NUCB2: roles in physiology and pathology

Nucleobindin2 (NUCB2) is a member of nucleobindin family which was first found in the nucleus of the hypothalamus, and had a relationship in diet and energy homeostasis. Its location in normal tissues such as stomach and islet further confirms that it plays a vital role in the regulation of physiological functions of the body. Besides, NUCB2 participates in tumorigenesis through activating various signal-pathways, more and more studies indicate that NUCB2 might impact tumor progression by promoting or inhibiting proliferation, apoptosis, autophagy, metastasis, and invasion of tumor cells. In this review, we comprehensively stated NUCB2’s expression and functions, and introduced the role of NUCB2 in physiology and pathology and its mechanism. What is more, pointed out the potential direction of future research. (AU)

¿Un nuevo caso de síndrome de Pitt-Hopkins like 2? / A new case of Pitt-Hopkins-like syndrome 2?

No disponible

Identification of polcalcin as a novel allergen of Amaranthus retroflexus pollen

Introduction: Amaranthus retroflexus (Redroot Pigweed) is one of the main sources of allergenic pollens in temperate areas. Polcalcin is a well-known panallergen involved in cross-reactivity between different plants. The aim of this study was the molecular cloning and expression of polcalcin, as well as evaluating its IgE-reactivity with A. retroflexus sensitive patients' sera. Methods: Allergenic extract was prepared from A. retroflexus pollen and the IgE-reactivity profile was determined by ELISA and immunoblotting using sera from twenty A. retroflexus sensitive patients. Polcalcin-coding sequence was amplified by conventional PCR method and the product was inserted into pET-21b(+) vector. The recombinant protein was expressed in E. coli BL21 and purified by metal affinity chromatography. The IgE-binding capability of the recombinant protein was analyzed by ELISA and immunoblotting assays, and compared with crude extract. Results: Of 20 skin prick test positive patients, 17 patients were positive in IgE-specific ELISA. Western blotting confirmed that approximately 53% of ELISA positive patients reacted with 10kDa protein in crude extract. The A. retroflexus polcalcin gene, encoding to 80 amino acid residues was cloned and expressed as a soluble protein and designated as Ama r 3. The recombinant polcalcin showed rather identical IgE-reactivity in ELISA and western blotting with 10 kDa protein in crude extract. These results were confirmed by inhibition methods, too. Conclusion: The recombinant form of A. retroflexus polcalcin (Ama r 3) could be easily produced in E. coli in a soluble form and shows rather similar IgE-reactivity with its natural counterpart

No disponible

Alpha-syntrophin dependent expression of tubulin alpha 8 protein in hepatocytes

The scaffold protein alpha-syntrophin (SNTA) is a component of the dystrophin glycoprotein complex and has been comprehensively studied in skeletal muscle and adipocytes. SNTA is further expressed in the liver where its biological role remains unclear. Unpublished data from our group suggested that SNTA deficiency is associated with altered tubulin alpha 8 (TUBA8) levels in fat. TUBA8 is highly expressed in different cell lines including hepatoma cells, and here we analyzed whether SNTA has a role herein. In Hepa1-6 cells, TUBA8 protein levels were increased upon SNTA knock down and were reduced upon overexpression of SNTA. This regulation was not identified when analyzing mRNA expression. In the liver of SNTA-deficient mice, TUBA8 protein was higher compared to the respective wild-type controls while RNA expression was even suppressed. Using the HaloTag platform, TUBA8 was found to form a complex with SNTA in Hepa1-6 cells. In the hepatic stellate cell line LX-2, the lack or overexpression of SNTA did, however, not change TUBA8 protein expression. SNTA and TUBA8 are described to regulate cell proliferation. Yet, knock down of SNTA did neither affect proliferation nor viability of Hepa1-6 cells. The present study shows that SNTA protein levels are inversely related to TUBA8 protein expression in the hepatocyte cell line Hepa1-6

Utilidad de la calprotectina fecal en la enfermedad celiaca pediátrica / Usefulness of the faecal calprotectin on the pediatric coeliac disease

Introducción: El objetivo del presente estudio es analizar el comportamiento de la calprotectina fecal en los pacientes pediátricos con enfermedad celiaca, comparando sus niveles mientras recibían dieta con y sin gluten. También se han incluido en la comparación pacientes sanos y con diversas patologías digestivas no inflamatorias. Material y métodos: Se han recogido muestras de heces de pacientes celiacos con diagnóstico de novo (con gluten) y pacientes en seguimiento (sin gluten). Se incluyeron en el grupo control niños sanos sin patología digestiva y otros con diversos trastornos digestivos no diagnosticados de enfermedad inflamatoria intestinal. Resultados: La calprotectina fecal fue significativamente más alta en los pacientes celiacos que recibieron una dieta con gluten (119,2 ± 122,6 µg/g) que en los que recibieron una dieta sin gluten (21,5 ± 24,7 µg/g). Estos últimos presentaron valores similares al grupo control sano. Conclusiones: La calprotectina fecal está elevada en los pacientes celiacos con ingesta de gluten respecto a los celiacos con dieta sin gluten y los pacientes sanos. Este marcador podría usarse para la detección precoz de la ingesta de gluten (AU)

Introduction: The objective of the present research is to study the behavior of the faecal calprotectin in the pediatric coeliac disease, comparing its levels while receiving a diet with and without gluten. For the comparison, there were also included healthy children, and patients with diverse non-inflammatory digestive pathologies. Materials and methods: There have been collected stool samples from de novo coeliac patients (with gluten) and from follow-up coeliac patients (without gluten). As control groups, there were included healthy children without any digestive pathology and others with diverse digestive non-diagnosed disorders from the inflammatory bowel disease. Results: The faecal calprotectin was significantly higher in the coeliac patients with gluten (119.2 ± 122.6 µg/g) than in the patients with the gluten-free diet (21.5 ± 24.7 µg/g). The later showed similar values to those in the healthy control group. Conclusions: The faecal calprotectin is higher in the coeliac patients with gluten ingestion than in the coeliac patients with the gluten-free diet and in the healthy group. This could be used as a marker for early detection of gluten ingestion (AU)

Calciprotein particle (CPP): a true culprit of phosphorus woes? / Partículas de calciproteínas (PCP): ¿verdaderas culpables de los problemas causados por el fósforo

No disponible

Biomarcadores de cáncer oral en saliva / Salivary analysis of oral cancer biomarkers

Esta revisión muestra los principales biomarcadores de cáncer oral en saliva. El aspecto clínico y el grado de displasia de las lesiones precancerosas de la cavidad bucal sugieren su capacidad de malignidad; sin embargo, éstas generalmente son diagnosticadas en estadios avanzados, disminuyendo la probabilidad de supervivencia, lo que justifica el diseño de nuevas pruebas diagnósticas que determinen el grado de alteración celular, permitan comprender el proceso degenerativo en el cáncer y establezcan diagnósticos precoz. Esta búsqueda para mejorar los métodos diagnósticos, apunta a que sean sensibles, específicos y menos invasivos, por lo cual el estudio de diferentes biomarcadores en saliva que desde una perspectiva molecular proporcionan información adicional al examen clínico e histopatológico, es considerada como una alternativa eficaz y más cómoda con respecto a los ensayos en sangre. Los biomarcadores que se han descrito en saliva algunos mostrando mayor relación con la carcinogénesis oral son: Ciclina D1, cyfra 21-1, endotelina-1, galectinas 1, 3 y 7, Ki67, lactato deshidrogenasa, metaloproteinasas 2 y 9, proteína p53, proteína de unión a calcio (S100P) y telomerasa (AU)

This review shows the main oral cancer biomarkers in saliva. The clinical appearance and the degree of dysplasia, precancerous lesions of the oral cavity suggests its ability to malignancy, but these are usually diagnosed in advanced stages, decreasing the likelihood of survival, justifying the design of new diagnostic tests to determine the degree of cell alteration as to understand the degenerative process in cancer diagnosis and establish early. This search for improved diagnostic methods, aims to be sensitive, specific and less invasive, so the study of biomarkers in saliva from a molecular perspective provide additional information to clinical and histopathological examination is considered as a more comfortable and effective to establish a diagnosis. Biomarkers that have been described in saliva some showing more related to oral carcinogenesis are cyclin D1, Cyfra 21-1, Endothelin-1, Galectins 1, 3 and 7, Ki67, Lactate dehydrogenase, Metalloproteinases 2 and 9, p53 protein, protein calcium-binding (S100P) and Telomerase (AU)

Identification of New Potential Allergens From Nile Perch (Lates niloticus) and Cod (Gadus morhua)

Antecedentes: La globalización de la industria alimentaria proporciona la exposición a nuevos pescados no domésticos y se hace necesaria la identificación de los alérgenos potenciales para diagnosticar las reacciones alérgicas. Objetivo: El objetivo de este estudio fue estudiar las proteínas fijadoras de IgE que constituyen los alérgenos de la perca del Nilo (L. niloticus). Métodos: Mediante electroforesis 2D en gel se separaron las proteínas del músculo del L. niloticus y G. morhua y se enfrentaron al suero de 12 pacientes con historia de reacción inmediata a pescado, así como al suero de pacientes atópicos y controles sanos. Las proteínas reactivas a IgE fueron identificadas mediante espectrofotometría de masas. Results: En los resultados, el paciente mostraba un índice bajo de fijación de IgE a parvalbúminas, sin embargo mostraba fijación de IgE a 8 alérgenos diferentes a la parvalbúmina de L. niloticus y 5 a la G. morhua. Observamos una sensibilización cruzada de 7/12 (58%) de los individuos alérgicos a pescado a la enolasa-3 del L. niloticus, mientras que 11/12 (92%) de los pacientes estaban sensibilizados a la enolasa-3 del G. morhua. Conclusión: La identificación de los alérgenos especie-específicos o de la sensibilización individual podría en el futuro mejorar las estrategias de evitación (AU)

Background: Globalization of the food industry has led to widespread exposure to new nondomestic fish species; therefore, identification of potential allergens is necessary in order to diagnose allergic reactions. Objective: Contact with a patient who was allergic to Nile perch (Lates niloticus) prompted us to investigate the immunoglobulin (Ig) E– reactive proteins that could be allergens of this species. Methods: 2D gel electrophoresis was used to separate the muscle proteins of L niloticus and Gadus morhua. Immunoblotting was performed with sera from 12 patients with a history of immediate-type allergic reaction to fish and from atopic and nonatopic controls. IgE-reactive proteins were detected and identifi ed using mass spectrometry. Results: The index patient had low levels of IgE binding to parvalbumins. However, 8 putative allergens other than parvalbumin from L niloticus and 5 from G morhua were identified. Further investigation revealed cross-sensitivity to enolase 3 from L niloticus in 7 of the 12 fish-allergic individuals (58%), whereas 11 of the 12 patients (92%) were sensitized to enolase 3 from G morhua. However, atopic control patients were also sensitized to enolase 3 from L niloticus and G morhua. Conclusion: Identification of species-specific allergens and individual sensitization could help us to improve avoidance strategies (AU)

Unraveling STIM2 function

The discovery of molecular players in capacitative calcium (Ca2+) entry, also referred to as store-operated Ca2+ entry (SOCE), supposed a great advance in the knowledge of cellular mechanisms of Ca2+ entry, which are essential for a broad range of cellular functions. The identification of STIM1 and STIM2 proteins as the sensors of Ca2+ stored in the endoplasmic reticulum unraveled the mechanism by which depletion of intracellular Ca2+ stores is communicated to store-operated Ca2+channels located in the plasma membrane, triggering the activation of SOCE and intracellular Ca2+-dependent signaling cascades. Initial studies suggested a dominant function of STIM1 in SOCE and SOCE-dependent cellular functions compared to STIM2, especially those that participate in immune responses. Consequently, most of the subsequent studies focused on STIM1. However, during the last years, STIM2 has been demonstrated to play a more relevant and complex function than initially reported, being even important to sustain normal life in mice. These studies have led to reconsider the role of STIM2 in SOCE and its relevance in cellular physiology. This review is intended to summarize and provide an overview of the current data available about this exciting isoform, STIM2, and its actual position together with STIM1 in the mechanism of SOCE (AU)

Chemical heterogeneity of the periglomerular neurons in the olfactory bulb. A review

Periglomerular cells are interneurones thatmodulate the primary sensory information inthe olfactory bulb. It was originally assumedthat periglomerular cells constituted a homogeneousGABAergic population in the rat olfactory bulb, but in other species studies addressing this are scarce. However, several authors have shown that this neuronal type exhibits extraordinarily heterogeneous neurochemicalfeatures. The aim of this review is to compile and describe in detail the expression patterns of neuronal markers in the rat olfactory bulb, in particular in periglomerular cells,and to compare such information with previous data on other macrosmatic and microsmaticanimals. Interspecies differences in the neurochemical composition of periglomerular cells could indicate different modes in the modulation of olfactory information (AU)

No disponible

Interaction between â-amyloid protein andthe á7 nicotinic acetylcholine receptorin cholinergic, gabaergic and calcium-bindingproteins-containing neurons in theseptum-diagonal band complex of the rat

The effects of intracerebral injection of thebeta-amyloid protein (Aâ1-40) on the á7subtype of nicotinic acetylcoline receptor protein(nAChR) in neurons of the septum-diagonalband (MS-nDBB) complex were studiedin rats. Focal deposition of Aâ in the retrosplenialcortex resulted in a selective reductionin the number of á7nAChR-immunoreactivecells in different parts of the MS-nDBB complex,especially in the horizontal nucleus ofthe diagonal band of Broca (HDB). The analysisrevealed a significant decrease of 37.27%in the number of á7nAChR-immunoreactivecells in the HDB ipsilateral to the Aâ-injectedside as compared to the correspondinghemisphere of non-treated control animals,and a reduction of 31.55% was observed inthe HDB ipsilateral to the Aâ-injected side ascompared to the contralateral HDB, whichcorresponds to the control (PBS)-injected side.A significant reduction (up to 20%) ofá7nAChR-containing neurons was also foundin the medial septal nucleus when comparedwith the corresponding hemisphere in nontreatedcontrol animals. The results alsorevealed that á7nAChR-positive immunoreactivityis highly localized within cytoplasmicgranules in cholinergic neurons and in a smallsubset of putative GABAergic cells of the MSnDBBcomplex. In conclusion, these findingssuggest an interaction of Aâ1-40 with theá7nAChR, which may contribute to impairmentsin cholinergic and GABAergic transmissionin the MS-nDBB complex (AU)

No disponible