RESUMO
Cardiomyocyte apoptosis plays key roles in the pathogenesis of heart diseases such as myocardial infarction. MicroRNAs are important regulators of gene expression, which are also involved in the regulation of cardiomyocyte apoptosis. However, cardiomyocyte apoptosis regulated by microRNA (miR)-122 is largely unexplored. The aim of this study focused on the role of miR-122 in cardiomyocyte apoptosis. Cardiomyocytes were isolated from neonatal mice and primarily cultured. MiR-122 mimic and inhibitor were transfected to cardiomyocytes and verified by qRT-PCR. Cell viability and apoptosis post-transfection were assessed by MTT assay and flow cytometry, respectively. Changes in expression of caspase-8 were quantified by qRT-PCR and western blot. Results showed that miR-122 mimic and inhibitor successfully induced changes in miR-122 levels in cultured cardiomyocytes (P<0.01). MiR-122 overexpression suppressed viability and promoted apoptosis of cardiomyocytes (P<0.05), and miR-122 knockdown promoted cell viability and inhibited apoptosis (P<0.05). The mRNA and protein levels of caspase-8 were elevated by miR-122 overexpression (P<0.01) and reduced by miR-122 knockdown (P<0.001). These results suggest an inductive role of miR-122 in cardiomyocyte apoptosis, which may be related to its regulation on caspase-8.
Assuntos
Apoptose/genética , Caspase 8/genética , Expressão Gênica/genética , MicroRNAs/genética , MicroRNAs/fisiologia , Miócitos Cardíacos/patologia , Animais , Animais Recém-Nascidos , Expressão Gênica/fisiologia , Camundongos , Camundongos Endogâmicos BALB CRESUMO
The primary aims of this study were to investigate mitochondrial metabolism during experimental allergic encephalomyelitis (EAE) animal model axonal injury and to determine the correlation among neurological function scores, pathological changes, and the activities of the BB isoenzyme of creatine kinase (CK-BB), catalase (CAT), and calpain in the brain tissues of EAE rats. Another goal was to preliminarily define the mechanism of mitochondrial metabolism resulting from the effect of beta 2 adrenergic agonists in the process of EAE animal model axonal damage. EAE was induced in specific pathogen free Wistar rats by guinea pig spinal cord homogenate, complete Freund's adjuvant, and pertussis vaccine. We recorded the behavioral change in EAE rats, detected pathological changes in central nervous tissue, and observed the changes of the CK-BB, CAT, and calpain in the EAE rat brain and spinal cord. The results indicated that the average neurologic function score increased in the EAE group compared to that of the controls (P < 0.01). In addition, CAT and CK-BB activities significantly decreased and the calpain activity significantly increased compared with those of the control group (P < 0.05). The decrease of the activity of central nervous CK-BB and CAT content, as well as the increase of calpain activity at the highest time point were considered to be the consequences of EAE. Furthermore, the results revealed that use of salbutamol could alleviate disease symptoms and reduce the recurrence of the EAE disease.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Axônios/efeitos dos fármacos , Encefalomielite Autoimune Experimental/tratamento farmacológico , Animais , Calpaína/metabolismo , Catalase/metabolismo , Encefalomielite Autoimune Experimental/metabolismo , Feminino , Cobaias , Ratos , Ratos WistarRESUMO
Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Apolipoproteína A-I/sangue , Apolipoproteínas/sangue , Transtorno Bipolar/sangue , Anidrase Carbônica I/sangue , Transtornos do Metabolismo dos Lipídeos/metabolismo , Lipoproteínas HDL/sangue , Proteômica , Transtorno Bipolar/complicações , Transtorno Bipolar/diagnóstico , Bases de Dados de Proteínas , Diagnóstico Diferencial , Progressão da Doença , Regulação para Baixo , Transtorno Depressivo Maior/diagnóstico , Eletroforese em Gel Bidimensional , Immunoblotting , Imunoprecipitação , Transtornos do Metabolismo dos Lipídeos/complicações , Espectrometria de Massas/métodosRESUMO
Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.
Assuntos
Apolipoproteína A-I/sangue , Apolipoproteínas/sangue , Transtorno Bipolar/sangue , Anidrase Carbônica I/sangue , Transtornos do Metabolismo dos Lipídeos/metabolismo , Lipoproteínas HDL/sangue , Proteômica , Adolescente , Adulto , Apolipoproteína L1 , Transtorno Bipolar/complicações , Transtorno Bipolar/diagnóstico , Bases de Dados de Proteínas , Transtorno Depressivo Maior/diagnóstico , Diagnóstico Diferencial , Progressão da Doença , Regulação para Baixo , Eletroforese em Gel Bidimensional , Feminino , Humanos , Immunoblotting , Imunoprecipitação , Transtornos do Metabolismo dos Lipídeos/complicações , Masculino , Espectrometria de Massas/métodos , Adulto JovemRESUMO
Distal radius fracture is a common wound. It is reduced by surgery under anesthesia. Emergence agitation can often occur after anesthesia. It is associated with increased morbidity and hospital costs. However, there have been almost no reports in the medical literature on the occurrence of emergence agitation in adults. This study aimed to compare emergence agitation between isoflurane and propofol anesthesia in adults after closed reduction of distal radius fracture. Forty adults (ASA I-II) undergoing closed reduction of distal radius fracture were randomly assigned to either the isoflurane or propofol group and anesthesia was maintained with isoflurane or propofol. The bispectral index was monitored and maintained within 40-60. After reduction of fracture and fixation with plaster, patients were transported to the post-anesthetic care unit (PACU) and agitation state scale was checked by Aono's four-point scale (AFPS). AFPS score of 3 or 4 was considered to be emergence agitation. Pain scores were measured by the numeric rating scale (NRS) on arrival and at peak value at PACU. Eight (40.0%) patients in the isoflurane group and 2 (10.0%) patients in the propofol group developed emergence agitation (P = 0.031). There was no correlation between peak NRS and AFPS. Propofol may decrease the incidence of emergence agitation compared to isoflurane in adults undergoing closed reduction of distal radius fracture.
Assuntos
Anestesia , Isoflurano/farmacologia , Propofol/farmacologia , Agitação Psicomotora/complicações , Fraturas do Rádio/complicações , Fraturas do Rádio/cirurgia , Adulto , Idoso , Demografia , Feminino , Humanos , Isoflurano/efeitos adversos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/etiologia , Propofol/efeitos adversosRESUMO
Because of their specific binding to carbohydrates, lectins play a crucial role in pathogen recognition and clearance in vertebrate animals. Previously, only two types of collectins had been isolated from bony fish: mannan-binding lectin (MBL) and galactose-binding lectin (GalBL). We sequenced a novel collectin (designated EALec1) from the red-spotted grouper, Epinephelus akaara. The gene structure of EALec1 and the alignment of the carbohydrate recognition domain of the three collectins demonstrated that EALec1 is a new type of collectin derived from MBL. We examined the expression pattern of the EALec1 transcripts in 12 tissues of the red-spotted grouper. The EALec1 gene was found to have multiple copies; their transcripts were detected in all 12 tissues. EALec1 was also recombined and expressed in Escherichia coli to investigate its immune functions and carbohydrate-binding characterization. We concluded that EALec1 belongs to the mannan-binding lectin group, despite its different Ca²âº-dependent sites in the carbohydrate recognition domain, and that it is involved in the recognition and clearance of invaders in the red-spotted grouper.