B1-Integrin blockade prevents podocyte injury in experimental models of minimal change disease / El bloqueo de la integrina B1 previene la lesión de los podocitos en modelos experimentales en la enfermedad de cambios mínimos

Introduction Activation of the focal adhesion kinase (FAK) in podocytes is involved in the pathogenesis of minimal change disease (MCD), but the pathway leading to its activation in this disease is unknown. Here, we tested whether podocyte β1 integrin is the upstream modulator of FAK activation and podocyte injury in experimental models of MCD-like injury. Methods We used lipopolysaccharide (LPS) and MCD sera to induce MCD-like changes in vivo and in cultured human podocytes, respectively. We performed functional studies using specific β1 integrin inhibitors in vivo and in vitro, and integrated histological analysis, western blotting, and immunofluorescence to assess for morphological and molecular changes in podocytes. By ELISA, we measured serum LPS levels in 35 children with MCD or presumed MCD (idiopathic nephrotic syndrome [INS]) and in 18 healthy controls. Results LPS-injected mice showed morphological (foot process effacement, and normal appearing glomeruli on light microscopy) and molecular features (synaptopodin loss, nephrin mislocalization, FAK phosphorylation) characteristic of human MCD. Administration of a β1 integrin inhibitor to mice abrogated FAK phosphorylation, and ameliorated proteinuria and podocyte injury following LPS. Children with MCD/INS in relapse had higher serum LPS levels than controls. In cultured human podocytes, β1 integrin blockade prevented cytoskeletal rearrangements following exposure to MCD sera in relapse. Conclusions Podocyte β1 integrin activation is an upstream mediator of FAK phosphorylation and podocyte injury in models of MCD-like injury (AU)

Antecedentes La activación de la quinasa de adhesión focal (FAK) en podocitos juega un papel en la patogénesis de la enfermedad de cambios mínimos (ECM), pero su mecanismo de activación en dicha enfermedad es desconocido. En este estudio investigamos si la integrina β1 de los podocitos modula la activación de FAK y del daño podocitario en modelos experimentales de la ECM. Métodos Utilizamos lipopolisacárido (LPS) y suero de pacientes con ECM para inducir daño podocitario in vivo e in vitro, respectivamente. Realizamos estudios funcionales usando inhibidores específicos de la integrina β1 in vivo e in vitro, así como estudios histológicos, western blots y técnicas de inmunofluorescencia para evaluar cambios morfológicos y moleculares en podocitos. Usando ELISA medimos los niveles séricos de LPS en 35 niños con ECM o sospecha de ECM (síndrome nefrótico idiopático [SNI]) y en 18 individuos sanos. Resultados Los ratones inyectados con LPS desarrollaron cambios morfológicos (fusión de pedicelos, con apariencia normal de los glomérulos) y moleculares (pérdida de la expresión de sinaptopodina, cambio en la localización de la nefrina fosforilada y fosforilzación de FAK), que son característicos de la ECM en humanos. La administración de un inhibidor de la integrina β1 en ratones disminuyó la fosforilación de FAK, proteinuria y daño podocitario que ocurre tras la inyección de LPS. En niños con ECM/SNI, los niveles séricos de LPS fueron más elevados que en controles. En cultivos de podocitos humanos, la adicción de un inhibidor de la integrina β1 al suero de niños con ECM en recaída evitó cambios en el citoesqueleto. Conclusiones La integrina β1 de los podocitos actúa como mediador de la activación de la FAK y del daño podocitario en modelos experimentales de la ECM (AU)

Snail-induced anaphylaxis in patients with underlying Artemisia vulgaris pollinosis: the role of carbohydrates

Purpose: The importance of carbohydrates in anaphylaxis has been described with some foods. The current work intends to obtain clinical and immunological evidence of the importance of the O-glycans for IgE binding activity in anaphylactic reactions due to Helix aspersa (HA) ingestión and Artemisia vulgaris (AV) exposition. Methods: The studio focused on two cases of IgE-mediated anaphylaxis induced by snail ingestion in patients with underlying rhino-conjunctivitis and asthma due to AV. We performed on both patients: skin prick tests ( SPTs) with HA and AV and with a battery of aeroallergen, controlled nasal challenge and specific IgE to HA and AV, ImmunoCAP ISAC®, and a differential pattern of IgE recognition with SDS-PAGE Immunoblotting (SDSI) when these allergens have suffered an O-deglycosylation procedure. Results: The patients showed positive results in SPTs, nasal challenges, and serum-specific IgE against HA and AV. In patient 1, the SDSI detected several IgE-binding proteins in AV with a molecular mass of 22, 24, and 44 kDa, whereas a band of 12 kDa was detected in HA. On the other hand, patient 2’s serum revealed an IgE-binding zone between 75 and 20 kDa in the AV and a band of 24 kDa in the HA. When glycans were removed, patient 1’s serum only revealed the AV’s 22 and 24 kDa bands, whereas patient 2’s serum did not detect any IgE-reactive protein in the HA. Conclusions: Our data suggest that O-glycosylation can be relevant in patients with anaphylaxis due to snails and allergy to Artemisia vulgaris. This new entity representing cross-reactivity between AV and HA could be named Snail-Artemisia Syndrome (AU)

Soy and Algae Combination Using Tempe FermentationMethod: A Proposed Opinion for the Development of Functional Food / Combinación de soja y algas usando el método de fermentación de Tempe: una propuesta de opinión para el desarrollo de alimentos funcionales

Backgrounds and Aims: Marine algae and plant-basedprotein have gained popularity among the most sought-afterfunctional food ingredients and appeared as emerging trendsfor functional food. Combining ingredients that are wellknown to exert beneficial properties towards health can beconsidered an innovative strategy for developing novel func-tional foods. Each functional ingredient may contribute differ-ently to health promotion and complement the beneficialproperties of other components, thus increasing the overallhealth values of novel functional foods. In addition, these in-gredients may exhibit synergistic activities that would improvethe functionality of novel functional foods. Therefore, we pro-pose that combining marine algae in the fermentation oftempe would be an innovative strategy to create a novel soy-bean-based functional food. This opinion-review article wouldprovide a thorough insight into the conception, feasibility, andfurther research regarding the algae-tempe combination as afuture functional food. Results and Conclusions: The supplementation of ma-rine algae in the fermentation of tempe would open a newhorizon about novel soybean-based functional food.Introducing marine algae in tempe production would bringadditional compounds that might not be naturally present insoybeans. These compounds are subject to mold fermenta-tion. We suggest that marine algae would improve the nutri-tional value of tempe by providing additional carbohydratesand protein. We suggest algal supplementation in tempe fer-mentation could be done by incorporating freeze-dried algalpowder into the pre-boiled soybeans and starters before fer-mentation. We also suspect that algal polysaccharides mightaffect the texture of the tempe and bind water required formold growth during fermentation. Therefore, the fermenta-tion parameters for this product would need optimizing.(AU)

Glycosylation and its research progress in endometrial cancer

Endometrial cancer (EC) is one of the most common tumors in the female reproductive system, which seriously threatens women's health, particularly in developed countries. 13% of the patients with EC have a poor prognosis due to recurrence and metastasis. Therefore, identifying good predictive biomarkers and therapeutic targets is critical to enable the early detection of metastasis and improve the prognosis. For decades, extensive studies had focused on glycans and glycoproteins in the progression of cancer. The types of glycans that are covalently attached to the polypeptide backbone, usually via nitrogen or oxygen linkages, are known as N‑glycans or O‑glycans, respectively. The degree of protein glycosylation and the aberrant changes in the carbohydrate structures have been implicated in the extent of tumorigenesis and reported to play a critical role in regulating tumor invasion, metabolism, and immunity. This review summarizes the essential biological role of glycosylation in EC, with a focus on the recent advances in glycomics and glycosylation markers, highlighting their implications in the diagnosis and treatment of EC. (AU)

Caveolin-1 knockout mice have altered serum N-glycan profile and sialyltransferase tissue expression

Caveolin-1 (Cav-1) is a constitutive protein within caveolar membranes. Previous studies from our group and others indicated that Cav-1 could mediate N-glycosylation, α2,6-sialylation, and fucosylation in mouse hepatocarcinoma cells in vitro. However, little is known about the effect of Cav-1 expression on glycosylation modifications in vivo. In this study, the N-glycan profiles in serum from Cav-1−/− mice were investigated by lectin microarray and mass spectrometric analysis approaches. The results showed that levels of multi-antennary branched, α2,6-sialylated, and galactosylated N-glycans increased, while high-mannose typed and fucosylated N-glycans decreased in the serum of Cav-1−/− mice, compared with that of wild-type mice. Furthermore, the real-time quantitative PCR analysis indicated that α2,6-sialyltransferase gene expression decreased significantly in Cav-1−/− mouse organ tissues, but α2,3- and α2,8-sialyltransferase did not. Of them, both mRNA and protein expression levels of the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) had dramatically reduced in Cav-1−/− mice organ tissues, which was consistent with the α2,6-sialyl Gal/GalNAc level reduced significantly in tissues instead of serum from Cav-1−/− mice. These results provide for the first time the N-glycans profile of Cav-1−/− mice serum, which will facilitate understanding the function of Cav-1 from the perspective of glycosylation. (AU)

Momordica charantia polysaccharides alleviate diarrhea-predominant irritable bowel syndrome by regulating intestinal inflammation and barrier via NF-kB pathway

Background: Momordica charantia exerts anti-inflammatory effect against ulcerative colitis. Momordica charantia polysaccharides (MCPs) attenuate gastritis through inhibition of ethanol- induced inflammatory response. Objective: The role of MCPs in diarrhea-predominant irritable bowel syndrome (IBS-D) is investigated. Materials and Methods: Chemical stimulation followed by acute and chronic pressure stimu-lation was used to establish rats model with IBS-D. The model rats were then administrated with MCPs. Defecation frequency, fecal water content and abdominal withdrawal reflex (AWR) score were then recorded. Pathologic changes in the colonic tissues were evaluated by hema-toxylin and eosin staining. Inflammation was detected by ELISA and qRT-PCR, and immunohis-tochemistry was used to assess intestinal mucosal permeability.Results: First, IBS-D of mice wasIBS-D ratsmice exhibited many abnormal clinical manifestations, including increased frequency of defecation, fecal water content, and abdominal withdrawal reflex (AWR) score. Second, the mice were administrated with MCPs, which reduced fre-quency of defecation, fecal water content, and AWR score, and 100-mg/kg MCPs indicated therapeutic effect on IBS-D mice equivalent to rifaximin. Moreover, MCPs also ameliorated pathologic changes in the colonic tissues of IBS-D mice. Third, inflammatory response in IBS-D mice was also suppressed by MCPs through up-regulation of Interleukin (IL)-10, and down-regulation of tumor necrosis factor-α (TNF-α), Interleukin(IL)-1β, and IL-6. MCPs enhanced levels of occludin (OCLN) and zona occludens protein-1 (ZO-1) in IBS-D mice to improve intestinal mucosal permeability. Finally, phosphorylation of p65 in IBS-D mice was reduced by MCP treatmen (AU)

Phosphorylated ERM Mediates Lipopolysaccharide Induced Pulmonary Microvascular Endothelial Cells Permeability Through Negatively Regulating Rac1 Activity / La fosforilación de ERM media la permeabilidad de las células endoteliales de la microvasculatura pulmonar inducida por polisacárido mediante regulación negativa de la actividad de Rac1

Introduction: The endotoxin lipopolysaccharide (LPS)-induced pulmonary endothelial barrier disruption is a key pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the molecular mechanisms underlying LPS-impaired permeability of pulmonary microvascular endothelial cells (PMVECs) are not fully understood. Methods: Rat PMVECs were isolated and monolayered cultured, then challenged with different doses of LPS (0.1 mg/L, 1 mg/L, and 10 mg/L). Trans-endothelial electrical resistance (TER) was utilized to measure the integrity of the endothelial barrier. Ras-related C3 botulinum toxin substrate 1 (Rac1) activity and the phosphorylation of Ezrin/Radixin/Moesin proteins (ERM) were assessed by pulldown assay and Western Blotting. Small interfering RNA (siRNA) inhibition of Rac1 and Moesin were applied to evaluate the effect of PMVEs permeability and related pathway. Results: LPS induced dose and time-dependent decreases in TER and increase in ERM threonine phosphorylation, while inactivated Rac1 activity in PMVEC. siRNA study demonstrated that both Rac1 and Moesin were involved in the mediation of the LPS-induced hyperpermeability in PMVECs monolayers, and Rac1 and Moesin could regulate each other. Conclusion: Phosphorylated ERM mediates LPS induced PMVECs permeability through negatively regulating Rac1 activity

Introducción: La disrupción de la barrera endotelial pulmonar inducida por endotoxina o lipopolisacárido (LPS) es un factor patogénico clave en la lesión pulmonar aguda (LPA) y el síndrome de distrés respiratorio agudo (SDRA). Sin embargo, los mecanismos que subyacen al empeoramiento de la permeabilidad de las células endoteliales de la microvasculatura pulmonar (PMVECs, por sus siglas en inglés) no se conocen. Métodos: Se aislaron y cultivaron en monocapa PMVEC de rata, y se expusieron a diferentes dosis de LPS (0,1, 1 y 10 mg/l). Se utilizó la resistencia eléctrica transendotelial (TER, por sus siglas en inglés) para medir la integridad de la barrera endotelial. Se analizó la actividad del sustrato 1 de la toxina botulínica C3 relacionado con Ras (Rac1) y la fosforilación de las proteínas erzina/raxidina/moesina (ERM) mediante ensayos pulldown y Western blot. Para evaluar la permeabilidad de las PMVEC y las vías relacionadas se inhibieron Rac1 y moesina mediante ARN pequeño de interferencia (siRNA, por sus siglas en inglés). Resultados: El LPS indujo una disminución dependiente de dosis y tiempo de la TER e incrementó la fosforilación en treonina de ERM, al mismo tiempo que inactivó a Rac1 en las PMVEC. El estudio con siRNA demostró que, tanto Rac1 como la moesina estaban implicadas en la mediación de la permeabilidad de las PMVEC en monocapa inducida por LPS, y que Rac1 y la moesina podrían regularse mutuamente. Conclusión: La fosforilación de ERM media la permeabilidad de las PMVECs inducida por LPS mediante la regulación negativa de la actividad de Rac1

Isolation and Characterization of Novel Lignolytic, Cellulolytic, and Hemicellulolytic Bacteria from Wood-Feeding Termite Cryptotermes brevis

In a natural ecosystem, various organisms digest and hydrolyze lignocellulose biomass efficiently. Termites are one of them. They digest lignocellulose biomass with the help of symbiotic microorganisms in their gut. Therefore, termites gut may harbor potential sources of microorganisms capable to degrade lignocellulose biomass. In this study, termite gut microbiomes of Cryptotermes brevis species were isolated and identified for their capability to degrade lignin and polysaccharides. Alkali lignin, carboxymethylcellulose, and xylan were used as the only carbon sources in the medium to isolate lignin-, cellulose-, and hemicellulose-degrading bacteria. By this method, two bacteria strains, Bacillus sp. BMP01 and Ochrobactrum oryzae BMP03 strain were isolated and identified. Bacillus sp. BMP01 strain has capabilities to hydrolyze carboxymethylcellulose and xylan to glucose and xylose, respectively. This strain showed high xylanase activity (about 0.21 U/ml) and carboxymethyl cellulase activity (about 0.25 U/ml). The ability to hydrolyze both carboxymethylcellulose and xylan makes it superior to other known cellulolytic bacteria. Ochrobactrum oryzae BMP03 strain showed laccase activity, which indicates its ability to depolymerize lignin. Lignocellulose-degrading bacteria play a vital role in the biological conversion of lignocellulose biomass to biofuel. Overall, this study shows that termite's gut microbiomes are potential sources of lignocellulose-degrading bacteria that can be cultured and used in the biological conversion of lignocellulose biomass to biofuel

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Vacunación antineumocócica en el paciente con enfermedad pulmonar obstructiva crónica: una asignatura a mejorar / Antipneumococcal vaccination in patients with chronic obstructive pulmonar disease: A matter of improvement

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Aproximación diagnóstica de la respuesta a vacunas en inmunodeficiencias / No disponible

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Anticoagulant properties of a high molecular weight polysaccharide fraction (1000RS) of the ascidian Microcosmus exasperatus / Propiedades anticoagulantes de una fracción polisacárida de alto peso molecular (1000RS) del ascidian Microcosmus exasperatus

Aims: The anticoagulant effect and cytotoxicity of a high molecular weight polysaccharide fraction (1000RS) obtained from the tunic of the ascidia Microcosmus exasperatus were evaluated. Methods: Anticoagulant properties of 1000RS was evaluated by activated Partial Thromboplastin Time (aPTT), Thrombin Time (TT), Prothrombin Time (PT), anti-factor Xa and lupic anticoagulant (dRVVT) assays. Cytotoxicity was tested on murine hematopoietic cells using MTT assay. Results: This galactose rich fraction showed to be a potential anticoagulant due to its inhibitory effect on the intrinsic coagulation pathway. At the same time, anticoagulant doses of this fraction have no effect on cellular viability, which means that it can be used as a therapeutic agent. Conclusion: In vitro anticoagulant effect of 1000RS occurs at innocuous doses, however, it still need to be tested using in vivo models and its cytotoxicity evaluated in normal human cell lines

Objetivos: El efecto anticoagulante y la citotoxicidad de una fracción de polisacáridos de alto peso molecular (1000RS), obtenida de la túnica de la ascidia Microcosmus exasperatus, fueron evaluados. Métodos: La actividad anticoagulante de 1000RS fue evaluada mediante los ensayos de tiempo de tromboplastina parcial activado (TTPa), tiempo de trombina (TT), tiempo de protrombina (TP), anti factor Xa y anticoagulante lúpico (dRVVT). La citotoxicidad sobre las células hematopoyéticas murinas, fue evaluada usando el método del MTT. Resultados: Esta fracción rica en galactosa mostró ser un anticoagulante potencial debido a su efecto inhibidor de la vía intrínseca de la coagulación. Así mismo, las dosis anticoagulantes de esta fracción no afectan la viabilidad celular, lo cual ratifica su potencial como agente terapéutico. Conclusión: El efecto anticoagulante in vitro de 1000RS ocurre a dosis inocuas, sin embargo, este debe ser evaluado en modelos in vivo, así como su citotoxicidad sobre células humanas normales

Characterization of high exopolysaccharideproducing Lactobacillus strains isolated from mustard pickles for potential probiotic applications

The aim of this study was to characterize high exopolysaccharide (EPS)-producing lactic acid bacteria (LAB) isolated from mustard pickles in República de China for potential probiotic applications. Among 39 collected LAB strains, four most productive EPS-producing strains were selected for further analysis. Comparative analyses of 16S rDNA genes rpoA and pheS sequences demonstrated that these strains were members of Lactobacillus plantarum-group (LPG). NCD 2, NLD 4, SLC 13, and NLD 16 showed survival rates of 95.83% ± 0.49%, 95.07% ± 0.64%, 105.84% ± 0.82%, and 99.65% ± 0.31% under simulated gastrointestinal conditions, respectively. No cytotoxic effects on macrophage RAW 264.7 cells were observed when they were treated with a low dose (1 μg/ml) of stimulants extracted from the tested LAB strains. The production of nitric oxide in RAW 264.7 cells incubated with various LAB stimulants showed a dose-dependent increase. Among the four strains, SLC 13 showed higher inhibitory activity on growth of Enterococcus faecalis (BCRC 12302) and Yersinia enterocolitica (BCRC 10807). NLD 4 showed strong inhibitory activity against Escherichia coli O157:H7 (ATCC 43894) as compared with the other three strains. In summary, our results suggest that Lactobacillus pentosus SLC 13 may be a good candidate for probiotic applications and for development of antibacterial compounds (AU)

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Glucomannan and glucomannan plusspirulina added to pork significantly block dietary cholesterol effects on lipoproteinemia, arylesterase activity, and CYP7A1 expression in Zucker fa/fa rats

Zucker fa/fa rats easily develop dyslipidemia and obesity. Restructured pork (RP) is a suitable matrix for including functional ingredients. The effects of glucomannan- RP or glucomannan plus spirulina-enriched RP on plasma lipid/lipoprotein levels, cytochrome P450 7A1 (CYP7A1) expression, and arylesterase activity in growing fa/fa rats fed high-energy, high-fat cholesterol-enriched diets were tested. Groups of six rats each received diet containing 15 % control-RP (C), 15 % glucomannan-RP diet (G), 15 % glucomannan + spirulina-RP diet (GS), and same diets enriched with 2.4 % cholesterol and 0.49 % cholic acid (cholesterol-enriched control (HC), cholesterol-enriched glucomannan (HG), and cholesterol-enriched glucomannan + spirulina (HGS) diets) over a 7-week period. C diet induced obesity, severe hyperglycemia, moderate hypercholesterolemia, and hypertriglyceridemia. Those facts were not significantly modified by G or GS diets. G diet increased CYP7A1 expression but decreased the total cholesterol/high density lipoproteins (HDL)-cholesterol ratio (p < 0.05) vs. C diet. GS vs. G diet increased (p < 0.05) CYP7A1 expression. HC vs. C diet reduced food intake, body weight gain, and plasma glucose (p < 0.01) but increased cholesterolemia (p < 0.01), lipidemia (plasma cholesterol plus triglycerides) (p < 0.001), cholesterol/triglyceride ratio in very low density lipoproteins (VLDL), and HDL (p < 0.05), cholesterol transported by VLDL and intermediate density lipoproteins (IDL) + low density lipoproteins (LDL), total cholesterol/HDL-cholesterol ratio and CYP7A1 expression (at least p < 0.05). HG and HGS diets vs. HC noticeably reduced lipidemia (p < 0.001), normalized VLDL and IDL + LDL lipid composition, and increased CYP7A1 expression (p < 0.01) but did not modify the cholesterol/HDL-cholesterol ratio. HGS vs. HG decreased triglyceridemia, the triglyceride-glucose (TyG) index and increased arylesterase/HDL-cholesterol activity (p < 0.05). In conclusion, G- and GS-RP act as functional foods and notably blocked the dietary cholesterol effects. In addition, HGS-RP improved the glucomannan hypolipidemic effects, increased arylesterase/HDL-cholesterol activity, and decreased insulin resistance

Enfermedad de Alzheimer: nuevas estrategias terapéuticas / Alzheimer's disease: New therapeutic strategies

El rápido aumento de las tasas de prevalencia de la enfermedad de Alzheimer hace que se necesiten con urgencia tratamientos dirigidos a prevenir, detener o revertir esta devastadora enfermedad. A pesar de los avances en la comprensión de su patología molecular, todavía no existen fármacos que puedan detener su progresión. Esta revisión hace un recorrido por aquellos estudios en fase 2, o superior, que ensayan agonistas de receptores, sustancias que interfieren en la agregación, inhibidores/moduladores de las secretasas, hipolipidemiantes, y, finalmente y con mayor extensión, las inmunoterapias. El hecho de que recientemente hayan fallado las fases 3 para bapineuzumab y solaneuzumab no invalida el potencial de la inmunoterapia, ya que cada vez disponemos de más información y se están iniciando nuevos ensayos clínicos (AU)

The rapid increase in prevalence rates of Alzheimer's disease means that treatments to prevent, stop or reverse this devastating disease are urgently needed. Despite advances in understanding its molecular pathology, there are no drugs that can halt its progression. This review takes a tour through phase 2, or higher studies, probing receptor agonist agents interfering with aggregation, inhibitors/modulators of secretases, lipid-lowering agents, and, finally and most extensively, immunotherapy. The fact that phase 3 studies with bapineuzumab and solaneuzumab have recently failed does not invalidate the potential of immunotherapy, as more information is available and new clinical trials are being initiated (AU)

Proyecto FIND: La importancia de un diagnóstico precoz / The FIND project: The importance of early diagnosis

Las mucopolisacaridosis (MPS) son un grupo heterogéneo de enfermedades lisosomales ocasionadas por la deficiencia de las enzimas responsables de la degradación de los glucosaminoglicanos (GAG). Gracias a los actuales avances terapéuticos y al hecho de que un diagnóstico y tratamiento precoces implican una mejor evolución clínica, nos hemos planteado el proyecto FIND. El objetivo es realizar un cribado selectivo para detectar posibles casos de MPS en niños. Para ello se facilita a los pediatras que deseen participar, un kit como herramienta diagnóstica en el que se suministra la información y el material necesario para la obtención de muestras de orina y sangre impregnadas en papel analítico. Sobre la muestra de orina se mide la concentración de GAG y creatinina urinarias. A aquellas muestras con una concentración elevada de GAG, se podrá realizar la cuantificación de la actividad enzimática presente en la muestra de sangre, con la finalidad de identificar el posible defecto enzimático (AU)

The mucopolysaccharidoses (MPS) are a heterogeneous group of lysosomal diseases caused by the enzymatic deficiency of glycosaminoglycans (GAG) degradation. Due to recent treatment advances and the fact that early diagnosis and treatment implicate a better clinical outcome, we have started the FIND project. This project is a selective screening to detect possible MPS cases in children using urine and blood samples impregnated in analytical paper, easily obtained in the Pediatrician consultation and supplied in the FIND kit. We carry out the GAG determination on urine sample. Over those urine samples with an elevated GAG concentration; we can perform the enzymatic activity on the blood sample, in order to identify the possible enzyme defect (AU)

Una deficiencia no tan selectiva de IGA / No disponible

Describimos el caso de una paciente con historia de bronquitis, neumonias y deteccion de bronquiectasias, que es diagnosticada de deficiencia selectiva de IgA, con IgG e IgM en valores normales. El estudio inmunológico orientado hacia una deficiencia humoral permitio detectar una insuficiente produccion de anticuerpos frente a antigenos polisacaridos a pesar de sus cifras conservadas de IgG (AU)

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Selenium-enriched exopolysaccharides improve skeletal muscle glucose uptake of diabetic KKAy mice via AMPK pathway

Selenium-enriched exopolysaccharides (EPS) produced by Enterobacter cloacae Z0206 have been proven to possess effect on reducing blood glucose level in diabetic mice. To investigate the specific mechanism, we studied the effects of oral supply with EPS on skeletal muscle glucose transportation and consumption in high-fat-diet-induced diabetic KKAy mice. We found that EPS supplementation increased expressions of glucose transporter 4 (Glut4), hexokinase 2 (hk2), phosphorylation of AMP-activated kinase subunit α2 (pAMPKα2), and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), and increased expression of characteristic protein of oxidative fibers such as troponin I and cytochrome c (Cytc). Furthermore, we found that EPS increased glucose uptake and expressions of pAMPKα2 and PGC-1α in palmitic acid (PA)-induced C2C12 cells. However, while EPS inhibited AMPKα2 with interference RNA (iRNA), effects of EPS on the improvement of glucose uptake diminished. These results indicated that EPS may improve skeletal muscle glucose uptake of diabetic KKAy mice through AMPKα2-PGC-1α pathway

Beta-Glucans in the treatment and prevention of allergic diseases

β-glucans are a group of biologically active polysaccharides of natural origin with a proven pleiotropic immunomodulation effect. Their efficacy has been confirmed in the therapeutic treatment and prevention of various infectious diseases, secondary immune defects and also of oncologic disorders. Allergic diseases are one of the most frequent diseases and their prevalence continues to increase. They develop as a consequence of dysregulation of the immune system, especially when there is failure in the equilibrium of the response of TH1/TH2 lymphocytes towards TH2. New therapeutic approaches in the treatment of immunopathological conditions (e.g. allergic or oncologic) are directed to restoring the equilibrium among different T lymphocyte subpopulations. Based on in vitro experiments, and also on animal and human clinical studies, there is much evidence for the importance of β-glucans in the treatment and also prevention of allergic diseases; this opens new perspectives on the use of this widespread and popular group of natural substances

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Lectins in human pathogenic fungi / Lectinas en hongos patógenos para el ser humano

Lectins are carbohydrate-binding proteins widely distributed in nature. They constitute a highly diverse group of proteins consisting of many different protein families that are, in general, structurally unrelated. In the last few years, mushroom and other fungal lectins have attracted wide attention due to their antitumour, antiproliferative and immunomodulatory activities. The present mini-review provides concise information about recent developments in understanding lectins from human pathogenic fungi. A bibliographic search was performed in the Science Direct and PubMed databases, using the following keywords "lectin", "fungi", "human" and "pathogenic". Lectins present in fungi have been classified; however, the role played by lectins derived from human pathogenic fungi in infectious processes remains uncertain; thus, this is a scientific field requiring more research. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012) (AU)

Las lectinas son proteínas que se unen a los hidratos de carbono y están ampliamente distribuidas en la naturaleza. Constituyen un grupo muy diverso de proteínas incluidas en muchas familias que en general carecen de relación estructural. En los últimos años, se ha prestado mucha atención a las lectinas fúngicas debido a sus actividades antitumorales, antiproliferativas e inmunomoduladoras. La presente revisión proporciona información sucinta sobre los progresos recientes acontecidos en la comprensión de estas moléculas a partir de hongos patógenos para el ser humano. Emprendimos una búsqueda bibliográfica de los estudios publicados en las bases de datos Science Direct y PubMed, usando las palabras claves: «lectin» (lectina), «fungi» (hongos), «human» (humano) y «pathogenic» (patogénico). Se han clasificado las lectinas presentes en los hongos; sin embargo, el papel que desempeñan en los procesos infecciosos de hongos patógenos para el ser humano sigue por dilucidar, por lo que este es un ámbito científico que requiere mayor investigación.Este manuscrito forma parte de la serie de artículos presentados en el «V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi» (Oaxaca, México, 2012) (AU)

Effect of Histoplasma capsulatum glucans on host innate immunity / Efecto de los glucanos de Histoplasma capsulatum sobre la inmunidad innata del huésped

Beta-1,3-Glucan is important for infective forms (mycelial phase) of Histoplasma capsulatum and shares many features allotted to pathogen-associated molecular patterns. These cell wall carbohydrates interact with phagocytes by binding to Toll and lectin-like receptors, present on cell surfaces of macrophages, neutrophils, and dendritic cells. This review focuses on recent findings of the major H. capsulatum and host carbohydrate-driven interactions that account for internalization of fungal infective forms into phagocytes, and its subsequent avoidance of intracellular elimination. The yeast phase of H. capsulatum possesses different modulating factors of the macrophagic-anti-fungal mechanisms, mainly alpha-1,3-glucan, which is considered relevant for virulence. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012) (AU)

El Beta-1,3-glucano es importante para las formas infectivas (fase micelial) de Histoplasma capsulatum y comparte varias características asignadas a los patrones moleculares asociados con patógenos. Estos hidratos de carbono de la pared celular interaccionan con los fagocitos uniéndose a receptores tipo Toll y tipo lectina, que están presentes en las superficies celulares de macrófagos, neutrófilos y células dendríticas. En esta revisión se presta atención a los hallazgos recientes sobre las principales interacciones entre H. capsulatum y las células del huésped mediadas por hidratos de carbono, que permiten la internalización de las formas infectivas del hongo por los fagocitos, así como la posterior evitación de su eliminación intracelular. Se discuten los datos experimentales relevantes publicados recientemente. La fase de levadura de H. capsulatum incluye distintos factores moduladores de los mecanismos de macrófagos y antifúngicos, sobre todo el alpha-1,3-glucano, que se considera relevante para la virulencia.Este artículo forma parte de una serie de estudios presentados en el «V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi» (Oaxaca, México, 2012) (AU)