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Background: Ricin has been reported as a potential chemical for cancer treatment. However, so far, the application of ricin in cancer treatment is very limited because of its non-specificity. Methods: In this study, ricin were conjugated/ encapsulated with DOTAP/DOPE liposome to form ricin-liposome complexes (ricin-lipososme1, ricin-liposome2, ricin-liposome3 and ricin-liposome4). Characteristics of ricin-liposome complexes were analyzed and their effects on survival, apoptosis, migration, invasion and tumor formation of SKMEL-28 melanoma cells were examined by carrying out the MTT assay, apoptosis assay, scratch wound healing assay, invasion assay and soft-agar colony formation assay, respectively. Results: Ricin-liposome complexes had even size-distribution with average size of around 340 nm. These ricin-liposome complexes were able to penetrate into the cells via endocytosis with the highest ability of the ricinliposome3. It also showed that ricin-liposome3 expressed very high toxicity with the IC50 of 62.4 ng/mL and followed by ricin-liposome4 (286.4 mg/mL), ricin-liposome2 (417.5 ng/mL), and ricin-liposome1 (604.3 ng/mL) to SKMEL-28 cells at 36 hours post treatment. At the concentrations of IC10 (10.1 ng/mL), ricin-liposome3 strongly induced necrosis and apoptosis of SKMEL-28 cells up to 25.6% and 11.4%, respectively. Moreover, ricin-liposome3 expressed great anticancer properties by decreasing the migration, invasion and tumor formation abilities of SKMEL-28 cells of 7.5 folds, 4.3 folds and 5.9 folds, respectively, compared with those of control SKMEL-28 cells. Conclusion: The obtained results from our study suggest that although ricin is listed as one of the most poisonous substances in nature, it can be used in the complex forms with liposome to increase its specificity to apply in treatment of melanoma and other cancers.

Ricin has been reported as a potential therapeutic agent for the treatment of various cancers due to its potency. In this study, we succeeded in isolating and purifying total ricin from seeds of the castor bean (ricinus communis) from Vietnam. We also revealed that total ricin showed strong cytotoxicity against melanoma cells; IC50 at 48h was 34.1 ng/mL for SKMEL28 cells and 5.2 ng/mL for HaCaT cells. We examined the ability of total ricin to inhibit tumorigenesis of SKMEL28 cells in vitro. At low concentrations (< 3ng/mL)total ricin did not cause death of HaCaT or SKMEL28 cells but strongly reduced the size of SKMEL28 tumor colonies formed in soft agar. The effect of ricin on tumorigenesis was also confirmed by apoptotic and immunoblot analyses. Our results showed that treatment with total ricin (3 ng/mL) resulted in decreased ERK and p-ERK expression in SKME28 cells but did not affect expression levels of thosegenes in HaCaT cells. We showed that, although ricin at 1 and 3 ng/mLdid not induce apoptosis of HaCaT cells, it significantly increased apoptosis of SKMEL28 up to 1.4 folds and 2.1 folds, respectively. The results from our study suggest that although ricin is listed as one of the most poisonous substances in nature, it has potential to be used as a drug for melanoma treatment.

For several hundred years, the design of railway tracks has practically remained unchanged. Traditionally, rail tracks are placed on a ballast layer due to several reasons, including economy, rapid drainage, and high load bearing capacity. The primary function of ballast is to distributing dynamic track loads to sub-ballast and subgrade layers, while also providing lateral resistance and allowing for rapid drainage. Upon repeated trainloads, the ballast becomes fouled due to ballast degradation and the intrusion of fines which adversely affects the strength and deformation behaviour of ballast. This paper presents the use of three-dimensional discrete element method (DEM) in studying the shear behaviour of the fouled ballast subjected to direct shear loading. Irregularly shaped particles of ballast were modelled by grouping many spherical balls together in appropriate sizes to simulate representative ballast aggregates. Fouled ballast was modelled by injecting a specified number of miniature spherical particles into the void spaces. The DEM simulation highlights that the peak shear stress of the ballast assembly decreases and the dilation of fouled ballast increases with an increase level of fouling. Additionally, the distributions of contact force chain and particle displacement vectors were captured during shearing progress, explaining the formation of shear band and the evolutions of volumetric change of fouled ballast.