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2.
Dig Dis Sci ; 64(6): 1560-1570, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30673982

RESUMEN

BACKGROUND: The activation of hepatic stellate cells (HSCs) is involved in hepatic fibrogenesis and is regulated by the decreased expression of peroxisome proliferator-activated receptor γ (PPARγ). Rosiglitazone (RGZ) is a highly potent agonist of PPARγ. AIMS: To clarify molecular regulatory mechanism of RGZ in the activation of HSCs in hepatic fibrosis. METHODS: A mouse model of hepatic fibrosis was established by carbon tetrachloride with or without RGZ intervention. A vector carrying pcDNA-HOTAIR was constructed and injected into a mouse model. HSCs were isolated from liver tissue and activated by transforming growth factor-ß. The expression of miR-124-3p, HOTAIR, Col1A1, α-SMA, and PPARγ mRNAs was measured by quantitative real-time PCR. The level of PPARγ was measured by Western blotting. The interaction between HOTAIR and PPARγ was assessed by RNA immunoprecipitation (RIP) and RNA pull-down. The target gene of miR-124-3p was determined by luciferase reporter assay and RNA interference approaches. RESULTS: The expression of Col1A1 and α-SMA was reduced after RGZ intervention. Different expressions of HOTAIR and miR-124-3p were observed in liver tissue and HSCs. The luciferase reporter assay and RNA interference approaches indicated that miR-124-3p negatively regulated HOTAIR expression. RIP and RNA pull-down results revealed that PPARγ was interacted by HOTAIR. The therapeutic effect of RGZ on hepatic fibrosis was reversed by overexpression of HOTAIR. CONCLUSIONS: RGZ inhibits the activation of HSCs by up-regulating miR-124-3p. The silencing of HOTAIR by miR-124-3p in HSC activation provided the foundation to understand interactions of ncRNAs and potential treatment target in hepatic fibrosis.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Células Estrelladas Hepáticas/efectos de los fármacos , Cirrosis Hepática Experimental/prevención & control , Hígado/efectos de los fármacos , MicroARNs/metabolismo , Rosiglitazona/farmacología , Animales , Tetracloruro de Carbono , Células Cultivadas , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática Experimental/genética , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/patología , Masculino , Ratones Endogámicos BALB C , MicroARNs/genética , PPAR gamma/agonistas , PPAR gamma/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba
3.
Oncol Lett ; 16(3): 3635-3641, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30127972

RESUMEN

Dynamin-1-like protein (DNM1L) encodes a member of the dynamin superfamily of GTPases. It mediates mitochondrial and peroxisomal division and is involved in the regulation of apoptosis. However, its role in gastric cancer remains unclear. MKN-45 gastric cancer cells were transfected with short hairpin RNA (shRNA) to suppress DNM1L expression. MTT, flow cytometry, and Transwell assays were used to detect the changes in cell proliferation, apoptosis, and invasion, respectively. Immunohistochemistry was used to detect DNM1L expression in gastric adenocarcinoma specimens, and the association of DNM1L expression with clinicopathological features and prognosis was analyzed. After the suppression of endogenous DNM1L expression in MKN-45 cells with shRNA, cell proliferation and invasion rates were significantly reduced, whereas apoptosis was significantly increased (all P<0.01). The expression of DNM1L was significantly higher in gastric adenocarcinoma specimens compared with that in pericarcinoma tissues (P<0.001). The expression of DNM1L increased with increasing infiltration depth, lymphatic metastasis, and higher tumor node metastasis stage (P<0.05). The expression of DNM1L associated negatively with prognosis (P<0.01). DNM1L plays a critical role in the proliferation, invasion and apoptosis of human gastric adenocarcinoma. DNM1L expression has prognostic significance for the survival of patients with gastric adenocarcinoma.

4.
Liver Int ; 36(12): 1836-1847, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27246112

RESUMEN

BACKGROUND & AIMS: BCAT1 initiates the catabolism of branched-chain amino acids. Here, we investigated the function of BCAT1 and its transcriptional regulatory mechanism in hepatocellular carcinoma (HCC). METHODS: RNASeq was used to evaluate BCAT1 mRNA levels in HCC and normal matched specimens. After the exogenous expression of BCAT1 in BEL-7404 cells and the suppression of endogenous BCAT1 expression with shRNA in HepG2 cells, the cell proliferation, clone-forming ability and cell-cycle changes were measured with MTT assay, colony-forming assay and flow cytometry respectively. A xenograft model was used to investigate the effect of BCAT1 on cancer growth in vivo. Chromatin immunoprecipitation and luciferase reporter technologies were used to confirm the transcriptional regulation of the BCAT1 gene by MYC. The expression of the BCAT1 and MYC proteins in 122 HCC tissues was determined with an immunohistochemical analysis. RESULTS: BCAT1 mRNA was clearly increased in HCC tissues and hepatomas. The ectopic expression of BCAT1 in BEL-7404 cells enhanced their proliferation, clone formation, tumourigenic properties, S-G2 /M phase transition and chemoresistance to cisplatin. The suppression of BCAT1 expression in HepG2 cells significantly inhibited their proliferation, clone formation, and S-G2 /M phase transition and caused their chemosensitization to cisplatin. MYC affected the transcriptional regulation of BCAT1. Clinical data showed that BCAT1 expression correlated with a significantly poorer prognosis. CONCLUSION: BCAT1 plays a pathogenic role in HCC by causing cell proliferation and chemoresistance. The MYC transcription factor is involved in regulating the transcriptional activity of BCAT1. BCAT1 expression has prognostic significance for the survival of patients with HCC.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma Hepatocelular/genética , Cisplatino/farmacología , Resistencia a Antineoplásicos , Neoplasias Hepáticas/genética , Transaminasas/genética , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , China , Modelos Animales de Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Pronóstico , Proteínas Proto-Oncogénicas c-myc/genética , ARN Interferente Pequeño/genética , Ensayos Antitumor por Modelo de Xenoinjerto
5.
World J Surg Oncol ; 13: 52, 2015 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-25890096

RESUMEN

BACKGROUND: Bone marrow-derived stem cells (BMSCs) are locally adjacent to the tumor tissues and may interact with tumor cells directly. The purpose of this study was to explore the effects of BMSCs on the proliferation and invasion of osteosarcoma cells in vitro and the possible mechanism involved. METHODS: BMSCs were co-cultured with osteosarcoma cells, and CCK-8 assay was used to measure cell proliferation. The ELISA method was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. Reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the expression of CXCR4 in osteosarcoma cells and BMSCs. Matrigel invasion assay was performed to measure tumor cell invasion. RESULTS: SDF-1 was detected in the supernatants of BMSCs, but not in osteosarcoma cells. Higher CXCR4 mRNA levels were detected in the osteosarcoma cell lines compared to BMSCs. In addition, conditioned medium from BMSCs can promote the proliferation and invasion of osteosarcoma cells, and AMD3100, an antagonist for CXCR4, can significantly downregulate these growth-promoting effects. CONCLUSIONS: BMSCs can promote the proliferation and invasion of osteosarcoma cells, which may involve the SDF-1/CXCR4 axis.


Asunto(s)
Células de la Médula Ósea/patología , Neoplasias Óseas/patología , Movimiento Celular , Proliferación Celular , Células Madre Mesenquimatosas/patología , Osteosarcoma/patología , Apoptosis , Western Blotting , Células de la Médula Ósea/metabolismo , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Citometría de Flujo , Humanos , Técnicas para Inmunoenzimas , Células Madre Mesenquimatosas/metabolismo , Osteosarcoma/genética , Osteosarcoma/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas
6.
Int J Clin Exp Pathol ; 8(11): 15007-12, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26823836

RESUMEN

CIP2A is highly expressed in a variety of malignancies. We determined the expression and clinical significance of CIP2A in patients with advanced gastric cancer. CIP2A protein was expressed in 25 of 37 cancer tissue specimens. There was no correlation between CIP2A and PGP, GST-π, Topo-II, and LRP expression. Survival analysis showed significant differences between the survival rate of the CIP2A protein-positive and -negative groups (χ(2)=4.509, P=0.034), but the degree of positive expression was unrelated to survival time (χ(2)=4.639, P=0.098). CIP2A expression may have no prospective value for optimizing chemotherapy regimens, but it can be an indicator for patient prognosis.


Asunto(s)
Subfamilia B de Transportador de Casetes de Unión a ATP/biosíntesis , Adenocarcinoma/patología , Autoantígenos/biosíntesis , Biomarcadores de Tumor/análisis , Proteínas de la Membrana/biosíntesis , Neoplasias Gástricas/patología , Subfamilia B de Transportador de Casetes de Unión a ATP/análisis , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Adulto , Anciano , Autoantígenos/análisis , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular , Estimación de Kaplan-Meier , Masculino , Proteínas de la Membrana/análisis , Persona de Mediana Edad , Pronóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad
7.
Prz Gastroenterol ; 9(1): 43-8, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24868298

RESUMEN

INTRODUCTION: Acute pancreatitis (AP) protease release induces lung parenchymal destruction via inflammatory mediators. Ginkgo biloba has been reported to have anti-inflammatory effects. AIM: To evaluate the effect of ginkgo biloba extract on experimental acute pancreatitis-associated lung injury in the rat and to investigate the underlying mechanisms. MATERIAL AND METHODS: Acute pancreatitis was induced in rats by injection of 5% sodium taurocholate into the biliary pancreatic duct. Ginkgo biloba extract (GBE) was administered and pancreas and lung injury were assessed by histological examination. Alveolar macrophages were harvested by bronchoalveolar lavage. Specificity fluorescent probe DAF-FM-DA was applied to observe nitric oxide (NO) bioavailability in alveolar macrophage. The expression of tumour necrosis factor α (TNF-α) and macrophage migration inhibitory factor (MIF) protein in alveolar macrophage was studied by ELISA. RESULTS: In sodium taurocholate-induced acute pancreatitis, treatment with GBE significantly protected rats against lung injury associated with pancreatitis in histological sections. Ginkgo biloba extract had a tendency to down-regulate NO bioavailability compared with the AP group, but without statistical significance. Moreover, TNF-α and MIF at protein levels in alveolar macrophage with GBE treatment were decreased compared with the AP group. CONCLUSIONS: These results suggest that GBE could effectively protect rats against acute pancreatitis-associated lung injury. The GBE may inhibit excessive activation of alveolar macrophages from acute pancreatitis-associated lung injury through down-regulation of generation of NO, TNF-α and MIF. These findings suggest that ginkgo biloba extract is a suitable candidate as an effective strategy against acute pancreatitis-associated lung injury.

8.
Phytother Res ; 28(9): 1342-8, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24596136

RESUMEN

The therapeutic potential of baicalein against hepatoma cells was evaluated in vitro and in vivo. In cell viability assays, baicalein showed significant cytotoxicity against the hepatocellular carcinoma cell lines H22, Bel-7404, and Hep G2 and moderate cytotoxicity against immortalized human hepatocytes. Baicalein induced G0/G1-phase arrest in hepatocellular carcinoma cells, inhibited AKT, and promoted the degradation of ß-catenin and cyclin D1 without activation of GSK-3ß. Furthermore, baicalein significantly inhibited H22 xenograft tumor growth without causing obvious adverse effects on weight or liver and spleen weight indexes in ICR mice. Immunohistochemical analysis showed that the inhibition of tumor growth in baicalein-treated mice was associated with decreased AKT, ß-catenin, and cyclin D1 expression ex vivo. Our data indicate that baicalein might regulate cyclin D1 transcription via a ß-catenin-dependent mechanism, leading to cell cycle arrest at G0/G1 phase and impaired cancer cell proliferation. These results suggest that baicalein is a potential candidate for the treatment of hepatocellular carcinoma.


Asunto(s)
Carcinoma Hepatocelular/patología , Flavanonas/farmacología , Neoplasias Hepáticas/patología , Animales , Carcinoma Hepatocelular/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclina D1/metabolismo , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Ratones Endogámicos ICR , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , beta Catenina/metabolismo
9.
Med Oncol ; 30(2): 512, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23435990

RESUMEN

The outcome is variable for unresectable locally advanced non-small-cell lung cancer (ULANSCLC) patients treated with radio(chemo)therapy. The aim of this study is to investigate whether single-nucleotide polymorphisms (SNPs) in the transforming growth factor-beta1 (TGF-ß1) gene are associated with overall survival (OS) in ULANSCLC patients treated with definitive radio(chemo)therapy. A total of 109 patients who had available blood samples and complete clinical and follow-up information were enrolled. DNA from blood was genotyped for two SNPs: TGF-ß1 C-509T and T+869C. Kaplan-Meier survival analysis, log-rank test, and Cox's proportional hazard model were used to evaluate associations between genotypes and OS. Log-rank test showed that TGF-ß1 C-509T significantly correlated with OS (pooled P = 0.017). Both univariate and multivariate analyses showed that TGF-ß1 C-509T CC genotype was significantly associated with better OS than CT or TT genotypes. These results indicate that TGF-ß1 C-509T CC genotype is significantly associated with better OS in ULANSCLC patients treated with radio(chemo)therapy as a potential independent survival predictor.


Asunto(s)
Pueblo Asiatico/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Quimioradioterapia , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple/genética , Factor de Crecimiento Transformador beta1/genética , Adulto , Anciano , Pueblo Asiatico/etnología , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/etnología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia/tendencias , Estudios de Cohortes , Femenino , Estudios de Asociación Genética/tendencias , Predisposición Genética a la Enfermedad/etnología , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/etnología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Resultado del Tratamiento
10.
World J Gastroenterol ; 18(28): 3696-704, 2012 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-22851861

RESUMEN

AIM: To investigate the mechanism of interleukin (IL)-6 secretion through blocking the IL-17A/IL-17A receptor (IL-17RA) signaling pathway with a short hairpin RNA (shRNA) in hepatic stellate cells (HSCs) in vitro. METHODS: HSCs were derived from the livers of adult male Sprague-Dawley rats. IL-6 expression was evaluated using real-time quantitative polymerase chain reaction and enzyme linked immunosorbent assay. The phosphorylation activity of p38 mitogen activated protein kinases (MAPK) and extracellular regulated protein kinases (ERK) 1/2 upon induction by IL-17A and suppression by IL-17RA shRNA were examined using Western blotting. RESULTS: IL-6 expression induced by IL-17A was significantly increased compared to control in HSCs (P < 0.01 in a dose-dependent manner). Suppression of IL-17RA using lentiviral-mediated shRNA inhibited IL-6 expression induced by IL-17A compared to group with only IL-17A treatment (1.44 ± 0.17 vs 4.07 ± 0.43, P < 0.01). IL-17A induced rapid phosphorylation of p38 MAPK and ERK1/2 after 5 min exposure, and showed the strongest levels of phosphorylation of p38 MAPK and ERK1/2 at 15 min in IL-17A-treated HSCs. IL-6 mRNA expression induced by IL-17A (100 ng/mL) for 3 h exposure was inhibited by preincubation with specific inhibitors of p38 MAPK (SB-203580) and ERK1/2 (PD-98059) compared to groups without inhibitors preincubation (1.67 ± 0.24, 2.01 ± 0.10 vs 4.08 ± 0.59, P < 0.01). Moreover, Lentiviral-mediated IL-17RA shRNA 1 inhibited IL-17A-induced IL-6 mRNA expression compared to random shRNA in HSCs (1.44 ± 0.17 vs 3.98 ± 0.68, P < 0.01). Lentiviral-mediated IL-17RA shRNA 1 inhibited phosphorylation of p38 MAPK and ERK1/2 induced by 15 min IL-17A (100 ng/mL) exposure. CONCLUSION: Down-regulation of the IL-17RA receptor by shRNA decreased IL-6 expression induced by IL-17A via p38 MAPK and ERK1/2 phosphorylation in HSCs. Suppression of IL-17RA expression may be a strategy to reduce the inflammatory response induced by IL-17A in the liver.


Asunto(s)
Regulación de la Expresión Génica , Células Estrelladas Hepáticas/citología , Interleucina-6/metabolismo , Lentivirus/genética , Receptores de Interleucina-17/metabolismo , Animales , Secuencia de Bases , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Vectores Genéticos , Inflamación , Cirrosis Hepática/patología , Masculino , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Datos de Secuencia Molecular , Fosforilación , Plásmidos/metabolismo , ARN Interferente Pequeño/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
11.
J Environ Sci (China) ; 17(4): 615-9, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16158590

RESUMEN

A novel thermal biosensor based on enzyme reaction for pesticides detection has been developed. This biosensor is a flow injection analysis system and consists of two channels with enzyme reaction column and identical reference column, which is set for eliminating the unspecific heat. The enzyme reaction takes place in the enzyme reaction column at a constant temperature (40 degrees C) realized by a thermoelectric thermostat. Thermosensor based on the thermoelectric module containing 127 serial BiTe-thermocouples is used to monitor the temperature difference between two effluents from enzyme reaction column and reference column. The ability of this biosensor to detect pesticides is demonstrated by the decreased degree of the hydrolytic heat in two types of thermosensor mode. The hydrolytic reaction is inhibited by 36% at 1 mg/L DDVP and 50% at 10 mg/L DDVP when cell-typed thermosensor is used. The percent inhibition is 30% at 1 mg/L DDVP and 42% at 10 mg/L DDVP in tube-typed thermosensor mode. The detection for real sample shows that this biosensor can be used for detection of organophosphate pesticides residue.


Asunto(s)
Técnicas Biosensibles , Esterasas/metabolismo , Plaguicidas/análisis , Animales , Pollos , Análisis de Inyección de Flujo , Hígado/enzimología
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