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Highlights • Cutaneous leishmaniasis topical therapy with paromomycin and anti-TNFα antibodies. • The combination produced similar reduction of parasite load. • The combination was more effective to control the local inflammation. • PM showed both antileishmanial/anti-inflammatory effect further enhanced with anti-TNFα antibodies. Abstract Background Cutaneous leishmaniasis (CL) skin lesions are the result of a deregulated immune response, which is unable to eliminate Leishmania parasites. The control of both, parasites and host immune response, is critical to prevent tissue destruction. The skin ulceration has been correlated with high TNF-α level. Objective Because human anti-TNF-α antibodies (Ab) have been successfully assayed in several mice inflammatory diseases, we hypothesized that their anti-inflammatory effect could optimize the healing of CL lesions achieved after topical application of paromomycin (PM), the current chemotherapy against CL. Methods and results We first compared the in vitro efficacy of PM and Ab alone and the drug given in combination with Ab to assess if the Ab could interfere with PM leishmanicidal activity in L. major- infected bone marrow-derived macrophages. The combination therapy had similar antileishmanial activity to the drug alone and showed no influence on NO production, which allows macrophage-mediated parasite killing. Next, we demonstrated in an in vivo model of Imiquimod®-induced inflammation that topical Ab and PM inhibit the infiltration of inflammatory cells in the skin. In the efficacy studies in L. major- infected BALB/c mice, PM combined with Ab led to a sharp infection reduction and showed a stronger anti-inflammatory activity than PM alone. This was confirmed by the down-regulation of TNF-α, IL-1β, iNOS, IL-17, and CCL3 as well as by a decrease of the neutrophilic infiltrate during infection upon treatment with the Ab. Conclusions In terms of parasite elimination and inflammation reduction, topical application of Ab in combination with PM was more effective than the drug alone. [ABSTRACT FROM AUTHOR]

Vaccine delivery using microneedles (MNs) represents a safe, easily disposable and painless alternative to traditional needle immunizations. The MN delivery of DNA vaccines to the dermis may result in a superior immune response and/or an equivalent immune response at a lower vaccine dose (dose-sparing). This could be of special interest for immunization programs against neglected tropical diseases such as leishmaniasis. In this work, we loaded a MN device with 60 μg of a plasmid DNA cocktail encoding the Leishmania infantum nucleosomal histones H2A, H2B, H3 and H4 and compared its immunogenicity and protective capacity against conventional s.c. or i.d. injection of the plasmid. Mice immunized with MNs showed increased ratios of IFN-γ/IL-10, IFN-γ/IL-13, IFN-γ/IL-4, and IFN-γ/TGF-β in the spleens and lymph nodes compared with mice immunized by s.c. and i.d. routes. Furthermore, CCXCL9, CXCL10 and CCL2 levels were also higher. These data suggest that the nucleic acid immunization using MNs produced a better bias towards a Th1 response. However, none of the immunizations strategies were able to control Leishmania major infection in BALB/c mice, as illustrated by an increase in lesion size and parasite burden. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate changes in color, betalain content, browning index, viscosity, physical stability, microbiological growth, antioxidant content and antioxidant activity of purple cactus pear juice during storage after thermoultrasonication at 80% amplitude level for 15 and 25 min in comparison with pasteurized juice. Thermoultrasound treatment for 25 min increased color stability and viscosity compared to treatment for 15 min (6.83 and 6.72 MPa, respectively), but this last parameter was significantly lower ( p < 0.05) compared to the control and pasteurized juices (22.47 and 26.32 MPa, respectively). Experimental treatment reduced significantly ( p < 0.05) sediment solids in juices. Total plate counts decreased from the first day of storage exhibiting values of 1.38 and 1.43 log CFU/mL, for 15 and 25 min treatment, respectively. Compared to the control, both treatments reduced enterobacteria counts (1.54 log CFU/mL), and compared to pasteurized juice decreased pectinmethylesterase activity (3.76 and 3.82 UPE/mL), maintained high values of ascorbic acid (252.05 and 257.18 mg AA/L) and antioxidant activity (by ABTS: 124.8 and 115.6 mg VCEAC/100 mL; and DPPH: 3114.2 and 2757.1 μmol TE/L). During storage thermoultrasonicated juices had a minimum increase in pectinmethylesterase activity (from day 14), and exhibited similar total plate counts to pasteurized juice. An increase of phenolic content was observed after 14 days of storage, particularly for treatment at 80%, 25 min, and an increase in antioxidant activity (ABTS, DPPH) by the end of storage. [ABSTRACT FROM AUTHOR]

The PI3K/Akt/mTOR/S6 ribosomal protein signalling pathway is a key potential target in breast cancer therapy, playing a central role in proliferation and cell survival. In this study, we found that the seleno-compound 2,4-dihydroselenoquinazoline ( 3a ) generally inhibited this signalling axis in MCF-7 breast cancer cells and caused downregulation of S6 ribosomal protein phosphorylation in a dose- and time-dependent manner. Furthermore, 3a caused a dose- and time-dependent decrease in MCF-7 cell viability as well as cell cycle arrest in G 2 /M. Interestingly 3a also induced apoptosis, as evidenced by cleavage of PARP and caspase-7, and inhibited autophagy, as demonstrated by accumulation of LC3-II and p62/SQSTM1. Given that induction of autophagy has been previously described as a mechanism by which some breast cancer cells counteract proapoptotic signalling and develop resistance to anti-hormone therapy, this suggests that this derivative, which both triggers apoptosis and inhibits autophagy, may be beneficial in preventing and overcoming resistance in breast cancer cells. The data also show the complexity of this signalling axis which is far from being understood. [ABSTRACT FROM AUTHOR]

Topical therapy is the ideal outpatient treatment of cutaneous leishmaniasis (CL) because of the ease of administration and lower cost. It could be suitable as monotherapy for localized cutaneous leishmaniasis (LCL) or in combination with systemic therapies for more severe forms of the disease. Although paromomycin (PM) ointment can be recommended for the treatment of LCL caused by Leishmaniamajor, a more effective topical treatment should be achieved regarding the physicochemical properties of this aminoglucoside and its rather poor intrinsic antileishmanial activity, that hampers the accumulation of enough amount of drug in the dermis (where the infected macrophages home) to exert its activity. In this work, we determined a 50% effective dose of 5.6 μM for a novel compound, bis-4-aminophenyldiselenide, against L. major intracellular amastigotes. This compound and PM were formulated in chitosan hydrogels and ex vivo permeation and retention studies in the different skin layers were performed with pig ear skin in Franz diffusion cells. The results showed that less than 2-4% of the diselenide drug penetrated and permeated through the skin. In contrast, the percentage of PM penetration was about 25-60% without important retention in the skin. When topically applied to lesions of L. major infected BALB/c mice, the novel diselenide chitosan formulation was unable to slow lesion progression and reduce parasite burden. Considerations during the process of novel drug development and formulation discovery algorithm for CL are discussed. [ABSTRACT FROM AUTHOR]

Highlights: [•] Models that relate mechanical properties with corrosion degree have been obtained. [•] The variation of yield stress and ultimate strength does not depend on the diameter. [•] Bar resistance reduction is lower than the one caused by section loss. [•] Deformation energy density undergoes higher decreases than yield stress or strength. [Copyright &y& Elsevier]

Abstract: Diselenide and sulfonamide derivatives have recently attracted considerable interest as leishmanicidal agents in drug discovery. In this study, a novel series of sixteen hybrid selenosulfonamides has been synthesized and screened for their in vitro activity against Leishmania infantum intracellular amastigotes and THP-1 cells. These assays revealed that most of the compounds exhibited antileishmanial activity in the low micromolar range and led us to identify three lead compounds (derivatives 2, 7 and 14) with IC50 values ranging from 0.83 to 1.47 μM and selectivity indexes (SI) over 17, much higher than those observed for the reference drugs miltefosine and edelfosine. When evaluated against intracellular amastigotes, hybrid compound 7 emerged as the most active compound (IC50 = 2.8 μM), showing higher activity and much less toxicity against THP-1 cells than edelfosine. These compounds could potentially serve as templates for future drug-optimization and drug-development efforts for their use as therapeutic agents in developing countries. [Copyright &y& Elsevier]

Thermosensitive hydrogels are of a great interest due to their many biomedical and pharmaceutical applications. In this study, we synthesized a new series of random poly (methyl vinyl ether-co-maleic anhydride) (Gantrez® AN, GZ) and Pluronic® F127 (PF127) copolymers (GZ–PF127), that formed thermosensitive hydrogels whose gelation temperature and mechanical properties could be controlled by the molar ratio of GZ and PF127 polymers and the copolymer concentration in water. Gelation temperatures tended to decrease when the GZm/PF127 ratio increased. Thus, at a fixed GZm/PF127 value, sol–gel temperatures decreased at higher copolymer concentrations. Moreover, these hydrogels controlled the release of proteins such as bovine serum albumin (BSA) and recombinant recombinant kinetoplastid membrane protein of Leishmania (rKMP-11) more than the PF127 system. Toxicity studies carried out in J774.2 macrophages showed that cell viability was higher than 80%. Finally, histopathological analysis revealed that subcutaneous administration of low volumes of these hydrogels elicited a tolerable inflammatory response that could be useful to induce immune responses against the protein cargo in the development of vaccine adjuvants. [ABSTRACT FROM AUTHOR]

Abstract: The genus Opuntia embraces different species of cactus, and many of them produce acid fruits known as xoconostle, which are considered valuable vegetable foods in Latin America. Xoconostle fruit contains an edible thick-acid-freshly mesocarp, and seeds that are considered as by-products. Given the high potential of its use and consumption, and the lack of information about its detailed chemical composition and bioactive compounds, the aim of this study was to evaluate the nutritional and antioxidant properties of pulp and seeds of two highly consumed commercial cultivars of xoconostle fruits (Opuntia joconostle F.A.C. Weber ex Diguet, cv. Cuaresmeño, and Opuntia matudae Scheinvar, cv. Rosa). This investigation shows that the pulp of the studied xoconostle cultivars had an appreciable amount of soluble fiber and antioxidant compounds such as ascorbic acid, while the seeds are a source of fiber, phenolics, flavonoids, PUFAs and tocopherols (specially γ-tocopherol), which provide a good antioxidant capacity. In the light of these results, xoconostle fruits should be considered of great interest for either promoting the conventional consumption, and also as sources of bioactive compounds for the addition to other food products, so that all the nutrients present are fully used, instead of being discarded. [Copyright &y& Elsevier]

Abstract: The synthesis, cytotoxic activities and selectivities of 35 derivatives related to quinazoline and pyrido[2,3-d]pyrimidine are described. The synthesized compounds were screened in vitro against four tumoral cell lines – leukemia (CCRF-CEM), colon (HT-29), lung (HTB-54) and breast (MCF-7) – and two cell lines derived from non-malignant cell lines, one mammary (184B5) and one from bronchial epithelium (BEAS-2B). MCF-7 and HTB-54 were the most sensitive cell lines with GI50 values below 10μM for eleven and ten compounds, respectively. Two compounds (2o and 3a) were identified that evoked a marked cytotoxic effect in all cell lines tested and one compound, 7h, was potent and selective against MCF-7. A preliminary study into the mechanism of the potent derivatives 2o, 3a and 7h indicated that the cytotoxic activities of these compounds might be mediated by inducing cell death without affecting cell cycle phases. [Copyright &y& Elsevier]

• This is the first in vivo study of a Se compound in visceral leishmaniasis. • Compound 1 showed high metabolic stability in vitro in mice liver microsomes. • The plasma concentration of 1 remained above the ED 50 for more than 24h. • 1 was well-tolerated in mice at the dose of 1mg/Kg daily administered. • 1 reduced the parasite load in liver, spleen and bone marrow. Compounds 1 and 2 (selenocyanate and diselenide derivatives, respectively) were evaluated for their potential use in vivo against visceral leishmaniasis (VL). Both entities showed low cytoxicity in vitro in Vero and Caco-2 cell lines. However, the compounds were not suitable for their oral administration, since they exhibited poor values of intestinal permeability in vitro. Microsomal stability assays did not show any metabolite for compound 1 after 120 min, whereas 2 was highly metabolized by the enzyme CYP450. Thus, the in vivo efficacy of compound 1 was assessed in a murine model of L. infantum VL. The daily i.v. administration of 1 mg/kg of compound 1 during 5 consecutive days reduced parasite load in liver, spleen and bone marrow (99.2%, 91.7% and 61.4%, respectively) compared to non-treated mice. To the best of our knowledge, this is the first time that a selenium compound has been tested in vivo against VL. Thus, this work evidences the possible usefulness of selenocyanate derivatives for the treatment of this disease. Image, graphical abstract [ABSTRACT FROM AUTHOR]

The purpose of this research was to optimize the thermoultrasound conditions for blackberry juice using the response surface methodology and considering juice quality parameters and antioxidant capacity. With the exception of microbial growth, the response variables showed high correlation coefficients with the mathematical model ( R 2 adj > 0.91). Thermoultrasound treatment inactivated all the evaluated microorganisms, and at the optimum conditions (50 ± 1 °C at 17 ± 1 min) it increased enzyme inactivation and antioxidant activity in comparison to pasteurized juice. The results demonstrated that thermoultrasound can be an alternative to pasteurization for the production of safe and high-quality juices with the added value of higher concentration of bioactive compounds and antioxidant capacity. [ABSTRACT FROM AUTHOR]

There is a lack of information on the potential use of xoconostle cultivars as sources of antioxidants for food, pharmaceutical and colorant industries. The aim of this study was to provide a phytochemical characterisation and antioxidant activity evaluation of Opuntia matudae Scheinvar cv. Rosa by-products (epicarp and endocarp mucilage’s), in order to evaluate their interest as sources of functional ingredients for human or animal foods. These by-products showed a high content in glucose, citric and linoleic acids, tocopherols, and isorhamnetin- O -(di-deoxyhexosyl-hexoside) (mainly in epicarp), and presented relevant antioxidant properties. The obtained results support the use of O. matudae Scheinvar cv. Rosa agro-industrial by-products as functional food ingredients, namely for antioxidant-enriched formulations, instead of being discarded. [ABSTRACT FROM AUTHOR]

Agroindustrial by-products derived from fruit processing are an important source of bioactive compounds that can be used as functional food ingredients. The genus Opuntia embraces different species of cactus, and many of them produce acidic fruits known as xoconostle, which are considered valuable foods in Latin America. Xoconostle fruit contains an edible thick-acid-freshly mesocarp, and seeds packed in a mucilaginous structure that together with the skin are considered by-products constitutes the endocarp. Given the high potential of its commercial use and consumption in Mexico, as well as the lack of information about its detailed chemical composition and bioactive compounds, the aim of this study was to evaluate the composition in bioactive compounds and antioxidant properties of the skin and mucilaginous part surrounding the seeds of the xoconostle fruit ( Opuntia joconostle F.A.C. Weber ex Diguet, cv. Cuaresmeño). These by-products stand out due to their high tocopherol content (mainly in epicarp), linoleic and citric acids (mainly in endocarp), and isorhamnetin O -hexoside di-ramnoside (mainly in epicarp), with high antioxidant properties. In the light of these results, xoconostle fruit cv. Cuaresmeño should be considered of great interest as a source of bioactive compounds for incorporation in other food products, so that all the bioactives present are fully used, instead of being discarded. [ABSTRACT FROM AUTHOR]

The parasite Entamoeba histolytica causes intestinal amebiasis and amebic liver abscess as its main extraintestinal manifestation. To study the in vivo events related to inflammation and the interactions between hosts and parasites during amebiasis, we designed a novel model of host-parasite interactions using cellulose membrane dialysis bags containing E. histolytica trophozoites. A bag is placed into the hamster peritoneal cavity, as has been reported in previous studies of programmed cell death (PCD) in E. histolytica trophozoites. To determine if virulence factors such as cysteine proteinases (EhCP2 and EhCP5) and Gal/GalNAc lectin could be involved in the host-parasite interaction using this model, we examined the relative expression of the ehcp2 and ehcp5 genes and the carbohydrate recognition domain ( crd ) of Gal/GalNAc lectin using real-time quantitative PCR (qRT-PCR). All analyzed genes were over-expressed 0.5 h after the initiation of the host-parasite interaction and were then progressively down-regulated. However, Gal/GalNAc lectin had the greatest increase in gene expression 1.5 h after host-parasite interaction; Gal/GalNAc lectin had a 250-fold increase with respect to the axenically grown trophozoites, which over-express Gal/GalNAc lectin in in vivo models. These results support the important role of these molecules in the initiation of cell damage by E. histolytica . [ABSTRACT FROM AUTHOR]

Abstract: Cactus pear (Opuntia ficus-indica) fruit is a berry with a tasty pulp full of seeds that constitutes about 10–15% of the edible pulp. In Mexico, cactus pear is mainly consumed fresh, but also has the potential to be processed in other products such as juice. The objective of this study was to evaluate the effect of different ultrasound conditions at amplitude levels ranging (40% and 60% for 10, 15, 25min; 80% for 3, 5, 8, 10, 15 and 25min) on the characteristics of purple cactus pear juice. The evaluated parameters were related with the quality (stability, °Brix, pH), microbial growth, total phenolic compounds, ascorbic acid and antioxidant activity (ABTS, DPPH and % chelating activity) of purple cactus pear juices. The ultrasound treatment for time period of 15 and 25min significantly reduced the microbial count in 15 and 25min, without affecting the juice quality and its antioxidant properties. Juice treated at 80% of amplitude level showed an increased of antioxidant compounds. Our results demonstrated that sonication is a suitable technique for cactus pear processing. This technology allows the achievement of juice safety and quality standards without compromising the retention of antioxidant compounds. [Copyright &y& Elsevier]

Abstract: A series of 17 symmetrical substituted imidothiocarbamate and imidoselenocarbamate derivatives has been synthesized by reacting appropriately substituted acyl chlorides with alkyl imidothiocarbamates and alkyl imidoselenocarbamates. The antitumoral activities of the compounds were evaluated in vitro by examining their cytotoxic effects against human prostate cancer cells (PC-3). Five compounds showed interesting activity levels and 3p (IC50 =1.85μM) was 7.3 times more active than the standard etoposide used in the treatment of prostate cancer and emerges as the most interesting compound. [Copyright &y& Elsevier]

Entamoeba histolytica is the primitive eukaryotic parasite responsible of human amoebiasis, a disease characterized by bloody intestinal diarrhea and invasive extraintestinal illness. The knowledge of the complete genome sequence of virulent E. histolytica and related non-pathogenic species allowed the development of novel genome-wide methodological approaches including protein expression profiling and cellular proteomics in the so called post-genomic era. Proteomics studies have greatly increased our understanding of the cell biology of this ancient parasite. This review summarizes the current works concerning proteomics studies on cell biology, life cycle, virulence and pathogenesis, novel therapies, and protein expression regulation mechanisms in E. histolytica parasite. Also, we discuss the use of proteomics data for the development of novel therapies, the identification of potential disease biomarkers and differential diagnosis between species. Entamoeba histolytica is the unicellular protozoan parasite responsible of human amoebiasis, a serious disease with worldwide distribution characterized by bloody intestinal diarrhea and invasive extraintestinal illness including peritonitis and liver, pulmonary and brain abscesses. The post-genomic era allowed the development of proteomic studies including protein expression profiling and cellular proteomics. These proteomics studies have greatly increased our understanding on cell biology, life cycle (cyst-trophozoite conversion), virulence, pathogenesis, novel therapies, and protein expression regulation mechanisms in E. histolytica. Importantly, proteomics has revealed the identity of proteins related to novel therapies, and the identification of potential disease biomarkers and proteins with use in diagnosis between species. Hopefully in the coming years, and through the use of more sophisticated omics tools, including deep proteomics, a more complete set of proteins involved in the aforementioned cellular processes can be obtained to understand the biology of this ancient eukaryote. Unlabelled Image • Entamoeba histolytica is the eukaryotic parasite responsible of human amoebiasis. • Proteomics studies have greatly increased our understanding of the cell biology of this ancient parasite. • Proteomics studies identified proteins involved in life cycle (cyst-trophozoite conversion). • Proteomic approaches identified proteins related to virulence and pathogenesis in E. histolytica parasite. • Proteomics data allows the identification of potential disease biomarkers and differential diagnosis between species. [ABSTRACT FROM AUTHOR]

The aim of this research was to determine the physicochemical properties, microbial counts and aflatoxin M 1 (AFM 1 ) levels of thermoultrasonicated, pasteurized and untreated milk (control) at days 1, 7 and 14 of storage. Thermoultrasound treatment was performed at a rate of 20 kHz for 10 or 15 min and 95% amplitude on homogenized and non-homogenized milk samples. Results showed that most physicochemical parameters were within the Mexican norms established for milk. Ultrasound treatment for 15 min reduced solids precipitation ( p  < 0.05) in unhomogenized milk during storage as compared to the pasteurized milk. All samples complied with aerobic mesophilic counts limits set by the Mexican norm except the control and the homogenized milk sample which was thermoultrasonicated for 10 min. Enterobacteriaceae counts of pasteurized and 15 min-thermoultrasound homogenized milks complied with the norm. The lowest levels of AFM 1 were found in the 10 min-thermoultrasound unhomogenized milk (0.15 ± 0.05 pg AFM⁠ 1 E/mL) one day after storage. Thermoultrasound did not affect the color of samples but homogenized milk treated for 10 min exhibited less total color difference. A high phenolic content was found in thermoultrasound and pasteurized milks on day 1. Thermoultrasound could be an alternative to milk pasteurization that preserves the physicochemical and microbiological quality of milk while reducing AFM 1 levels. [ABSTRACT FROM AUTHOR]

In the last two decades, trans -sialidase of Trypanosoma cruzi (TcTS) has been an important pharmacological target for developing new anti-Chagas agents. In a continuous effort to discover new potential TcTS inhibitors, 3-amino-3-arylpropionic acid derivatives (series A) and novel phthaloyl derivatives (series B, C and D) were synthesized and molecular docking, TcTS enzyme inhibition and determination of trypanocidal activity were carried out. From four series obtained, compound D-11 had the highest binding affinity value (−11.1 kcal/mol) compared to reference DANA (−7.8 kcal/mol), a natural ligand for TS enzyme. Furthermore, the 3D and 2D interactions analysis of compound D-11 showed a hydrogen bond, π-π stacking, π-anion, hydrophobic and Van der Waals forces with all important amino acid residues (Arg35, Arg245, Arg314, Tyr119, Trp312, Tyr342, Glu230 and Asp59) on the active site of TcTS. Additionally, D-11 showed the highest TcTS enzyme inhibition (86.9% ± 5) by high-performance ion exchange chromatography (HPAEC). Finally, D-11 showed better trypanocidal activity than the reference drugs nifurtimox and benznidazole with an equal % lysis (63 ± 4 and 65 ± 2 at 10 μg/mL) and LC 50 value (52.70 ± 2.70 μM and 46.19 ± 2.36 μM) on NINOA and INC-5 strains, respectively. Therefore, D-11 is a small-molecule with potent TcTS inhibition and a strong trypanocidal effect that could help in the development of new anti-Chagas agents. [ABSTRACT FROM AUTHOR]

The flavonoid kaempferol obtained from Helianthemum glomeratum , an endemic Mexican medicinal herb used to treat gastrointestinal disorders, has been shown to inhibit growth of Entamoeba histolytica trophozoites in vitro; however, the mechanisms associated with this activity have not been documented. Several works reported that kaempferol affects cytoskeleton in mammalian cells. In order to gain insights into the action mechanisms involved in the anti-amoebic effect of kaempferol, here we evaluated the effect of this compound on the pathogenic events driven by the cytoskeleton during E. histolytica infection. We also carried out a two dimensional gel-based proteomic analysis to evidence modulated proteins that could explain the phenotypical changes observed in trophozoites. Our results showed that kaempferol produces a dose-dependent effect on trophozoites growth and viability with optimal concentration being 27.7 μM. Kaempferol also decreased adhesion, it increased migration and phagocytic activity, but it did not affect erythrocyte binding nor cytolytic capacity of E. histolytica . Congruently, proteomic analysis revealed that the cytoskeleton proteins actin, myosin II heavy chain and cortexillin II were up-regulated in response to kaempferol treatment. In conclusion, kaempferol anti-amoebic effects were associated with deregulation of proteins related with cytoskeleton, which altered invasion mechanisms. [ABSTRACT FROM AUTHOR]

Pre-mRNA 3′ end processing in the nucleus is essential for mRNA stability, efficient nuclear transport, and translation in eukaryotic cells. In Human, the cleavage/polyadenylation machinery contains the 25 kDa subunit of the Cleavage Factor Im (CFIm25), which specifically recognizes two UGUA elements and regulates the assembly of polyadenylation factors, poly(A) site selection and polyadenylation. In Entamoeba histolytica , the protozoan parasite responsible for human amoebiasis, EhCFIm25 has been reported as a RNA binding protein that interacts with the Poly(A) Polymerase. Here, we follow-up with the study of EhCFIm25 to characterize its interaction with RNA. Using in silico strategy, we identified Leu135 and Tyr236 in EhCFIm25 as conserved amino acids among CFIm25 homologues. We therefore generated mutant EhCFIm25 proteins to investigate the role of these residues for RNA interaction. Results showed that RNA binding activity was totally abrogated when Leu135 and Tyr236 were replaced with Ala residue, and Tyr236 was changed for Phe. In contrast, RNA binding activity was less affected when Leu135 was substituted by Thr. Our data revealed for the first time -until we know-the functional relevance of the conserved Leu135 and Tyr236 in EhCFIm25 for RNA binding activity. They also gave some insights about the possible chemical groups that could be interacting with the RNA molecule. [ABSTRACT FROM AUTHOR]

A molecular modeling study has been carried out on two previously reported series of symmetric diselenide derivatives that show remarkable antileishmanial in vitro activity against Leishmania infantum intracellular amastigotes and in infected macrophages (THP-1 cells), in addition to showing favorable selectivity indices. Series 1 consists of compounds that can be considered as central scaffold constructed with a diaryl/dialkylaryl diselenide central nucleus, decorated with different substituents located on the aryl rings. Series 2 consists of compounds constructed over a diaryl diselenide central nucleus, decorated in 4 and 4′ positions with an aryl or heteroaryl sulfonamide fragment, thus forming the diselenosulfonamide derivatives. With regard to the diselenosulfonamide derivatives (2 series), the activity can be related, as a first approximation, with (a) the ability to release bis(4-aminophenyl) diselenide, the common fragment which can be ultimately responsible for the activity of the compounds. (b) the anti-parasitic activity achieved by the sulfonamide pharmacophore present in the analyzed derivatives. The data that support this connection include the topography of the molecules, the conformational behavior of the compounds, which influences the bond order, as well as the accessibility of the hydrolysis point, and possibly the hydrophobicity and polarizability of the compounds. [ABSTRACT FROM AUTHOR]

Human amoebiasis is an intestinal disease with a global distribution. Due to reports of parasite resistance or susceptibility reduction to metronidazole treatment, there is a renewed interest for the search of new molecules with antiamoebic activity. The flavonoid (−)-epicatechin that was isolated from the Mexican medicinal plant Geranium mexicanum HBK has an in vitro activity against E. histolytica trophozoites, however its molecular effects have been poorly documented. Using a proteomic approach based on two-dimensional gel electrophoresis and mass spectrometry (ESI-MS/MS) analysis, we evidenced that E. histolytica cytoskeleton proteins exhibit differential abundance in response to (−)-epicatechin treatment. Moreover, functional assays revealed modification on pathogenic mechanisms associated with cytoskeleton functionality, namely, adhesion, migration, phagocytosis and cytolysis. Consequently, these data suggested that (−)-epicatechin could affect virulence properties of this human pathogen. Biological significance This work contributes with some advances in the action mechanisms involved in the antiamoebic effect of the flavonoid (−)-epicatechin. We found that this flavonoid has an unusual effect on trophozoites growth that is dependent of its concentration. Additionally, we reported that (−)-epicatechin affects mainly amebic cytoskeleton proteins, which results in alteration on important virulence mechanisms, like adhesion, migration, phagocytosis and cytolysis. This study provides new knowledge about a potential alternative therapy directed to the treatment of amoebiasis. This article is part of a Special Issue entitled: Proteomics, mass spectrometry and peptidomics, Cancun 2013. Guest Editors: César López-Camarillo, Victoria Pando-Robles and Bronwyn Jane Barkla. [ABSTRACT FROM AUTHOR]

• The elastic properties of a high-fired gypsum have been obtained by a remote method. • The digital image correlation approach allows us to determine the Poisson's ratio. • Different correlations have been found between the variables evaluated. The main purpose of this work is to analyze the elastic properties (i.e. Young's modulus and Poisson's ratio) of gypsum specimens manufactured by traditional methods (non-industrial kilns). More specifically we have evaluated the Bajo Aragon variant by means of a low-cost digital image correlation approach. The accuracy of the data was contrasted with the press, obtaining an RMSE of 0.008%, corroborating the viability of the method. The results obtained during this experimental campaign revealed a gypsum with an average compressive strength, Young's modulus and Poisson's ratio of 4.01 MPa, 2989 MPa and 0.24 respectively. [ABSTRACT FROM AUTHOR]

A series of thirty-one selenocompounds covering a wide chemical space was assessed for in vitro leishmanicidal activities against Leishmania infantum amastigotes. The cytotoxicity of those compounds was also evaluated on human THP-1 cells. Interestingly most tested derivatives were active in the low micromolar range and seven of them (A.I.3 , A.I.7 , B.I.1 , B.I.2 , C.I.7 C.I.8 and C.II.8) stood out for selectivity indexes higher than the ones exhibited by reference compounds mitelfosine and edelfosine. These leader compounds were evaluated against infected macrophages and their trypanothione reductase (TryR) inhibition potency was measured to further approach the mechanism by which they caused their action. Among them diselenide tested structures were pointed out for their ability to reduce infection rates. Three of the leader compounds inhibited TryR effectively, therefore this enzyme may be implicated in the mechanism of action by which these compounds cause their leishmanicidal effect. [ABSTRACT FROM AUTHOR]