RESUMEN
The protective effect and the mechanism of estrogen receptor ß (ERß) on myocardial infarction (MI) in mice were explored. A total of 12 female Tg-ERß transgenic mice and 12 non-transgenic littermate control (NLC) wild-type C57 mice were used for the present study. Both transgenic and wild-type mice had similar baseline data such as age, sex, and weight. The mouse model of MI was established by coronary artery ligation method, and the cardiac structure and function changes of the mouse were observed by ultrasonic echocardiography on days 1, 3 and 7 after the operation. RT-PCR method was used to detect the expression of collagen I, α-SMA, TGF-ß mRNA in the mouse heart, and Masson staining was used to detect cardiac fibrosis. At 3 days after operation, echocardiographic posterior wall thickness at end diastole (PWTD) and end systolic PWTS of Tg-ERß mice were significantly reduced, and left ventricular systolic diameter and left ventricular diastolic diameter significantly increased (P<0.05) compared with NLC mice. The levels of expression of Tg-ERß cardiac tissue collagen I, α-SMA, TGF-ß mRNA were significantly lower than those in the NLC mice (P<0.05). In conclusion, Tg-ERß exerts a protective effect on MI.
RESUMEN
Viral myocarditis (VM), a severe clinical condition characterized by cardiac inflammation, is most frequently induced as a result of coxsackievirus infection. Evidence suggests that microRNAs may have significant roles in the progression of cardiac injury during coxsackievirus infection. Concurrently, microRNA (miR)-214 was found to be upregulated in the plasma and myocardial cells during this process. In the present study, eight candidate miRNAs, the functions of which are associated with myocarditis, were selected and their expression levels were evaluated by reverse transcription-quantitative polymerase chain reaction. miR-146b and miR-214 were found to have significantly upregulated expression levels in the heart tissues of patients with VM compared with those of the control subjects. Predictions via the use of online bioinformatics tools and confirmed by dual-luciferase assay and western blot analysis, revealed that ITCH, an NF-κB signaling suppressor, was a target gene of miR-214. To investigate the biological function of miR-214, tumor necrosis factor-α and interleukin-6 expression levels were evaluated in HeLa cell culture supernatant. The results revealed that miR-214 overexpression enhanced the expression of the two cytokines. In addition, the function of miR-214 was partially rescued by ITCH overexpression. Subsequently, concurrent results were obtained following experiments in murine cardiac myocytes. In conclusion, the results of the present study demonstrated that miR-214 contributed to the adverse inflammatory response to viral infection of the heart during coxsackievirus infection and is therefore a potential therapeutic target for the treatment of viral myocarditis.
Asunto(s)
Infecciones por Coxsackievirus/genética , Infecciones por Coxsackievirus/patología , MicroARNs/genética , Miocarditis/genética , Miocarditis/patología , Proteínas Represoras/genética , Ubiquitina-Proteína Ligasas/genética , Animales , Animales Recién Nacidos , Secuencia de Bases , Infecciones por Coxsackievirus/metabolismo , Infecciones por Coxsackievirus/virología , Enterovirus Humano B/patogenicidad , Enterovirus Humano B/fisiología , Regulación de la Expresión Génica , Genes Reporteros , Células HeLa , Interacciones Huésped-Patógeno , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Luciferasas/genética , Luciferasas/metabolismo , Ratones , Ratones Endogámicos BALB C , MicroARNs/metabolismo , Datos de Secuencia Molecular , Miocarditis/metabolismo , Miocarditis/virología , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Miocitos Cardíacos/virología , Cultivo Primario de Células , Proteínas Represoras/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
OBJECTIVES: To evaluate the clinical significance of HMGB1 expression in T-cell lymphoma. METHODS: Immunohistochemical staining for HMGB1 and survivin was performed with specimens from 120 cases of T-cell lymphoma and 40 cases of reactive lymphoid hyperplasia with antibodies against human HMGB1 and survivin. RESULTS: The expression of HMGB1 and survivin was significantly higher in tissues of T-cell lymphoma than in reactive lymphoid hyperplasia. Positive expression of HMGB1 and survivin was observed in 63.7% (65/102) and 61.8% (63/102) of T-cell lymphoma cases, respectively. While was associated with gender, age, and tumor location, significant correlations with malignancy and clinical stage were observed. Spearman rank correlation analysis revealed that the expression of HMGB1 and survivin was positively correlated in T-cell lymphomas (P<0.01). CONCLUSIONS: Expression of HMGB1 and survivin in T-cell lymphomas is significantly associated with malignancy and clinical stage, but not with gender, age and tumor location. Elevated expression of HMGB1 may be an important biomarker for the development and progression of T-cell lymphoma.
