ABSTRACT
In the past few decades, organic solvent nanofiltration (OSN) has attracted numerous researchers and broadly applied in various fields. Unlike conventional nanofiltration, OSN always faced a broad spectrum of solvents including polar solvents and non-polar solvents. Among those recently developed OSN membranes in lab-scale or widely used commercial membranes, researchers preferred to explore intrinsic materials or introduce nanomaterials into membranes to fabricate OSN membranes. However, the hydrophilicity of the membrane surface towards filtration performance was often ignored, which was the key factor in conventional aqueous nanofiltration. The influence of surface hydrophilicity on OSN performance was not studied systematically and thoroughly. Generally speaking, the hydrophilic OSN membranes performed well in the polar solvents while the hydrophobic OSN membranes work well in the non-polar solvent. Many review papers reviewed the basics, problems of the membranes, up-to-date studies, and applications at various levels. In this review, we have focused on the relationship between the surface hydrophilicity of OSN membranes and OSN performances. The history, theory, and mechanism of the OSN process were first recapped, followed by summarizing representative OSN research classified by surface hydrophilicity and types of membrane, which recent OSN research with its contact angles and filtration performance were listed. Finally, from the industrialization perspective, the application progress of hydrophilic and hydrophobic OSN membranes was introduced. We started with history and theory, presented many research and application cases of hydrophilic and hydrophobic OSN membranes, and discussed anticipated progress in the OSN field. Also, we pointed out some future research directions on the hydrophilicity of OSN membranes to deeply develop the effect made by membrane hydrophilicity on OSN performance for future considerations and stepping forward of the OSN industry.
ABSTRACT
ß-elemene, a plant-derived drug extracted from Curcuma wenyujin, has demonstrated marked antiproliferative effects on glioblastoma, while toxicity remains low. However, the underlying molecular mechanisms of the antitumor activity of ß-elemene remain to be elucidated. Previously, it was identified that the glia maturation factor ß (GMFß)/mitogen-activated protein kinase kinase (MAPK) 3/6/p38 pathway participates in the antiproliferative activity of ß-elemene on glioblastoma. In the present study, in order to illustrate the association of GMFß and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, U87 and U251 cells were treated with ß-elemene at various doses and for different durations, and the expression of phosphorylated ERK1/2 (p-ERK1/2), ERK1/2, B-cell lymphoma 2 (Bcl-2), Bcl2-associated X and survivin was examined by western blot analysis. Following treatment with ß-elemene and the ERK1/2 inhibitor PD98059, U87 cell viability was evaluated using a Cell Counting Kit-8 (CCK-8) assay, and the expression levels of Bcl-2 and survivin were examined by western blot analysis. GMFß was then downregulated by RNA interference in ß-elemene-treated U87 cells, and the effect of this on the expression of ERK1/2 and p-ERK1/2 was determined by western blot analysis. Finally, the chemosensitisation of U87 cells to temozolomide (TMZ) through ß-elemene was examined using the CCK-8 assay. The results demonstrated that ß-elemene inhibited the proliferation of U87 glioblastoma cells through the GMFßdependent inactivation of the ERK1/2-Bcl-2/survivin pathway. Furthermore, inhibition of ERK1/2 by PD98059 enhanced the antitumor effect of ß-elemene and impaired the expression levels of Bcl-2 and survivin. ß-elemene also increased the sensitivity of U87 glioblastoma cells to the chemotherapeutic TMZ, which was synergistically enhanced by PD98059. In conclusion, these results suggested that GMFß-dependent inactivation of the ERK1/2-Bcl-2/survivin pathway mediated the antiproliferative effect of ß-elemene on glioblastoma. Therefore, ß-elemene is a promising chemosensitizer or adjuvant therapeutic for TMZ against glioblastoma brain tumors.
Subject(s)
Antineoplastic Agents, Phytogenic/toxicity , Cell Proliferation/drug effects , Glia Maturation Factor/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Sesquiterpenes/toxicity , Cell Line, Tumor , Cell Survival/drug effects , Curcuma/chemistry , Curcuma/metabolism , Dacarbazine/analogs & derivatives , Dacarbazine/toxicity , Down-Regulation/drug effects , Drug Resistance, Neoplasm/drug effects , Flavonoids/pharmacology , Glia Maturation Factor/antagonists & inhibitors , Glia Maturation Factor/genetics , Glioblastoma/metabolism , Glioblastoma/pathology , Humans , Inhibitor of Apoptosis Proteins/metabolism , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Phosphorylation/drug effects , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA Interference , RNA, Small Interfering/metabolism , Survivin , TemozolomideABSTRACT
Accumulating evidence indicates that glioblastoma stem-like cells (GSCs) are key factors in tumour development, recurrence and chemoresistance. The impairment of stemness and the enhancement of differentiation contributes to the weakening of radiation and chemotherapy resistance of GSCs. We previously found that ß-elemene was an effective anti-glioblastoma agent and chemosensitizer. In this study, we examined the distribution of CD133(+) cells in human glioblastoma tissues by immunohistochemistry. Following treatment with ß-elemene, the formation of GSC spheres was investigated by manual counting, the proliferation of GSCs was measured with a Cell Counting Kit-8 (CCK-8) assay, and the dispersion of GSC spheres was observed with an inverted microscope. GSC spheres were treated with ß-elemene, and the expression levels of CD133, ATP-binding cassette subfamily G member 2 (ABCG2) and glial fibrillary acidic protein (GFAP) were examined by western blotting. After treatment with ß-elemene, the volumes and weights of GSC xenografts were measured, and the expression of CD133, ABCG2 and GFAP was evaluated through immunohistochemistry analysis. After treatment with ß-elemene and temozolomide (TMZ), GSC viability was examined by the CCK-8 assay, and the volumes and weights of xenografts were measured. We found that CD133(+) cells were assembled in some vascular walls and also sparsely distributed in other parts of glioblastoma tissues. ß-elemene decreased the formation of GSC spheres, dispersed GSC spheres and inhibited the proliferation of GSCs in vitro and in vivo. In the GSC spheres and xenografts treated with ß-elemene, the expression of CD133 and ABCG2 was significantly downregulated, and the expression of GFAP increased. Furthermore, the sensitivity of GSCs to TMZ was enhanced in vitro and in vivo. These results suggest that ß-elemene impaired the stemness of GSC spheres, promoted their differentiation and sensitized GSCs to TMZ. ß-elemene will hopefully become a valuable agent to enhance the effects of radiotherapy and chemotherapy.