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1.
Med Sci Monit ; 28: e936542, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35236816

RESUMO

This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study and the manuscript. Reference: Yun-Qian Wang, Cong-Cong Fan, Bao-Ping Chen, Jun Shi. Resistin-Like Molecule Beta (RELM-ß) Regulates Proliferation of Human Diabetic Nephropathy Mesangial Cells via Mitogen-Activated Protein Kinases (MAPK) Signaling Pathway. Med Sci Monit 2017; 23:3897-3903. DOI: 10.12659/MSM.905381.

2.
Front Oncol ; 11: 699889, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367983

RESUMO

PURPOSE: Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is associated with high invasiveness, high metastatic occurrence and poor prognosis. Protein tyrosine kinase 7 (PTK7) plays an important role in multiple cancers. However, the role of PTK7 in TNBC has not been well addressed. This study was performed to evaluate the role of PTK7 in the progression of TNBC. METHODS: Correlation of PTK7 expression with clinicopathological parameters was assessed using tissue microarray immunohistochemistry (IHC) staining in 280 patients with breast cancer. PTK7 expression in TNBC (MDA-MB-468, MDA-MB-436 and MDA-MB-231) and non-TNBC (MCF7 and SK-BR-3) breast cancer cell lines were examined using immunoblotting assay. PTK7 correlated genes in invasive breast carcinoma were analyzed using cBioPortal breast cancer datasets including 1,904 patients. PTK7 overexpressed or knockdown TNBC cell lines (MDA-MB-468 and MDA-MB-436) were used to analyze the potential roles of PTK7 in TNBC metastasis and tumor progression. A TNBC tumor bearing mouse model was established to further analyze the role of PTK7 in TNBC tumorigenicity in vivo. RESULTS: PTK7 is highly expressed in breast cancer and correlates with worse prognosis and associates with tumor metastasis and progression in TNBC. Co-expression analysis and gain- or loss-of-function of PTK7 in TNBC cell lines revealed that PTK7 participates in EGFR/Akt signaling regulation and associated with extracellular matrix organization and migration genes in breast cancer, including COL1A1, FN1, WNT5B, MMP11, MMP14 and SDC1. Gain- or loss-of-function experiments of PTK7 suggested that PTK7 promotes proliferation and migration in TNBC cell lines. PTK7 knockdown MDA-MB-468 cell bearing mouse model further demonstrated that PTK7-deficiency inhibits TNBC tumor progression in vivo. CONCLUSION: This study identified PTK7 as a potential marker of worse prognosis in TNBC and revealed PTK7 promotes TNBC metastasis and progression via EGFR/Akt signaling pathway.

3.
J Cell Mol Med ; 25(11): 4922-4937, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33939247

RESUMO

Long non-coding RNA (lncRNA) lnc-ISG20 has been found aberrantly up-regulated in the glomerular in the patients with diabetic nephropathy (DN). We aimed to elucidate the function and regulatory mechanism of lncRNA lnc-ISG20 on DN-induced renal fibrosis. Expression patterns of lnc-ISG20 in kidney tissues of DN patients were determined by RT-qPCR. Mouse models of DN were constructed, while MCs were cultured under normal glucose (NG)/high glucose (HG) conditions. The expression patterns of fibrosis marker proteins collagen IV, fibronectin and TGF-ß1 were measured with Western blot assay. In addition, the relationship among lnc-ISG20, miR-486-5p, NFAT5 and AKT were analysed using dual-luciferase reporter assay and RNA immunoprecipitation. The effect of lnc-ISG20 and miR-486/NFAT5/p-AKT axis on DN-associated renal fibrosis was also verified by means of rescue experiments. The expression levels of lnc-ISG20 were increased in DN patients, DN mouse kidney tissues and HG-treated MCs. Lnc-ISG20 silencing alleviated HG-induced fibrosis in MCs and delayed renal fibrosis in DN mice. Mechanistically, miR-486-5p was found to be a downstream miRNA of lnc-ISG20, while miR-486-5p inhibited the expression of NFAT5 by binding to its 3'UTR. NFAT5 overexpression aggravated HG-induced fibrosis by stimulating AKT phosphorylation. However, NFAT5 silencing reversed the promotion of in vitro and in vivo fibrosis caused by lnc-ISG20 overexpression. Our collective findings indicate that lnc-ISG20 promotes the renal fibrosis process in DN by activating AKT through the miR-486-5p/NFAT5 axis. High-expression levels of lnc-ISG20 may be a useful indicator for DN.


Assuntos
Nefropatias Diabéticas/complicações , Exorribonucleases/genética , Fibrose/patologia , Nefropatias/patologia , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Fatores de Transcrição/metabolismo , Animais , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Fibrose/etiologia , Fibrose/metabolismo , Humanos , Nefropatias/etiologia , Nefropatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fosforilação , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Fatores de Transcrição/genética
4.
J Cell Mol Med ; 25(23): 10798-10813, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-31568645

RESUMO

Diabetic nephropathy (DN) remains one of the severe complications associated with diabetes mellitus. It is worthwhile to uncover the underlying mechanisms of clinical benefits of human urine-derived stem cells (hUSCs) in the treatment of DN. At present, the clinical benefits associated with hUSCs in the treatment of DN remains unclear. Hence, our study aims to investigate protective effect of hUSC exosome along with microRNA-16-5p (miR-16-5p) on podocytes in DN via vascular endothelial growth factor A (VEGFA). Initially, miR-16-5p was predicated to target VEGFA based on data retrieved from several bioinformatics databases. Notably, dual-luciferase report gene assay provided further verification confirming the prediction. Moreover, our results demonstrated that high glucose (HG) stimulation could inhibit miR-16-5p and promote VEGFA in human podocytes (HPDCs). miR-16-5p in hUSCs was transferred through the exosome pathway to HG-treated HPDCs. The viability and apoptosis rate of podocytes after HG treatment together with expression of the related factors were subsequently determined. The results indicated that miR-16-5p secreted by hUSCs could improve podocyte injury induced by HG. In addition, VEGA silencing could also ameliorate HG-induced podocyte injury. Finally, hUSC exosomes containing overexpressed miR-16-5p were injected into diabetic rats via tail vein, followed by qualification of miR-16-5p and observation on the changes of podocytes, which revealed that overexpressed miR-16-5p in hUSCs conferred protective effects on HPDCs in diabetic rats. Taken together, the present study revealed that overexpressed miR-16-5p in hUSC exosomes could protect HPDCs induced by HG and suppress VEGFA expression and podocytic apoptosis, providing fresh insights for novel treatment of DN.


Assuntos
Nefropatias Diabéticas/genética , Exossomos/genética , MicroRNAs/genética , Podócitos/patologia , Células-Tronco/patologia , Animais , Apoptose/genética , Linhagem Celular , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/patologia , Glucose/genética , Células HEK293 , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular
5.
Int J Mol Med ; 45(5): 1627, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32323729

RESUMO

Int J Mol Med 41: [Related article:] 1030­1038, 2018; DOI: 10.3892/ijmm.2017.3268. An interested reader drew to our attention the fact that the western blots featured in Fig. 2B in the above article contained duplicated data: The data shown for the TGF­ß and vimentin protein bands were apparently identical; furthermore, there was a strong likelihood that the protein bands featured for the ZO­1 and SMAD­3 experiments were also the same, but flipped horizontally relative to the other. Following an investigation, the Journal was able to confirm that this duplication of the research data had probably occurred. On those grounds, the Editor of International Journal of Molecular Medicine has decided that the above paper should be retracted. We were unable to make contact with the authors of the article published in International Journal of Molecular Medicine, despite every effort to do so. The Editor deeply regrets any inconvenience that this retraction has caused to the the readership of the Journal.

6.
Int J Mol Med ; 41(2): 1030-1038, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29207016

RESUMO

The present study aimed to explore the roles of microRNA-21 (miR­21) and the transforming growth factor-ß (TGF-ß)/Smad signaling pathway in the development of peritoneal fibrosis (PF). First, dialysis effluents from 30 patients with PF were collected, and after the establishment of a mouse model of PF, hematoxylin and eosin (H&E) and Masson's staining were used to observe peritoneal tissues, inflammatory cells and blood vessels. High glucose was used to stimulate human peritoneal mesothelial cell lines and these stimulated cells were then transfected with miR­21 inhibitor. Immunofluorescence microscopy was applied for the observation of the transfected cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR­21, and RT-qPCR and western blot analysis were used to detect the mRNA and protein expression of Zonula occludens-1 (ZO-1), TGF-ß, Smad, vimentin and connective-tissue growth factor (CTGF). The mRNA and protein expression levels TGF-ß, Smad-3, vimentin and CTGF were elevated, while ZO-1 mRNA and protein expression was decreased with the prolonged duration of dialysis treatment in the patients with PF. The experiments using the mouse model of PF revealed that the peritoneal connective tissue was thickened, while the numbers of inflammatory cells and blood vessels were increased. The expression levels of miR­21, and the mRNA and protein expression levels of TGF-ß, Smad-3, vimentin and CTGF were increased over time, whereas the mRNA and protein expression levels ZO-1 constantly decreased in the mice in the experimental group. Moreoever, the expression of miR­21 positively correlated with the expression levels of TGF-ß, Smad-3, vimentin and CTGF, while it negatively correlated with the expression of ZO-1. The results of H&E and Masson's staining revealed that miR­21 expression was associated with the degree of PF. These findings thus indicate that miR­21 promotes the progression of PF through the activation of the TGF-ß/Smad signaling pathway.


Assuntos
MicroRNAs/genética , Fibrose Peritoneal/genética , Peritônio/metabolismo , Animais , Fator de Crescimento do Tecido Conjuntivo/genética , Progressão da Doença , Regulação da Expressão Gênica , Humanos , Camundongos , Fibrose Peritoneal/patologia , Peritônio/patologia , Transdução de Sinais , Proteína Smad3/genética , Fator de Crescimento Transformador beta/genética , Proteína da Zônula de Oclusão-1/genética
7.
Med Sci Monit ; 23: 3897-3903, 2017 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-28801998

RESUMO

BACKGROUND Resistin-like molecule beta (RELM-ß) has been reported to be associated with diabetic nephropathy (DN). However, the role of RELM-ß in DN is poorly understood. This study was conducted to delineate the underlying mechanisms of action and to investigate the role of RELM-ß in the primitive development of DN via MAPK signaling pathways. MATERIAL AND METHODS Lentivirus-mediated vectors and RNAi technology were used to establish the model of RELM-ß up-regulated and down-regulated expression in human mesangial cells (HMCs). The proliferation of HMCs was detected through CCK-8 method. The cell cycle and cell proliferation of HMCs was detected through flow cytometry. The MAPKs pathway protein activity was detected through Western blotting. RESULTS The HMCs with up-regulated and down-regulated expression of RELM-ß increased or decreased significantly at 2-3 days. The HMCs with high glucose intervention reversed the proliferation inhibition. The HMCs with exogenous glucose or RELM-ß protein intervention partially reversed the cell cycle inhibition. Among the MAPKs pathway, the phosphorylation activity of p38MAPK and JNK increased or decreased and ERK1/2 did not change in the overexpression or inhibition of RELM-ß. The p38 MAPK pathway inhibitor SB202190 significantly inhibited the proliferation of HMCs caused by overexpression of RELM-ß. Up-regulated expression of RELM-b induced the phosphorylation of p38 MAPK, JNK in HMCs and promoted HMCs proliferation and participated in early DN through the MAPKs pathway. CONCLUSIONS The results provide evidence that RELM-b is a potential molecular target for the treatment of DN.


Assuntos
Nefropatias Diabéticas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Sistema de Sinalização das MAP Quinases , Ciclo Celular/fisiologia , Divisão Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Nefropatias Diabéticas/patologia , Humanos , Células Mesangiais/metabolismo , Células Mesangiais/patologia , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
8.
FEBS Open Bio ; 6(1): 33-42, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27047740

RESUMO

Y-box-binding protein 1 (YB1) is a multifunctional transcription factor with vital roles in proliferation, differentiation and apoptosis. In this study, we have examined the role of its C-terminal domain (YB1 CTD) in proliferation, angiogenesis and tumorigenicity in breast cancer. Breast cancer cell line SK-BR-3 was infected with GFP-tagged YB1 CTD adenovirus expression vector. An 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) proliferation assay showed that YB1 CTD decreased SK-BR-3 cell proliferation, and down-regulated cyclin B1 and up-regulated p21 levels in SK-BR-3 cells. YB1 CTD overexpression changed the cytoskeletal organization and slightly inhibited the migration of SK-BR-3 cells. YB1 CTD also inhibited secreted VEGF expression in SK-BR-3 cells, which decreased SK-BR-3-induced EA.hy926 endothelial cell angiogenesis in vitro. YB1 CTD overexpression attenuated the ability of SK-BR-3 cells to form tumours in nude mice, and decreased in vivo VEGF levels and angiogenesis in the xenografts in SK-BR-3 tumour-bearing mice. Taken together, our findings demonstrate the vital role of YB1 CTD overexpression in inhibiting proliferation, angiogenesis and tumorigenicity of breast cancer cell line SK-BR-3.

9.
FEBS Open Bio ; 5: 147-54, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25834779

RESUMO

Krüppel-like factor 4 (KLF4) functions as either a tumor suppressor or an oncogene in different tissues by regulating the expression of various genes. The aim of this study was to reveal the functions of KLF4 in regulating breast cancer apoptosis, proliferation, and tumorigenic progression. KLF4 expression levels in breast cancer tissues and breast cancer cell lines were found to be much lower than those in nontumorous tissues and a nontransformed mammary epithelial cell line. KLF4 was upregulated in the tumor necrosis factor-α-induced SK-BR-3 breast cancer cell apoptotic process. Overexpression of KLF4 promoted SK-BR-3 breast cancer cell apoptosis and suppressed SK-BR-3 cell tumorigenicity in vivo.

10.
Anal Quant Cytopathol Histpathol ; 37(6): 353-63, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26860011

RESUMO

OBJECTIVE: To conduct a metaanalysis in order to determine the association between matrix metalloproteinase (MMP)-2 expression and renal cell carcinoma (RCC) progression. STUDY DESIGN: Cohort studies were identified after an exhaustive search of the following electronic databases: PubMed, China Biomedicine, Web of Science, Wanfang database, and China National Knowledge Infrastructure. Summary odds ratios with 95% confidence interval were calculated. RESULTS: Seventeen clinical studies were eligible for the present metaanalysis. Overall, increased MMP-2 protein expression levels had a positive correlation with several RCC clinical parameters, such as tumor node metastasis (TNM) stage, differentiation grade, lymph node metastasis (LNM), and tumor size (all p < 0.05). Country-stratified analysis revealed statistically significant differences in MMP-2 expression levels, based on the 4 clinical parameters studied, in the Chinese population (all p < 0.05). The results indicated that the MMP-2 protein level in RCC patients with non-clear cell type was higher than that in the patients with clear cell carcinoma (p < 0.05). A positive correlation was found between RCC differentiation grade and MMP-2 protein levels in only the streptavidin-peroxidase subgroup (p < 0.05), while there were significant associations between MMP-2 protein level and TNM stage, LNM, and tumor size (p < 0.05). CONCLUSION: Our metaanalysis suggests that RCC patients with a high MMP-2 expression level exhibit rapid progression of RCC and that high MMP-2 expression level is associated with poor prognosis.


Assuntos
Carcinoma de Células Renais/enzimologia , Neoplasias Renais/enzimologia , Adenocarcinoma de Células Claras/patologia , Humanos , Metástase Linfática , Metaloproteinase 2 da Matriz , Prognóstico , Neoplasias Gástricas/patologia
11.
Zhonghua Yi Xue Za Zhi ; 93(30): 2385-7, 2013 Aug 13.
Artigo em Chinês | MEDLINE | ID: mdl-24300208

RESUMO

OBJECTIVE: To explore the effects of low-dose radiation on the expression of immunogenic membrane molecules calreticulin (CRT) and MHC-I/II on the surface of human renal clear cell carcinoma 786-0 cells. METHODS: The inhibitory activity of low-dose radiation on cell line 786-0 was examined by CCK-8 assay. And the post-radiation membrane expressions of CRT, MHC-I and MHC-II were measured by flow cytometry while CRT was visualized by immunofluorescence photography. RESULTS: The inhibition rates on the proliferative capacities of four 786-0 cell lines rose with the incremental radiation doses of 0, 6, 12 and 24 Gy. And the CRT expression levels of each experimental group was significantly higher than that of the control group (P < 0.001). Along with incremental doses of irradiation, the average calreticulin fluorescence intensities increased gradually initially and then there was a downward trend. The membrane expressions of MHC-I and MHC-II of each experimental group was significantly higher than those of the control group (P < 0.05). As the irradiation dose increased, the average MHC-I fluorescence intensities increased gradually in a dose-dependent manner. CONCLUSION: The low-dose radiotherapy may up-regulate CRT and MHC class I/II related with the immunogenicity of tumor cells to induce immune response against tumors.


Assuntos
Calreticulina/genética , Carcinoma de Células Renais/imunologia , Genes MHC da Classe II/genética , Genes MHC Classe I/genética , Calreticulina/metabolismo , Humanos , Dosagem Radioterapêutica , Células Tumorais Cultivadas/imunologia , Células Tumorais Cultivadas/efeitos da radiação
12.
Chin Med J (Engl) ; 125(5): 794-800, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22490577

RESUMO

BACKGROUND: Adoptive transfer of allogeneic tumor-specific T cells often results in severe graft-versus-host disease (GVHD). Here, we sought to maximize graft-versus-tumor and minimize GVHD by using haploidentical T cells in pre-irradiated B16-melanoma bearing mice. METHODS: C57BL/6 mice bearing B16-melanoma tumors were irradiated with 0, 5, or 7 Gy total body irradiation (TBI), or 7 Gy TBI plus bone marrow transplantation. Tumor areas were measured every 3 days to assess the influence of irradiation treatment on tumor regression. B16-melanoma bearing mice were irradiated with 7 Gy TBI; sera and spleens were harvested at days 1, 3, 5, 7, 9, 11, and 13 after irradiation. White blood cell levels were measured and transforming growth factor ß1 (TGF-b1) and interleukin 10 (IL-10) levels in serum were detected using enzyme-linked immunosorbent assay (ELISA) kits. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry were performed to test TGF-b1, IL-10 and Foxp3 mRNA levels and the proportion of CD4+CD25+Foxp3+ T-regulatory cells (Tregs) in spleens. B16-melanoma bearing C57BL/6 mice were irradiated with 7 Gy TBI followed by syngeneic (Syn1/Syn2) or haploidentical (Hap1/Hap2), dendritic cell-induced cytotoxic T lymphocytes (DC-CTLs) treatment, tumor areas and system GVHD were observed every 3 days. Mice were killed 21 days after the DC-CTLs adoptive transfer; histologic analyses of eyes, skin, liver, lungs, and intestine were then performed. RESULTS: Irradiation with 7 Gy TBI on the B16-melanoma-bearing mice did not influence tumor regression compared to the control group; however, it down-regulated the proportion of Tregs in spleens and the TGF-b1 and IL-10 levels in sera and spleens, suggesting inhibition of autoimmunity and intervention of tumor microenvironment. Adoptive transfer of haploidentical DC-CTLs significantly inhibited B16-melanoma growth. GVHD assessment and histology analysis showed no significant difference among the groups. CONCLUSION: Adoptive transfer of haploidentical tumor-specific T cells in irradiation-pretreated B16-melanoma bearing mice preserved antitumor capacity without causing a GVHD response.


Assuntos
Melanoma Experimental/terapia , Linfócitos T/imunologia , Animais , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Doença Enxerto-Hospedeiro , Imunoterapia Adotiva/métodos , Masculino , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Linfócitos T Reguladores/imunologia
13.
Artigo em Chinês | MEDLINE | ID: mdl-21038665

RESUMO

OBJECTIVE: To determine the effect of activation of lambda-opioid receptor with U50, 488H, a selective kappa-opioid receptor agonist, on the changes in electrical coupling during prolonged ischemia and to explore the possible mechanism. METHODS: The isolated rat heart was perfused in a Langendorff apparatus. The effect of U50, 488H on electrical coupling parameters including onset of uncoupling, plateau time, slope and fold increase in r(t) was observed in isolated perfused rat heart subjected to global no-flow ischemia. The effect of U50, 488H on connexin 43 (Cx43) expression of ventricular muscle during ischemia was determined by immunohistochemistry. RESULTS: In the prolonged ischemia model, U50, 488H concentration dependently delayed the onset of uncoupling, increased time to plateau, and decreased the maximal rate of uncoupling during ischemia. The effect of U50, 488H on electrical uncoupling parameters during ischemia was abolished by a selective kappa-opioid receptor antagonist nor-BNI or a PKC inhibitor chelerythrine. The amount of Cx43 immunoreactive signal in ventricular muscle was greatly reduced after ischemia. U50, 488H markedly increased Cx43 expression during ischemia and its effect was also attenuated by nor-BNI or chelerythrine. CONCLUSION: These results demonstrated that U50, 488H delayed the onset of uncoupling and plateau time, decreased the maximal rate of uncoupling and increased Cx43 expression of ventricular muscle during ischemia, and these effects of U50, 488H were mediated by kappa-opioid receptor, in which activation of PKC was involved. The effect of U50, 488H on electrical coupling during ischemia was probably correlated with preservation of Cx43 in cardiac muscle.


Assuntos
(trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Animais , Benzofenantridinas/farmacologia , Conexina 43/metabolismo , Feminino , Coração/efeitos dos fármacos , Técnicas In Vitro , Miocárdio/metabolismo , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Opioides kappa/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Nat Genet ; 42(9): 759-63, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20729853

RESUMO

We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.


Assuntos
Povo Asiático/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Loci Gênicos , Proteínas de Membrana/genética , Fosfoinositídeo Fosfolipase C/genética , Idoso , Carcinoma de Células Escamosas/etnologia , Estudos de Casos e Controles , Cromossomos Humanos Par 10 , Cromossomos Humanos Par 20 , Neoplasias Esofágicas/etnologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Proteínas de Membrana Transportadoras , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/fisiologia
15.
Artigo em Chinês | MEDLINE | ID: mdl-21186618

RESUMO

AIM: To determine whether the cardioprotection of ischemic postconditioning and heptanol in ischemic heart against ischemia/reperfusion (I/R) is mediated by gap junction. METHODS: The effect of ischemic postconditioning, heptanol at different doses (0.03, 0.06, 0.30, and 0.60 mg/kg) and AAP10 (10 mg/kg) on the intact rat heart during 30 min ischemia and 2 h of reperfusion was observed. Ischemic postconditioning was achieved by 3 cycles of 10 s reperfusion/10 s regional ischemia starting at the beginning of the reperfusion. The infarct size and the arrhythmia scores were measured. The effect of ischemic postconditioning, heptanol at different doses (0.05, 0.10, 0.50 and 1.00 mmol/L) and AAP10 (1 x 10(-7)mol/L) on the isolated heart during 30 min ischemia and 2 h of reperfusion was observed. Ischemic postconditioning was achieved by 6 cycles of 10 s reperfusion/10 s global ischemia starting at the beginning of the reperfusion. The arrhythmia scores and conduction velocity of ventricle muscle were measured. RESULTS: In the intact rat heart model, ischemic postconditioning and heptanol reduced infarct size and arrhythmia scores. In the Langendorff perfused rat heart model, ischemic postconditioning and heptanol reduced arrhythmia scores and conduction velocity of ventricle muscle. Administration of AAP10, an opener of gap junction attenuated the cardioprotection of ischemic postconditioning and heptanol. CONCLUSION: The cardioprotection of ischemic postconditioning and heptanol may be related to the attenuation of gap junction communication on myocardiac ischemia/reperfusion injury.


Assuntos
Junções Comunicantes/fisiologia , Pós-Condicionamento Isquêmico/métodos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Animais , Heptanol/farmacologia , Masculino , Isquemia Miocárdica/fisiopatologia , Ratos , Ratos Sprague-Dawley
17.
J Physiol Biochem ; 62(1): 1-8, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16909926

RESUMO

Diabetic cardiomyopathy is characterized by reduced cardiac contractility due to direct changes in myocardium function independent of vascular disease. This study is to investigate the alterations of cardiac sarcoplasmic reticulum Ca2+ -ATPase activity and cardiac function in streptozotocin-induced diabetic rats. Diabetes mellitus (DM) was induced in male Wistar rats by intraperitoneal injection of streptozotocin. The activity of myocardium sarcoplasmic reticulum Ca2+ -ATPase and the left ventricular hemodynamic parameters were measured in DM rats 4 weeks, 6 weeks and 8 weeks after streptozotocin was administered. Phospholamban mRNA expression was detected by reverse transcription-polymerase chain reaction, and the protein levels of phospholamban and sarcoplasmic reticulum Ca2+ -ATPase were determined by Western blot. Normal rats served as control group. It was found that in DM rats 4 weeks after streptozotocin injection, the cardiac function, myocardium sarcoplasmic reticulum Ca2+ -ATPase activity, phospholamban mRNA and phospholamban protein were not significantly changed compared with those in the control rats. At 6 and 8 weeks after the streptozotocin injection, DM rats showed a significant decrease in sarcoplasmic reticulum Ca2+ -ATPase activity and cardiac function, as indicated by an increase of LVEDP and a marked depression in LVSP and +/- dP/dtmax. At the same time points, increases in phospholamban mRNA and protein levels were observed in DM rats. Sarcoplasmic reticulum Ca2+ -ATPase protein level showed no significant alterations in all DM rats compared with that in control rats. Our work confirms that sarcoplasmic reticulum Ca2+ -ATPase activity is depressed in rats with streptozotocin-induced DM, which is accompanied by elevated phospholamban protein level thus contribute to the pathogenesis of cardiac dysfunction in diabetic rats.


Assuntos
ATPases Transportadoras de Cálcio/metabolismo , Diabetes Mellitus Experimental/metabolismo , Disfunção Ventricular Esquerda/metabolismo , Animais , Pressão Sanguínea/fisiologia , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Expressão Gênica/genética , Coração/fisiopatologia , Masculino , Miocárdio/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Disfunção Ventricular Esquerda/fisiopatologia
18.
Artigo em Chinês | MEDLINE | ID: mdl-21186583

RESUMO

AIM: To determine whether activation of kappa-opioid receptor with U50,488H, a selective kappa-opioid receptor agonist, produces any changes in electrical uncoupling during prolonged ischemia and whether these changes in electrical uncoupling is associated with the cardioprotection induced by kappa-opioid receptor activation, and to explore the possible mechanism. METHODS: (1) To observe the effect of U50,488H (10(-7), 10(-6), 3 x10(-6) and 10(-5) mol/L), a selective kappa-opioid receptor agonist, or with a selective kappa-opioid receptor antagonist nor-BNI (5 x 10(-6) mol/L), or with a mitochondrial K(ATP) channel inhibitor 5-HD on myocardium during ischemia/reperfusion in isolated perfused rat heart. Parameters of measurements include hemodynamic data, formazan content, heart rate, coronary flow, and lactate dehydrogenase (LDH). (2) To examine the effect of U50,488H of different concentration on electrical coupling parameters (including onset of uncoupling, plateau time, slope, and fold increase in r1) during 70 min myocardial ischemia in isolated perfused rat heart. RESULTS: (1) Pretreatment with U50,488H concentration dependently increased formazan content and reduced LDH release induced by 30 min of ischemia and 120 min of reperfusion. (2) The onset of electrical uncoupling and plateau time during prolonged ischemia was delayed by kappa-opioid receptor activation with U50,488H. (3) Linear regression analysis shown that the increase in formazan content and decrease in LDH release produced by kappa-opioid receptor activation was associated with delayed electrical uncoupling during prolonged ischemia. (4) The effects of U50,488H on formazan content, LDH release and on electrical coupling were abolished by nor-BNI, or 5-HD. CONCLUSION: This results demonstrate that the onset of electrical uncoupling during prolonged ischemia is delayed by kappa-opioid receptor activation with a selective kappa-opioid receptor agonist U50,488H, and that delayed electrical uncoupling is associated with the cardioprotection induced by kappa-opioid receptor activation with U50,488H. These effects of kappa-opioid receptor activation with U50,488H are mediated by mitochondrial K(ATP) channels.


Assuntos
Coração/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Receptores Opioides kappa , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Animais , Anti-Hipertensivos , Coração/efeitos dos fármacos , Técnicas In Vitro , Masculino , Miocárdio/metabolismo , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Canais de Potássio/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Opioides kappa/agonistas
19.
Scand Cardiovasc J ; 39(6): 375-82, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16352491

RESUMO

OBJECTIVES: To determine whether the kappa-opioid receptor agonist U50,488H affects electrical uncoupling during prolonged ischemia and, if so, whether the changes are associated with its cardioprotective action. DESIGN: The isolated rat heart was perfused in a Langendorff apparatus. Formazan content, lactate dehydrogenase (LDH) and hemodynamic parameters were measured to confirm the cardioprotective effect of U50,488H. The effects of U50,488H on electrical coupling during prolonged ischemia were also measured. RESULTS: U50,488H concentration-dependently increased formazan content and reduced LDH release, and the ameliorating effect of 10(-5) mol/L U50,488H was abolished by 5 x 10(-6) mol/L nor-binaltorphimine (nor-BNI), a selective kappa-opioid receptor antagonist, or 10(-4) mol/L 5-hydroxydecanoate (5-HD), a selective mitochondrial ATP-sensitive K(+) (K(ATP)) channel blocker. The onset of electrical uncoupling during prolonged ischemia was delayed by U50,488H, and the delay was not only abolished, but also advanced by nor-BNI or 5-HD relative to the control group. CONCLUSIONS: These results demonstrate that delayed uncoupling during prolonged ischemia is associated with the cardioprotection of U50,488H, and these effects of U50,488H are mediated by mitochondrial K(ATP) channels.


Assuntos
(trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Cardiotônicos/farmacologia , Coração/efeitos dos fármacos , Isquemia Miocárdica/prevenção & controle , Canais de Potássio/efeitos dos fármacos , Receptores Opioides kappa/agonistas , Animais , Comunicação Celular , Técnicas Eletrofisiológicas Cardíacas , Formazans , Junções Comunicantes/efeitos dos fármacos , Proteínas de Choque Térmico HSC70/efeitos dos fármacos , Coração/fisiopatologia , Masculino , Isquemia Miocárdica/fisiopatologia , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
20.
Clin Exp Pharmacol Physiol ; 32(8): 655-62, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16120193

RESUMO

1. It is known that infusion of the gap junction uncoupler heptanol, before ischaemia or during reperfusion, limits myocardial infarct size. However, whether this cardiac effect is linked to the effect of heptanol on communication across gap junctions has not been elucidated. The aims of the present study were to examine the effect of heptanol on infarct size, arrhythmias and myocardial tissue resistance and to assess whether changes in electrical coupling correlate with cardiac protection. 2. Rat isolated, perfused hearts were subjected to a 24 min infusion of heptanol (0.05, 0.1, 0.5 or 1.0 mmol/L) followed by 20 min regional ischaemia and 60 min reperfusion, or by 70 min global no-flow ischaemia. The effective refractory period, action potential and conduction velocity were measured in papillary muscles from the right ventricle. Heptanol markedly decreased arrhythmia scores during ischaemia and reperfusion, as well as reducing infarct size to a degree similar to that induced by ischaemic preconditioning. In the prolonged ischaemia model, heptanol delayed the onset of uncoupling, increased time to plateau and decreased the maximal rate of uncoupling during ischaemia. Ischaemic preconditioning had similar effects on these parameters. In papillary muscle, heptanol reduced the conduction velocity of the action potential in a dose-dependent manner, but had no significant effect on resting potential, action potential amplitude, action potential duration, maximal upstroke of depolarization or effective refractory period. 3. These results demonstrate that treatment with the gap junction uncoupler heptanol confers cardioprotection against ischaemia and this effect is related to delayed electrical uncoupling during prolonged ischaemia.


Assuntos
Coração/efeitos dos fármacos , Heptanol/farmacologia , Isquemia Miocárdica/prevenção & controle , Isquemia Miocárdica/fisiopatologia , Animais , Relação Dose-Resposta a Droga , Eletrofisiologia , Junções Comunicantes/efeitos dos fármacos , Masculino , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Técnicas de Cultura de Órgãos , Músculos Papilares/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
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