Mosloflavone from Fissistigma petelotii ameliorates oncogenic multidrug resistance by STAT3 signaling modulation and P-glycoprotein blockade.

BACKGROUND: Oncogenic multidrug resistance (MDR) is a tough question in cancer therapy. However, no effective medications targeting oncogenic MDR are currently available. Studies have demonstrated that mosloflavone exerts anti-inflammatory effects, yet, its potential to ameliorate MDR remains unclear. PURPOSE: This study aimed to access the capability and elucidate molecular mechanisms of mosloflavone as a MDR resensitizing candidate. METHODS: We investigated the ability of mosloflavone to reverse oncogenic MDR and investigated its underlying mechanisms through cytotoxicity assay, cell cycle assay, apoptosis assay, and zebrafish xenograft model. The modulatory interplay between mosloflavone and P-gp was investigated through analysis of calcein-AM uptake, substrate efflux, ATPase assays, and molecular docking simulation. RESULTS: Mosloflavone inhibited P-gp efflux function in an uncompetitive manner without altering ABCB1 gene expression. In addition, it stimulated P-gp ATPase activity by binding to an active site distinct from that of verapamil. Regarding MDR reversal potential, mosloflavone resensitized MDR cancer cells to chemotherapies by arresting cell cycle and triggering apoptosis, possibly by enhancing reactive oxygen species accumulation and reducing phospho-STAT3. Moreover, in the zebrafish xenograft model, mosloflavone significantly potentiated the antitumor effect of paclitaxel. CONCLUSION: Our findings underscore the potential of mosloflavone as a novel dual modulator of STAT3 and P-gp, indicating it is a promising candidate for overcoming MDR in cancer treatment.

Pharmacological Interventions for Excessive Daytime Sleepiness in Adults with Narcolepsy: A Systematic Review and Network Meta-Analysis.

Narcolepsy is a neurological disease characterized by a core symptom of excessive daytime sleepiness (EDS). Although effective pharmacological interventions for narcolepsy have been developed, a lack of comparative evidence supporting the relative efficacy among these medications leads to clinical treatment challenge. Therefore, we performed a network meta-analysis to overcome this lack of head-to-head comparisons. Databases were searched systematically for randomized controlled trials that compared pharmacological interventions for narcolepsy. The primary outcomes were changes in the Epworth Sleepiness Scale (ESS) and the Maintenance of Wakefulness Test (MWT). A random-effects frequentist network meta-analysis was conducted. A total of 19 RCTs involving 2504 patients were included. Solriamfetol achieved the highest ranking based on the P-scores, and was superior to pitolisant (MD -2.88, 95% CI -4.89--0.88) and sodium oxybate (MD -2.56, 95% CI -4.62--0.51) for ESS change. Consistently, solriamfetol achieved the highest ranking according to MWT change, and was superior to pitolisant (SMD 0.45, 95% CI 0.02-0.88) and modafinil (SMD 0.42, 95% CI 0.05-0.79). Although solriamfetol demonstrated superior efficacy in EDS improvement, evidence from the clustered ranking plot supported that efficacy-safety profiles of pitolisant, sodium oxybate, and modafinil are more balanced than solriamfetol. Therefore, the choice of medication for EDS in narcolepsy should be made on an individual basis.

A low-damage plasma surface modification method of stacked graphene bilayers for configurable wettability and electrical properties.

In this work, we study surface functionalization effects of artificially stacked graphene bilayers (ASGBs) to control its wetting properties via low-damage plasma. The ASGBs were prepared on a SiO2/Si substrate by stacking two monolayer graphene, which was grown by chemical vapor deposition. As a result, the low-damage plasma functionalization of ASGBs could hold both the key characteristics of surface functionalization and electrical transport properties of graphene sheets. To characterize ASGBs, Raman and x-ray photoelectron spectroscopy (XPS) were used to determine the degree of defect formation and functionalization. Meanwhile, the degree of the wettability of the ASGBs surface was determined by optical contact angle (CA) measurements. Based on experimental results, the compositional ratio of C-OH + COOH was found to increase 67% based on the analysis of XPS spectra after low-damage plasma treatment. This treatment effect can also be found with 75.3% decrease in the CA of water droplet on graphene. In addition, we found that the ratio of 2D/(D + G') in Raman spectra shows strong correlation to the measured CA; it can be a reliable indicator of ASGBs surface wettability modification. This work showed that we obtained a higher degree functionalization of ASGBs without degrading the under-layer structure of ASGBs due to the moderate low-damage plasma treatment. The presented process technique of controllable wettability through low-damage plasma treatment can be employed for potential application in graphene-based sensors/devices.