Integrated transcriptomics establish macrophage polarization signatures and have potential applications for clinical health and disease

Growing evidence defines macrophages (Mφ) as plastic cells with wide-ranging states of activation and expression of different markers that are time and location dependent. Distinct from the simple M1/M2 dichotomy initially proposed, extensive diversity of macrophage phenotypes have been extensively demonstrated as characteristic features of monocyte-macrophage differentiation, highlighting the difficulty of defining complex profiles by a limited number of genes. Since the description of macrophage activation is currently contentious and confusing, the generation of a simple and reliable framework to categorize major Mφ phenotypes in the context of complex clinical conditions would be extremely relevant to unravel different roles played by these cells in pathophysiological scenarios. In the current study, we integrated transcriptome data using bioinformatics tools to generate two macrophage molecular signatures. We validated our signatures in in vitro experiments and in clinical samples. More importantly, we were able to attribute prognostic and predictive values to components of our signatures. Our study provides a framework to guide the interrogation of macrophage phenotypes in the context of health and disease. The approach described here could be used to propose new biomarkers for diagnosis in diverse clinical settings including dengue infections, asthma and sepsis resolution

Capacidad antimicrobiana de fitoproteasas autóctonas sobre cepas bacterianas patógenas de importancia clínica y alimentaria

Los productos naturales y las drogas relacionadas son usados en el tratamiento del 87% de las enfermedades que afectan al hombre inclusive en las infecciones bacterianas, en cáncer y en desórdenes inmunológicos. Es así que muchos países en desarrollo basan su medicina popular en compuestos obtenidos a partir de plantas. A diferencia de los animales, las plantas carecen de sistema inmunológico y la respuesta inmunitaria de ellas comprende mensajeros químicos sistémicos que se distribuyen por toda la planta. En los últimos años se ha reportado el aislamiento de diferentes tipos de proteínas vegetales con actividad antimicrobiana, entre ellas quitinasas, β-1,3-glucanasas, defensinas, tioninas, inhibidores de proteasas e incluso enzimas proteolíticas (Rojas et al., 2006). En consecuencia, la búsqueda de nuevas fuentes de agentes antimicrobianos se hace imprescindible, dado el creciente aumento de la resistencia de microorganismos a los antibióticos tradicionales. En este contexto, la investigación en compuestos biológicamente activos de origen natural resulta de gran interés. Se ha observado que algunas proteasas están involucradas en procesos de inhibición del crecimiento bacteriano (Guevara et al., 2004) y es por eso que el objetivo de este trabajo es determinar la capacidad antimicrobiana in vitro de dos endopeptidasas autóctonas frente a distintas cepas patógenas de importancia clínica y alimentaria. Se purificaron los extractos crudos de látex de frutos de Araujia hortorum y de frutos maduros de Salpichroa origanifolia. La actividad antimicrobiana de las fracciones purificadas fue ensayada sobre cepas seleccionadas de Staphylococcus aureus, Salmonella enteritidis, Escherichia coli, Serratia marcescen y Kebsiella pneumoniae. El ensayo in vitro se realizó incubando las proteasas en medio de cultivo líquido (caldo tripteína soja) a 37ºC frente a las distintas cepas bacterianas. El seguimiento de la cinética de crecimiento bacteriano en ausencia o en presencia del compuesto antimicrobiano se realizó midiendo la turbidez a 650 nm durante 20 hs de incubación, en un espectrofotómetro GeneQuant. El porcentaje de inhibición se calculó como el cociente entre las mediciones de DO con y sin peptidasa. Como conclusión podemos afirmar que las endopeptidasas cisteínicas presentes en Araujia hortorum (araujaína) demostraron actividad antimicrobiana frente Salmonella enteritidis (90% de inhibición) y en menor grado frente a Escherichia coli (25%). En el caso de las aspartil peptidasas de Salpichroa origanifolia (salpichroína), se observó un 95% de inhibición frente a cepas de Staphylococcus aureus, Klebsiella pneumoniae, Serratia marcescens y en menor grado de Escherichia coli (75%). Estos resultados podrían contribuir al desarrollo de nuevos agentes antimicrobianos en el área de salud, además de tener aplicación en la industria de los alimentos y/o en el sector agronómico.Centro de Investigación de Proteínas Vegetale

Shortened telomere length in bipolar disorder: a comparison of the early and late stages of disease

Objective: Bipolar disorder (BD) has been associated with increased rates of age-related diseases, such as type II diabetes, metabolic syndrome, osteoporosis, and cardiovascular disorders. Several biological findings have been associated with age-related disorders, including increased oxidative stress, inflammation, and telomere shortening. The objective of this study was to compare telomere length among participants with BD at early and late stages and age- and gender-matched healthy controls. Methods: Twenty-six euthymic subjects with BD and 34 healthy controls were recruited. Genomic DNA was extracted from peripheral blood and mean telomere length was measured using real-time quantitative polymerase chain reaction. Results: Telomere length was significantly shorter in both the early and late subgroups of BD subjects when compared to the respective controls (p = 0.002 and p = 0.005, respectively). The sample size prevented additional subgroup analyses, including potential effects of medication, smoking status, and lifestyle. Conclusion: This study is concordant with previous evidence of telomere shortening in BD, in both early and late stages of the disorder, and supports the notion of accelerated aging in BD

A Pilot Study of Body Composition and Bone Mineral Density in Healthy Men From Argentina

A precise assessment of bone mineral density (BMD) and body composition can be performed using dual-energy X-ray absorptiometry (DXA). Values of body composition for males would be useful to evaluate the occurrence of alterations in body composition in a number of diseases. The objectives of this study were to establish BMD and body composition values in healthy men and to analyze age-related changes. BMD and body composition of total body and subareas were determined in 116 healthy men (aged 20e79 yr) using DXA. Comparison between 20e29- and 70e79-yr-old men showed that older subjects were shorter ( p!0.03), and had a higher body mass index ( p!0.01). Fat mass increased (þ46.7%; p!0.001) especially in the trunk. Lean mass (LM) decreased (9.4%; p!0.05) mainly in the arms and legs. Bone mineral content (BMC) and BMD decreased (15.3% [p!0.001], 6.3% [p!0.05], respectively). Correlation was observed between BMC and LM (r50.7, p!0.01). Values of BMD and body composition in healthy men were obtained. A relation was observed between bone mass and body composition, suggesting that the age-related decrease in LM may be associated to bone mass loss. Further studies should be conducted to elucidate the role of body composition in the occurrence of osteoporosis in men.Fil: Seijo, Mariana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. División Osteopatías; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Deferrari, Juan M.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. División Osteopatías; ArgentinaFil: Bagur, Alicia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. División Osteopatías; ArgentinaFil: Fernandez, Maria C.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. División Osteopatías; ArgentinaFil: Mastaglia, Silvina Rosana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. División Osteopatías; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Parisi, Muriel Solange. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. División Osteopatías; ArgentinaFil: Oliveri, María Beatriz. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. División Osteopatías; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentin

A concept for integrated care pathways for atopic dermatitis-A GA 2 LEN ADCARE initiative

The integrated care pathways for atopic dermatitis (AD-ICPs) aim to bridge the gap between existing AD treatment evidence-based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co-ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. The GA 2 LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD-ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL 2 EN ADCARE centres. The AD-ICPs outline the diagnostic procedures, possible co-morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. The AD-ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD