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1.
Neurooncol Adv ; 3(1): vdaa150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33506198

RESUMO

BACKGROUND: Gliomas typically escape surgical resection and recur due to their "diffuse invasion" phenotype, enabling them to infiltrate diffusely into the normal brain parenchyma. Over the past 80 years, studies have revealed 2 key features of the "diffuse invasion" phenotype, designated the Scherer's secondary structure, and include perineuronal satellitosis (PS) and perivascular satellitosis (PVS). However, the mechanisms are still unknown. METHODS: We established a mouse glioma cell line (IG27) by manipulating the histone H3K27M mutation, frequently harboring in diffuse intrinsic pontine gliomas, that reproduced the diffuse invasion phenotype, PS and PVS, following intracranial transplantation in the mouse brain. Further, to broadly apply the results in this mouse model to human gliomas, we analyzed data from 66 glioma patients. RESULTS: Increased H3K27 acetylation in IG27 cells activated glucose transporter 1 (Glut1) expression and induced aerobic glycolysis and TCA cycle activation, leading to lactate, acetyl-CoA, and oncometabolite production irrespective of oxygen and glucose levels. Gain- and loss-of-function in vivo experiments demonstrated that Glut1 controls the PS of glioma cells, that is, attachment to and contact with neurons. GLUT1 is also associated with early progression in glioma patients. CONCLUSIONS: Targeting the transporter Glut1 suppresses the unique phenotype, "diffuse invasion" in the diffuse glioma mouse model. This work leads to promising therapeutic and potential useful imaging targets for anti-invasion in human gliomas widely.

2.
Int J Mol Sci ; 21(20)2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33086766

RESUMO

Osteoarthritis (OA), a disease that greatly impacts quality of life, has increasing worldwide prevalence as the population ages. However, its pathogenic mechanisms have not been fully elucidated and current therapeutic treatment strategies are inadequate. In recent years, abnormal endochondral ossification in articular cartilage has received attention as a pathophysiological mechanism in OA. Cartilage is composed of abundant extracellular matrix components, which are involved in tissue maintenance and regeneration, but how these factors affect endochondral ossification is not clear. Here, we show that the application of aggrecan-type proteoglycan from salmon nasal cartilage (sPG) exhibited marked proliferative capacity through receptor tyrosine kinases in chondroprogenitor cells, and also exhibited differentiation and three-dimensional structure formation via phosphorylation of Insulin-like Growth Factor-1 Receptor and Growth Differentiation Factor 5 expression. Furthermore, sPG inhibited calcification via expression of Runx2 and Col10 (factors related to induction of calcification), while increasing Mgp, a mineralization inhibitory factor. As a result of analyzing the localization of sPG applied to the cells, it was localized on the surface of the cell membrane. In this study, we found that sPG, as a biomaterial, could regulate cell proliferation, differentiation and calcification inhibition by acting on the cell surface microenvironment. Therefore, sPG may be the foundation for a novel therapeutic approach for cartilage maintenance and for improved symptoms in OA.


Assuntos
Diferenciação Celular , Membrana Celular/metabolismo , Microambiente Celular , Condrogênese , Proteoglicanas/farmacologia , Calcificação Fisiológica/efeitos dos fármacos , Cartilagem Articular/metabolismo , Diferenciação Celular/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Microambiente Celular/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Receptores ErbB/metabolismo , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor IGF Tipo 1/metabolismo
3.
Biomolecules ; 10(9)2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899694

RESUMO

The use of molecular biomarkers for the early detection of heart disease, before their onset of symptoms, is an attractive novel approach. Ideal molecular biomarkers, those that are both sensitive and specific to heart disease, are likely to provide a much earlier diagnosis, thereby providing better treatment outcomes. Galectin-3 is expressed by various immune cells, including mast cells, histiocytes and macrophages, and plays an important role in diverse physiological functions. Since galectin-3 is readily expressed on the cell surface, and is readily secreted by injured and inflammatory cells, it has been suggested that cardiac galectin-3 could be a marker for cardiac disorders such as cardiac inflammation and fibrosis, depending on the specific pathogenesis. Thus, galectin-3 may be a novel candidate biomarker for the diagnosis, analysis and prognosis of various cardiac diseases, including heart failure. The goals of heart disease treatment are to prevent acute onset and to predict their occurrence by using the ideal molecular biomarkers. In this review, we discuss and summarize recent developments of galectin-3 as a next-generation molecular biomarker of heart disease. Furthermore, we describe how galectin-3 may be useful as a diagnostic marker for detecting the early stages of various heart diseases, which may contribute to improved early therapeutic interventions.


Assuntos
Galectina 3/metabolismo , Cardiopatias/diagnóstico , Animais , Biomarcadores , Modelos Animais de Doenças , Diagnóstico Precoce , Fibrose/diagnóstico , Fibrose/metabolismo , Cardiopatias/metabolismo , Cardiopatias/patologia , Humanos , Prognóstico
4.
BMC Med Educ ; 20(1): 67, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143611

RESUMO

BACKGROUND: Clinical decision-making skills are essential for providing high-quality patient care. To enhance these skills, many institutions worldwide use case-based learning (CBL) as an educational strategy of pre-clinical training. However, to date, the influence of different learning modalities on students' clinical decision-making processes has not been fully explored. This study aims to explore the influence of video and paper case modalities on the clinical decision-making process of midwifery students during CBL. METHODS: CBL involving a normal pregnant woman was provided for 45 midwifery students. They were divided into 12 groups; six groups received the video modality, and six groups received the paper modality. Group discussions were video-recorded, and focus groups were conducted after the CBL. Transcripts of the group discussions were analysed in terms of their interaction patterns, and focus groups were thematically analysed based on the three-stage model of clinical decision-making, which includes cue acquisition, interpretation, and evaluation/decision-making. RESULTS: The students in the video groups paid more attention to psychosocial than biomedical aspects and discussed tailored care for the woman and her family members. They refrained from vaginal examinations and electric fetal heart monitoring. Conversely, the students in the paper groups paid more attention to biomedical than psychosocial aspects and discussed when to perform vaginal examinations and electric fetal heart monitoring. CONCLUSION: This study clarified that video and paper case modalities have different influences on learners' clinical decision-making processes. Video case learning encourages midwifery students to have a woman- and family-centred holistic perspective of labour and birth care, which leads to careful consideration of the psychosocial aspects. Paper case learning encourages midwifery students to have a healthcare provider-centred biomedical perspective of labour and childbirth care, which leads to thorough biomedical assessment.


Assuntos
Tomada de Decisão Clínica , Aprendizagem , Tocologia/educação , Gravação em Vídeo , Adulto , Feminino , Grupos Focais , Humanos , Gravidez , Pesquisa Qualitativa , Adulto Jovem
5.
Biomolecules ; 10(3)2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32138174

RESUMO

Galectin-3 is a ß-galactoside-binding lectin which is important in numerous biological activities in various organs, including cell proliferation, apoptotic regulation, inflammation, fibrosis, and host defense. Galectin-3 is predominantly located in the cytoplasm and expressed on the cell surface, and then often secreted into biological fluids, like serum and urine. It is also released from injured cells and inflammatory cells under various pathological conditions. Many studies have revealed that galectin-3 plays an important role as a diagnostic or prognostic biomarker for certain types of heart disease, kidney disease, viral infection, autoimmune disease, neurodegenerative disorders, and tumor formation. In particular, it has been recognized that galectin-3 is extremely useful for detecting many of these diseases in their early stages. The purpose of this article is to review and summarize the recent literature focusing on the biomarker characteristics and long-term outcome predictions of galectin-3, in not only patients with various types of diseases, but associated animal models.


Assuntos
Doenças Autoimunes , Biomarcadores Tumorais/metabolismo , Proteínas Sanguíneas/metabolismo , Galectinas/metabolismo , Cardiopatias , Nefropatias , Neoplasias , Doenças Neurodegenerativas , Viroses , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/metabolismo , Cardiopatias/diagnóstico , Cardiopatias/metabolismo , Humanos , Nefropatias/diagnóstico , Nefropatias/metabolismo , Neoplasias/diagnóstico , Neoplasias/metabolismo , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/metabolismo , Viroses/diagnóstico , Viroses/metabolismo
6.
J Oncol ; 2019: 2964783, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31320900

RESUMO

Glioblastoma (GBM) is the most common and the most malignant primary brain tumor and is characterized by rapid proliferation, invasion into surrounding normal brain tissues, and consequent aberrant vascularization. In these characteristics of GBM, invasive properties are responsible for its recurrence after various therapies. The histomorphological patterns of glioma cell invasion have often been referred to as the "secondary structures of Scherer." The "secondary structures of Scherer" can be classified mainly into four histological types as (i) perineuronal satellitosis, (ii) perivascular satellitosis, (iii) subpial spread, and (iv) invasion along the white matter tracts. In order to develop therapeutic interventions to mitigate glioma cell migration, it is important to understand the biological mechanism underlying the formation of these secondary structures. The main focus of this review is to examine new molecular pathways based on the histopathological evidence of GBM invasion as major prognostic factors for the high recurrence rate for GBMs. The histopathology-based pharmacological and biological targets for treatment strategies may improve the management of invasive and resistant GBMs.

7.
Cancer Prev Res (Phila) ; 12(7): 413-420, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31101635

RESUMO

Cancer stem cells (CSC) have attracted a great deal of interest for their clinical relevance in a range of cancers, including colorectal cancer. CSCs were initially considered to be cell populations with homogeneous, well-defined phenotypic and molecular characteristics. However, accumulating evidence suggests that CSCs represent phenotypically and functionally heterogeneous populations. Recent studies demonstrate colorectal CSCs to be dynamic rather than static, and continuously altered by multiple extrinsic and intrinsic factors. Thus, CSCs no longer should be viewed as a fixed target population, and we should note that their heterogeneous and dynamic nature presents a serious problem for the development and implementation of specific therapeutic strategies. This review summarizes past and current literature related to the heterogeneity and dynamics of colorectal CSC populations, focusing on evidence for distinct subpopulations, and signaling pathways, and intra- and extratumoral factors involved in their regulation in cancer tissues.


Assuntos
Neoplasias Colorretais/patologia , Células-Tronco Neoplásicas/patologia , Animais , Neoplasias Colorretais/metabolismo , Humanos , Células-Tronco Neoplásicas/metabolismo , Transdução de Sinais
8.
Adv Exp Med Biol ; 1139: 115-126, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31134498

RESUMO

Colorectal cancer (CRC) remains the fourth leading cause of cancer death worldwide. Cancer stem cells (CSCs) have attracted a great deal of interest because of their potential clinical implications in a range of cancers, including CRC. CSCs were initially considered to be cell populations with well-defined phenotypic and molecular characteristics. However, accumulating evidence suggests that CSCs represent a phenotypically and functionally heterogeneous population. Recent studies also demonstrate colorectal CSCs to be dynamic rather than static populations that are continuously altered by various extrinsic factors in addition to intrinsic cellular factors such as genetic and epigenetic alterations. Thus, CSCs do not represent a fixed target population any longer, and their heterogeneous and dynamic nature present a serious problem in establishing specific therapeutic strategies. This chapter summarizes past and current literature related to CSC population heterogeneity and dynamics in CRC tissues, including evidence of the presence of distinct CSC subpopulations and signaling pathways and intra- and extra-tumoral factors involved in the regulation of CSCs in cancer tissues.


Assuntos
Neoplasias do Colo/patologia , Neoplasias Colorretais/patologia , Células-Tronco Neoplásicas/citologia , Humanos , Transdução de Sinais
9.
PLoS One ; 14(1): e0210971, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30673749

RESUMO

Galectin-3 is a ß-galactoside-binding lectin which is important in cell proliferation and apoptotic regulation. Recently, serum galectin-3 has been shown to have prognostic value as a biomarker in heart failure. Encephalomyocarditis virus (EMCV) can cause severe myocarditis, congestive heart failure and dilated cardiomyopathy as well as encephalitis in various animals including mice. The pathophysiological role of galectin-3 in acute myocarditis following viral infection is not fully understood. The goal of this study is to determine the cardiac localization and the time-course of galectin-3 expression in heart failure after viral inoculation with EMCV. At 12, 24, 48, 96 hours, 7 and 10 days after intraperitoneal EMCV inoculation, animals were examined histologically and analyzed for the expression of galectin-3 and Iba1. Galectin-3 was up-regulated in degenerated fibrotic lesions of cardiac tissues 96 hours after viral inoculation and were followed by myocardial fibrosis. At the same time, Iba1 positive macrophages were observed within the inflammatory sites. A time-course correlation between the number of galectin-3 positive cells and the cardiac area of degenerated fibrotic lesions was detected-serum galectin-3 increased at 96 hours and correlated well with the number of cardiac galectin-3 positive cells. Our results indicate that galectin-3 expression may be a useful biomarker of cardiac fibrotic degeneration in acute myocarditis following viral infection. In addition, measuring serum galectin-3 levels might be an early diagnostic method for detecting cardiac degeneration in acute myocarditis.


Assuntos
Infecções por Cardiovirus/sangue , Infecções por Cardiovirus/metabolismo , Vírus da Encefalomiocardite , Galectina 3/sangue , Galectina 3/metabolismo , Miocardite/sangue , Miocardite/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/metabolismo , Infecções por Cardiovirus/patologia , Modelos Animais de Doenças , Vírus da Encefalomiocardite/patogenicidade , Fibrose , Imuno-Histoquímica , Cinética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas dos Microfilamentos/metabolismo , Miocardite/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Prognóstico , Sarcoglicanas/deficiência , Sarcoglicanas/genética
10.
BMC Med Educ ; 18(1): 47, 2018 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-29587725

RESUMO

BACKGROUND: It is known that empathic communication is important for physicians to achieve higher patient satisfaction and health outcomes. Emotional intelligence (EI), empathy and personality in medical students predict students' individual disposition and their emotional and empathic perceptions. This study aimed to investigate: 1) The association between empathy, EI and personality, and 2) Gender differences in the association between empathy, EI and personality. METHOD: Participants were 357 1st year medical students from 2008 to 2011 at one medical school in Japan. Students completed self-report questionnaires comprising three validated instruments measuring EI: Trait Emotional Intelligence Questionnaire-Short Form (TEIQue-SF), empathy: Jefferson Scale of Physician Empathy- student version (JSPE) and personality: NEO-Five-Factor Inventory (NEO-FFI), which explores 5 dimensions of personality Neuroticism (N), Extraversion (E), Openness to experience (O), Agreeableness (A), and Conscientiousness (C). RESULTS: Pearson Correlations showed weak association between TEIQue-SF and JSPE. TEIQue-SF and NEO-FFI showed positive correlation for E and C, and strong negative correlation for N and weak positive correlation for A and O. Weak positive correlation between JSPE and the NEO-FFI were observed for E and A. Although effect sizes were small, N, A and empathy were significantly higher in females (unpaired t-test). However, hierarchical multiple-regression analysis when controlling for gender and personality showed no association between EI, empathy and gender. A, TEIQue-SF and N were found to make small contributions in respect of predictions for JSPE. Personality contributed significantly to the prediction of TEIQue-SF. N had the largest independent negative contribution (ß = - 0,38). CONCLUSION: In our study population of 1st year medical students, females had significantly higher N, A and empathy scores than males. Medical students' N score was strongly negatively associated with EI. Empathy was weakly associated with EI and A. However, when controlling gender and personality in regression analysis, gender did not affect EI and empathy, rather personality is the most important factor. Our findings indicate that N is a major factor that negatively affects EI. It is important to mitigate N using thoughtful training, taking into account students' personalities, to reduce N. In future studies, we will assess how communication trainings for students might enhance EI.


Assuntos
Inteligência Emocional , Empatia , Personalidade , Estudantes de Medicina/psicologia , Feminino , Humanos , Japão , Masculino , Satisfação do Paciente , Autorrelato , Fatores Sexuais , Inquéritos e Questionários
11.
Life Sci ; 158: 70-7, 2016 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-27373423

RESUMO

AIMS: The molecular mechanism of osteoarthritis (OA) has never been understood clearly, but it has been suggested that imbalance of degradation and synthesis in cartilage contribute to the underlying mechanisms of OA. In this study, we investigated the effectiveness in the cartilage metabolism of the artichoke extract that includes the compound cynaropicrin. MAIN METHODS: We evaluated the efficacy of the artichoke extract or cynaropicrin in the cartilage metabolism factors and NF-κB signaling activity stimulated by inflammatory cytokine in chondrogenic cell lines, OUMS-27 and SW1353, using qRT-PCR, immunofluorescence and immunoblotting. KEY FINDINGS: We initially found that an artichoke extract and cynaropicrin both inhibited the increase of cartilage degradation factor MMP13 and further decreased the synthesis factor aggrecan induced by TNF-α in OUMS-27. In addition, cynaropicrin suppressed the enhancement of master regulator HIF-2α on cartilage degradation and further reduced the master regulator Sox9 on cartilage synthesis induced by TNF-α. We observed that cynaropicrin suppresses NF-κB signaling, which controls HIF-2α and Sox9. Since, HIF-2α is induced by p65 (RelA), we evaluated the effect of cynaropicrin and observed that it suppressed the nuclear transport of p65 (RelA) by inhibiting phosphorylation of IκBα. Moreover, cynaropicrin not only suppressed TNF-α stimulation, it had a similar effect on IL-1ß stimulation. No significant cytotoxicity with cynaropicrin was observed. SIGNIFICANCE: These finding suggest that cynaropicrin is an effective substance that can improve the balance of cartilage metabolism, by altering the equilibrium of cartilage degradation and synthesis induced by multiple mediators know to contribute to OA.


Assuntos
Cartilagem/metabolismo , Lactonas/metabolismo , Sesquiterpenos/metabolismo , Agrecanas/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Cartilagem/enzimologia , Linhagem Celular , Humanos , Hidrólise , Metaloproteinase 13 da Matriz/metabolismo , NF-kappa B/metabolismo , Fatores de Transcrição SOX9/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
12.
Neuroreport ; 27(5): 311-7, 2016 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-26848998

RESUMO

Recent evidence has suggested that the hippocampal CA2 region plays an important role in the recognition process. We have reported that ischemic damage in the hippocampal CA2 region following transient ischemia is caused by apoptosis, but the underlying mechanisms are still not clear. Galectin-3 is a ß-galactosidase-binding lectin that is important in cell proliferation and apoptotic regulation. We have also reported that galectin-3 was expressed in activated microglia in the CA1 region 96 h after transient ischemia. The aim of this study is to determine the localization and time course of galectin-3 expression in the CA2 region following transient forebrain ischemia. Galectin-3 immunostaining was observed in both interior side of CA1 region and CA2 region in hippocampus 60 h after ischemic insult. At 66 h, galectin-3 was observed in the whole CA1 region adjacent to the CA2 region in the hippocampus. Both galectin-3 expression and neuronal cell death in the CA2 region were significantly inhibited by hypothermia and by apoptosis-inhibiting reagents. These results suggest that galectin-3 in the CA2 region is expressed independent of that in the CA1 region. Protection of the expression of galectin-3 in the CA2 region might contribute toward the survival of CA2 pyramidal neurons.


Assuntos
Região CA2 Hipocampal/patologia , Galectina 3/biossíntese , Ataque Isquêmico Transitório/patologia , Animais , Apoptose/efeitos dos fármacos , Região CA2 Hipocampal/efeitos dos fármacos , Região CA2 Hipocampal/metabolismo , Modelos Animais de Doenças , Gerbillinae , Hipotermia Induzida , Imuno-Histoquímica , Ataque Isquêmico Transitório/metabolismo , Masculino , Fármacos Neuroprotetores/farmacologia , Prosencéfalo/patologia
13.
Int J Mol Sci ; 17(1)2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26784179

RESUMO

The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-D-aspartate- and CoCl2-induced), autoimmune (experimental autoimmune encephalomyelitis), mechanical stress (optic nerve crush-induced, light-induced) and ischemia (transient retinal ischemia-induced). The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insight into the underlying mechanisms of the disease, and will facilitate the development of novel effective therapeutic drugs to treat retinal cell damage.


Assuntos
Degeneração Retiniana/patologia , Neurônios Retinianos/patologia , Animais , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/complicações , Encefalomielite Autoimune Experimental/patologia , Isquemia/complicações , Isquemia/patologia , Luz/efeitos adversos , Traumatismos do Nervo Óptico/complicações , Traumatismos do Nervo Óptico/patologia , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/etiologia , Neurônios Retinianos/efeitos dos fármacos , Neurônios Retinianos/efeitos da radiação
14.
Neurosci Lett ; 592: 107-12, 2015 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-25736950

RESUMO

Galectin-3 is a ß-galactosidase-binding lectin which is important in cell proliferation and apoptotic regulation. Encephalomyocarditis virus (EMCV), which includes the Enterovirus genus, can cause not only acute myocarditis but also neuronal degeneration of central nervous system in various animals including mice. The pathophysiological role of galectin-3 in central nervous system following acute viral infection is not fully understood. The goal of this study is to determine the localization and time-course of galectin-3 expression after acute viral inoculation with EMCV. Galectin-3 is up-regulated in degenerated lesions of brain area including cerebellum, hippocampus, thalamus and cerebral hemisphere, 96 h after EMCV inoculation. At the same time, Iba-1 positive microglia was morphologically activated within and around the focus of infection. Interestingly, in cerebellum, the microlesions containing a few galectin-3 cells were detected in the immediate-early phase of infection, as early as 48 h after EMCV inoculation. Thus, our results indicate that galectin-3 expression may be a key mediator between viral infection and neuronal degeneration in central nervous system including cerebellum. Furthermore, detection of galectin-3 might be an early diagnostic method for neuronal degeneration after virus infection.


Assuntos
Encéfalo/metabolismo , Infecções por Cardiovirus/metabolismo , Encefalite Viral/metabolismo , Vírus da Encefalomiocardite , Galectina 3/metabolismo , Animais , Encéfalo/patologia , Infecções por Cardiovirus/patologia , Cerebelo/metabolismo , Cerebelo/patologia , Encefalite Viral/patologia , Masculino , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Fatores de Tempo , Regulação para Cima
15.
Neurosci Lett ; 564: 120-5, 2014 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-24530381

RESUMO

Indoleamine 2,3-dioxygenase1 (IDO1) is the rate-limiting enzyme in the kynurenine pathway that converts l-tryptophan to l-kynurenine. Encephalomyocarditis virus (EMCV) can cause acute myocarditis in various animals including mice. Previously, IDO1 has been reported to have an important immunomodulatory function in immune-related diseases. However, the pathophysiological roles of IDO1 following acute viral infection of central nervous system are not fully understood. We observed that acute EMCV infection leads to a highly reproducible neuronal degeneration in mouse cerebellum. The goal of this study is to determine tissue/cell-specific and time-dependent expressions of IDO1 during acute EMCV infection in mouse cerebellum. IDO1 was up-regulated in microglia, which was recognized to be activated morphologically and positive for ionized calcium-binding adapter molecule 1 (Iba-1), a protein expressed in microglia, within EMCV-induced cerebellar lesions showing neuronal degeneration although the very weak expression of IDO1 is detected only in cytoplasm of Purkinje cells. No GFAP immunostaining was observed in EMCV-induced cerebellar lesions although many reactive astrocytes surrounding the lesions showed strongly positive immunostaining for GFAP 10 days after the viral inoculation. Thus, IDO1 expression may affect EMCV-induced neuronal degeneration in cerebellum.


Assuntos
Infecções por Cardiovirus/metabolismo , Cerebelo/enzimologia , Encefalite Viral/enzimologia , Vírus da Encefalomiocardite , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Microglia/enzimologia , Animais , Infecções por Cardiovirus/virologia , Encefalite Viral/virologia , Vírus da Encefalomiocardite/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regulação para Cima
16.
BMC Med Educ ; 13: 82, 2013 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-23742245

RESUMO

BACKGROUND: There has been considerable interest in Emotional Intelligence (EI) in undergraduate medical education, with respect to student selection and admissions, health and well-being and academic performance. EI is a significant component of the physician-patient relationship. The emotional well-being of the physician is, therefore, a significant component in patient care. The aim is to examine the measurement of TEIQue-SF in Asian medical students and to explore how the practice of listening to the feelings of others and expressing one's own feelings influences an individual's EI, set in the context of the emotional well-being of a medical practitioner. METHODS: A group of 183 international undergraduate medical students attended a half-day workshop (WS) about mental-health and well-being. They completed a self-reported measure of EI on three occasions, pre- and post-workshop, and a 1-year follow-up. RESULT: The reliability of TEIQue-SF was high and the reliabilities of its four factors were acceptable. There were strong correlations between the TEIQue-SF and personality traits. A paired t-test indicated significant positive changes after the WS for all students (n=181, p=.014), male students (n=78, p=.015) and non-Japanese students (n=112, p=.007), but a repeated measures analysis showed that one year post-workshop there were significant positive changes for all students (n=55, p=.034), female students (n=31, p=.007), especially Japanese female students (n=13, p=.023). Moreover, 80% of the students reported that they were more attentive listeners, and 60% agreed that they were more confident in dealing with emotional issues, both within themselves and in others, as a result of the workshop. CONCLUSION: This study found the measurement of TEIQue-SF is appropriate and reliable to use for Asian medical students. The mental health workshop was helpful to develop medical students' EI but showed different results for gender and nationality. The immediate impact on the emotional awareness of individuals was particularly significant for male students and the non-Japanese group. The impact over the long term was notable for the significant increase in EI for females and Japanese. Japanese female students were more conscious about emotionality. Emotion-driven communication exercises might strongly influence the development of students' EI over a year.


Assuntos
Inteligência Emocional , Emoções , Estudantes de Medicina/psicologia , Adolescente , Adulto , Ásia , Povo Asiático/psicologia , Comunicação , Educação , Educação de Graduação em Medicina/métodos , Feminino , Humanos , Japão , Masculino , Personalidade , Inventário de Personalidade , Projetos Piloto , Testes Psicológicos , Fatores Sexuais , Adulto Jovem
17.
Neurosci Lett ; 517(1): 47-51, 2012 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-22521582

RESUMO

Free radicals have been suggested to be involved in the genesis of ischemic brain damage, as shown by the protective effects of alpha-phenyl-N-tert-butyl nitrone (PBN), a spin trapping agent, in ischemic cerebral injury. However, the involvement of free radicals in transient ischemic-induced delayed neuronal death is not fully understood. To clarify this, in the present study, we evaluated the effect of PBN on delayed neuronal death and on the levels of free radicals in hippocampal CA1 region in the gerbil. The administration of PBN (10 mg/kg, i.v.) failed to show any preventive effect on the delayed neuronal death, examined by hematoxylin and eosin staining and the TUNEL method. Furthermore, we observed no free radical formation in delayed neuronal death, determined immunohistochemically using a specific 8-OHdG antibody, after transient ischemic insult. These results suggest that free radical formation may not contribute to the formation of delayed neuronal death.


Assuntos
Região CA1 Hipocampal/efeitos dos fármacos , Óxidos N-Cíclicos/farmacologia , Ataque Isquêmico Transitório/tratamento farmacológico , Animais , Região CA1 Hipocampal/patologia , Morte Celular/efeitos dos fármacos , Radicais Livres/metabolismo , Gerbillinae , Masculino , Traumatismo por Reperfusão/tratamento farmacológico
18.
Neurosci Lett ; 504(3): 199-203, 2011 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-21945545

RESUMO

The ischemic damage in the hippocampal CA1 region following transient forebrain ischemia, delayed neuronal death, is a typical apoptotic response, but the underlying mechanisms are not fully understood. We have reported that mild hyperthermia (38 °C) accelerates DNA fragmentation of the gerbil CA1 pyramidal neurons following transient forebrain ischemia. Recently, we reported that galectin-3, a ß-galactosidase-binding lectin, is spatio-temporally expressed only by activated microglial cells located within CA1 region following transient forebrain ischemia in gerbils. Furthermore, expression of galectin-3 and Iba-1 (a specific microglial cell marker) are strongly reduced by hypothermia during ischemic insult. To further elucidate the effect of hyperthermia on the expression of galectin-3 by micloglia in delayed neuronal death, we examined immunohistochemical expression of galectin-3 and Iba-1, in situ terminal dUTP-biotin nick end labeling of DNA fragmentation (for determination of cell death) and hematoxylin and eosin staining (for morphological observation). We observed that between 37 °C and 39 °C, there was a temperature-dependent enhancement of galectin-3 expression in microglial cells in the CA1 region following transient ischemia. Apoptotic DNA fragmentation, detected by TUNEL staining, was observed in CA1 region in normothermia. This TUNEL staining was enhanced by hyperthermia at 37.5 °C and 38 °C, but not at 39 °C. Ischemia-induced neuronal degeneration in CA1 region in gerbil hippocampus subjected to hyperthermia (37.5 °C, 38 °C and 39 °C) observed by HE staining is similar to that in normothermic gerbils. These findings imply that galectin-3 expression in microglia may influence the survival of CA1 pyramidal neurons in cases such as hyperthermia-related neuronal injury.


Assuntos
Região CA1 Hipocampal/patologia , Galectina 3/biossíntese , Hipertermia Induzida , Ataque Isquêmico Transitório/patologia , Microglia/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Neurônios/patologia , Animais , Apoptose , Região CA1 Hipocampal/irrigação sanguínea , Região CA1 Hipocampal/metabolismo , Estenose das Carótidas , Fragmentação do DNA , Galectina 3/genética , Gerbillinae , Marcação In Situ das Extremidades Cortadas , Ataque Isquêmico Transitório/metabolismo , Masculino , Proteínas do Tecido Nervoso/genética
19.
Brain Res ; 1382: 266-74, 2011 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-21262205

RESUMO

The ischemic damage in the hippocampal CA1 sector following transient ischemia, delayed neuronal death, is a typical apoptosis, but the mechanism underlying the delayed neuronal death is still far from fully understood. Galectin-3 is a ß-galactosidase-binding lectin which is important in cell proliferation and apoptotic regulation. Galectin-3 is expressed by microglial cells in experimental models of adult stroke. It has been reported that activated microglial cells are widely observed in the brain, including in the hippocampal CA1 region after transient ischemic insult. In the present study, time course expression of galectin-3 following transient forebrain ischemia in gerbils was examined by immunohistochemistry, combined with Iba-1 immunostaining (a specific microglial cell marker), hematoxylin and eosin staining (for morphological observation), and in situ terminal dUTP-biotin nick end labeling of DNA fragments method (for determination of cell death). Following transient ischemia, we observed a transient increase of galectin-3 expression in CA1 region, which was maximal 96h after reperfusion. Galectin-3 expression was predominately localized within CA1 region and observed only in cells which expressed Iba-1. The galectin-3-positive microglial cells emerge after the onset of neuronal cell damage. Expressions of galectin-3 and Iba-1 were strongly reduced by hypothermia during ischemic insult. Prevention of galectin-3 and Iba-1 expression in microglia by hypothermia has led us to propose that hypothermia either inhibits microglial activation or prevents delayed neuronal death itself. Our results indicate that galectin-3 might exert its effect by modulating the neuronal damage in delayed neuronal death.


Assuntos
Isquemia Encefálica/metabolismo , Região CA1 Hipocampal/metabolismo , Morte Celular/fisiologia , Galectina 3/antagonistas & inibidores , Galectina 3/genética , Hipotermia Induzida/métodos , Degeneração Neural/metabolismo , Animais , Temperatura Corporal/fisiologia , Isquemia Encefálica/patologia , Região CA1 Hipocampal/patologia , Temperatura Baixa , Modelos Animais de Doenças , Galectina 3/biossíntese , Gerbillinae , Hipotermia/metabolismo , Microglia/metabolismo , Microglia/patologia , Degeneração Neural/patologia , Degeneração Neural/terapia , Fatores de Tempo
20.
Neurosci Lett ; 477(3): 138-43, 2010 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-20434522

RESUMO

Transplanted embryonic stem (ES) cells can be integrated into the retinas of adult mice as well-differentiated neuroretinal cells. However, the transplanted ES cells also have a tumorigenic activity as they have the ability for multipotent differentiation to various types of tissues. In the present study, human ES (hES) cells were transplanted into adult nude mouse retinas by intravitreal injections 20 h after intravitreal N-methyl-D-aspartate (NMDA) administration. After the transplantation of hES cells, the folate antagonist, methotrexate (MTX) was administrated in order to control the differentiation of the transplanted hES cells. Neuronal differentiation and teratogenic potential of hES cells were examined immunohistochemically 5 weeks after transplantation. The proliferative activity of transplanted cells was determined by both the mitotic index and the Ki-67 proliferative index. Disappearance of Oct-4-positive hES cells showing undifferentiated morphology was observed after intraperitoneal MTX treatment daily, for 15 days. Decreased mitotic and Ki-67 proliferative indices, and increased neuronal differentiation were detected in the surviving hES cells after the MTX treatment. These results suggest two important effects of intraperitoneal MTX treatment for hES cells transplanted into nude mouse retina: (1) MTX treatment following transplantation induces neuronal differentiation, and (2) MTX decreases proliferative activity and tumorigenic potential.


Assuntos
Células-Tronco Embrionárias/efeitos dos fármacos , Antagonistas do Ácido Fólico/farmacologia , Metotrexato/farmacologia , Neurônios/efeitos dos fármacos , Retina/efeitos dos fármacos , Animais , Diferenciação Celular , Depressão Química , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Células-Tronco Embrionárias/transplante , Humanos , Antígeno Ki-67/metabolismo , Camundongos , Camundongos Nus , Mitose , Neuroglia/citologia , Neuroglia/efeitos dos fármacos , Neurônios/citologia , Neurônios/metabolismo , Fator 3 de Transcrição de Octâmero/metabolismo , Retina/patologia , Transplante de Células-Tronco/efeitos adversos , Teratoma/etiologia , Teratoma/patologia , Teratoma/prevenção & controle
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