Supplementation with a New Standardized Extract of Green and Black Tea Exerts Antiadipogenic Effects and Prevents Insulin Resistance in Mice with Metabolic Syndrome.

Insulin resistance is one of the main characteristics of metabolic syndrome (MetS) and the main cause of the development of type II diabetes. The high prevalence of this syndrome in recent decades has made it necessary to search for preventive and therapeutic agents, ideally of natural origin, with fewer side effects than conventional pharmacological treatments. Tea is widely known for its medicinal properties, including beneficial effects on weight management and insulin resistance. The aim of this study was to analyze whether a standardized extract of green and black tea (ADM® Complex Tea Extract (CTE)) prevents the development of insulin resistance in mice with MetS. For this purpose, C57BL6/J mice were fed for 20 weeks with a standard diet (Chow), a diet with 56% kcal from fat and sugar (HFHS) or an HFHS diet supplemented with 1.6% CTE. CTE supplementation reduced body weight gain, adiposity and circulating leptin levels. Likewise, CTE also exerted lipolytic and antiadipogenic effects in 3T3-L1 adipocyte cultures and in the C. elegans model. Regarding insulin resistance, CTE supplementation significantly increased plasma adiponectin concentrations and reduced the circulating levels of insulin and the HOMA-IR. Incubation of liver, gastrocnemius muscle and retroperitoneal adipose tissue explants with insulin increased the pAkt/Akt ratio in mice fed with Chow and HFHS + CTE but not in those fed only with HFHS. The greater activation of the PI3K/Akt pathway in response to insulin in mice supplemented with CTE was associated with a decrease in the expression of the proinflammatory markers Mcp-1, IL-6, IL-1ß or Tnf-α and with an overexpression of the antioxidant enzymes Sod-1, Gpx-3, Ho-1 and Gsr in these tissues. Moreover, in skeletal muscle, mice treated with CTE showed increased mRNA levels of the aryl hydrocarbon receptor (Ahr), Arnt and Nrf2, suggesting that the CTE's insulin-sensitizing effects could be the result of the activation of this pathway. In conclusion, supplementation with the standardized extract of green and black tea CTE reduces body weight gain, exerts lipolytic and antiadipogenic effects and reduces insulin resistance in mice with MetS through its anti-inflammatory and antioxidant effects.

Effect-Directed, Chemical and Taxonomic Profiling of Peppermint Proprietary Varieties and Corresponding Leaf Extracts.

During the development of novel, standardized peppermint extracts targeting functional applications, it is critical to adequately characterize raw material plant sources to assure quality and consistency of the end-product. This study aimed to characterize existing and proprietary, newly bred varieties of peppermint and their corresponding aqueous extract products. Taxonomy was confirmed through genetic authenticity assessment. Non-target effect-directed profiling was developed using high-performance thin-layer chromatography-multi-imaging-effect-directed assays (HPTLC-UV/Vis/FLD-EDA). Results demonstrated substantial differences in compounds associated with functional attributes, notably antioxidant potential, between the peppermint samples. Further chemical analysis by high-performance liquid chromatography-photodiode array/mass spectrometry detection (HPLC-PDA/MS) and headspace solid-phase microextraction-gas chromatography-flame ionization/MS detection (headspace SPME-GC-FID/MS) confirmed compositional differences. A broad variability in the contents of flavonoids and volatiles was observed. The peppermint samples were further screened for their antioxidant potential using the Caenorhabditis elegans model, and the results indicated concordance with observed content differences of the identified functional compounds. These results documented variability among raw materials of peppermint leaves, which can yield highly variable extract products that may result in differing effects on functional targets in vivo. Hence, product standardization via effect-directed profiles is proposed as an appropriate tool.

Immunomodulatory and Antioxidant Properties of a Novel Potential Probiotic Bacillus clausii CSI08.

Spore-forming bacteria of the Bacillus genus have demonstrated potential as probiotics for human use. Bacillus clausii have been recognized as efficacious and safe agents for preventing and treating diarrhea in children and adults, with pronounced immunomodulatory properties during several in vitro and clinical studies. Herein, we characterize the novel strain of B. clausii CSI08 (Munispore®) for probiotic attributes including resistance to gastric acid and bile salts, the ability to suppress the growth of human pathogens, the capacity to assimilate wide range of carbohydrates and to produce potentially beneficial enzymes. Both spores and vegetative cells of this strain were able to adhere to a mucous-producing intestinal cell line and to attenuate the LPS- and Poly I:C-triggered pro-inflammatory cytokine gene expression in HT-29 intestinal cell line. Vegetative cells of B. clausii CSI08 were also able to elicit a robust immune response in U937-derived macrophages. Furthermore, B. clausii CSI08 demonstrated cytoprotective effects in in vitro cell culture and in vivo C. elegans models of oxidative stress. Taken together, these beneficial properties provide strong evidence for B. clausii CSI08 as a promising potential probiotic.

Lipoteichoic acid from Bifidobacterium animalis subsp. lactis BPL1: a novel postbiotic that reduces fat deposition via IGF-1 pathway.

Obesity and its related metabolic disorders, such as diabetes and cardiovascular disease, are major risk factors for morbidity and mortality in the world population. In this context, supplementation with the probiotic strain Bifidobacterium animalis subsp. lactis BPL1 (CECT8145) has been shown to ameliorate obesity biomarkers. Analyzing the basis of this observation and using the pre-clinical model Caenorhabditis elegans, we have found that lipoteichoic acid (LTA) of BPL1 is responsible for its fat-reducing properties and that this attribute is preserved under hyperglycaemic conditions. This fat-reducing capacity of both BPL1 and LTA-BPL1 is abolished under glucose restriction, as a result of changes in LTA chemical composition. Moreover, we have demonstrated that LTA exerts this function through the IGF-1 pathway, as does BPL1 strain. These results open the possibility of using LTA as a novel postbiotic, whose beneficial properties can be applied therapeutically and/or preventively in metabolic syndrome and diabetes-related disorders.

Small flexible automated system for monitoring Caenorhabditis elegans lifespan based on active vision and image processing techniques.

Traditionally Caenorhabditis elegans lifespan assays are performed by manually inspecting nematodes with a dissection microscope, which involves daily counting of live/dead worms cultured in Petri plates for 21-25 days. This manual inspection requires the screening of hundreds of worms to ensure statistical robustness, and is therefore a time-consuming approach. In recent years, various automated artificial vision systems have been reported to increase the throughput, however they usually provide less accurate results than manual assays. The main problems identified when using these vision systems are the false positives and false negatives, which occur due to culture media changes, occluded zones, dirtiness or condensation of the Petri plates. In this work, we developed and described a new C. elegans monitoring machine, SiViS, which consists of a flexible and compact platform design to analyse C. elegans cultures using the standard Petri plates seeded with E. coli. Our system uses an active vision illumination technique and different image-processing pipelines for motion detection, both previously reported, providing a fully automated image processing pipeline. In addition, this study validated both these methods and the feasibility of the SiViS machine for lifespan experiments by comparing them with manual lifespan assays. Results demonstrated that the automated system yields consistent replicates (p-value log rank test 0.699), and there are no significant differences between automated system assays and traditionally manual assays (p-value 0.637). Finally, although we have focused on the use of SiViS in longevity assays, the system configuration is flexible and can, thus, be adapted to other C. elegans studies such as toxicity, mobility and behaviour.

Heat-Treated Bifidobacterium longum CECT-7347: A Whole-Cell Postbiotic with Antioxidant, Anti-Inflammatory, and Gut-Barrier Protection Properties.

Non-viable preparations of probiotics, as whole-cell postbiotics, attract increasing interest because of their intrinsic technological stability, and their functional properties, such as immune system modulation, gut barrier maintenance, and protection against pathogens. However, reports on Bifidobacteria-derived postbiotics remain scarce. This study aims to demonstrate the functional properties of a heat-treated (HT), non-viable, Bifidobacterium longum strain, CECT-7347, a strain previously selected for its anti-inflammatory phenotype and ability to improve biomarkers of intestinal integrity in clinical trials. The study used the nematode Caenorhabditis elegans and HT-29 cell cultures as eukaryotic model systems. Our results show that HT-CECT-7347 preserves the capacity to protect against oxidative stress damage, while it also reduces acute inflammatory response and gut-barrier disruption, and inhibits bacterial colonization, by activating pathways related to innate immune function. These findings highlight the interest of the ingredient as a novel postbiotic and pave the way to broaden the range of HT-CECT-7347 applications in gut health.

Evaluation of Carotenoids Protection Against Oxidative Stress in the Animal Model Caenorhabditis elegans.

The nematode Caenorhabditis elegans is a versatile and powerful model organism for animal experimental research and, despite being an invertebrate, displays remarkably similar molecular bases and conserved cellular pathways to those of humans. Oxidative stress is an etiological factor that influences numerous diseases, degenerative processes and aging. C. elegans has revealed as an opportune and feasible organism to investigate the antioxidant effects of different bioactives or complex food matrices, and a number of protocols have been developed by using different oxidative stressors. Carotenoids are recognized as quenchers and scavengers of reactive oxygen species, and many of their related health benefits attributed in the diet are tightly linked to their antioxidant properties. In this chapter, we report a simple and rapid assay to evaluate the protection capacity of pure carotenoids or complex carotenoid extracts against oxidative stress in the model system C. elegans. The protocol describes a representative feeding experiment by adding carotenoids to the nematode growth medium and after an incubation period, the C. elegans populations fed with carotenoids are exposed to an acute oxidative stress by using H2O2 as oxidative agent. The protection against oxidative stress is evaluated as the survival rate of the nematodes fed with the carotenoid prior to receiving oxidative treatment compared with the survival rate of control nematode population. In order to confirm the carotenoid intake by the nematodes during the feeding experiment a bioassimilation experiment is also reported.

ß-Cryptoxanthin Reduces Body Fat and Increases Oxidative Stress Response in Caenorhabditis elegans Model.

ß-Cryptoxanthin (BCX) is a major dietary pro-vitamin A carotenoid, found mainly in fruits and vegetables. Several studies showed the beneficial effects of BCX on different aspects of human health. In spite of the evidence, the molecular mechanisms of action of BCX need to be further investigated. The Caenorhabditis elegans model was used to analyze in vivo the activity of BCX on fat reduction and protection to oxidative stress. Dose-response assays provided evidence of the efficacy of BCX at very low dose (0.025 µg/mL) (p < 0.001) on these processes. Moreover, a comparative analysis with other carotenoids, such as lycopene and ß-carotene, showed a stronger effect of BCX. Furthermore, a transcriptomic analysis of wild-type nematodes supplemented with BCX revealed upregulation of the energy metabolism, response to stress, and protein homeostasis as the main metabolic targets of this xanthophyll. Collectively, this study provides new in vivo evidence of the potential therapeutic use of BCX in the prevention of diseases related to metabolic syndrome and aging.

Toxicological assessment of mesoporous silica particles in the nematode Caenorhabditis elegans.

Here we report the toxicological evaluation of mesoporous silica particles (MSPs) in the nematode C. elegans. Specifically, we have investigated the effect of bare micro- (M0) and nano-sized (N0) MSPs, and their corresponding functionalized particles with a starch derivative (Glu-N) (M1 and N1, respectively) on C. elegans ageing parameters. The toxicity of MSPs, their impact on C. elegans lifespan, movement capacity, progeny and ability to survive upon exposure to acute oxidative stress were assessed. This study demonstrated that both size particles assayed (M0 and N0), labeled with rhodamine and monitored through fluorescence microscopy, are ingested by the nematode. Moreover, toxicity assays indicated that bare nano-sized particles (N0) have a negative impact on the C. elegans lifespan, reducing mobility and progeny production. By contrast, micro-sized particles (M0) proved innocuous for the nematodes. Furthermore, functionalization of nanoparticles with starch derivative reduced their toxicity in C. elegans. Thus, oral intake of N1 comparatively increased the mean lifespan and activity rates as well as resistance to oxidative stress. The overall findings presented here demonstrate the influence of MSP size and surface on their potential toxicity in vivo and indicate the silica-based mesoporous particles to be a potential support for encapsulation in oral delivery applications. Furthermore, the good correlation obtained between healthy aging variables and viability (mean lifespan) validates the use of C. elegans as a multicellular organism for nanotoxicology studies of MSPs.

Monitorización del riesgo cardiovascular y metabólico en niños y adolescentes en tratamiento antipsicótico: un estudio descriptivo transversal / Cardiovascular and metabolic monitoring of children and adolescents on antipsychotic treatment: a cross-sectional descriptive study

Antecedentes. El control cardiovascular y metabólico en pacientes que toman antipsicóticos es fundamental y adquiere una especial relevancia en la edad pediátrica, por ser pacientes más vulnerables y porque cada vez se prescriben fármacos de este tipo en más ocasiones. Objetivo. Describir el grado de cumplimiento de las recomendaciones de control de parámetros cardiovasculares y metabólicos en un grupo de niños y jóvenes en tratamiento antipsicótico. Método. Se trata de un estudio descriptivo transversal en el que se comparan un grupo de 220 pacientes de 8-17 años, diagnosticados de trastorno mental (TM) y en tratamiento antipsicótico, con otro grupo de referencia constituido por 199 individuos asmáticos no expuestos a antipsicóticos del mismo grupo de edad. Los datos se extrajeron de la historia clínica informatizada ECAP en el año 2013. Resultados. La edad de los niños se sitúa entre los 8 y 17 años. La media de edad es de 12 años. La risperidona es el antipsicótico pautado más frecuentemente (62,7%). El porcentaje de registro de peso, talla, índice de masa corporal (IMC) y presión arterial (PA) es de aproximadamente un 50% en los pacientes del grupo TM. En el grupo TM se observa un mayor registro de los parámetros físicos de control cardiovascular (peso, talla, IMC y PA) en comparación con el grupo Asma. En conjunto, se registran más los parámetros físicos que los parámetros bioquímicos. Conclusiones. Este estudio evidencia la necesidad de seguir insistiendo en la monitorización de los parámetros cardiovasculares y metabólicos en los niños y jóvenes en tratamiento con antipsicóticos (AU)

Background. Cardiovascular and metabolic monitoring of patients on antipsychotic medication is essential. This becomes more important in those of paediatric age, as they are more vulnerable, and also because prescriptions of this kind of drugs are still increasing. Aim. To evaluate the monitoring of cardiovascular and metabolic risk factors in a group of children and young people on antipsychotic medication. Method. A descriptive cross-sectional study was conducted in which a group of 220 patients aged 8-17 years, diagnosed with a mental disorder and on antipsychotic treatment. They were compared to a control group of 199 asthmatic patients not exposed to antipsychotic drugs. Data was extracted from the computerised clinical history ECAP in 2013. Results. The mean age of the children was 12 years (8-17). Risperidone (67%) was the most frequent treatment. The recording of Body Mass Index (BMI) and blood pressure (AP) was 50% in Mental Disorder (MD) patients. A higher number of cardiovascular monitoring physical parameters (weight, height, BMI and BP) were observed in the MD group compared to the control Asthma control group. Altogether, more physical parameters than biochemistry parameters were recorded. Conclusions. This study shows that the recording of cardiovascular parameters and metabolic studies needs to be improved in children and adolescents on treatment with antipsychotics (AU)

Cardiovascular and metabolic monitoring of children and adolescents on antipsychotic treatment: A cross-sectional descriptive study. / Monitorización del riesgo cardiovascular y metabólico en niños y adolescentes en tratamiento antipsicótico: un estudio descriptivo transversal.

BACKGROUND: Cardiovascular and metabolic monitoring of patients on antipsychotic medication is essential. This becomes more important in those of paediatric age, as they are more vulnerable, and also because prescriptions of this kind of drugs are still increasing. AIM: To evaluate the monitoring of cardiovascular and metabolic risk factors in a group of children and young people on antipsychotic medication. METHOD: A descriptive cross-sectional study was conducted in which a group of 220 patients aged 8-17 years, diagnosed with a mental disorder and on antipsychotic treatment. They were compared to a control group of 199 asthmatic patients not exposed to antipsychotic drugs. Data was extracted from the computerised clinical history ECAP in 2013. RESULTS: The mean age of the children was 12 years (8-17). Risperidone (67%) was the most frequent treatment. The recording of Body Mass Index (BMI) and blood pressure (AP) was 50% in Mental Disorder (MD) patients. A higher number of cardiovascular monitoring physical parameters (weight, height, BMI and BP) were observed in the MD group compared to the control Asthma control group. Altogether, more physical parameters than biochemistry parameters were recorded. CONCLUSIONS: This study shows that the recording of cardiovascular parameters and metabolic studies needs to be improved in children and adolescents on treatment with antipsychotics.

A nutritional supplement containing lactoferrin stimulates the immune system, extends lifespan, and reduces amyloid ß peptide toxicity in Caenorhabditis elegans.

Lactoferrin is a highly multifunctional glycoprotein involved in many physiological functions, including regulation of iron absorption and immune responses. Moreover, there is increasing evidence for neuroprotective effects of lactoferrin. We used Caenorhabditis elegans as a model to test the protective effects, both on phenotype and transcriptome, of a nutraceutical product based on lactoferrin liposomes. In a dose-dependent manner, the lactoferrin-based product protected against acute oxidative stress and extended lifespan of C. elegans N2. Furthermore, Paralysis of the transgenic C. elegans strain CL4176, caused by Aß1-42 aggregates, was clearly ameliorated by treatment. Transcriptome analysis in treated nematodes indicated immune system stimulation, together with enhancement of processes involved in the oxidative stress response. The lactoferrin-based product also improved the protein homeostasis processes, cellular adhesion processes, and neurogenesis in the nematode. In summary, the tested product exerts protection against aging and neurodegeneration, modulating processes involved in oxidative stress response, protein homeostasis, synaptic function, and xenobiotic metabolism. This lactoferrin-based product is also able to stimulate the immune system, as well as improving reproductive status and energy metabolism. These findings suggest that oral supplementation with this lactoferrin-based product could improve the immune system and antioxidant capacity. Further studies to understand the molecular mechanisms related with neuronal function would be of interest.

Probiotic Strain Bifidobacterium animalis subsp. lactis CECT 8145 Reduces Fat Content and Modulates Lipid Metabolism and Antioxidant Response in Caenorhabditis elegans.

Recently, microbial changes in the human gut have been proposed as a possible cause of obesity. Therefore, modulation of microbiota through probiotic supplements is of great interest to support obesity therapeutics. The present study examines the functional effect and metabolic targets of a bacterial strain, Bifidobacterium animalis subsp. lactis CECT 8145, selected from a screening in Caenorhabditis elegans. This strain significantly reduced total lipids (40.5% ± 2.4) and triglycerides (27.6% ± 0.5), exerting antioxidant effects in the nematode (30% ± 2.8 increase in survival vs control); activities were also preserved in a final food matrix (milk). Furthermore, transcriptomic and metabolomic analyses in nematodes fed with strain CECT 8145 revealed modulation of the energy and lipid metabolism, as well as the tryptophan metabolism (satiety), as the main metabolic targets of the probiotic. In conclusion, our study describes for the first time a new B. animalis subsp. lactis strain, CECT 8145, as a promising probiotic for obesity disorders. Furthermore, the data support future studies in obesity murine models.

Comparative genomic analysis reveals a critical role of de novo nucleotide biosynthesis for Saccharomyces cerevisiae virulence.

In recent years, the number of human infection cases produced by the food related species Saccharomyces cerevisiae has increased. Whereas many strains of this species are considered safe, other 'opportunistic' strains show a high degree of potential virulence attributes and can cause infections in immunocompromised patients. Here we studied the genetic characteristics of selected opportunistic strains isolated from dietary supplements and also from patients by array comparative genomic hybridization. Our results show increased copy numbers of IMD genes in opportunistic strains, which are implicated in the de novo biosynthesis of the purine nucleotides pathway. The importance of this pathway for virulence of S. cerevisiae was confirmed by infections in immunodeficient murine models using a GUA1 mutant, a key gene of this pathway. We show that exogenous guanine, an end product of this pathway in its triphosphorylated form, increases the survival of yeast strains in ex vivo blood infections. Finally, we show the importance of the DNA damage response that activates dNTP biosynthesis in yeast cells during ex vivo blood infections. We conclude that opportunistic yeasts may use an enhanced de novo biosynthesis of the purine nucleotides pathway to increase survival and favor infections in the host.

Immunoproteomic profiling of Saccharomyces cerevisiae systemic infection in a murine model.

Saccharomyces cerevisiae is considered a safe microorganism widely used as a dietary supplement. However, in the latest decades several cases of S. cerevisiae infections have been reported. Recent studies in a murine model of systemic infection have also revealed the virulence of some S. cerevisiae dietary strains. Here we use an immunoproteomic approach based on protein separation by 2D-PAGE followed by Western-blotting to compare the serological response against a virulent dietary and a non-virulent laboratory strains leading to the identification of highly different patterns of antigenic proteins. Thirty-six proteins that elicit a serological response in mice have been identified. Most of them are involved in stress responses and metabolic pathways. Their selectivity as putative biomarkers for S. cerevisiae infections was assessed by testing sera from S. cerevisiae-infected mice against Candida albicans and C. glabrata proteins. Some chaperones and metabolic proteins showed cross-reactivity. We also compare the S. cerevisiae immunodetected proteins with previously described C. albicans antigens. The results point to the stress-related proteins Ahp1, Yhb1 and Oye2, as well as the glutamine synthetase Gln1 and the oxysosterol binding protein Kes1 as putative candidates for being evaluated as biomarkers for diagnostic assays of S. cerevisiae infections. BIOLOGICAL SIGNIFICANCE: S. cerevisiae can cause opportunistic infections, and therefore, a precise diagnosis of fungal infections is necessary. This immunoproteomic analysis of sera from a model murine infection with a virulent dietary S. cerevisiae strain has been shown to be a source of candidate proteins for being evaluated as biomarkers to develop assays for diagnosis of S. cerevisiae infections. To our knowledge, this is the first study devoted to the identification of S. cerevisiae immunogenic proteins and the results allowed the proposal of five antigens to be further investigated.

Pathogenic potential of Saccharomyces strains isolated from dietary supplements.

Saccharomyces cerevisiae plays a beneficial role in health because of its intrinsic nutritional value and bio-functional properties, which is why it is also used as a dietary supplement. However, the perception that S. cerevisiae is harmless has changed due to an increasing number of infections caused by this yeast. Given this scenario, we have tested whether viable strains contained in dietary supplements displayed virulence-associated phenotypic traits that could contribute to virulence in humans. We have also performed an in vivo study of the pathogenic potential of these strains using a murine model of systemic infection by intravenous inoculation. A total of 5 strains were isolated from 22 commercial products and tested. Results highlight one strain (D14) in terms of burden levels in brains and kidneys and ability to cause death, whereas the other two strains (D2 and D4) were considered of low virulence. Our results suggest a strong relationship between some of the virulence-associated phenotypic traits (ability to grow at 39°C and pseudohyphal growth) and the in vivo virulence in a mouse model of intravenous inoculation for isolates under study. The isolate displaying greatest virulence (D14) was evaluated in an experimental murine model of gastrointestinal infection with immunosuppression and disruption of mucosal integrity, which are common risk factors for developing infection in humans, and results were compared with an avirulent strain (D23). We showed that D14 was able to spread to mesenteric nodes and distant organs under these conditions. Given the widespread consumption of dietary supplements, we recommend only safe strains be used.

A cocoa peptide protects Caenorhabditis elegans from oxidative stress and ß-amyloid peptide toxicity.

BACKGROUND: Cocoa and cocoa-based products contain different compounds with beneficial properties for human health. Polyphenols are the most frequently studied, and display antioxidant properties. Moreover, protein content is a very interesting source of antioxidant bioactive peptides, which can be used therapeutically for the prevention of age-related diseases. METHODOLOGY/PRINCIPAL FINDINGS: A bioactive peptide, 13L (DNYDNSAGKWWVT), was obtained from a hydrolyzed cocoa by-product by chromatography. The in vitro inhibition of prolyl endopeptidase (PEP) was used as screening method to select the suitable fraction for peptide identification. Functional analysis of 13L peptide was achieved using the transgenic Caenorhabditis elegans strain CL4176 expressing the human Aß1₋42 peptide as a pre-clinical in vivo model for Alzheimer's disease. Among the peptides isolated, peptide 13L (1 µg/mL) showed the highest antioxidant activity (P≤0.001) in the wild-type strain (N2). Furthermore, 13L produced a significant delay in body paralysis in strain CL4176, especially in the 24-47 h period after Aß1₋42 peptide induction (P≤0.0001). This observation is in accordance with the reduction of Aß deposits in CL4176 by western blot. Finally, transcriptomic analysis in wild-type nematodes treated with 13L revealed modulation of the proteosomal and synaptic functions as the main metabolic targets of the peptide. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the cocoa 13L peptide has antioxidant activity and may reduce Aß deposition in a C. elegans model of Alzheimer's disease; and therefore has a putative therapeutic potential for prevention of age-related diseases. Further studies in murine models and humans will be essential to analyze the effectiveness of the 13L peptide in higher animals.

Caenorhabditis elegans as a model to study the effectiveness and metabolic targets of dietary supplements used for obesity treatment: the specific case of a conjugated linoleic acid mixture (Tonalin).

The antiobesity effect of conjugated linoleic acid (CLA) has previously been described in different animal models. The aim of the present study was to investigate the effect of a commercial mixture (Tonalin) on Caenorhabditis elegans to assess their potential use for functional ingredient screenings. Body-fat reduction with Tonalin was demonstrated in wild-type strain N2. The 1 µg/mL dose was the most effective, either alone or added to a food matrix, and also significantly decreased triglyceride content in nematodes fed on the CLA mixture. Furthermore, the antiobesity effect was related to the CLA isomer trans-10, cis-12. Finally, the transcriptional study showed C. elegans fed with Tonalin (1 µg/mL) underwent an upregulation of energy metabolism, reproduction, protein metabolism and oxidative stress processes. In conclusion, the results presented here clearly correlate well with other animal studies, demonstrating the value of C. elegans as a useful model to evaluate antiobesity compounds/ingredients.

Transcriptomics in human blood incubation reveals the importance of oxidative stress response in Saccharomyces cerevisiae clinical strains.

BACKGROUND: In recent years an increasing number of yeast infections in humans have been related to certain clinical isolates of Saccharomyces cerevisiae. Some clinical strains showed in vivo and in vitro virulence traits and were able to cause death in mice whereas other clinical strains were avirulent. RESULTS: In this work, we studied the transcriptional profiles of two S. cerevisiae clinical strains showing virulent traits and two control non-virulent strains during a blood incubation model and detected a specific transcriptional response of clinical strains. This response involves an mRNA levels increase of amino acid biosynthesis genes and especially oxidative stress related genes. We observed that the clinical strains were more resistant to reactive oxygen species in vitro. In addition, blood survival of clinical isolates was high, reaching similar levels to pathogenic Candida albicans strain. Furthermore, a virulent strain mutant in the transcription factor Yap1p, unable to grow in oxidative stress conditions, presented decreased survival levels in human blood compared with the wild type or YAP1 reconstituted strain. CONCLUSIONS: Our data suggest that this enhanced oxidative stress response in virulent clinical isolates, presumably induced in response to oxidative burst from host defense cells, is important to increase survival in human blood and can help to infect and even produce death in mice models.

Clinical Saccharomyces cerevisiae isolates cannot cross the epithelial barrier in vitro.

Saccharomyces cerevisiae is generally considered to be a safe organism and is essential to produce many different kinds of foods as well as being widely used as a dietary supplement. However, several isolates, which are genetically related to brewing and baking yeasts, have shown virulent traits, being able to produce human infections in immunodeficient patients. Previously it has been shown that the administration of S. cerevisiae clinical isolates can lead to systemic infections, reaching several organs in murine systems. In this work, we studied S. cerevisiae clinical isolates in an in vitro intestinal epithelial barrier model, comparing their behaviour with that of several strains of the related pathogens Candida glabrata and Candida albicans. The results showed that, in contrast to C. glabrata and C. albicans, S. cerevisiae was not able to cross the intestinal barrier. We concluded that S. cerevisiae can only perform opportunistic or passive crossings when epithelial barrier integrity is previously compromised.