Publications

Abstract Aluminum (Al) toxicity limits crops growth and production in acidic soils. Compared to roots, less is known about the toxic effects of Al in leaves. Al subcellular compartmentalization is also largely unknown. Using rye (Secale cereale L.) Beira (more tolerant) and RioDeva (more sensitive to Al) genotypes, we evaluated the patterns of Al accumulation in leaf cell organelles and the photosynthetic and metabolic changes to cope with Al toxicity. The tolerant genotype accumulated less Al in all organelles, except the vacuoles. This suggests that Al compartmentalization plays a role in Al tolerance of Beira genotype. PSII efficiency, stomatal conductance, pigment biosynthesis, and photosynthesis metabolism were less affected in the tolerant genotype. In the Calvin cycle, carboxylation was compromised by Al exposure in the tolerant genotype. Other Calvin cycle-related enzymes, phoshoglycerate kinase (PGK), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), triose-phosphate isomerase (TPI), and fructose 1,6-bisphosphatase (FBPase) activities decreased in the sensitive line after 48 h of Al exposure. Consequentially, carbohydrate and organic acid metabolism were affected in a genotype-specific manner, where sugar levels increased only in the tolerant genotype. In conclusion, Al transport to the leaf and compartmentalization in the vacuoles tolerant genotype's leaf cells provide complementary mechanisms of Al tolerance, protecting the photosynthetic apparatus and thereby sustaining growth.

Abstract Purpose Soil is a complex open system covering various physical and chemical attributes. In soil testing, multivariate analysis (MVA) has an important application because it allows the interpretation of a large amount of data for the design of relevant environmental scenarios. The purpose of this research is to summarize recent applications of MVA for identifying soil types or characteristics and for predicting soil attributes with a critical evaluation. Methods Based on a comprehensive search of the available database, in this review, we have provided updated information on the most representative classification and regression MVA applied in the past decade in soil surveys. Regression MVA were compared in terms of applicability, efficiency, and predictive power of different soil attributes. Results Principal component analysis (PCA) allows the grouping of soils into independent clusters according to their differences in texture or physicochemical composition, which may mirror local or regional environmental signatures. PCA is also used to reduce the dimensionality of spectral data before their application in regression MVA. Partial least square regression (PLSR) is the most commonly applied regression MVA for predicting soil attributes after the correlation of spectra (e.g., Vis-NIR) vs. conventional analysis results. The resulting PLSR models, evaluated by correlation coefficient (R-2) and root mean squared error (RMSE), can be valid for the estimation of several soil attributes (e.g., organic carbon, clay). Conclusions Application of regression MVA may have limitations in predicting some soil attributes. Objective interpretation of the dynamic nature of soils requires the selection of representative samples as well as appropriate MVA, which can have significant potential in an effective soil survey.

Abstract Since metal contamination compromises crop growth and food safety, eco-friendly responses to prevent this are needed. This study provided an integrative evaluation of the potential of wrack (macroalgae debris) to increase the tolerance of Hordeum vulgare L. (barley plant) to copper (Cu).Plants were grown in a soil mixed with 219 mg Cu kg(-1) with/without 2% (m/m) wrack for 14 days. Copper impaired all growth-related parameters. Wrack application counteracted most of these negative impacts and lowered metal accumulation in roots. Metal exposure increased reactive oxygen species content [superoxide anion (O-2(center dot-)) and hydrogen peroxide [H2O2]) and lipid peroxidation degree, which was evaluated through the quantification of malondialdehyde, while co-treatment with wrack partially reverted some of these effects. The non-enzymatic antioxidant (AOX) system was mainly activated by Cu, with accumulated glutathione (GSH), ascorbate (AsA) and phenols, mostly in roots, while proline content was reduced. Wrack protective action was through a modulation of GSH and AsA redox state and enhanced ascorbate peroxidase. The results suggest wrack's potential to alleviate Cu-induced phytotoxicity, which probably relies on the reduction of Cu-induced oxidative stress through a more efficient activity of AOX metabolites and by limiting Cu absorption and bioaccumulation, especially in roots of barley plants.

Abstract Plant biostimulants such as seaweed extracts, present a sustainable alternative to agrochemicals. Moreover, the accumulation of beach-cast seaweed (wrack), due to climate change and anthropic pressures, is expected to increase in the coming decades. Thus, from a perspective of circular economy, based on the valorisation of an organic residue, this study aimed at achieving an elemental and biochemical characterisation of beach wrack and understanding the effects of an aqueous extract prepared from this residue on the mitigation of metal-induced stress, using barley (Hordeum vulgare L.) as a model. The quantification of wrack's macro- and micronutrients showed that K, Ca and Na were the most abundant elements, being this composition similar to that of other organic fertilisers. Furthermore, despite the studied wrack having lower values of photosynthetic pigments, amino acids and sugars, higher amounts of phenols and flavonoids (8.35 +/- 0.24 and 3.95 +/- 1.22 mg g(-1) dry matter respectively) were detected when compared to freshly collected seaweeds. This work highlighted that wrack showed potential as a fertiliser-through increasing root biomass (63%) and leaf biometry (up to 45%) in plants treated with 5.0 and 7.5 g L-1 wrack extract alone-also being a possible cost-effective, eco-friendly and sustainable biostimulant to mitigate the phytotoxic effects of Cu, since plants treated with 7.5 g wrack L-1 showed an increase of 34% in leaf length, when compared to seedlings exposed only to Cu.

Abstract Human monoamine oxidases (hMAOs) are well-established targets for the treatment of neurological disorders such as depression, Parkinson's disease and Alzheimer's disease. Despite the efforts carried out over the years, few selective and reversible MAO inhibitors are on the market. Thus, a continuous search for new compounds is needed. Herein, MAO inhibitors were searched among the non-chiral constituents of Bergamot Essential Oil (BEO) with the aid of computational tools. Accordingly, molecular modeling simulations were carried out on both hMAO-A and hMAO-B for the selected constituents. The theoretically predicted target recognition was then used to select the most promising compounds. Among the screened compounds, Bergamottin, a furocoumarin, showed selective hMAO-B inhibitory activity, fitting its active site well. Molecular dynamics simulations were used to deeply analyze the target recognition and to rationalize the selectivity preference. In agreement with the computational results, experimental studies confirmed both the hMAO inhibition properties of Bergamottin and its preference for the isoform B.

Abstract Diabetic foot ulcers (DFUs) are a common result of a complex secondary complication of diabetes mellitus. More than half of DFUs become infected due to frequent colonization with Staphylococcus aureus. The use of topical antibiotics is proposed, especially in combination with natural adjuvants, to minimize the negative impacts caused by generalized use of systemic antibiotics. In this study, 13 different phytochemicals-namely chalcone, juglone, cinnamic acid, trigonelline, Furvina-and four nitrovinylfuran derivatives-guaiazulene, alpha-bisabolol, farnesol and nerolidol-were selected to be tested as antibiotic enhancers. After minimum inhibitory and bactericidal concentration (MIC and MBC) determination of each molecule against different strains of S. aureus, including clinical isolates from diabetic foot wounds (CECT 976, Xu212, SA 1199B, RN4220, MJMC102, MJMC109, MJMC110 and MJMC111), their potentiation effects on the antibiotics fusidic acid, mupirocin, gentamicin, oxacillin and methicillin were evaluated through the disc diffusion method. Farnesol at sub-MIC was able to restore the activity of methicillin and oxacillin on the MJMC102 and MJMC111 strains, as well as two MRSA clinical isolates, and potentiated the effect of the remaining antibiotics. The results obtained demonstrate the great potential for the topical application of phytochemicals and derivatives as antibiotic resistance modifier agents to combat multidrug resistance in bacterial wound infections.

Abstract The discovery of effective drugs for the treatment of neurodegenerative disorders (NDs) is a deadlock. Due to their complex etiology and high heterogeneity, progresses in the development of novel NDs therapies have been slow, raising social/economic and medical concerns. Nanotechnology and nanomedicine evolved exponentially in recent years and presented a panoply of tools projected to improve diagnosis and treatment. Drug-loaded nanosystems, particularly nanoparticles (NPs), were successfully used to address numerous drug glitches, such as efficacy, bioavailability and safety. Polymeric nanoparticles (PNPs), mainly based on polylactic-co-glycolic acid (PLGA), have been already validated and approved for the treatment of cancer, neurologic dysfunctions and hormonal-related diseases. Despite promising no PNPs-based therapy for neurodegenerative disorders is available up to date. To stimulate the research in the area the studies performed so far with polylactic-co-glycolic acid (PLGA) nanoparticles as well as the techniques aimed to improve PNPs BBB permeability and drug targeting were revised. Bearing in mind NDs pharmacological therapy landscape huge efforts must be done in finding new therapeutic solutions along with the translation of the most promising results to the clinic, which hopefully will converge in the development of effective drugs in a foreseeable future.

Abstract Coumarin is a privilege scaffold in medicinal chemistry. Coumarin derivatives are still an emerging class of highly potent pharmaceutical drugs, best known in the field of antimicrobials and anticoagulants. Thiocoumarins are a particular class of coumarins in which one or two of the oxygen atoms are replaced by a sulfur. They are chemically subdivided in three groups: Thiocoumarins, 2-thioxocoumarins, and dithiocoumarins. This review emphasizes the rationale behind the synthesis and biological applications of the most relevant publications related to this family of compounds. Particular attention has been given to their potential as drug candidates, with particular emphasis in the last 5 years. This article is based on the most relevant information collected from multiple electronic databases, including SciFinder, Pubmed, Espacenet, and Mendeley.

Abstract Targeting antioxidants to mitochondria is considered a promising strategy to prevent cellular senescence and skin ageing. In this study, we investigate whether four hydroxybenzoic acid-based mitochondria-targeted antioxidants (MitoBENs, MB1-4) could be used as potential active ingredients to prevent senescence in skin cells. Firstly, we evaluated the chemical stability, cytotoxicity, genotoxicity and mitochondrial toxicity of all compounds. We followed this by testing the antioxidant protective capacity of the two less toxic compounds on human skin fibroblasts. We then assessed the effects of the best hit on senescence, inflammation and mitochondrial remodeling on a 3D skin cell model, while also testing its mutagenic potential. Cytotoxicity and mitochondrial toxicity rankings were produced: MB3 < MB4 similar or equal to MB1 < MB2 and MB3 < MB1 < MB4 < MB2, respectively. These results suggest that pyrogallol-based compounds (MB2 and MB4) have lower cytotoxicity. The pyrogallol derivative, MB2, containing a 6-carbon spacer, showed a more potent antioxidant protective activity against hydrogen peroxide cytotoxicity. In a 3D skin cell model, MB2 also decreased transcripts related to senescence. In sum, MB2's biological safety profile, good chemical stability and lack of mutagenicity, combined with its anti-senescence effect, converts MB2 into a good candidate for further development as an active ingredient for skin anti-ageing products.

Abstract Small-cell carcinoma of the ovary of hypercalcemic type (SCCOHT) and endometrial cancer from type 1 and type 2 are gynecological tumors that affect women worldwide. The treatment encompasses the use of cytotoxic drugs that are nonspecific and inefficient. Mitocans, a family of drugs that specifically target tumor cells' mitochondria, might be a solution, as they conjugate compounds, such as antioxidants, with carriers, such as lipophilic cations, that direct them to the mitochondria. In this study, caffeic acid was conjugated with triphenylphosphonium (TPP), 4-picolinium, or isoquinolinium, forming 3 new compounds (Mito6_TPP, Mito6_picol., and Mito6_isoq.) that were tested on ovarian (COV434) and endometrial (Hec50co and Ishikawa) cancer cells. The results of MTT and neutral red assays suggested a time- and concentration-dependent decrease in cell viability in all tumor cell lines. The presence of apoptosis was indicated by the Giemsa and Hoechst staining and by the decrease in mitochondrial membrane potential. The measurement of intracellular reactive oxygen species demonstrated the antioxidant properties of these compounds, which might be related to cell death. Generally, Mito6_TPP was more active at lower concentrations than Mito6_picol. or Mito6_isoq., but was accompanied by more cytotoxic effects, as shown by the lactate dehydrogenase release. Non-tumorous cells (HFF-1) showed no changes after treatment. This study assessed the potential of these compounds as anticancer agents, although further investigation is needed.