86 results on '"Carlessi AS"'
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2. Caminhos que se bifurcam na implementação de uma Farmácia Viva em Promissão/SP: Uma entrevista com a farmacêutica Andresa Baja
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Luiza Paiva De Angelis and Pedro Crepaldi Carlessi
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Fitoterapia ,Plantas medicinais ,Sistema Único de Saúde ,Medicine - Abstract
Nesta entrevista, Andresa Baja apresenta o caminho percorrido pela cidade de Promissão/SP na implementação do programa farmácia viva.
- Published
- 2023
Catalog
3. Prefácio: Experiências atuais em fitoterapia e farmácias vivas no Estado de São Paulo: um trabalho multidisciplinar
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Fabio Carmona, Pedro Crepaldi Carlessi, Renata Cavalcanti Carnevale, Nelson Filice Barros, and Ana Maria Soares Pereira
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Medicine - Published
- 2023
4. Entrevista: Entre o arranjo produtivo local e o mercado farmacêutico industrial: contrariedades da oferta pública de fitoterápicos em Ribeirão Preto
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Pedro Crepaldi Carlessi and Katellyn Costa Silva
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Fitoterapia ,Plantas medicinais ,Sistema único de saúde ,Medicine - Abstract
Nesta entrevista, Lúcia Helena Terenciani Rodrigues Pereira apresenta o itinerário seguido por Ribeirão Preto/SP ao implementar a oferta de fitoterápicos no município.
- Published
- 2023
5. Targeted knockout of the gene OsHOL1 removes methyl iodide emissions from rice plants
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Martina Carlessi, Lorenzo Mariotti, Francesca Giaume, Fabio Fornara, Pierdomenico Perata, and Silvia Gonzali
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Medicine ,Science - Abstract
Abstract Iodine deficiency represents a public health problem worldwide. To increase the amount of iodine in the diet, biofortification strategies of plants have been tried. They rely on the exogenous administration of iodine to increase its absorption and accumulation. However, iodine is not stable in plants and can be volatilized as methyl iodide through the action of specific methyltransferases encoded by the HARMLESS TO OZONE LAYER (HOL) genes. The release of methyl iodide in the atmosphere represents a threat for the environment due to its ozone depletion potential. Rice paddies are among the strongest producers of methyl iodide. Thus, the agronomic approach of iodine biofortification is not appropriate for this crop, leading to further increases of iodine emissions. In this work, we used the genome editing CRISPR/Cas9 technology to knockout the rice HOL genes and investigate their function. OsHOL1 resulted a major player in methyl iodide production, since its knockout abolished the process. Moreover, its overexpression reinforced it. Conversely, knockout of OsHOL2 did not produce effects. Our experiments helped elucidating the function of the rice HOL genes, providing tools to develop new rice varieties with reduced iodine emissions and thus more suitable for biofortification programs without further impacting on the environment. more...
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- 2021
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6. Anxiety, depression, somatization and experiential avoidance indicators in peruvian university students in quarantine by COVID-19
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Héctor Hugo Sánchez Carlessi, Luis Alberto Yarlequé Chocas, Leda Javier Alva, Edith Rocío Nuñez LLacuachaqui, Carlos Arenas Iparraguirre, Maria Luisa Matalinares Calvet, Eduardo Gutiérrez Santayana, Irma Egoavil Medina, Jorge Solis Quispe, and Ceyda Fernandez Figueroa more...
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anexiety ,depression ,somatoform disorders ,experiental avoidance ,quarantine ,pandemics ,covid-19 ,Medicine ,Medicine (General) ,R5-920 - Abstract
Introduction: The COVID-19 quarantine has greatly affected university students in Peru, generating a series of physical, psychological and behavioral effects. Objective: To determine the factors associated with anxiety, depression, somatization and experiential avoidance in peruvian university students quarantined by COVID-19. Methods: A cross-sectional observational study was carried out. The sample was made up of 1264 university students from various departments of Peru, anxiety, depression, somatization and experiential avoidance were taken as dependent variables, which were evaluated with the questionnaire "The Inventory of unadjusted psychosocial behavior, in the presence of COVID-19 in the Peruvian population” and the AAQ II, for the statistical analysis the chi square was used Results: More than half of the university students in Peru present between 3 and 6 of the 6 anxiety indicators, and this same number of depression indicators is presented by 45% of the sample. 30% of the sample has between 3 and 6 indicators of somatization and 40.3% of the sample is located in the middle upwards on the experiential avoidance scale. Conclusions: There are differences in the levels of anxiety, somatization and experiential avoidance between men and women, it was also found that older students had lower levels of anxiety, depression and experiential avoidance, but not in somatization. more...
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- 2021
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7. Will for the study and academic work in students of a private university of Lima
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Héctor Hugo Sánchez Carlessi, Elio Iván Rodríguez Chávez, and Patricia Roxana Matos Ramírez
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willingness to learn ,academic work ,Medicine ,Medicine (General) ,R5-920 - Abstract
Introduction: Willingness to learn is an important study variable for any educational institution, since it isconsistent with institutional policy of improving quality to the provided educational services.Objective:The main objective is to identify and compare the different levels of Willingness to Learn, consideringthe gender and different academic programs or careers, among the students of a private university.Methods:Descriptive and comparative study, through the administration of the Willingness to LearnScale, in a sample of 762 male and female university students of Medical School, Psychology, Law, CivilEngineering, Administration and Management School (IVth, Vth and VIth academic semester).Results:Wefound significant differences considering gender; women show better or higher levels of Willingness toLearn, compared to men. Students of Engineering program showed a lower level of Willingness to Learn.Conclusion:We found significant differences among levels of Willingness to Learn, considering genderand academic program or career more...
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- 2020
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8. LA INVESTIGACION FORMATIVA EN LA ACTIVIDAD CURRICULAR
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Héctor Hugo Sánchez Carlessi
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Medicine ,Medicine (General) ,R5-920 - Abstract
Se ofrece una visión general de la investigación formativa como una de las modalidades de investigación activa y participativa que debe realizarse en toda institución de educación superior universitaria, sobre todo a través del trabajo curricular en el aula bajo la conducción del profesor. Se enfatiza el empleo de la investigación formativa como estrategia didáctica para propiciar la adquisición de nuevos aprendizajes por parte de los alumnos de una manera activa, constructiva y participativa, considerando los objetivos y contenidos de cada asignatura, así como las líneas de investigación que se deben precisar para cada campo profesional. Se resalta la importancia de la investigación formativa como una forma de investigación acción participativa, presentando así mismo las limitaciones de su realización según la naturaleza de la asignatura. more...
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- 2017
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9. GLP-1 receptor signalling promotes β-cell glucose metabolism via mTOR-dependent HIF-1α activation
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Rodrigo Carlessi, Younan Chen, Jordan Rowlands, Vinicius F. Cruzat, Kevin N. Keane, Lauren Egan, Cyril Mamotte, Rebecca Stokes, Jenny E. Gunton, Paulo Ivo Homem de Bittencourt, and Philip Newsholme
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Medicine ,Science - Abstract
Abstract Glucagon-like peptide-1 (GLP-1) promotes insulin secretion from pancreatic β-cells in a glucose dependent manner. Several pathways mediate this action by rapid, kinase phosphorylation-dependent, but gene expression-independent mechanisms. Since GLP-1-induced insulin secretion requires glucose metabolism, we aimed to address the hypothesis that GLP-1 receptor (GLP-1R) signalling can modulate glucose uptake and utilization in β-cells. We have assessed various metabolic parameters after short and long exposure of clonal BRIN-BD11 β-cells and rodent islets to the GLP-1R agonist Exendin-4 (50 nM). Here we report for the first time that prolonged stimulation of the GLP-1R for 18 hours promotes metabolic reprogramming of β-cells. This is evidenced by up-regulation of glycolytic enzyme expression, increased rates of glucose uptake and consumption, as well as augmented ATP content, insulin secretion and glycolytic flux after removal of Exendin-4. In our model, depletion of Hypoxia-Inducible Factor 1 alpha (HIF-1α) impaired the effects of Exendin-4 on glucose metabolism, while pharmacological inhibition of Phosphoinositide 3-kinase (PI3K) or mTOR completely abolished such effects. Considering the central role of glucose catabolism for stimulus-secretion coupling in β-cells, our findings suggest that chronic GLP-1 actions on insulin secretion include elevated β-cell glucose metabolism. Moreover, our data reveal novel aspects of GLP-1 stimulated insulin secretion involving de novo gene expression. more...
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- 2017
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10. Modelo de éxito del curso taller de titulación por tesis en medicina humana: publicación de repercusión internacional
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Jhony Alberto De La Cruz Vargas, Lucy Elena Correa Lopez, María del Socorro A. Gutiérrez Vda. de Bambarén, and Hugo H. Sánchez Carlessi
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Medicine ,Medicine (General) ,R5-920 - Abstract
Promover la Investigación en Estudiantes de Medicina y elevar la producción científica en las universidades del Perú y de Latinoamérica es una prioridad y una necesidad. Es un honor compartir con ustedes que recientemente publicamos en la prestigiosa revista Educación Medica, de Elsevier, indexada en Scopus, el articulo científico que resume la experiencia y el modelo de éxito del Curso Taller de Tesis que se dicta en la Facultad de MedicinaHumana de la Universidad Ricardo Palma: Promoting research in medical students and increasing scientific production in universities: Experience of the Undergraduate Thesis Workshop Course. La tesis de pregrado representa el trabajo académico con rigor científico, considerado como el primer paso serio de los estudiantes universitarios en el campo de la investigación, que según la nueva ley universitaria 30220 vigente en el Perú, constituye un requisito indispensable para obtener el titulo universitario. more...
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- 2019
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11. Validation of the Patient Health Questionnaire-9 (PHQ-9) in human medicine interns at a reference university in Peru during the COVID-19 pandemic
- Author
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Luis Alberto Yarlequé Chocas, Leda Javier Alva, Jorge Solis Quispe, Héctor Hugo Sánchez Carlessi, Carlos Arenas Iparraguirre, Eduardo Gutiérrez Santayana, Irma Egoavil Medina, Edith Rocío Nuñez LLacuachaqui, María Matalinares Calvet, and Ceyda Fernandez Figueroa more...
- Subjects
education.field_of_study ,Population ,General Medicine ,medicine.disease ,Experiential avoidance ,medicine ,Chi-square test ,Anxiety ,Observational study ,medicine.symptom ,education ,Psychology ,Psychosocial ,Somatization ,Depression (differential diagnoses) ,Clinical psychology - Abstract
Introduction: The COVID-19 quarantine has greatly affected university students in Peru, generating a series of physical, psychological and behavioral effects. Objective: To determine the factors associated with anxiety, depression, somatization and experiential avoidance in peruvian university students quarantined by COVID-19. Methods: A cross-sectional observational study was carried out. The sample was made up of 1264 university students from various departments of Peru, anxiety, depression, somatization and experiential avoidance were taken as dependent variables, which were evaluated with the questionnaire "The Inventory of unadjusted psychosocial behavior, in the presence of COVID-19 in the Peruvian population” and the AAQ II, for the statistical analysis the chi square was used Results: More than half of the university students in Peru present between 3 and 6 of the 6 anxiety indicators, and this same number of depression indicators is presented by 45% of the sample. 30% of the sample has between 3 and 6 indicators of somatization and 40.3% of the sample is located in the middle upwards on the experiential avoidance scale. Conclusions: There are differences in the levels of anxiety, somatization and experiential avoidance between men and women, it was also found that older students had lower levels of anxiety, depression and experiential avoidance, but not in somatization. more...
- Published
- 2022
- Full Text
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12. Tumor vascular remodeling by thrombospondin-1 enhances drug delivery and antineoplastic activity
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Andrea Resovi, Patrizia Borsotti, Fabio Sangalli, Enrico Davoli, Alexander Berndt, Lorena Zentilin, Massimo Zucchetti, Raffaella Giavazzi, Alice Passoni, Dorina Belotti, Giovanni Valbusa, Denise Pinessi, Mauro Giacca, Giulia Taraboletti, Lavinia Morosi, and Elena Carlessi more...
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Cisplatin ,Tumor microenvironment ,Neovascularization, Pathologic ,business.industry ,Angiogenesis ,Angiogenesis Inhibitors ,Antineoplastic Agents ,Vascular Remodeling ,chemistry.chemical_compound ,Pharmaceutical Preparations ,Paclitaxel ,chemistry ,In vivo ,Drug delivery ,Thrombospondin 1 ,Cancer research ,Humans ,Medicine ,Ectopic expression ,business ,Molecular Biology ,medicine.drug - Abstract
The disorganized and inefficient tumor vasculature is a major obstacle to the delivery and efficacy of antineoplastic treatments. Antiangiogenic agents can normalize the tumor vessels, improving vessel function and boosting the distribution and activity of chemotherapy. The type III repeats (T3R) domain of thrombospondin-1 contains different potential antiangiogenic sequences. We therefore hypothesized that it might affect the tumor vasculature. Ectopic expression of the T3R domain by the tumor cells or by the host, or administration of recombinant T3R, delayed the in vivo growth of experimental tumors. Tumors presented marked reorganization of the vasculature, with abundant but smaller vessels, associated with substantially less necrosis. Mechanistically, the use of truncated forms of the domain, containing different active sequences, pointed to the FGF2/FGFR/ERK axis as a target for T3R activity. Along with reduced necrosis, the expression of T3R promoted tumor distribution of chemotherapy (paclitaxel), with a higher drug concentration and more homogeneous distribution, as assessed by HPLC and MALDI imaging mass spectrometry. T3R-expressing tumors were more responsive to paclitaxel and cisplatin. This study shows that together with its known role as a canonical inhibitor of angiogenesis, thrombospondin-1 can also remodel tumor blood vessels, affecting the morphological and functional properties of the tumor vasculature. The ability of T3R to reduce tumor growth and improve the response to chemotherapy opens new perspectives for therapeutic strategies based on T3R to be used in combination therapies. more...
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- 2021
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13. Sex-related patterns of the gut-microbiota-brain axis in the neuropsychiatric conditions
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Luana M. Manosso, João Quevedo, Anelise S. Carlessi, Cinara L. Gonçalves, Gislaine Z. Réus, Kelen C.C. Recco, and Jaime Lin
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Male ,0301 basic medicine ,Context (language use) ,Gut flora ,03 medical and health sciences ,0302 clinical medicine ,Neurochemical ,Neurotrophic factors ,Brain-Gut Axis ,Animals ,Humans ,Medicine ,biology ,business.industry ,Mental Disorders ,General Neuroscience ,medicine.disease ,biology.organism_classification ,Gastrointestinal Microbiome ,030104 developmental biology ,Schizophrenia ,Autism spectrum disorder ,Autism ,Major depressive disorder ,Female ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Sex differences are often observed in psychiatric patients, especially major depressive disorders (MDD), schizophrenia, and developmental disorders, including autism spectrum disorders (ASDs). The prevalence rates between males and females seem variate according to the clinical condition. Although the findings are still incipient, it is suggested that these differences can involve neuroanatomical, neurochemical, and physiological sex differences. In this context, the microbiota-gut-brain axis hypothesis arises to explain some aspects of the complex pathophysiology of neuropsychiatric disorders. The microbiota composition is host-specific and can change conforming to age, sex, diet, medication, exercise, and others. The communication between the brain and the gut is bidirectional and may impact the entire system homeostasis. Many pathways appear to be involved, including neuroanatomic communication, neuroendocrine pathways, immune system, bacteria-derived metabolites, hormones, neurotransmitters, and neurotrophic factors. Although the clinical and preclinical studies are sparse and not very consistent, they suggest that sex differences in the gut microbiota may play an essential role in some neuropsychiatric conditions. Thus, this narrative review has as a mainly aim to show the points sex-related patterns associated to the gut-microbiota-brain axis in the MDD, ASDs, and schizophrenia. more...
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- 2021
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14. Hepatology Basic Science
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ND Abu Bakar, Nina Tirnitz-Parker, Daniel Poppe, George C.T. Yeoh, Elena Denisenko, Rodrigo Carlessi, Alistair R. R. Forrest, Julia Köhn-Gaone, and Matt Jones
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medicine.anatomical_structure ,Hepatology ,business.industry ,Gastroenterology ,Medicine ,RNA ,business ,Molecular biology ,Nucleus - Published
- 2020
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15. Fructose‐1,6‐bisphosphate induces generation of reactive oxygen species and activation of p53‐dependent cell death in human endometrial cancer cells
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Krist Helen Antunes Fernandes, Marcella Tornquist Nassr, Bruna Pasqualotto Costa, Fernando Mendonça Diz, Leonardo Pfeiff Carlessi, Fernanda Bordignon Nunes, Gisele Branchini, and Jarbas Rodrigues de Oliveira more...
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Programmed cell death ,Fructose 1,6-bisphosphate ,Antineoplastic Agents ,Apoptosis ,Fructose ,010501 environmental sciences ,Toxicology ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,Downregulation and upregulation ,Cell Line, Tumor ,Fructosediphosphates ,medicine ,Humans ,Cell Proliferation ,030304 developmental biology ,0105 earth and related environmental sciences ,chemistry.chemical_classification ,0303 health sciences ,Reactive oxygen species ,Cell Death ,Chemistry ,Cell growth ,Endometrial cancer ,medicine.disease ,Endometrial Neoplasms ,Mitochondria ,Cell biology ,Cell culture ,Female ,Tumor Suppressor Protein p53 ,Reactive Oxygen Species - Abstract
Fructose-1,6-bisphosphate (F1,6BP), an intermediate of the glycolytic pathway, has been found to play a promising anticancer effect; nevertheless, the mechanisms involved remain poorly understood. The present study aimed to evaluate the effect and mechanisms of F1,6BP in a human endometrial cancer cell line (Ishikawa). F1,6BP showed an antiproliferative and non-cytotoxic effect on endometrial cancer cells. These effects are related to the increase in reactive oxygen species (ROS) levels and mitochondrial membrane potential (ΔΨm). These harmful stimuli trigger the upregulation of the expression of pro-apoptotic genes (p53 and Bax), leading to the reduction of cell proliferation through inducing programmed cell death by apoptosis. Furthermore, F1,6BP-treated cells had the formation of autophagosomes induced, as well as a decrease in their proliferative capacity after withdrawing the treatment. Our results demonstrate that F1,6BP acts as an anticancer agent through the generation of mitochondrial instability, loss of cell function, and p53-dependent cell death. Thus, F1,6BP proves to be a potential molecule for use in the treatment against endometrial cancer. more...
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- 2020
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16. Antidiabetic effects and mechanisms of action of γ-conglutin from lupin seeds
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Ranjeet P. Utikar, Stuart K. Johnson, Mrunmai Tapadia, Philip Newsholme, and Rodrigo Carlessi
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Lupin seeds ,Nutrition and Dietetics ,Glycogen ,Chemistry ,Myogenesis ,Nutrition. Foods and food supply ,Glucose transporter ,Proteolytic enzymes ,Medicine (miscellaneous) ,Incretin ,Skeletal muscle ,chemistry.chemical_compound ,DPP4 inhibitor ,medicine.anatomical_structure ,Biochemistry ,Antidiabetic ,Protein biosynthesis ,medicine ,TX341-641 ,γ-conglutin ,Insulin mimetic ,Food Science ,Hormone - Abstract
The glucose modulating properties of lupin have been attributed to its seed protein γ-conglutin. Here we explored the antidiabetic potential of γ-conglutin purified from lupin seeds in-vitro. To mimic the effects of an orally administered supplement, purified γ-conglutin was hydrolysed by gastrointestinal proteolytic enzymes and the resulting peptides evaluated for their antidiabetic effects in pancreatic β-cells and primary human skeletal muscle myotubes. γ-conglutin peptides did not promote insulin secretion in β-cells but elicited a potent insulin-mimetic action by activating insulin signalling pathways responsible for glycogen, protein synthesis, and glucose transport into myotubes. Additionally, the peptides potently suppressed the activity of DPP4 indicating their potential to increase the half-life of incretin hormones in circulation. These results substantiate the health benefits of consuming lupin seeds as part of a healthy diet and can drive the current market for lupins from primarily stockfeed, towards value-added lupin-based food products for human consumption. more...
- Published
- 2021
17. Analysis of cardiac involvement in patients recovered from Covid-19 without troponin elevation, evaluated by cardiovascular magnetic resonance
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Adrián Carlessi, Paula Di Rienzo, Ariel Ballina, Martin Maillo, Diego Vergara, Luciana Vegetti, Leonel Perello, Lucas Costa, Armando Borsini, Martin Gonzalez Vara, Lucia Rossi, Julian Leonardi, Cristian Froullet, Sebastian Wustten, Paula Gonzalo, Cristian Carlos Pantaley, and Florencia Gimenez more...
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medicine.medical_specialty ,medicine.diagnostic_test ,biology ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Elevation ,Magnetic resonance imaging ,Troponin ,Internal medicine ,cardiovascular system ,medicine ,Cardiology ,biology.protein ,In patient ,cardiovascular diseases ,business - Abstract
Background The disease caused by coronavirus (COVID-19) affects the cardiovascular system, whether by direct viral aggression or indirectly through systemic inflammation and multiple organ compromise. A widely used method to determine cardiac injury is troponin measurement. The aim of this study is to evaluate the prevalence of cardiac involvement (CINV) in a population recovered from COVID-19, referred to cardiac MRI (CMR), who did not present troponin elevation. Methods There were 156 patients that recovered from COVID-19 and who did not present troponin elevation referred to CMR. CINV was considered to be the presence of: late gadolinium enhancement (LGE), edema, myocarditis, pericarditis, left ventricular systolic dysfunction (LVSD) and/or depressed right ventricular systolic dysfunction (RVSD). Results Prevalence of CINV was 28.8%, being more frequent in men (p = 0.002), in patients who required hospitalization (p = 0.04) and in those who experienced non-mild cases of infection (p = 0.007). RVSD (17.9%) and LVSD (13.4%) were the most frequent findings. The rate of myocarditis was 0.6%. LGE manifested in 7.1% of patients and its presence was related to less left ventricular ejection fraction (LVEF) (p = 0.0001) and right ventricular ejection fraction (RVEF) (p = 0.04). Conclusion In patients who recovered from COVID-19, 28.8% of CINV was found. It was more frequent in men, in patients who required admission and in patients with cases of non-mild infection. The patients that presented LGE had less LVEF and RVSF. more...
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- 2021
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18. Oxidative stress pathways in pancreatic β-cells and insulin-sensitive cells and tissues: importance to cell metabolism, function, and dysfunction
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Kevin N. Keane, Philip Newsholme, Rodrigo Carlessi, and Vinicius Fernandes Cruzat
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0301 basic medicine ,Physiology ,medicine.medical_treatment ,030209 endocrinology & metabolism ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Nutrient ,Abundance (ecology) ,Insulin-Secreting Cells ,medicine ,Animals ,Humans ,Insulin ,Uncoupling protein ,chemistry.chemical_classification ,Reactive oxygen species ,Cell Biology ,Oxidative Stress ,030104 developmental biology ,Cell metabolism ,Diabetes Mellitus, Type 2 ,chemistry ,Biochemistry ,Insulin Resistance ,Energy Metabolism ,Reactive Oxygen Species ,Function (biology) ,Oxidative stress ,Signal Transduction - Abstract
It is now accepted that nutrient abundance in the blood, especially glucose, leads to the generation of reactive oxygen species (ROS), ultimately leading to increased oxidative stress in a variety of tissues. In the absence of an appropriate compensatory response from antioxidant mechanisms, the cell, or indeed the tissue, becomes overwhelmed by oxidative stress, leading to the activation of intracellular stress-associated pathways. Activation of the same or similar pathways also appears to play a role in mediating insulin resistance, impaired insulin secretion, and late diabetic complications. The ability of antioxidants to protect against the oxidative stress induced by hyperglycemia and elevated free fatty acid (FFA) levels in vitro suggests a causative role of oxidative stress in mediating the latter clinical conditions. In this review, we describe common biochemical processes associated with oxidative stress driven by hyperglycemia and/or elevated FFA and the resulting clinical outcomes: β-cell dysfunction and peripheral tissue insulin resistance. more...
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- 2019
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19. Sex Differences in the Brain-Blood Barrier in Rats Exposed to Early life Stress and the Treatment with Antidepressants and Psychobiotic
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Laura A. Borba, Camille M. Generoso, Maria Eduarda M. Botelho, Luana M. Manosso, Larissa R. Maciel, Anelise S. Carlessi, João Quevedo, Allan Collodel, Clara Vitória Bencke, Nicoly S. Martinello, Tatiana Barichello, Airam B. de Moura, Jaqueline S. Generoso, Bruna F. Lodetti, Gislaine Z. Réus, and Natalia M. Andrade more...
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nervous system ,business.industry ,Early life stress ,Physiology ,Medicine ,business - Abstract
Major depressive disorder is a debilitating mental disorder. Although the etiology is not fully understood, the impairment to the blood-brain barrier (BBB) integrity may be involved. Maternal deprivation was performed in the first 10 postnatal days for 3h/day. Male and female rats were divided into control and maternal deprivation. Maternal deprivation animals were subdivided and received treatment with saline, escitalopram, ketamine, or probiotic. The integrity of BBB was evaluated in the prefrontal cortex and hippocampus at postnatal days 11, 21, 41, and 61. Maternal deprivation caused BBB breakdown in the prefrontal cortex and hippocampus in female and male rats in all ages evaluated, except in the prefrontal cortex of females at postnatal day 41. In females, escitalopram, ketamine, and probiotic reversed BBB breakdown in all ages evaluated, except probiotic at postnatal day 21 (prefrontal cortex), and ketamine at postnatal days 21 and 41 (hippocampus). In males, escitalopram, ketamine, and probiotic reversed BBB breakdown in the prefrontal cortex in all ages evaluated, except escitalopram at postnatal days 41 and 61. In the hippocampus of males, BBB damage was reversed by escitalopram at postnatal day 21 and ketamine at postnatal day 41. Treatment with escitalopram, ketamine, or probiotics can prevent changes in the BBB integrity, depending on the age and sex of the animal. Clinically it is important to evaluate different treatments depending on age and sex. more...
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- 2021
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20. Indicadores de ansiedad, depresión, somatización y evitación experiencial en estudiantes universitarios del Perú en cuarentena por Covid-19
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Irma Egoavil Medina, Ceyda Fernandez Figueroa, Héctor Hugo Sánchez Carlessi, Edith Rocío Nuñez LLacuachaqui, Carlos Arenas Iparraguirre, Luis Alberto Yarlequé Chocas, Leda Javier Alva, Jorge Solis Quispe, María Matalinares Calvet, and Eduardo Gutiérrez Santayana more...
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Coronavirus disease 2019 (COVID-19) ,Anxiety depression ,education ,depresión ,lcsh:Medicine ,pandemics ,law.invention ,MeSH NLM) [pandemics. (Source] ,law ,Quarantine ,Pandemic ,Experiential avoidance ,medicine ,experiental avoidance ,Anexiety ,anexiety ,pandemia. (Fuente DeCS) ,Depression (differential diagnoses) ,evitación experiencial ,lcsh:R5-920 ,lcsh:R ,cuarentena ,quarantine ,COVID-19 ,General Medicine ,somatoform disorders ,medicine.disease ,covid-19 ,depression ,trastorno somatomorfo ,Psychology ,lcsh:Medicine (General) ,Somatization ,Clinical psychology - Abstract
RESUMEN Introducción: La cuarentena por COVID-19 ha afectado de gran manera a los estudiantes universitarios del Perú, generando una serie de efectos físicos, psicológicos y conductuales. Objetivo: Determinar los factores asociados a ansiedad, depresión, somatización y evitación experiencial en estudiantes universitarios del Perú en cuarentena por COVID-19. Métodos: Se realizó un estudio observacional transversal. La muestra estuvo constituida por 1264 estudiantes universitarios de diversos departamentos del Perú, se tomó como variables dependientes a la ansiedad, depresión, somatización y evitación experiencial, las cuales se evaluaron con el cuestionario de “El Inventario de comportamiento psicosocial desajustado, ante la presencia del COVID-19 en la población peruana” y el AAQ II, para el análisis estadístico se empleó el chi cuadrado. Resultados: Más de la mitad de los estudiantes universitarios del Perú, presenta entre 3 y 6 de los 6 indicadores de ansiedad, y este mismo número de indicadores de depresión lo presenta el 45% de la muestra. El 30 % de la muestra presenta entre 3 y 6 indicadores de somatización y el 40,3% de la muestra se ubica de la mitad hacia arriba en la escala de evitación experiencial. Conclusiones: Existen diferencias en los niveles de ansiedad, somatización y evitación experiencial entre varones y mujeres, asimismo se encontró que los estudiantes de mayor edad presentaban niveles más bajos de ansiedad, depresión y evitación experiencial, pero no en somatización. ABSTRACT Introduction: The COVID-19 quarantine has greatly affected university students in Peru, generating a series of physical, psychological and behavioral effects. Objective: To determine the factors associated with anxiety, depression, somatization and experiential avoidance in peruvian university students quarantined by COVID-19. Methods: A cross-sectional observational study was carried out. The sample was made up of 1264 university students from various departments of Peru, anxiety, depression, somatization and experiential avoidance were taken as dependent variables, which were evaluated with the questionnaire "The Inventory of unadjusted psychosocial behavior, in the presence of COVID-19 in the Peruvian population ”and the AAQ II, for the statistical analysis the chi square was used. Results: More than half of the university students in Peru present between 3 and 6 of the 6 anxiety indicators, and this same number of depression indicators is presented by 45% of the sample. 30% of the sample has between 3 and 6 indicators of somatization and 40.3% of the sample is located in the middle upwards on the experiential avoidance scale. Conclusions: There are differences in the levels of anxiety, somatization and experiential avoidance between men and women, it was also found that older students had lower levels of anxiety, depression and experiential avoidance, but not in somatization. more...
- Published
- 2021
21. Maraviroc prevents hcc development by suppressing macrophages and the liver progenitor cell response in a murine chronic liver disease model
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Joaquín Fernández-Irigoyen, Sarah B. McSpadden, Luke A. Diepeveen, Janina E.E. Tirnitz-Parker, Alfredo Martínez, Bernard A. Callus, Weihao Zhao, Enrique Santamaría, Caryn L. Elsegood, Hyerin Park, Ken H. Woo, Andy Chevigné, Adam M. Passman, Laura Ochoa-Callejero, Roslyn London, George C.T. Yeoh, José Ramón Blanco, Martyna Szpakowska, Robyn P. Strauss, Laura Medina-Ruiz, Megan Finch-Edmondson, Rodrigo Carlessi, Murray V. Baker, Neil Andrewartha, Universidad Pública de Navarra. Departamento de Ciencias de la Salud, and Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila more...
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Cancer Research ,Hepatocellular carcinoma ,CCL5 chemokine ,CCR5 receptor antagonist ,Biology ,Chronic liver disease ,Article ,Maraviroc ,Liver progenitor cells ,chemistry.chemical_compound ,medicine ,Macrophage ,Progenitor cell ,Receptor ,STAT3 ,Protein kinase B ,RC254-282 ,Macrophages ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,musculoskeletal system ,Mara-viroc ,body regions ,Oncology ,chemistry ,biology.protein ,Cancer research ,human activities - Abstract
Maraviroc (MVC), a CCR5 antagonist, reduces liver fibrosis, injury and tumour burden in mice fed a hepatocarcinogenic diet, suggesting it has potential as a cancer therapeutic. We investigated the effect of MVC on liver progenitor cells (LPCs) and macrophages as both have a role in hepatocarcinogenesis. Mice were fed the hepatocarcinogenic choline-deficient, ethionine-supplemented diet (CDE) ± MVC, and immunohistochemistry, RNA and protein expression were used to determine LPC and macrophage abundance, migration and related molecular mechanisms. MVC reduced LPC numbers in CDE mice by 54%, with a smaller reduction seen in macrophages. Transcript and protein abundance of LPC-associated markers correlated with this reduction. The CDE diet activated phosphorylation of AKT and STAT3 and was inhibited by MVC. LPCs did not express Ccr5 in our model, in contrast, macrophages expressed high levels of this receptor, suggesting the effect of MVC is mediated by targeting macrophages. MVC reduced CD45+ cells and macrophage migration in liver and blocked the CDE-induced transition of liver macrophages from an M1- to M2-tumour-associated macrophage (TAM) phenotype. These findings suggest MVC has potential as a re-purposed therapeutic agent for treating chronic liver diseases where M2-TAM and LPC numbers are increased, and the incidence of HCC is enhanced. more...
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- 2021
22. Prevalencia de disfunción diastólica de acuerdo con las guías diagnósticas de 2009 y 2016. Relación con la valoración hemodinámica no invasiva
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Evangelina Garello, Adrián Carlessi, Leonel Perello, and Carlos Valli
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Gynecology ,Univariate analysis ,medicine.medical_specialty ,business.industry ,Non invasive ,Diastole ,Medicine ,Hemodynamics ,Guideline ,Normal values ,Cardiology and Cardiovascular Medicine ,business ,Independent predictor - Abstract
Objetivos Evaluar la prevalencia de DD de acuerdo con los criterios de las guias del 2009 y 2016, y su relacion con la distensibilidad arterial sistemica (DAS) y la resistencia vascular periferica (RVP). Material y metodos Se analizo a 306 pacientes ≥ 40 anos de edad, con fraccion de expulsion ≥ 50%. Se calcularon en todos DAS y RVP. Resultados La prevalencia de DD fue de 32.7% y 22.9% segun las guias de 2009 y 2016, respectivamente (p = 1,400 mmHg.min.l-1 segun ambas guias. En el analisis multivariado, la DD, de acuerdo con las guias del 2009, persistio como predictor independiente de RVP > 1,400 mmHg.min.l-1. Conclusion Las guias del 2016 reducen la prevalencia de DD. Esta, tanto en las guias del 2009 como en las del 2106, fue predictor univariado de DAS 1,400 mmHg.min.l-1. La DD, de acuerdo con las guias de 2009, resulto predictora independiente de RVP > 1,400 mmHg.min.l-1. Objectives To assess the prevalence of developmental disabilities (DD) according to the criteria of the 2009 and 2016 guidelines, and its association with systemic arterial compliance (DAS) and peripheral vascular resistance (RVP). Material and methods 306 patients aged ≥ 40 years, with ejection fraction ≥ 50% were analyzed. It was estimated in all DAS and RVP. Results The prevalence of DD was 32.7% and 22.9% according to the 2009 and 2016 guidelines, respectively (p ≤ 0.0001). Patients with DD according to the 2009 guideline had a lower average of DAS than those with normal function (p = 0.0001). Similar with the 2016 guide (p = 0.0007). The presence of DD according to the 2009 and 2016 guideline showed higher RVP values than normal values (p = 0.005 and p = 0.018, respectively). The DD according to both guidelines was a predictor, in the univariate analysis, of DAS 1400 mmHg.min.l−1. The DD according to the 2009 guideline persisted as an independent predictor, in the multivariate analysis, of RVP > 1400 mmHg.min.l−1. Conclusion The 2016 guide decreases the prevalence of DD. The DD, both from the 2009 and 2106 guidelines, were univariate predictors of DAS 1400 mmHg.min.l−1. The DD according to the 2009 guide, was an independent predictor of RVP > 1400 mmHg.min.l−1. more...
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- 2020
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23. Previous liver regeneration induces fibro-protective mechanisms during thioacetamide-induced chronic liver injury
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Francis D. Gratte, Rodrigo Carlessi, Sara Pasic, Tatiana Kisseleva, N. Dianah B. Abu Bakar, Janina E.E. Tirnitz-Parker, John K. Olynyk, David A. Brenner, Grant A. Ramm, Jully Gogoi-Tiwari, and Xiao Liu more...
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0301 basic medicine ,Liver Cirrhosis ,Male ,Thioacetamide ,Chronic liver disease ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Fibrosis ,Hepatic Stellate Cells ,Medicine ,Animals ,Progenitor cell ,Sirius Red ,Cells, Cultured ,Liver injury ,business.industry ,Stem Cells ,Cell Biology ,medicine.disease ,Liver regeneration ,Coculture Techniques ,Liver Regeneration ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Liver ,030220 oncology & carcinogenesis ,Cancer research ,Hepatic stellate cell ,Chemical and Drug Induced Liver Injury ,Wound healing ,business - Abstract
Chronic liver injury is characterised by continuous or repeated epithelial cell loss and inflammation. Hepatic wound healing involves matrix deposition through activated hepatic stellate cells (HSCs) and the expansion of closely associated Ductular Reactions and liver progenitor cells (LPCs), which are thought to give rise to new epithelial cells. In this study, we used the murine thioacetamide (TAA) model to reliably mimic these injury and regeneration dynamics and assess the impact of a recovery phase on subsequent liver injury and fibrosis. Age-matched naive or 6-week TAA-treated/4-week recovered mice (C57BL/6 J, n = 5-9) were administered TAA for six weeks (C57BL/6 J, n = 5-9). Sera and liver tissues were harvested at key time points to assess liver injury biochemically, by real-time PCR for fibrotic mediators, Sirius Red staining and hydroxyproline assessment for collagen deposition as well as immunofluorescence for inflammatory, HSC and LPC markers. In addition, primary HSCs and the HSC cell line LX-2 were co-cultured with the well-characterised LPC line BMOL and analysed for potential changes in expression of fibrogenic mediators. Our data demonstrate that recovery from a previous TAA insult, with LPCs still present on day 0 of the second treatment, led to a reduced TAA-induced disease progression with less severe fibrosis than in naive TAA-treated animals. Importantly, primary activated HSCs significantly reduced pro-fibrogenic gene expression when co-cultured with LPCs. Taken together, previous TAA injury established a fibro-protective molecular and cellular microenvironment. Our proof-of principle HSC/LPC co-culture data demonstrate that LPCs communicate with HSCs to regulate fibrogenesis, highlighting a key role for LPCs as regulatory cells during chronic liver disease. more...
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- 2020
24. P1086Prevalence and predictors of left atrial thrombi in patients scheduled for electrical cardioversion of nonvalvular atrial fibrillation
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C Rosller, C Pantaley, L Perello, L Rossi, A Abud, A Carlessi, M Santillan, and E Garello
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medicine.medical_specialty ,Ejection fraction ,business.industry ,Renal function ,Atrial fibrillation ,medicine.disease ,Left atrial ,Physiology (medical) ,Heart failure ,Internal medicine ,CHA2DS2–VASc score ,medicine ,Cardiology ,Thrombus ,Cardiology and Cardiovascular Medicine ,business ,Atrial flutter - Abstract
Background Transesophageal echocardiography (TEE) showed the presence of thrombi in 12 to 26% of patients with atrial fibrillation (AF). Purpose To assess clinical and echocardiographic variables associated with thrombi in the left atrium (LA) prior to electrical cardioversion in patients with nonvalvular atrial fibrillation (AF). Methods Cross-sectional study including 188 patients. Clinical and echocardiographic variables were analyzed. Qualitative variables are expressed in percentages and quantitative variables in mean and standard deviations. Qualitative variables were analyzed by the Chi square method. A value of p Results Mean age was 60.7 ± 12.3 and 75.5% males. The mean CHA2DS2-VASc and HAS-BLED scores were 2.43 ± 1.6 and 1.06 ± 1. The percentage of paroxysmal AF was 49.7%, nonparoxysmal 23.2% and atrial flutter 27%. Mean ejection fraction (EF) was 52.2 ± 13%. The prevalence of thrombus was 12.3%. Female gender (p = 0.0275), heart failure (p = 0.0006), CHA2DS2-VASc score ≥2 (p = 0.0015), EF History of previous anticoagulation for over thirty days or creatinine clearance Conclusion Female gender, heart failure, EF more...
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- 2020
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25. Argentine Registry of Transesophageal Echocardiography
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Diego Funes, Rodrigo Bagnati, Adrián Carlessi, Federico Matias Cintora, Javier Sánchez, Javier Fabián Ventrici, Claudio Miguel Marigo, Silvia Makhoul, Sergio Baratta, and Natalio Gastaldello
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business.industry ,Medicine ,business - Published
- 2018
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26. Mild hypoxia enhances proliferation and multipotency of human neural stem cells.
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Guido Santilli, Giuseppe Lamorte, Luigi Carlessi, Daniela Ferrari, Laura Rota Nodari, Elena Binda, Domenico Delia, Angelo L Vescovi, and Lidia De Filippis
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Medicine ,Science - Abstract
Neural stem cells (NSCs) represent an optimal tool for studies and therapy of neurodegenerative diseases. We recently established a v-myc immortalized human NSC (IhNSC) line, which retains stem properties comparable to parental cells. Oxygen concentration is one of the most crucial environmental conditions for cell proliferation and differentiation both in vitro and in vivo. In the central nervous system, physiological concentrations of oxygen range from 0.55 to 8% oxygen. In particular, in the in the subventricular zone niche area, it's estimated to be 2.5 to 3%.We investigated in vitro the effects of 1, 2.5, 5, and 20% oxygen concentrations on IhNSCs both during proliferation and differentiation. The highest proliferation rate, evaluated through neurosphere formation assay, was obtained at 2.5 and 5% oxygen, while 1% oxygen was most noxious for cell survival. The differentiation assays showed that the percentages of beta-tubIII+ or MAP2+ neuronal cells and of GalC+ oligodendrocytes were significantly higher at 2.5% compared with 1, 5, or 20% oxygen at 17 days in vitro. Mild hypoxia (2.5 to 5% oxygen) promoted differentiation into neuro-oligodendroglial progenitors as revealed by the higher percentage of MAP2+/Ki67+ and GalC+/Ki67+ residual proliferating progenitors, and enhanced the yield of GABAergic and slightly of glutamatergic neurons compared to 1% and 20% oxygen where a significant percentage of GFAP+/nestin+ cells were still present at 17 days of differentiation.These findings raise the possibility that reduced oxygen levels occurring in neuronal disorders like cerebral ischemia transiently lead to NSC remaining in a state of quiescence. Conversely, mild hypoxia favors NSC proliferation and neuronal and oligodendroglial differentiation, thus providing an important advance and a useful tool for NSC-mediated therapy of ischemic stroke and neurodegenerative diseases like Parkinson's disease, multiple sclerosis, and Alzheimer's disease. more...
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- 2010
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27. Insulin and IGF-1 receptor autocrine loops are not required for Exendin-4 induced changes to pancreatic β-cell bioenergetic parameters and metabolism in BRIN-BD11 cells
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Jordan Rowlands, Philip Newsholme, Rodrigo Carlessi, and Vinicius Fernandes Cruzat
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0301 basic medicine ,endocrine system ,Small interfering RNA ,Physiology ,medicine.medical_treatment ,Stimulation ,Biochemistry ,Glucagon-Like Peptide-1 Receptor ,Receptor, IGF Type 1 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Endocrinology ,Insulin-Secreting Cells ,Diabetes Mellitus ,medicine ,Animals ,Humans ,Insulin ,Receptor ,Autocrine signalling ,PI3K/AKT/mTOR pathway ,biology ,Chemistry ,TOR Serine-Threonine Kinases ,Hypoxia-Inducible Factor 1, alpha Subunit ,Receptor, Insulin ,Rats ,Cell biology ,Autocrine Communication ,Insulin receptor ,Glucose ,030104 developmental biology ,biology.protein ,Exenatide ,Energy Metabolism ,Flux (metabolism) - Abstract
Pharmacological long lasting Glucagon-like peptide-1 (GLP-1) analogues, such as Exendin-4, have become widely used diabetes therapies. Chronic GLP-1R stimulation has been linked to β-cell protection and these pro-survival actions of GLP-1 are dependent on the activation of the mammalian target of rapamycin (mTOR) leading to accumulation of Hypoxia inducible factor 1 alpha (HIF-1α). Recent studies from our lab indicate that prolonged GLP-1R stimulation promotes metabolic reprograming of β-cells towards a highly glycolytic phenotype and activation of the mTOR/HIF-1α pathway was required for this action. We hypothesised that GLP-1 induced metabolic changes depend on the activation of mTOR and HIF-1α, in a cascade that occurs after triggering of a potential Insulin-like growth factor 1 receptor (IGF-1R) or the Insulin receptor (IR) autocrine loops. Loss of function of these receptors, through the use of small interfering RNA, or neutralizing antibodies directed towards their products, was undertaken in conjunction with functional assays. Neither of these strategies mitigated the effect of GLP-1 on glucose uptake, protein expression or bioenergetic flux. Our data indicates that activation of IGF-1R and/or the IR autocrine loops resulting in β-cell protection and function, involve mechanisms independent to the enhanced metabolic effects resulting from sustained GLP-1R activation. more...
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- 2018
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28. Methoxyeugenol deactivates hepatic stellate cells and attenuates liver fibrosis and inflammation through a PPAR-ɣ and NF-kB mechanism
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Eliane Romanato Santarém, Vitor Giancarlo Schneider Levorse, Matheus Scherer Bastos, Leonardo Pfeiff Carlessi, Martí Ortega-Ribera, Jordi Gracia-Sancho, Carolina Luft, Eduardo Cassel, Gabriela Viegas Haute, Bruno de Souza Basso, Géssica Luana Antunes, Jarbas Rodrigues de Oliveira, and Márcio Vinícius Fagundes Donadio more...
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Liver Cirrhosis ,Male ,Cirrhosis ,Inflammation ,Chronic liver disease ,Cell Line ,Mice ,Liver disease ,Fibrosis ,Eugenol ,Drug Discovery ,Hepatic Stellate Cells ,medicine ,Animals ,Humans ,Pharmacology ,Carbon Tetrachloride Poisoning ,business.industry ,NF-kappa B ,medicine.disease ,PPAR gamma ,Oxidative Stress ,medicine.anatomical_structure ,Gene Expression Regulation ,Hepatocyte ,Cancer research ,Hepatic stellate cell ,Liver function ,medicine.symptom ,business ,Food Analysis - Abstract
Ethnopharmacological relevance Studies have shown interest in nutraceuticals for the prevention of liver diseases. Methoxyeugenol, is a molecule found in foods, such as nutmeg (Myristica fragrans Houtt.) and Brazilian red propolis. These two sources of methoxyeugenol, propolis and nutmeg, are used in folk medicine for the treatment of hepatic and gastrointestinal disorders, although little is known about their effects on the prevention of liver fibrosis. Natural PPAR (Peroxisome proliferator-activated receptor) agonists would represent unique molecules for therapy, considering the lack of therapeutics to treat liver fibrosis in chronic liver disease. Thus, investigation on new alternatives are necessary, including the search for natural compounds from renewable and sustainable sources. Liver fibrosis is a pathological process characterized by an exacerbated cicatricial response in the hepatic tissue, which compromises liver function. Therefore, inhibition of HSC (hepatic stellate cell) activation and hepatocyte damage are considered major strategies for the development of new anti-fibrotic treatments. Aim of the study This study aimed to investigate the effects of methoxyeugenol treatment on HSC phenotype modulation in human and murine cells, hepatocyte damage prevention, and protective effects in vivo, in order to evaluate its therapeutic potential for liver fibrosis prevention. Methods We investigated the effects of methoxyeugenol in (i) in vitro models using human and murine HSC and hepatocytes, and (ii) in vivo models of CCl4 (carbon tetrachloride) -induced liver fibrosis in mice. Results We herein report that methoxyeugenol decreases HSC activation through the activation of PPAR-ɣ, ultimately inducing a quiescent phenotype highlighted by an increase in lipid droplets, loss of contraction ability, and a decrease in the proliferative rate and mRNA expression of fibroblast markers. In addition, methoxyeugenol prevented hepatocytes from oxidative stress damage. Moreover, in mice submitted to chronic liver disease through CCl4 administration, methoxyeugenol decreased the inflammatory profile, liver fibrosis, mRNA expression of fibrotic genes, and the inflammatory pathway signaled by NF-kB (Nuclear factor kappa B). Conclusion We propose methoxyeugenol as a novel and potential therapeutic approach to treat chronic liver disease and fibrosis. more...
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- 2021
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29. Therapeutic effect of uridine phosphorylase 1 (UPP1) inhibitor on liver fibrosis in vitro and in vivo
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Bruno de Souza Basso, Maria Claudia Rosa Garcia, Luiz Augusto Basso, Gabriela Viegas Haute, Márcio Vinícius Fagundes Donadio, Géssica Luana Antunes, Elisa Feller Gonçalves da Silva, Marcella Tornquist Nassr, Carine Raquel Richter Schmitz, Pablo Machado, Vitor Giancarlo Schneider Levorse, Leonardo Pfeiff Carlessi, Carolina Luft, Matheus Scherer Bastos, Jarbas Rodrigues de Oliveira, Eliane Romanato Santarém, Bruna Pasqualotto Costa, Florencia María Barbé-Tuana, Krist Helen Antunes Fernandes, and Camille Kirinus Reghelin more...
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0301 basic medicine ,Liver Cirrhosis ,Male ,Pharmacology ,Lung injury ,Bleomycin ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Random Allocation ,0302 clinical medicine ,In vivo ,Fibrosis ,medicine ,Hepatic Stellate Cells ,Animals ,Enzyme Inhibitors ,Carbon Tetrachloride ,Uridine phosphorylase 1 ,Cell Line, Transformed ,Mice, Inbred BALB C ,Uridine Phosphorylase ,Dose-Response Relationship, Drug ,medicine.disease ,In vitro ,Uridine ,030104 developmental biology ,chemistry ,Hepatic stellate cell ,030217 neurology & neurosurgery - Abstract
Potassium 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-olate (CPBMF65) is a potent inhibitor of the uridine phosphorylase 1 (UPP1) enzyme. Its non-ionized analog has already demonstrated biological properties by reducing adverse effects caused by the chemotherapeutic 5-fluorouracil (5-FU). In addition, it has been demonstrated that uridine inhibits inflammation and fibrosis in bleomycin lung injury, decreasing collagen production. The purpose of this study was to investigate the in vitro and in vivo effects of CPBMF65 on activated hepatic stellate cells (HSC) and on carbon tetrachloride-induced liver fibrosis in mice. After incubation with CPBMF65, decreased cell proliferation and phenotype reversion were observed in vitro. In addition, CPBMF65 promoted a protective effect on tetrachloride-induced liver fibrosis in mice, demonstrated by its antifibrotic and anti-inflammatory actions. The results of the present study indicate that the UPP1 inhibitor (CPBMF65) may have potential as a novel therapeutic agent for the treatment of liver fibrosis. more...
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- 2019
30. Mouse Models of Hepatocellular Carcinoma
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Julia Köhn-Gaone, John K. Olynyk, Janina E.E. Tirnitz-Parker, and Rodrigo Carlessi
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Transcriptome ,Cirrhosis ,business.industry ,Hepatocellular carcinoma ,medicine ,Etiology ,Effective treatment ,Cancer ,medicine.disease ,Malignancy ,business ,Bioinformatics ,Cause of death - Abstract
Hepatocellular carcinoma (HCC) represents a major and steadily increasing global health challenge as the most common primary liver malignancy and leading cause of death in cirrhotic patients. The only hope for curative treatment or significant increase in life expectancy is early detection. Once patients have progressed towards end-stage HCC, effective treatment options are extremely limited on the background of a very high degree of heterogeneity in clinical presentation and outcome. Experimental chronic liver injury and cancer have been used extensively to mimic the human disease. In particular, mouse studies have advanced the field due to the ability to easily manipulate the mouse genome and transcriptome for mechanistic evaluations. In addition, they offer the opportunity to screen new therapeutic strategies cost effectively and in quick high-throughput, large-scale formats. The most commonly used mouse models in HCC research can be categorized as chemotoxic, diet-induced, and genetically engineered models. It is important to note that no particular model mimics all features of a given HCC etiology or histological subtype, and each model poses advantages and disadvantages that need to be carefully considered. more...
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- 2019
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31. Gut microbiota-brain axis in depression: The role of neuroinflammation
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Laura A. Borba, João Quevedo, Gislaine Z. Réus, Alexandra I. Zugno, and Anelise S. Carlessi
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Central nervous system ,Inflammation ,Gut flora ,Systemic inflammation ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Humans ,Neuroinflammation ,030304 developmental biology ,0303 health sciences ,Depressive Disorder, Major ,Microglia ,biology ,business.industry ,Depression ,General Neuroscience ,Probiotics ,Brain ,medicine.disease ,biology.organism_classification ,Gastrointestinal Microbiome ,medicine.anatomical_structure ,Major depressive disorder ,Antidepressant ,medicine.symptom ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Major depressive disorder (MDD) is a psychiatric condition that affects a large number of people in the world, and the treatment existents do not work for all individuals affected. Thus, it is believed that other systems or pathways which regulate brain networks involved in mood regulation and cognition are associated with MDD pathogenesis. Studies in humans and animal models have been shown that in MDD there are increased levels of inflammatory mediators, including cytokines and chemokines in both periphery and central nervous system (CNS). In addition, microglial activation appears to be a key event that triggers changes in signaling cascades and gene expression that would be determinant for the onset of depressive symptoms. Recent researches also point out that changes in the gut microbiota would lead to a systemic inflammation that in different ways would reach the CNS modulating inflammatory pathways and especially the microglia, which could influence responses to treatments. Moreover, pre- and probiotics have shown antidepressant responses and anti-inflammatory effects. This review will focus on studies that show the relationship of inflammation with the gut microbiota-brain axis and its relation with MDD. more...
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- 2019
32. Mechanisms of vitamin D action in skeletal muscle
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Rodrigo Carlessi, Philip Newsholme, Karina Romeu Montenegro, and Vinicius Fernandes Cruzat
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0301 basic medicine ,Muscle Fibers, Skeletal ,Medicine (miscellaneous) ,030209 endocrinology & metabolism ,Muscle Development ,Calcitriol receptor ,03 medical and health sciences ,0302 clinical medicine ,Calcitriol ,medicine ,Vitamin D and neurology ,Animals ,Humans ,Vitamin D ,Protein kinase A ,Muscle, Skeletal ,Protein kinase B ,Cell Proliferation ,Regulation of gene expression ,Nutrition and Dietetics ,Myogenesis ,Chemistry ,Skeletal muscle ,Cell Differentiation ,medicine.disease ,Cell biology ,Mitochondria, Muscle ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Sarcopenia ,Receptors, Calcitriol ,Mitogen-Activated Protein Kinases ,Signal Transduction - Abstract
Vitamin D receptor expression and associated function have been reported in various muscle models, including C2C12, L6 cell lines and primary human skeletal muscle cells. It is believed that 1,25-hydroxyvitamin D3(1,25(OH)2D3), the active form of vitamin D, has a direct regulatory role in skeletal muscle function, where it participates in myogenesis, cell proliferation, differentiation, regulation of protein synthesis and mitochondrial metabolism through activation of various cellular signalling cascades, including the mitogen-activated protein kinase pathway(s). It has also been suggested that 1,25(OH)2D3and its associated receptor have genomic targets, resulting in regulation of gene expression, as well as non-genomic functions that can alter cellular behaviour through binding and modification of targets not directly associated with transcriptional regulation. The molecular mechanisms of vitamin D signalling, however, have not been fully clarified. Vitamin D inadequacy or deficiency is associated with muscle fibre atrophy, increased risk of chronic musculoskeletal pain, sarcopenia and associated falls, and may also decrease RMR. The main purpose of the present review is to describe the molecular role of vitamin D in skeletal muscle tissue function and metabolism, specifically in relation to proliferation, differentiation and protein synthesis processes. In addition, the present review also includes discussion of possible genomic and non-genomic pathways of vitamin D action. more...
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- 2019
33. Relationship of Oxidative Stress as a Link between Diabetes Mellitus and Major Depressive Disorder
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João Quevedo, Ritele H. Silva, Anelise S. Carlessi, Luciane Bisognin Ceretta, and Gislaine Z. Réus
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Male ,Aging ,medicine.medical_specialty ,Population ,Inflammation ,Review Article ,medicine.disease_cause ,Biochemistry ,Diabetes Complications ,Insulin resistance ,Diabetes mellitus ,Internal medicine ,Diabetes Mellitus ,Medicine ,Humans ,Risk factor ,lcsh:QH573-671 ,education ,Depression (differential diagnoses) ,education.field_of_study ,Depressive Disorder, Major ,business.industry ,lcsh:Cytology ,Cell Biology ,General Medicine ,medicine.disease ,Oxidative Stress ,Endocrinology ,Major depressive disorder ,Female ,medicine.symptom ,business ,Oxidative stress - Abstract
Both conditions, major depressive disorder (MDD) and diabetes mellitus (DM) are chronic and disabling diseases that affect a very significant percentage of the world’s population. Studies have been shown that patients with DM are more susceptible to develop depression, when compared to the general population. The opposite also happens; MDD could be a risk factor for DM development. Some mechanisms have been proposed to explain the pathophysiological mechanisms involved with these conditions, such as excess of glucocorticoids, hyperglycemia, insulin resistance, and inflammation. These processes can lead to an increase in damage to biomolecules and a decrease in antioxidant defense capacity, leading to oxidative stress. more...
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- 2019
34. Molecular mechanisms of ROS production and oxidative stress in diabetes
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Rodrigo Carlessi, Kevin N. Keane, Philip Newsholme, Vinicius Fernandes Cruzat, and Paulo Ivo Homem de Bittencourt
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0301 basic medicine ,medicine.medical_specialty ,Protein Carbonylation ,medicine.medical_treatment ,Inflammation ,Oxidative phosphorylation ,Biology ,medicine.disease_cause ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Insulin-Secreting Cells ,Internal medicine ,Diabetes mellitus ,Diabetes Mellitus ,medicine ,Animals ,Humans ,Insulin ,Molecular Biology ,chemistry.chemical_classification ,Reactive oxygen species ,Cell Biology ,medicine.disease ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,chemistry ,medicine.symptom ,Reactive Oxygen Species ,030217 neurology & neurosurgery ,Oxidative stress - Abstract
Oxidative stress and chronic inflammation are known to be associated with the development of metabolic diseases, including diabetes. Oxidative stress, an imbalance between oxidative and antioxidative systems of cells and tissues, is a result of over production of oxidative-free radicals and associated reactive oxygen species (ROS). One outcome of excessive levels of ROS is the modification of the structure and function of cellular proteins and lipids, leading to cellular dysfunction including impaired energy metabolism, altered cell signalling and cell cycle control, impaired cell transport mechanisms and overall dysfunctional biological activity, immune activation and inflammation. Nutritional stress, such as that caused by excess high-fat and/or carbohydrate diets, promotes oxidative stress as evident by increased lipid peroxidation products, protein carbonylation and decreased antioxidant status. In obesity, chronic oxidative stress and associated inflammation are the underlying factors that lead to the development of pathologies such as insulin resistance, dysregulated pathways of metabolism, diabetes and cardiovascular disease through impaired signalling and metabolism resulting in dysfunction to insulin secretion, insulin action and immune responses. However, exercise may counter excessive levels of oxidative stress and thus improve metabolic and inflammatory outcomes. In the present article, we review the cellular and molecular origins and significance of ROS production, the molecular targets and responses describing how oxidative stress affects cell function including mechanisms of insulin secretion and action, from the point of view of possible application of novel diabetic therapies based on redox regulation more...
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- 2016
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35. Pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through NADPH oxidase-dependent reactive oxygen species production
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Crispin R. Dass, Philip Newsholme, Arun Dharmarajan, Revathy Carnagarin, and Rodrigo Carlessi
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0301 basic medicine ,medicine.medical_specialty ,Biology ,medicine.disease_cause ,Biochemistry ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,PEDF ,Internal medicine ,medicine ,Animals ,Humans ,Glycolysis ,Nerve Growth Factors ,Eye Proteins ,Muscle, Skeletal ,Serpins ,chemistry.chemical_classification ,Reactive oxygen species ,NADPH oxidase ,NADPH Oxidases ,Skeletal muscle ,Cell Biology ,Oxidative Stress ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,chemistry ,biology.protein ,Reactive Oxygen Species ,Flux (metabolism) ,Nicotinamide adenine dinucleotide phosphate ,Oxidative stress - Abstract
Pigment epithelium-derived factor is a multifunctional serpin implicated in insulin resistance in metabolic disorders. Recent evidence suggests that exposure of peripheral tissues such as skeletal muscle to PEDF has profound metabolic consequences with predisposition towards chronic conditions such as obesity, type 2 diabetes, metabolic syndrome and polycystic ovarian syndrome. Chronic inflammation shifts muscle metabolism towards increased glycolysis and decreased oxidative metabolism. In the present study, we demonstrate a novel effect of PEDF on cellular metabolism in mouse cell line (C2C12) and human primary skeletal muscle cells. PEDF addition to skeletal muscle cells induced enhanced phospholipase A2 activity. This was accompanied with increased production of reactive oxygen species in a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent manner that triggered a shift towards a more glycolytic phenotype. Extracellular flux analysis and glucose consumption assays demonstrated that PEDF treatment resulted in enhanced glycolysis but did not change mitochondrial respiration. Our results demonstrate that skeletal muscle cells express a PEDF-inducible oxidant generating system that enhances glycolysis but is sensitive to antioxidants and NADPH oxidase inhibition. more...
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- 2016
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36. Pigment epithelium-derived factor (PEDF) regulates metabolism and insulin secretion from a clonal rat pancreatic beta cell line BRIN-BD11 and mouse islets
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Revathy Carnagarin, Rodrigo Carlessi, Nikita L. Walz, Fang-Xu Jiang, Philip Newsholme, Younan Chen, Kevin N. Keane, Vinicius Fernandes Cruzat, Abraham Neelankal John, and Crispin R. Dass
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0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Palmitic Acid ,Gene Expression ,Mice, Transgenic ,030209 endocrinology & metabolism ,Carbohydrate metabolism ,Biology ,Biochemistry ,Cell Line ,Mice ,03 medical and health sciences ,Adenosine Triphosphate ,0302 clinical medicine ,Endocrinology ,Insulin resistance ,PEDF ,Insulin-Secreting Cells ,Internal medicine ,Insulin Secretion ,medicine ,Animals ,Insulin ,Glycolysis ,Nerve Growth Factors ,Eye Proteins ,Molecular Biology ,Serpins ,Lipid Metabolism ,medicine.disease ,IRS2 ,Rats ,Glucose ,030104 developmental biology ,Adipose triglyceride lipase ,Beta cell ,Energy Metabolism - Abstract
Pigment epithelium-derived factor (PEDF) is a multifunctional glycoprotein, associated with lipid catabolism and insulin resistance. In the present study, PEDF increased chronic and acute insulin secretion in a clonal rat β-cell line BRIN-BD11, without alteration of glucose consumption. PEDF also stimulated insulin secretion from primary mouse islets. Seahorse flux analysis demonstrated that PEDF did not change mitochondrial respiration and glycolytic function. The cytosolic presence of the putative PEDF receptor - adipose triglyceride lipase (ATGL) - was identified, and ATGL associated stimulation of glycerol release was robustly enhanced by PEDF, while intracellular ATP levels increased. Addition of palmitate or ex vivo stimulation with inflammatory mediators induced β-cell dysfunction, effects not altered by the addition of PEDF. In conclusion, PEDF increased insulin secretion in BRIN-BD11 and islet cells, but had no impact on glucose metabolism. Thus elevated lipolysis and enhanced fatty acid availability may impact insulin secretion following PEDF receptor (ATGL) stimulation. more...
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- 2016
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37. ATM-deficient neural precursors develop senescence phenotype with disturbances in autophagy
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Jacek Lenart, Ewa Sikora, Leonora Buzanska, Domenico Delia, Justyna Augustyniak, Luigi Carlessi, and Piotr Sunderland
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0301 basic medicine ,Senescence ,Aging ,DNA damage ,Induced Pluripotent Stem Cells ,Ataxia Telangiectasia Mutated Proteins ,Biology ,medicine.disease_cause ,Ataxia Telangiectasia ,03 medical and health sciences ,0302 clinical medicine ,Drug Discovery ,Mitophagy ,Autophagy ,otorhinolaryngologic diseases ,medicine ,Humans ,Cellular Senescence ,Neurons ,Interleukin-6 ,Interleukin-8 ,Neurodegeneration ,beta-Galactosidase ,medicine.disease ,Neural stem cell ,Cell biology ,Oxidative Stress ,stomatognathic diseases ,030104 developmental biology ,Mutation ,Ataxia-telangiectasia ,030217 neurology & neurosurgery ,Oxidative stress ,DNA Damage ,Signal Transduction ,Developmental Biology - Abstract
ATM is a kinase involved in DNA damage response (DDR), regulation of response to oxidative stress, autophagy and mitophagy. Mutations in the ATM gene in humans result in ataxi A-Telangiectasia disease (A-T) characterized by a variety of symptoms with neurodegeneration and premature ageing among them. Since brain is one of the most affected organs in A-T, we have focused on senescence of neural progenitor cells (NPCs) derived from A-T reprogrammed fibroblasts. Accordingly, A-T NPCs obtained through neural differentiation of iPSCs in 5% oxygen possessed some features of senescence including increased activity of SA-β-gal and secretion of IL6 and IL8 in comparison to control NPCs. This phenotype of A-T NPC was accompanied by elevated oxidative stress. A-T NPCs exhibited symptoms of impaired autophagy and mitophagy with lack of response to chloroquine treatment. Additional sources of oxidative stress like increased oxygen concentration (20 %) and H2O2 respectively aggravated the phenotype of senescence and additionally disturbed the process of mitophagy. In both cases only A-T NPCs reacted to the treatment. We conclude that oxidative stress may be responsible for the phenotype of senescence and impairment of autophagy in A-T NPCs. Our results point to senescent A-T cells as a potential therapeutic target in this disease. more...
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- 2020
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38. Glutamine deprivation induces metabolic adaptations associated with beta cell dysfunction and exacerbate lipotoxicity
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Rodrigo Carlessi, Cyril D. S. Mamotte, Heloisa Helena de Oliveira Alves, Gaewyn Ellison, Jordan Rowlands, and Philip Newsholme
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0301 basic medicine ,Blood Glucose ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Glucose uptake ,Glutamine ,Palmitates ,030209 endocrinology & metabolism ,Apoptosis ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Insulin-Secreting Cells ,medicine ,Animals ,Insulin ,Secretion ,Rats, Wistar ,Molecular Biology ,Chemistry ,Mitochondria ,Rats ,Oxidative Stress ,030104 developmental biology ,Lipotoxicity ,Saturated fatty acid ,Beta cell ,Energy Metabolism ,Intracellular ,Signal Transduction - Abstract
Studies have reported that plasma glutamine is reduced in type 2 diabetes (T2D) patients. Glutamine supplementation improves glycaemic control, however the mechanisms are unclear. Here, we evaluated in vitro the pancreatic beta cell bioenergetic and insulin secretory responses to various levels of glutamine availability, or treatment in the presence of an inhibitor of intracellular glutamine metabolism. The impact of glutamine deprivation to the pathological events induced by the saturated fatty acid palmitate was also investigated. Glutamine deprivation induced a reduction in mitochondrial respiration and increase in glucose uptake and utilization. This phenotype was accompanied by impairment in beta cell function, as demonstrated by diminished insulin production and secretion, and activation of the unfolded protein response pathway. Palmitate led to insulin secretory dysfunction, loss of viability and apoptosis. Importantly, glutamine deprivation significantly exacerbated these phenotypes, suggesting that low glutamine levels could participate in the process of beta cell dysfunction in T2D. more...
- Published
- 2019
39. The A allele of the UCP2 -866G/A polymorphism changes UCP2 promoter activity in HUVECs treated with high glucose
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Ana Paula Bouças, Liana Paula Abreu da Silva, Rodrigo Carlessi, Bianca Marmontel de Souza, Luis Henrique Santos Canani, Michelle Rodrigues, and Daisy Crispim
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0301 basic medicine ,Genotype ,Mitochondrion ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Genes, Reporter ,Genetics ,medicine ,Human Umbilical Vein Endothelial Cells ,Humans ,Luciferase ,Uncoupling Protein 2 ,Allele ,Promoter Regions, Genetic ,Molecular Biology ,Alleles ,chemistry.chemical_classification ,Reactive oxygen species ,General Medicine ,Transfection ,Hydrogen Peroxide ,Molecular biology ,Oxidative Stress ,030104 developmental biology ,Glucose ,chemistry ,030220 oncology & carcinogenesis ,G cell ,Oxidative stress - Abstract
The mitochondrial uncoupling protein 2 (UCP2) decreases reactive oxygen species (ROS) formation by mitochondria. Our group previously showed that the UCP2 -866A allele was associated with risk of diabetic retinopathy (DR), which is caused by hyperglycemia-induced oxidative stress. To date, it is still unclear if the -866A allele directly affects UCP2 expression in endothelial cells. Thus, we investigated the effect of the A allele on UCP2 promoter activity in HUVECs treated with high glucose (HG) or hydrogen peroxide (H2O2). To quantify UCP2 promoter activity, HUVECs were transfected with pGL3 plasmids containing the UCP2 promoter and the firefly luciferase coding sequence. Experimental groups were: (1) pGL3-866G-transfected cells and (2) pGL3-866A cells, both under normal (4 mM) or HG (25 mM) concentrations for 24 h and 48 h or incubated with H2O2 (0.1 mM) for 1 h. UCP2 promoter activity was monitored by Luminescent Dual-luciferase Assay. HG induced an upregulation of UCP2 promoter activity in PGL3-866G cells after 24 h of treatment (P = 0.027), but not after 48 h. Compared to pGL3-866G cells, pGL3-866A cells seems to have reduced UCP2 promoter activity following 24 h and 48 h of normal glucose treatment (P = 0.087 and P = 0.022). After HG treatment, pGL3-866A cells had more marked UCP2 downregulation (24 h: − 3.2-folds, P more...
- Published
- 2019
40. Neuro-Immune Interactions in Depression: Mechanisms and Translational Implications
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João Quevedo, Ritele H. Silva, Anelise S. Carlessi, Helena M. Abelaira, and Gislaine Z. Réus
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Microglia ,business.industry ,Mechanism (biology) ,Inflammasome ,Disease ,medicine.disease ,Pyrin domain ,medicine.anatomical_structure ,Immune system ,Medicine ,Antidepressant ,Major depressive disorder ,business ,Neuroscience ,medicine.drug - Abstract
An emerging area of science that promises novel pathways to antidepressant actions and therapies has followed from evidence that immunological factors play major roles in the pathophysiology of major depressive disorder (MDD). Preclinical and clinical studies have suggested that episodes of depression have been characterized by an activation of microglia and increase of pro-inflammatory cytokines centrally and peripherally. In addition, pro-inflammatory cytokines may activate the inflammasome protein complex, including the Nod-like receptor pyrin containing three inflammasome (NLRP3), and this relationship also could be considered an important target to treat depression. Accumulating evidence also suggests that the gut microbiota-brain axis plays a role in the pathogenesis of MDD, thereby contributing to the antidepressant actions of certain compounds. However, despite advances in understanding of the neurobiology of MDD, no established mechanism can explain all aspects of the disease. Thus, the aim of this chapter is to highlight the role of central and peripheral cytokines, microglial activation, gut-brain axis, and NLRP3 inflammasome in the pathophysiology of MDD. more...
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- 2019
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41. Method Protocols for Metabolic and Functional Analysis of the BRIN-BD11 β-Cell Line: A Preclinical Model for Type 2 Diabetes
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Nikita L. Walz, Joanne Rowles, Kevin N. Keane, Philip Newsholme, Rodrigo Carlessi, and Jordan Rowlands
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0301 basic medicine ,Cell physiology ,Bioenergetics ,business.industry ,Insulin ,medicine.medical_treatment ,030209 endocrinology & metabolism ,Metabolism ,Type 2 diabetes ,medicine.disease ,Bioinformatics ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Cell culture ,Diabetes mellitus ,Metabolic control analysis ,medicine ,business - Abstract
In type 2 diabetes, prolonged dysregulation of signalling and β-cell metabolic control leads to β-cell dysfunction, and is increasingly associated with abnormal metabolic states which disrupt normal cellular physiology. Utilization of appropriate β-cell models enables a systematic approach to understand the impact of perturbations to the biological system. The BRIN-BD11 β-cell line is a useful, pre-clinical cell model for β-cell dysfunction associated with type 2 diabetes, among other metabolic disorders. The present chapter describes detection and analysis of β-cell dysfunction with respect to changes in bioenergetics and metabolism, generation of intracellular reactive oxygen species, and acute and chronic insulin secretion in the BRIN-BD11 cell line. more...
- Published
- 2018
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42. Pleiotropic Effects of GLP-1 and Analogs on Cell Signaling, Metabolism, and Function
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Jordan Rowlands, Philip Newsholme, Rodrigo Carlessi, and Julian Heng
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0301 basic medicine ,endocrine system ,Cell signaling ,Endocrinology, Diabetes and Metabolism ,Incretin ,Review ,Pharmacology ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Neuroprotection ,03 medical and health sciences ,Endocrinology ,medicine ,Glucose homeostasis ,Protein kinase A ,lcsh:RC648-665 ,diabetes ,business.industry ,Endoplasmic reticulum ,cell function and integrity ,digestive, oral, and skin physiology ,Neurodegeneration ,Autophagy ,medicine.disease ,030104 developmental biology ,GLP-1 ,signaling ,business ,metabolism - Abstract
The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its ‘incretin effect’ in restoring glucose homeostasis in diabetics, however, it is now apparent that it has a broader range of physiological effects in the body. Both in vitro and in vivo studies have demonstrated that GLP-1 mimetics alleviate endoplasmic reticulum stress, regulate autophagy, promote metabolic reprogramming, stimulate anti-inflammatory signaling, alter gene expression and influence neuroprotective pathways. A substantial body of evidence has accumulated with respect to how GLP-1 and its analogues act to restore and maintain normal cellular functions. These findings have prompted several clinical trials which have reported GLP-1 analogues improve cardiac function, restore lung function and reduce mortality in patients with obstructive lung disease, influence blood pressure and lipid storage, and even prevent synaptic loss and neurodegeneration. Mechanistically, GLP-1 elicits its effects via acute elevation in cAMP levels, and subsequent protein kinase(s) activation, pathways well defined in pancreatic β-cells which stimulate insulin secretion in conjunction with elevated Ca2+ and ATP. More recently, new studies have shed light on additional downstream pathways stimulated by chronic GLP-1 exposure, findings which have direct relevance to our understanding of the potential therapeutic effects of longer lasting analogues recently developed for clinical use. In this review, we provide a comprehensive description of the diverse roles for GLP-1 across multiple tissues, describe downstream pathways stimulated by acute and chronic exposure, and discuss novel pleiotropic applications of GLP-1 mimetics in the treatment of human disease. more...
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- 2018
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43. Antioxidant treatment ameliorates experimental diabetes-induced depressive-like behaviour and reduces oxidative stress in brain and pancreas
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Beatriz I. Matias, Stephanie E. Titus, Alexandra I. Zugno, Livia Bruchchen, João Quevedo, Luciane Bisognin Ceretta, Helena M. Abelaira, Drielly Florentino, Fabricia Petronilho, Andriele Vieira, Gislaine Z. Réus, Anelise S. Carlessi, and Maria Augusta B Dos Santos more...
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0301 basic medicine ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Hippocampus ,Nucleus accumbens ,medicine.disease_cause ,Lipid peroxidation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Diabetes mellitus ,Internal medicine ,Alloxan ,Internal Medicine ,medicine ,Prefrontal cortex ,business.industry ,medicine.disease ,Deferoxamine ,030104 developmental biology ,chemistry ,business ,030217 neurology & neurosurgery ,Oxidative stress ,medicine.drug - Abstract
Studies have shown a relationship between diabetes mellitus (DM) and the development of major depressive disorder. Alterations in oxidative stress are associated with the pathophysiology of both diabetes mellitus and major depressive disorder. This study aimed to evaluate the effects of antioxidants N-acetylcysteine and deferoxamine on behaviour and oxidative stress parameters in diabetic rats. To this aim, after induction of diabetes by a single dose of alloxan, Wistar rats were treated with N-acetylcysteine or deferoxamine for 14 days, and then depressive-like behaviour was evaluated. Oxidative stress parameters were assessed in the prefrontal cortex, hippocampus, amygdala, nucleus accumbens and pancreas. Diabetic rats displayed depressive-like behaviour, and treatment with N-acetylcysteine reversed this alteration. Carbonyl protein levels were increased in the prefrontal cortex, hippocampus and pancreas of diabetic rats, and both N-acetylcysteine and deferoxamine reversed these alterations. Lipid damage was increased in the prefrontal cortex, hippocampus, amygdala and pancreas; however, treatment with N-acetylcysteine or deferoxamine reversed lipid damage only in the hippocampus and pancreas. Superoxide dismutase activity was decreased in the amygdala, nucleus accumbens and pancreas of diabetic rats. In diabetic rats, there was a decrease in catalase enzyme activity in the prefrontal cortex, amygdala, nucleus accumbens and pancreas, but an increase in the hippocampus. Treatment with antioxidants did not have an effect on the activity of antioxidant enzymes. In conclusion, animal model of diabetes produced depressive-like behaviour and oxidative stress in the brain and periphery. Treatment with antioxidants could be a viable alternative to treat behavioural and biochemical alterations induced by diabetes. more...
- Published
- 2015
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44. Exendin‐4 attenuates brain death–induced liver damage in the rat
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Natália Emerim Lemos, Rodrigo Carlessi, Daisy Crispim, Ana Luiza Perez Olive Dias, Jarbas Rodrigues de Oliveira, Cristiane Bauermann Leitão, Andrea Carla Bauer, and Letícia de Almeida Brondani
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Male ,Brain Death ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Immunoblotting ,Apoptosis ,Inflammation ,Liver transplantation ,Pharmacology ,Real-Time Polymerase Chain Reaction ,Liver disease ,chemistry.chemical_compound ,Glucagon-Like Peptide 1 ,Lactate dehydrogenase ,medicine ,Animals ,Hypoglycemic Agents ,Organ donation ,Rats, Wistar ,Transplantation ,Dose-Response Relationship, Drug ,Hepatology ,medicine.diagnostic_test ,Caspase 3 ,Venoms ,business.industry ,Liver Diseases ,medicine.disease ,Immunohistochemistry ,Liver Transplantation ,Rats ,Disease Models, Animal ,Gene Expression Regulation ,Liver ,chemistry ,Cytokines ,Exenatide ,Surgery ,medicine.symptom ,Peptides ,Liver function tests ,business - Abstract
The majority of liver grafts destined for transplantation originate from brain dead donors. However, significantly better posttransplantation outcomes are achieved when organs from living donors are used, suggesting that brain death (BD) causes irreversible damage to the liver tissue. Recently, glucagon-like peptide-1 (GLP1) analogues were shown to possess interesting hepatic protection effects in different liver disease models. We hypothesized that donor treatment with the GLP1 analogue exendin-4 (Ex-4) could alleviate BD-induced liver damage. A rat model of BD was employed in order to estimate BD-induced liver damage and Ex-4's potential protective effects. Liver damage was assessed by biochemical determination of circulating hepatic markers. Apoptosis in the hepatic tissue was assessed by immunoblot and immunohistochemistry using an antibody that only recognizes the active form of caspase-3. Gene expression changes in inflammation and stress response genes were monitored by quantitative real-time polymerase chain reaction. Here, we show that Ex-4 administration to the brain dead liver donors significantly reduces levels of circulating aspartate aminotransferase and lactate dehydrogenase. This was accompanied by a remarkable reduction in hepatocyte apoptosis. In this model, BD caused up-regulation of tumor necrosis factor and stress-related genes, confirming previous findings in clinical and animal studies. In conclusion, treatment of brain dead rats with Ex-4 reduced BD-induced liver damage. Further investigation is needed to determine the molecular basis of the observed liver protection. After testing in a randomized clinical trial, the inclusion of GLP1 analogues in organ donor management might help to improve organ quality, maximize organ donation, and possibly increase liver transplantation success rates. more...
- Published
- 2015
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45. Exendin-4 protects rat islets against loss of viability and function induced by brain death
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Natália Emerim Lemos, Ana Luiza Perez Olive Dias, Fernanda dos Santos de Oliveira, Cristiane Bauermann Leitão, Letícia de Almeida Brondani, Rodrigo Carlessi, Luis Henrique Santos Canani, Daisy Crispim, and Andrea Carla Bauer more...
- Subjects
Male ,endocrine system ,medicine.medical_specialty ,Brain Death ,Cell Survival ,MAP Kinase Signaling System ,medicine.medical_treatment ,Interleukin-1beta ,SOD2 ,Anti-Inflammatory Agents ,Gene Expression ,Inflammation ,Apoptosis ,HMGB1 ,Biochemistry ,Ion Channels ,Mitochondrial Proteins ,Islets of Langerhans ,Endocrinology ,Stress, Physiological ,Internal medicine ,Insulin Secretion ,medicine ,Animals ,Insulin ,Uncoupling Protein 2 ,Rats, Wistar ,Molecular Biology ,Cells, Cultured ,Heat-Shock Proteins ,geography ,geography.geographical_feature_category ,biology ,Superoxide Dismutase ,Tumor Necrosis Factor-alpha ,Venoms ,Islet ,Transplantation ,Cytoprotection ,Unfolded protein response ,biology.protein ,Exenatide ,Pancreatic islet transplantation ,medicine.symptom ,Peptides ,Transcription Factor CHOP - Abstract
Islet quality loss after isolation from brain-dead donors still hinders the implementation of human islet transplantation for treatment of type 1 diabetes. In this scenario, systemic inflammation elicited by donor brain death (BD) is among the main factors influencing islet viability and functional impairment. Exendin-4 is largely recognized to promote anti-inflammatory and cytoprotective effects on β-cells. Therefore, we hypothesized that administration of exendin-4 to brain-dead donors might improve islet survival and insulin secretory capabilities. Here, using a rat model of BD, we demonstrate that exendin-4 administration to the brain-dead donors increases both islet viability and glucose-stimulated insulin secretion. In this model, exendin-4 treatment produced a significant decrease in interleukin-1β expression in the pancreas. Furthermore, exendin-4 treatment increased the expression of superoxide dismutase-2 and prevented BD-induced elevation in uncoupling protein-2 expression. Such observations were accompanied by a reduction in gene expression of two genes often associated with endoplasmic reticulum (ER) stress response in freshly isolated islets from treated animals, C/EBP homologous protein and immunoglobulin heavy-chain binding protein. As ER stress response has been shown to be triggered by and to participate in cytokine-induced β-cell death, we suggest that exendin-4 might exert its beneficial effects through alleviation of pancreatic inflammation and oxidative stress, which in turn could prevent islet ER stress and β-cell death. Our findings might unveil a novel strategy to preserve islet quality from brain-dead donors. After testing in the human pancreatic islet transplantation setting, this approach might sum to the ongoing effort to achieve consistent and successful single-donor islet transplantation. more...
- Published
- 2015
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46. Beckwith–Wiedemann syndrome prenatal diagnosis by methylation analysis in chorionic villi
- Author
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Rosamaria Silipigni, Silvana Guerneri, Nicole Carlessi, Laura Fontana, Stefano Fiori, Leda Paganini, Silvia Motta, Anna Cereda, Monica Miozzo, Silvia Tabano, Faustina Lalatta, and Silvia M. Sirchia
- Subjects
Cancer Research ,medicine.medical_specialty ,Beckwith-Wiedemann Syndrome ,Beckwith–Wiedemann syndrome ,Prenatal diagnosis ,Biology ,Genomic Imprinting ,Pregnancy ,Internal medicine ,medicine ,Humans ,Promoter Regions, Genetic ,Molecular Biology ,Cells, Cultured ,DNA methylation ,prenatal diagnosis ,Methylation ,chorionic villi ,medicine.disease ,Uniparental disomy ,Endocrinology ,Differentially methylated regions ,medicine.anatomical_structure ,Chorionic villi ,Female ,imprinting ,Genomic imprinting ,Research Paper - Abstract
Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder that can be prenatally suspected or diagnosed based on established clinical guidelines. Molecular confirmation is commonly performed on amniocytes. The possibility to use fresh (CVF) and cultured (CVC) chorionic villi has never been investigated. To verify whether CVF and CVC are reliable sources of DNA to study fetal methylation, we used pyrosequencing to test the methylation level of a number of differentially methylated regions (DMRs) at several imprinted loci (ICR1, ICR2, H19, PWS/AS-ICR, GNASXL, GNAS1A, ZAC/PLAGL1, and MEST) and at non-imprinted MGMT and RASSF1A promoters. We analyzed these regions in 19 healthy pregnancies and highlighted stable methylation levels between CVF and CVC at ICR1, ICR2, GNASXL, PWS/AS-ICR, and MEST. Conversely, the methylation levels at H19 promoter, GNAS1A and ZAC/PLAGL1 were different in CVC compared to fresh CV. We also investigated ICR1 and ICR2 methylation level of CVF/CVC of 2 BWS-suspected fetuses (P1 and P2). P1 showed ICR2 hypomethylation, P2 showed normal methylation at both ICR1 and ICR2. Our findings, although limited to one case of BWS fetus with an imprinting defect, can suggest that ICR1 and ICR2, but not H19, could be reliable targets for prenatal BWS diagnosis by methylation test in CVF and CVC. In addition, PWS/AS-ICR, GNASXL, and MEST, but not GNAS1A and ZAC/PLAGL1, are steadily hemimethylated in CV from healthy pregnancies, independently from culture. Thus, prenatal investigation of genomic imprinting in CV needs to be validated in a locus-specific manner. more...
- Published
- 2015
47. A single dose of S-ketamine induces long-term antidepressant effects and decreases oxidative stress in adulthood rats following maternal deprivation
- Author
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Anelise S. Carlessi, Livia Bruchchen, Stephanie E. Titus, Jaine R. da Luz, Drielly Florentino, Gislaine Z. Réus, Fabricia Petronilho, João Quevedo, Zuleide M. Ignácio, Helena M. Abelaira, Beatriz I. Matias, and Andriele Vieira more...
- Subjects
medicine.medical_specialty ,Maternal deprivation ,biology ,Antagonist ,Pharmacology ,medicine.disease_cause ,Superoxide dismutase ,Lipid peroxidation ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Endocrinology ,Developmental Neuroscience ,chemistry ,Catalase ,Internal medicine ,medicine ,biology.protein ,Antidepressant ,Ketamine ,Oxidative stress ,medicine.drug - Abstract
Ketamine, an antagonist of N-methyl-d-aspartate receptors, has produced rapid antidepressant effects in patients with depression, as well as in animal models. However, the extent and duration of the antidepressant effect over longer periods of time has not been considered. This study evaluated the effects of single dose of ketamine on behavior and oxidative stress, which is related to depression, in the brains of adult rats subjected to maternal deprivation. Deprived and nondeprived Wistar rats were divided into four groups nondeprived+saline; nondeprived+S-ketamine (15 mg/kg); deprived+saline; deprived+S-ketamine (15 mg/kg). A single dose of ketamine or saline was administrated during the adult phase, and 14 days later depressive-like behavior was assessed. In addition, lipid damage, protein damage, and antioxidant enzyme activities were evaluated in the rat brain. Maternal deprivation induces a depressive-like behavior, as verified by an increase in immobility and anhedonic behavior. However, a single dose of ketamine was able to reverse these alterations, showing long-term antidepressant effects. The brains of maternally deprived rats had an increase in protein oxidative damage and lipid peroxidation, but administration of a single dose of ketamine reversed this damage. The activities of antioxidant enzymes superoxide dismutase and catalase were reduced in the deprived rat brains. However, ketamine was also able to reverse these changes. In conclusion, these findings indicate that a single dose of ketamine is able to induce long-term antidepressant effects and protect against neural damage caused by oxidative stress in adulthood rats following maternal deprivation. more...
- Published
- 2015
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48. Association between Asp299Gly and Thr399Ile Polymorphisms in Toll-Like Receptor 4 Gene and Type 2 Diabetes Mellitus: Case-Control Study and Meta- Analysis
- Author
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Rodrigo Carlessi, Carmen Maldonado-Bernal, Letícia de Almeida Brondani, Taís Silveira Assmann, Natália Emerim Lemos, Luis Henrique Santos Canani, Daisy Crispim, and Miguel Cruz
- Subjects
Genetics ,Oncology ,medicine.medical_specialty ,endocrine system diseases ,business.industry ,Case-control study ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,Odds ratio ,Polymorphism (computer science) ,Internal medicine ,Meta-analysis ,Genotype ,medicine ,Allele ,business ,Allele frequency - Abstract
Objective: This paper describes a case-control study and a meta-analysis conducted to determine whether the TLR4 Asp299Gly (rs4986790) and Thr399Ile (rs4986791) polymorphisms are associated with type 2 diabetes mellitus (T2DM). Methods: In the case-control study were enrolled 1683 T2DM patients and 584 nondiabetic subjects from Brazil. A literature search was conducted in order to identify studies that investigated associations between the referred TLR4 polymorphisms and T2DM. Pooled odds ratios (OR) were calculated for allele contrast and dominant inheritance models. Results: In the case-control study, genotype and allele frequencies of the Asp299Gly and Thr399Ile polymorphisms differed between T2DM patients and nondiabetic subjects (P more...
- Published
- 2018
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49. Ketamine ameliorates depressive-like behaviors and immune alterations in adult rats following maternal deprivation
- Author
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João Quevedo, Francieli Vuolo, Helena M. Abelaira, Renata C. Gonçalves, Débora B. Tomaz, Felipe Dal-Pizzol, André F. Carvalho, Maria Augusta B Dos Santos, Jaine R. da Luz, Anelise S. Carlessi, Marcos Paulo Nacif, and Gislaine Z. Réus more...
- Subjects
Male ,medicine.medical_specialty ,Glutamatergic ,Immune system ,Internal medicine ,medicine ,Animals ,Ketamine ,Rats, Wistar ,Receptor ,Maternal deprivation ,Depression ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Maternal Deprivation ,General Neuroscience ,Antagonist ,Glutamate receptor ,Antidepressive Agents ,Endocrinology ,Cytokines ,NMDA receptor ,Female ,Psychology ,Interleukin-1 ,medicine.drug - Abstract
A growing body of evidence points toward an association between the glutamatergic system, as well as immune system dysregulation and major depression. So, the present study was aimed at evaluating the behavioral and molecular effects of the ketamine, an antagonist of the N-methyl-D-aspartate (NMDA) receptor of glutamate in maternally deprived adult rats. In deprived rats treated with saline, we observed an increase in the immobility time; however, ketamine treatment reversed this effect, decreasing immobility time. In addition, maternal deprivation induced an increase in cytokines: TNF-α and IL-1 in serum, and in IL-6 in serum and cerebrospinal fluid (CSF). Interestingly, ketamine treatment reduced the levels of all the cytokines in deprived rats. In conclusion, these findings further support a relationship between immune activation and depression. Considering the action of ketamine, this study suggested that antagonists of the NMDA receptor, such as ketamine, could exert their effects by modulation of the immune system. more...
- Published
- 2015
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50. Nutrient regulation of β-cell function: what do islet cell/animal studies tell us?
- Author
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Cyril D. S. Mamotte, Kevin N. Keane, Philip Newsholme, and Rodrigo Carlessi
- Subjects
0301 basic medicine ,Blood Glucose ,medicine.medical_specialty ,medicine.medical_treatment ,Cell ,Medicine (miscellaneous) ,Type 2 diabetes ,Biology ,Bioinformatics ,03 medical and health sciences ,Islets of Langerhans ,Diabetes mellitus ,Internal medicine ,Insulin Secretion ,medicine ,Animals ,Humans ,Insulin ,geography ,Nutrition and Dietetics ,geography.geographical_feature_category ,Pancreatic islets ,medicine.disease ,Islet ,Obesity ,Diet ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Diabetes Mellitus, Type 2 ,Hyperglycemia ,Animal studies - Abstract
Diabetes mellitus is widely recognised as one of the most serious metabolic diseases worldwide, and its incidence in Asian countries is growing at an alarming rate. Type 2 diabetes (T2DM) is closely associated with age, sedentary lifestyle and poor diet. In T2DM, β-cell dysfunction will occur before hyperglycaemia develops. Excessive levels of glucose, lipid and various inflammatory factors interact at the level of the pancreatic islet to promote β-cell dysfunction. Pancreatic β-cell lines have been widely utilised since the early 1980s and have contributed a large volume of important information regarding molecular, metabolic and genetic mechanisms that regulate insulin secretion. The purpose of this review is to describe the origin and characteristics of the most commonly used β-cell lines and their contribution to discovery of fundamental regulatory processes that control insulin production and release. Pancreatic islets obtained from rodents as well as other animals have additionally provided information on the architecture and three-dimensional design of this endocrine tissue that allows precise regulation of hormone release. Understanding the nature of failure of physiologic and metabolic processes leading to insufficient insulin release and subsequent diabetes has allowed development of novel anti-diabetic therapeutics, now in common use, worldwide. more...
- Published
- 2017
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