Plasma levels of ghrelin, des-acyl ghrelin and LEAP2 in children with obesity: Correlation with age and insulin resistance

Objective: The octanoylated peptide hormone ghrelin regulates appetite and glycaemic control. Des-acyl ghrelin abolishes some effects of ghrelin, but does not bind to ghrelin receptor. LEAP2 is a novel ligand for ghrelin receptor that blocks the effects of ghrelin. Some evidences show that plasma levels of these peptides are altered adults with obesity, but their levels in childhood obesity remain poorly studied. Therefore, the objective of this study was to assess fasting plasma levels of ghrelin, des-acyl ghrelin and LEAP2 in children with normoweight, overweight/obesity and their association with different anthropometric and metabolic variables. Design: A total of 42 females and 40 males, ages 3-12 years-old were enrolled as a cross-sectional cohort. Results: Plasma levels of des-acyl ghrelin and LEAP2 (but not ghrelin) were lower and ghrelin/des-acyl ghrelin ratio was higher in children with overweight/obesity. Des-acyl ghrelin negatively correlated with age, BMI z-score, insulin and HOMA index, and the correlations were stronger in children with overweight/obesity. LEAP2 levels negatively correlated with BMI z-score. No gender differences were found. Conclusions: Our findings suggest that ghrelin tone is increased in childhood obesity, due to a decrease on plasma levels of des-acyl ghrelin and LEAP2, and that des-acyl ghrelin is associated to insulin resistance, particularly in children with overweight/obesity.Fil: Fittipaldi, Antonela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Hernandez, Julieta. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata. Instituto de Desarrollo e Investigaciones Pediátricas; ArgentinaFil: Castrogiovanni, Daniel Cayetano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Lufrano, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: de Francesco, Pablo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Garrido, Verónica. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata. Instituto de Desarrollo e Investigaciones Pediátricas; ArgentinaFil: Vitaux, Patrick. Bertin Technologies; FranciaFil: Fasano, María Victoria. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Matemáticas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata. Instituto de Desarrollo e Investigaciones Pediátricas; ArgentinaFil: Fehrentz, Jean Alain. Bertin Technologies; Francia. Université Montpellier II; FranciaFil: Fernández, Adriana. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata. Instituto de Desarrollo e Investigaciones Pediátricas; ArgentinaFil: Andreoli, María F.. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata. Instituto de Desarrollo e Investigaciones Pediátricas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perello, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentin

Shiga Toxin 1 Induces on Lipopolysaccharide-Treated Astrocytes the Release of Tumor Necrosis Factor-alpha that Alter Brain-Like Endothelium Integrity

The hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia and renal dysfunction. The typical form of HUS is generally associated with infections by Gram-negative Shiga toxin (Stx)-producing Escherichia coli (STEC). Endothelial dysfunction induced by Stx is central, but bacterial lipopolysaccharide (LPS) and neutrophils (PMN) contribute to the pathophysiology. Although renal failure is characteristic of this syndrome, neurological complications occur in severe cases and is usually associated with death. Impaired blood-brain barrier (BBB) is associated with damage to cerebral endothelial cells (ECs) that comprise the BBB. Astrocytes (ASTs) are inflammatory cells in the brain and determine the BBB function. ASTs are in close proximity to ECs, hence the study of the effects of Stx1 and LPS on ASTs, and the influence of their response on ECs is essential. We have previously demonstrated that Stx1 and LPS induced activation of rat ASTs and the release of inflammatory factors such as TNF-α, nitric oxide and chemokines. Here, we demonstrate that rat ASTs-derived factors alter permeability of ECs with brain properties (HUVECd); suggesting that functional properties of BBB could also be affected. Additionally, these factors activate HUVECd and render them into a proagregant state promoting PMN and platelets adhesion. Moreover, these effects were dependent on ASTs secreted-TNF-α. Stx1 and LPS-induced ASTs response could influence brain ECs integrity and BBB function once Stx and factors associated to the STEC infection reach the brain parenchyma and therefore contribute to the development of the neuropathology observed in HUS

Aprendizajes y prácticas educativas en las actuales condiciones de época: COVID-19

“Esta obra colectiva es el resultado de una convocatoria a docentes, investigadores y profesionales del campo pedagógico a visibilizar procesos investigativos y prácticas educativas situadas en el marco de COVI-19. La misma se inscribe en el trabajo llevado a cabo por el equipo de Investigación responsable del Proyecto “Sentidos y significados acerca de aprender en las actuales condiciones de época: un estudio con docentes y estudiantes de la educación secundarias en la ciudad de Córdoba” de la Facultad de Filosofía y Humanidades. Universidad Nacional de Córdoba. El momento excepcional que estamos atravesando, pero que también nos atraviesa, ha modificado la percepción temporal a punto tal que habitamos un tiempo acelerado y angustiante que nos exige la producción de conocimiento provisorio. La presente publicación surge como un espacio para detenernos a documentar lo que nos acontece y, a su vez, como oportunidad para atesorar y resguardar las experiencias educativas que hemos construido, inventado y reinventando en este contexto. En ella encontrarán pluralidad de voces acerca de enseñar y aprender durante la pandemia. Este texto es una pausa para reflexionar sobre el hacer y las prácticas educativas por venir”.Fil: Beltramino, Lucia (comp.). Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Archivología; Argentina

Analyse fonctionnelle du facteur de transcription KLF6 dans le contrôle de la prolifération cellulaire : interactions avec des oncoprotéines cellulaires et virales

Le facteur de transcription Kruppel-like 6 (KLF6) est impliqué dans des rôles essentiels tels que la transduction du signal liée à la croissance, la prolifération et la différenciation cellulaire, le développement, l'apoptose et l'angiogenèse. En outre, KLF6 semble être un facteur clé lors du développement et la progression de cancers et son expression est finement régulée par plusieurs stimuli qui endommagent les cellules. Le but de cette thèse était de caractériser les signaux biochimiques régulant la fonction de KLF6 et d'analyser leurs effets sur la prolifération cellulaire et l'apoptose. Nous avons tout d'abord caractérisé le rôle des voies de transduction de signal JNK et p38 dans l'expression et la fonction KLF6. Puis nous avons étudié les effets de KLF6 en réponse au stress cellulaire généré par le rayonnement UV et analysé leurs conséquences sur l'onco-protéine c-Jun et l'apoptose. Enfin, nous avons déterminé des effets de KLF6 dans le contexte de stress cellulaire généré par l'infection à adénovirus qui est capable d'induire la prolifération cellulaire ou l'apoptose.The mammalian Krüppel-like factor 6 (KLF6) is involved in critical roles such as growth-related signal transduction, cell proliferation and differentiation, development, apoptosis and angiogenesis. Additionally, KLF6 appears to be an emerging key factor during cancer development and progression. Its expression is thoroughly regulated by several celldamaging stimuli. The aim of this thesis was to characterize the biochemical signals that regulate the function of KLF6 and analyze their effects on cell proliferation and apoptosis. We first characterized the role of JNK and p38 signal transduction pathways in the expression and function of KLF6. Then we studied the effects of KLF6 in response to cellular stress generated by UV radiation and analyzed their effects on the c-Jun onco-protein and on apoptosis. Finally, we determined the effects of KLF6 in the context of cellular stress generated by infection with adenovirus that is able to induce cell proliferation or apoptosis

Analyse fonctionnelle du facteur de transcription KLF6 dans le contrôle de la prolifération cellulaire : interactions avec des oncoprotéines cellulaires et virales

Le facteur de transcription Kruppel-like 6 (KLF6) est impliqué dans des rôles essentiels tels que la transduction du signal liée à la croissance, la prolifération et la différenciation cellulaire, le développement, l'apoptose et l'angiogenèse. En outre, KThe mammalian Krüppel-like factor 6 (KLF6) is involved in critical roles such as growth-related signal transduction, cell proliferation and differentiation, development, apoptosis and angiogenesis. Additionally, KLF6 appears to be an emerging key factor

Functional analysis of KLF6 transcription factor in the control of cell proliferation. Interactions with cellular and viral oncoproteins.

Le facteur de transcription Kruppel-like 6 (KLF6) est impliqué dans des rôles essentiels tels que la transduction du signal liée à la croissance, la prolifération et la différenciation cellulaire, le développement, l'apoptose et l'angiogenèse. En outre, KLF6 semble être un facteur clé lors du développement et la progression de cancers et son expression est finement régulée par plusieurs stimuli qui endommagent les cellules. Le but de cette thèse était de caractériser les signaux biochimiques régulant la fonction de KLF6 et d’analyser leurs effets sur la prolifération cellulaire et l'apoptose. Nous avons tout d’abord caractérisé le rôle des voies de transduction de signal JNK et p38 dans l'expression et la fonction KLF6. Puis nous avons étudié les effets de KLF6 en réponse au stress cellulaire généré par le rayonnement UV et analysé leurs conséquences sur l'onco-protéine c-Jun et l'apoptose. Enfin, nous avons déterminé des effets de KLF6 dans le contexte de stress cellulaire généré par l'infection à adénovirus qui est capable d'induire la prolifération cellulaire ou l'apoptose.The mammalian Krüppel-like factor 6 (KLF6) is involved in critical roles such as growth-related signal transduction, cell proliferation and differentiation, development, apoptosis and angiogenesis. Additionally, KLF6 appears to be an emerging key factor during cancer development and progression. Its expression is thoroughly regulated by several celldamaging stimuli. The aim of this thesis was to characterize the biochemical signals that regulate the function of KLF6 and analyze their effects on cell proliferation and apoptosis. We first characterized the role of JNK and p38 signal transduction pathways in the expression and function of KLF6. Then we studied the effects of KLF6 in response to cellular stress generated by UV radiation and analyzed their effects on the c-Jun onco-protein and on apoptosis. Finally, we determined the effects of KLF6 in the context of cellular stress generated by infection with adenovirus that is able to induce cell proliferation or apoptosis

Análisis funcional del factor de transcripción KLF6 en el control de la proliferación celular (interacción con oncoproteínas celulares y virales)

Le facteur de transcription Kruppel-like 6 (KLF6) est impliqué dans des rôles essentiels tels que la transduction du signal liée à la croissance, la prolifération et la différenciation cellulaire, le développement, l'apoptose et l'angiogenèse. En outre, KLF6 semble être un facteur clé lors du développement et la progression de cancers et son expression est finement régulée par plusieurs stimuli qui endommagent les cellules. Le but de cette thèse était de caractériser les signaux biochimiques régulant la fonction de KLF6 et d analyser leurs effets sur la prolifération cellulaire et l'apoptose. Nous avons tout d abord caractérisé le rôle des voies de transduction de signal JNK et p38 dans l'expression et la fonction KLF6. Puis nous avons étudié les effets de KLF6 en réponse au stress cellulaire généré par le rayonnement UV et analysé leurs conséquences sur l'onco-protéine c-Jun et l'apoptose. Enfin, nous avons déterminé des effets de KLF6 dans le contexte de stress cellulaire généré par l'infection à adénovirus qui est capable d'induire la prolifération cellulaire ou l'apoptose.The mammalian Krüppel-like factor 6 (KLF6) is involved in critical roles such as growth-related signal transduction, cell proliferation and differentiation, development, apoptosis and angiogenesis. Additionally, KLF6 appears to be an emerging key factor during cancer development and progression. Its expression is thoroughly regulated by several celldamaging stimuli. The aim of this thesis was to characterize the biochemical signals that regulate the function of KLF6 and analyze their effects on cell proliferation and apoptosis. We first characterized the role of JNK and p38 signal transduction pathways in the expression and function of KLF6. Then we studied the effects of KLF6 in response to cellular stress generated by UV radiation and analyzed their effects on the c-Jun onco-protein and on apoptosis. Finally, we determined the effects of KLF6 in the context of cellular stress generated by infection with adenovirus that is able to induce cell proliferation or apoptosis.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

c-Jun Proto-Oncoprotein Plays a Protective Role in Lung Epithelial Cells Exposed to Staphylococcal α-Toxin

c-Jun is a member of the early mammalian transcriptional regulators belonging to the AP-1 family, which participates in a wide range of cellular processes such as proliferation, apoptosis, tumorigenesis, and differentiation. Despite its established role in cell survival upon stress, its participation in the stress response induced by bacterial infections has been poorly investigated. To study the potential role of c-Jun in this context we choose the widely studied α-toxin produced by Staphylococcus aureus, a pore-forming toxin that is a critical virulence factor in the pathogenesis of these bacteria. We analyzed the effect of α-toxin treatment in the activation, expression, and protein levels of c-Jun in A549 lung epithelial cells. Furthermore, we explored the role of c-Jun in the cellular fate after exposure to α-toxin. Our results show that staphylococcal α-toxin per se is able to activate c-Jun by inducing phosphorylation of its Serine 73 residue. Silencing of the JNK (c-Jun N-terminal Kinase) signaling pathway abrogated most of this activation. On the contrary, silencing of the ERK (Extracellular Signal-Regulated Kinase) pathway exacerbated this response. Intriguingly, while the exposure to α-toxin induced a marked increase in the levels of c-Jun transcripts, c-Jun protein levels noticeably decreased in the same time-frame as a consequence of active proteolytic degradation through the proteasome-dependent pathway. In addition, we established that c-Jun promoted cell survival when cells were challenged with α-toxin. Similarly, c-Jun phosphorylation was also induced in cells upon intoxication with the cytolysin produced by Vibrio cholerae in a JNK-dependent manner, suggesting that c-Jun-JNK axis would be a conserved responsive cellular pathway to pore-forming toxins. This study contributes to understanding the role of the multifaceted c-Jun proto-oncoprotein in cell response to bacterial pore-forming toxins, positioning it as a relevant component of the complex early machinery mounted to deal with staphylococcal infections