Vascular-confined multi-passage discoidal nanoconstructs for the low-dose docetaxel inhibition of triple-negative breast cancer growth

Taxane efficacy in triple negative breast cancer(TNBC)is limited by insufficient tumor accumulation and severe off-target effects.Nanomedicines offer a unique opportunity to enhance the anti-cancer potency of this drug.Here,1,000 nm×400 nm discoidal polymeric nanoconstructs(DPN)encapsulating docetaxel(DTXL)and the near infrared compound Iipid-Cy5 were engineered.DPN were obtained by filling multiple times cylindrical wells in a poly(vinyl alcohol)template with a polymer mixture comprising poly(lactic-co-glycolic acid)(PLGA)and poly(ethylene glycol)diacrylate(PEG-DA)chains together with therapeutic and imaging agents.The resulting“multi-passage”DPN exhibited higher DTXL loading,Iipid-Cy5 stability,and stiffness as compared to the conventional"single-passage"approach.Confocal microscopy confirmed that DTXL-DPN were not taken up by MDA-MB-231 cells but would rather sit next to the cell membrane and slowly release DTXL thereof.Empty DPN had no toxicity on TNBC cells,whereas DTXL-DPN presented a cytotoxic potential comparable to free DTXL(IC₅₀=2.6 nM±1.0 nM vs.7.0 nM±1.09 nM at 72 h).In orthotopic murine models,DPN accumulated in TNBC more efficiently than free-DTXL.With only 2 mg/kg DTXL,intravenously administered every 2 days for a total of 13 treatments,DTXL-DPN induced tumor regression and were associated to an overall 80%survival rate as opposed to a 30%survival rate for free-DTXL,at 120 days.All untreated mice succumbed before 90 days.Collectively,this data demonstrates that vascular confined multi-passage DPN,biomimicking the behavior of circulating platelets,can efficiently deliver chemotherapeutic molecules to malignant tissues and effectively treat orthotopic TNBC at minimal taxane doses.     

Effect of food intake on protein quality measured in chicks by traditional or biochemical methods

Previous studies have shown that the activities of the hepatic enzymes xanthine dehydrogenase and nucleoside phosphorylase, as well as the uric acid excreted, can be used to determine the quality of the protein consumed in chickens, in a short time and using a small amount of the test protein. A common observation in protein quality evaluation is that the food intake of the control animals is considerably greater than that observed in those receiving proteins of low quality. Since this can affect the results, this study measured the quality of garbanzo bean and black bean proteins in chickens fed these beans ad libitum, feeding the bean diets at the level observed in the controls (soy protein+methionine) by enteral intubation or pair feeding the controls with the amount of food consumed by the chickens receiving the bean diets. In every case, protein quality was determined by protein efficiency ratio, net protein utilisation or the biochemical methods used in this study. The results showed that, when fed ad libitum, the animals assigned to the bean diets exhibited a lower food intake than the controls but, by tube feeding, food intake was made equal in both groups. Equal consumption, between these groups, was also obtained by reducing the amount of food offered to the controls to the levels measured in the groups assigned to the bean diets (pair feeding). These feeding strategies had a marked effect on growth, carcass protein content, protein catabolism and also in the results of protein quality. Thus, the control whose intake was reduced grew less, accumulated less protein in tissues and catabolised more of the protein consumed than the control fed ad libitum. In contrast, the chickens assigned to the bean diets, but whose food intake was increased by tube feeding, grew better, accumulated more protein in tissues and catabolised less protein. In general, the results of these experiments confirm the effectiveness of the biochemical methods for estimating protein quality and indicate that the protein quality of both garbanzo beans and black beans increased when it was measured at a food intake equivalent to that measured in the control animals. Since the overall purpose of this study was to evaluate techniques for protein quality determination meant to be applicable to humans nutrition rather than poultry nutrition, single proteins were used instead of combinations of proteins. © 1998 Society of Chemical Industry.     

Changes in phenolic composition of apple juices by HPLC with direct injection

An analytical procedure for the quantitative determination of the major polyphenols in apple juices which successfully employs a RP-HPLC system without prior treatment of the sample is described. Apple juices were clarified by microfiltration and ultrafiltration without previous treatment. Polyphenols monitored were influenced by clarification technology employed for stabilising the apple juices. The p-coumaric acid derivative was significantly affected by membrane type and filtration time, while (−)-epicatechin and phloridzin were influenced by filtration time. © 1998 Society of Chemical Industry.     

Assessing the antiproliferative effect of biogenic silver chloride nanoparticles on glioblastoma cell lines by quantitative image‐based analysis

Glioblastoma is the most life‐threatening tumour of the central nervous system. Temozolomide (TMZ) is the first‐choice oral drug for the treatment of glioblastoma, although it shows low efficacy. Silver nanoparticles (AgNPs) have been shown to exhibit biocidal activity in a variety of microorganisms, including some pathogenic microorganisms. Herein, the antiproliferative effect of AgCl‐NPs on glioblastoma cell lines (GBM02 and GBM11) and on astrocytes was evaluated through automated quantitative image‐based analysis (HCA) of the cells. The cells were treated with 0.1‐5.0 μg/ml AgCl‐NPs or with 9.7‐48.5 μg/ml TMZ. Cells that received combined treatment were also analysed. At a maximum tested concentration of AgCl‐NPs, GBM02 and GBM11, the growth decreased by 93% and 40%, respectively, following 72 h of treatment. TMZ treatment decreased the proliferation of GBM02 and GBM11 cells by 58% and 34%, respectively. Combinations of AgCl‐NPs and TMZ showed intermediate antiproliferative effects; the lowest concentrations caused an inhibition similar to that obtained with TMZ, and the highest concentrations caused inhibition similar to that obtained with AgCl‐NPs alone. No significant changes in astrocyte proliferation were observed. The authors’ findings showed that HCA is a fast and reliable approach that can be used to evaluate the antiproliferative effect of the nanoparticles at the single‐cell level and that AgCl‐NPs are promising agents for glioblastoma treatment.     

Spherical Silica Functionalized by 2-Naphthalene Methanol Luminophores as a Phosphorescence Sensor

Photoluminescence is known to have huge potential for applications in studying biological systems. In that respect, phosphorescent dye molecules open the possibility to study the local slow solvent dynamics close to hard and soft surfaces and interfaces using the triplet state (TSD: triplet state solvation dynamics). However, for that purpose, probe molecules with efficient phosphorescence features are required with a fixed location on the surface. In this article, a potential TSD probe is presented in the form of a nanocomposite: we synthesize spherical silica particles with 2-naphthalene methanol molecules attached to the surface with a predefined surface density. The synthesis procedure is described in detail, and the obtained materials are characterized employing transmission electron microscopy imaging, Raman, and X-ray photoelectron spectroscopy. Finally, TSD experiments are carried out in order to confirm the phosphorescence properties of the obtained materials and the route to develop phosphorescent sensors at silica surfaces based on the presented results is discussed.     

Dissimilarity of the oxidations of rapeseed and butter oil triacylglycerols and their mixtures in the absence of tocopherols

Although fatty acid composition is the most important attribute used to control oxidation stability, all edible oils are affected by lipid oxidation irrespective of whether they are highly unsaturated or not. The aim of the study was to compare the oxidation of rapeseed oil (RO) and butter oil (BO) triacylglycerols (TAGs) and their mixtures containing 10% or 20% of the other. Oxidation of the TAGs at 40°C was followed by formation of primary and secondary products. Statistical methods were used to interpret the data. The RO and BO TAGs and their mixtures began to oxidise without any induction periods. In the RO TAGs more hydroperoxides and p‐anisidine reactive compounds were formed than in the BO TAGs. The BO TAGs oxidised more than would be expected by their fatty acid composition. High susceptibility of BO TAGs to oxidation was caused by the easy breakdown of their hydroperoxides. Heptadienal and heptenal were specific products of oxidised RO TAGs and heptanal and nonenal of oxidised BO TAGs. Mixtures of RO and BO TAGs behaved according to which was dominant in the mixture. However, as little as 10% of RO or BO TAG introduced its specific oxidation products to the mixture. © 1999 Society of Chemical Industry     

Alleviating mechanical degradation of hexacyanoferrate via strain locking during Na+insertion/extraction for full sodium ion battery

Generation of large strains upon Na+intercalation is one of the prime concerns of the mechanical degradation of Prussian blue(PB)and its analogs.Structural cons...     

Mutations That Affect the Surface Expression of TRPV6 Are Associated with the Upregulation of Serine Proteases in the Placenta of an Infant

Recently, we reported a case of an infant with neonatal severe under-mineralizing skeletal dysplasia caused by mutations within both alleles of the TRPV6 gene. One mutation results in an in frame stop codon (R₅₁₀stop) that leads to a truncated, nonfunctional TRPV6 channel, and the second in a point mutation (G₆₆₀R) that, surprisingly, does not affect the Ca²⁺ permeability of TRPV6. We mimicked the subunit composition of the unaffected heterozygous parent and child by coexpressing the TRPV6 G₆₆₀R and R₅₁₀stop mutants and combinations with wild type TRPV6. We show that both the G₆₆₀R and R₅₁₀stop mutant subunits are expressed and result in decreased calcium uptake, which is the result of the reduced abundancy of functional TRPV6 channels within the plasma membrane. We compared the proteomic profiles of a healthy placenta with that of the diseased infant and detected, exclusively in the latter two proteases, HTRA1 and cathepsin G. Our results implicate that the combination of the two mutant TRPV6 subunits, which are expressed in the placenta of the diseased child, is responsible for the decreased calcium uptake, which could explain the skeletal dysplasia. In addition, placental calcium deficiency also appears to be associated with an increase in the expression of proteases.     

Comparison of Aging Resistance and Antimicrobial Properties of Ethylene–Norbornene Copolymer and Poly(Lactic Acid) Impregnated with Phytochemicals Embodied in Thyme (Thymus vulgaris) and Clove (Syzygium aromaticum)

The effects of plant-based extracts on the solar aging and antimicrobial properties of impregnated ethylene–norbornene (EN) copolymer and poly(lactic acid) (PLA) were investigated. In this study, the impregnation yield of polyolefin, lacking in active centers capable of phytochemical bonding, and polyester, abundant in active sides, was measured. Moreover, two different extracts plentiful in phytochemicals—thyme (TE) and clove (CE)—were employed in the solvent-based impregnation process. The effect of thymol and eugenol, the two main compounds embodied in the extracts, was studied as well. Interestingly, oxidation induction times (OIT) for the impregnation of EN with thyme and clove extracts were established to be, respectively, 27.7 and 39.02 min, which are higher than for thymol (18.4 min) and eugenol (21.1 min). Therefore, an aging experiment, mimicking the full spectrum of sunlight, was carried out to investigate the resistance to common radiation of materials impregnated with antioxidative substances. As expected, the experiment revealed that the natural extracts increased the shelf-life of the polymer matrix by inhibiting the degradation processes. The aging resistance was assessed based on detected changes in the materials’ behavior and structure that were examined with Fourier-transform infrared spectroscopy, contact angle measurements, color quantification, tensile tests, and hardness investigation. Such broad results of solar aging regarding materials impregnated with thyme and clove extracts have not been reported to date. Moreover, CE was found to be the most effective modifying agent for enabling material with antimicrobial activity against Escherichia coli to be obtained.