Cordyceps militaris (CM), an entomopathogenic fungus belonging to the class ascomycetes, possesses various pharmacological activities, including cytotoxic effects, on various types of human tumor cells. The present study investigated the anti-hepatocellular carcinoma (HCC) and anti-breast cancer effects of CM in in vitro and in vivo models. CM aqueous extract reduced cell viability, suppressed cell proliferation, inhibited cell migration ability, caused the over-release of lactate dehydrogenase, induced mitochondrial dysfunction and enhanced apoptotic rates in MCF-7 and HepG2 cells. The expression levels of cleaved poly (ADP ribose) polymerase and caspase-3, biomarkers of apoptosis, were increased following treatment with CM aqueous extract for 24 h. Furthermore, in the MCF-7 and HepG2 cells, enhanced levels of B cell-associated X protein and cleaved caspase-8 were observed in the CM-treated cells. Finally, the antitumor activities of CM in HCC and breast cancer were also confirmed in MCF-7- and HepG2-xengraft nude mice models. Collectively, the data obtained in the present study suggested that the cytotoxic effects of CM aqueous extract on HCC and breast cancer are associated with the caspase-dependent mitochondrial pathway.
Mg-Sn-based alloys are considered as a promising precipitation-hardening system for applications at elevated temperatures, but the hardening effect is not satisfactory owing to sluggish nucleation and rapid coarsening of the major Mg 2 Sn lath precipitates. In this study, Cu and Al are added to a Mg-6Sn-1Mn base alloy. The age-hardening response and the microstructures of these modified alloys have been investigated and are compared to that of the base alloy. The additional elements are found to bring several beneficial effects to the alloys for applications at elevated temperatures. Firstly, a eutectic structure consisting of strong intermetallic phases, i.e. Mg 2 Cu in the Mg-6Sn-1Mn-2Cu alloy and Al 0.93 Cu 1.07 Mg in the Mg-6Sn-1Mn-2Cu-2Al alloy, remains stable along the grain boundaries after solution and ageing heat treatments. Secondly, the precipitate density has been increased significantly and the precipitate size has been refined remarkably during ageing at 200°C. Moreover, the growth of the precipitates is inhibited remarkably during the over-ageing period. Therefore, the age-hardening response and over-ageing resistance are notably improved.
Tumor metastasis has become a key obstacle to cancer treatment, which causes high mortality. Nowadays, it involves multiple complex pathways, and conventional treatments are not effective due to fewer targets. The aims of the present study were to construct a novel liposome delivery system co-loading a specific PLD inhibitor 5-fluoro-2-indolyldes-chlorohalopemide (FIPI) in combination with antitumor drug doxorubicin (DOX) and functional excipient D-alpha tocopheryl acid succinate (α-TOS) for anti-metastasis. In this study, the liposomes containing three components (DFT-Lip) with different physicochemical properties were successfully prepared by film dispersion method combined with pH-gradient method. Physicochemical parameters such as particles size, potential, encapsulation efficiency, stability, and release profiles were investigated. In vitro and in vivo anti-metastasis effectiveness against highly metastatic breast cancer MDA-MB-231 cell line was evaluated. The liposomes showed uniform particle size (approximately 119 nm), high drug encapsulation efficiency (> 90%), slow release characteristics and stability. In vitro anti-tumor cell metastasis study demonstrated DFT-Lip could greatly inhibit motility, migration and invasion of MDA-MB-231 cells compared to other liposomes, predicting a synergistic anti-tumor metastasis effect between FIPI with α-TOS in liposomes. In vivo anti-metastasis study showed that DFT-Lip prevented the initiation and the progression of metastasis of high metastatic breast cancer. These results suggested that the liposomes containing DOX, FIPI, and α-TOS might be a promising strategy for metastatic tumor therapy in clinics.
As novel amphiphilic materials, six uncharged alkyl rhamnosides incorporating various alkyl chain and one rhamnose amine quaternary ammonium salt were successfully synthesized in this study. Their amphiphilic properties (HLB and CMC), antimicrobial and anti-biofilm activity against S. aureus and P. aeruginosa were investigated. Differentially regulated proteins and pathways were identified by comparative proteomics research to first give a sight on how alkyl rhamnosides performed the anti-biofilm activity at protein and pathway levels. Among the uncharged alkyl rhamnosides, dodecyl rhamnoside and octyl rhamnoside showed the best antimicrobial and anti-biofilm ability against S. aureus and against P. aeruginosa, respectively. Interestingly, the relationships between amphiphilic properties or MIC with anti-biofilm activity were first established. Uncharged alkyl rhamnoside with an optimized HLB value of 5.0 had both the strongest antibacterial and anti-biofilm activity against S. aureus, and MIC was the maximum biofilm inhibitory concentration for all alkyl rhamnosides. Alkyl rhamnosides have a significant overall regulatory effect on the proteomics and pathways of bacterial biofilms, including energy production, substrates transportation, signal transduction, key molecules balance, and so on. These amphiphilic materials have a great potential to be used as additives in pharmaceutic, cosmetic, food industry, hospital and in other non-medical fields.
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