The Secretome of Human Neonatal Mesenchymal Stem Cells Modulates Doxorubicin-Induced Cytotoxicity: Impact in Non-Tumor Cells

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.     

Platelet-Derived Extracellular Vesicles for Regenerative Medicine

Extracellular vesicles (EVs) present a great potential for the development of new treatments in the biomedical field. To be used as therapeutics, many different sources have been used for EVs obtention, while only a few studies have addressed the use of platelet-derived EVs (pEVs). In fact, pEVs have been shown to intervene in different healing responses, thus some studies have evaluated their regenerative capability in wound healing or hemorrhagic shock. Even more, pEVs have proven to induce cellular differentiation, enhancing musculoskeletal or neural regeneration. However, the obtention and characterization of pEVs is widely heterogeneous and differs from the recommendations of the International Society for Extracellular Vesicles. Therefore, in this review, we aim to present the main advances in the therapeutical use of pEVs in the regenerative medicine field while highlighting the isolation and characterization steps followed. The main goal of this review is to portray the studies performed in order to enhance the translation of the pEVs research into feasible therapeutical applications.     

Synergistic effects between κ-carrageenan and locust bean gum on physicochemical properties of edible films made thereof

The development of mixed systems, formed by locust bean gum (LBG), and κ-carrageenan (κ-car) can offer new interesting applications such as the development of edible films with particular properties. κ-car/LBG blend films with different ratios were developed, and their effects on films’ physical properties were assessed. Thermogravimetric analysis (TGA), X-ray diffraction (XRD) patterns, dynamic mechanical analysis (DMA) and Fourier-transform infrared (FTIR) spectroscopy techniques were used to highlight the interactions between the two polysaccharides. The addition of κ-car to LBG improved the barrier properties of the films leading to a decrease of water vapor permeability (WVP). Improved values of elongation-at-break (EB) were registered when the ratio of κ-car/LBG was 80/20 or 40/60 (% w/w). Moreover, the κ-car/LBG blend films enhance the tensile strength (TS) compared to κ-car and LBG films. FTIR results suggested that hydrogen bonds interactions between κ-car and LBG have a great influence in films’ properties e.g. moisture content, WVP. Therefore, different κ-car/LBG ratios can be used to tailor edible films with enhanced barrier and mechanical properties.     

Lipid Droplet Biosynthesis Impairment through DGAT2 Inhibition Sensitizes MCF7 Breast Cancer Cells to Radiation

Breast cancer is the most frequent cancer in women worldwide and late diagnosis often adversely affects the prognosis of the disease. Radiotherapy is commonly used to treat breast cancer, reducing the risk of recurrence after surgery. However, the eradication of radioresistant cancer cells, including cancer stem cells, remains the main challenge of radiotherapy. Recently, lipid droplets (LDs) have been proposed as functional markers of cancer stem cells, also being involved in increased cell tumorigenicity. LD biogenesis is a multistep process requiring various enzymes, including Diacylglycerol acyltransferase 2 (DGAT2). In this context, we evaluated the effect of PF-06424439, a selective DGAT2 inhibitor, on MCF7 breast cancer cells exposed to X-rays. Our results demonstrated that 72 h of PF-06424439 treatment reduced LD content and inhibited cell migration, without affecting cell proliferation. Interestingly, PF-06424439 pre-treatment followed by radiation was able to enhance radiosensitivity of MCF7 cells. In addition, the combined treatment negatively interfered with lipid metabolism-related genes, as well as with EMT gene expression, and modulated the expression of typical markers associated with the CSC-like phenotype. These findings suggest that PF-06424439 pre-treatment coupled to X-ray exposure might potentiate breast cancer cell radiosensitivity and potentially improve the radiotherapy effectiveness.     

家庭住宅 法国拉马蒂埃尔

正几个世纪以来,不同的地理环境一直都采用这类封闭的庭院形式——每一次都根据当地气候、风俗习惯和建筑实践进行改造。作为一种在建筑物内捕捉户外景观的手段,庭院由建筑内部结构决定。流畅的庭院不但提供内外部隐私保护,而且也不断地向外延伸,积极融入周边景观。该住宅遵守严格的分区指导方针,同时通过在屋顶上扩建自然植物区系与景观融合。坐落在橄榄树林、松树和葡萄园内,该住宅充分利用坡地,从而获得可持续的拓展和种植     

Sustainability assessment of dwellings – a comparison of methodologies

Building sustainability assessment tools (BSATs) aim to promote and rank the sustainability of building stock. This paper makes a deep comparative analysis on how dwellings are evaluated by five BSAT and one performance-based design tool. The comparison is based on: (i) the purpose of assessment; (ii) sustainability dimensions considered; (iii) indicators addressed; (iv) life cycle phases considered by the indicators; (v) type of indicators; (vi) measurements; (vii) aggregation processes; and (vii) life cycle phases during which the assessment was carried out. The evaluation showed that the scope of BSAT varies significantly as well as the life cycle phases addressed in the assessment. Financial issues are often excluded from the assessment. None of the schemes is totally quantitative or qualitative in their measurement system; all have different types of indicators and different ways to assess them. This research provides researchers and stakeholders with important inside knowledge on the tools that allow the development and construction of more sustainable buildings.     

Value creation through project risk management

Risk management is a common and widely adopted project practice. Practitioners use risk management based on a common assumption that risk management adds value to projects. Yet, in the complex and ambiguous environment of a project, value is often subjective. If this is the case, then how do stakeholders perceive project risk management to create value? This paper presents a literature review and an empirical study of project risk management as a means of creating value. The empirical study is based on interviews, analyzed through qualitative analysis, to unravel the subjective value of project risk management. Specifically, we addressed how practitioners perceived the connection between project risk management practices and value creation. We found that stakeholders' perceptions of value played an important role in how value was created through project risk management. What a stakeholder perceives to be important, such as the prospective outcomes of a project, influences the perceived value of a given project risk management practice. The empirical findings indicate the need for a contextualized understanding of the value of project risk management, and thereby provide a more nuanced view of the variety of forms through which project risk management can create value. The findings question the “universal ideal” of PRM value creation portrayed in the academic and practitioner literature.     

Application of the Nernst-Planck approach to lead ion exchange in Ca-loaded Pelvetia canaliculata

Ca-loaded Pelvetia canaliculata biomass was used to remove Pb²⁺ in aqueous solution from batch and continuous systems. The physicochemical characterization of algae Pelvetia particles by potentiometric titration and FTIR analysis has shown a gel structure with two major binding groups - carboxylic (2.8 mmol g⁻¹) and hydroxyl (0.8 mmol g⁻¹), with an affinity constant distribution for hydrogen ions well described by a Quasi-Gaussian distribution. Equilibrium adsorption (pH 3 and 5) and desorption (eluents: HNO₃ and CaCl₂) experiments were performed, showing that the biosorption mechanism was attributed to ion exchange among calcium, lead and hydrogen ions with stoichiometry 1:1 (Ca:Pb) and 1:2 (Ca:H and Pb:H). The uptake capacity of lead ions decreased with pH, suggesting that there is a competition between H⁺ and Pb²⁺ for the same binding sites. A mass action law for the ternary mixture was able to predict the equilibrium data, with the selectivity constants α_Ca^H = 9 ± 1 and α_Ca^Pb = 44 ± 5, revealing a higher affinity of the biomass towards lead ions. Adsorption (initial solution pH 4.5 and 2.5) and desorption (0.3 M HNO₃) kinetics were performed in batch and continuous systems. A mass transfer model using the Nernst-Planck approximation for the ionic flux of each counter-ion was used for the prediction of the ions profiles in batch systems and packed bed columns. The intraparticle effective diffusion constants were determined as 3.73 × 10⁻⁷ cm² s⁻¹ for H⁺, 7.56 × 10⁻⁸ cm² s⁻¹ for Pb²⁺ and 6.37 × 10⁻⁸ cm² s⁻¹ for Ca²⁺.