Aspirin and COX-2 Inhibitor Nimesulide Potentiate Adrenergic Contractions of Human Gastroepiploic Artery

Background The aim of the present study was to evaluate the intervention of COX-1- and COX-2-derived prostaglandins in the responses of human gastroepiploic artery to sympathetic stimulation and norepinephrine. Methods Rings of human gastroepiploic artery were obtained from 45 patients (26 men and 19 women) undergoing gastrectomy. The rings were suspended in organ baths for isometric recording of tension. We studied the responses to electrical field stimulation, norepinephrine, and acetylcholine, in the absence and presence of COX-1 or COX-2 inhibition. Results The COX-1 and COX-2 inhibitor aspirin at high concentrations (10 −6 to 10 −5 mol/L) and the COX-2 inhibitor nimesulide (10 −6 mol/L…

Aprendiendo de forma cooperativa a través del método científico

[EN] Usually, students tend to divide tasks unequally when they have to work in groups, everyone prepares a part of the manuscript and later they bind all parts together and deliver it. In this way, learning is fragmented and the desired goal is not achieved: to work cooperatively. In our experience we proposed students to work as a group of scientists. From a brief background they had to write an introduction, design a protocol using the indicated experimental technique and finally they had to speculate and discuss on the expected results. The activity should have raised the cooperation among all group members, because the correct understanding of a section required of the understanding of…

Centenarians overexpress BCL-xL, which confers them a protection against apoptosis, oxidative stress and immunosenescence

Centenarians not only have an extraordinary longevity, but also show a compression of morbidity. They preserve the capacity of maintaining homeostasis, and this is the reason for them to reach such a long life. We studied their mRNA expression profile and identified 1721 mRNAs differentially expressed by centenarians when compared with septuagenarians and young people. A sub-network analysis showed six common genes: interferon, T-cell receptor, tumor necrosis factor, SP1 transcription factor, transforming growth factor and IL-32.These six centenarian-specific genes are related to Bcl-xL, Fas, and Fas ligand all of them involved in the control of apoptosis. RT-PCR analysis confirmed that cen…

The NSL Chromatin-Modifying Complex Subunit KANSL2 Regulates Cancer Stem-like Properties in Glioblastoma That Contribute to Tumorigenesis.

KANSL2 is an integral subunit of the nonspecific lethal (NSL) chromatin-modifying complex that contributes to epigenetic programs in embryonic stem cells. In this study, we report a role for KANSL2 in regulation of stemness in glioblastoma (GBM), which is characterized by heterogeneous tumor stem-like cells associated with therapy resistance and disease relapse. KANSL2 expression is upregulated in cancer cells, mainly at perivascular regions of tumors. RNAi-mediated silencing of KANSL2 in GBM cells impairs their tumorigenic capacity in mouse xenograft models. In clinical specimens, we found that expression levels of KANSL2 correlate with stemness markers in GBM stem-like cell populations. M…

Basal release of nitric oxide in the mesenteric artery in portal hypertension and cirrhosis: Role of dimethylarginine dimethylaminohydrolase

Background and Aim Increased basal release of nitric oxide (NO) in the splanchnic circulation contributes to elevated plasma levels of NO observed in decompensated cirrhosis. We evaluated in rat mesenteric arteries whether the differences in basal release of NO, revealed by asymmetric dimethylarginine (ADMA)- and NG-nitro-L-arginine methyl ester (L-NAME)-induced contractions, were associated with changes in messenger RNA (mRNA) expression of endothelial NO synthase (eNOS) and dimethylarginine dimethylaminohydrolases (DDAHs). Methods Rat small mesenteric arteries from 14 Sham-control, from 14 with partial portal vein ligation (PPVL), and from 14 with bile duct excision (BDE)-induced cirrhosi…

Experiencia de gamificación en Docencia Universitaria: aprendizaje activo y entretenido

[EN] The main objective of this paper is to describe the experience developed in university teaching using gamification as a teaching tool. Gamification is the term used to refer to the application of game mechanics in areas in which gaming is not typically used. Our working hypothesis is based on the idea that gaming can be a new methodology that favors the settlement and internalizing the concepts taught by making the learning process and integrate asset and related contents of an attractive and motivating way for students.In order to assess the experience of students we have spent an anonymous survey and we have analyzed their answers. Our conclusion is that gamification has a good welco…

Nitric oxide triggers mammary gland involution after weaning: remodelling is delayed but not impaired in mice lacking inducible nitric oxide synthase

During mammary gland involution, different signals are required for apoptosis and tissue remodelling. To explore the role of NO in the involution of mammary tissue after lactation, NOS2 (inducible nitric oxide synthase)-KO (knockout) mice were used. No apparent differences were observed between NOS2-KO and WT (wild-type) animals during pregnancy and lactation. However, upon cessation of lactation, a notable delay in involution was observed, compared with WT mice. NOS2-KO mice showed increased phosphorylation of STAT (signal transducer and activator of transcription) 5 during weaning, concomitant with increased beta-casein mRNA levels when compared with weaned WT glands, both hallmarks of th…

Dysfunctional mitochondrial fission impairs cell reprogramming

We have recently shown that mitochondrial fission is induced early in reprogramming in a Drp1-dependent manner; however, the identity of the factors controlling Drp1 recruitment to mitochondria was unexplored. To investigate this, we used a panel of RNAi targeting factors involved in the regulation of mitochondrial dynamics and we observed that MiD51, Gdap1 and, to a lesser extent, Mff were found to play key roles in this process. Cells derived from Gdap1-null mice were used to further explore the role of this factor in cell reprogramming. Microarray data revealed a prominent down-regulation of cell cycle pathways in Gdap1-null cells early in reprogramming and cell cycle profiling uncovered…

Centenarian offspring: A model for understanding healthy aging

Centenarians exhibit extreme longevity showing a compression of morbidity. We showed previously that microRNA expression profiles and plasma protein carbonylation in centenarians and young people are similar, whereas they are very different from that found in old individuals. This suggests that centenarians have a better control of homeostasis and are protected against oxidative damage. In this study, we aimed to determine if such characteristic microRNA expression profile and lower protein oxidation status in centenarians may be inherited by their offspring. For this purpose, we collected plasma and peripheral blood mononuclear cells from 90 septuagenarians, 68 centenarians and 46 centenar…

Validation of the Sepsis MetaScore for Diagnosis of Neonatal Sepsis

What’s known on this subject Neonates are at increased risk for developing sepsis, but this population often exhibits ambiguous clinical signs that complicate the diagnosis of infection. No biomarker has yet shown enough diagnostic accuracy to rule out sepsis at the time of clinical suspicion. What this study adds We show that a gene-expression-based signature is an accurate objective measure of the risk of sepsis in a neonate or preterm infant, and it substantially improves diagnostic accuracy over that of commonly used laboratory-based testing. Implementation might decrease inappropriate antibiotic use. Background Neonatal sepsis can have devastating consequences, but accurate diagnosis i…

Defense Responses in Two Ecotypes of Lotus japonicus against Non-Pathogenic Pseudomonas syringae

Lotus japonicus is a model legume broadly used to study many important processes as nitrogen fixing nodule formation and adaptation to salt stress. However, no studies on the defense responses occurring in this species against invading microorganisms have been carried out at the present. Understanding how this model plant protects itself against pathogens will certainly help to develop more tolerant cultivars in economically important Lotus species as well as in other legumes. In order to uncover the most important defense mechanisms activated upon bacterial attack, we explored in this work the main responses occurring in the phenotypically contrasting ecotypes MG-20 and Gifu B-129 of L. ja…

Effects of aspirin, nimesulide, and SC-560 on vasopressin-induced contraction of human gastroepiploic artery and saphenous vein.

Objective: The present experiments were designed to evaluate differences in the effects of cyclooxygenase (COX)-1 and COX-2 inhibition on contractile responses of human gastroepiploic artery and saphenous vein elicited by vasopressin. Design: Laboratory investigation. Setting: University laboratory. Subjects: Rings of human gastroepiploic artery were obtained from 32 patients undergoing gastrectomy, and rings of saphenous vein were obtained from 30 patients undergoing coronary artery bypass surgery. Interventions: The rings were suspended in organ baths for isometric recording of tension. We studied the responses to vasopressin in the absence and in the presence of either the vasopressin V …

miRNomic Signature in Very Low Birth-Weight Neonates Discriminates Late-Onset Gram-Positive Sepsis from Controls

Background and Objectives. Neonatal sepsis is a serious condition with a high rate of mortality and morbidity. Currently, the gold standard for sepsis diagnosis is a positive blood culture, which takes 48–72 h to yield results. We hypothesized that identifying differentially expressed miRNA pattern in neonates with late-onset Gram-positive sepsis would help with an earlier diagnosis and therapy. Methods. This is a prospective observational study in newborn infants with late-onset Gram positive bacterial sepsis and non-septic controls. Complementary to blood culture, an aliquot of 0.5 mL of blood was used to determine small non-coding RNA expression profiling using the GeneChip miRNA 4.0 Arr…

New pattern of EGFR amplification in glioblastoma and the relationship of gene copy number with gene expression profile

Gene amplification is a process that is characterized by an increase in the copy number of a restricted region in a chromosome arm, and is frequently associated with an overexpression of the corresponding amplified gene. Amplified DNA can be organized either as extrachromosomal elements, repeated units at a single locus or scattered throughout the genome. The amplification of the gene for epidermal growth factor receptor (EGFR) is a common finding in glioblastomas and the amplified gene copies appears as double minutes. The aim of this study was to investigate the different patterns of EGFR amplification in 40 cases of glioblastoma using FISH analysis in metaphases and paraffin sections, an…

Response to long-term NaHCO3-derived alkalinity in model Lotus japonicus Ecotypes Gifu B-129 and Miyakojima MG-20: transcriptomic profiling and physiological characterization.

The current knowledge regarding transcriptomic changes induced by alkalinity on plants is scarce and limited to studieswhere plants were subjected to the alkaline salt for periods not longer than 48 h, so there is no information availableregarding the regulation of genes involved in the generation of a new homeostatic cellular condition after long-termalkaline stress.Lotus japonicusis a model legume broadly used to study many important physiological processes includingbiotic interactions and biotic and abiotic stresses. In the present study, we characterized phenotipically the response toalkaline stress of the most widely usedL. japonicusecotypes, Gifu B-129 and MG-20, and analyzed global t…

A novel nutrient blend mimics calorie restriction transcriptomics differentially in multiple tissues of mice

Identification of caloric restriction mimetics (CRMs), compounds that mimic the beneficial effects of caloric restriction (CR) without restriction of dietary energy would be an advancement in anti-aging science. The present study investigated whether the transcriptional profiles of a putative CRM nutrient blend could mimic that of CR in diverse tissues following long-term feeding in B6C3F1 male mice. Study design: Young Controls (YC; 5 mo.) and 3 groups treated from 14-30 mo.: Old Controls (OC), Old CR (OCR; 25% CR) and Old Supplemented (OS); n=7/group. Gene expression profiling in cerebral cortex (CCT), skeletal muscle (gastrocnemius)(SKL), heart (HRT), white adipose tissue (WAT) and liver…

Experiencias en la aplicación de la gamificación en 1º Curso de Grado de Ciencias de la Salud

[EN] This paper analyzes the use of gamification in university education. Gamification is the term used to refer to the application of game mechanics in areas in which gaming is not typically used. Our working hypothesis is based on the idea that gaming can be a tool to promote the reinforcement of the concepts taught in the lecture. One of our objectives was to know the features that a game targeted at university students should include. To figure it out, we proposed two game types and a third option that combines both games. In order to assess whether the game is effective on consolidating concepts and improving attentiveness compared to the lecture, we did a survey on students and we ana…

Analysis of metabolic and gene expression changes after hydrodynamic DNA injection into mouse liver.

The hydrodynamic injection in mice tail vein of a plasmid (40 mg DNA) bearing the human a1-antitrypsin gene mediates: a) good liver gene transfer resulting in therapeutic plasma levels of human protein (1 mg/ml, approximately) from days 1—10 after injection; b) low liver injury as demonstrated by a poor and transient increase of aspartate aminotransferase (AST) and alanine transaminase (ALT) in mouse plasma; 3) limited expression and metabolic changes in host liver genes and metabolites as evaluated on days 2 and 10 after injection. Groups of three mice were uninjected (control) or hydrodynamically injected with saline or plasmid DNA and then sacrificed on days 2 and 10 after injection. The…

Gamificación en la universidad: una experiencia basada en el “bring your own device” en educación superior

[EN] Technological development offers several new opportunities to improve the quality of teaching. Under the ongoing task as a teachers of motivating and teaching how to learn to our students, we present the results of a session that consisted of two gamificated and groupal activities (quiz format) and a single self-assessment, based all of them on the use of their own electronic enabled devices (bring your own device). This implies an enriching, fun and practical experience to approach the course, and it provided interesting feedback to continue implementing new technologies at the university.

Los descendientes de centenarios como modelo de envejecimiento saludable

Transcriptomic identification of miR-205 target genes potentially involved in metastasis and survival of cutaneous malignant melanoma

AbstractCutaneous melanoma is an aggressive neoplasm and is responsible for the majority of skin cancer deaths. Several miRNAs are involved in melanoma tumor progression. One of them is miR-205, the loss of which contributes to the development of melanoma metastasis. We evaluated whole-genome mRNA expression profiling associated with different miR-205 expression levels in melanoma cells. Differential expression analysis identified 243 differentially expressed transcripts including inositol polyphosphate 5′-phosphatase-like protein-1 (INPPL1) and BTB/POZ Domain-Containing Protein 3 (BTBD3). INPPL1 and BTBD3 were downregulated when melanoma cells expressed miR-205, indicating that these genes…

Ovarian Transcriptomic Analysis Reveals Differential Expression Genes Associated with Cell Death Process after Selection for Ovulation Rate in Rabbits

[EN] Transcriptomic analysis showed nineteen potential biomarkers in ovarian tissue from females belonged to a rabbit line selected for ovulation rate for 10 generations and the control line. These females differed not only in ovulation rate but also in prenatal survival since similar litter size were observed. Litter size is an essential trait in rabbit meat production but with low heritability. A selection experiment for ovulation rate has been performed for 10 generations to improve litter size in rabbits. The selected line increased two ova more than the control line but nevertheless a negative correlation was observed with prenatal survival. A transcriptomic study was performed, using …

Role of Ca2+-Activated K+ Channels on Adrenergic Responses of Human Saphenous Vein

Background We studied the participation of K + channels on the adrenergic responses in human saphenous veins as well as the intervention of dihydropyridine-sensitive Ca 2+ channels on modulation of adrenergic responses by K + channels blockade. Methods Saphenous vein rings were obtained from 40 patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. Results Iberiotoxin (10 −7 mol/L), an inhibitor of large conductance Ca 2+ -activated K + channels, and charybdotoxin (10 −7 mol/L), an inhibitor of both large and intermediate conductance Ca 2+ -activated K + channels, enhanced the contractions elicited by elec…

Upregulation of microRNAs by centenarians

Estudio interuniversitario en estudiantes de Ciencias de la Salud: uso de los dispositivos móviles con fines educativos

[EN] The use of smartphones, despite being mainly social, has begun to be implemented in the university environment as a tool for working in class and for communication between students regarding teaching material. However, before creating teaching methodologies that use these devices, it is important to know the opinion that the students have of them. Our objective was to analyze the personal and academic use of Smartphones by Health Sciences students from different Universities. With this objective, a form was created consisting of sociodemographic questions and the Questionnaire on perceptions and attitudes towards learning through mobile devices (CPAAM). Subsequently, a descriptive anal…

MicroRNA Profile in Response to Doxorubicin Treatment in Breast Cancer

UNLABELLED Chemotherapy treatment is the standard in triple negative breast cancers, a cancer subgroup which lacks a specific target. The mechanisms leading to the response, as well as any markers that allow the differentiation between responder and non-responder groups prior to treatment are unknown. In parallel, miRNAs can act as oncogenes or tumor suppressors and there is evidence of their involvement in promoting resistance to anticancer drugs. Therefore we hypothesized that changes in miRNA expression after doxorubicin treatment may also be relevant in treatment response. OBJECTIVE To study miRNAs that are differentially expressed in response to doxorubicin treatment. METHODS One lumin…

Gamificación en la universidad II: aprendemos a divertirnos enseñando. Se divierten aprendiendo

[EN] After the success last year using gamification as a motivating method in the degree of Biomedical Engineering (UV-UPV), we introduce it this year in degree in Podiatry (UV). On the basis of the results of our first study, we focus on the use of Kahoot application in order to improve our students’ motivation and subsequently, their califications. Despite the short timeexperience, the improvement in academic results has been evident. Although it could be due to many causes, it has been influenciated by this action. In addition, during the development of this type of activity the involvement and fun of our students does not cease to amaze us. They enjoy their successes and also their fail…

Material multimedia para aumentar el rendimiento académico de los trabajos en grupo

[EN] Multimedia can be considered a useful tool for improving the learning. In this study we analyze the marks that students get in a group activity with and without the use of a multimedia material made by teachers. The scores are obtained using a rubric previously tested for this activity and the results show an increase in the final qualification for student groups who used the multimedia material. We also analyze the scores by units following the rubric and we note that scores increase 4.0 points for a maximum of 10 in the methodology unit. Moreover, we collect the opinion of our students about the multimedia material and how it helped them to better understand the work they had to do i…

NF-ĸB as node for signal amplification during weaning.

Post-lactational involution has been reported to share common features with breast tumor development. A deep characterization of the signaling triggered after weaning would help to unveil the complex relationship between involution and breast cancer. NF-κB, a crucial factor in the involuting gland, might be an important regulatory node for signal amplification after weaning; however there is limited information about the identity of NF-κB-target genes and the molecular mechanisms leading to the selection of genes involved in a particular biological process. We identified 4532 target genes in mammary gland at 48h weaning, by genome-wide analysis of regions bound by RelA(p65)-NF-κB in vivo. I…

Respuesta de preosteoblastos a compuestos de estroncio o calcio: proliferación, diferenciación, mineralización y respuesta génica global

Fundamento: Los mecanismos que desencadenan la osteogénesis todavía no están aclarados. El objetivo de este estudio fue valorar el papel de estroncio y calcio, aportados en distinto soporte molecular, como inductores de distintos mecanismos de estímulo osteoblástico, incluyendo proliferación, diferenciación y mineralización de células preosteoblásticas. Se investigó también la respuesta global genómica con la técnica de microarray. Métodos: Se diseñó un estudio experimental con células pre-osteoblásticas murinas MC3T3-E1, que fueron estimuladas durante 3 horas y 7 días. Se realizaron estudios bioquímicos y de expresión génica del genoma de ratón (Affymetrix). Resultados: El estroncio unido …

Gene expression profiles of metabolic aggressiveness and tumor recurrence in benign meningioma.

Around 20% of meningiomas histologically benign may be clinically aggressive and recur. This strongly affects management of meningioma patients. There is a need to evaluate the potential aggressiveness of an individual meningioma. Additional criteria for better classification of meningiomas will improve clinical decisions as well as patient follow up strategy after surgery. The aim of this study was to determine the relationship between gene expression profiles and new metabolic subgroups of benign meningioma with potential clinical relevance. Forty benign and fourteen atypical meningioma tissue samples were included in the study. We obtained metabolic profiles by NMR and recurrence after s…

Centenarians maintain miRNA biogenesis pathway while it is impaired in octogenarians.

Centenarians but not octogenarians up regulate the expression of miRNAs, as we previously reported. We have looked into miRNA biogenesis. We show that RNA POL II, DROSHA, EXPORTIN 5 and DICER, are up-regulated in centenarians compared with octogenarians. Furthermore, factors involved in the control of these miRNAs biogenesis genes are also up-regulated in centenarians. Therefore, the up-regulation of miRNA expression in centenarians can be explained in part because miRNA biogenesis pathway is depressed in octogenarians (ordinary aging) while it is maintained in centenarians (extraordinary aging).

Transcriptomic profile of epileptic children treated with ketogenic therapies.

Background: Ketogenic dietary therapies (KDT) are used as a treatment in childhood epilepsy. However, their mechanism has not yet been established. The main objective of this study was to determine the changes in the transcriptomic profile induced by KDT in children with epilepsy in order to shed light on its possible mechanisms. Methods: Eight children with refractory epilepsy were enrolled in the study. Peripheral blood mononuclear cells were obtained before and after the children were treated with KDT for a minimum of 6 months. RNA was extracted and mRNA and miRNA profiling were performed and analyzed. Results: Our intervention with KDT significantly reduced the seizure number in seven o…

Bifidobacterium pseudocatenulatum CECT 7765 supplementation restores altered vascular function in an experimental model of obese mice

Aims. Bifidobacterium pseudocatenulatum CECT 7765 improves metabolic and immunological altered functions in high fat fed mice, however little is known about the effects of potential probiotics on vascular reactivity. The aim of the present study was to investigate the effects of a potential probiotic strain, Bifidobacterium pseudocatenulatum CECT 7765, on vascular response in obese mice. Methods. Aorta samples were obtained from mice, which were divided into three groups: a control group, receiving a standard diet; an obese group, receiving a high-fat diet; and an obese group receiving high-fat diet and a daily dose of B. pseudocatenulatum CECT 7765 by oral gavage. Aortic rings were suspend…

MiRNome of epileptic children suggests the involvement of antioxidant pathways in the neuroprotective role of ketogenic diet

Ketogenic diet (KD) has been used as treatment for refractory epilepsy in children since the 1920s. However, the neuroprotective mechanism of this diet is still unknown. Recent evidence points to a multifactorial effect of KD that involves a decrease of oxidative stress. Mononuclear cells from 14 children with refractory epilepsy, from the Paediatric Hospital “Nino Jesus” in Madrid, were obtained before and after treatment with a ketogenic diet for 6 months. A global analysis of miRNA expression (miRNome) indicates that there are 230 miRNAs which are expressed differently before and after the treatment with KD. If additionally, we restrict the miRNAs with a fold change > |1.3|we obtain 11 r…

Gene expression profile induced by ovariectomy in bone marrow of mice: a functional approach to identify new candidate genes associated to osteoporosis risk in women.

Osteoporosis is a multifactorial skeletal pathology with a main genetic component. To date, however, the majority of genes associated with this pathology remain unknown since genes cataloged to date only explain a part of the heritability of bone phenotypes. In the present study, we have used a genome-wide gene expression approach by means of microarrays to identify new candidate genes involved in the physiopathology of osteoporosis, using as a model the ovariectomized (OVX) mice by comparing global bone marrow gene expression of the OVX mice with those of SHAM operated mice. One hundred and eighty transcripts were found to be differentially expressed between groups. The analysis showed 23 …

Thirteen miRNAs involved in the response of breast cancer cells to doxorubicin.

e12019 Background: Mature microRNAs (miRNAs) are a class of naturally occurring, small non-coding RNA molecules, about 21–25 nucleotides. Growing evidence shows that miRNAs exhibit a variety of regulatory functions related to cell growth, development, and differentiation, and are associated with a wide variety of human diseases. Several miRNAs have been linked to cancer; since expression analysis studies have revealed perturbed miRNA expression in tumors compared to normal tissues. As a consequence, human miRNAs are likely to be highly useful as biomarkers, especially for future cancer diagnostics, and are emerging as targets for disease intervention. Since doxorubicin (DOX) has been used …

Análisis de la percepción del alumnado ante la metodología de trabajar en grupos tutorizados

[EN] The main objective of this paper is to analyze the opinion and perspective that the students have in view of the methodology of working in tutored groups. This methodology adopted in the teaching-learning process is important for the development of competences. The ability to work in a team and the ability to communicate are very significant transversal competences that have a great impact or potential in student learning. This paper presents an analysis of student assessments collected through anonymous opinions after the elaboration of a tutorial work carried out in a group in the Medicine Degree of the University of Valencia during the years 2015-2016 and 2016- 2017. It is essential…

Does Pasteurized Donor Human Milk Efficiently Protect Preterm Infants Against Oxidative Stress?

International audience; Pasteurized donor human milk (DHM) is the preferred alternative for infant nutrition when own mother's milk (OMM) is unavailable. Whether DHM is an efficient means for protecting preterm infants from oxidative stress remains unknown. We quantified a panel of oxidative stress biomarkers in urine samples from preterm infants (≤32 weeks of gestation and a birth weight ≤1500 g) receiving ≥80% of feeding volume as either DHM or OMM. The noninvasive in vivo assessment of oxidative stress showed no statistically significant difference between both groups at the time when full enteral nutrition (150 mL/kg body weight) was achieved and until hospital discharge. In addition, t…

Analysis of Exosomal Cargo Provides Accurate Clinical, Histologic and Mutational Information in Non-Small Cell Lung Cancer

Simple Summary Non-small cell lung cancer (NSCLC) is the second most commonly diagnosed cancer and the leading cause of cancer-related death worldwide. Clinical decision-making depends on the histological classification; however, tissue biopsy is frequently not technically feasible due to tumor location or limited tissue samples. Therefore, we propose to find clinical, molecular and histological biomarkers using a minimally invasive approach based on the analysis of the cargo of the blood extracellular vesicles. Exosomes are membranous vesicles present in several biological fluids, which carry biological information to distant tissues, regulating several tumor processes. This study aims to …

Biotin-Genomic Run-On (Bio-GRO): A High-Resolution Method for the Analysis of Nascent Transcription in Yeast

Transcription is a highly complex biological process, with extensive layers of regulation, some of which remain to be fully unveiled and understood. To be able to discern the particular contributions of the several transcription steps it is crucial to understand RNA polymerase dynamics and regulation throughout the transcription cycle. Here we describe a new nonradioactive run-on based method that maps elongating RNA polymerases along the genome. In contrast with alternative methodologies for the measurement of nascent transcription, the BioGRO method is designed to minimize technical noise that arises from two of the most common sources that affect this type of strategies: contamination wi…

Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging.

24 páginas, 7 figuras. Borras C, et al. Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging. Aging (Albany NY). 2016 Oct 28;8(12):3185-3208. doi: 10.18632/aging.101078.

Impact of Donor Human Milk in the Preterm Very Low Birth Weight Gut Transcriptome Profile by Use of Exfoliated Intestinal Cells

[Background] Own mother’s milk (OMM) is the optimal nutrition for preterm infants. However, pasteurized donor human milk (DHM) is a valid alternative. We explored the differences of the transcriptome in exfoliated epithelial intestinal cells (EEIC) of preterm infants receiving full feed with OMM or DHM.

Sepsis in preterm infants causes alterations in mucosal gene expression and microbiota profiles compared to non-septic twins

Sepsis is a life-threatening condition in preterm infants. Neonatal microbiota plays a pivotal role in the immune system maturation. Changes in gut microbiota have been associated to inflammatory disorders; however, a link with sepsis in the neonatal period has not yet been established. We aimed to analyze gut microbiota and mucosal gene expression using non-invasively obtained samples to provide with an integrative perspective of host-microbe interactions in neonatal sepsis. For this purpose, a prospective observational case-control study was conducted in septic preterm dizygotic twins and their non-septic twin controls. Fecal samples were used for both microbiota analysis and host genome-…

A Novel Micronutrient Blend Mimics Calorie Restriction Transcriptomics in Multiple Tissues of Mice and Increases Lifespan and Mobility in C. elegans

Background: We previously described a novel micronutrient blend that behaves like a putative calorie restriction mimetic. The aim of this paper was to analyze the beneficial effects of our micronutrient blend in mice and C. elegans, and compare them with calorie restriction. Methods: Whole transcriptomic analysis was performed in the brain cortex, skeletal muscle and heart in three groups of mice: old controls (30 months), old + calorie restriction and old + novel micronutrient blend. Longevity and vitality were tested in C. elegans. Results: The micronutrient blend elicited transcriptomic changes in a manner similar to those in the calorie-restricted group and different from those in the c…

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

BACKGROUND: Bacterial sepsis is associated with high morbidity and mortality in preterm infants. However, diagnosis of sepsis and identification of the causative agent remains challenging. Our aim was to determine genome-wide expression profiles of very low birth weight (VLBW) infants with and without bacterial sepsis and assess differences. METHODS: This was a prospective observational double-cohort study conducted in VLBW (<1500 g) infants with culture-positive bacterial sepsis and non-septic matched controls. Blood samples were collected as soon as clinical signs of sepsis were identified and before antibiotics were initiated. Total RNA was processed for genome-wide expression an…

Age-dependent changes in the transcription profile of long-lived Drosophila over-expressing glutamate cysteine ligase

Abstract In our prior studies ( Orr et al., 2005 ) we achieved a 30–50% increase in the life span of Drosophila by manipulating glutathione (GSH) production in neuronal tissues, through over-expression of glutamate-cysteine ligase (GCL), a key enzyme in glutathione biosynthesis. In the present study, we identified gene response patterns from which plausible mechanisms responsible for the observed effects on life span might be inferred. Functional clustering analysis of the transcriptome data revealed that biological processes affected by GCLc in young flies (10 days) were generally related to cell morphogenesis and differentiation, while those in older flies were associated with nucleosome …

Glucose 6-P dehydrogenase delays the onset of frailty by protecting against muscle damage.

Background: Frailty is a major age-associated syndrome leading to disability. Oxidative damage plays a significant role in the promotion of frailty. The cellular antioxidant system relies on reduced nicotinamide adenine dinucleotide phosphate (NADPH) that is highly dependent on glucose 6-P dehydrogenase (G6PD). The G6PD-overexpressing mouse (G6PD-Tg) is protected against metabolic stresses. Our aim was to examine whether this protection delays frailty. Methods: Old wild-type (WT) and G6PD-Tg mice were evaluated longitudinally in terms of frailty. Indirect calorimetry, transcriptomic profile, and different skeletal muscle quality markers and muscle regenerative capacity were also investigate…

a1D-Adrenoceptors are responsible for the high sensitivity and the slow time-course of noradrenaline-mediated contraction in conductance arteries.

The objective of this study was to determine whether the different time-course characteristics of α1-adrenoceptor-mediated contraction in arteries can be related to the subtypes involved. Contractile responses to noradrenaline (NA) were compared with inositol phosphate accumulation and extracellular signal-regulated kinase (ERK)1/2 phosphorylation after α1-agonist stimuli in the same vessels in the presence or absence of α1-antagonists in rat or in α1-subtype knockout (KO) mice. Aorta, where α1D-AR is the main functional subtype, had higher sensitivity to NA (in respect of inositol phosphate [IP], pERK1/2, and contractile response) than tail artery, where the α1A-adrenoceptor subtype is pre…

Correlation between EGFR Amplification and the Expression of MicroRNA-200c in Primary Glioblastoma Multiforme

Extensive infiltration of the surrounding healthy brain tissue is a critical feature in glioblastoma. Several miRNAs have been related to gliomagenesis, some of them related with the EGFR pathway. We have evaluated whole-genome miRNA expression profiling associated with different EGFR amplification patterns, studied by fluorescence in situ hybridization in tissue microarrays, of 30 cases of primary glioblastoma multiforme, whose clinicopathological and immunohistochemical features have also been analyzed. MicroRNA-200c showed a very significant difference between tumors having or not EGFR amplification. This microRNA plays an important role in epithelial-mesenchymal transition, but its impl…

Anti-Aging Physiological Roles of Aryl Hydrocarbon Receptor and Its Dietary Regulators

The vast majority of the literature on the aryl hydrocarbon receptor is concerned with its functions in xenobiotic detoxification. However, in the course of evolution, this receptor had to have physiological (rather than toxicological) functions. Our aim was to review the aryl hydrocarbon receptor’s role in the physiological functions involved in aging. This study was performed by searching the MEDLINE and Google Academic databases. A total of 34 articles were selected that focused specifically on the aryl hydrocarbon receptor and aging, the aryl hydrocarbon receptor and physiological functions, and the combination of both. This receptor’s main physiological functions (mediated by the modul…

Role of the aryl hydrocarbon receptor (AhR) signaling pathway in exceptional longevity in humans

Centenarians are the best example of successfully aging in humans. Thus, the characterization of the biological processes and pathways in this population is an excellent strategy to understand the lifespan extension. The aryl hydrocarbon receptor (AhR) is a ligand-activated-transcription factor historically known for regulating expression of several important drug-detoxifying proteins. But recently its role in the immune response and in cellular homeostasis has been recognized. Furthermore, AhR is activated in C. Elegans in extreme longevity due to a dietary restriction. We report here results of a whole transcriptome analysis of centenarians. The main biological process was the immune resp…

The Status of EGFR Modulates the Effect of miRNA-200c on ZEB1 Expression and Cell Migration in Glioblastoma Cells

Migration of glioblastoma cells into surrounding tissue is one of the main features that makes this tumor incurable. We evaluated whole-genome miRNA expression profiling associated with different EGFR amplification patterns in 30 cases of primary glioblastoma. From the 64 miRNAs that showed differential expression between tumors with a high level of EGFR amplification and tumors without EGFR amplification, 40% were related with cell migration, being miR-200c the most differentially expressed between these two groups. We investigated the effect of miR-200c on ZEB1 expression and cell migration in an in vitro transfection model with a miR-200c mimic, a miR-200c inhibitor and siRNA targeting E…

Dysfunctional mitochondrial fission impairs cell reprogramming

We have recently shown that mitochondrial fission is induced early in reprogramming in a Drp1-dependent manner; however, the identity of the factors controlling Drp1 recruitment to mitochondria was unexplored. To investigate this, we used a panel of RNAi targeting factors involved in the regulation of mitochondrial dynamics and we observed that MiD51, Gdap1 and, to a lesser extent, Mff were found to play key roles in this process. Cells derived from Gdap1-null mice were used to further explore the role of this factor in cell reprogramming. Microarray data revealed a prominent down-regulation of cell cycle pathways in Gdap1-null cells early in reprogramming and cell cycle profiling uncovered…