Mitophagy in Human Diseases.

Mitophagy is a selective autophagic process, essential for cellular homeostasis, that eliminates dysfunctional mitochondria. Activated by inner membrane depolarization, it plays an important role during development and is fundamental in highly differentiated post-mitotic cells that are highly dependent on aerobic metabolism, such as neurons, muscle cells, and hepatocytes. Both defective and excessive mitophagy have been proposed to contribute to age-related neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases, metabolic diseases, vascular complications of diabetes, myocardial injury, muscle dystrophy, and liver disease, among others. Pharmacological or dietary interventions that restore mitophagy homeostasis and facilitate the elimination of irreversibly damaged mitochondria, thus, could serve as potential therapies in several chronic diseases. However, despite extraordinary advances in this field, mainly derived from in vitro and preclinical animal models, human applications based on the regulation of mitochondrial quality in patients have not yet been approved. In this review, we summarize the key selective mitochondrial autophagy pathways and their role in prevalent chronic human diseases and highlight the potential use of specific interventions.

Intestinal Effects of Filtered Alkalinized Water in Lean and Obese Zucker Rats.

This study evaluated the intestinal effects of alkalinized filtered water in lean and obese adult Zucker rats. For 3 months, 12-week-old rats consumed either tap water or filtered alkalinized tap water from Madrid city. Weight gain was monitored, changes in metabolism were evaluated by indirect calorimetry, and total antioxidant capacity and levels of inflammatory mediators were measured in plasma. Feces were collected, their microbial composition was analyzed and histological analysis of the small and large intestine was performed, assessing the general state of the mucosa (MUC2), the inflammatory state (F4/80) and the presence of oxidative modifications in protein 4-Hydroxynonenal (4-HNE) by immunofluorescence (IF) and immunohistochemistry (IHC). The results obtained showed that the consumption of alkalinized filtered water improved the composition of the intestinal microbiome and the state of the intestinal mucosa, reducing both local and systemic inflammation and the level of oxidative stress. These changes were accompanied by a better maintenance of the oxidative status in rats. No differences were observed in antioxidant capacity nor in weight gain. The incorporation of probiotics in the diet had a significant impact on the microbiome. These effects were indicative of an improvement in general metabolic, oxidative and inflammatory status.

Culture of Bovine Aortic Endothelial Cells in Galactose Media Enhances Mitochondrial Plasticity and Changes Redox Sensing, Altering Nrf2 and FOXO3 Levels.

Understanding the complex biological processes of cells in culture, particularly those related to metabolism, can be biased by culture conditions, since the choice of energy substrate impacts all of the main metabolic pathways. When glucose is replaced by galactose, cells decrease their glycolytic flux, working as an in vitro model of limited nutrient availability. However, the effect of these changes on related physiological processes such as redox control is not well documented, particularly in endothelial cells, where mitochondrial oxidation is considered to be low. We evaluated the differences in mitochondrial dynamics and function in endothelial cells exposed to galactose or glucose culture medium. We observed that cells maintained in galactose-containing medium show a higher mitochondrial oxidative capacity, a more fused mitochondrial network, and higher intercellular coupling. These factors are documented to impact the cellular response to oxidative stress. Therefore, we analyzed the levels of two main redox regulators and found that bovine aortic endothelial cells (BAEC) in galactose media had higher levels of FOXO3 and lower levels of Nrf2 than those in glucose-containing media. Thus, cultures of endothelial cells in a galactose-containing medium may provide a more suitable target for the study of in vitro mitochondrial-related processes than those in glucose-containing media; the medium deeply influences redox signaling in these cells.

Multimodular Bio-Inspired Organized Structures Guiding Long-Distance Axonal Regeneration.

Axonal bundles or axonal tracts have an aligned and unidirectional architecture present in many neural structures with different lengths. When peripheral nerve injury (PNI), spinal cord injury (SCI), traumatic brain injury (TBI), or neurodegenerative disease occur, the intricate architecture undergoes alterations leading to growth inhibition and loss of guidance through large distance. In order to overcome the limitations of long-distance axonal regeneration, here we combine a poly-L-lactide acid (PLA) fiber bundle in the common lumen of a sequence of hyaluronic acid (HA) conduits or modules and pre-cultured Schwann cells (SC) as cells supportive of axon extension. This multimodular preseeded conduit is then used to induce axon growth from a dorsal root ganglion (DRG) explant placed at one of its ends and left for 21 days to follow axon outgrowth. The multimodular conduit proved effective in promoting directed axon growth, and the results may thus be of interest for the regeneration of long tissue defects in the nervous system. Furthermore, the hybrid structure grown within the HA modules consisting in the PLA fibers and the SC can be extracted from the conduit and cultured independently. This "neural cord" proved to be viable outside its scaffold and opens the door to the generation of ex vivo living nerve in vitro for transplantation.

Impact of lung ultrasound during the SARS-CoV-2 pandemic: Distinction between viral and bacterial pneumonia.

INTRODUCTION: Lung Ultrasound is an accessible, low-cost technique that has demonstrated its usefulness in the prognostic stratification of COVID-19 patients. In addition, according to previous studies, it can guide us towards the potential aetiology, especially in epidemic situations such as the current one. PATIENTS AND METHODS: 40 patients were prospectively recruited, 30 with confirmed SARS-CoV-2 pneumonia and 10 with community-acquired pneumonia (CAP). The patients included underwent both a chest X-ray and ultrasound. RESULTS: There were no differences in the 2 groups in terms of clinical and laboratory characteristics. The main ultrasound findings in the SARS-CoV-2 group were the presence of confluent B lines and subpleural consolidations and hepatinization in the CAP group. Pleural effusion was more frequent in the CAP group. There were no normal lung ultrasound exams. Analysis of the area under the curve (AUC) curves showed an area under the curve for Lung Ultrasound of 89.2% (95% CI: 75%.0-100%, p < .001) in the identification of SARS-CoV-2 pneumonia. The cut-off value for the lung score of 10 had a sensitivity of 93.3% and a specificity of 80.0% (p < .001). DISCUSSION: The combination of the findings of the Lung Ultrasound, with a Lung Score greater than 10, added to the rest of the additional tests, can be an excellent tool to predict the aetiology of the pneumonia.

Effects of a Mealworm (Tenebrio molitor) Extract on Metabolic Syndrome-Related Pathologies: In Vitro Insulin Sensitivity, Inflammatory Response, Hypolipidemic Activity and Oxidative Stress.

The mealworm (Tenebrio molitor Linnaeus 1758) is gaining importance as one of the most popular edible insects. Studies focusing on its bioactivities are increasing, although alternative forms of consumption other than the whole insect or flour, such as bioactive non-protein extracts, remain underexplored. Furthermore, the incidence of metabolic syndrome-related pathologies keeps increasing, hence the importance of seeking novel natural sources for reducing the impact of certain risk factors. The aim was to study the potential of a non-protein mealworm extract on metabolic syndrome-related pathologies, obtained with ethanol:water (1:1, v/v) by ultrasound-assisted extraction. We characterized the extract by gas-chromatography mass-spectrometry and assessed its hypolipidemic potential, its ability to scavenger free radicals, to attenuate the inflammatory response in microglial cells, to affect mitochondrial respiration and to enhance insulin sensitivity in mouse hepatocytes. The extract contained fatty acids, monoglycerides, amino acids, certain acids and sugars. The mealworm extract caused a 30% pancreatic lipase inhibition, 80% DPPH· scavenging activity and 55.9% reduction in the bioaccessibility of cholesterol (p = 0.009). The extract was effective in decreasing iNOS levels, increasing basal, maximal and ATP coupled respiration as well as enhancing insulin-mediated AKT phosphorylation at low insulin concentrations (p < 0.05). The potential of a non-protein bioactive mealworm extract against metabolic syndrome-related pathologies is shown, although further studies are needed to elucidate the mechanisms and relationship with compounds.

[Impact of Lung Ultrasound dUring the SARS-CoV-2 Pandemic: Distinction Between Viral and Bacterial Pneumonia]. / Impacto de la ecografía pulmonar Durante la pandemia por SARS-CoV-2: distinción entre la neumonía viral y la bacteriana.

Introduction: Lung ultrasound is an accessible, low-cost technique that has demonstrated its usefulness in the prognostic stratification of COVID-19 patients. In addition, according to previous studies, it can guide us towards the potential aetiology, especially in epidemic situations such as the current one. Patients and methods: 40 patients were prospectively recruited, 30 with confirmed SARS-CoV-2 pneumonia and 10 with community-acquired pneumonia. The patients included underwent both a chest X-ray and ultrasound. Results: There were no differences in the 2 groups in terms of clinical and laboratory characteristics. The main ultrasound findings in the SARS-CoV-2 group were the presence of confluent B lines and subpleural consolidations and hepatinization in the community-acquired pneumonia group. Pleural effusion was more frequent in the community-acquired pneumonia group. There were no normal lung ultrasound exams. Analysis of the area under the curve curves showed an area under the curve for lung ultrasound of 89.2% (95% CI: 75.0-100%, p < .001) in the identification of SARS-CoV-2 pneumonia. The cut-off value for the lung score of 10 had a sensitivity of 93.3% and a specificity of 80.0% (p < .001). Discussion: The combination of the findings of the lung ultrasound, with a lung score greater than 10, added to the rest of the additional tests, can be an excellent tool to predict the aetiology of the pneumonia.

Engineered axon tracts within tubular biohybrid scaffolds.

Injuries to the nervous system that involve the disruption of axonal pathways are devastating to the individual and require specific tissue engineering strategies. Here we analyse a cells-biomaterials strategy to overcome the obstacles limiting axon regenerationin vivo, based on the combination of a hyaluronic acid (HA) single-channel tubular conduit filled with poly-L-lactide acid (PLA) fibres in its lumen, with pre-cultured Schwann cells (SCs) as cells supportive of axon extension. The HA conduit and PLA fibres sustain the proliferation of SC, which enhance axon growth acting as a feeder layer and growth factor pumps. The parallel unidirectional ensemble formed by PLA fibres and SC tries to recapitulate the directional features of axonal pathways in the nervous system. A dorsal root ganglion (DRG) explant is planted on one of the conduit's ends to follow axon outgrowth from the DRG. After a 21 d co-culture of the DRG + SC-seeded conduit ensemble, we analyse the axonal extension throughout the conduit by scanning, transmission electronic and confocal microscopy, in order to study the features of SC and the grown axons and their association. The separate effects of SC and PLA fibres on the axon growth are also experimentally addressed. The biohybrid thus produced may be considered a synthetic axonal pathway, and the results could be of use in strategies for the regeneration of axonal tracts.

A Hyaluronic Acid Demilune Scaffold and Polypyrrole-Coated Fibers Carrying Embedded Human Neural Precursor Cells and Curcumin for Surface Capping of Spinal Cord Injuries.

Tissue engineering, including cell transplantation and the application of biomaterials and bioactive molecules, represents a promising approach for regeneration following spinal cord injury (SCI). We designed a combinatorial tissue-engineered approach for the minimally invasive treatment of SCI-a hyaluronic acid (HA)-based scaffold containing polypyrrole-coated fibers (PPY) combined with the RAD16-I self-assembling peptide hydrogel (Corning® PuraMatrix™ peptide hydrogel (PM)), human induced neural progenitor cells (iNPCs), and a nanoconjugated form of curcumin (CURC). In vitro cultures demonstrated that PM preserves iNPC viability and the addition of CURC reduces apoptosis and enhances the outgrowth of Nestin-positive neurites from iNPCs, compared to non-embedded iNPCs. The treatment of spinal cord organotypic cultures also demonstrated that CURC enhances cell migration and prompts a neuron-like morphology of embedded iNPCs implanted over the tissue slices. Following sub-acute SCI by traumatic contusion in rats, the implantation of PM-embedded iNPCs and CURC with PPY fibers supported a significant increase in neuro-preservation (as measured by greater ßIII-tubulin staining of neuronal fibers) and decrease in the injured area (as measured by the lack of GFAP staining). This combination therapy also restricted platelet-derived growth factor expression, indicating a reduction in fibrotic pericyte invasion. Overall, these findings support PM-embedded iNPCs with CURC placed within an HA demilune scaffold containing PPY fibers as a minimally invasive combination-based alternative to cell transplantation alone.

Biohybrids for spinal cord injury repair.

Spinal cord injuries (SCIs) result in the loss of sensory and motor function with massive cell death and axon degeneration. We have previously shown that transplantation of spinal cord-derived ependymal progenitor cells (epSPC) significantly improves functional recovery after acute and chronic SCI in experimental models, via neuronal differentiation and trophic glial cell support. Here, we propose an improved procedure based on transplantation of epSPC in a tubular conduit of hyaluronic acid containing poly (lactic acid) fibres creating a biohybrid scaffold. In vitro analysis showed that the poly (lactic acid) fibres included in the conduit induce a preferential neuronal fate of the epSPC rather than glial differentiation, favouring elongation of cellular processes. The safety and efficacy of the biohybrid implantation was evaluated in a complete SCI rat model. The conduits allowed efficient epSPC transfer into the spinal cord, improving the preservation of the neuronal tissue by increasing the presence of neuronal fibres at the injury site and by reducing cavities and cyst formation. The biohybrid-implanted animals presented diminished astrocytic reactivity surrounding the scar area, an increased number of preserved neuronal fibres with a horizontal directional pattern, and enhanced coexpression of the growth cone marker GAP43. The biohybrids offer an improved method for cell transplantation with potential capabilities for neuronal tissue regeneration, opening a promising avenue for cell therapies and SCI treatment.

La labor del tutor de las Ciencias Médicas desde la dimensión curricular / The work of Medical Sciences tutors from the curricular dimension

El tutor constituye el eje fundamental de la formación de los estudiantes de las Ciencias Médicas este no es cualquier trabajador o especialista; debe ser un experto en su área de competencia laboral, además de un educador y un gran comunicador capaz de motivar y de ejercer una influencia positiva sobre los educandos. En las esferas cognitivas como afectivas con su dedicación y formación dependen en gran parte de la adquisición de los conocimientos, habilidades y responsabilidades necesarios para ejercer eficazmente el rol que les corresponde y el grado de satisfacción de los estudiantes dentro del proceso educativo. Se plantea que la enseñanza tutelar constituye un pilar esencial en la formación del médico, del enfermero y el tecnólogo, pues le permite al educando lograr un mayor grado de independencia, creatividad y sentido de responsabilidad (AU).

The tutor is a main factor in training Medical Sciences students; he is not any worker or specialist: he should be an expert in his area of occupational competence, besides being an educator and a great communicator able of motivating and positively influencing the students in. Their dedication and training mostly depend on the acquisition of knowledge, skills and abilities to efficaciously play the role they have to play, and to reach the students´ satisfaction level in the teaching process. It is assumed that tutored teaching is an essential pillar in training physicians, nurses and technologists, because it allows the teacher to achieve a higher level of independence, creativity and sense of responsibility (AU).

Impacto de la ecografía pulmonar Durante la pandemia por SARS-CoV-2: distinción entre la neumonía viral y la bacteriana / Impact of Lung Ultrasound dUring the SARS-CoV-2 Pandemic: Distinction Between Viral and Bacterial Pneumonia

Introducción: La ecografía pulmonar es una técnica accesible, de bajo costo y que ha demostrado su utilidad en la estratificación pronóstica en pacientes con COVID-19. Además, según estudios previos, nos puede orientar hacia la potencial etiología, especialmente en situaciones epidémicas como la actual. Pacientes y métodos: Se reclutaron prospectivamente 40 pacientes, 30 con neumonía por SARS-CoV-2 y 10 por neumonía adquirida en la comunidad. A los pacientes incluidos, se les realizó tanto una radiografía como ecografía de tórax. Resultados: No hubo diferencias en los 2 grupos en cuanto a las características clínicas y analíticas. Los principales hallazgos ecográficos fueron en el grupo de SARS-CoV-2 la presencia de líneas B confluyentes y consolidaciones subpleurales y la hepatinización en el grupo de neumonía adquirida en la comunidad. El derrame pleural fue más frecuente en el grupo de neumonía adquirida en la comunidad. En ningún caso la ecografía pulmonar fue normal. El análisis de las curvas ROC mostró un área bajo la curva para la ecografía pulmonar del 89,2% (IC 95%: 75,0- 100%, p <0,001) en la identificación de la neumonía por SARS-CoV-2. El valor de corte para la puntuación del puntaje pulmonar de 10 tuvo una sensibilidad del 93,3% y especificidad del 80,0% (p <0,001). Discusión: La combinación de los hallazgos de la ecografía pulmonar, con un puntaje pulmonar mayor de 10, complementando el resto de las pruebas complementarias, puede ser una excelente herramienta para predecir la etiología de la neumonía.(AU)

Introduction: Lung ultrasound is an accessible, low-cost technique that has demonstrated its usefulness in the prognostic stratification of COVID-19 patients. In addition, according to previous studies, it can guide us towards the potential aetiology, especially in epidemic situations such as the current one. Patients and methods: 40 patients were prospectively recruited, 30 with confirmed SARS-CoV-2 pneumonia and 10 with community-acquired pneumonia. The patients included underwent both a chest X-ray and ultrasound. Results: There were no differences in the 2 groups in terms of clinical and laboratory characteristics. The main ultrasound findings in the SARS-CoV-2 group were the presence of confluent B lines and subpleural consolidations and hepatinization in the community-acquired pneumonia group. Pleural effusion was more frequent in the community-acquired pneumonia group. There were no normal lung ultrasound exams. Analysis of the area under the curve curves showed an area under the curve for lung ultrasound of 89.2% (95% CI: 75.0-100%, p <.001) in the identification of SARS-CoV-2 pneumonia. The cut-off value for the lung score of 10 had a sensitivity of 93.3% and a specificity of 80.0% (p <.001). Discussion: The combination of the findings of the lung ultrasound, with a lung score greater than 10, added to the rest of the additional tests, can be an excellent tool to predict the aetiology of the pneumonia.(AU)