Melatonin regulates cancer migration and stemness and enhances the anti-tumour effect of cisplatin.

Melatonin, a lipophilic hormone released from the pineal gland, has oncostatic effects on various types of cancers. However, its cancer treatment potential needs to be improved by deciphering its corresponding mechanisms of action and optimising therapeutic strategy. In the present study, melatonin inhibited gastric cancer cell migration and soft agar colony formation. Magnetic-activated cell sorting was applied to isolate CD133+ cancer stem cells. Gene expression analysis showed that melatonin lowered the upregulation of LC3-II expression in CD133+ cells compared to CD133- cells. Several long non-coding RNAs and many components in the canonical Wnt signalling pathway were altered in melatonin-treated cells. In addition, knockdown of long non-coding RNA H19 enhanced the expression of pro-apoptotic genes, Bax and Bak, induced by melatonin treatment. Combinatorial treatment with melatonin and cisplatin was investigated to improve the applicability of melatonin as an anticancer therapy. Combinatorial treatment increased the apoptosis rate and induced G0/G1 cell cycle arrest. Melatonin can regulate migration and stemness in gastric cancer cells by modifying many signalling pathways. Combinatorial treatment with melatonin and cisplatin has the potential to improve the therapeutic efficacy of both.

BAP31 Regulates Wnt Signaling to Modulate Cell Migration in Lung Cancer.

B-cell receptor-associated protein 31 (BAP31) has been shown to overexpress in a wide range type of cancers. The present study aims to investigate the role of BAP31 on migration in lung cancer. Results showed that the migration of BAP31 knockdown cells was weaken than the control cells. Applying TGFß to treat BAP31 knockdown cells could reduce cell migration. The enhancement on proliferation by TGFß treatment was downregulated after BAP31 knockdown. The cell death and G0/G1 phase arrest was increased in the cells with TGFß and BAP31 siRNA treatment when compared with TGFß treatment alone. Gene expression analysis showed that Bax/Bcl2, MLKL and LC3 was upregulated in the cells with combinatorial treatment of TGFß and BAP31 siRNA. In addition, BAP31 was shown to regulate multiple signaling pathways, especially for Wnt signaling. It found that BAP31 knockdown cells treated with TGFß decreased ß-catenin cytosolic expression and nuclear localization. Wnt signaling activator BIO could restore the downregulation of proliferation by BAP31 knockdown. This finding suggested that BAP31 regulated cancer cell migration is possibly involved with cell death mechanisms and Wnt signaling.

Modulation of lncRNA H19 enhances resveratrol-inhibited cancer cell proliferation and migration by regulating endoplasmic reticulum stress.

The phytoalexin resveratrol exhibits anti-tumour activity in many types of cancer. In this study, we showed that resveratrol suppressed the survival of gastric tumour cells both in vivo and in vitro. Resveratrol promoted apoptosis, autophagy and endoplasmic reticulum (ER) stress in a dose-dependent manner. RNA-seq analysis showed that multiple cell death signalling pathways were activated after resveratrol treatment, while the use of ER stress activators (tunicamycin and thapsigargin) in combinatorial with resveratrol led to further inhibition of cancer cell survival. Results also showed that resveratrol altered the expression of several long non-coding RNAs (lncRNAs), including MEG3, PTTG3P, GAS5, BISPR, MALAT1 and H19. Knockdown of H19 in resveratrol-treated cells further enhanced the effects of resveratrol on apoptosis, ER stress and cell cycle S-phase arrest. Furthermore, the migratory ability of resveratrol-treated cells was dramatically decreased after H19 knockdown. In conclusion, resveratrol inhibited cancer cell survival, while knockdown of lncRNA H19 resulted in increased sensitivity to resveratrol therapy.

The dark side of creativity: Neural correlates of malevolent creative idea generation.

Malevolent creativity, as one dark side of creativity, refers to manifestations people propose to harm themselves or others materially, mentally, or physically in an innovative way. This study aimed to explore the neural correlates of malevolent creative idea generation using task-based static and dynamic functional connectivity (FC) analysis across different time periods. We collected 34 participants who performed malevolent creativity task (MCT), benevolent creativity task (BCT), and realistic presented problems task (RPPT) in the fMRI scanner. The static connectivity analysis showed lower FC strength and global and local efficiency between the dorsal somatomotor network (dSMN), visual network (VN), default mode network (DMN), and reward network (RN) in MCT and RPPT than BCT. Dynamic connectivity analysis showed higher dynamic network reconfiguration in the DMN during MCT than BCT and RPPT. The behavioral results showed higher anxiety, anger, and lower pleasure in MCT than in BCT and RPPT. These findings indicate that the dSMN, VN, RN, and DMN are specifically involved in malevolent creative idea generation. Our findings provide the neural correlates of malevolent creative idea generation using neuroimaging techniques for the first time, which provides insight into the future study of malevolent creativity.

Magnesium-Assisted Cisplatin Inhibits Bladder Cancer Cell Survival by Modulating Wnt/ß-Catenin Signaling Pathway.

Magnesium, an essential mineral micronutrient, plays a role in the activation of various transporters and enzymes. The present study aimed to investigate the possibility of applying magnesium to enhance the efficacy of cisplatin which is still ranked as one of the major chemotherapeutic drugs for bladder cancer patients. Results showed that the survival rate and colony formation of bladder cancer cells were reduced by combinatorial treatment with cisplatin and magnesium chloride (MgCl2). The proportion of apoptotic cells was also increased in UC3 bladder cancer cells treated with a combination of cisplatin and MgCl2. Most importantly, a marked decrease in nuclear ß-catenin was observed in cells that received cisplatin treatment. In addition, the nuclear ß-catenin in cisplatin treated cells was further down-regulated by supplementing MgCl2. 6-bromoindirubin-3'-oxime (BIO), an inhibitor of glycogen synthase kinase-3 (GSK-3) that activates the Wnt/ß-catenin signaling pathway by modulating ß-catenin activity, was thus applied to further exploit the role of this signaling pathway in magnesium aided cancer treatment. The survival rate of bladder cancer cells was decreased by BIO treatment at concentrations of 1.0, 2.5 and 5.0 µM accompanied by increased ß-catenin expression. However, the expression of ß-catenin in MgCl2-treated cells was lower than in untreated cells under the same BIO concentration. The expression of cleaved caspase-3, cleaved caspase-9 and microtubule-associated protein 1 light chain 3- II (LC3-II) was highest in cells treated with MgCl2 and 5.0 µM BIO among the examined groups. Our findings reveal that magnesium could contribute to cisplatin-based chemotherapy by moderately regulating the Wnt/ß-catenin signaling pathway.

Characterization of in-use light-duty gasoline vehicle emissions by remote sensing in Beijing: impact of recent control measures.

China's national government and Beijing city authorities have adopted additional control measures to reduce the negative impact of vehicle emissions on Beijing's air quality. An evaluation of the effectiveness of these measures may provide guidance for future vehicle emission control strategy development. In-use emissions from light-duty gasoline vehicles (LDGVs) were investigated at five sites in Beijing with remote sensing instrumentation. Distance-based mass emission factors were derived with fuel consumption modeled on real world data. The results show that the recently implemented aggressive control strategies are significantly reducing the emissions of on-road vehicles. Older vehicles are contributing substantially to the total fleet emissions. An earlier program to retrofit pre-Euro cars with three-way catalysts produced little emission reduction. The impact of model year and driving conditions on the average mass emission factors indicates that the durability of vehicles emission controls may be inadequate in Beijing.