitro. Finally, we found that angelicin could inhibit the growth of tumor and reduce the expression of YAP in the subcutaneous xenograft model of GBM in nude mice and the syngeneic intracranial orthotopic model of GBM in C57BL/6 mice. Taken together, our results suggest that the natural product angelicin exerts its anticancer effects on GBM via YAP signaling pathway, and is expected to be a promising compound for the treatment of GBM.

Fraxinellone inhibits progression of glioblastoma via regulating the SIRT3 signaling pathway.

Glioblastoma (GBM) is the most prevalent type of adult primary brain tumor and chemotherapy of GBM was limited by drug-resistance. Fraxinellone is a tetrahydro-benzofuranone derivative with various pharmacological activities. However, the pharmacological effects of fraxinellone on GBM remains largely unknown. Here, we found that fraxinellone inhibited the proliferation and growth of GBM cells in a dose-dependent manner in vitro. Subsequently, we found that fraxinellone suppressed the migration and induced apoptosis of GBM cells in vitro. Using western blot and immunostaining, we further found that fraxinellone downregulated the expressions of sirtuin 3 (SIRT3), and superoxide dismutase 2 (SOD2), a downstream of SIRT3 in GBM cells. Meanwhile, reactive oxygen species (ROS) were increased in these fraxinellone-treated GBM cells. Interestingly, overexpression of SIRT3 (SIRT3-OE) indeed partially restored the inhibition of both cell proliferation and migration of GBM cells induced by fraxinellone. Finally, we found that fraxinellone could inhibit the growth of GBM in xenograft model through the inactivation of SIRT3 signaling pathway. Taken together, these results suggest that fraxinellone suppressed the growth and migration of GBM cells by downregulating SIRT3 signaling in vitro, and inhibited the tumorigenesis of GBMs in vivo.