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Inflammation has been acknowledged as one of the pathological alterations in various cardiovascular disorders. Parkin has been found to be associated with mitochondrial protection. In the present study, we explored the influence of Parkin overexpression on cardiomyocyte induced by LPS-mediated inflammation response. Our results demonstrated that cardiomyocyte viability was reduced and apoptotic rate was increased upon LPS treatment, an effect that may be caused by cardiomyocyte oxidative stress. At the molecular levels, LPS treatment promoted ROS production, a result that was followed by a drop in the levels of anti-oxidants. Interestingly, Parkin overexpression significantly promoted cardiomyocyte survival and this cardioprotective was attributable to the anti-oxidative property. Parkin overexpression enhanced the expression of anti-oxidative factors such as GSH, SOD and GPX, resulting into depressed ROS production. Further, we found that Parkin modulated cellular anti-oxidative capacity through the Nrf2/ARE signaling pathway. This finding demonstrates that oxidative stress could be considered as the core of inflammation response. Further, therapeutic approaches targeting Parkin would improve cardiomyocyte anti-oxidative capacity through activating Nrf2/ARE signaling pathway.
Assuntos
Elementos de Resposta Antioxidante , Antioxidantes/farmacologia , Apoptose , Inflamação/fisiopatologia , Miócitos Cardíacos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Inflamação/induzido quimicamente , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Mitocôndrias , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Ubiquitina-Proteína Ligases/genéticaRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor with high fatality rate. Recent studies reported that up-regulation of long non-coding RNA antisense non-coding RNA in the INK4 locus (lncRNA ANRIL) was found in HCC tissues, and which could affect HCC cells biological processes. However, the potential molecular mechanism of ANRIL in HCC is still unclear. The study aimed to uncover the effect of ANRIL on HepG2 cells growth, migration and invasion. METHODS: The knockdown expression vectors of ANRIL were transfected into HepG2 cells, and qRT-PCR, CCK-8, flow cytometry, Transwell and western blot assays were performed to analyze the effect of ANRIL on cell proliferation, apoptosis, migration and invasion. The relative expression of miR-191 was then examined in ANRIL knockdown vector transfected cells. These experiments were repeated again for exploring the effect of miR-191 on HepG2 cells. NF-κB and Wnt/ß-catenin signaling pathways were examined by using western blot assay. RESULTS: Knockdown of ANRIL inhibited proliferation, induced apoptosis, meanwhile suppressed migration and invasion of HepG2 cells. Additionally, the results showed that the expression level of miR-191 was down-regulated by ANRIL knockdown in HepG2 cells. Importantly, overexpression of miR-191 reversed the anti-tumor effect of ANRIL on cell proliferation, apoptosis, migration and invasion in HepG2 cells. Besides, we found that ANRIL knockdown inactivated NF-κB and Wnt/ß-catenin pathways by regulating miR-191. CONCLUSIONS: These data demonstrated that ANRIL knockdown suppressed proliferation, migration, invasion, and promoted apoptosis in HepG2 cells by down-regulating miR-191 and inactivating NF-κB and Wnt/ß-catenin signaling pathways.
Assuntos
Carcinoma Hepatocelular/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , MicroRNAs/genética , Interferência de RNA , RNA Longo não Codificante/genética , Adolescente , Apoptose/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Técnicas de Silenciamento de Genes , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , MasculinoRESUMO
PURPOSE: Fucoidan is a natural bioactive product with broad therapeutic applications. Hepatocellular carcinoma (HCC) is a common malignancy of the liver associated with a relatively high mortality rate; thus, effective treatments are urgently needed. Here, the effects of fucoidan on HCC and the underlying mechanism were explored. METHODS: The proliferation and apoptosis of two HCC cell lines (BEL-7402 and LM3) treated with different concentrations of fucoidan or saline were assessed. The levels of proliferating cell nuclear antigen (PCNA) and CCK8 assay were used to determine proliferative capabilities of BEL-7402 and LM3 cells. Apoptosis of LM3 cells was assessed by Hoechst 33342 staining, Western blotting and flow cytometry. The capability of fucoidan to inhibit the growth of LM3 cells was investigated by monitoring of the p38 MAPK/ERK pathways and the upstream kinases, PI3K/Akt. LM3 xenograft tumors were used for in vivo verification. RESULTS: Cell proliferation and apoptosis assays consistently showed that fucoidan has an inhibitory effect on cell growth. Fucoidan significantly promoted apoptosis of LM3 cells through a mechanism involving activation of caspases 8, 9, and 3 accompanied by changes in B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax), as well as changes in the phosphorylation of p38 MAPK and ERK. Fucoidan also altered the phosphorylation of its upstream kinase, Akt. Fucoidan treatment markedly reduced the growth of LM3 xenograft tumors, consistent with the in vitro results. CONCLUSION: Fucoidan conveys antitumor effects and, thus, should be further explored as a potential treatment option for HCC.
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RATIONALE: With the development of endoscopic technique and the improvement of available accessories, endoscopic therapy became to play an important role in the management of gastrointestinal submucosal tumors (SMTs). PATIENTS CONCERNS: A gastric SMT which was suspected to be gastrointestinal stroma tumor (GIST) was diagnosed in a liver transplant recipient who received transplanted operation 11 months ago. DIAGNOSIS: gastric SMT, post-liver transplantation INTERVENTIONS:: Endoscopic full-thickness resection (EFR) was preformed to remove the tumor. The operation time was 50 minutes and oral immunosuppressant drug was not interrupted in the postoperative period. OUTCOMES: The clinical course was uneventful and slightly elevated liver enzyme was observed on the fourth day after operation. The pathological diagnosis was GIST with complete capsule. LESSONS: Our successful experience showed that EFR is a feasible, safe and efficacious treatment for small (<2âcm) gastric GIST in liver transplant recipients, providing the advantages of little damage, short operative time, stable graft function, without compromising postoperative outcomes.
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Gastrectomia/métodos , Tumores do Estroma Gastrointestinal/cirurgia , Neoplasias Gástricas/cirurgia , Transplantados , Adulto , Idoso , Endoscopia/métodos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Humanos , Imunossupressores/uso terapêutico , Transplante de Fígado , Masculino , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Gastric adenocarcinoma of fundic gland type (GA-FG) has recently been proposed as a novel histological type of gastric cancer. CASE SUMMARY: We report a case of GA-FG in a 77-year-old Chinese woman with epigastric distention who was referred to endoscopy for the management of an incidentally found submucosal tumor-like elevated lesion in the lower part of the gastric body. The tumor occurred after Helicobacter pylori (H. pylori) eradication therapy without long-term use of proton pump inhibitors. Complete and curable removal of the tumor was performed by endoscopic submucosal dissection. Histopathological findings showed numerous cells with basophilic cytoplasm and mildly atypical nuclei-like chief cells of the fundic gland. The tumor was observed to have the so-called "endless glands" pattern of the well-differentiated mixed phenotype. A safe resection margin without lymphatic and venous invasion was observed. As the tumor occurred after H. pylori eradication therapy, it is unknown whether there was a relationship with H. pylori eradication. The patient will be followed up by periodic gastroscopic observation. CONCLUSION: In conclusion, we report a case of GA-FG after H. pylori eradication therapy without long-term proton pump inhibitors use. Further analysis of similar cases will reveal the clinical behavior of GA-FG.
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A simple method was developed for the determination of biogenic amines in aquatic food products using a reverse-phase high-performance liquid chromatography with postcolumn automatic o-phthalaldehyde derivatization and fluorescence detection. The linearity, repeatability, and recovery of the method for seven amines (tyramine, putrescine, cadaverine, histamine, agmatine, spermidine, and spermine) were evaluated. This optimized method was applied to detect biogenic amines in squid and white prawn during refrigerated storage. Sensory analysis, pH value, and total volatile base nitrogen value were combined to evaluate the freshness quality of these two raw materials. Agmatine and cadaverine in squid, cadaverine, and putrescine in white prawn were the most obviously changed amines during the storage at two different temperatures, and these biogenic amines could be the effective quality indicators for the freshness of the raw aquatic materials.
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Aminas Biogênicas/análise , Cromatografia Líquida de Alta Pressão/métodos , Crustáceos/química , Decapodiformes/química , Animais , Temperatura Baixa , Conservação de Alimentos , Reprodutibilidade dos TestesRESUMO
The aim of this study is to identify and consolidate reliable endoscopic features associated with H. pylori infection in gastric mucosa, which is one of the major causes of gastric cancer. A total of 256 Chinese patients with symptomatic stomach disturbances were enrolled. Pathological examination was conducted using a light microscope and biopsy specimens stained with hematoxylin-eosin. Endoscopic examination was performed using a high resolution video endoscope. The association between endoscopic features and pathological H. pylori diagnosis was compared, and endoscopic features significantly associated with H. pylori infection were identified. A total of 14 endoscopic features were observed. Six of the 14 endoscopic features, including mucus on the gastric mucosa, diffuse redness, spotty redness of fundic mucosa, enlarged fold, mucosal edema, and RAC (type D and type I), were highly associated with H. pylori infection and were significantly sensitive and specific predictors for H. pylori diagnosis. The type R RAC was not significantly associated with H. pylori diagnosis. Our results indicate that conventional endoscopy features can be used to diagnose H. pylori in Chinese patients and can help determine the risk factor for gastric cancer.
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AIM: To study the therapeutic effects of zhaoyangwan (ZYW) on chronic hepatitis B and hepatic cirrhosis and the anti-virus, anti-fibrosis and immunoregulatory mechanisms of ZYW. METHODS: Fifty cases of chronic hepatitis B and posthepatic cirrhosis with positive serum HBsAg, HBeAg, anti-Hbc and HBV-DNA were divided randomly and single-blindly into the treatment group (treated with ZYW) and the control group (treated with interferon). After 3 month treatment, the effects of the treatment group and the control group were evaluated. RESULTS: The serum ALT normalization was 83.3% (30/36) in the treatment group and 85.7% (12/14) in the control group, with no significant difference (chi2=0.043, P>0.05). After the course, the negative expression rates of the serum HBV-DNA and HBeAg were 44.4% (16/36) and 50% (18/36) in the treatment group, and 50% (7/14) and 50% (7/14) in the control group, respectively, with no significant difference (chi2=0.125, chi2=0.00, both P>0.05). Negative HBsAg and positive HBsAb appeared in 4 cases of the treatment group and 1 case of the control group. Serum anti-HBc turned negative in 6 cases of the treatment group and 1 case of the control group, respectively. After the ZYW treatment, serum CD3+, CD4+, CD8+, CD4+/CD8+ and NK cell activation were significantly increased. Only serum CD3+ and NK cell activation were significantly increased in the control group with a significant difference between the two groups. The serum C4, C1q, C3, B and C9 were significantly increased in the treatment group. In the control group only the serum C4 was increased. The concentration of serum interferon had no change after treatment with ZYW, while it was significantly increased in the control group after treatment with interferon. The ultrastructure of the liver restored, which helped effectively to reduce the degeneration and necrosis of hepatic cells,infiltration of inflammatory cells and hepatic cirrhosis. CONCLUSION: ZYW is a pure Chinese herbal medicine. It can exert potent therapeutic effects on chronic hepatitis B and posthepatic cirrhosis. ZYW has similar therapeutic effects to those of interferon. It is cheap and easily administered with no obvious side-effects. It can be widely used in clinical practice.
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Medicamentos de Ervas Chinesas/administração & dosagem , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Adolescente , Adulto , Alanina Transaminase/sangue , Antivirais/administração & dosagem , Proteínas do Sistema Complemento/metabolismo , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Hepatite B Crônica/imunologia , Hepatite B Crônica/patologia , Humanos , Interferons/administração & dosagem , Fígado/patologia , Fígado/fisiologia , Cirrose Hepática/imunologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Linfócitos T/efeitos dos fármacos , Resultado do TratamentoRESUMO
A technique for the analysis of flavour compounds from fish muscle employing microwave distillation (MD), solid phase microextraction ( SPME) coupled with gas chromatography-mass spectrometry (GC-MS) and olfactometry is described, and 53 compounds responsible for the aroma of bighead carp were identified from NIST 02 MS data base. The extraction of microwave distillation was developed by optimizing the flow rate of carrier gas, heating time and power. Solid phase microextraction procedure was optimized by using different kinds of fiber for the qualitative determination of the volatile compounds observed in the headspace of microwave distillation, including extraction time, temperature, magnetic stirring speed and desorption time in GC-MS equipment. Furthermore, a simple data acquisition and processing system was developed by using human nose as a sensitive detector for the identification of flavour arid off-flavour key compounds in fish tissue. The result showed that the components associated with fish flavour were mostly 6 - 9 carbon aldehydes, ketones and alcohols. According to the olfactory analysis, these compounds were characterized by grassy, fishy, earthy or muddy odors separately, and their synergistic actions were forming the distinct fishy and earthy odors of bighead carp. The rapid method developed by this study may be applied to quantitative analysis of the volatileoff-flavour compounds in fresh-water fish.