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1.
J Cell Biol ; 223(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38695719

RESUMO

Microglia sense the changes in their environment. How microglia actively translate these changes into suitable cues to adapt brain physiology is unknown. We reveal an activity-dependent regulation of cortical inhibitory synapses by microglia, driven by purinergic signaling acting on P2RX7 and mediated by microglia-derived TNFα. We demonstrate that sleep induces microglia-dependent synaptic enrichment of GABAARs in a manner dependent on microglial TNFα and P2RX7. We further show that microglia-specific depletion of TNFα alters slow waves during NREM sleep and blunt memory consolidation in sleep-dependent learning tasks. Together, our results reveal that microglia orchestrate sleep-intrinsic plasticity of synaptic GABAARs, sculpt sleep slow waves, and support memory consolidation.


Assuntos
Microglia , Receptores de GABA-A , Sono de Ondas Lentas , Sinapses , Fator de Necrose Tumoral alfa , Animais , Masculino , Camundongos , Consolidação da Memória , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Plasticidade Neuronal/fisiologia , Receptores de GABA-A/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Receptores Purinérgicos P2X7/genética , Transdução de Sinais , Sono/fisiologia , Sinapses/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
2.
Int J Mol Sci ; 22(6)2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33804754

RESUMO

Lipids play an essential role in platelet functions. It is known that polyunsaturated fatty acids play a role in increasing platelet reactivity and that the prothrombotic phenotype plays a crucial role in the occurrence of major adverse cardiovascular events. The ongoing increase in cardiovascular diseases' incidence emphasizes the importance of research linking lipids and platelet function. In particular, the rebound phenomenon that accompanies discontinuation of clopidogrel in patients receiving dual antiplatelet therapy has been associated with changes in the lipid profile. Our many years of research underline the importance of reduced HDL values for the risk of such a rebound effect and the occurrence of thromboembolic events. Lipids are otherwise a heterogeneous group of molecules, and their signaling molecules are not deposited but formed "on-demand" in the cell. On the other hand, exosomes transmit lipid signals between cells, and the profile of such changes can be monitored by lipidomics. Changes in the lipid profile are organ-specific and may indicate new drug action targets.


Assuntos
Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Metabolismo dos Lipídeos , Lipídeos , Inibidores da Agregação Plaquetária/farmacologia , Animais , Humanos , Lipídeos/química , Lipoproteínas HDL/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/química , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico
3.
Int. j. morphol ; 38(6): 1528-1534, Dec. 2020. tab
Artigo em Inglês | LILACS | ID: biblio-1134472

RESUMO

SUMMARY: The aim of this research was to determine the differences among the male basketball players of the National team of Montenegro U18 and the National team of Republic of North Macedonia, in terms of their anthropometric characteristics and body composition. A sample of 27 subjects was divided into two sub-samples. The first sub-sample of the subjects consisted of 15 players of the National team of Montenegro, average age 17.6±0.63, while the other sub-sample consisted of 12 players of the National team of Republic of North Macedonia, average age of 17.17± 0.72. All players were tested in Podgorica, in lasting period of two days, while they held preparations for the European Championship. Anthropometric characteristics and body composition were evaluated by a battery of eleven variables: body height (cm), body weight (kg), triceps skinfold, back skinfold, biceps skinfold, abdominal skinfold, thigh skinfold, calf skinfold, body mass index (BMI), percentage of fat and muscle mass (kg). Differences in anthropometric characteristic and composition of the body of the basketball players of two national teams were determined by using a discriminatory parametric procedure with t-test for small independent samples (p<0.05). The players of the two teams were found to differ statistically in thigh skinfold. Furthermore, it is concluded that Montenegro players are taller and heavier and have higher muscle mass than North Macedonian players, with approximate skinfolds, BMI and fat percentage values.


RESUMEN: El objetivo de esta investigación fue determinar las diferencias en las características antropométricas y composición corporal entre los jugadores de baloncesto masculino del equipo nacional de Montenegro U18 y el equipo nacional de la República de Macedonia del Norte. Una muestra de 27 sujetos se dividió en dos submuestras. La primera sub muestra consistió en 15 jugadores del equipo nacional de Montenegro, con una edad promedio de 17,6 ± 0,63 años. La otra muestra consistió en 12 jugadores del equipo nacional de la República de Macedonia del Norte, con un promedio edad de 17,17 ± 0,72 años. Todos los jugadores fueron evaluados en Podgorica, durante un período de dos días, mientras realizaban los preparativos para el Campeonato de Europa. Las características antropométricas y la composición corporal se evaluaron mediante una batería de once variables: altura (cm), peso (kg), pliegue de tríceps, pliegue de espalda, pliegue de bíceps, pliegue abdominal, pliegue de muslos, pliegue de pantorrilla, índice de masa corporal (IMC), porcentaje de grasa y masa muscular (kg). Se determinaron las diferencias en las características antropométricas y la composición del cuerpo de los jugadores de baloncesto de dos equipos nacionales a través de un procedimiento paramétrico discriminatorio con prueba t para muestras independientes (p <0,05). Se determinó que los jugadores de ambos equipos difieren estadísticamente en el pliegue del muslo. Además, se concluyó que en comparación con los jugadores de Macedonia del Norte los jugadores de Montenegro son de mayor altura y peso, además de contar con una mayor masa muscular, con valores aproximados de pliegues cutáneos, IMC y porcentaje de grasa.


Assuntos
Humanos , Masculino , Adolescente , Composição Corporal , Basquetebol , Dobras Cutâneas , Estatura , Índice de Massa Corporal , Antropometria , Montenegro
4.
Comput Biol Med ; 126: 104045, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33099047

RESUMO

BACKGROUND: High-dose-rate mono brachytherapy (HDR-MB) is employed in the treatment of prostate carcinoma (CaP). As an ideal plan of CaP brachytherapy cannot be created, it is necessary to identify a reliable tool to optimise the parameters of HDR-MB. This paper applies a multilayer artificial neural network (MANN) and a genetic algorithm (GA) to optimise brachytherapy parameters based on an individual dose-volumetric analysis. METHODS: Patients with localised CaP of various risks were treated with HDR-MB. Consecutive levels of the biochemical control parameter (prostate specific antigen (PSA) nadir) have been collected after completion of HDR-MB in the range 2-9 years. The Kaplan-Meier regression analysis of biochemical-free survival (BFS) was applied. The clinical risk of recurrent CaP (RCaP), the therapy dose (TD), TD coverage index (CI100%) and PSA nadir were modelled using the MANN and GA. RESULTS: In the low-risk group, BFS was achieved in 100% of treated patients, while in the group of patients with high risk, BFS was achieved in 95.8% of treated patients. The MANN-GA model optimises a TD of 47.3 Gy and CI100% of 1.14 as well as a TD of 50.4 Gy and CI100% of 1.6 for the low-risk group and high-risk group, respectively, of localised CaP. The optimised PSA nadir was 0.047 and 0.25 ng cm-3 for low-risk group and high-risk group, respectively. CONCLUSIONS: The developed MANN-GA model presents a method for optimising the treatment parameters in radiation therapy, which could be a valuable tool in planning of the HDR-MB.


Assuntos
Braquiterapia , Carcinoma , Neoplasias da Próstata , Algoritmos , Seguimentos , Humanos , Masculino , Redes Neurais de Computação , Projetos Piloto , Próstata , Neoplasias da Próstata/radioterapia
5.
Med Pregl ; 62(11-12): 555-68, 2009.
Artigo em Inglês, Sérvio | MEDLINE | ID: mdl-20491382

RESUMO

The term cardiodynamics refers to dynamic events associated with cardiac contraction and relaxation. The occurring wave of excitement spreads very quickly along the entire atrial musculature and after a brief AV retention it affects all muscle cells of the ventricles. Excitation, that is, the increase in action potentials, precedes the contraction of the myocardium, which follows the "all or none" rule. Each contraction results in relaxation of the myocardium, so that the contraction and relaxation cycles continually follow each other in succession. The entire cardiodynamics, hemnodinamics, i.e., signaling mechanisms of the heart are altered in the remodeling (alternation) condition of the left ventricular myocardium, i.e., the musculature and the whole arterial wall. Remodeling of the cardiac wall and layers of the arterial wall is a negative factor, because it leads to disturbances of the cardiac contraction and relaxation cycles and incites progression of the arterial hypertension, emergence of atherosclerosis and arterial stenosis. Today, the genetic base of the cardiac remodeling is the object of intensive studies. Cardiomyopathies are primary disorders of the myocardium associated with abnormalities of the cardiac wall thickness, the size of chambers, contractions, relaxations, signal conduct and rhythm. They are the major cause of morbidity and mortality for all age groups. Mechanisms of these events on the molecular level will be discussed in the following study.


Assuntos
Cardiomiopatias/fisiopatologia , Contração Miocárdica/fisiologia , ATPases Transportadoras de Cálcio/metabolismo , Cardiomegalia/fisiopatologia , Humanos , Miocárdio/metabolismo , Sarcolema/metabolismo , Remodelação Ventricular/fisiologia
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