HIF-1α and Pro-Inflammatory Signaling Improves the Immunomodulatory Activity of MSC-Derived Extracellular Vesicles

Despite the strong evidence for the immunomodulatory activity of mesenchymal stromal cells (MSCs), clinical trials have so far failed to clearly show benefit, likely reflecting methodological shortcomings and lack of standardization. MSC-mediated tissue repair is commonly believed to occur in a paracrine manner, and it has been stated that extracellular vesicles (EVs) secreted by MSCs (EVMSC) are able to recapitulate the immunosuppressive properties of parental cells. As a next step, clinical trials to corroborate preclinical studies should be performed. However, effective dose in large mammals, including humans, is quite high and EVs industrial production is hindered by the proliferative senescence that affects MSCs during massive cell expansion. We generated a genetically modified MSC cell line overexpressing hypoxia-inducible factor 1-alpha and telomerase to increase the therapeutic potency of EVMSC and facilitate their large-scale production. We also developed a cytokine-based preconditioning culture medium to prime the immunomodulatory response of secreted EVs (EV_MSC-T-HIF^c). We tested the efficacy of this system in vitro and in a delayed-type hypersensitivity mouse model. MSC-T with an HIF-1α-GFP lentiviral vector (MSC-T-HIF) can be effectively expanded to obtain large amounts of EVs without major changes in cell phenotype and EVs composition. EV_MSC-T-HIF^c suppressed the proliferation of activated T-cells more effectively than did EVs from unmodified MSC in vitro, and significantly blunted the ear-swelling response in vivo by inhibiting cell infiltration and improving tissue integrity. We have developed a long-lived EV source that secretes high quantities of immunosuppressive EVs, facilitating a more standard and cost-effective therapeutic product.     

The assessment of ceramic and mixed recycled aggregates for high strength and low shrinkage concretes

Very few studies on recycled aggregate concretes (RC) have been extended to the use of recycled ceramic and mixed aggregates in relation with high strength concretes. In the main they concentrate only on the analysis of the physical and mechanical properties. This study deals with the investigation of the influence that different percentages (up to 30% substitution for natural aggregates) of high porous ceramic and mixed recycled aggregates have over the plastic, autogenous and drying shrinkage of the concretes. The physical and mechanical properties as well as the chloride resistance were also determine in order to assess the viability of the use of ceramic and mixed recycled aggregates in high strength concretes. The results revealed that the employment of highly porous recycled aggregates reduced the plastic and autogenous shrinkage values of the concrete with respect to those obtained by conventional concrete (CC). Although the total drying shrinkage of the recycled concrete proved to be 25% higher than that of the CC concrete, the CC concrete had in fact a higher shrinkage value than that of the RC from 7 to 150 days of drying. It can be concluded that the RC concrete produced employing up to 30% of fine ceramic aggregates (FCA, with 12% of absorption capacity) achieved the lowest shrinkage values and higher mechanical and chloride ion resistance. In addition, the concrete produced with low percentage (10–15%) of recycled mixed aggregates also had similar properties to conventional concrete.     

Influence of the processing parameters and composition on the thermal stability of PLA/nanoclay bio‐nanocomposites

Poly(lactic acid) (PLA) is one the most promising bio‐based and biodegradable polymer. However, its low thermal stability limits the range of applications and complicates its transformation via the most industrial common processes. The novelty of this work is studying the thermal stability of PLA and PLA/clay nanocomposites during use, as a function of the composition and using a wide range of extrusion and injection moulding processing parameters. To improve the thermal stability of the PLA, laminar silicates containing different organomodifications have been added (Cloisite 20A and Cloisite 30B). The results show that the processing conditions and composition define the morphology of the bio‐nanocomposites, which plays key role in defining final thermal properties of the material. In general, clays improve the thermal stability of the processed material, increasing the degradation temperature and decreasing the degradation rate under a wide range of processing conditions. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40747.     

Illicit drug consumption estimations derived from wastewater analysis: A critical review

The consumption of illicit drugs causes indisputable societal and economic damage. Therefore it is necessary to know their usage levels and trends for undertaking targeted actions to reduce their use. Recently, a new approach (namely sewage epidemiology) was developed for the estimation of illicit drug use based on measurements of urinary excreted illicit drugs and their metabolites in untreated wastewater. This review aims at critically evaluating the published literature and identifying research gaps of sewage epidemiology. Firstly, the existing analytical procedures for the determination of the four most used classes of illicit drugs worldwide (cannabis, cocaine, opiates and amphetamine-like stimulants) and their metabolites in wastewater are summarized and discussed. The focus lies on the sample preparation and on the analysis with chromatographic techniques coupled to mass spectrometry. Secondly, back-calculations used to transform measured concentrations in wastewater (in ng/L) into an amount of used illicit drug (in g/day per 1000 inhabitants or doses/day per 1000 inhabitants) are discussed in detail for the four groups of illicit drugs. Sewage epidemiology data from Spain, Belgium, UK, Italy, Switzerland and USA are summarized and compared with data from international organisations, such as the European Monitoring Centre for Drug and Drug Addiction (EMCDDA) and the United Nations Office on Drugs and Crime (UNODC). The results derived from wastewater analysis show in general good agreement with existing prevalence data (percentage of a population that uses illicit drugs at a given time) and demonstrate the potential of sewage epidemiology. However, this review confirms that future work should focus on further optimisation and standardisation of various important parameters (e.g. sample collection and back-calculations). In the future, sewage epidemiology could be used in routine drug monitoring campaigns as a valuable tool in addition to the classical socio-epidemiological studies for the determination of local, national and international illicit drug use.     

Peroxisome proliferation as a biomarker in environmental pollution assessment

Peroxisome proliferators comprise a heterogeneous group of compounds known for their ability to cause massive proliferation of peroxisomes and liver carcinogenesis in rodents. In recent years it has become evident that other animals may be threatened by peroxisome proliferators, in particular aquatic organisms living in coastal and estuarine areas. These animals are exposed to a variety of pollutants of industrial, agricultural and urban origin which are potential peroxisome proliferators. Both laboratory and field studies have shown that phthalate ester plasticizers, PAHs and oil derivatives, PCBs, certain pesticides, bleached kraft pulp and paper mill effluents, alkylphenols and estrogens provoke peroxisome proliferation in different fish or bivalve mollusc species. The response appears to be mediated by peroxisome-proliferator activated receptors, members of the nuclear receptor family, recently cloned in fish. Based on these results it is proposed that peroxisome proliferation could be used as a biomarker of exposure to a variety of pollutants in environmental pollution assessment. This is illustrated by a case study in which mussels, used worldwide as sentinels of environmental pollution, were transplanted from reference to contaminated areas and vice versa. In mussels native to an area polluted with PAHs and PCBs, peroxisomal acyl-CoA oxidase (AOX) activity and peroxisomal volume density were 2-3 fold and 5-fold higher, respectively, compared to the reference site. When animals were transplanted to the polluted station, with increased concentration of organic xenobiotics, a concomitant significant increase of AOX was recorded. Conversely, in animals transplanted to the cleaner station, AOX activity and peroxisomal volume density decreased significantly. These results indicate that peroxisome proliferation is a rapid (i.e., two days) and reversible response to pollution in mussels. Before peroxisome proliferation can be implemented as a biomarker in biomonitoring programs, a well-defined protocol should be established and validated in intercalibration and quality assurance programmes. Furthermore, the influence of biotic and abiotic factors, some of which are known to affect peroxisome proliferation (season, tide level, interpopulation and interindividual variability), should be taken into consideration. The possible hepatocarcinogenic effects as well as the potential adverse effects on reproduction, development, and growth of peroxisome proliferators are unknown in aquatic organisms, thus providing a challenge for future investigations.     

Background arsenic concentrations in Southeastern Spanish soils

The arsenic content in the province of Granada (SE Spain) was quantified, based on 93 soils at two different depths and their corresponding parent materials. The arsenic concentrations fit a log-normal distribution. Four different statistical procedures to estimate the arsenic background range in the region were tested. Upper background limits clearly exceeded limits reported for natural soils when based on the Tukey box plot or means and standard deviations of the dataset (M+/-2sdev) or of the calculated distribution function (Mf+/-2sigma) but not when based on median values (Md+/-2MAD). The relative cumulative frequency curve not only adequately estimates the background range but also delivers a clear and detailed visualisation of the data distribution and identifies subpopulations with specific background ranges related to combinations of parent materials and degree of soil development.     

Application of different macrokinetic models to the isothermal crystallization of PP/talc blends

The crystallization kinetics of neat polypropylene (PP) and of PP composites containing 2, 5, 10 and 30 wt% of talc was studied. Various kinetic equations, namely the Avrami, Velisaris–Seferis, Dietz, Khanna, Malkin models, have been applied to describe the kinetics of crystallization from the melt state under isothermal conditions. The results suggested that experimental data of the Avrami’s exponent, “n”, is approximately 2, meaning that the crystallization of PP alone and of its composites with talc is a two-dimensional growth process. Experimental data of PP alone can be best described by the Avrami, Velisaris–Seferis, Dietz and Malkin models; whereas the models that in the case of composites better correlate their behavior are those of Velisaris–Seferis, followed by Avrami’s.