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Free Radic Biol Med ; 172: 578-589, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34242792


Acetaminophen (APAP) is the leading cause of acute liver failure (ALF), which is characterized by GSH depletion, oxidative stress and mitochondrial dysfunction. However, the specific mechanism of APAP-induced ALF remains to be clarified. In this study, we demonstrated that indoleamine 2,3-dioxygenase 1 (IDO1) aggravated APAP-induced ALF associated with excess lipid peroxidation, which was reversed by lipid peroxidation inhibitor (ferrostatin-1). Meanwhile, IDO1 deficiency effectively decreased the accumulation of reactive nitrogen species. Additionally, IDO1 deficiency prevented against APAP-induced liver injury through suppressing the activation of macrophages, thereby reduced their iron uptake and export, eventually reduced iron accumulation in hepatocytes through transferrin and transferrin receptor axis. In summary, our study confirmed that APAP-induced IDO1 aggravated ALF by triggering excess oxidative and nitrative stress and iron accumulation in liver. These results offer new insights for the clinical treatment of ALF or iron-dysregulated liver diseases in the future.

Doença Hepática Induzida por Substâncias e Drogas , Dioxigenases , Falência Hepática Aguda , Acetaminofen/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Dioxigenases/metabolismo , Hepatócitos , Ferro/metabolismo , Fígado/metabolismo , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo
Front Pharmacol ; 12: 616409, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33716743


Alcoholic liver disease (ALD) has become a heavy burden on health worldwide. Ginsenoside Rb1 (GRb1), extracted from Panax quinquefolium L., has protective effects on many diseases, but the effect and mechanisms of GRb1 on ALD remain unknown. This study aimed to investigate the protective effects of GRb1 on ALD and to discover the potential mechanisms. Zebrafish larvae were exposed to 350 mM ethanol for 32 h to establish a model of acute alcoholic liver injury, and the larvae were then treated with 6.25, 12.5, or 25 µM GRb1 for 48 h. The human hepatocyte cell line was stimulated by 100 mM ethanol and meanwhile incubated with 6.25, 12.5, and 25 µM GRb1 for 24 h. The lipid changes were detected by Oil Red O staining, Nile Red staining, and triglyceride determination. The antioxidant capacity was assessed by fluorescent probes in vivo, and the expression levels of inflammatory cytokines were detected by immunohistochemistry, immunofluorescence, and quantitative real-time PCR. The results showed that GRb1 alleviated lipid deposition in hepatocytes at an optimal concentration of 12.5 µM in vivo. GRb1 reversed the reactive oxygen species accumulation caused by alcohol consumption and partially restored the level of glutathione. Furthermore, GRb1 ameliorated liver inflammation by inhibiting neutrophil infiltration in the liver parenchyma and downregulating the expression of nuclear factor-kappa B pathway-associated proinflammatory cytokines, including tumor necrosis factor-α and interleukin-1ß. This study revealed that GRb1 has a protective effect on alcohol-induced liver injury due to its resistance to lipid deposition as well as antioxidant and anti-inflammatory actions. These findings suggest that GRb1 may be a promising candidate against ALD.

Patient Prefer Adherence ; 13: 1487-1495, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31507316


Objective: The self-reported scale is a widely used method to assess patients' medication adherence in clinical practice, but there is still a lack of medicine adherence measurement scale for patients with Chronic Kidney Disease (CKD). Therefore, this study aimed to develop a medication adherence measurement scale of traditional Chinese medicine and Western medicine, providing a tool for evaluating medicine adherence of CKD patients. Methods: In the preliminary stage, we formed the prediction scale after three rounds Delphi method and it was filled by 20 patients, who were selected randomly. After pre-investigation and language adaption, we adjusted the prediction measurement scale which included 31 items based on Knowledge-Attitude-Belief Theory. Then, 222 CKD patients in Guangdong Hospital of traditional Chinese Medicine were investigated by this 31-item scale. We screened 31 items by Items analysis theory, including critical ratio, item correlation analysis, internal consistency analysis, principal component analysis and other methods. The left 26 items made up a formal scale. We collected and analyzed data of the 26-item scale and Chinese version of MGL scale, and took their scores correlation analysis as the criterion validity of the 26-item scale. At the same time, we evaluated content validity, Cronbach alpha coefficient and retest reliability of the 26-item scale. Results: We developed a scale with 26 items and 5 dimensions finally. In the validation analysis, the scale had good construct validity and content validity. The Pearson relation index between respective scores of the scale and Chinese version of MGL scale was 0.426, P<0.01. The scale also had good reliability as its 0.915 in Cronbach alpha, 0.753 in retest reliability and P<0.01. Conclusion: The scale revealed great reliability and validity, which could be used as a measurement tool to evaluate the medication adherence of patients with CKD.

Exp Ther Med ; 9(6): 2275-2280, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26136973


This study aimed to compare the therapeutic effects and adverse events of the multikinase inhibitors sorafenib, sunitinib, pazopanib and axitinib in advanced renal cell carcinoma (RCC). A meta-analysis of randomized controlled trials was performed to assess the effects of multikinase inhibitors among patients with advanced RCC. The data of median progression-free survival (PFS), median overall survival (OS), progressive disease rate (PDR), objective response rate (ORR) and grade 3/4 adverse events were extracted to assess therapeutic effects and toxicity, respectively. It was found that multikinase inhibitors are more effective in extending PFS [hazard ratio (HR)=0.58; 95% confidence interval (CI): 0.45-0.74; P<0.0001), controlling tumor progression [relative risk (RR)=0.67; 95% CI: 0.55-0.83; P=0.0002) and ORR (RR=2.93; 95% CI: 1.40-6.14; P=0.004) compared with placebo or interferon-α. Patients treated with multikinase inhibitors had significantly higher rates of grade 3 or 4 hypertension (RR=6.00; 95% CI: 3.36-10.69; P<0.00001), diarrhea (RR=5.84; 95% CI: 3.06-11.16; P<0.00001), nausea (RR=2.30; 95% CI: 1.16-4.54; P=0.02), vomiting (RR=1.84; 95% CI: 1.00-3.41; P=0.05) and hand-foot skin reaction (RR=11.78; 95% CI: 5.16-26.93; P<0.00001). Multikinase inhibitors can significantly control disease progress and improve the ORR. However, they are also associated with a higher risk of grade 3 and 4 hypertension and gastrointestinal events. Proper management of these events is necessary to improve patient quality of life.

Cancer Epidemiol ; 37(6): 1010-3, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24139593


AIM: Heparanase-2 expression has been suggested to up-regulate in several types of human cancers. However, the expression patterns of heparanase-2 in gastric cancer and its effect on prognosis of gastric cancer patients are unclear. METHODS: In this study, the methods of tissue microarray, immunohistochemistry (IHC), and western blot were used to investigate heparanase-2 expression in gastric cancer and the adjacent non-cancerous tissues. Heparanase-2 expression was analyzed by immunohistochemistry in 95 clinicopathologically characterized gastric cancer cases. In addition Fisher's exact test, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the results. RESULTS: High expression of cytoplasmic heparanase-2 was observed in 70.5% (67/95) of gastric cancer, when compared with its normal counterpart. Overexpression of heparanase-2 was correlated with tumor size and differentiation (P<0.05). Further analysis showed that a significant correlation between high expression of heparanase-2 and favorable prognosis (P<0.05). In multivariate analysis, high expression of heparanase-2 was evaluated as an independent prognostic factor in gastric cancer (P<0.05). CONCLUSIONS: Our data suggest for the first time that the high expression of heparanase-2 is associated significantly with tumor growth and differentiation. Importantly, heparanase-2 may be a potential molecular marker for predicting prognosis of gastric cancer.

Biomarcadores Tumorais/metabolismo , Polissacarídeo-Liases/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Análise Serial de Tecidos