Pursuing precision in medicine and nutrition: the rise of electrochemical biosensing at the molecular level

In the era that we seek personalization in material things, it is becoming increasingly clear that the individualized management of medicine and nutrition plays a key role in life expectancy and quality of life, allowing participation to some extent in our welfare and the use of societal resources in a rationale and equitable way. The implementation of precision medicine and nutrition are highly complex challenges which depend on the development of new technologies able to meet important requirements in terms of cost, simplicity, and versatility, and to determine both individually and simultaneously, almost in real time and with the required sensitivity and reliability, molecular markers of different omics levels in biofluids extracted, secreted (either naturally or stimulated), or circulating in the body. Relying on representative and pioneering examples, this review article critically discusses recent advances driving the position of electrochemical bioplatforms as one of the winning horses for the implementation of suitable tools for advanced diagnostics, therapy, and precision nutrition. In addition to a critical overview of the state of the art, including groundbreaking applications and challenges ahead, the article concludes with a personal vision of the imminent roadmap.The financial support of PID2019-103899RBI00 (Spanish Ministerio de Ciencia e Innovación), and PMP22/00084, PI17CIII/00045, PI20CIII/00019 and PI22/00727 (AES-ISCIII) cofounded with FEDER funds Research Projects and the TRANSNANOAVANSENS-CM Program from the Comunidad de Madrid (Grant S2018/NMT-4349) are gratefully acknowledged. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.S

Gender and tobacco consumption among University students

In 2019, an estimated 155 million people aged between 15 and 24 were smokers. It is also known that 82.6% of current smokers started smoking between 14 and 25 years old. Tobacco uses in adolescents and young adults can lead to the development of serious and potentially life-threatening health problems. The aim of the present investigation is to identify and describe the practices related to the consumption of tobacco products and their distribution according to gender among students at the University of Algarve. This is an exploratory, cross-sectional study with a quantitative approach. For inferential statistics, a non-parametric analysis (χ 2 ) was performed. The sample consisted of 326 university students, 75.5% female, with an average age of 26.03 years. In this sample, 45% of men and 57.7% of women reported never having smoked. In male students, the pattern of combined consumption is more frequent, with female students preferring conventional cigarettes. Statistically significant differences were found between genders for the pattern of tobacco consumption, the number of colleagues/peers who smoke, the opinion about tobacco-free outdoor spaces and the knowledge about new forms of tobacco/nicotine consumption. The university campus is identified by students as the second space where they most consume tobacco products and where they are most exposed to tobacco smoke. This fact forces a reflection on the strategies to be implemented to develop a healthier universityinfo:eu-repo/semantics/publishedVersio

Inhibition of PTEN by peroxynitrite activates the phosphoinositide-3-kinase/Akt neuroprotective signaling pathway

El derivado del óxido nítrico, peroxinitrito, activa una cascada de señalización de supervivencia en neuronas. El mecanismo implica la oxidación de la fosfatasa PTEN, que permite incrementar la forma fosforilada (neuroprotectora) de akt.Peroxynitrite is usually considered as a neurotoxic nitric oxidederivative. However, an increasing body of evidence suggests that, at low concentrations, peroxynitrite affords transient cytoprotection, both in vitro and in vivo. Here, we addressed the signaling mechanism responsible for this effect, and found that rat cortical neurons in primary culture acutely exposed to peroxynitrite (0.1 mmol/L) rapidly elicited Akt-Ser473 phosphorylation. Inhibition of phosphoinositide-3-kinase (PI3K)/Akt pathway with wortmannin or Akt small hairpin RNA (shRNA) abolished the ability of peroxynitrite to prevent etoposide-induced apoptotic death. Endogenous peroxynitrite formation by short-term incubation of neurons with glutamate stimulated Akt-Ser473 phosphorylation, whereas Akt shRNA enhanced the vulnerability of neurons against glutamate. We further show that Akt-Ser473 phosphorylation was consequence of the oxidizing, but not the nitrating properties of peroxynitrite. Peroxynitrite failed to nitrate or phosphorylate neurotrophin tyrosine kinase receptors (Trks), and it did not modify the ability of brain-derived neurotrophic factor (BDNF), to phosphorylate its cognate receptor, TrkB; however, peroxynitrite enhanced BDNF-mediated Akt-Ser473 phosphorylation. Finally, we found that peroxynitrite-stimulated Akt-Ser473 phosphorylation was associated with an increased proportion of oxidized phosphoinositide phosphatase, PTEN, in neurons. Moreover, peroxynitrite prevented the increase of apoptotic neuronal death caused by over-expression of PTEN. Thus, peroxynitrite exerts neuroprotection by inhibiting PTEN, hence activating the anti-apoptotic PI3K/Akt pathway in primary neurons

Tuning the nanoaggregates of sialylated biohybrid photosensitizers for intracellular activation of the photodynamic response

In the endeavor of extending the clinical use of photodynamic therapy (PDT) for the treatment of superficial cancers and other neoplastic diseases, deeper knowledge and control of the subcellular processes that determine the response of photosensitizers (PS) are needed. Recent strategies in this direction involve the use of activatable and nanostructured PS. Here, both capacities have been tuned in two dendritic zinc(II) phthalocyanine (ZnPc) derivatives, either asymmetrically or symmetrically substituted with 3 and 12 copies of the carbohydrate sialic acid (SA), respectively. Interestingly, the amphiphilic ZnPc-SA biohybrid (1) self-assembles into well-defined nanoaggregates in aqueous solution, facilitating cellular internalization and transport whereas the PS remains inactive. Within the cells, these nanostructured hybrids localize in the lysosomes, as usually happens for anionic and hydrophilic aggregated PS. Yet, in contrast to most of them (e. g., compound 2), hybrid 1 recovers the capacity for photoinduced ROS generation within the target organelles due to its amphiphilic character; this allows disruption of aggregation when the compound is inserted into the lysosomal membrane, with the concomitant highly efficient PDT responseThis work was supported by EU (CosmoPHOS-nano, EU-FP7- NMP-2012-LARGE-6, 310337), MINECO-Feder funds (CTQ2017- 85393-P (T.T.), CTQ-2014-53673-P and CTQ-2017-89539-P (A.d.l.E.), Instituto de Salud Carlos III; PI18/00708 (A.J.), and PCIN-2017-042/EuroNanoMed2017-191, TEMPEAT (T.T.)), and Comunidad Autonoma de Madrid (FOTOCARBON, S2013/MIT 2841). DLS measurements were carried out by VAM with a Nanotrac Wave analyzer, during an internship in the MESA+ Institute for Nanotechnology of the University of Twente. IMDEA Nanociencia also acknowledges support from the “Severo Ochoa” Programme for Centres of Excellence in R&D (MINECO, grant SEV-2016-0686

Evaluación del riesgo de alcoholismo en estudiantes de la secundaria básica Vicente Quesada. Bayamo

Alcoholism is universally accepted as one of the main public health problems throughout the world and represents a serious threat to the well-being and life of humanity, endangering both individual and social development. With the objective of assessing the risk of alcoholism in the ninth grade students of ESBU Vicente Quesada, a quantitative, prospective and descriptive study was conducted from September 2016 to July 2017. The most frequent age among at-risk students is 14 to 15 years, with a predominance of males. The school grade with the highest risk is ninth, 6 females (23.1 %) and 20 males (76.9 %), the family functionality is represented by extended families with 19 patients (47.4 %), the average family income predominates with the highest percentage among nuclear families, as well as inappropriate behaviour in more than three quarters of these patients and within these the risky previous consumption.El alcoholismo se acepta universalmente como uno los principales problemas de la salud pública en todo el mundo y representa una grave amenaza al bienestar y a la vida de la humanidad, pone en peligro tanto el desarrollo individual como el social. Con el objetivo de evaluar el riesgo de alcoholismo en los estudiantes de noveno grado de la ESBU Vicente Quesada, se realizó un estudio cuantitativo, prospectivo y descriptivo, de septiembre de 2016 a julio 2017. La edad más frecuente entre los estudiantes de riesgo es de 14 a 15 años, con predominio del sexo masculino. El grado escolar con mayor riesgo es noveno, 6 féminas (23.1 %) y 20 varones (76.9 %), la funcionalidad familiar está representada por las familias ampliadas con 19 pacientes (47.4 %), el ingreso familiar medio predomina con el mayor porcentaje entre las familias nucleares, así como la conducta no adecuada en más de las tres cuartas partes de estos pacientes y dentro de estos el consumo anterior riesgoso

Abrogating mitochondrial ROS in neurons or astrocytes reveals cell-specific impact on mouse behaviour

Article 101917, (2021)[EN]Cells naturally produce mitochondrial reactive oxygen species (mROS), but the in vivo pathophysiological significance has long remained controversial. Within the brain, astrocyte-derived mROS physiologically regulate behaviour and are produced at one order of magnitude faster than in neurons. However, whether neuronal mROS abundance differentially impacts on behaviour is unknown. To address this, we engineered genetically modified mice to down modulate mROS levels in neurons in vivo. Whilst no alterations in motor coordination were observed by down modulating mROS in neurons under healthy conditions, it prevented the motor discoordination caused by the pro-oxidant neurotoxin, 3-nitropropionic acid (3-NP). In contrast, abrogation of mROS in astrocytes showed no beneficial effect against the 3-NP insult. These data indicate that the impact of modifying mROS production on mouse behaviour critically depends on the specific cell-type where they are generated

Glutamate Excitoxicity Is the Key Molecular Mechanism Which Is Influenced by Body Temperature during the Acute Phase of Brain Stroke

Glutamate excitotoxicity, metabolic rate and inflammatory response have been associated to the deleterious effects of temperature during the acute phase of stroke. So far, the association of temperature with these mechanisms has been studied individually. However, the simultaneous study of the influence of temperature on these mechanisms is necessary to clarify their contributions to temperature-mediated ischemic damage. We used non-invasive Magnetic Resonance Spectroscopy to simultaneously measure temperature, glutamate excitotoxicity and metabolic rate in the brain in animal models of ischemia. The immune response to ischemia was measured through molecular serum markers in peripheral blood. We submitted groups of animals to different experimental conditions (hypothermia at 33°C, normothermia at 37°C and hyperthermia at 39°C), and combined these conditions with pharmacological modulation of glutamate levels in the brain through systemic injections of glutamate and oxaloacetate. We show that pharmacological modulation of glutamate levels can neutralize the deleterious effects of hyperthermia and the beneficial effects of hypothermia, however the analysis of the inflammatory response and metabolic rate, demonstrated that their effects on ischemic damage are less critical than glutamate excitotoxity. We conclude that glutamate excitotoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke

Traceability of the local cultivar ‘Caaveiro’ in flour mixtures used to produce Galician bread by simple sequence repeats and droplet digital polymerase chain reaction technology

The analysis of simple sequence repeats (SSRs) and of bulk ground samples by droplet digital polymerase chain reaction (ddPCR) was investigated as an alternative to individual kernel testing for assessing the presence of local cultivars in common wheat (Triticum aestivum L.) varietal blends. The recent Protected Geographical Indication (PGI) of ‘Pan Galego’ (Galician bread) requires that the flour comprise a minimum 25% local wheat cultivars. As a test for compliance with this minimum level, wheat flours were prepared by mixing commercial flours with 0%, 5%, 20%, 25% and 30% ‘Caaveiro’ and 100% ‘Caaveiro’ and 100% commercial flours were used as controls. A second analysis was performed with a second set of wheat flours with 5% and 25% ‘Caaveiro’. These were mixed with two different commercial flours to assess the potential ability of five SSRs to identify the percentage of ‘Caaveiro’, constituting the first reference of the use of SSRs in the traceability of specific autochthonous cultivars in flour blends. ddPCR using the QX200 system platform was used to the targeted proportions across the simulated range with two out of five SSRs, indicating that they can be used in the traceability of ‘Caaveiro’ in mixed flours and breadsS

Ultrahigh temperature Raman-based distributed optical fiber sensor with gold-coated fiber

An ultrahigh temperature distributed sensor based on a Raman optical-time-domain-reflectometry (ROTDR) and two types of fibers: a standard multimode fiber and multimode gold-coated fiber are experimentally validated in this paper. A calibration technique has been implemented to correct the dynamic variation of the optical loss in the gold-coated fiber. Distributed temperature measurements up to 600º C have been carried out.This work was supported in part by the ENSA through TOMATIN project (cofounded by the Cantabria government) and in part by the Spanish Ministry of Economy and Competitiveness through the Projects TEC2013-47264-C2-1-R and TEC2016-76021-C2-2-R

The MDM2-p53 pathway is involved in preconditioning-induced neuronal tolerance to ischemia

Article number: 1610 (2018)[EN]Brain preconditioning (PC) refers to a state of transient tolerance against a lethal insult that can be evoked by a prior mild event. It is thought that PC may induce different pathways responsible for neuroprotection, which may involve the attenuation of cell damage pathways, including the apoptotic cell death. In this context, p53 is a stress sensor that accumulates during brain ischemia leading to neuronal death. The murine double minute 2 gene (MDM2), a p53-specific E3 ubiquitin ligase, is the main cellular antagonist of p53, mediating its degradation by the proteasome. Here, we study the role of MDM2-p53 pathway on PC-induced neuroprotection both in cultured neurons (in vitro) and rat brain (in vivo). Our results show that PC increased neuronal MDM2 protein levels, which prevented ischemia-induced p53 stabilization and neuronal death. Indeed, PC attenuated ischemia-induced activation of the p53/PUMA/caspase-3 signaling pathway. Pharmacological inhibition of MDM2-p53 interaction in neurons abrogated PC-induced neuroprotection against ischemia. Finally, the relevance of the MDM2-p53 pathway was confirmed in rat brain using a PC model in vivo. These findings demonstrate the key role of the MDM2-p53 pathway in PC-induced neuroprotection against a subsequent ischemic insult and poses MDM2 as an essential target in ischemic tolerance