Background
Thalidomide is an immunomodulatory agent, which arrests angiogenesis. The mechanism of anti-angiogenic activity of thalidomide is not fully understood. As nitric oxide is involved in angiogenesis, we speculate a cross-talk between thalidomide and nitric oxide signaling pathway to define angiogenesis. The aim of present study is to understand the mechanistic aspects of thalidomide-mediated attenuation of angiogenesis induced by nitric oxide at the cellular level.
Methods
To study the cellular mechanism of thalidomide-mediated blocking of angiogenesis triggered by nitric oxide, we used two endothelial cell based models: 1) wound healing and 2) tube formation using ECV 304, an endothelial cell line. These cell-based models reflect pro-angiogenic events
in vivo
. We also studied the effects of thalidomide on nitric oxide mediated egg yolk angiogenesis. Thalidomide could block the formation of blood vessels both in absence and presence of nitric oxide. Thalidomide effects on migration of, and actin polymerization in, ECV 304 cells were studied at the single cell level using live cell imaging techniques and probes to detect nitric oxide.
Results
Results demonstrate that thalidomide blocks nitric oxide-mediated angiogenesis in egg yolk model and also reduces the number of tubes formed in endothelial cell monolayers. We also observed that thalidomide arrests wound healing in presence and absence of nitric oxide in a dose-dependent fashion. Additionally, thalidomide promotes actin polymerization and antagonizes the formation of membrane extensions triggered by nitric oxide in endothelial cells. Experiments targeting single tube structure with thalidomide, followed by nitric oxide treatment, show that the tube structures are insensitive to thalidomide and nitric oxide. These observations suggest that thalidomide interferes with nitric oxide-induced migration of endothelial cells at the initial phase of angiogenesis before cells co-ordinate themselves to form organized tubes in endothelial cells and thereby inhibits angiogenesis.
Conclusion
Thalidomide exerts inhibitory effects on nitric oxide-mediated angiogenesis by altering sub-cellular actin polymerization pattern, which leads to inhibition of endothelial cell migration.
Zeolite (ZSM-5) and functionalised zeolite blended polyphenylsulfone (PPSU) mixed matrix membranes (MMMs) were fabricated for comparing their performance with virgin PPSU.
The synergistic effects of polyacrylonitrile (PAN) and
nanokaolinite
particles were studied using PAN/nanokaolinite mixed-matrix membranes
(MMMs). Nanokaolinite was obtained from naturally available kaolin
clay by an intercalation/exfoliation method. The kaolinite nanoparticles
were added in varying compositions from 2.5 to 10 wt % at an increment
of 2.5 wt % to PAN in the presence of the solvent N,N′-dimethylformamide (DMF). The uniform
dispersion of nanokaolinite in the PAN matrix was achieved with the
help of ultrasonication. The PAN/nanokaolinite material was characterized
by attenuated-total-reflectance-infrared (ATR-IR) spectroscopy. Contact-angle
measurements showed increased hydrophilicity due to the nanokaolinite
addition that, in turn, helped reduce membrane fouling. Thermal stability
and miscibility were characterized using thermal gravimetric analysis
(TGA) and differential scanning calorimetry (DSC). The pure-water
permeability flux increased from 122.8 to 264.93 L m–2 h–1 with increasing nanokaolinite concentration
from 0 to 7.5 wt %. Rejection studies using protein showed an improved
rejection efficiency of 92.7%, which is higher than that of the neat
PAN membrane. PAN/nanokaolinite MMMs were also investigated in the
separation of synthetic rhodamine B dye with and without the macroligand
poly(diallyldimethylammonium chloride) (PDDA) for which the dye removal
efficiency and flux were compared. Nanokaolinite-based MMMs are an
inexpensive material and provide enhanced properties such as porosity,
hydrophilicity, thermal stability, rejection, and productivity.
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