Mixtures of four organochlorines enhance human breast cancer cell proliferation.

In view of the large differences between the concentrations of estrogenic chemicals needed to elicit effects in in vitro assays and their levels in human tissues, it is hard to explain possible health risks in terms of exposure to individual compounds. Human populations, however, are exposed to mixtures of estrogenic and estrogen-like agents and it is necessary to consider the impact of combined effects. We assessed the combined effects of 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2,2-trichloroethane (o,p'-DDT), 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH), and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (p,p'-DDT) on the induction of cell proliferation in MCF-7 cells. All four compounds are persistent organochlorines that can be found in human tissues. We performed extensive concentration-response analyses with the single agents to predict the effects of two mixtures of all four compounds with different mixture ratios. We calculated the predictions by using the pharmacologically well-founded models of concentration addition and independent action and then tested them experimentally. o,p'-DDT, p,p'-DDE, beta-HCH, and p,p'-DDT acted together to produce proliferative effects in MCF-7 cells. The combined effect of the four agents could be predicted on the basis of data about single agent concentration-response relationships. Regression analysis demonstrated that there were combination effects even when each mixture component was present at levels at or below its individual no-observed-effect-concentration. We assessed combination effects in two ways: First, evaluations in relation to the proliferative responses induced by single mixture components revealed that the combination effects were stronger than the effects of the most potent constituent. Thus, according to this method of evaluation, the combined effects may be termed synergistic. Second, comparisons with the expected effects, as predicted by concentration addition and independent action, showed excellent agreement between prediction and observation. With this approach, the combined effect of all four compounds can be termed additive

Morphological and physiological responses induced by protein hydrolysate-based biostimulant and nitrogen rates in greenhouse spinach

Plant-derived protein hydrolysates (PHs) are gaining prominence as biostimulants due to their potential to improve yield and nutritional quality even under suboptimal nutrient regimens. In this study, we investigated the effects of foliar application of a legume-derived PH (0 or 4 ml L−1) on greenhouse baby spinach (Spinacia oleracea L.) under four nitrogen (N) fertilization levels (0, 15, 30, or 45 kg ha−1) by evaluating morphological and colorimetric parameters, mineral composition, carbohydrates, proteins, and amino acids. The fresh yield in untreated and biostimulant-treated spinach plants increased in response to an increase in N fertilization from 1 up to 30 kg ha−1, reaching a plateau thereafter indicating the luxury consumption of N at 45 kg ha−1. Increasing N fertilization rate, independently of PH, lead to a significant increase of all amino acids with the exception of alanine, GABA, leucine, lysine, methionine, and ornithine but decreased the polyphenols content. Interestingly, the fresh yield at 0 and 15 kg ha−1 was clearly greater in PH-treated plants compared to untreated plants by 33.3% and 24.9%, respectively. This was associated with the presence in of amino acids and small peptides PH ‘Trainer®’, which act as signaling molecules eliciting auxin- and/or gibberellin-like activities on both leaves and roots and thus inducing a “nutrient acquisition response” that enhances nutrients acquisition and assimilation (high P, Ca, and Mg accumulation) as well as an increase in the photochemical efficiency and activity of photosystem II (higher SPAD index). Foliar applications of the commercial PH decreased the polyphenols content, but on the other hand strongly increased total amino acid content (+45%, +82%, and +59% at 0, 15, and 30 kg ha−1, respectively) but not at a 45-kg ha−1-rate. Overall, the use of PH could represent a sustainable tool for boosting yield and nitrogen use efficiency and coping with soil fertility problems under low input regimens

Calpain 3 Is a Rapid-Action, Unidirectional Proteolytic Switch Central to Muscle Remodeling

Calpain 3 (CAPN3) is a cysteine protease that when mutated causes Limb Girdle Muscular Dystrophy 2A. It is thereby the only described Calpain family member that genetically causes a disease. Due to its inherent instability little is known of its substrates or its mechanism of activity and pathogenicity. In this investigation we define a primary sequence motif underlying CAPN3 substrate cleavage. This motif can transform non-related proteins into substrates, and identifies >300 new putative CAPN3 targets. Bioinformatic analyses of these targets demonstrate a critical role in muscle cytoskeletal remodeling and identify novel CAPN3 functions. Among the new CAPN3 substrates are three E3 SUMO ligases of the Protein Inhibitor of Activated Stats (PIAS) family. CAPN3 can cleave PIAS proteins and negatively regulates PIAS3 sumoylase activity. Consequently, SUMO2 is deregulated in patient muscle tissue. Our study thus uncovers unexpected crosstalk between CAPN3 proteolysis and protein sumoylation, with strong implications for muscle remodeling

Morpho-physiological and homeostatic adaptive responses triggered by omeprazole enhance lettuce tolerance to salt stress

Natural or synthetic small molecules (< 500 Da), bioactive at very low concentrations, can potentially increaseplant tolerance and resilience to abiotic stresses and improve the resources use efficiency (RUE) of a wide rangeof crops. Hence, they represent a promising tool in coping with the increasing global food demand imposed byclimate change. In this study, the responses of butterhead lettuce (cv. Trocadero) treated with omeprazole(OMP), a benzimidazole inhibitor of animal proton pumps, were studied. OMP was applied as substrate drench atfive rates (0, 10, 50, 100 or 200μM) on lettuce plants grown under nonsaline or saline conditions of 1 or30 mM NaCl. Increasing NaCl concentration decreased lettuce fresh and dry biomass by 37% and 25% in the0μM OMP treatment, respectively; whereas these reductions were mitigated by the 10μM (12% and 19%, re-spectively) and 50μM (15% and 14%, respectively) OMP application. Though OMP was not directly involved inion homeostasis and K+/Na+ratio regulation, treatment with 10μM OMP under saline conditions decreasedNa+in leaves and Cl−in leaves and roots while increasing NO3−concentration in both organs. The synthesis ofnitrogenous osmolytes may be implicated in increasing salt tolerance and the sustenance of transpiration andphotosynthesis. Under nonsaline conditions, OMP increased root biomass, improving nutrient and water uptake,and therefore RUE.Natural or synthetic small molecules (<500 Da), bioactive at very low concentrations, can potentially increase plant tolerance and resilience to abiotic stresses and improve the resources use efficiency (RUE) of a wide range of crops. Hence, they represent a promising tool in coping with the increasing global food demand imposed by climate change. In this study, the responses of butterhead lettuce (cv. Trocadero) treated with omeprazole (OMP), a benzimidazole inhibitor of animal proton pumps, were studied. OMP was applied as substrate drench at five rates (0, 10, 50, 100 or 200 μM) on lettuce plants grown under nonsaline or saline conditions of 1 or 30 mM NaCl. Increasing NaCl concentration decreased lettuce fresh and dry biomass by 37% and 25% in the 0 μM OMP treatment, respectively; whereas these reductions were mitigated by the 10 μM (12% and 19%, respectively) and 50 μM (15% and 14%, respectively) OMP application. Though OMP was not directly involved in ion homeostasis and K+/Na+ratio regulation, treatment with 10 μM OMP under saline conditions decreased Na+in leaves and Cl−in leaves and roots while increasing NO3−concentration in both organs. The synthesis of nitrogenous osmolytes may be implicated in increasing salt tolerance and the sustenance of transpiration and photosynthesis. Under nonsaline conditions, OMP increased root biomass, improving nutrient and water uptake, and therefore RUE

Chitosan Gel to Treat Pressure Ulcers: A Clinical Pilot Study

Chitosan is biopolymer with promising properties in wound healing. Chronic wounds represent a significant burden to both the patient and the medical system. Among chronic wounds, pressure ulcers are one of the most common types of complex wound. The efficacy and the tolerability of chitosan gel formulation, prepared into the hospital pharmacy, in the treatment of pressure ulcers of moderate severity were evaluated. The endpoint of this phase II study was the reduction of the area of the lesion by at least 20% after four weeks of treatment. Thus, 20 adult volunteers with pressure ulcers within predetermined parameters were involved in a 30 days study. Dressing change was performed twice a week at outpatient clinic upon chronic wounds management. In the 90% of patients involved in the study, the treatment was effective, with a reduction of the area of the lesion and wound healing progress. The study demonstrated the efficacy of the gel formulation for treatment of pressure ulcers, also providing a strong reduction of patient management costs

Sensory and functional quality characterization of protected designation of origin ‘Piennolo del Vesuvio’ cherry tomato landraces from Campania-Italy

Compositional characterization was performed on seven ‘Pomodorino del Piennolo del Vesuvio’ (PPV) tomato landraces, a signature product of Campania (Italy) threatened by genetic erosion. Characterization encompassed determinations of macro-minerals, soluble carbohydrates, starch, acidity, lycopene, polyphenols, anthocyanins, protein and free amino acids. Exceptionally high dry matter (13.0 ± 0.2%) and sugar content (101.3 ± 3.8 μmol g −1 fw) and very low (0.007–0.009) Na/K ratio were invariably obtained across landraces, contrasted by significant variation in acidity (28.5–3.9 g kg −1 dw). Giagiù, Acampora and Riccia San Vito differentiated by high polyphenols content (131.8 ± 2.5 mg 100 g −1 ) while Acampora, Cozzolino and Fofò by high lycopene content (13.3 ± 10.6 mg 100 g −1 fw). Glutamate, GABA and glutamine represented 65% of the 22 detected amino acids mean total content. Glutamate, linked to umami taste, was highest (19.2 µmol g −1 fw) in Fofò. Our results will contribute towards the systematic documentation of sensory and functional quality profiles of an important collection of tomato landraces