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1.
Clin Chim Acta ; 503: 19-34, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31923423

RESUMO

Hypertriglyceridemia is a risk factor for a series of diseases, such as cardiovascular disease (CVD), diabetes and nonalcoholic fatty liver disease (NAFLD). Angiopoietin-like proteins (ANGPTLs) family, especially ANGPTL3, ANGPTL4 and ANGPTL8, which regulate lipoprotein lipase (LPL) activity, play pivotal roles in triglyceride (TG) metabolism and related diseases/complications. There are many transcriptional and post-transcriptional factors that participate in physiological and pathological regulation of ANGPTLs to affect triglyceride metabolism. This review is intended to focus on the similarity and difference in the expression, structural features, regulation profile of the three ANGPTLs and inhibitory models for LPL. Description of the regulatory factors of ANGPTLs and the properties in regulating the lipid metabolism involved in the underlying mechanisms in pathological effects on diseases will provide potential therapeutic approaches for the treatment of dyslipidemia related diseases.

2.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(6): 925-929, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31880126

RESUMO

OBJECTIVE: To compare the difference of health-related quality of life after oncologic esophagectomy between the patients using Jiang's gastroesophageal anastomosis and traditional end-to-end gastroesophageal anastomosis. METHODS: A total of 419 patients (223 in Jiang's anastomosis group, and 196 in end-to-end anastomosis group) underwent minimal invasive esophagectomy with cervical anastomosis from October 2012 to August 2016. All patients received radical esophageal cancer resection and cervical anastomosis. EORTC-QLQ-C30 and QLQ-OES18 were used to assess the health-related quality of life at the 1st, 3rd, 6th, 12th, 24th month after esophagectomy. RESULTS: There were 25 dimensions and items in EORTC-QLQ-C30 and QLQ-OES18. The postoperative quality of life decreased obviously at the 1st month and then recovered obviously at the 6th month after the surgery, and it ranged small at the 12th and 24th month. Compared with end-to-end anastomosis group, Jiang's anastomosis group had less reflux and less cough at the 1st month (P=0.023, P=0.010) and the 3rd month (P=0.004, P=0.013), then had better emotional function, less reflux and less cough at the 6th month (P=0.013, P=0.014, P=0.043), better emotional function, less nausea, and less reflux at the 12th month(P=0.004, P=0.023, P=0.021), as well as less reflux at the 24th month (P=0.020). There was no significant difference in other dimensions and items between the two groups during the follow-up period. CONCLUSION: Jiang's anastomosis is safe and feasible, and could improve the postoperative quality of life of the patients with esophagectomy. It is worth to further application in clinical practice.


Assuntos
Neoplasias Esofágicas , Refluxo Gastroesofágico , Anastomose Cirúrgica , Esofagectomia , Humanos , Qualidade de Vida
3.
Atherosclerosis ; 289: 143-161, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31518965

RESUMO

BACKGROUND AND AIMS: Krüppel-like factor 14 (KLF14) is known to play a role in atherosclerosis, but the underlying mechanisms are still largely unknown. The aim of our study was to explore the effects of KLF14 on lipid metabolism and inflammatory response, providing a potential target for lowering the risk of atherosclerosis-causing disease. METHODS AND RESULTS: mRNA and protein levels of KLF14 were significantly decreased in oxidized low-density lipoprotein (oxLDL)-treated macrophages and in the atherosclerotic lesion area. Chromatin immunoprecipitation (ChIP) and luciferase reporter gene assays were used to confirm that KLF14 positively regulated miR-27a expression by binding to its promoter. We also found that KLF14 could restored appropriate cellular lipid homeostasis and inflammatory responses via negatively regulating lipoprotein lipase (LPL) expression in THP1-derived macrophages through miR-27a. In addition, gypenosides (GP), a KLF14 activator, delayed the development of atherosclerosis in apolipoprotein E deficient (apoE-/-) mice. CONCLUSIONS: KLF14 plays an antiatherogenic role via the miR-27a-dependent down-regulation of LPL and subsequent inhibition of proinflammatory cytokine secretion and lipid accumulation.

4.
Int J Mol Med ; 37(6): 1661-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27081862

RESUMO

Doxorubicin (DOX) is an efficient drug used in cancer therapy that also produces reactive oxygen species (ROS) that induces severe cytotoxicity, which limits its clinical application. Hydrogen sulfide (H2S), a novel gasotransmitter, has been shown to exert cardioprotective effects. The present study aimed to determine whether exogenous H2S protects H9c2 cardiac cells against DOX-induced cytotoxicity and whether these protective effects are mediated through the PI3K/Akt/FoxO3a pathway. The H9c2 cardiac cells were exposed to 5 µM DOX for 24 h to establish a model of DOX-induced cardiotoxicity. The results showed that the treatment of H9c2 cardiac cells with sodium hydrosulfide (NaHS) for 30 min prior to DOX exposure markedly attenuated the phosphorylation of Akt and FoxO3a. Notably, pre-treatment of the H9c2 cells with NaHS significantly attenuated the nuclear localization of FoxO3a as well as the apoptosis of H9c2 cells induced by DOX. The treatment of H9c2 cells with N-acetyl-L-cysteine (NAC), a scavenger of ROS, prior to DOX exposure, also markedly increased the phosphorylation of Akt and FoxO3a which was inhibited by DOX alone. Furthermore, pre-treatment with LY294002, a selective inhibitor of PI3K/Akt, reversed the protective effect of H2S against DOX-induced injury of cardiomyocytes, as demonstrated by an increased number of apoptotic cells, a decrease in cell viability and the reduced phosphorylation of Akt and FoxO3a. These findings suggested that exogenous H2S attenuates DOX-induced cytotoxic effects in H9c2 cardiac cells through the PI3K/Akt/FoxO3a pathway.


Assuntos
Cardiotônicos/farmacologia , Doxorrubicina/antagonistas & inibidores , Sulfeto de Hidrogênio/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Sulfetos/farmacologia , Acetilcisteína/farmacologia , Animais , Apoptose/efeitos dos fármacos , Cardiotoxicidade/prevenção & controle , Linhagem Celular , Cromonas/farmacologia , Doxorrubicina/farmacologia , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/metabolismo , Regulação da Expressão Gênica , Modelos Biológicos , Morfolinas/farmacologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais , Sulfetos/química
5.
Mol Med Rep ; 13(2): 1281-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26675978

RESUMO

Doxorubicin (DOX) is an efficient drug used in cancer therapy; however, it has severe cardiotoxic side effects. The aim of the present study was to investigate the effects of resveratrol on the adenosine monophosphate-activated protein kinase (AMPK)/P53 pathway in mediating DOX-induced cytotoxicity. H9c2 cells were exposed to 5 µM DOX for 24 h to establish a model of DOX-induced cardiotoxicity. DOX administration amplified P53 and B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) expression and decreased Bcl-2 expression in H9c2 cells. Resveratrol increased the cell viability and decreased the apoptotic rate. In addition, resveratrol markedly increased the phosphorylation of AMPK. Of note, resveratrol protected against DOX-induced increases of P53 and Bax and also prevented the downregulation of Bcl-2 in H9c2 cells. Furthermore, AMPK inhibitor Compound C abolished the protective effects of resveratrol. The results of the present study therefore indicated that resveratrol protected H9c2 cells from DOX-induced apoptosis via the AMPK/P53 pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Apoptose/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Linhagem Celular , Doxorrubicina/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ratos , Resveratrol , Transdução de Sinais/efeitos dos fármacos , Estilbenos/administração & dosagem , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/biossíntese , Proteína X Associada a bcl-2/genética
6.
Int Surg ; 100(1): 133-6, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25594653

RESUMO

This study aims to report a relatively rare entity-intramedullary tuberculum of cervical spine-and describe its management and some key learning points. Intramedullary tuberculomas are rare entities. Intramedullary tuberculoma is most commonly found in the thoracic cord of a patient and is rarely seen in the cervical cord. We present an intramedullary cervical tuberculoma in a 21-year-old patient with finding of spinal cord compression. All 4 limbs were spastic, with grade 1 power on the right side and grade 3 power on the left side. Sensory deficit was found below the C6 level. Magnetic resonance imaging showed an intramedullary lesion at the C5 to C6 levels. Intramedullary tuberculoma was diagnosed based on clinical symptoms, physical examination, previous history, and magnetic resonance imaging. A C5 to C7 laminectomy was performed. Intramedullary tuberculoma was resected by microsurgery. One year after the surgery, strength returned to normal grade 5. Excellent clinical outcome was obtained with a combination of both medical and surgical treatments. Intramedullary cervical tuberculoma should be removed without delay to eliminate any mass effect on the neurons as soon as possible.


Assuntos
Vértebras Cervicais , Tuberculoma/diagnóstico , Tuberculose da Coluna Vertebral/diagnóstico , Vértebras Cervicais/cirurgia , Humanos , Laminectomia , Imagem por Ressonância Magnética , Masculino , Tuberculoma/cirurgia , Tuberculose da Coluna Vertebral/cirurgia , Adulto Jovem
7.
Spine (Phila Pa 1976) ; 37(17): 1463-9, 2012 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-22842538

RESUMO

STUDY DESIGN: Retrospective multicenter study. OBJECTIVE: To compare clinical outcomes and surgical-related adverse events in patients with multilevel cervical myelopathy (MCM) undergoing simple anterior, simple posterior, or 1-stage posterior-anterior surgical decompression strategies. SUMMARY OF BACKGROUND DATA: Simple anterior, simple posterior, and 1-stage posterior-anterior surgical decompression strategies have been advocated for MCM treatment in both Western and Chinese populations. However, there is limited evidence on whether 1-stage posterior-anterior strategy may offer equal or more advantages than the other 2 strategies for patients with MCM. METHODS: A retrospective review of medical records was conducted for 255 patients with MCM who had undergone surgical decompression in 3 Chinese spinal centers from 1999 to 2010. Neurological status, perioperative variables, and surgical complications were assessed. Multiple linear regression was used to evaluate factors associated with the outcomes of each strategy. RESULTS: Analyses were conducted on a total of 229 patients with MCM undergoing surgical decompression via 1-stage posterior-anterior (68 patients), simple anterior (102 patients), and simple posterior approaches (59 patients). One-stage posterior-anterior approach had the highest Japanese Orthopaedic Association recovery rate after adjusted for age and sex (adjusted mean ± SD: 50.0 ± 3.2, P < 0.001) and additionally adjusted for smoking, duration from onset of symptoms to surgery, comorbidities, preoperative Japanese Orthopaedic Association score, Ishihara's curvature index and Pavlov ratio, operative blood loss, operating time, anterior operated disc levels, and posterior operated levels (adjusted mean ± SD: 51.6 ± 11.6, P < 0.01). Anterior approach had the largest difference between the pre- and postoperative Ishihara's curvature indexes after adjusted for age and sex (adjusted mean ± SD: 5.3 ± 1.0, P < 0.01) and after multivariable adjustment (adjusted mean ± SD: 6.5 ± 2.8, P = 0.003). CONCLUSION: One-stage posterior-anterior strategy can be a reliable and effective treatment strategy for MCM in a subgroup of patients with anterior and posterior compression on spinal cord simultaneously.


Assuntos
Descompressão Cirúrgica/métodos , Doenças da Medula Espinal/cirurgia , Medula Espinal/cirurgia , Adulto , Idoso , Obstrução das Vias Respiratórias/etiologia , Grupo com Ancestrais do Continente Asiático , Vértebras Cervicais , China , Descompressão Cirúrgica/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Compressão da Medula Espinal/etnologia , Compressão da Medula Espinal/fisiopatologia , Compressão da Medula Espinal/cirurgia , Doenças da Medula Espinal/etnologia , Doenças da Medula Espinal/fisiopatologia , Resultado do Tratamento
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