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1.
Chin Med J (Engl) ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32044814

RESUMO

BACKGROUND: A novel coronavirus (2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and analyze the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak. METHODS: Clinical data from 137 2019-nCoV-infected patients admitted to the respiratory departments of the respiratory departments of nine tertiary hospitals in Hubei province from December 30, 2019 to January 24, 2020 were retrospectively collected, including general status, clinical manifestations, laboratory test results, imaging characteristics, and treatment regimens. RESULTS: None of the 137 patients (61 males, 76 females, aged 20-83 years, median age 57 years) had a definite history of exposure to Huanan Seafood Wholesale Market. Major initial symptoms included fever (112/137, 81.8%), coughing (66/137, 48.2%), and muscle pain or fatigue (44/137, 32.1%), with other, less typical initial symptoms observed at low frequency, including heart palpitations, diarrhea, and headache. Nearly 80% of the patients had normal or decreased white blood cell counts, and 72.3% (99/137) had lymphocytopenia. Lung involvement was present in all cases, with most chest computed tomography scans showing lesions in multiple lung lobes, some of which were dense; ground-glass opacity co-existed with consolidation shadows or cord-like shadows. Given the lack of effective drugs, treatment focused on symptomatic and respiratory support. Immunoglobulin G was delivered to some critically ill patients according to their conditions. Systemic corticosteroid treatment did not show significant benefits. Notably, early respiratory support facilitated disease recovery and improved prognosis. The risk of death was primarily associated with age, underlying chronic diseases, and median interval from the appearance of initial symptoms to dyspnea. CONCLUSIONS: The majority of patients with 2019-nCoV pneumonia present with fever as the first symptom, and most of them still showed typical manifestations of viral pneumonia on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.

2.
Cancer Lett ; 473: 74-89, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-31904482

RESUMO

Gastrointestinal cancer causes countless deaths every year due to therapeutic resistance. However, whether metabolic alterations contribute to chemoresistance is not well understood. In this study, we report that fatty acid (FA) catabolism was activated in gastrointestinal cancer cells treated with oxaliplatin, which exhibited higher expression of the rate-limiting enzymes carnitine palmitoyltransferase 1B (CPT1B) and CPT2. The clinical analysis also showed that high expression of these enzymes was associated with poor oxaliplatin-based chemotherapy outcomes in patients. Furthermore, genetic or pharmacological inhibition of CPT2 with perhexiline disturbed NADPH and redox homeostasis and increased reactive oxygen species (ROS) generation and cell apoptosis in gastrointestinal cancer cells following oxaliplatin treatment. Specifically, the combination of oxaliplatin and perhexiline significantly suppressed the progression of gastrointestinal cancer in cell-based xenograft and patient-derived xenograft (PDX) models. Mechanistically, CPT2 was transcriptionally upregulated by nuclear factor of activated T cells 3 (NFATc3), which translocated to the nucleus in response to oxaliplatin treatment. In summary, our study suggests that the inhibition of CPT-mediated FA catabolism combined with conventional chemotherapy is a promising therapeutic strategy for patients with gastrointestinal cancers.

3.
Oncogene ; 39(3): 637-650, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31530934

RESUMO

Patients with stage II or III colorectal cancer (CRC) exhibit various clinical outcomes after radical treatments. The 5-year survival rate was between 50 and 87%. However, the underlying mechanisms of the variation remain unclear. Here we show that AMPKα1 is overexpressed in CRC patient specimens and the high expression is correlated with poor patient survival. We further reveal a previously unrecognized function of AMPKα1, which maintains high level of reduced glutathione to keep reduction-oxidation reaction (redox) homeostasis under stress conditions, thus promoting CRC cell survival under metabolic stress in vitro and enhancing tumorigenesis in vivo. Mechanistically, AMPKα1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity. Suppression of AMPKα1 by using nano-sized polymeric vector induces a favorable therapeutic effect, especially when in combination with oxaliplatin. Our study uncovers a novel function of AMPKα1 in redox regulation and identifies a promising therapeutic strategy for treatment of CRC.

4.
Mol Cancer ; 18(1): 174, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791342

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) play nonnegligible roles in the epigenetic regulation of cancer cells. This study aimed to identify a specific lncRNA that promotes the colorectal cancer (CRC) progression and could be a potential therapeutic target. METHODS: We screened highly expressed lncRNAs in human CRC samples compared with their matched adjacent normal tissues. The proteins that interact with LINRIS (Long Intergenic Noncoding RNA for IGF2BP2 Stability) were confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assays. The proliferation and metabolic alteration of CRC cells with LINRIS inhibited were tested in vitro and in vivo. RESULTS: LINRIS was upregulated in CRC tissues from patients with poor overall survival (OS), and LINRIS inhibition led to the impaired CRC cell line growth. Moreover, knockdown of LINRIS resulted in a decreased level of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), a newly found N6-methyladenosine (m6A) 'reader'. LINRIS blocked K139 ubiquitination of IGF2BP2, maintaining its stability. This process prevented the degradation of IGF2BP2 through the autophagy-lysosome pathway (ALP). Therefore, knockdown of LINRIS attenuated the downstream effects of IGF2BP2, especially MYC-mediated glycolysis in CRC cells. In addition, the transcription of LINRIS could be inhibited by GATA3 in CRC cells. In vivo experiments showed that the inhibition of LINRIS suppressed the proliferation of tumors in orthotopic models and in patient-derived xenograft (PDX) models. CONCLUSION: LINRIS is an independent prognostic biomarker for CRC. The LINRIS-IGF2BP2-MYC axis promotes the progression of CRC and is a promising therapeutic target.

5.
J Immunother Cancer ; 7(1): 264, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31623662

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have achieved impressive success in different cancer types, yet responses vary and predictive biomarkers are urgently needed. Growing evidence points to a link between DNA methylation and anti-tumor immunity, while clinical data on the association of genomic alterations in DNA methylation-related genes and ICI response are lacking. METHODS: Clinical cohorts with annotated response and survival data and matched mutational data from published studies were collected and consolidated. The predictive function of specific mutated genes was first tested in the discovery cohort and later validated in the validation cohort. The association between specific mutated genes and tumor immunogenicity and anti-tumor immunity was further investigated in the Cancer Genome Altas (TCGA) dataset. RESULTS: Among twenty-one key genes involving in the regulation of DNA methylation, TET1-mutant (TET1-MUT) was enriched in patients responding to ICI treatment in the discovery cohort (P < 0.001). TET1 was recurrently mutated across multiple cancers and more frequently seen in skin, lung, gastrointestinal, and urogenital cancers. In the discovery cohort (n = 519), significant differences were observed between TET1-MUT and TET1-wildtype (TET1-WT) patients regarding objective response rate (ORR, 60.9% versus 22.8%, P < 0.001), durable clinical benefit (DCB, 71.4% versus 31.6%, P < 0.001), and progression-free survival (PFS, hazard ratio = 0.46 [95% confidence interval, 0.25 to 0.82], P = 0.008). In the validation cohort (n = 1395), significant overall survival (OS) benefit was detected in the TET1-MUT patients compared to TET1-WT patients (hazard ratio = 0.47 [95% confidence interval, 0.25 to 0.88], P = 0.019), which was, importantly, independent of tumor mutational burden and high microsatellite instability; as well as not attributed to the prognostic impact of TET1-MUT (P > 0.05 in both two non-ICI-treated cohorts). In TCGA dataset, TET1-MUT was strongly associated with higher tumor mutational burden and neoantigen load, and inflamed pattern of tumor-infiltrating T lymphocytes, immune signatures and immune-related gene expressions. CONCLUSIONS: TET1-MUT was strongly associated with higher ORR, better DCB, longer PFS, and improved OS in patients receiving ICI treatment, suggesting that TET1-MUT is a novel predictive biomarker for immune checkpoint blockade across multiple cancer types.

7.
J Natl Compr Canc Netw ; 17(7): 805-811, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31319395

RESUMO

BACKGROUND: Previous meta-analyses have suggested primary tumor location as a predictive factor for efficacy of anti-epidermal growth factor receptor (EGFR) therapies in patients with metastatic colorectal cancer (mCRC). However, the recent phase III TAILOR trial addressing this issue was not included in those analyses. This meta-analysis incorporated data from the TAILOR trial to evaluate the efficacy of chemotherapy plus anti-EGFR agents (cetuximab [Cet] or panitumumab [Pani]) versus chemotherapy alone for RAS wild-type (wt) right- and left-sided mCRC. PATIENTS AND METHODS: A PubMed-based literature search was conducted to identify randomized controlled trials (RCTs) studying the additional efficacy of Cet/Pani in combination with chemotherapy versus chemotherapy alone in RAS wt left- and right-sided mCRC. Study-level pooled analyses of hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and odds ratios (ORs) for objective response rate (ORR) were performed. RESULTS: Three first-line RCTs (CRYSTAL, PRIME, and TAILOR) and one second-line RCT (20050181) were included. Significant OS benefits from Cet/Pani were observed in the left-sided (HR, 0.76; 95% CI, 0.66-0.86) but not right-sided subgroups (HR, 0.99; 95% CI, 0.78-1.27). However, the addition of Cet/Pani to chemotherapy significantly improved PFS and ORR in both the left-sided (HR, 0.70; 95% CI, 0.57-0.86, and OR, 3.28; 95% CI, 1.95-5.51, respectively) and right-sided subgroups (HR, 0.76; 95% CI, 0.59-0.99, and OR, 1.78; 95% CI, 1.08-2.93, respectively). CONCLUSIONS: The addition of Cet/Pani to chemotherapy significantly benefits PFS and ORR in patients with RAS wt right-sided mCRC, indicating that anti-EGFR therapies may remain an option for selected patients.

8.
JAMA Netw Open ; 2(5): e193433, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31050784

RESUMO

Importance: Immune checkpoint inhibitors (ICIs) have unique patterns of response and survival that differ from conventional chemotherapies. Novel intermediate end points are urgently required to detect the early signals of ICI activity. Objective: To evaluate milestone rate (Kaplan-Meier estimates of survival probabilities at given time points) and milestone restricted mean survival time (RMST, the area under survival curves up to given time points) as potential intermediate end points for ICI trials. Data Sources: Electronic databases (pre-MEDLINE, MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials) were searched for randomized clinical trials published between January 1, 2000, and December 31, 2017. Study Selection: Phase 2 and phase 3 randomized clinical trials evaluating ICIs in advanced solid tumors. Data Extraction and Synthesis: Two investigators extracted the data and reconstructed individual patient data to estimate the milestone rate or milestone RMST from the published Kaplan-Meier curves. Main Outcomes and Measures: Trial-level milestone rates or milestone RMSTs were estimated for 6-month and 9-month progression-free survival (PFS) and 9-month and 12-month overall survival (OS). A weighted linear regression model evaluated the correlations of ratios of milestone rates or milestone RMSTs with OS hazard ratios (HRs). Results: Twenty-six trials examining 8 different tumor types were identified, including 12 892 patients. Overall survival HR was correlated with the ratio of 9-month OS milestone rate (R2 = 0.45; 95% CI, 0.27-0.74), and with the ratio of 12-month OS milestone rate (R2 = 0.40; 95% CI, 0.22-0.70). The ratio of 9-month OS milestone RMST (R2 = 0.60; 95% CI, 0.28-0.74) and ratio of 12-month OS milestone RMST were correlated with OS HR (R2 = 0.64; 95% CI, 0.42-0.78). No correlations were observed between OS HR and the ratio of 6-month or 9-month PFS milestone rates or milestone RMSTs. Conclusions and Relevance: Ratios of OS milestone RMSTs had a stronger correlation with OS HRs than ratios of OS milestone rates, whereas ratios of PFS milestone rates and ratios of PFS milestone RMSTs were not correlated with OS HRs. The OS milestone RMST could be further studied as an intermediate end point in future ICI trials.

9.
Oncogene ; 37(46): 6025-6040, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29995871

RESUMO

Anoikis is a critical obstacle to cancer metastasis. Colorectal cancer (CRC) exhibits a high rate of metastasis, leading to death, and the mechanisms involved in anoikis resistance are still unclear. We identified that the fatty acid oxidation (FAO) pathway was activated in detached CRC cells. Multiple genes in the FAO pathway, specifically the rate-limiting enzyme CPT1A, were upregulated in CRC cells grown in suspension. Reactive oxygen species elimination mediated by CPT1A in CRC cells was vital to anoikis resistance. In vivo experiments showed that CPT1A-suppressed CRC cells colonized the lung at a much lower rate than normal CRC cells, suggesting that CPT1A-mediated FAO activation increased metastatic capacity. In clinical tissue specimens from CRC patients, elevated expression of CPT1A was observed in metastatic sites compared with primary sites. Our results demonstrate that CPT1A-mediated FAO activation induces CRC cells to resist anoikis, suggesting that CPT1A is an attractive target for treating metastatic CRC.


Assuntos
Anoikis/fisiologia , Carnitina O-Palmitoiltransferase/metabolismo , Neoplasias Colorretais/patologia , Ácidos Graxos/metabolismo , Metástase Neoplásica/patologia , Animais , Células CACO-2 , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Células HCT116 , Células HT29 , Humanos , Metabolismo dos Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Oxirredução , Espécies Reativas de Oxigênio/metabolismo
10.
Med Sci Monit ; 24: 3702-3709, 2018 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-29858912

RESUMO

BACKGROUND Revascularization is a successful therapeutic strategy for myocardial infarction. However, restoring coronary blood flow can lead to ischemia-reperfusion (I/R) injury. Low-dose 4-hydroxy-2-nonenal (HNE) therapy appears to play a key role in myocardial tolerance to I/R injury. We hypothesized that the positive effects of HNE on myocardial I/R injury may be UCP3-dependent. MATERIAL AND METHODS Adult male wild-type (WT) or UCP3 knockout (UCP3-/-) mice were pre-treated with the UCP inhibitor genipin or saline 1 h before ischemia and underwent 30-min coronary artery ligation followed by 24-h reperfusion. Mice were treated with intravenous HNE (4 mg/kg) or saline 5 min before reperfusion. Echocardiography was conducted to measure left ventricular end-diastolic posterior wall thickness (LVPWd), end-diastolic diameter (LVEDD), and fractional shortening (FS). Infarct size was measured by TTC staining. qRT-PCR and Western blotting were used to assess the expression of UCP3, UCP2, and the apoptosis markers cytochrome C and cleaved caspase-3. RESULTS HNE improved survival at 24 h post-MI in wild-type mice (p<0.05) but not in UCP3-/- mice. HNE preserved LVEDD and FS in WT mice (p<0.05) but not in UCP3-/- mice. HNE reduced infarct size in WT mice (p<0.05) but not in UCP3-/- mice. HNE upregulated UCP3 expression (p<0.05) but did not affect UCP2 expression. HNE reduced apoptosis marker expression in WT mice (p<0.05) but not in UCP3-/- mice. HNE's positive effects were abrogated by genipin in an UCP3-dependent manner. CONCLUSIONS Low-dose HNE reperfusion therapy attenuates murine myocardial I/R injury in an UCP3-dependent manner. These effects are abrogated by genipin in an UCP3-dependent manner.


Assuntos
Aldeídos/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Aldeídos/metabolismo , Animais , Apoptose , Vasos Coronários/metabolismo , Coração/fisiopatologia , Iridoides/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/metabolismo , Reperfusão Miocárdica , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Traumatismo por Reperfusão/metabolismo , Proteína Desacopladora 3/genética , Proteína Desacopladora 3/metabolismo
12.
Theranostics ; 8(5): 1312-1326, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29507622

RESUMO

Rationale: The antitumor activity of high-dose ascorbate has been re-evaluated recently, but the mechanism underlying cell-specific sensitivity to ascorbate has not yet been clarified. Methods: The effects of high-dose ascorbate on gastric cancer were assessed using cancer cell lines with high and low expression of GLUT1 via flow cytometry and colony formation assays in vitro and patient-derived xenografts in vivo. Results: In this study, we demonstrated that gastric cancer cells with high GLUT1 expression were more sensitive to ascorbate treatment than cells with low GLUT1 expression. GLUT1 knockdown significantly reversed the therapeutic effects of pharmacological ascorbate, while enforced expression of GLUT1 enhanced the sensitivity to ascorbate treatment. The efficacy of pharmacological ascorbate administration in mice bearing cell line-based and patient-derived xenografts was influenced by GLUT1 protein levels. Mechanistically, ascorbate depleted intracellular glutathione, generated oxidative stress and induced DNA damage. The combination of pharmacological ascorbate with genotoxic agents, including oxaliplatin and irinotecan, synergistically inhibited gastric tumor growth in mouse models. Conclusions: The current study showed that GLUT1 expression was inversely correlated with sensitivity of gastric cancer cells to pharmacological ascorbate and suggested that GLUT1 expression in gastric cancer may serve as a marker for sensitivity to pharmacological ascorbate.


Assuntos
Ácido Ascórbico/farmacologia , Transportador de Glucose Tipo 1/metabolismo , Oxaliplatina/farmacologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Animais , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Glutationa/metabolismo , Humanos , Irinotecano/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Modelos Biológicos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Prognóstico , Espécies Reativas de Oxigênio/metabolismo , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Mol Med Rep ; 15(6): 3591-3598, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28440403

RESUMO

Ginsenoside Rh2 (GRh2) and ginsenoside Rg3 (GRg3) are primary bioactive components in Panax ginseng. The present study aimed to investigate the underlying mechanisms of apoptotic cell­death induced by GRh2 and GRg3 in human leukemia Jurkat cells. The Cell Counting kit­8 assay was used to determine cell proliferation. Apoptosis was detected by nuclear morphologic observation by Hoechst 33342 staining and Annexin V-allophycocyanin and 7-amino-actinomycin D assay. mitoTEMPO, a mitochondrial reactive oxygen species (ROS) scavenger, was used to examine the effects of mitochondrial ROS on cell viability and mitochondrial membrane potential (MMP). Finally, the expression levels of numerous mitochondrial­associated apoptosis proteins were assessed by western blot analysis. These results demonstrated that GRh2 and GRg3 inhibited cell growth and induced apoptosis, and that GRh2 had greater cytotoxicity than GRg3. GRh2 induced generation of more mitochondrial ROS compared with GRg3 in Jurkat cells; however, this effect was ameliorated by subsequent treatment with mitoTEMPO. Furthermore, excess mitochondrial ROS induced by GRh2 was more potent than GRg3 in inhibiting cell proliferation and reducing MMP. In addition, expression levels of apoptosis­associated proteins were significantly increased in Jurkat cells treated with GRh2 than GRg3. In conclusion, these findings suggested that GRh2 and GRg3 induce mitochondrial-associated apoptosis by increasing mitochondrial ROS in human leukemia Jurkat cells. GRh2 may more effectively inhibit cell growth and accelerate apoptosis than GRg3. This study provides a potential novel strategy for the treatment of acute lymphoblastic leukemia.


Assuntos
Apoptose/efeitos dos fármacos , Ginsenosídeos/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Expressão Gênica , Humanos , Células Jurkat , Metaloproteinases da Matriz/metabolismo
14.
Zhonghua Bing Li Xue Za Zhi ; 42(12): 815-8, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24507099

RESUMO

OBJECTIVE: To investigate the etiology, pathogenesis, clinicopathologic characteristics, clinical prognosis and treatment of Dandy-Walker syndrome. METHODS: Nine cases of Dandy-Walker syndrome were included in the study. The autopsy findings and clinical history were evaluated along with review of the literature. The causes, pathogenetic mechanism, pathologic features and prognosis of Dandy-Walker syndrome were analyzed. RESULTS: Among 9 Dandy-Walker syndrome cases, six patients presented with variants of Dandy-Walker complex and 3 cases had classic Dandy-Walker malformation. In addition, 4 patients presented with combined lateral ventricle expansion and multiple malformations were seen in 7 cases. Combined umbilical cord abnormality was noted in 4 patients with variant of Dandy-Walker complex and combined placental abnormality was seen in one classic Dandy-Walker syndrome. CONCLUSIONS: Dandy-Walker syndrome is a rare disease. In addition to complex pathogenesis with possible genetic and environmental antigenic etiologies, placental and umbilical cord abnormality may be also related to its development.


Assuntos
Síndrome de Dandy-Walker/patologia , Doenças Fetais/patologia , Ultrassonografia Pré-Natal , Aborto Induzido , Autopsia , Síndrome de Dandy-Walker/diagnóstico por imagem , Feminino , Doenças Fetais/diagnóstico por imagem , Feto/patologia , Idade Gestacional , Humanos , Ventrículos Laterais/patologia , Masculino , Insuficiência Placentária/patologia , Gravidez , Estudos Retrospectivos
15.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 35(3): 238-44, 2006 May.
Artigo em Chinês | MEDLINE | ID: mdl-16764023

RESUMO

OBJECTIVE: To investigate the effect of losartan (an angiotensin II type I receptor antagonist) on endothelial cells exposed to high glucose in vitro and related mechanism. METHODS: Vascular endothelial cells of human umbilical vein were cultured in media with high glucose levels. The activities of SOD and CAT, the level of MDA were measured by spectrophotometry in the conditioned media of endothelial cells, the VEGF mRNA expression was performed using semi-quantitative reverse transcription PCR (RT-PCR) in the cell lysates, and the protein expression of VEGF was examined by enzyme-linked immunosorbent assay (ELISA) in the supernatants of cultured cells. RESULT: When endothelial cells were cultured in high glucose, the activities of SOD and CAT were significantly decreased, but the level of MDA was markedly increased. However, the high glucose-induced effects were inhibited by losartan. The application of high glucose upregulated the mRNA and protein expression of VEGF in endothelial cells, which was also attenuated by losartan. CONCLUSION: High glucose disrupts the oxidative equilibrium and increases the expression of VEGF in endothelial cells, which can be inhibited by losartan.


Assuntos
Endotélio Vascular/citologia , Glucose/farmacologia , Losartan/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Células Cultivadas , Endotélio Vascular/metabolismo , Humanos , Peroxidase/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Superóxido Dismutase/metabolismo , Veias Umbilicais/citologia , Fatores de Crescimento do Endotélio Vascular/biossíntese , Fatores de Crescimento do Endotélio Vascular/genética
16.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 35(3): 245-50, 2006 May.
Artigo em Chinês | MEDLINE | ID: mdl-16764024

RESUMO

OBJECTIVE: To investigate the protective effect of PPARgamma ligands rosiglitazone on myocardium in diabetic cardiomyopathy of rats. METHODS: The rat model of diabetes was induced by administration of streptozotocin (STZ) for 6 or 10 weeks. In the treatment group the STZ-induced diabetic rats were treated with rosiglitazone. The left ventricular muscle specimens were taken from treatment and control group; then were examined under transmission electron microscope. RESULT: Cardiac myofibrils of diabetic rats in control group were obviously fewer and broken. There were fewer and smaller dissolved mitochondria with incomplete membrane and mixed cristae and karyopyknosis. Myocardium of diabetic rats treated with rosiglitazone was markedly improved although their blood glucose levels were still high. CONCLUSION: Hyperglycemia can cause destruction of myocardial cell structure. Rosiglitazone has protective effect on myocardial cells of diabetic rats, which seems to be independent of blood glucose levels.


Assuntos
Cardiomiopatias/patologia , Diabetes Mellitus Experimental/complicações , Miocárdio/ultraestrutura , PPAR gama/uso terapêutico , Tiazolidinedionas/uso terapêutico , Animais , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/etiologia , Cardiotônicos/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Ligantes , Masculino , Ratos , Ratos Sprague-Dawley , Rosiglitazona
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