Doxorubicin (Dox) is one of the most widely used treatments for breast cancer, although limited by the well-documented cardiotoxicity and other off-target effects. Mesenchymal stem cell (MSC) secretome has shown immunomodulatory and regenerative properties, further potentiated under 3D conditions. This work aimed to uncover the effect of the MSC-derived secretome from 3D (CM3D) or 2D (CM2D) cultures, in human malignant breast cells (MDA-MB-231), non-tumor breast epithelial cells (MCF10A) and differentiated AC16 cardiomyocytes, co-treated with Dox. A comprehensive proteomic analysis of CM3D/CM2D was also performed to unravel the underlying mechanism. CM3D/CM2D co-incubation with Dox revealed no significant differences in MDA-MB-231 viability when compared to Dox alone, whereas MCF10A and AC16 viability was consistently improved in Dox+CM3D-treated cells. Moreover, neither CM2D nor CM3D affected Dox anti-migratory and anti-invasive effects in MDA-MB-231. Notably, Ge-LC-MS/MS proteomic analysis revealed that CM3D displayed protective features that might be linked to the regulation of cell proliferation (CAPN1, CST1, LAMC2, RANBP3), migration (CCN3, MMP8, PDCD5), invasion (TIMP1/2), oxidative stress (COX6B1, AIFM1, CD9, GSR) and inflammation (CCN3, ANXA5, CDH13, GDF15). Overall, CM3D decreased Dox-induced cytotoxicity in non-tumor cells, without compromising Dox chemotherapeutic profile in malignant cells, suggesting its potential use as a chemotherapy adjuvant to reduce off-target side effects. 相似文献
This work aimed to incorporate prebiotic FOS from yacon in apple slices using vacuum impregnation (VI). Three FOS concentrations (10.3, 14.1 and 18.9 g per 100 g of dry matter (DM)), two temperatures (25 and 35 °C), reuse of extracts and stability of the impregnated slices were evaluated. The highest impregnation level (30.5 g per 100 g DM) was obtained at 35 °C with 14.1% FOS extract while levels of common sugars were reduced. Total phenolics and ABTS antioxidant capacity (AC) slightly decreased while ORAC AC was reduced by 55%. Reuse of the impregnation solution in successive cycles after restoring the FOS level maintained the FOS concentration and profile (GF2–GF7), sugars and phenolic antioxidants. FOS in apple slices remained stable during 4 week storage, while aw, colour and fracture point changed during storage. This work demonstrated the feasibility of yacon FOS to improve the functional properties of dehydrated apple slices. 相似文献
The addition of nisin into a gelatin matrix can change properties of the film. The aim of this work was to develop gelatin-based films containing different nisin concentrations in order to study their influence on the film's antimicrobial and physical properties and their rheological properties as a film-forming solution (FFS). The FFS was characterised by rheological assays, and the gelatin-based active films were characterised and assessed by the effects of nisin concentrations on their various properties, including antimicrobial activity. Nisin's concentration affected not only its viscoelastic properties of FFS but also its film solubility in water, film surface roughness and light barrier. The addition of nisin also slightly modified the water contact angle and the mechanical properties of the gelatin films. Finally, the films demonstrated activity against Staphylococcus aureus and Listeria monocytogenes at concentrations above 56 mg of nisin g−1 of gelatin. 相似文献
In this study, the suitability of fumed silica nanoparticles (FNS) and its derivatives (amino-modified FNS (AFNS), cyanuric chloride-activated AFNS (CCAFNS) and epoxy-modified FNS (GFNS)), for covalent immobilisation of two commercial protease preparations Alcalase® and Flavourzyme® was investigated. The highest hydrolytic activities of immobilised preparations were 25 IU g−1 support (Alcalase-GFNS) and 2.95 IU g−1 support (Flavourzyme-CCAFNS). Furthermore, the immobilised preparations showed 43% and 20% of initial specific activities of commercial protease preparations, respectively. Flavourzyme-CCAFNS also exhibited the highest exopeptidase activity of 22.83 L-pNAU g−1 support. Finally, these two nanobiocatalysts were successfully applied for hydrolysis of sunflower meal protein isolate (SMPI), providing two times higher hydrolysis yields in comparison to free enzymes, justifying the applied immobilisation process. Namely, the highest hydrolysis yield (30%) was gained by the sequential hydrolysis with Alcalase-GFNS and Flavourzyme-CCAFNS, which resulted in the formation of small hydrophobic and hydrophilic peptides, ≤5 kDa, confirmed by HPLC analysis and electrophoretic separation. 相似文献
Based on research carried out at 67 tailings dams in Spain: (1) tailings dams contain alternating sedimentary layers with contractive and dilative geomechanical behaviours; (2) tailings saturate quickly but drain more than 10 times slower due to the high-suction capacity of the porous sediments (2–300 MPa); and (3) over the long-term, a stationary flow regime is attained within a tailings basin. Four temporal and spatial conditions must all be present for a tailing dams flow failure to occur: (1) the tailings must experience contractive behaviour; (2) the tailings must be fully saturated; (3) the effective stress due to static or dynamic load must approach zero; and (4) the shear stress must exceed the tailings residual shear stress. Our results also indicate that the degree of saturation (Sr) is the most influential factor controlling dam stability. The pore-pressure coefficient controls geotechnical stability: when it exceeds 0.5 (Sr = 0.7), the safety factor decreases dramatically. Therefore, controlling the degree of tailings saturation is instrumental to preventing dam failures, and can be achieved using a double drainage system, one for the unconsolidated foundation materials and another for the overlying tailings.
Gluten-free products have emerged in response to the increasing prevalence of gluten-related disorders, namely celiac disease. Therefore, the quantification of gluten in products intended for consumption by individuals who may suffer from these pathologies must be accurate and reproducible, in a way that allows their proper labeling and protects the health of consumers. Immunochemical methods have been the methods of choice for quantifying gluten, and several kits are commercially available. Nevertheless, they still face problems such as the initial extraction of gluten in complex matrices or the use of a standardized reference material to validate the results. Lately, other methodologies relying mostly on mass spectrometry-based techniques have been explored, and that may allow, in addition to quantitative analysis, the characterizationof gluten proteins. On the other hand, although the level of 20 mg/kg of gluten detected by these methods is sufficient for a product to be considered gluten-free, its immunogenic potential for celiac patients has not been clinically validated. In this sense, in vitro and in vivo models, such as the organoid technology applied in gut-on-chip devices and the transgenic humanized mouse models, respectively, are being developed for investigating both the gluten-induced pathogenesis and the treatment of celiac disease. Due to the ubiquitous nature of gluten in the food industry, as well as the increased prevalence of gluten-related disorders, here we intend to summarize the available methods for gluten quantification in food matrices and for the evaluation of its immunogenic potential concerning the development of novel therapies for celiac disease to highlight active research and discuss knowledge gaps and current challenges in this field. 相似文献
Experiments conducted in vitro and in vivo, as well as clinical trials for hypoglycemic therapeutics, support the hypoglycemic properties of the lectin γ-conglutin, a Lupinus seed storage protein, by a mechanism not yet been clarified. Structural studies established that binding of γ-conglutin, in native and denatured form, to insulin occurs by a strong binding that resists rupture when 0.4 M NaCl and 0.4 M galactose are present, suggesting that strong electrostatic interactions are involved. Studies on binding of γ-conglutin in native and denatured form to HepG2 membrane glycosylated receptors were conducted, which reveal that only the native form of γ-conglutin with lectin activity is capable of binding to these receptors. Glycosylated insulin receptors were detected on purified HepG2 cell membranes and characterized by 1D and 2D analyses. Preclinical assays with male mice (CD-1) indicated that native and denatured γ-conglutins display antihyperglycemic effect, decreasing glucose in blood comparable after 120 min to that exhibited by the animal group treated with metformin, used to treat T2D and used as a positive control. Measurement of organ injury/functional biomarkers (hepatic, pancreatic, renal, and lipid profile) was comparable to that of metformin treatment or even better in terms of safety endpoints (pancreatic and hepatic biomarkers). 相似文献
This study deals with the effects of climate fluctuations and anthropogenic impacts on fisheries of Paraná River over the last 100 years. It is the first attempt to appraise the influence of hydro‐climatic and anthropogenic variables on the population changes of the most important inland fisheries of Argentina. Datasets covering more than eight decades (1935–2016) of a number of frequent and abundant commercial species inhabiting the main channel as well as the large floodplain of Paraná River were used. Our results suggest that fish catches and structure changed over time. Long and short‐term changes and reductions were closely related to fluctuations of 18 hydro‐climatic variables. Positive effects on the ichthyofauna were recorded during humid periods (1930–1940 and 1970–2000), when the frequency of large spring–summer floods increased. An increase in anthropic impacts (accounted for with nine variables) were recorded during the last two decades. We highlight the usefulness of the approach to support the management of the resources, ensuring sustainability of commercial fish assemblages and the long‐term conservation of biodiversity in big rivers. 相似文献
Versioning is an important aspect of web service development, which has not been adequately addressed so far. In this article, we propose extensions to WSDL and UDDI to support versioning of web service interfaces at development-time and run-time. We address service-level and operation-level versioning, service endpoint mapping, and version sequencing. We also propose annotation extensions for developing versioned web services in Java. We have tested the proposed solution for versioning in two real-world environments and identified considerable improvements in service development and maintenance efficiency, improved service reuse, and simplified governance. 相似文献
The autocorrelation function (acf) of powered absolute returns and their cross-correlations with original returns are derived, for any value of the power parameter, in the context of long-memory stochastic volatility models with leverage effect and Gaussian noises. These autocorrelations and cross-correlations generalize and correct recent results on the acf of squared and absolute returns. 相似文献