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This work describes the design, synthesis, and biological activities of new selenoester derivatives and its homologs thioesters. Thirty-two compounds were developed following an economical synthetic route, achieving small molecules, with structural characteristics similar to those present in antileishmanial drugs such as miltefosine (MIL) and paromomycin (PMN). These compounds were tested in vitro against strains of Leishmania major (L. major) and Leishmania infantum (L. infantum). The L. infantum strain (causative agent of visceral leishmaniasis) exhibited the highest sensitivity. Thus, four selanylacetic acid derivatives (A4, A5, A6 and A8) presented IC50 values below 40 µM in this strain. These derivatives also demonstrated low toxicity and high selectivity in PMA-differentiated THP-1 macrophages. The A4–A6 and A8 derivatives were evaluated in order to determine their pharmacological behavior, using drug combination studies with the reference drugs amphotericin B (AMB), MIL and PMN. Compounds A6 and A8 presented a potent synergistic interaction with MIL, which is the only oral drug available for the treatment of visceral leishmaniasis. Therefore, compounds A6 and A8 present significant potential as therapeutic candidates for the treatment of leishmaniasis based on their remarkable leishmanicidal characteristics and pharmacological synergism. [ABSTRACT FROM AUTHOR]

Proliferative fasciitis (PF) is a benign fibroblastic reaction with histological and clinical characteristics that overlap with those of malignant soft tissue tumors; thus, it is referred to as a pseudosarcomatous reaction. It continues to be an important cause of diagnostic error and overtreatment. The childhood PF subtype has some distinct histological and immunohistochemical characteristics that make differential diagnosis with malignant tumors even harder, especially with sarcoma. These proliferations generally occur in the lower limbs, and the periorbital region is a rare location of appearance. Here, we describe a case of childhood subtype PF in a 16-year-old girl located in the periorbital area. To the best of our knowledge, this is the first reported case of childhood subtype PF in the periorbital area, and the third case if PF subtypes are not taken into account. [ABSTRACT FROM AUTHOR]

Objectives: More effective topical treatments remain an unmet need for the localized forms of cutaneous leishmaniasis (CL). The aim of this study was to evaluate the efficacy and safety of a topical berberine cream in BALB/c mice infected with Leishmania major parasites.Methods: A cream containing 0.5% berberine-β-glycerophosphate salt and 2.5% menthol was prepared. Its physicochemical and stability properties were determined. The cream was evaluated for its capacity to reduce lesion size and parasitic load as well as to promote wound healing after twice-a-day administration for 35 days. Clinical biochemical profile was used for estimating off-target effects. In vitro time-to-kill curves in L. major-infected macrophages and skin and plasma pharmacokinetics were determined, aiming to establish pharmacokinetic/pharmacodynamic relationships.Results: The cream was stable at 40°C for 3 months and at 4°C for at least 8 months. It was able to halt lesion progression in all treated mice. At the end of treatment, parasite load in the skin was reduced by 99.9% (4 log) and genes involved in the wound healing process were up-regulated compared with untreated mice.The observed effects were higher than expected from in vitro time-to-kill kinetic and plasma berberine concentrations, which ranged between 0.07 and 0.22 μM.Conclusions: The twice-a-day administration of a topical berberine cream was safe, able to stop parasite progression and improved the appearance of skin CL lesions. The relationship between drug plasma levels and in vivo effect was unclear. [ABSTRACT FROM AUTHOR]

Background: Immunohistochemistry (IHQ) is commonly used for the detection of mismatch repair proteins deficiency (MMRD). One very infrequent abnormal pattern of MMR protein expression is the loss of PMS2 and MSH6, with intact expression of MLH1 and MSH2. Case presentation: We review the frequency of this MMRD IHC pattern among 108 colorectal (CRCs) and 35 endometrial cancers in our files with loss of expression of at least one protein, and present two CRCs showing loss of PMS2 and MSH6 protein expression (1.9% of CRCs). NGS analysis of these tumours identified PMS2 mutations (R134* germline mutation in one tumour and M1R and c.1239delA somatic mutation in the other) as the primary event and somatic MSH6 mutation (c.3261dupC) as the secondary event in both tumours. Conclusions: This study suggests that Next Generation Sequencing (NGS) tumour analysis should be considered in the algorithm of Lynch syndrome screening to detect MMR gen somatic mutation in inconclusive cases. [ABSTRACT FROM AUTHOR]

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]

Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disorder characterized by cognitive decline, memory loss, behavioral changes, and other neurological symptoms. Considering the urgent need for new AD therapeutics, in the present study we designed, synthesized, and evaluated multitarget compounds structurally inspired by sulfonylureas and pitolisant with the aim of obtaining multitarget ligands for AD treatment. Due to the diversity of chemical scaffolds, a novel strategy has been adopted by merging into one structure moieties displaying H3R antagonism and acetylcholinesterase inhibition. Eight compounds, selected by their binding activity on H3R, showed a moderate ability to inhibit acetylcholinesterase activity in vitro, and two of the compounds (derivatives 2 and 7) were also capable of increasing acetylcholine release in vitro. Among the tested compounds, derivative 2 was identified and selected for further in vivo studies. Compound 2 was able to reverse scopolamine-induced cognitive deficits with results comparable to those of galantamine, a drug used in clinics for treating AD. In addition to its efficacy, this compound showed moderate BBB permeation in vitro. Altogether, these results point out that the fragment-like character of compound 2 leads to an optimal starting point for a plausible medicinal chemistry approach for this novel strategy. [ABSTRACT FROM AUTHOR]

Abstract: The objective of this study was to evaluate the effect of ultrasound (60 and 80% amplitude, 15 and 25 min) of blackberry juice on physicochemical (pH and total soluble solids), microbiological analysis (total plate count and Enterobacteria), and in vitro intestinal bioaccessibility of polyphenols and antioxidant activity (ABTS, DPPH). Ultrasound treatment caused a decrease of microbial count of blackberry juice and remained its physicochemical properties without change. The blackberry juice had a high antioxidant activity, however, after of the in vitro digestion process only 28% of total polyphenols were considered as intestinally bioaccessible, with the contribution of 30 to 60% of antioxidant activity in the bioaccesible fraction. The treatment at 80% amplitude for 15 min was the better treatment due it had an increase of bioaccessibility of polyphenols and antioxidant activity measured by ABTS. Our results showed that ultrasound treatment can preserve the blackberry juice without impairing to its antioxidant characteristics. Practical applications: Blackberries are mostly consumed fresh but are also commercialized as individually quick frozen packs, bulk, frozen, seedless or seeded puree, freeze‐dried, juice, or concentrate. During fruit juices processing, thermal treatment and other conditions such as oxidation, light exposure, sugar addition, changes in pH, and temperature readily reduce the content of antioxidant compounds and its nutritional properties. Ultrasound is a non‐thermal processing technology with potential to replace the traditional thermal pasteurization, achieve microbial safety in fruit juices and remained its antioxidant properties of the blackberry juice. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are the leading causes of death in the world, and epidemiological evidence points to dietary habits, stress, and obesity as major risk factors promoting pathological conditions like atherosclerosis, hypertension, and thrombosis. Current therapeutic approaches for CVDs rely on lifestyle changes and/or the use of drug agents. However, since the efficacy of such interventions is often limited by poor compliance and/or significant side effects, continued research on new preventive and therapeutic approaches is much needed. Our study is aimed to determine the bioaccessibility, total content of phenolic compounds, and antioxidant capacity (DPPH ·, ABTS ·+) of a methanolic extract from Mangifera indica L. leaves (MEM), and its lipid-lowering effect on an induced dyslipidemia model in Wistar rats. Our results showed that mangiferin is the main component of MEM. The extract showed a total content of polyphenol compounds of 575.28 gallic acid equivalents per dry matter basis (GAE/g db), antioxidant activity 77.68 μmol Trolox equivalents per gram (TE/g) db as measured by DPPH· and 20,630 μmol TE/g db by ABTS ·+, and 12% of phenolic compounds were bioaccessible, and 100 mg/kg of MEM reduced hyperlipidemia levels induced in Wistar rats. Further study on the potential use of MEM as a nutraceutical to prevent CVDs in high-fat diet consumers is required. [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]

Amniotic fluid sludge (AFS) is defined as the presence of particulate matter in the amniotic fluid in close proximity to the cervix. Although its prevalence is known to correlate with the risk of preterm delivery, initial reports describe a strong association between AFS and microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis. However, AFS is also present in uncomplicated pregnancies, and its prevalence appears to increase with gestational age. Recent evidence debates the usefulness of AFS as a marker of early preterm delivery risk. We present four cases with AFS diagnosed by transvaginal ultrasound at admission for cervical insufficiency between 20 and 24 weeks of gestation, with confirmed lower genital tract and intra-amniotic infections by amniocentesis and histological chorioamnionitis and funisitis. Our findings reinforce the presence of AFS as a useful marker of MIAC, chorioamnionitis and funisitis that increase the likelihood of preterm delivery at an extreme gestational age. [ABSTRACT FROM PUBLISHER]

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]

In recent years, much effort has been invested into developing multifunctional drug delivery systems to overcome the drawbacks of conventional carriers. Magnetic nanoparticles are not generally used as carriers but can be functionalised with several different biomolecules and their size can be tailored to present a hyperthermia response, allowing for the design of multifunctional systems which can be active in therapies. In this work, we have designed a drug carrier nanosystem based on Fe3O4 nanoparticles with large heating power and 4-amino-2-pentylselenoquinazoline as an attached drug that exhibits oxidative properties and high selectivity against a variety of cancer malignant cells. For this propose, two samples composed of homogeneous Fe3O4 nanoparticles (NPs) with different sizes, shapes, and magnetic properties have been synthesised and characterised. The surface modification of the prepared Fe3O4 nanoparticles has been developed using copolymers composed of poly(ethylene-alt-maleic anhydride), dodecylamine, polyethylene glycol and the drug 4-amino-2-pentylselenoquinazoline. The obtained nanosystems were properly characterised. Their in vitro efficacy in colon cancer cells and as magnetic hyperthermia inductors was analysed, thereby leaving the door open for their potential application as multimodal agents. [ABSTRACT FROM AUTHOR]

The high consumption of maize tortillas in Mexico has prompted the widespread use of instant maize flours in the food industry, lowering the fibre and calcium contents in tortillas compared to the traditional nixtamal process. The inclusion of food sources such as cladodes could improve the nutritional value of maize tortillas. The aim of this study was to assess the physicochemical (rheology, puffing, rollability, and colour) and nutritional (chemical composition and in vitro intestinal bioaccessibility of calcium) parameters of maize tortillas made from commercial flour, substituted with 3% and 6% cladode flour. Partial substitution of maize flour with dried cladodes proved to be a good alternative to conventional tortillas both from a sensorial and a physical point of view. An improved rheological behaviour was observed in the dough, in addition to good puffing and rollability characteristics and an attractive colour of maize tortillas. The substitution of 6% maize flour with dried cladodes increased soluble fibre and calcium contents, and improved calcium intestinal absorption (bioaccessibility 48%), giving a value closer to that of traditional nixtamal maize tortillas. The introduction of cladode-supplemented instant maize flours on the market could help improve the fibre and calcium intake –and thus the health status– of the Mexican population. [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 young stems of Opuntia spp., known as cladodes are widely consumed in Mexico, and appreciated for their high content of fiber and beneficial effects in the metabolism of glucose. Since, boiling process is often applied to these vegetables, the objective of this study was to evaluate the influence of this process on the chemical composition, antioxidant capacity and physicochemical properties of two cladode cultivars. The components most affected were the soluble compounds (sugars, minerals, vitamin C and phenolics), while proteins, lipids and fiber showed a high retention. The losses of phytochemicals were related to the decrease of the antioxidant capacity. Cladodes presented good hydration properties inducing a non-Newtonian, pseudoplastic and thixotropic behavior in suspension. Heat treatment reduced the viscosity and gel consistency and these changes affected the physiological properties related to capacity of cladodes to hold glucose and control the glycemic response. The intake of these compounds and the estimation of some properties may be overestimated when data of raw sources are used. Further research to determine boiling conditions to minimize the changes on composition of these vegetables is necessary. [Copyright &y& Elsevier]

Currently, cancer, leishmaniasis and bacterial infections represent a serious public health burden worldwide. Six cinnamyl and benzodioxyl derivatives incorporating selenium (Se) as selenocyanate, diselenide, or selenide were designed and synthesized through a nucleophilic substitution and/or a reduction using hydrides. Ferrocene was also incorporated by a Friedel–Crafts acylation. All the compounds were screened in vitro for their antiproliferative, antileishmanial, and antibacterial properties. Their capacity to scavenge free radicals was also assessed as a first approach to test their antioxidant activity. Benzodioxyl derivatives 2a–b showed cytotoxicity against colon (HT-29) and lung (H1299) cancer cell lines, with IC50 values below 12 µM, and were also fairly selective when tested in nonmalignant cells. Selenocyanate compounds 1–2a displayed potent antileishmanial activity in L. major and L. infantum, with IC50 values below 5 µM. They also exhibited antibacterial activity in six bacterial strains, notably in S. epidermidis with MIC and MBC values of 12.5 µg/mL. Ferrocene-containing selenide 2c was also identified as a potent antileishmanial agent with radical scavenging activity. Remarkably, derivative 2a with a selenocyanate moiety was found to act as a multitarget compound with antiproliferative, leishmanicidal, and antibacterial activities. Thus, the current work showed that 2a could be an appealing scaffold to design potential therapeutic drugs for multiple pathologies. [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]

Background: Primary cardiac lymphomas are extremely rare entities (< 2% of cardiac tumours) and the most frequent histologic type is diffuse large B-cell lymphoma (DLBCL). Fibrin-associated DLBCL (FA-DLBCL) is a very unusual form of DLBCL associated with chronic inflammation, and only case reports and small series have been described. In the heart, it usually occurs in the context of a cardiac myxoma or cardiac prostheses and it is not bulk forming. These lymphomas frequently present with non-germinal center phenotype and are associated with Epstein-Barr virus (EBV) type III latency. Case presentation: We describe a case of FA-DLBCL arising in a cardiac myxoma, with plasmacytic differentiation and type I EBV latency. Conclusions: Although they are very rare, FA-DLBCLs should be known for their diagnostic difficulty, due to its unspecified clinical manifestations, and for their more favourable prognosis, sometimes even without additional treatment after surgical resection. [ABSTRACT FROM AUTHOR]

Berberine (BER)—an anti-inflammatory quaternary isoquinoline alkaloid extracted from plants—has been reported to have a variety of biologic properties, including antileishmanial activity. This work addresses the preparation of BER-loaded liposomes with the aim to prevent its rapid liver metabolism and improve the drug selective delivery to the infected organs in visceral leishmaniasis (VL). BER liposomes (LP-BER) displayed a mean size of 120 nm, negative Z-potential of −38 mV and loaded 6 nmol/μmol lipid. In vitro, the loading of BER in liposomes enhanced its selectivity index more than 7-fold by decreasing its cytotoxicity to macrophages. In mice, LP-BER enhanced drug accumulation in the liver and the spleen. Consequently, the liposomal delivery of the drug reduced parasite burden in the liver and spleen by three and one logarithms (99.2 and 93.5%), whereas the free drug only decreased the infection in the liver by 1-log. The organ drug concentrations—far from IC50 values— indicate that BER immunomodulatory activity or drug metabolites also contribute to the efficacy. Although LP-BER decreased 10-fold—an extremely rapid clearance of the free drug in mice—the value remains very high. Moreover, LP-BER reduced plasma triglycerides levels. [ABSTRACT FROM AUTHOR]

The oral administration of dapsone (DAP) for the treatment of cutaneous leishmaniasis (CL) is effective, although serious hematological side effects limit its use. In this study, we evaluated this drug for the topical treatment of CL. As efficacy depends on potency and skin penetration, we first determined its antileishmanial activity (IC50 = 100 μM) and selectivity index in vitro against Leishmania major-infected macrophages. In order to evaluate the skin penetration ex vivo, we compared an O/W cream containing DAP that had been micronized with a pluronic lecithin emulgel, in which the drug was solubilized with diethylene glycol monoethyl ether. For both formulations we obtained similar low flux values that increased when the stratum corneum and the epidermis were removed. In vivo efficacy studies performed on L. major-infected BALB/c mice revealed that treatment not only failed to cure the lesions but made their evolution and appearance worse. High plasma drug levels were detected and were concomitant with anemia and iron accumulation in the spleen. This side effect was correlated with a reduction of parasite burden in this organ. Our results evidenced that DAP in these formulations does not have an adequate safety index for use in the topical therapy of CL. [ABSTRACT FROM AUTHOR]

Functional beverages market requires conservation methods where bioactive compounds could persist for their bioavailability. The aim of this work was determined the extraction yield, antioxidant capacity and bioaccessibility of a cactus pear (Opuntia ficus-indica) juice blended using different solvent to extraction after pasteurization (PAST) or thermoultrasonication (TUS) treatment. The best properties were exhibited by TUS juice, showing 575.8 ± 11.1 mg GAE·L-1 for total phenolic, and 392.78 ± 4.1 mg BE·L-1 for pigment content. Which resulted in a greater antioxidant activity bioaccessible (87% DPPH; 38% ABTS). The highest antioxidant activity was found in the TUS methanolic extraction, exhibiting higher bioaccessibility than the juice (78% ABTS; 179% DPPH). It can be concluded that thermoultrasonication and methanolic extraction of a cactus pear juice blend allows a higher amount of antioxidant compounds to be bioavailable. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare drinkable yogurts added with purple cactus pear powder without ultrasonication (WY) and ultrasonicated (UY); with formulated yogurt with synthetic dyes (DY) and commercial saborized yogurt evaluating pH, titratable acidity, water holding capacity, viscosity, color, microbiology and in vitro bioaccessibility of antioxidants. The WY and UY showed an increase in functional properties, high ascorbic acid, and phenolic content (129.83 and 57.27 mg AAE/100 ml; 26.64 and 22.87 mg GAE/100 ml, respectively). The UY increased the antioxidant activity measured by ABTS (6.41 ± 0.11 mg VCEAC/100 ml) and DPPH (38.38 ± 0.92 µM TE/100 ml) in comparison to WY. After bioaccessibility assay, the UY had high phenolic content and antioxidant activity by ABTS, just below DY which presented the major content with respect to the other samples. The ultrasonicated purple cactus pear powder addition could be an alternative to drinkable yogurt with bioaccessible antioxidants. Practical applications: The benefits of yogurt make it a popular food with high consumption by its nutritional aspect, mainly if the product has natural additives that provide antioxidant compounds related to beneficial health effects, such as heart disease, diabetes, cancer, and among others. The different raw matter of purple cactus pear juice powder could provide an intense color as a natural additive to dairy products such as yogurt, which can be an alternative to synthetic additives since they play an important role in the quality of the product and consumer acceptance. In addition, the yogurt added with purple cactus pear juice powder also provides antioxidant content and high bioaccessibility, with light changes in their physicochemical characteristics. [ABSTRACT FROM AUTHOR]

Peritoneal cancer is the invasion by malignant cells of serous membrane that lines the abdominal cavity, the viscera, and the coelom of the amniotes. Histologically, it is indistinguishable from ovarian counterpart, although in the former, it commonly involves the ovary only superficially, or it may totally lack an ovarian component, but with extensive involvement of the peritoneum, calcified perihepatic peritoneal nodules, or involvement of the omentum, in most cases. The current study describes the case of a 54-year-old female patient referring a history of colitis and dairy intolerance. A transvaginal ultrasound and a computed tomography (CT) scan revealed a tumor measuring 70 × 61 × 63 mm. CA-125 serum levels were 880 U/ml. Laparotomy surgery was indicated, and tumor was found at the level of the rectovaginal septum without evidence of metastasis. Tumor dissection and protective colostomy with loop sigmoid colon were performed. A pathological study gave a diagnosis of a high-grade peritoneal serous carcinoma with a micropapillary pattern. The present study describes the case of papillary serous peritoneal cancer presented as a single tumor mass without extensive involvement of the peritoneum. Additionally, the need for routine tests for its diagnosis and documenting hormonal alterations as the cause of its origin are suggested. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new library of 20 selenocyanate and diselenide derivatives were synthesized. • Compounds B8 and B9 show EC 50 of 7.7 µM and 5.7 µM in L. major amastigotes. • Diselenides B8 and B9 present EC 50 of 6.0 µM and 7.4 µM in L. infantum amastigotes. • B8 and B9 exert high selectivity (60 < SI > 70) in bone marrow-derived macrophages. • TryR inhibition activity of B8 and B9 (IC 50 7.6 and 9.2 µM) is higher than mepacrine. Nowadays, leishmaniasis is still treated with outdated drugs that present several obstacles related to their high toxicity, long duration, parenteral administration, high costs and drug resistance. Therefore, there is an urgent demand for safer and more effective novel drugs. Previous studies indicated that selenium compounds are promising derivatives for innovative therapy in leishmaniasis treatment. With this background, a new library of 20 selenocyanate and diselenide derivatives were designed based on structural features present in the leishmanicidal drug miltefosine. Compounds were initially screened against promastigotes of L. major and L. infantum and their cytotoxicity was evaluated in THP-1 cells. Compounds B8 and B9 were the most potent and less cytotoxic and were further screened for the intracellular back transformation assay. The results obtained revealed that B8 and B9 showed EC 50 values of 7.7 µM and 5.7 µM, respectively, in L. major amastigotes, while they presented values of 6.0 µM and 7.4 µM, respectively, against L. infantum amastigotes. Furthermore, they exerted high selectivity (60 < SI > 70) towards bone marrow-derived macrophages. Finally, these compounds exhibited higher TryR inhibitory activity than mepacrine (IC 50 7.6 and 9.2 µM, respectively), and induced nitric oxide (NO) and reactive oxygen species (ROS) production in macrophages. These results suggest that the compounds B8 and B9 could not only exert a direct leishmanicidal activity against the parasite but also present an indirect action by activating the microbicidal arsenal of the macrophage. Overall, these new generation of diselenides could constitute promising leishmanicidal drug candidates for further studies. [ABSTRACT FROM AUTHOR]

This work analyzed the antidiabetic activity of peptides from whey proteins after hydrolysis by Lactobacillus rhamnosus GG and Streptococcus thermophilus SY-102, emphasizing the differences between the proteolytic systems of both bacteria. Peptide fractions from whey proteins may have biological functions, such as antidiabetic functions, which inhibit the DPP-IV enzyme, and lactic acid bacteria could release them. A whey solution of 10% was fermented with selected lactic acid bacteria in monoculture and coculture, analyzing kinetic parameters and the proteolytic profile, using the 2,4,6-trinitrobenzene sulfonic acid technique for free amino groups' determination and Tris-tricine polyacrylamide gel electrophoresis. An in vitro inhibition assay of the DPP-IV enzyme was used. The kinetic parameters showed a faster duplication rate in the monoculture with L. rhamnosus GG than in the co-culture, which was related to lactic acid production. Co-culture does not have the highest production of free amino groups and peptides. Still, peptide fractions with lower molecular weight (<2 kDa) were found and showed a high DPP-IV inhibitory capacity that was maintained from the middle of the fermentation to the end (55.4%). In comparison, the monoculture of L. rhamnosus GG increased from 0 to 63.3%. This demonstrates that the proteolytic capacity and the proteolytic system of each lactic acid bacteria determine the structure of the released peptides. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most frequent causes of drug hypersensitivity reactions, affecting 1%-3% of general population; the prevalence of NSAID hypersensitivity is higher in patients with chronic rhinosinusitis, nasal polyposis, asthma, or chronic urticaria, affecting up to 30% of patients[1]. This is a prospective, real-life, observational study aimed to evaluate all direct and indirect health costs of patients that consulted in our outpatient clinic for suspected NSAID hypersensitivity reactions. One of the advantages of performing a study of NSAID hypersensitivity is de-labeling of purported NSAID hypersensitivity patients. [Extracted from the article]

Leishmania mexicana (L. mexicana) is a causal agent of cutaneous leishmaniasis (CL), a "Neglected disease", for which the search for new drugs is a priority. Benzimidazole is a scaffold used to develop antiparasitic drugs; therefore, it is interesting molecule against L. mexicana. In this work, a ligand-based virtual screening (LBVS) of the ZINC15 database was performed. Subsequently, molecular docking was used to predict the compounds with potential binding at the dimer interface of triosephosphate isomerase (TIM) of L. mexicana (LmTIM). Compounds were selected on binding patterns, cost, and commercial availability for in vitro assays against L. mexicana blood promastigotes. The compounds were analyzed by molecular dynamics simulation on LmTIM and its homologous human TIM. Finally, the physicochemical and pharmacokinetic properties were determined in silico. A total of 175 molecules with docking scores between −10.8 and −9.0 Kcal/mol were obtained. Compound E2 showed the best leishmanicidal activity (IC50 = 4.04 µM) with a value similar to the reference drug pentamidine (IC50 = 2.23 µM). Molecular dynamics analysis predicted low affinity for human TIM. Furthermore, the pharmacokinetic and toxicological properties of the compounds were suitable for developing new leishmanicidal agents. [ABSTRACT FROM AUTHOR]

Protein-protein interactions (PPI) play a key role in predicting the function of a target protein and drug ability to affect an entire biological system. Prediction of PPI networks greatly contributes to determine a target protein and signal pathways related to its function. Polyadenylation of mRNA 3'-end is essential for gene expression regulation and several polyadenylation factors have been shown as valuable targets for controlling protozoan parasites that affect human health. Here, by using a computational strategy based on sequence-based prediction approaches, phylogenetic analyses, and computational prediction of PPI networks, we compared interactomes of polyadenylation factors in relevant protozoan parasites and the human host, to identify key proteins and define potential targets for pathogen control. Then, we used Entamoeba histolytica as a working model to validate our computational results. RT-qPCR assays confirmed the coordinated modulation of connected proteins in the PPI network and evidenced that silencing of the bottleneck protein EhCFIm25 affects the expression of interacting proteins. In addition, molecular dynamics simulations and docking approaches allowed to characterize the relationships between EhCFIm25 and Ehnopp34, two connected bottleneck proteins. Interestingly, the experimental identification of EhCFIm25 interactome confirmed the close relationships among proteins involved in gene expression regulation and evidenced new links with moonlight proteins in E. histolytica, suggesting a connection between RNA biology and metabolism as described in other organisms. Altogether, our results strengthened the relevance of comparative genomics and interactomics of polyadenylation factors for the prediction of new targets for the control of these human pathogens. [ABSTRACT FROM AUTHOR]

During the industrial processing of juice high amounts of by-products are obtained which are discarded. The objective of this study was to optimize the conditions of ultrasound process using response surface methodology (RMS) based on antioxidant compounds extraction (total phenolic content (TPC) and ascorbic acid (AA) and antioxidant activity (ABTS and DPPH) of mango waste and its comparison with two conventional extraction methods (aqueous and hydroalcoholic). All response variables were fitted to the mathematical model (R2 ≥ 95). The optimal processing conditions corresponded to 91% of amplitude with a treatment time of 7 min, reaching the highest extraction of TPC and AA, as well as antioxidant activity. And in comparison, to conventional extraction methods (aqueous and hydroalcoholic), the optimal ultrasound conditions had (p< 0.05) highest antioxidant content with 8800 mg GAE/100 g dry weight (dw) to total phenolic content, 5600 mg AAE/100 g dw in ascorbic acid, 60000 and 7500 µmol TE/100 g dw for DPPH• and ABTS•+ assays, respectively. These results demonstrate that ultrasound is an alternative method to enhance the extraction of antioxidants from mango industrial waste which could be used as additives in food products. [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]

Blackberry (Rubus fruticosus spp.) fruit has high antioxidant activity due to its significant content of anthocyanins and antioxidant compounds. Among emerging technologies for food preservation, thermoultrasound is a technique that reduces microbial loads and releases compounds with antioxidant properties. The objective of this study was to determine the antioxidant content and fatty acid profile of blackberry juice subjected to thermoultrasound treatment in comparison to pasteurized juice. Blackberry juice and n-hexane extracts from a control (untreated juice), pasteurized, and thermoultrasonicated samples were evaluated for antioxidant activity, fatty acid profile, and antioxidant content. The juice treated with thermoultrasound exhibited significantly (p < 0.05) higher levels of total phenols (1011 mg GAE/L), anthocyanins (118 mg Cy-3-GlE/L); antioxidant activity by ABTS (44 mg VCEAC/L) and DPPH (2665 μmol TE/L) in comparison to the control and pasteurized samples. Oil extract from thermoultrasound juice also had the highest antioxidant activity (177.5 mg VCEAC/L and 1802.6 μmol TE/L). The fatty acid profile of the n-hexane extracts showed the presence of myristic, linolenic, stearic, oleic, and linoleic acids and was not affected by the treatments except for stearic acid, whose amount was particularly higher in the control. Our results demonstrated that thermoultrasound can be an alternative technology to pasteurization that maintains and releases antioxidant compounds and preserves the fatty acids of fruit juice. [ABSTRACT FROM AUTHOR]

The norbornene scaffold has arisen as a promising structure in medicinal chemistry due to its possible therapeutic application in cancer treatment. The development of norbornene-based derivatives as potential chemotherapeutic agents is attracting significant attention. Here, we report an unprecedented review on the recent advances of investigations into the antitumoral efficacy of different compounds, including the abovementioned bicyclic scaffold in their structure, in combination with chemotherapeutic agents or forming metal complexes. The impact that structural modifications to these bicyclic compounds have on the antitumoral properties and the mechanisms by which these norbornene derivatives act are discussed in this review. In addition, the use of norbornene, and its related compounds, encapsulation in nanosystems for its use in cancer therapies is here detailed. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome in children (MIS-C) has been widely reported in some children diagnosed with SARS-CoV-2. Clinical signs of MIS-C are manifested at 2 to 4 weeks after SARS-CoV-2 infection, where elevated biomarkers of inflammation and cardiac dysfunction are the hallmark of this syndrome when infection or exposure to SARS-CoV-2 has been confirmed. However, after two years of acknowledgment, MIS-C treatment is still under research to reach safety and effectiveness in the acute phase in children. Therefore, in this review, we discuss the potential use of natural compounds with antioxidant and anti-inflammatory effects to reduce collateral damage caused by hyperinflammation in MIS-C pathology for new research in treatment and interventions. [ABSTRACT FROM AUTHOR]

Our clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs. First, NBIA genes were analysed by Sanger sequencing and 59 patients achieved a diagnosis, including the detection of the founder mutation PANK2 p.T528M in Romani people. Then, we used a custom panel MovDisord and/or exome sequencing; 29 cases were solved with a great genetic heterogeneity (34 different mutations in 23 genes). Three patients presented brain iron deposits with Fe-sensitive MRI sequences and mutations in FBXO7, GLB1, and KIF1A, suggesting an NBIA-like phenotype. Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in ITPR1, KIF1A, SPTBN2, PLA2G6, PMPCA, and PRDX3. The novel variants were investigated by structural modelling, luciferase analysis, transcript/minigenes studies, or immunofluorescence assays. Our findings expand the phenotypes and the genetics of MDs and ataxias with early-onset CA and cortical hyperintensities and highlight that the abnormal brain iron accumulation or early cerebellar gliosis may resembling an NBIA phenotype. [ABSTRACT FROM AUTHOR]

Trypanosoma cruzi (T. cruzi) is a parasite that affects humans and other mammals. T. cruzi depends on glycolysis as a source of adenosine triphosphate (ATP) supply, and triosephosphate isomerase (TIM) plays a key role in this metabolic pathway. This enzyme is an attractive target for the design of new trypanocidal drugs. In this study, a ligand-based virtual screening (LBVS) from the ZINC15 database using benzimidazole as a scaffold was accomplished. Later, a molecular docking on the interface of T. cruzi TIM (TcTIM) was performed and the compounds were grouped by interaction profiles. Subsequently, a selection of compounds was made based on cost and availability for in vitro evaluation against blood trypomastigotes. Finally, the compounds were analyzed by molecular dynamics simulation, and physicochemical and pharmacokinetic properties were determined using SwissADME software. A total of 1604 molecules were obtained as potential TcTIM inhibitors. BP2 and BP5 showed trypanocidal activity with half-maximal lytic concentration (LC50) values of 155.86 and 226.30 µM, respectively. Molecular docking and molecular dynamics simulation analyzes showed a favorable docking score of BP5 compound on TcTIM. Additionally, BP5 showed a low docking score (−5.9 Kcal/mol) on human TIM compared to the control ligand (−7.2 Kcal/mol). Both compounds BP2 and BP5 showed good physicochemical and pharmacokinetic properties as new anti-T. cruzi agents. [ABSTRACT FROM AUTHOR]

Objective: Determine the relationship between obesity and abnormal cardiopulmonary parameters in school children. Materials and Methods: The sample involved 78 children between five and 11 years of age: 47 males (60.3%) and 31 females (39.7%). All were enrolled in a specific elementary school in the city of Pachuca (Mexico). Body mass (BMI), waist circumference (WC), body fat (GC), heart rate (HR), blood pressure (BP), respiratory rate (RR) and spirometry were evaluated. A chi-square (x2) statistical test, the odds ratio and Spearman's rank-order correlation (rs) were used. Results: In all, 23.1% of the students who were evaluated were overweight and 29.5% were obese; 38.5% and 11.5% had a HR and BP above the normal parameters, in that order; 3.8% of the population in question had a HR above average and 11.5% showed abnormal spirometric values. A relationship was found between BMI and BF and WC, BF and WC, WC and HR, BF and BP, and HR and RF. Conclusions: The prevalence of overweight and obesity found in this study was high. Children who are overweight or obese might be at increased risk of experiencing cardiopulmonary abnormalities compared to children of normal weight. It is suggested that studies on this subject be continued with a broader sample. [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]

Human immunodeficiency virus (HIV) infection has continued to be the subject of study since its discovery nearly 40 years ago. Significant advances in research and intake of antiretroviral therapy (ART) have slowed the progression and appearance of the disease symptoms and the incidence of concomitant diseases, which are the leading cause of death in HIV+ persons. However, the prolongation of ART is closely related to chronic degenerative diseases and pathologies caused by oxidative stress (OS) and alterations in lipid metabolism (increased cholesterol levels), both of which are conditions of ART. Therefore, recent research focuses on using natural therapies to diminish the effects of ART and HIV infection: regulating lipid metabolism and reducing OS status. The present review summarizes current information on OS and cholesterol metabolism in HIV+ persons and how the consumption of certain phytochemicals can modulate these. For this purpose, MEDLINE and SCOPUS databases were consulted to identify publications investigating HIV disease and natural therapies and their associated effects. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the effect on metabolic indicators (total cholesterol, triacylglycerides, HDL, LDL and glycemia) in university students, after the daily consumption of 1.00 g of a cocoa paste bar (PCB) and 0.50 g of a white chocolate bar (BCB) during two months. The population was characterized according to their sex, weight, height, body mass index (BMI), physical activity and diet. The pre- and post-metabolic levels were measured in the control group (BCB) and experimental group (BPC). The students have normal weight (22.90 kg/m2 and 24.99 kg/m2), average physical activity was predominat (55.60 %) and their nutrition was inadequate. The study groups presented metabolic levels within the normal parameter. However, the consumption of 1 g of PCB for two months increases HDL levels (36.94 ± 13.42 mg/dL vs 59.74 ± 9.41 mg/dL), an effect that is highly desirable in a food. [ABSTRACT FROM AUTHOR]

The disparity between men and women in science is a hot topic in gender studies and a relevant target of scientific policies. The leaky pipeline metaphor illustrates the decreasing number of women along senior positions in academia; however many questions remain unanswered. What factors progressively diminish the number of women in scientific careers and why do they appear to be less successful than their male colleagues? In order to discover new insight, this work compares men's and women's career paths by taking into account academic and family milestones achieved throughout the life course. An innovative and interdisciplinary methodology (from bibliometrics, statistics, and sociology) has been constructed to examine men's and women's trajectories. Findings display gender differences in scientists' trajectories. The evolution of scientists' careers reveals linear careers for males, whilst women develop non-linear careers. Motherhood emerges as a problem for developing linear careers. And collegiate decisions of gatekeepers seem to systematically disfavour women scientists' careers. [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]