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Neuroendocrinology ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34847556


Background Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder characterized by high androgen levels. The aim of this study was to evaluate the effects of hyperandrogenism on the hypothalamus, and subsequently on the food intake and obesity in females. Methods A dihydroxy testosterone (DHT)-induced rat model was established to recapitulate the hyperandrogenism features of PCOS patients. Body weight and food intake of the rats were recorded. The food intake of DHT-induced rats was restricted by pair feeding to exclude possible effects of weight gain on the hypothalamus. The expression levels of relevant proteins and mRNAs in the hypothalamus, primary hypothalamic neurons exposed to DHT were analyzed by Western blotting and RT-PCR respectively. The leptin levels in serum and cerebrospinal fluid (CSF) were measured, and leptin was injected via the intracerebroventricular (ICV) route to test the leptin sensitivity of hypothalamus. Results The excessive pre-puberty androgen levels in the DHT-induced rats markedly elevated food intake prior to weight gain. Consistent with this, the expression of NPY and Agouti-related peptide (Agrp) mRNAs were up-regulated, which occurred prior to obesity and even with restricted food intake. In addition, the hypothalamic sensitivity to insulin and leptin was also impaired in the DHT-induced rats before obesity and with restricted food intake. DHT significantly reduced the leptin levels in the CSF, and ICV injection of leptin inhibited the DHT-induced increase in food intake. Conclusions Androgen excess increased food intake in rats and promoted obesity by down-regulating insulin and leptin signaling in the hypothalamus, most likely by suppressing leptin levels in the CSF.

BMC Cancer ; 18(1): 88, 2018 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-29357836


BACKGROUND: Scavenger receptor class B type I (SR-BI) has been reported to be involved in carcinogenesis of several human cancers. However, it is currently unknown whether SR-BI plays a role in clear cell renal cell carcinoma (ccRCC). Here, we aimed to evaluate a tumor promotive mechanism for SR-BI in ccRCC. METHODS: The expression of SR-BI was evaluated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry (IHC) in ccRCC tissues and cell lines. Lipid droplets in ccRCC tissues and normal kidney tissues were examined by Oil Red O (ORO) and hematoxylin-eosin (HE) staining. The correlation between SR-BI mRNA levels and clinicopathological features was analyzed by Pearson's chi-square test or Fisher's exact test. Kaplan-Meier analysis and Cox model were used to evaluate the difference in progression-free survival (PFS) associated with expression of SR-BI. Inhibition of SR-BI was conducted by using small interfering RNA (siRNA). In vitro assays were performed to assess the impact of SR-BI knockdown on cell biological behaviors. High density lipoprotein (HDL)-cholesterol content in ccRCC cells and extracellular media was also measured after transfection with siRNA. RESULTS: The expression of SR-BI was markedly up-regulated in ccRCC tissues and tumor cell lines. ORO and HE staining revealed huge amounts of lipid droplets accumulation in ccRCC. Clinical analysis showed that over-expression of SR-BI was positively associated with tumor size, grade, distant metastasis and inversely correlated with PFS. Furthermore, SR-BI was proved to be an independent prognostic marker in ccRCC patients. The inhibition of SR-BI attenuated the tumorous behaviors of ccRCC cells, expression of metastasis and AKT pathway related proteins. The content of HDL-cholesterol was reduced in cells while increased in extracellular media after transfection with si-SR-BI. CONCLUSIONS: Our results demonstrate that SR-BI functions as an oncogene and promotes progression of ccRCC. SR-BI may serve as a potential prognostic biomarker and therapeutic target for ccRCC.

Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Prognóstico , Receptores Depuradores Classe B/genética , Adulto , Idoso , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , HDL-Colesterol/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Gotículas Lipídicas/metabolismo , Gotículas Lipídicas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , RNA Mensageiro/genética
Int J Cardiovasc Imaging ; 33(6): 857-868, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28255826


The aim of this study was to investigate the usefulness of three-dimensional (3D) speckle tracking echocardiography (STE) for assessment of both left and right ventricular systolic function in patients with lymphoma after anthracycline chemotherapy, compared with two-dimensional (2D) STE. Totally eighty-nine patients undergoing anthracycline containing chemotherapy were studied. Echocardiographic assessment included 2D and 3D left ventricular (LV) global longitudinal strain (GLS), global circumferential strain (GCS) and right ventricular (RV) GLS. All the parameters were analyzed at baseline, after the completion of four cycles and at the end of the regimen respectively. The area under the receiver operating characteristic curve was calculated to determine the capability of various echocardiographic parameters to discriminate between before and after chemotherapy. Compared with those at baseline, the 3D GLS and GCS of LV and GLS of RV decreased significantly after four cycles of the therapy (all p < 0.01). At the end of the treatment, 2D GLS and GCS of LV deteriorated markedly (both p < 0.05). The area under the curve for GLS, GCS of LV and GLS of RV derived by 3D were 0.81, 0.66 and 0.78, respectively. The cutoff value with -20.4% of LV GLS by 3D had sensitivity of 81% and specificity of 66% for differentiating patients after therapy from baselines. The cutoff value with -21.9% of RV GLS by 3D had sensitivity of 71% and specificity of 74% fordifferentiating patients after therapy from baselines. The data from this study demonstrated that both 2D and 3D STE can be conducted to evaluate the slight myocardial damage for lymphoma patients after anthracycline chemotherapy. 3D STE could examine subclinical biventricular dysfunction in earlier point than 2D STE.

Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Ecocardiografia Doppler de Pulso , Ecocardiografia Tridimensional , Cardiopatias/induzido quimicamente , Cardiopatias/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , Fenômenos Biomecânicos , Cardiotoxicidade , Diagnóstico Precoce , Feminino , Cardiopatias/sangue , Cardiopatias/fisiopatologia , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Fatores de Risco , Estresse Mecânico , Sístole , Fatores de Tempo , Adulto Jovem
Urol Oncol ; 35(1): 36.e7-36.e14, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27633984


OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is the most frequent and lethal subtype of renal cell carcinoma, whose most effective measure of curing remains diagnosis and nephrectomy in its early phase. However, there is no feasible and recognized plasma biomarker for the clinical diagnosis of ccRCC. The objective of this study is to identify a novel plasma microRNA (miRNA) acting as an efficient diagnostic plasma biomarker in ccRCC. METHODS AND MATERIALS: The plasma miRNA expression profile was quantified by miRNA microarray. Validation of miRNA levels of plasmas and tissues were performed by quantitative reverse transcription polymerase chain reaction in 106 ccRCC, 28 renal angiomyolipomas (AML), and 123 healthy control plasmas and in 110 ccRCC tissues. RESULTS: We found that plasma miR-144-3p levels in 106 ccRCC plasmas were remarkably up-regulated compared with that in healthy individuals and in patients with AML. miR-144-3p served as a promising plasma biomarker for yielding an area under the receiver operating characteristic curve of 0.91 with 87.10% sensitivity and 83.02% specificity in discriminating ccRCC from healthy individuals, and an area under the curve of 0.82 with 75.00% sensitivity and 71.70% specificity in discriminating ccRCC from patients with AML. In addition, plasma miR-144-3p levels were significantly decreased after surgery in 106 patients with ccRCC. Next, we examined miR-144-3p levels in 110 human ccRCC tissues, and found that miR-144-3p levels in ccRCC tissues were increased compared with adjacent normal tissues. Pearson correlation analysis revealed that miR-144-3p levels in tumor tissues were positively correlated with preoperative plasma miR-144-3p levels in the matched samples from patients with ccRCC. In addition, the miR-144-3p levels in ccRCC plasmas and tissues were increased in patients with advanced pT stage. CONCLUSIONS: Our data indicate that miR-144-3p, which is significantly up-regulated in ccRCC plasmas and tissues, particularly with advanced pT stage, is a novel and excellent plasma biomarker for the diagnosis of ccRCC.

Angiomiolipoma/diagnóstico , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/diagnóstico , Neoplasias Renais/metabolismo , MicroRNAs/sangue , Angiomiolipoma/sangue , Área Sob a Curva , Biomarcadores Tumorais/sangue , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Rim/metabolismo , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nefrectomia , Análise de Sequência com Séries de Oligonucleotídeos , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima