RESUMO
Interferon regulatory factor 3 (IRF3) is a member of IRF family which plays a significant role in the innate immune response, apoptosis, and oncogenesis. Mounting evidence has demonstrated that IRF3 was involved in central nervous system disease such as cerebral ischemic injury through promoting neuronal apoptosis. However, it remains unclear about the underlying mechanisms of IRF3 upon neuronal apoptosis following intracerebral hemorrhage (ICH). In the present study, we established an adult rat ICH model by injecting autologous whole blood into the right basal ganglia and evaluated their neurological deficits by behavioral tests. IRF3 protein level was up-regulated adjacent to the hematoma following ICH when compared with the sham brain cortex by western blot and immunohistochemistry. Immunofluorescent staining indicated IRF3 was mainly localized in neurons, a few in astrocytes. In addition, we also detected that IRF3 co-localized with active caspase-3 which is a neuronal apoptosis marker. Furthermore, in vitro study, knocking down IRF3 by using IRF3 interference in primary cortical neurons reduced the expression of active caspase-3 and Bax while increased Bcl-2. In conclusion, we speculated that IRF3 might exert pro-apoptotic function in neurons after ICH.
Assuntos
Apoptose/fisiologia , Astrócitos/metabolismo , Hemorragia Cerebral/metabolismo , Fator Regulador 3 de Interferon/metabolismo , Neurônios/metabolismo , Animais , Caspase 3/metabolismo , Técnicas de Silenciamento de Genes/métodos , Masculino , Ratos , Ratos Sprague-Dawley , Ativação Transcricional/fisiologia , Regulação para CimaRESUMO
BACKGROUND AND AIMS: Use the MDRD (Modification of Diet in Renal Disease) and 2021 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation void of race coefficients (CKD-EPICrea, CKD-EPICys-C, and CKD-EPICrea+Cys-C) to estimate the BV (Biological variation) of eGFR (estimated glomerular filtration rate) within 24 h in a healthy population to help explain future studies using eGFR in the context of a known BV. METHODS: Blood samples were collected from 30 healthy subjects at six time points within 24 h. Serum creatinine (S-Crea) and serum cystatin C (S-Cys-C) were measured, and the BV of eGFR was calculated. Outlier and variance homogeneity analyses were performed, followed by CV-ANOVA on trend-corrected data. RESULTS: The eGFR CVI for the four equations (MDRD, CKD-EPICrea, CKD-EPICys-C, and CKD-EPICrea+Cys-C) were 8.39% (7.50-9.51%), 3.90% (3.49-4.42%), 6.58% (5.88-7.46%), and 5.03% (4.50-5.71%), respectively. The corresponding II and RCVpos/neg values were 0.69, 0.48, 0.51, and 0.31, and (29.30%, - 22.66%), (12.69%, - 11.2 6%), (20.97%, - 17.33%), and (15.88%, - 13.70%), respectively; RCVpos /neg of eGFR was highest in the MDRD equation and lowest in the CKD-EPI Crea equation. Additionally, the RCVpos/neg values of the individual was highest in the MDRD equation and lowest in the CKD-EPICrea+Cys-C equation; they are (56.51%, - 36.11%) and (5.01%, - 4.77%), respectively. CONCLUSIONS: We present data on the 24 h BV eGFR of the 2021 CKD-EPI equations. The presence of BV has impact on the interpretation of GFR results, affecting CKD disease grading. The RCVpos/neg differences were large among the individuals. When using eGFRs based on the MDRD and CKD-EPI equations, it is necessary to combine RCVpos/neg values before interpreting the results.
Assuntos
Creatinina , Cistatina C , Taxa de Filtração Glomerular , Insuficiência Renal Crônica , Humanos , Taxa de Filtração Glomerular/fisiologia , Masculino , Feminino , Cistatina C/sangue , Adulto , Creatinina/sangue , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/sangue , Voluntários Saudáveis , Adulto Jovem , IdosoRESUMO
The present study aimed to detect the expression of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and microRNA (miR)-619-5p in colorectal carcinoma (CRC), and to evaluate the significance of MALAT1 and miR-619-5p expression in the clinical diagnosis and prognosis of CRC. Quantitative polymerase chain reaction was used to detect MALAT1 and miR-619-5p expression in 120 colorectal carcinoma and 120 adjacent normal tissue samples. The expression levels of MALAT1 and miR-619-5p were significantly different between colorectal carcinoma and adjacent normal tissues (P<0.05). MALAT1 exhibited an average 2.52-fold increase in colorectal adenoma when compared with adjacent normal tissues, while miR-619-5p exhibited an average 5.79-fold decrease in colorectal adenoma when compared with adjacent normal tissues. There was a significant difference between the MALAT1 expression in CRC tissues obtained from men and women (P=0.027), and in tumor-node-metastasis (TNM) stage II and stage III lesions (P=0.019). MALAT1 expression was associated with lymphovascular invasion (P=0.047) and perineural invasion (P=0.012). In addition, miR-619-5p expression was also significantly different between men and women (P=0.032), and between TNM stage II and stage III lesions (P=0.012). miR-619-5p expression was also associated with lymphovascular invasion (P=0.023) and perineural invasion (P=0.009). Patients with high expression of MALAT1 and low expression of miR-619-5p demonstrated significantly shorter disease-free survival (DFS) (P=0.002) and overall survival (OS) times (P=0.004) compared with patients with low MALAT1 expression and high miR-619-5p expression. Patients with perineural invasion demonstrated significantly shorter DFS (P=0.001) and OS times (P=0.003) compared with patients without perineural invasion. In addition, there was a negative correlation between MALAT1 expression and miR-619-5p expression (r=-0.415, P=0.004) in CRC tissues. In conclusion, MALAT1 and miR-619-5p have potential for the molecular diagnosis of CRC patients, and combined assaying of MALAT1 and miR-619-5p may improve the accuracy of the diagnosis of CRC and act as a good prognostic indicator in CRC patients.
RESUMO
Apoptosis-linked-gene-2-interacting protein 1 (Alix) is involved in the endosome-lysosome system in the cytoplasm. The normal function of Alix may be altered by ALG-2 toward a destructive role during active cell death. Alix also may play a role in regulation of cell proliferation. However, the role of Alix in human glioma has not been elucidated yet. This study intended to clarify the relationship between Alix and glioma pathologic grades and its role in the proliferation of glioma cells. Our findings showed that Alix protein concentrations were significantly elevated in high-grade glioma tissue compared with low-grade glioma (P < .0001). Immunohistochemical study revealed that Alix was overexpressed in 75 resected glioma tissues and may forecast poor survival. Alix expression was increased in resting serum-stimulated glioma cells. Additionally, we reduced Alix expression in U251MG cells and then found that cell viability was decreased significantly when p21 expression increased. Colony formation assay and flow cytometry analysis demonstrated that reduced Alix expression may lead to growth inhibition and cell cycle arrest. In summary, our findings suggest that Alix plays an important role in the proliferation of glioma cells and may be a novel therapeutic target.
Assuntos
Neoplasias Encefálicas/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Glioma/metabolismo , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Proteínas de Ligação ao Cálcio/genética , Ciclo Celular , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/mortalidade , Glioma/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Interferência de RNA , Transdução de Sinais , Fatores de Tempo , TransfecçãoRESUMO
RBQ3, also known as RBBP5 (RB-binding protein 5), was an RB-binding protein. Besides, it was one of core components of MLL1 (mixed lineage leukemia 1), which were required for H3K4 methyltransferase activity. MLL1 dysfunction was found to be associated with the progression of some cancers such as acute leukemias. However, the precise role of RBQ3 in tumor progression remains obscure. In this study, we explored the expression and clinical role of RBQ3 in gliomas. Our results showed that RBQ3 was significantly upregulated in clinical glioma specimens by Western blot and immunohistochemistry. Moreover, its level was significantly associated with the pathology grades. High RBQ3 expression was suggested to be an independent prognostic factor for glioma patients' survival by univariate and multivariate analyses. Serum starvation and refeeding assay indicated that the expression of RBQ3 increased 8h after serum-stimulation, together with percentage of cells at S phase. In addition, knockdown of RBQ inhibited U87-MG cell proliferation with CCK8 kit, flow cytometry assays and colony formation analyses; while the depletion of RBQ3 induced the apoptosis of U87-MG cells. All the findings suggested that RBQ3 might play an important role in glioma, and RBQ3 inhibitors might be novel anti-tumor agents.
Assuntos
Neoplasias Encefálicas/patologia , Encéfalo/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Glioma/patologia , Proteínas Nucleares/metabolismo , Adulto , Apoptose/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Distribuição de Qui-Quadrado , Ensaio de Unidades Formadoras de Colônias , Meios de Cultura Livres de Soro/farmacologia , Proteínas de Ligação a DNA , Feminino , Glioma/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Sincalida/metabolismo , TransfecçãoRESUMO
Proteasomes are major intracellular extralysosomal organelle for protein degradation and a central source of antigenic peptides in the endogenous pathway. Proteasome beta-4 subunit (PSMB4) was recently identified as potential cancer driver genes in several tumors. However, information regarding its regulation and possible function in the central nervous system is still limited. The present study was designed to elucidate dynamic changes in PSMB4 expression and distribution in the cerebral cortex in a lipopolysaccharide (LPS)-induced neuroinflammation rat model. It was found that PSMB4 expression was increased significantly in apoptotic neurons in the brain cortex after LPS injection. Moreover, there was a concomitant up-regulation of active caspase-3, cyclin D1, and CDK4 in vivo and vitro studies. In addition, these three proteins in cortical primary neurons were decreased after knocking down PSMB4 by siRNA. Collectively, these results suggested that PSMB4 may be involved in neuronal apoptosis in neuroinflammation after LPS injection.
Assuntos
Apoptose/genética , Regulação da Expressão Gênica , Inflamação/genética , Neurônios/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , Animais , Encéfalo/metabolismo , Imuno-Histoquímica , Inflamação/imunologia , Lipopolissacarídeos/imunologia , Masculino , Fenótipo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ratos , Regulação para CimaRESUMO
The prognosis of glioma patients is generally poor, so it is urgent to find out the underlying molecular mechanisms. PFTK1 is a member of cyclin-dependent kinases (Cdks) family and has been reported to contribute to tumor migration and invasion. In this study, we aimed to explore the expression and function in human glioma. Western blot and immunohistochemistry were used to evaluate the expression of PFTK1. PFTK1 expression was higher in glioma tissues compared with normal brain tissues, and its level was associated with the WHO grade in Western blot analysis. The suppression of PFTK1 expression by RNA interference was shown to inhibit the migration of glioma cells. Knockdown of PFTK1 increases E-cadherin expression and decreases vimentin expression. These data show that PFTK1 may participate in the pathogenic process of glioma, suggesting that PFTK1 can become a potential therapeutic strategy for gastric cancer.