Protective role of Decylubiquinone against secondary melanoma at lung in B16F10 induced mice by reducing E-cadherin expression and ameliorating ROCKII-Limk1/2-Cofiliin mediated metastasis.

Melanoma is one of the most consequential skin cancer with a rising death incidences. Silent but belligerent nature of metastatic sprouting is the leading cause of melanoma related mortality. Invasion of metastatic cells and re-expression of E-Cadherin play the crucial role in the establishment of secondary tumor at distal sites. Thus, manipulation of tumor cell invasion in parallel to regulation of E-Cadherin expression can be considered as potential anti-metastatic strategy. Evidences suggested key role of reactive oxygen species associated ROCK activities in the modulation of metastatic invasion via F-actin stabilization. Here, we first-time report Decylubiquinone, a dietary Coenzyme Q10 analog, as an effective attenuator of pulmonary metastatic melanoma in C57BL/6 mice. Current study depicted detailed molecular interplay associated with Decylubiquinone mediated phosphorylation of ROCKII at Tyr722 along with reduced phosphorylation of ROCKII Ser1366 leading to suppression of Limk1/2-Cofilin-F-actin stabilization axis that finally restricted B16F10 melanoma cell invasion at metastatic site. Analysis further deciphered the role of HNF4α as its nuclear translocation modulated E-Cadherin expression, the effect of reactive oxygen species dependent ROCKII activity in secondarily colonized B16F10 melanoma cells at lungs. Thus unbosoming of related signal orchestra represented Decylubiquinone as a potential remedial agent against secondary lung melanoma.

Activity of ROCKII not ROCKI promotes pulmonary metastasis of melanoma cells via modulating Smad2/3-MMP9 and FAK-Src-VEGF signalling.

Rho-associated coiled-coil kinase (ROCK) inhibition decreases tumourogenic growth, proliferation and angiogenesis. Multifaceted evidences are there about the role of ROCK in cancer progression, but isoform specific analysis in secondary pulmonary melanoma is still unaddressed. This study explored the operating function of ROCK in the metastasis of B16F10 mice melanoma cell line. Inhibition by KD-025 indicated dual wielding role of ROCKII as it is associated with the regulation of MMP9 activity responsible for extra-cellular matrix (ECM) degradation as well as angiogenic invasion as an effect of Src-FAK-STAT3 interaction dependent VEGF switching. We found the assisting role of ROCKII, not ROCKI in nuclear localization of Smads that effectively increased MMP9 expression and activity (p < 0.01). This cleaved the protein components of ECM thereby played a crucial role in tissue remodeling at secondary site during establishment of metastatic tumour. ROCKII phosphorylation at Ser1366 as an activation of the same was imprinted essential for oncogenic molecular bagatelle leading to histo-architectural change of pulmonary tissue with extracellular matrix degradation as a consequence of invasion. Direct correlation of pROCKIISer1366 with MMP9 as well as VEGF expression in vivo studies cue to demonstrate the importance of pROCKIISer1366 inhibition in the context of angiogenesis, and metastasis suggesting ROCKII signaling as a possible target for the treatment of secondary lung cancer specially in metastatic melanoma.

Cathepsin B mediated scramblase activation triggers cytotoxicity and cell cycle arrest by andrographolide to overcome cellular resistance in cisplatin resistant human hepatocellular carcinoma HepG2 cells.

Andrographolide regimen in single or in combination with anticancer drugs is a promising new strategy to reverse chemoresistance in heaptocellular carcinoma. Apoptosis inducing factor (AIF) may regulate a complementary, cooperative or redundant pathway, along with caspase cascades. Despite these findings, mechanisms underlying caspase-dependent and-independent signaling pathways in andrographolide -induced apoptosis in cisplatin-resistant human hepatocellular carcinoma cell line (HepG2CR) remain unclear. Andrographolide treatment effectively reduced NF-κß nuclear localization by modulating protein kinase A- protein phosphatase 2 A- Iκß kinase (PKA/PP2 A/IKK) axis that in turn maintains initiator caspase8 activity. Lysosomal distribution of tBid stimulates cytosolic cathepsin B resulting accumulation of truncated-AIF with induction in scramblase mediated phosphatidylserine exposure in HepG2CR cells. Andrographolide treatment thereby switch on subG1 phase arrest by modulating cellular check points (cyclin A, B, cyclin dependent kinase-1) cueing to the apoptosis event. Collectively, this study suggested antineoplastic potential of andrographolide through PKA/PP2 A/IKK pathway in HepG2CR cells.

Modeling of Polyelectrolyte Adsorption from Micellar Solutions onto Biomimetic Substrates.

Depositing cationic polyelectrolytes (PEs) from micellar solutions that include surfactants (SU) onto surfaces is a rich, complex, highly relevant, and challenging topic that covers a broad field of practical applications (e.g., from industrial to personal care). The role of the molecular architecture of the constituents of the PEs are often overruled, or at least and either, underestimated in regard to the surface properties. In this work, we aim to evaluate the effect of a model biomimetic surface that shares the key characteristics of the extreme surface of hair and its concomitant chemo- and physisorbed properties onto the deposition of a complex PEs:SU system. To tackle out the effect of the molecular architecture of the PEs, we consider (i) a purely linear and hydrophilic PE (P100) and (ii) a PE with lateral amphiphilic chains (PegPE). Using numerical self-consistent field calculations, we show that the architecture of the constituents interfere with the surface properties in a nonintuitive way such that, depending on the amphiphilicity and hydrophilicity of the PEs and the hydrophobicity of the surface, a re-entrant adsorbing transition can be observed, the lipid coverage of the model hair surface being the unique control parameter. Such a behavior is rationalized by the anticooperative associative properties of the coacervate micelles in solution, which is also controlled by the architecture of the PEs and SU. We now expect that PEs adsorption, as a rule, is governed by the molecular details of the species in solution as well as the surface specificities. We emphasize that molecular realistic modeling is essential to rationalize and optimize the adsorption process of, for example, polymer conditioning agents in water-rinsed cosmetic or textile applications.

A liquid CO2-compatible hydrocarbon surfactant: experiment and modelling.

Surfactants soluble in liquid CO2 are rare and knowledge on interfacial and self-assembly behaviour is fragmented. We found that polyoxyethylene (5) isooctylphenyl ether is interfacially active at the water-liquid CO2 interface. Water-liquid CO2 interfacial tension was measured at various surfactant concentrations at 50 bar and 283 K using the pendant drop method, and a CMC like cusp was observed at a surfactant concentration of ~50 mM in the bulk liquid CO2. This system was modelled applying the self-consistent field theory of Scheutjens and Fleer (SF-SCF). We use a free-volume approach, wherein the chemical potential of the vacancies was linked to the pressure and the molecules were described using a freely-jointed chain model on a united atom level. The model indicates that typically the water-vapour interface is wet by CO2. Interestingly, a window of partial wetting was identified at the water-vapour interface as a function of the chemical potential of the surfactant. The second-order nature of both wetting transitions is attributed to the close proximity to the critical point of the CO2-vapour system. Furthermore, the SF-SCF theory was used to study the self-assembly of the surfactant in bulk CO2 or water, focusing on the three-phase coexistence, that is at P/Psat = 1. Above ~40 mM in the CO2-rich phase, the theory indicates stable water swollen reverse micelles with an aggregation number of ~100. The analysis further shows the stability of compressible CO2-swollen surfactant bilayers in the bulk water phase at elevated surfactant concentrations. Finally it was found that the critical reverse micellar concentration (in liquid CO2) increases and the aggregation number decreases with increasing pressure.

Interfacial tension and wettability in water-carbon dioxide systems: experiments and self-consistent field modeling.

This paper presents experimental and modeling results on water-CO2 interfacial tension (IFT) together with wettability studies of water on both hydrophilic and hydrophobic surfaces immersed in CO2. CO2-water interfacial tension (IFT) measurements showed that the IFT decreased with increasing pressure and the negative slopes of IFT-pressure isotherms decreased with increasing temperature. Water contact angle on a cellulose surface (hydrophilic) immersed in CO2 increased with pressure, whereas the water contact angle on a hydrophobic surface such as hexamethyl disilazane (HMDS) coated silicon surface was almost independent of pressure. These experimental findings were augmented by modeling using the self-consistent field theory. The theory applies the lattice discretization scheme of Scheutjens and Fleer, with a discretization length close to the size of the molecules. In line with this we have implemented a primitive molecular model, with just small variations in the molar volume. The theory makes use of the Bragg-Williams approximation and has binary Flory-Huggins interaction parameters (FH) between CO2, water, and free volume. Using this model, we generated the complete IFT-pressure isotherms at various temperatures, which coincided well with the trends reported in literature, that is, the water-CO2 interfacial tension decreased with increasing pressure for pressures ≤100 bar and became independent of pressure >100 bar. The transition point occurred at higher pressures with increasing temperature. At three-phase coexistence (water-CO2-free volume) and at the water-vapor interface (water-free volume), we always found the CO2 phase in between the water-rich and free volume-rich phases. This means that for the conditions studied, the water-vapor interface is always wet by CO2 and there are no signs of a nearby wetting transition. Calculation of the water contact angle on a solid surface was based on the computed adsorption isotherms of water from a vapor or from a pressurized CO2-rich phase and analysis of surface pressures at water-vapor or water-CO2 coexistence. The results matched reasonably well with the experimental contact angle data. Besides, we also computed the volume fraction profiles of the CO2, H2O, and the V phase, from which the preferential adsorption of CO2 near the hydrophilic surface was deduced.

Effect of surface roughness and softness on water capillary adhesion in apolar media.

The roughness and softness of interacting surfaces are both important parameters affecting the capillary condensation of water in apolar media, yet are poorly understood at present. We studied the water capillary adhesion between a cellulose surface and a silica colloidal probe in hexane by AFM force measurements. Nanomechanical measurements show that the Young's modulus of the cellulose layer in water is significantly less (~7 MPa) than in hexane (~7 GPa). In addition, the cellulose surface in both water and hexane is rather rough (6-10 nm) and the silica probe has a comparable roughness. The adhesion force between cellulose and silica in water-saturated hexane shows a time-dependent increase up to a waiting time of 200 s and is much (2 orders of magnitude) lower than that expected for a capillary bridge spanning the whole silica probe surface. This suggests the formation of one or more smaller bridges between asperities on both surfaces, which is confirmed by a theoretical analysis. The overall growth rate of the condensate cannot be explained from diffusion mediated capillary condensation alone; thin film flow due to the presence of a wetting layer of water at both the surfaces seems to be the dominant contribution. The logarithmic time dependence of the force can also be explained from the model of the formation of multiple capillary bridges with a distribution of activation times. Finally, the force-distance curves upon retraction show oscillations. Capillary condensation between an atomically smooth mica surface and the silica particle show less significant oscillations and the adhesion force is independent of waiting time. The oscillations in the force-distance curves between cellulose and silica may stem from multiple bridge formation between the asperities present on both surfaces. The softness of the cellulose surface can bring in additional complexities during retraction of the silica particle, also resulting in oscillations in the force-distance curves.

Colloidal interactions in liquid CO2--a dry-cleaning perspective.

Liquid CO(2) is a viable alternative for the toxic and environmentally harmful solvents traditionally used in dry-cleaning industry. Although liquid CO(2) dry-cleaning is being applied already at a commercial scale, it is still a relatively young technique which poses many challenges. The focus of this review is on the causes of the existing problems and directions to solve them. After presenting an overview of the state-of-the-art, we analyze the detergency challenges from the fundamentals of colloid and interface science. The properties of liquid CO(2) such as dielectric constant, density, Hamaker constant, refractive index, viscosity and surface tension are presented and in the subsequent chapters their effects on CO(2) dry-cleaning operation are delineated. We show, based on theory, that the van der Waals forces between a model soil (silica) and model fabric (cellulose) through liquid CO(2) are much stronger compared to those across water or the traditional dry-cleaning solvent PERC (perchloroethylene). Prevention of soil particle redeposition in liquid CO(2) by electrostatic stabilization is challenging and the possibility of using electrolytes having large anionic parts is discussed. Furthermore, the role of different additives used in dry-cleaning, such as water, alcohol and surfactants, is reviewed. Water is not only used as an aid to remove polar soils, but also enhances adhesion between fabric and soil by forming capillary bridges. Its role as a minor component in liquid CO(2) is complex as it depends on many factors, such as the chemical nature of fabrics and soil, and also on the state of water itself, whether present as molecular solution in liquid CO(2) or phase separated droplets. The phenomena of wicking and wetting in liquid CO(2) systems are predicted from the Washburn-Lucas equation for fabrics of various surface energies and pore sizes. It is shown that nearly complete wetting is desirable for good detergency. The effect of mechanical action and fluid dynamic conditions on dry-cleaning is analyzed theoretically. From this it follows that in liquid CO(2) an order of magnitude higher Reynold's number is required to exceed the binding forces between fabric and soil as opposed to PERC or water, mainly due to the strong van der Waals forces and the low viscosity of CO(2) at dry-cleaning operational conditions.