Obesity generates metabolic alterations in the myocardium leading to changes in mitochondrial membrane permeability

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Gut microbial composition and functionality of school-age Mexican population with metabolic syndrome and type-2 diabetes mellitus using shotgun metagenomic sequencing

Gut metagenome in pediatric subjects with metabolic syndrome (MetS) and type-2 diabetes mellitus (T2DM) has been poorly studied, despite an alarming worldwide increase in the prevalence and incidence of obesity and MetS within this population. The objective of this study was to characterize the gut microbiome taxonomic composition of Mexican pediatric subjects with MetS and T2DM using shotgun metagenomics and analyze the potential relationship with metabolic changes and proinflammatory effects. Paired-end reads of fecal DNA samples were obtained through the Illumina HiSeq X Platform. Statistical analyses and correlational studies were conducted using gut microbiome data and metadata from all individuals. Gut microbial dysbiosis was observed in MetS and T2DM children compared to healthy subjects, which was characterized by an increase in facultative anaerobes (i.e., enteric and lactic acid bacteria) and a decrease in strict anaerobes (i.e., Erysipelatoclostridium, Shaalia, and Actinomyces genera). This may cause a loss of gut hypoxic environment, increased gut microbial nitrogen metabolism, and higher production of pathogen-associated molecular patterns. These metabolic changes may trigger the activation of proinflammatory activity and impair the host's intermediate metabolism, leading to a possible progression of the characteristic risk factors of MetS and T2DM, such as insulin resistance, dyslipidemia, and an increased abdominal circumference. Furthermore, specific viruses (Jiaodavirus genus and Inoviridae family) showed positive correlations with proinflammatory cytokines involved in these metabolic diseases. This study provides novel evidence for the characterization of MetS and T2DM pediatric subjects in which the whole gut microbial composition has been characterized. Additionally, it describes specific gut microorganisms with functional changes that may influence the onset of relevant health risk factors

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Exposome and foetoplacental vascular dysfunction in gestational diabetes mellitus

A balanced communication between the mother, placenta and foetus is crucial to reach a successful pregnancy. Several windows of exposure to environmental toxins are present during pregnancy. When the women metabolic status is affected by a disease or environmental toxin, the foetus is impacted and may result in altered development and growth. Gestational diabetes mellitus (GDM) is a disease of pregnancy characterised by abnormal glucose metabolism affecting the mother and foetus. This disease of pregnancy associates with postnatal consequences for the child and the mother. The whole endogenous and exogenous environmental factors is defined as the exposome. Endogenous insults conform to the endo-exposome, and disruptors contained in the immediate environment are the ecto-exposome. Some components of the endo-exposome, such as Selenium, vitamins D and B12, adenosine, and a high-fat diet, and ecto-exposome, such as the heavy metals Arsenic, Mercury, Lead and Copper, and per- and polyfluoroakyl substances, result in adverse pregnancies, including an elevated risk of GDM or gestational diabesity. The impact of the exposome on the human placenta's vascular physiology and function in GDM and gestational diabesity is reviewed

Políticas públicas para el desarrollo y la competitividad en la industria manufacturera

Las pequeñas y medianas empresas generan gran parte de los empleos en los países industrializados, sin embargo, la mayoría de los gobiernos muestran una gran falta de atención a las mismas, por considerarlas actividades poco importantes o de escaso aporte a sus economías. En México apenas se está iniciando el debate entre gobernantes, políticos y grandes empresarios, sobre la función de las pymes. Entre las cuestiones principales que se discuten están: ¿cuál es la importancia real de su contribución al crecimiento eocnómico de estos países?, ¿son un motor clave en la creación de empleos para las economías nacionales

Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial Treatments

Due to the emergence of multi-drug resistant strains, development of novel antibiotics has become a critical issue. One promising approach is the use of transition metals, since they exhibit rapid and significant toxicity, at low concentrations, in prokaryotic cells. Nevertheless, one main drawback of transition metals is their toxicity in eukaryotic cells. Here, we show that the barriers to use them as therapeutic agents could be mitigated by combining them with silver. We demonstrate that synergism of combinatorial treatments (Silver/transition metals, including Zn, Co, Cd, Ni, and Cu) increases up to 8-fold their antimicrobial effect, when compared to their individual effects, against E. coli and B. subtilis. We find that most combinatorial treatments exhibit synergistic antimicrobial effects at low/ non-toxic concentrations to human keratinocyte cells, blast and melanoma rat cell lines. Moreover, we show that silver/(Cu, Ni, and Zn) increase prokaryotic cell permeability at sub-inhibitory concentrations, demonstrating this to be a possible mechanism of the synergistic behavior. Together, these results suggest that these combinatorial treatments will play an important role in the future development of antimicrobial agents and treatments against infections. In specific, the cytotoxicity experiments show that the combinations have great potential in the treatment of topical infections

Cardiac responses to β‐adrenoceptor stimulation is partly dependent on mitochondrial calcium uniporter activity

Background and Purpose: Despite the importance of mitochondrial Ca2+ to metabolic regulation and cell physiology, little is known about the mechanisms that regulate Ca2+ entry into the mitochondria. Accordingly, we established a system to determine the role of the mitochondrial Ca2+ uniporter in an isolated heart model, at baseline and during increased workload following β-adrenoceptor stimulation. Experimental Approach: Cardiac contractility, oxygen consumption and intracellular Ca2+ transients were measured in ex vivo perfused murine hearts. Ru360 and spermine were used to modify mitochondrial Ca2+ uniporter activity. Changes in mitochondrial Ca2+ content and energetic phosphate metabolite levels were determined. Key Results: The addition of Ru360, a selective inhibitor of the mitochondrial Ca2+ uniporter, induced progressively and sustained negative inotropic effects that were dose-dependent with an EC50 of 7 μM. Treatment with spermine, a uniporter agonist, showed a positive inotropic effect that was blocked by Ru360. Inotropic stimulation with isoprenaline elevated oxygen consumption (2.7-fold), Ca2+-dependent activation of pyruvate dehydrogenase (5-fold) and mitochondrial Ca2+ content (2.5-fold). However, in Ru360-treated hearts, this parameter was attenuated. In addition, β-adrenoceptor stimulation in the presence of Ru360 did not affect intracellular Ca2+ handling, PKA or Ca2+/calmodulin-dependent PK signalling. Conclusions and Implications: Inhibition of the mitochondrial Ca2+ uniporter decreases β-adrenoceptor response, uncoupling between workload and production of energetic metabolites. Our results support the hypothesis that the coupling of workload and energy supply is partly dependent on mitochondrial Ca2+ uniporter activity.Centro de Investigaciones Cardiovasculare

CiTiEs (Ciudades: Tiempo + Espacio). Implementación de itinerarios didácticos para la enseñanza virtual y presencial del Patrimonio cultural de Madrid a través del aprendizaje cooperativo

Retomando los itinerarios didácticos diseñados en un PID anterior (2019/20, nº 363), se implementarán materiales digitales para la Educación patrimonial de Madrid. Se utilizarán técnicas de aprendizaje cooperativo y recursos para la enseñanza virtual.Depto. de Didáctica de las Ciencias Experimentales , Sociales y MatemáticasFac. de EducaciónFALSEsubmitte