RESUMO
OBJECTIVES: Although studies have reported that miR-596 extensively participates in multiple cancer progression, the biological mechanisms and effects of miR-596 in prostatic cancer remain unclear. The literature is aimed to reveal the function and possible molecular mechanisms of miR-596 in prostatic cancer carcinogenesis. MATERIALS AND METHODS: qRT-PCR was applied to examine miR-596 expression in prostatic cancer cell lines and samples, also methylation-specific PCR was used to detect the methylation status of the promoter CpG islands in prostatic cancer samples. Meanwhile, the tumor-related effects of miR-596 were detected via cell viability, clone formation assay, migration assay, flow cytometric and AO/EB assay. qRT-PCR and Western blots were applied to investigate the function of miR-596 on malignant behavior in prostatic cancer cells. RESULTS: We found that miR-596 mRNA was decreased in prostatic cancer samples and cell lines. miR-596 mRNA level was also correlated to cancer stage, Gleason scores, while miR-596 promoter methylation was related to cancer tumor stage, Gleason score and preoperative PSA levels. miR-596 inhibited the cell growth and activity by causing cell apoptosis, and also suppressed the migration of prostatic cancer cells by revealing the epithelial-mesenchymal transition process. In addition, Western blot indicates that miR-596 overexpression deregulated Wnt/ß-catenin signaling, by restraining phosphorylation levels of ß-catenin and expression levels of downstream targets. CONCLUSIONS: In summary, this research indicates that miR-596 overexpression could be potentially useful in the cell growth and migration of prostatic cancer and serves as a potential molecular marker in prostatic cancer.
Assuntos
Movimento Celular/genética , Proliferação de Células/genética , Epigênese Genética/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Humanos , Masculino , MicroRNAs , Pessoa de Meia-Idade , Células Tumorais CultivadasRESUMO
PURPOSE: Glioblastoma multiforme (GBM) represents the most common and the most malignant type of brain tumor. Cell division cycle 6 (CDC6), a gene associated with DNA replication initiation, has been proven to be associated with the prognosis of multiple tumors. In this study, we aim to explore the association between CDC6 expression and GBM carcinogenesis and prognosis. METHODS: CDC6 expression in normal cells and GBM cells was explored by analyzing TCGA dataset, as well as by RT-PCR and western blot methods. Survival analysis was performed by the Kaplan-Meier method. Multivariate Cox-regression analysis was adopted to estimate the independence of CDC6 as a GBM prognostic factor. RESULTS AND CONCLUSIONS: Elevated CDC6 levels in GBM tumor tissues compared with those in normal brain tissues were illustrated by analyzing the gene expression profiles from TCGA dataset, and confirmed by RT-PCR and western blot assays in GBM tumor and normal human astrocyte cell lines. Kaplan-Meier analysis indicated the negative influence of high CDC6 expression on GBM overall survival (OS) probability and days to progression (D2P) after initial treatment, but not on days to recurrence (D2R) after initial treatment. Multivariate Cox regression analysis showed CDC6 as an independent signature marker gene for GBM prognosis. In addition, the combination of CDC6 mRNA expression and CpG island methylator phenotype (CIMP) could sensitively predict 3-year OS and D2P. In conclusion, our study uncovered the role of CDC6 in GBM carcinogenesis and prognosis for the first time, which could shed new light on GBM diagnosis and treatment.
Assuntos
Neoplasias Encefálicas/genética , Proteínas de Ciclo Celular/genética , Glioblastoma/genética , Proteínas Nucleares/genética , Western Blotting , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Ilhas de CpG/genética , Bases de Dados Genéticas , Feminino , Expressão Gênica , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sobrevida , Transcriptoma , Regulação para CimaRESUMO
Cerebroprotein hydrolysate is an extract from porcine brain tissue that acts on the central nervous system in various ways to protect neurons and improve memory, attention, and vigilance. This study examined the effect and mechanism of cerebroprotein hydrolysate on learning and memory in mice with scopolamine-induced impairment. Mice were given an intraperitoneal injection of scopolamine hydrobromide to establish a murine model of learning and memory impairment. After 35 successive days of cerebroprotein hydrolysate treatment, their behaviors were observed in the Morris water maze and step-down test. Superoxide dismutase (SOD), Na(+)-K(+)-ATPase, and acetylcholinesterase (AChE) activity, and malondialdehyde (MDA), γ-aminobutyric acid (GABA), and glutamic acid (Glu) levels in the brain tissue of the mice were determined, and pathological changes in the hippocampus were examined. The results of the water-maze test showed that cerebroprotein hydrolysate shortened the escape latency and increased the number of platform crossings. In the step-down test, cerebroprotein hydrolysate treatment prolonged the step-down latency and reduced the number of errors; cerebroprotein hydrolysate increased the activity of SOD, Na(+)-K(+)-ATPase, and AChE, reduced the levels of MDA, decreased the Glu/GABA ratio in brain tissue, and reduced pathological changes in the hippocampus. The results indicate that cerebroprotein hydrolysate can improve learning and memory in mice with scopolamine-induced impairment. This effect may be associated with its ability to reduce injury caused by free radicals, improve acetylcholine function, and modulate the Glu/GABA learning and memory regulation system, reducing excitotoxicity caused by Glu.
Assuntos
Aminoácidos/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Hipocampo/metabolismo , Masculino , Malondialdeído/metabolismo , Transtornos da Memória/tratamento farmacológico , Camundongos , Camundongos Endogâmicos ICR , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Superóxido Dismutase/metabolismo , SuínosRESUMO
Numerous epidemiological investigations have evaluated the association between adiponectin gene T45G polymorphism and risk of nonalcoholic fatty liver disease (NAFLD). However, the results of these studies have proven to be inconsistent. Therefore, we conducted a meta-analysis to obtain a more accurate estimation of this association. Published articles were retrieved from PubMed and Web of Science databases and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effect models. Five case-control studies incorporating 597 cases and 701 controls were included in this meta-analysis. No association between adiponectin gene T45G polymorphism and NAFLD was established (TT vs GG: OR = 0.83, 95%CI = 0.37-1.86; TG vs GG: OR = 0.76, 95%CI = 0.33-1.79; dominant model: OR = 0.83, 95%CI = 0.37-1.84; recessive model: OR = 1.10, 95%CI = 0.69-1.76). Moreover, in a subgroup analysis, no significant correlation was found among Asian subjects. In conclusion, the T45G polymorphism of the adiponectin gene may not constitute an NAFLD risk factor. However, this needs to be further validated in single large well-designed future studies.
Assuntos
Adiponectina/genética , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo de Nucleotídeo Único , Povo Asiático , Estudos de Casos e Controles , Expressão Gênica , Genótipo , Humanos , Modelos Genéticos , Hepatopatia Gordurosa não Alcoólica/etnologia , Hepatopatia Gordurosa não Alcoólica/patologia , Razão de Chances , Fatores de Risco , População BrancaRESUMO
We investigated the effect of high phosphorus content on the sodium-phosphate cotransporter (NaPi-IIa and NaPi-IIl). Forty-eight Sprague-Dawley rats were divided into 3 groups: high-phosphorus group (HP) with fructose diphosphate sodium injection; self-manufactured low-phosphorus diet group (LP); and normal diet group (NP). At the 1st, 2nd, 4th, and 6th weeks, 4 rats from each group were sacrificed for detecting serum levels of calcium, phosphorus, and intact parathyroid hormone. Semi-quantitative retrovirus-polymerase chain reaction was used to detect the expression of NaPi-IIa and NaPi-III mRNA in kidney. At the 1st, 2nd, 4th, and 6th weeks, serum phosphorus and parathyroid hormone levels in HP group were significantly higher than those in LP and NP groups (P < 0.05). Serum calcium levels in the 3 groups showed no difference (P > 0.05). Comparing the expression of NaPi-IIa mRNA in HP group with LP and NP groups, NaPi-IIa mRNA expression was significantly reduced in HP group (P < 0.05), while NaPi-IIa mRNA expression in LP group began increasing at the 4th week (P < 0.05). At the 1st, 2nd, and 4th weeks, the expression of NaPi-III mRNA in HP, LP, and NP groups showed no clear differences (P > 0.05), while at the 6th week in HP group, NaPi-III mRNA expression was slightly increased compared to in LP and NP groups (P < 0.05). Hyperphosphatemia significantly affected NaPi-IIa and NaPi-III mRNA expression, and a factor promote an increase in intact parathyroid hormone independently of calcium.
Assuntos
Hiperfosfatemia/genética , Rim/metabolismo , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/genética , Animais , Cálcio/sangue , Regulação da Expressão Gênica , Hiperfosfatemia/metabolismo , Rim/efeitos dos fármacos , Hormônio Paratireóideo/sangue , Fosfatos/administração & dosagem , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/metabolismo , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/metabolismoRESUMO
We investigated serum visceral adipose tissue-derived serpin (vaspin) levels in patients with normal glucose regulation and recently diagnosed type 2 diabetes (T2DM) and explored the association between vaspin and body mass index, age, gender, glucose, lipid metabolism, and insulin sensitivity. Fasting serum vaspin levels in 66 patients with T2DM and 48 normal subjects were detected using enzyme-linked immunosorbent assay. We found that serum vaspin levels in the DM group were 0.65 ± 0.13 mg/L in non-obese patients and 1.13 ± 0.25 mg/L in obese patients. Serum vaspin levels in the control group were 0.38 ± 0.18 mg/L in non-obese patients and 0.95 ± 0.11 mg/L in obese patients. Average serum vaspin levels were significantly higher in obese patients than in non-obese patients in both the DM group and control group. In the DM group, the serum vaspin level was 0.76 ± 0.22 mg/L in males and 0.92 ± 0.35 mg/L in females. In the control group, the serum vaspin level was 0.48 ± 0.14 mg/L in males and 1.05 ± 0.21 mg/L in females. Association analysis showed that serum vaspin levels were significantly associated with body mass index, waist-to-rip ratio (WHR), fat percentage, triglyceride, fasting plasma insulin, and insulin sensitivity index. Stepwise multiple regression analysis showed that gender, insulin sensitivity index, and WHR were the most significant independent factors affecting vaspin. Therefore, serum vaspin levels were significantly elevated in obese people and were independently associated with WHR, gender, and index sensitivity index.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Serpinas/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Caracteres SexuaisRESUMO
We established a rat model of hyperphosphatemia and investigated the systemic effects of high phosphorus (P). Sprague Dawley rats were randomly divided into high (HP), low (LP), and normal (NP) P groups (N = 12 each), which received injections of fructose diphosphate sodium, or were fed self-manufactured low phosphorus or normal diets, respectively. In each group, 4 rats were sacrificed at the first, third, and sixth week to detect the serum (Scr) and urinary creatinine and P, and calcium (Ca) levels. The HP group's serum P and intact parathyroid hormone (iPTH) were significantly higher than those in the other groups at the first, third, and sixth weeks, (P < 0.05); the LP group's serum P was lower than the NP group's at the third week (P < 0.05), while at the sixth week, the serum P and iPTH were lower (P < 0.05). No significant differences were detected for blood Ca+ (P > 0.05). The HP group's Scr increased (P < 0.01), whereas the fractional excretion decreased (P < 0.05) significantly. Thighbone and lumbar spine bone densities differed significantly between groups in the third week (P < 0.05); LP group densities were lower than NP group measures (P < 0.05). Crystallized stones were not observed microscopically following hematoxylin and eosin staining of the kidney. We successfully established a hyperphosphatemia rat model, and high blood P was found to significantly influence renal function and bone density. These results might provide a foundation to study the effects of hyperphosphatemia in rats.
Assuntos
Modelos Animais de Doenças , Hiperfosfatemia/sangue , Animais , Densidade Óssea , Fosfatos de Cálcio/sangue , Creatinina/sangue , Fêmur/diagnóstico por imagem , Fêmur/metabolismo , Fêmur/patologia , Hiperfosfatemia/diagnóstico por imagem , Rim/patologia , Hormônio Paratireóideo/sangue , Radiografia , Ratos Sprague-DawleyRESUMO
We investigated the expression and clinical value of the soluble major histocompatibility complex class I-related chain A (sMICA) molecule in the serum of patients with renal tumors. Sixty patients diagnosed with renal tumors were enrolled in the experimental group, whereas 20 healthy volunteers served as the control group. The sMICA levels were measured via enzyme-linked immunosorbent assay, and the results were analyzed in combination with data from pathol-ogy examination. The experimental group had a statistically significant higher sMICA level (P < 0.05) than the control group. The sMICA level was higher in patients with malignant tumors than in those with be-nign tumors. We also observed a positive relationship among different tumor-node-metastasis (TNM) pathological stages with more advanced diseases exhibiting higher sMICA levels. As a tumor-associated antigen, MICA has a close relationship with renal tumorigenesis and immune es-cape. Our results indicated that sMICA levels were related to tumor pathol-ogy, TNM stage, and metastasis. Therefore, sMICA might be a potential marker for tumor characteristics, prognosis, and recurrence prediction.
Assuntos
Biomarcadores Tumorais/genética , Antígenos de Histocompatibilidade Classe I/genética , Neoplasias Renais/genética , Recidiva Local de Neoplasia/genética , Neoplasias/genética , Idoso , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Feminino , Expressão Gênica , Antígenos de Histocompatibilidade Classe I/sangue , Humanos , Neoplasias Renais/sangue , Neoplasias Renais/diagnóstico , Neoplasias Renais/imunologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/imunologia , Estadiamento de Neoplasias , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/imunologia , Solubilidade , Evasão Tumoral/genéticaRESUMO
The aim of this study was to detect the serum adipose triglyceride lipase (ATGL) levels in obesity and newly diagnosed type 2 diabetes patients, and to explore the association between ATGL with glucose and lipid metabolism. We enrolled 66 patients with type 2 diabetes and 48 patients with normal glucose regulation, who were divided into an overweight or obese subgroup and a normal weight subgroup according to body mass index (BMI) ≥ 25 kg/m(2). The enzyme-linked immunosorbent assay was used to detect fasting blood glucose, blood lipids, fasting insulin, and ATGL levels. The serum ATGL level in the overweight or obese group was lower than that in the non-obese group including patients with type 2 diabetes and normal glucose regulation: 239 ± 61 vs 355 ± 54 mg/L and 242 ± 60 vs 383 ± 58 mg/L, respectively (t = 22.53, t = 8.23, P < 0.05). The Pearson correlation analysis showed that fasting serum ATGL was negatively correlated with body fat content, BMI, waist-to-hip ratio, triglycerides, and the homeostatic model assessment-insulin resistance level (r = -0.271, r = -0.238, r = -0.375, r = -0.313, and r = -0.164, respectively, P < 0.05). The stepwise regression analysis showed that the waist-to-hip ratio and body fat content were independently associated with the serum ATGL level. Our results indicated that the ATGL level may be closely related to obesity.
Assuntos
Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Lipase/sangue , Obesidade/sangue , Tecido Adiposo/metabolismo , Adulto , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/enzimologia , Ensaio de Imunoadsorção Enzimática , Jejum/sangue , Feminino , Humanos , Insulina/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/enzimologiaRESUMO
To investigate the chemerin level in the Chinese Han population with metabolic syndrome and its relationship with each metabolic syndrome component [body mass index (BMI), blood pressure, blood lipids, and blood glucose], we selected 30 patients with metabolic syndrome and 30 healthy control subjects. The chemerin level was measured by enzyme immunoassay in these 2 groups. The subjects' weight, blood pressure, BMI, waist circumference, fasting blood glucose, fasting insulin, lipids, and glycated hemoglobin were simultaneously detected. The t-test, correlation analysis, and multiple regression analysis were used to perform statistical analysis. We found that plasma chemerin level was higher in the metabolic syndrome group than that in the control group (97.61 ± 6.49 vs 70.26 ± 6.97, t = 15.73, P < 0.05). The plasma chemerin level was positively correlated with systolic blood pressure, waist circumference, BMI, waist-to-hip ratio, fasting blood glucose, fasting insulin, and glycated hemoglobin (r = 0.548, 0.442, 0.359, 0.556, 0.613, 0.581, and 0.572, respectively; all P < 0.05). However, it was negatively correlated with high-density lipoprotein cholesterol (r = -0.378, P < 0.05). Therefore, we concluded that plasma chemerin level was correlated with obesity, blood pressure, and high-density lipoprotein cholesterol, suggesting that it may play a role in the pathogenesis of metabolic syndrome.