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Microplastics released from textiles during the washing process represent the most prevalent type of microparticles found in different environmental compartments and ecosystems around the world. Release of microfibres during the washing process of synthetic textiles is due to the mechanical and chemical stresses that clothes undergo in washing machines. Several washing process parameters, conditions, formulations of laundering additives have been correlated to microfibre release and some of them have been identified to affect microfibre release during washing process, while no correlation has been evaluated between microfibre release and washing load. In the present study, microfibre release was evaluated as function of the washing load in a real washing process, indicating a progressive decrease of microfibre release with increasing washing load. The quantity of released microfibres increased by around 5 times by decreasing the washing load due to a synergistic effect between water-volume to fabric ratio and mechanical stress during washing. Moreover, the higher mechanical stress to which the fabric is subjected in the case of a low washing load, hinders the discrimination of the effect on the release of other washing parameters like the type of detergent and laundry additives used.

Hypothesis In the last years, several cost-effective technologies have been investigated to functionalize textile substrates for large scale applications and industrial production. However, several limitations of currently used technologies still restrict the capability to form functional coatings finely controlling the textile surface properties and topographic structure of the coatings at sub-micrometric scale. Experiments Herein, we introduced a new non-conventional electrofluidodynamic technology – based on the use of electrostatic forces to polymer/composite solutions – for the application onto textile fabrics of functional coatings. With respect to particle/fibrous coatings usually applied through conventional electrospraying/electrospinning processes, the proposed approach is able to realize homogeneous and continuous coatings by a one-step process, imparting tailored functionalities to the textiles surfaces through the use of customized experimental setups. Findings We proved that this process can be successfully used to realize functional coatings based on a bioderived polymer, namely polylactic acid (PLA), on commercial woven polyamide (PA) fabrics. In addition, due to the usage of graphene derivatives or photochromic dyes in combination with PLA, the applied coatings are able to confer peculiar functionalities (i.e., electrical conductivity, photochromic properties, etc.) to polyamide fabrics, as proved by SEM, conductivity and UV irradiation measurements, for innovative applications in smart textiles, e-health and wearable electronics.

Duodenal hyperpermeability and low-grade inflammation in functional dyspepsia is potentially related to duodenal acid exposure. We aimed to evaluate in healthy volunteers the involvement of mast cell activation on the duodenogastric reflex and epithelial integrity during duodenal acidification. This study consisted of 2 parts: (1) Duodenal infusion of acid or saline during thirty minutes in a randomized, double-blind cross-over manner with measurement of intragastric pressure (IGP) using high resolution manometry and collection of duodenal biopsies to measure epithelial barrier function and the expression of cell-to-cell adhesion proteins. Mast cells and eosinophils were counted and activation and degranulation status were assessed. (2) Oral treatment with placebo or mast cell stabilizer disodiumcromoglycate (DSCG) prior to duodenal perfusion with acid, followed by the procedures described above. Compared with saline, acidification resulted in lower IGP (P

APEH is a ubiquitous and cytosolic serine protease belonging to the prolyl oligopeptidase (POP) family, playing a critical role in the processes of degradation of proteins through both exo- and endopeptidase events. Endopeptidase activity has been associated with protein oxidation; however, the actual mechanisms have yet to be elucidated. We show that a synthetic fragment of GDF11 spanning the region 48–64 acquires sensitivity to the endopeptidase activity of APEH only when the methionines are transformed into the corresponding sulphoxide derivatives. The data suggest that the presence of sulphoxide-modified methionines is an important prerequisite for the substrates to be processed by APEH and that the residue is crucial for switching the enzyme activity from exo- to endoprotease. The cleavage occurs on residues placed on the C-terminal side of Met(O), with an efficiency depending on the methionine adjacent residues, which thereby may play a crucial role in driving and modulating APEH endoprotease activity.

A new sustainable solution to water and air pollution based on spontaneously adsorbent materials is presented in this work. For the first time, high surface area micro/mesoporous hyper-crosslinked resins (XDV) were engineered in hydrogels and aerogels based on reduced graphene oxide (rGO) and montmorillonite (MMT). Hydrogels and aerogels were obtained through a mild and environmental-friendly procedure based on graphene oxide (GO) reduction by vitamin C and eventual lyophilization. In all systems, the XDV specific surface area (SSA) is completely exposed and exploitable for adsorption application in water and air. rGO/XDV and rGO/MMT/XDV aerogels containing 50 wt% of XDV show hierarchical porosity and high SSA, reaching values of 1000–1200 m2/g. Hydrogels and aerogels show tuneable polar character on the basis of their composition, which is exploitable to develop customized adsorbents for water and air remediation from aromatic and polar pollutants. Indeed, while hydrogels containing MMT show high adsorption capacity towards cationic dyes such as rhodamine 6G, rGO and rGO/XDV systems show marked affinity for toluene. In all cases, the embedding of the hyper-crosslinked resins in the hydrogels and aerogels further enhances their adsorption capacity, with uptakes up to 482 mg/g of rhodamine 6G for rGO/MMT/XDV hydrogels and up to 500 mg/g of toluene vapours for rGO/XDV aerogels. Both systems show regenerable adsorption properties with efficiency higher than 96% over 5 adsorption/desorption cycles.

Nuclear factor erythroid 2–related factor2 (Nrf2) is a redox-sensitive transcription factor. Its activation by low dietary intake of ligands leads to antioxidant effects (eustress), while pro-oxidant effects (oxidative distress) may be associated with high doses. NADPH oxidases (NOXs) and the mitochondrial electron transport chain are the main sources of intracellular ROS, but their involvement in the biphasic/hormetic activity elicited by Nrf2 ligands is not fully understood. In this study, we investigated the involvement of NOX expression and mitochondrial function in the hormetic properties of omega-3 typically present in fish oil (FO) and conjugated linoleic acid (CLA) in the mouse liver. Four-week administration of FO, at both low and high doses (L-FO and H-FO) improves Nrf2-activated cyto-protection (by phase 2 enzymes), while a significant increase in respiration efficiency occurs in the liver mitochondria of H-FO BALB/c mice. Eustress conditions elicited by low dose CLA (L-CLA) are associated with increased activity of phase 2 enzymes, and with higher NOX1-2, mitochondrial defences, mitochondrial uncoupling protein 2 (UCP2), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression, compared with controls. Steatogenic effects (lipid accumulation and alteration of lipid metabolism) elicited by high CLA (H-CLA) elicited that are associated with oxidative distress, increased mitochondrial complex I/III activity and reduced levels of phase 2 enzymes, in comparison with L-CLA-treated mice. Our results confirm the steatogenic activity of H-CLA and first demonstrate the role of NOX1 and NOX2 in the eustress conditions elicited by L-CLA. Notably, the negative association of the Nrf2/PGC-1α axis with the different CLA doses provides new insight into the mechanisms underlying the hormetic effect triggered by this Nrf2 ligand.

Fluorene-based molecules exhibit significant nonlinear optical responses and multiphoton absorption in the visible region, which, combined with the high fluorescence quantum yield in organic solvents, could make this class of materials potentially engaging in diverse photonics applications. Thus, herein, we have determined the two-photon absorption (2PA) of oligofluorenes containing three, five, and seven repetitive units by employing the wavelength-tunable femtosecond Z-scan technique. Our outcomes have shown that the 2PA cross-section in oligofluorenes presents an enhanced value of around 18 GM per Neff, in which Neff is the effective number of π-electrons, for the pure 2PA allowed transition (11Ag-like → 21Ag-like). Furthermore, a weak 2PA transition was observed in the same spectral region strongly allowed by one-photon absorption (11Ag-like → 11Bu-like). This last result suggests a molecular symmetry perturbation, probably induced by the molecular disorder triggered by the increase of moieties in the oligofluorene structure. We have calculated the permanent dipole moment difference related to the lowest-energy transition using the Lippert-Matagaformalism and the 2PA sum-over-states approach to confirm this assumption. Moreover, we have estimated the fundamental limits for the 2PA cross-section in oligofluorenes.

Cartilage is a specialized tissue that has a relatively homogenous endogenous cell population but a diverse extracellular matrix (ECM) with depth-dependent mechanical properties. Cartilage repair remains an elusive clinical goal, with biological interventions preferred to arthroplasty in younger patients. Osteochondral transplantation (OCT) has emerged for the treatment of cartilage defects and osteoarthritis. Fresh allografts stored at 4 °C for periods of time have been utilized, though matrix and cell viability loss remained an issue. To address this, several studies have developed media formulations to maintain cartilage explants in vitro. One promising factor for these applications is sprifermin, a human-recombinant fibroblast growth factor-18 which stimulates chondrocyte proliferation and matrix synthesis and is in clinical trials for osteoarthritis treatment. We hypothesized that addition of sprifermin during storage would maintain the unique depth-dependent mechanical profile of cartilage explants, a feature of cartilage not often evaluated. In this study, cartilage explants were maintained for up to 6 weeks with or without a weekly 24-hour exposure to sprifermin (100 ng/ml) and the compressive modulus was assessed. Results showed that sprifermin treated samples maintained their depth-dependent mechanical profile through 3 weeks, whereas untreated samples lost their mechanical integrity over 1 week of culture. Sprifermin also affected ECM balance by maintaining levels of extracellular collagen and suppression of matrix metalloproteinase production. These findings support the use of sprifermin as a medium additive for OCT allografts during in vitro storage, and present a potential mechanism where sprifermin may impact a functional characteristic of cartilage in repair strategies.

An overproduction of free radicals or reactive oxygen species, often due to environmental factors, can alter the DNA structure and irreversibly modify proteins and lipids in the living cells. The superoxide anion (O2−) is one of the strongest oxidant molecules produced under oxidative stress conditions but it can be neutralized by the action of the enzymes SuperOxide Dismutases (SODs). In all the human tissues, SODs are essential for the prevention of serious diseases and the protection against oxidative stress damages. In the dermo-cosmetic sector, SODs have found promising applications, but their use is limited due to the loss of activity following the addition of the enzyme in the skin care formulas and the exposure of the skin to UV radiations and heat. Extremophile organisms, which proliferate in extreme physical and/or geochemical conditions, represent a potential source of stable SOD enzymes, able to function even in harsh conditions of high temperature, acid pH and long UV exposures. In the present study we investigated on a Mn-SOD deriving from the extremophilic bacterium Deinococcus radiodurans and, after its expression in E.coli, the Mn-SOD was characterized in terms of chemical and physical properties. Its extraordinary features in terms of UV resistance prompted us to investigate further about its potential applications in the dermo-cosmetic sector. It was expressed in Solanum lycopersicum (tomato) cell cultures with the main goal of developing a new ingredient, capable of keeping its ROS neutralizing activity once exposed to UV radiations and even when added to skin care formulas.

In this work, we propose the synthesis of a novel bromine chalcone (E)-3-(2-bromophenyl)-1-(2-((phenylsulfonyl)amine))phenyl)prop-2-en-1-one (BRC) that has been crystallized by the slow evaporation...

Organophosphorus chlorpyrifos (CPF) is currently considered an endocrine disruptor (ED), as it can imitate hormone actions both in vitro and in vivo. We recently reported that CPF induces migration and invasion in 2D cultures and changes the expression of key molecular markers involved in epithelial mesenchymal transition in MCF-7 and MDA-MB-231 cell lines. In this study, we investigated whether CPF could behave as a predisposing factor for tumors to become more metastatic and aggressive using 3D culture models. In MCF-7 cells, 0.05 μM CPF induced an increase in the number and size of mammospheres via estrogen receptor alpha (ERα) and c-SRC. Furthermore, 0.05 μM CPF increased the area of spheroids generated from MCF-7 cells, induced invasion using both Matrigel® and type 1 collagen matrices, and increased cell migration capacity via ERα in this 3D model. In turn, 50 μM CPF increased cell migration capacity and invasion using type 1 collagen matrix. In monolayers, CPF increased the phosphorylation and membrane translocation of c-SRC at both concentrations assayed. CPF at 0.05 μM boosted p-AKT, p-GSK-3β and p-P38. While p-AKT rose in a ERα-dependent way, p-GSK-3β was dependent on ERα- and c-SRC, and p-P38 was only dependent on c-SRC. On the other hand, the increase in p-AKT and p-P38 induced by 50 μM CPF was dependent on the c-SRC pathway. We also observed that 0.05 μM CPF increased IGF-1R and IRS-1 expression and that 50 μM CPF induced IGF-1Rβ phosphorylation. In the MDA-MB-231 cell line, 0.05 and 50 μM CPF increased p-c-SRC. Finally, p-AKT and p-GSK-3β were also induced by CPF at 0.05 and 50 μM, and an increase in p-P38 was observed at 50 μM. Taken together, these data provide support for the notion that CPF may represent a risk factor for breast cancer development and progression.

In this study, microparticles of bionanomaterials were obtained by polyvinylpyrrolidone, montmoril-lonite, and zinc oxide bionanosystems produced through solution intercalation technique combined with a spray-drying process, aiming for possible application as drug delivery systems. The final microparticles obtained were evaluated in terms of their production yield, which varies between 39.2% and 56.9%. Thermal analysis showed no major changes in Tg of the nanocomposites, compared to the pure PVP polymer. Scanning electron microscopy analysis revealed a pseudo-spherical shape and confirmed the micrometric size of the microparticles. Transmission electron microscopy analysis corroborated the embedding of montmorillonite and ZnO within the polymer phase. Nuclear magnetic resonance and X-rays diffraction were used to study the nanoparticles dispersion, indicating a predominant intercalated morphology. This study suggests that the applied methodology is suitable for the high yields synthesis of nanocomposites PVP based microparticles with uniform size and shape, which can be promising for the production of a new drug delivery system.

In this study, a combined experimental and theoretical study of the nonlinear optical properties (NLO) of two chalcone derivatives, (E)-3-(2-methoxyphenyl)-1-(2-(phenylsulfonylamine)phenyl)prop-2-en-1-one (MPSP) and (E)-3-(3-nitrophenyl)-1-(2-(phenylsulfonylamine)phenyl)prop-2-en-1-one (NPSP), in DMSO is reported. The single crystal structures of the compounds, which differ only by the type and position of one substituent, were grown using the slow evaporation technique, and the main structural differences are discussed. The two-photon absorption and first-order hyperpolarizability measurements were performed via the Z-scan technique and hyper-Rayleigh scattering experiment in DMSO. The theoretical calculations were performed using the Density Functional Theory (DFT) at the CAM-B3LYP/6-311++G(d,p) level, and the sum-over-states (SOS) approach in both static and dynamic cases. Besides the electron conjugation achieved by the aromatic rings, olefins, and carbonyl groups, both compounds have a nearly flat chalcone backbone, which is believed to contribute to the nonlinear optical properties. MPSP and NPSP have different positions, even though they have roughly the same conformation and form C–H⋯O interactions. For several studied frequencies, the HRS first hyperpolarizability values for MPSP are greater than those for NPSP, indicating that in most cases the NLO properties of MPSP are better. The comparison among the theoretical and experimental HRS first hyperpolarizability results showed a good agreement. In addition, the two-dimensional second order nonlinear optical spectra obtained from the sum-over-states model indicate good second-order NLO responses of the two chalcone derivatives under external fields. Our findings are important not only to show the potential nonlinear optical application of the two new compounds but also to gain an insight into how different chemical compositions might affect the crystal structures and physico-chemical properties.

Oxidative stress is a key mediator of autoimmune/neurodegenerative disorders. The antioxidant/anti-inflammatory effect of a synthetic conjugated linoleic acid (CLA) mixture in MRL/MpJ-Fas lpr mice (MRL/lpr), an animal model of neuropsychiatric lupus, was previously associated with the improvement of nuclear factor-E2-related factor 2 (Nrf2) defenses in the spleen and liver. However, little is known about the neuroprotective ability of a CLA mixture. This study investigated the age-dependent progression of oxidative stress and the hyperactivation of redox-sensitive compensatory pathways (macroautophagy, Nrf2) in old/diseased MRL/lpr mice brains and examines the effect produced by dietary CLA supplementation. Disrupted redox homeostasis was evidenced in the blood, liver, and brain of 21- to 22-week-old MRL/lpr (Old) mice compared with 8- to 10-week-old MRL/lpr (Young) animals. This alteration was associated with significant hyperactivation of compensatory mechanisms (macroautophagy, Nrf2, and astrocyte activation) in the brains of Old mice. Five-week daily supplementation with CLA (650 mg/kg-1 body weight) of 16-week-old (CLA+Old) mice diminished all the pathological hallmarks at a level comparable to Young mice or healthy controls (BALB/c). Such data demonstrated that MRL/lpr mice can serve as a valuable model for the evaluation of the effectiveness of neuroprotective drugs. Notably, the preventive effect provided by CLA supplementation against age-associated neuronal damage and hyperactivation of compensatory mechanisms suggests that the activation of an adaptive response is at least in part accountable for its neuroprotective ability.

Dietary supplementation with pure cis9, trans11 isomer of Conjugated Linoleic Acid –known as Rumenic Acid (RA)– improves cytoprotective defenses downstream through the activation of nuclear factor-E2-related factor-2(Nrf2). This capability, when Rumenic Acid is consumed in the form of foods, is still unknown. The ability of standard (St) or cow milk naturally-enriched in RA (En) to activate Nrf2 pathway and its impact on dextran sodium sulfate (DSS)-induced colitis was comparatively evaluated. Activity of Nrf2 pathway was investigated in colonic tissue of BALB/c mice, receiving 4-week supplement with skimmed milk (SK), St or St reinforced with pure RA (RSt) providing increasing RA dose (0, 124 or 404 mg RA/kg-1 b.w, respectively). Next, the anti-oxidant/ anti-inflammatory effect produced by St or En treatment (383 mg RA/kg-1 b.w.) was explored. Finally, macroscopic and histomorphologic features of colitis were evaluated in animals challenged with 5% (w/v) DSS, at the end of St or En treatment. Significant activation of Nrf2 pathway is associated with RSt and En intake (P

Loranthus europaeus is a well-known and important medicinal plant, with a long history of traditional medicine use. Several studies showed that it contains many bioactive compounds with a wide range of pharmacological effects. In light of these past researches, L. europaeus were chosen to consider its potential antimicrobial action. To this aim, different protocols were performed to selectively extract protein compounds, from L. europaeus yellow fruits, and evaluate the antimicrobial activity against four phytopathogenic fungi (Aspergillus niger, Alternaria spp., Penicillium spp., Botritis cinereus) and a number of foodborne bacterial pathogens (Listeria monocytogenes, Staphylococcus aureus strains, Salmonella Typhimurium and Escherichia coli) by using serial dilutions and colony formation assays. Results evidenced no antifungal activity but a notable bactericidal efficiency of a crude protein extract against two foodborne pathogens, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values between 0.2 and 0.5 mg/mL, being S. aureus strains the most susceptible bacteria. Moreover, a strong bactericidal activity against S. aureus M7 was observed by two partially purified protein fractions of about 600 and 60 kDa molecular mass in native conditions. Therefore, these plant protein extracts could be used as natural alternative preventives to control food poisoning diseases and preserve foodstuff avoiding health hazards of chemically antimicrobial applications.

Corrosion inhibitors are largely exploited for the development of highly performing polymeric active coatings. One of the major drawbacks, however, relies in their UV sensitivity, which may compromise their ability to effectively prevent corrosion processes. This issue is particularly relevant in the field of cultural heritage preservation, in which polymeric active coating which are able to ensure a reliable and long-lasting protection against corrosion are highly needed. Besides proving that UV-induced photodegradation impressively lowers the corrosion inhibition ability of benzotriazole (BTA), in the present work we show that this phenomenon can be largely prevented by exploiting inorganic nanocarriers. More specifically, BTA molecules loaded into functionalized mesoporous silica nanoparticles are preserved from photodegradation and released in the host coating only in the presence of acid-related external stimuli. Accelerated corrosion tests carried out on a commercial acrylic-based coating containing engineered mesoporous silica nanoparticles loaded with BTA demonstrated that the developed system possesses an excellent anticorrosion ability.

Sandy beaches represent environmental compartments particularly vulnerable to litter pollution, and they reflect the magnitude of pollution of adjacent compartments: water and coastal areas. The substitution of conventional polymers by biodegradable materials is generally considered as an alternative for reducing environmental accumulation of plastic debris. The present study is aimed to investigate the degradation of poly(lactic acid), poly (?-caprolactone), poly(butylenesuccinate adipate) and poly(3-hydroxybutyrate) buried in sand for 267 days, simulating them as beach litter. The analysed polyesters showed different degradation mechanisms and kinetics. PLA is mainly subjected to weathering by physical aging; after an initial faster degradation of the amorphous phase, PCL showed a decrease of its degradation rate; similarly to PCL, the degradation of PBSA started from the amorphous phase; PHB is clearly subjected to biological degradation. The degradation trend of the investigated materials in sand decreased in the order PHB > PBSA > PCL > PLA. PLA, PCL and PBSA did not undergo complete degradation in sand during the testing time.

Absorption and relaxation dynamics of electronic states of free-base, Co(II), Cu(II) and Zn(II) porphyrins bearing a β-(2,2-difluoro-1,3,2-dioxaborinin-5-yl) group were investigated in dimethyl sulfoxide by using distinct time-resolved spectroscopic techniques. Furthermore, excited state absorption cross-section spectra were determined by combining white light continuum Z-Scan and transient absorption techniques. In the case of the free-base (2H) and Zn(II) porphyrins, we were able to quantify singlet–triplet conversion by analyzing the evolution of time-resolved fluorescence. Relaxation lifetimes from the excited to the ground state were observed in both porphyrins at nanosecond time scale. However, for Co(II) and Cu(II) metalloporphyrins it was observed in the picosecond time scale through femtosecond transient absorption, indicating that both compounds relax back to the ground state only by internal conversion processes. Co(II) and Cu(II) heavy atoms seem to prohibit the radiative and intersystem crossing processes.

Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function., Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät; 19

Chlorpyrifos (CPF) is one of the most frequently used pesticide in extensive agriculture around the world and can be incorporated by humans and animals with possible consequences on health. The effects of this pesticide on carcinogenesis are not clear and there is no consensus concerning the risks of this compound. In previous work, we demonstrated that CPF induces proliferation of breast cancer cells both in vivo and in vitro. In this work we investigate whether CPF promotes the epithelial-mesenchymal transition (EMT) in breast cancer cells. Herein, we demonstrate that 50 μM CFP induces invasion in MCF-7 and MDA-MB-231 cells. In addition, 0.05 and 50 μM CPF increases migration in both cell lines. In MCF-7 cells, 0.05 and 50 μM CPF increase the metalloprotease MMP2 expression and decrease E-Cadherin and β-Catenin expression diminishing their membrane location. Furthermore, 50 μM CPF induces Vimentin expression and Slug nuclear translocation in MCF-7 cells. 0.05 and 50 μM CPF increase MMP2 gelatinolytic activity and expression, decrease β-Catenin expression and increase Vimentin expression in MDA-MB-231 cells. Inhibition of the oncoprotein c-Src reverses all the effects induced by CPF in MDA-MB-231 but not in MCF-7 indicating that c-Src is a kinase with a crucial role in the cells which grow in an estrogen-independent way. In MCF-7 cells both c-Src and estrogen receptor alpha must be blocked to completly inhibit the CPF-mediated effects. Our results show for the first time that the exposure to subthreshold concentrations of CPF promotes the modulation of EMT-molecular markers and pathways. These results, together with the ubiquitous distribution of the pesticide CPF, make it of utmost importance to take measures to minimize the risk of exposure to this compound. Fil: Lasagna, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Hielpos, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Ventura, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Mardirosian, Mariana Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Martín, G.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Miret, Noelia Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina Fil: Randi, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina Fil: Núñez, M.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Cocca, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina

Serine hydrolases play crucial roles in many physiological and pathophysiological processes and a panel of these enzymes are targets of approved drugs. Despite this, most of the human serine hydrolases remain poorly characterized with respect to their biological functions and substrates and only a limited number of in vivo active inhibitors have been so far identified. Acylpeptide hydrolase (APEH) is a member of the prolyl-oligopeptidase class, with a unique substrate specificity, that has been suggested to have a potential oncogenic role. In this study, a set of peptides was rationally designed from the lead compound SsCEI 4 and in vitro screened for APEH inhibition. Out of these molecules, a dodecapeptide named Ala 3 showed the best inhibitory effects and it was chosen as a candidate for investigating the anti-cancer effects induced by inhibition of APEH in SAOS-2 cell lines. The results clearly demonstrated that Ala 3 markedly reduced cell viability via deregulation of the APEH-proteasome system. Furthermore, flow cytometric analysis revealed that Ala 3 anti-proliferative effects were closely related to the activation of a caspase-dependent apoptotic pathway. Our findings provide further evidence that APEH can play a crucial role in the pathogenesis of cancer, shedding new light on the great potential of this enzyme as an attractive target for the diagnosis and the quest for selective cancer therapies.

Breast cancer is the most common cancer type in females worldwide. Environmental exposure to pesticides affecting hormonal homeostasis does not necessarily induce DNA mutations but may influence gene expression by disturbances in epigenetic regulation. Expression of long interspersed nuclear element-1 (LINE-1) has been associated with tumorigenesis in several cancers. In nearly all somatic cells, LINE-1 is silenced by DNA methylation in the 5́′UTR and reactivated during disease initiation and/or progression. Strong ligands of aryl hydrocarbon receptor (AhR) activate LINE-1 through the transforming growth factor-β1 (TGF-β1)/Smad pathway. Hexachlorobenzene (HCB) and chlorpyrifos (CPF), both weak AhR ligands, promote cell proliferation and migration in breast cancer cells, as well as tumor growth in rat models. In this context, our aim was to examine the effect of these pesticides on LINE-1 expression and ORF1p localization in the triple-negative breast cancer cell line MDA-MB-231 and the non-tumorigenic epithelial breast cell line NMuMG, and to evaluate the role of TGF-β1 and AhR pathways. Results show that 0.5 μM CPF and 0.005 μM HCB increased LINE-1 mRNA expression through Smad and AhR signaling in MDA-MB-231. In addition, the methylation of the first sites in 5́′UTR of LINE-1 was reduced by pesticide exposure, although the farther sites remained unaffected. Pesticides modulated ORF1p localization in MDA-MB-231: 0.005 μM HCB and 50 μM CPF increased nuclear translocation, while both induced cytoplasmic retention at 0.5 and 5 μM. Moreover, both stimulated double-strand breaks, enhancing H2AX phosphorylation, coincidentally with ORF1p nuclear localization. In NMuMG similar results were observed, since they heighten LINE-1 mRNA levels. CPF effect was through AhR and TGF-β1 signaling, whereas HCB action depends only of AhR. In addition, both pesticides increase ORF1p expression and nuclear localization. Our results provide experimental evidence that HCB and CPF exposure modify LINE-1 methylation levels and induce LINE-1 reactivation, suggesting that epigenetic mechanisms could contribute to pesticide-induced breast cancer progression. Fil: Miret, Noelia Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina Fil: Zappia, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Altamirano, Gabriela Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Pontillo, Carolina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina Fil: Zárate, Lorena Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina Fil: Gomez, Ayelen Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Lasagna, Marianela. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisótopos; Argentina Fil: Cocca, Claudia Marcela. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Radioisótopos; Argentina Fil: Kass, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Salud y Ambiente del Litoral. Universidad Nacional del Litoral. Instituto de Salud y Ambiente del Litoral; Argentina Fil: Monczor, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Randi, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina

Poly(lactic acid) nanocomposites containing calcium carbonate nanoparticles and two different low molecular weight plasticizers have been prepared by a two-step melt mixing process. Up to 9 wt% of nanoparticles were successfully added preserving the plasticity of nanocomposites and with beneficial effects on the elastic modulus and yield stress. Mechanical, thermal and transport properties were measured as a function of aging time, up to 20 weeks, to evaluate the phase evolution of the plasticized nanocomposites. An interesting improvement in the time stability of mechanical and transport properties was highlighted and related to the effect of particles/plasticizer interactions on phase structure.

New nanocomposite microporous materials obtained by adding functionalized multi-walled carbon nanotubes (MWCNT) to styrene/vinylbenzyl chloride/divinylbenzene hyper-crosslinked resins were prepared and characterized. In order to promote the embedding of the MWCNT within the gel-type precursor, a suitable surface modi fi cation strategy was set up, based on the grafting of a poly(vinylbenzyl chloride) (PVBC) resin, able to participate in the hyper-crosslinking step, onto the nanotube surface. Characterization of the nanocomposites by FTIR spectroscopy and electron microscopy enabled the assessment of the e ff ect of the nanotubes on the structure and the morphology of the resin. Moreover, gas sorption measurements indicated that by addition of nanotubes it is possible to modulate the pore size distribution, the uptake of CO 2 and H 2 and the CO 2 /N 2 selectivity. Finally, modi fi ed MWCNT are also able to improve the adsorption capacity of phenol from water solutions, suggesting the possible application of the new microporous nanocomposites for water remediatio

Inflammation and oxidative stress play an important role in the pathogenesis of depressive disorders and Nuclear erythroid related factor 2 (Nrf2), a regulator of RedOx homeostasis and inflammation, is a promising target for depression prevention/treatment. As fish oil (FO) and Conjugated Linoleic Acid (CLA) are known Nrf2 inducer, their protective ability was comparatively evaluated in a murine model of depression (MRL/MpJ-Faslpr ). Oxidative stress, fatty acids content and critical factors reflecting brain functioning - namely brain-derived neurotrophic factor (BDNF), synaptic markers and cholinergic signaling - were preliminarily evaluated in frontal cortex of 8-weeks (Young) and in 22-weeks old animals (Old), which were used as model of depression. These markers were measured in Old mice at the end of a 5-week pre-treatment with FO or CLA (728 or 650 mg kg-1, respectively). Old mice exhibited disrupted Redox homeostasis, compensatory Nrf2 hyperactivation, lower Docosaheaxaenoic acid (DHA), lower BDNF and synaptic function proteins compared to Young mice. FO and CLA treatment relieved almost all the pathophysiological hallmarks at a level comparable to Young mice. Presented data provide the first evidence for the comparable efficacy of FO or CLA supplementation in preventing depression signs in Old MRL/lpr mice, likely through their ability of improving Nrf2-mediated antioxidant defenses.

The polar functionalization of vinylbenzyl chloride hyper-crosslinked (HCL) resins with ethanolamine at variable functionalization extent is reported. The functionalization reaction was investigated by a multitechnique approach to confirm the reaction mechanism and to calculate the yield of functionalization. Increasing the amount of ethanolamine grafted onto the HCL resin, the total pore volume of the resins decreased, while the microporous fraction increased and the pore size distribution evolved from bimodal to unimodal. The effect of the functionalization on the adsorption properties of the resins was investigated for CO2 sequestration and water purification applications. Both CO2 adsorption capacity and phenol removal efficiency from water solutions over the total pore volume of the resins were significantly improved. Moreover, the CO2/N2 selectivity significantly increased for the HCL resin at intermediate functionalization degree, which represents the optimal trade-off between high functionalization extent and porosity distribution evolution.

New amino-functionalized vinylbenzyl chloride/divinylbenzene-based hyper-crosslinked resins (HCLRs) were synthesized with the objective of improving the HCLR polarity and affinity to carbon dioxide and polar dyes. The HCLRs chemical structure and textural properties were investigated and correlated to the adsorption performance of the modified (XDV-NH2) and plain resin (XDV). The functionalization induced a reduction of the HCLR total porosity, while promoting the formation of a highly microporous structure with significant porosity narrower than 1 nm. Tested for CO2 adsorption at 0 degrees C and 25 degrees C, despite a reduced total porosity, the amino-functionalized XDV-NH2 resin showed up to 3 times increased adsorption capacity, higher CO2 heat of adsorption and CO2/N-2 selectivity with respect to the pristine XDV. XDV-NH2 also showed superior equilibrium and dynamic adsorption capacity of indigo carmine from solution with respect to XDV. These results demonstrate that the strategy proposed for the realization of amino-functionalized hyper-crosslinked resins is highly effective to obtain a microporous polymers with a significantly increased polar character and enhanced adsorption of CO2 and polar dyes.

Photophysical investigations of PPIX were described in order to determine the triplet conversion efficiency. Time resolved fluorescence and pulse train fluorescence were employed to characterize the main mechanism responsible for deactivation of the first singlet excited state (excited singlet and triplet states). Single pulse and Z-Scan analysis were employed to measure the singlet excited state absorption cross-sections. Theoretical calculations were performed in order to get some properties of PPIX in ground state, first singlet and triplet excited state. A TD-DFT result shows a great possibility of ISC associated to out-of-plane distortions in porphyrinic ring. Furthermore, the B and Q bands in the calculated spectrum are assigned to the four frontier molecular orbitals as proposed by Gouterman for free-based porphyrins.

Poly(ethylene terephthalate) (PET) was treated with vacuum UV (VUV) (λ = 104.8 and 106.7 nm) photo-oxidation using a microwave (MW) plasma of Ar as the radiation source and the results were compared to treatment with O atoms produced from a remote MW plasma of a gaseous mixture of Ar-O2 in the absence of radiation. X-ray photo-electron spectroscopy (XPS) detected a lower saturation level for the atomic % of O with VUV photo-oxidation (32 at%) than with O atom treatment (34 at% O). The C 1s curve fitting results for both treatment methods show a decrease in aromatic sp2 carbons and an increase in the amount of carbon-oxygen bonding due to the formation of the carbonyl (C=O) and carbonate-like (O-(C=O)-O) moieties for VUV photo-oxidation; and C-O-C, C=O, and O-C=O moieties for O atom treatment, respectively. Advancing water contact angle measurements showed more of an increase in hydrophilicity with the O atom treated samples than VUV photo-oxidation. Atomic Force Microscopy images displayed smoothe...

In this work, a new synthetic route is exploited to functionalize high surface area hyper-crosslinked resins by introducing amino groups into the hyper-crosslinked aromatic structure. The proposed functionalization aims to enhance the adsorption properties of the resin towards aromatic polar compounds, such as textile dyes. The obtained adsorbent was tested for the decontamination of wastewater from Indigo Carmine, used as model polar dye of the textile industry.

Chronic kidney disease (CKD) is a common disease in elderly dogs. The present study aims to evaluate the efficacy of a dietary supplement containing calcium carbonate, calcium-lactate gluconate, chitosan and sodium bicarbonate in dogs with IRIS stage 3 of CKD. Twenty dogs were enrolled in the study, ten were administered the new dietary supplementation for 180 days (T group) while the others were used as control group (C group). Haematologic, biochemical and urinalysis were performed every 30 days. A significant reduction in the T group compared to the C group in serum phosphorus level and increase in serum bicarbonate and ionized calcium values were recorded. The urine protein-to-creatinine ratio (UPC) was significantly lower in the T group at the end of the study compared to the C group. The tested supplement could be considered as a supportive treatment for dogs with advanced CKD.

Fluorescent organic molecules have received great attention due to their largest applications, for example, in DNA and RNA spectroscopies studies, development of new photoluminescence bioprobes, an...

Membrane fusion/fission is a highly dynamic and conserved process that responds to intra- and extracellular signals. Whereas the molecular machineries involved in membrane fusion/fission have been dissected, regulation of membrane dynamics remains poorly understood. The lysosomal vacuole of budding yeast (Saccharomyces cerevisiae) has served as a seminal model in studies of membrane dynamics. We have previously established that yeast ENV7 encodes an ortholog of STK16-related kinases that localizes to the vacuolar membrane and downregulates vacuolar membrane fusion. Additionally, we have previously reported that Env7 phosphorylation in vivo depends on YCK3, a gene that encodes a vacuolar membrane casein kinase I (CKI) homolog that nonredundantly functions in fusion regulation. Here, we report that Env7 physically interacts with and is directly phosphorylated by Yck3. We also establish that Env7 vacuole fusion/fission regulation and vacuolar localization are mediated through its Yck3-dependent phosphorylation. Through extensive site-directed mutagenesis, we map phosphorylation to the Env7 C terminus and confirm that Ser-331 is a primary and preferred phosphorylation site. Phospho-deficient Env7 mutants were defective in negative regulation of membrane fusion, increasing the number of prominent vacuoles, whereas a phosphomimetic substitution at Ser-331 increased the number of fragmented vacuoles. Bioinformatics approaches confirmed that Env7 Ser-331 is within a motif that is highly conserved in STK16-related kinases and that it also anchors an SXXS CKI phosphorylation motif ((328)SRFS(331)). This study represents the first report on the regulatory mechanism of an STK16-related kinase. It also points to regulation of vacuolar membrane dynamics via a novel Yck3–Env7 kinase cascade.

Metabolic reprogramming of cancer cells results in a high production of acidic substances that must be extruded to maintain tumor-cell viability. The voltage-gated proton channel (Hv1) mediates highly selective effluxes of hydronium-ion (H+ ) that prevent deleterious cytoplasmic acidification. In the work described here, we demonstrated for the first time that the amino-terminal-truncated isoform of Hv1 is more highly expressed in tumorigenic breast-cancer-cell lines than in nontumorigenic breast cells. With respect to Hv1 function, we observed that pharmacologic inhibition of that channel, mediated by the specific blocker 5-chloro-2-guanidinobenzimidazole, produced a drop in intracellular pH and a decrease in cell viability, both in monolayer and in three-dimensional cultures, and adversely affected the cell-cycle in tumorigenic breast cells without altering the cycling of nontumorigenic cells. In conclusion, our results demonstrated that the Hv1 channel could be a potential tool both as a biomarker and as a therapeutic target in breast-cancer disease.

In this work, we propose the synthesis of a novel bromine chalcone (E)-3-(2-bromophenyl)-1-(2phenylsulfonylamine)-phenyl)prop-2-en-1-one (BRC) that has been crystallized by slow evaporation technique. The second order molecular optical scattering and two-photon absorption(2PA) spectrumof the BRC molecule dissolved in Dimethyl Sulfoxide (DMSO) were evaluated by using Hyper Rayleigh Scattering and femtosecond tunable Z-Scan techniques. The first order hyperpolarizability of BRC dissolved in DMSO was estimated by using a simplified two-level model, in which one- and two-photon absorption parameters were used as input information to the model. The BRC crystal was characterized from single crystal X-ray diffraction (DRX) and spectroscopy analyzes. Also, the thermogravimetric analyses and the fluorescence spectra were obtained. In addition, an ab-initio calculation method, which includes the Moller-Plesset Perturbation Theory (MP2) and the Density Functional Theory (DFT) at CAM-B3LYP level,was used to estimate the crystal linear refractive index and the third-order electric susceptibility. Also, the average first hyperpolarizability of BRC molecules dissolved in DMSO was calculated and compared with the experimental results. The obtained values are good and qualify BRC crystal as a potential candidate for application in nonlinear optical devices.

Composites based on poly(butylene succinate-co-butylene adipate) (PBSA) containing amorphized and crystalline cellulose reinforcements have been prepared and characterized. In order to improve the polymer/filler interfacial adhesion, an efficient compatibilizing agent has been synthesized by chemical modification of PBSA and characterized by FT-IR, FT-NIR and 1H NMR spectroscopy. Uncompatibilized and compatibilized composites have been tested through morphological, mechanical, calorimetric and thermogravimetric analysis. Moreover, water vapor permeability and biodegradation kinetics of composites have been investigated. The addition to PBSA of cellulose fillers differing from each other by crystallinity degree and morphology, and the use of a compatibilizing agent have allowed modulating tensile and thermal properties, water vapor transmission rate and biodegradation kinetic of the composites.

The footwear market is addressing eco-sustainable solutions to the continuous demand for materials that at the same time show lighter weight with higher comfort. Toward this aim, a biodegradable matrix, poly(vinyl alcohol) (PVA), was used to obtain foams through an eco-sustainable methodology based on high speed mixing, without the use of chemical blowing agents. Moreover, considering that good thermoregulating performance in terms of heat transfer and perspiration is required for good quality shoes, microencapsulated phase change materials (PCMs) were incorporated into PVA foams. Foam morphologies investigated by SEM reveal that PCMs are finely dispersed through the PVA matrix. Mechanical properties of foams were analyzed in terms of compression behavior and shape memory recovery, triggering the dimensional changes by both temperature and relative humidity. The thermoregulating properties confirm that the presence of microcapsules affects the heat transfer phenomenon, since part of the heat provided by the source is involved in the wax phase transition.

Two oligomers of lactic acid (OLAs), carboxyl (OLA-COOH) or hydroxyl (OLA-OH) end capped, were employed to modulate physical and mechanical properties of poly(lactic acid), PLA. Blends up to 25 wt.% by weight of OLAs were prepared by melt mixing. Mechanical, thermal and transport properties of the materials were tested as a function of OLA functional moieties and blend composition. Moreover, the effect of physical aging on structure and properties of blends was studied by storing the samples in controlled temperature and humidity conditions, up to 8 weeks. OLAs significantly affect mechanical properties of PLA; blends showed an interesting ductility even after aging, suggesting their use as flexible films. Moreover, gas transport and total migration properties of blends are suitable for packaging applications.

Washing processes of synthetic clothes have been identified as the main source of microplastic pollution in marine ecosystems. Textile microfibres have been found in marine sediments and organisms, posing a real threat for the environment. The development of mitigation approaches is strongly needed to prevent the impact of microplastics. In this work, an innovative finishing treatment of polyamide fabrics is proposed to mitigate the microplastic impact, by preventing the damage of fabrics during washings. The treatment is based on the use of pectin, a natural polysaccharide present in the cell walls of plants. To functionalize the fabric, pectin was firstly modified with glycidyl methacrylate (GMA) and then grafted on polyamide. Washing tests of treated fabrics showed the effectiveness of the treatment in reducing of about 90% the amount of microfibres released by untreated fabrics. Post-wash analysis of the treated fabrics revealed a promising resistance to the washing process.

The new bipyridyl-corrole dye 10-(4-methyl-bipyridyl)-5,15-(pentafluorophenyl)corrole, encompassing a coordenative methyl-bipyridine moiety (corrole 2 ), was prepared starting from 5-(pentafluorophenyl)dipyrromethane and reacting it with methyl-bipyridyl-carboxaldehyde by Grykos methodology. It was further characterized by spectroscopic and electrochemical methods. In addition, we investigated experimental photophysical properties, photostability, reactive oxygen species generation (ROS) and aggregation phenomena, which are relevant when selecting photosensitizers used in photodynamic therapy and many other applications. Photophysical properties have demonstrated that the corrole 2 dissolved in dichloromethane has a triplet quantum yield formation of about 51%. Fluorescence and internal conversion quantum yields of 4% and 45%, respectively, have also been determined in order to evaluate which could be was the main pathway of the excited state relaxation. Triplet state formation was also confirmed by measuring indirectly 1 O 2 generation. Additionally, quantum chemistry calculations indicated that the most probable intersystem-crossing pathway takes place through S 1 -T 1 , corroborating our rate equation model.

Breast cancer incidence is increasing globally and pesticides exposure may impact risk of developing this disease. Hexachlorobenzene (HCB) and chlorpyrifos (CPF) act as endocrine disruptors, inducing proliferation in breast cancer cells. Vascular endothelial growth factor-A (VEGF-A), cyclooxygenase-2 (COX-2) and nitric oxide (NO) are associated with angiogenesis. Our aim was to evaluate HCB and CPF action, both weak aryl hydrocarbon receptor (AhR) ligands, on angiogenesis in breast cancer models. We used: (1) in vivo xenograft model with MCF-7 cells, (2) in vitro breast cancer model with MCF-7, and (3) in vitro neovasculogenesis model with endothelial cells exposed to conditioned medium from MCF-7. Results show that HCB (3 mg/kg) and CPF (0.1 mg/kg) stimulated vascular density in the in vivo model. HCB and CPF low doses enhanced VEGF-A and COX-2 expression, accompanied by increased levels of nitric oxide synthases (NOS), and NO release in MCF-7. HCB and CPF high doses intensified VEGF-A and COX-2 levels but rendered different effects on NOS, however, both pesticides reduced NO production. Moreover, our data indicate that HCB and CPF-induced VEGF-A expression is mediated by estrogen receptor and NO, while the increase in COX-2 is through AhR and NO pathways in MCF-7. In conclusion, we demonstrate that HCB and CPF environmental concentrations stimulate angiogenic switch in vivo. Besides, pesticides induce VEGF-A and COX-2 expression, as well as NO production in MCF-7, promoting tubulogenesis in endothelial cells. These findings show that pesticide exposure could stimulate angiogenesis, a process that has been demonstrated to contribute to breast cancer progression.

Palmitic acid (PA), a long-chain saturated fatty acid, might activate innate immune cells. PA plays a role in chronic liver disease, diabetes and Crohn&rsquo, s disease, all of which are associated with impaired intestinal permeability. We investigated the effect of PA, at physiological postprandial intestinal concentrations, on gut epithelium as compared to lipopolysaccharide (LPS) and ethanol, using an in vitro gut model, the human intestinal epithelial cell line Caco-2 grown on transwell inserts. Cytotoxicity and oxidative stress were evaluated, epithelial barrier integrity was investigated by measuring the paracellular flux of fluorescein, and through RT-qPCR and immunofluorescence of tight junction (TJ) and adherens junction (AJ) mRNAs and proteins, respectively. In PA-exposed Caco-2 monolayers, cytotoxicity and oxidative stress were not detected. A significant increase in fluorescein flux was observed in PA-treated monolayers, after 90 min and up to 360 min, whereas with LPS and ethanol, this was only observed at later time-points. Gene expression and immunofluorescence analysis showed TJ and AJ alterations only in PA-exposed monolayers. In conclusion, PA affected intestinal permeability without inducing cytotoxicity or oxidative stress. This effect seemed to be faster and stronger than those with LPS and ethanol. Thus, we hypothesized that PA, besides having an immunomodulatory effect, might play a role in inflammatory and functional intestinal disorders in which the intestinal permeability is altered.

Although the optical properties and applicability of chalcones as potential nonlinear optical(NLO) materials is well known, hybrids having both chalcone and sulfonamide portions are relatively scarce. In this sense, we are seeking to show if combining both into a double functionalized compound will still have similar or better NLO responses. For this, we have synthetized three sulfonamide-chalcone analogues by changing the substituent bonded to the sulfonamide ring (I = ethoxy; II = Cl and III = Br). These compounds were characterized by spectroscopic methods (NMR, IR and HRMS) and thermal methods (HSM and DSC/TGA). Their crystal structures were determined by Single Crystal X-ray Diffraction (SCXRD) and their molecular structures were compared. Crystallographic results showed that one compound crystallizes in a triclinic system whereas the others crystallize in a monoclinic crystal system. Moreover, their crystal packing is dominated by C–H ⋯ O interactions. In addition to this study and to first characterize these compounds, linear and nonlinear optical (NLO) properties were performed on all three compounds dissolved in dimethyl sulfoxide. One-photon and two-photon absorption (2PA) spectra and incoherent second harmonic generation were obtained by employing different spectroscopic techniques. The interesting results observed in the linear and NLO measurements showed that different groups bounded to the same main backbone did not significantly modify their optical properties, although they strongly affect their crystal structures. σ2PA spectra reveal that the first excited state is allowed by both 1PA and 2PA, which indicates asymmetry in the charge distribution along the π-conjugated molecule structure. NLO properties of compounds I-III agree with other chalcones previously studied, which indicates that adding the benzenesulfonyl group does not influence these properties. Considering the similar experimental values for different substituents, the results further motivate investigation on substituent-based optical properties for other sulfonamide-chalcone hybrids.

Hexachlorobenzene (HCB) is a dioxin-like compound widely distributed and is a weak ligand of the aryl hydrocarbon receptor (AhR). Endometriosis is a disease characterized by growth of endometrial tissue in ectopic sites. Our aim was to investigate the impact of HCB on the endocrine, invasion and inflammatory parameters in a rat endometriosis model surgically induced. Female rats were exposed to HCB (1, 10 and 100 mg/kg b.w.) during 30 days. Results showed that HCB increases endometriotic like-lesions (L) volume in a dose-dependent manner. In L, HCB10 increases microvessel density (immunohistochemistry) and the vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and AhR levels (Western Blot), while HCB1 enhances aromatase expression (Western Blot). In addition, in eutopic endometrium (EU), HCB10/HCB100 augments microvessel density, VEGF and MMP-9 expression, while HCB1/HCB10 increases tumor necrosis factor-α (TNF-α) content in peritoneal fluid (ELISA). Interestingly, both L and EU from HCB-treated rats exhibited higher estrogen receptor α (ERα) (immunohistochemistry) and metalloproteases (MMP)-2 and −9 levels (Western Blot), as well as lower progesterone receptor (PR) expression (immunohistochemistry) than in control rats. Environmentally relevant concentrations of HCB could contribute to abnormal changes associated with endometriosis progression and development. Fil: Chiappini, Florencia Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Sánchez, Marcela. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina Fil: Miret, Noelia Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina Fil: Cocca, Claudia Marcela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Zotta, Elsa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentina Fil: Ceballos, Leandro Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina Fil: Pontillo, Carolina Andrea. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Bilotas, Mariela Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Randi, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina

Cystalline-Cc and ultra-milled Amorphous-Ca cellulose were used as reactive filler to tune the performances of composite polyurethane-cellulose-foams, PUC. The effect of Cc and Ca on chemo-physical and mechanical properties of PUC was analysed through FTIR, morphological analysis, thermal conductivity and compression measurements. FTIR results show that, both Cc and Ca react with isocyanate through the OH functional groups contributing to the formation of a tough cellulose-polyurethane network. Morphological observations show that the addition of both Cc and Ca induces a decrease of average cell-size compared to the pristine-PU, thus confirming that they act as nucleating agent. In addition, the better dispersion of the Ca in the polyol, with respect to Cc induces, a finer cell leading to a reduction of the thermal conductivity around 33 % (for the composite loaded with 20 %wt-Ca) with respect to pristine-PU. Finally, the addition of Ca highly reactive modifies the mechanical behaviour from rigid-brittle to semi-rigid.