Kaempferol inhibited invasion and metastasis of gastric cancer cells by targeting AKT/GSK3ß pathway based on network pharmacology and molecular docking.

This study aims to explore the mechanisms of the inhibitory effect of kaempferol on the invasion and metastasis of gastric cancer (GC) cells through network pharmacology prediction and experimental verification. It identifies core targets via PPI network analysis and finds that kaempferol binds to these targets well. In vitro experiments showed that kaempferol could inhibit the proliferation, colony formation, migration and invasion of GC cells. Western blotting indicated kaempferol may reduce AKT and GSK3ß phosphorylation, leading to lower expression of invasion-related genes SRC, MMP9, CXCR4, KDR, and MMP2. Overall, kaempferol may prevent migration and invasion of GC cells via the AKT/GSK3ß signaling pathway.

Impact of statins on ALI/ARDS: A meta-analysis.

BACKGROUND: Statins may be beneficial in treating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), but their application remains controversial. OBJECTIVES: This meta-analysis of published studies investigated their potential benefit in ALI/ARDS treatment. METHODS: PubMed, EMBASE, Google Scholar and Cochrane databases were searched and all randomized controlled trials (RCT) and cohort studies with head-to-head comparison between statin and standard care were included. RESULTS: Three RCTs and six cohort studies were included. Overall, statins treatment had no significant effect on mortality compared with placebo (RCTs: OR = 0.99, 95% CI = 0.72, 1.37; cohorts: OR = 0.99, 95% CI = 0.71, 1.37). In addition, ventilator-free days were comparable between the two groups (RCTs: SMD = 0.08, 95% CI = -0.03, 0.19; cohorts: SMD = 0.06, 95% CI = -0.17, 0.29). The one-way sensitivity analysis confirmed the stability of results. CONCLUSION: The results did not show that statins had effects on mortality and ventilator-free days among ALI/ARDS patients. However, this meta-analysis is limited by the number of RCTs included.

Mechanisms involved in the HMGB1 modulation of tumor multidrug resistance (Review).

Tumor multidrug resistance (MDR) remains one of the most challenging barriers to successful cancer treatment. Several previous studies have suggested that high mobility group box 1 (HMGB1) may be a promising therapeutic target for overcoming cancer drug resistance. Emerging evidence has indicated that HMGB1 functions as a 'double­edged sword' that plays both pro­ and anti­tumor roles in the development and progression of multiple types of cancer. HMGB1 has also been found to be a key regulator of several cell death and signaling pathways, and is involved in MDR by mediating cell autophagy and apoptosis, ferroptosis, pyroptosis and multiple signaling pathways. Additionally, HMGB1 is regulated by a variety of non­coding RNAs (ncRNAs), such as microRNAs, long ncRNAs and circular RNAs that are involved in MDR. Thus far, studies have been conducted to identify strategies with which to overcome HMGB1­mediated MDR by the targeted silencing of HMGB1 and the targeted interference of HMGB1 expression using drugs and ncRNAs. Therefore, HMGB1 is closely associated with tumor MDR and is a promising therapeutic target.

ß3-Adrenoceptor activation upregulates apolipoprotein A-I expression in HepG2 cells, which might further promote cholesterol efflux from macrophage foam cells.

OBJECTIVE: The aim of this study was to explore the effects of ß3-adrenoceptor (ß3-AR) activation on HepG2 cells and its influence on cholesterol efflux from macrophage foam cells. MATERIALS AND METHODS: HepG2 cells were cultured and treated with the ß3-AR agonist, BRL37344, and antagonist, SR52390A, and the expression of apolipoprotein (Apo) A-I, ApoA-II, ApoB, and ß3-AR in the supernatants and cells was determined. The expression of peroxisome proliferator-activated receptor (PPAR) γ and PPARα in the HepG2 cells was also assessed. Next, using the RAW264.7 macrophage foam cell model, we also assessed the influence of the HepG2 cell supernatants on lipid efflux. The cholesterol content of the foam cells was also measured, and the cholesterol efflux from the macrophages was examined by determining 3H-labeled cholesterol levels. Expression of ATP-binding cassette transporter (ABC) A1 and ABCG1 of the macrophage foam cells was also assessed. RESULTS: ß3-AR activation increased ApoA-I expression in both the HepG2 cells and the supernatants; PPARγ expression was upregulated, but PPARα expression was not. Treatment with GW9662 abolished the increased expression of ApoA-I induced by the ß3-AR agonist. The HepG2 cell supernatants decreased the lipid accumulation and increased the cholesterol efflux from the macrophage foam cells. ABCA1 expression, but not ABCG1 expression, increased in the macrophage foam cells treated with BRL37344-treated HepG2 cell supernatants. CONCLUSION: Activation of ß3-AR in HepG2 cells upregulates ApoA-I expression, which might further promote cholesterol efflux from macrophage foam cells. PPARγ might be required for the induction of ApoA-I expression.

Comparison of Secondary Prevention Status between Percutaneous Coronary Intervention and Coronary Artery Bypass Patients.

BACKGROUND: Data are scarce regarding disparities in cardiovascular risk factor management between patients treated with percutaneous coronary intervention (PCI) and those treated with coronary artery bypass grafting (CABG). OBJECTIVE: Whether the goal achievement rates of cardiovascular risk factors were different between PCI and CABG patients. METHODS: We retrospectively reviewed the data retrieved from a clinical record database of patients admitted to Beijing Anzhen Hospital between January 1, 2014, and December 31, 2014, who underwent PCI or CABG. RESULTS: Compared with the CABG group, low-density lipoprotein cholesterol (LDL-C) < 1.8 mmol/L (28.6% vs. 24.7%; p < 0.01), LDL-C < 2.07 mmol/L (43.5% vs. 39.4%; p < 0.01) and blood pressure (BP) < 140/90 mm Hg (85.6% vs. 77.7%; p < 0.01) goal achievement rates were significantly higher in the PCI group. Compared with patients ≥ 60 years old: patients < 60 years old had better BP < 140/90 mm Hg goal achievement rates (87.7% vs. 84.4%; p < 0.01) in the PCI group, and better fasting blood-glucose (FBG) < 7 mmol/L (79.4% vs.72.0%; p < 0.01) and HbA1c < 7% (79.4% vs. 70.1%; p < 0.01) goal achievement rates in the CABG group. Compared with females: males had better LDL-C < 2.07 mmol/L (24.7% vs. 28.5%; p < 0.01), FBG < 7 mmol/L (71.8% vs.75.2%; p < 0.01) and HbA1c < 7% (70.4% vs. 74.1%; p < 0.01) goal achievement rates in the PCI group. CONCLUSION: Patients in the PCI group were generally more likely than those in the CABG group to achieve LDL-C < 1.8 mmol/L and BP goals. The control of cardiovascular risk factors differed between patients ≥ 60 years old and < 60 years old. Female patients were less likely to achieve LDL-C, FBG and HbA1c goals.

Effect and mechanism of salvianolic acid B on the myocardial ischemia-reperfusion injury in rats.

OBJECTIVE: To investigate the effect of salvianolic acid B on rats with myocardial ischemia-reperfusion injury. METHODS: SD rats were randomly divided into five groups (n=10 in each group): A sham operation group, B ischemic reperfusion group model group, C low dose salvianolic acid B group, D median dose salvianolic acid B group, E high dose salvianolic acid B group. One hour after establishment of the myocardial ischemia-reperfusion model, the concentration and the apoptotic index of the plasma level of myocardial enzymes (CTn I, CK-MB), SOD, MDA, NO, ET were measured. Heart tissues were obtained and micro-structural changes were observed. RESULTS: Compared the model group, the plasma CTn, CK-MB, MDA and ET contents were significantly increased, NO, T-SOD contents were decreased in the treatment group (group C, D, and E) (P<0.05); compared with group E, the plasma CTn I, CK-MB, MDA and ET levels were increased, the NO, T-SOD levels were decreased in groups C and D (P<0.05). Infarct size was significantly reduced, and the myocardial ultrastructural changes were improved significantly in treatment group. CONCLUSIONS: Salvianolic acid B has a significant protective effect on myocardial ischemia-reperfusion injury. It can alleviate oxidative stress, reduce calcium overload, improve endothelial function and so on.

Effect of rosiglitazone on rabbit model of myocardial ischemia-reperfusion injury.

OBJECTIVE: To explore mechanism and protective effect of rosiglitazone on myocardial ischemia reperfusion (I/R) injury. METHODS: A total of 48 male Japanese white big-ear rabbits were randomly divided into control group (A), I/R group (B), low dose of rosiglitazone group (C), high dose of rosiglitazone group (D). Plasma concentration of and also reduced the concentration of plasma serum creatine kinase (CK), CK-MB, high-sensitivity C-reactive protein (hsCRP), ultra-superoxide dismutase (SOD), malondialdehyde (MDA), lactic acid glutathione skin peroxidase (GSH-PX), nitric oxide (NO) and endothelin (ET) were measured 1 h later after I/R. Twenty-four hours after I/R the hearts were harvested for pathological and ultrastructural analysis. Area of myocardial infarction were tested. RESULTS: Plasma concentration of CK, CK-MB, hsCRP, NO, MDA and ET were decreased in C, D group compared with group B. Plasma concentration of T-SOD and GSH-Px were increased significantly in C, D group compared with group B. Compared with group B, pathological and ultrastructural changes in C and D group were slightly. There was significant difference in myocardial infarction area between group C, D and group B (P<0.05). Myocardial infarction area and arrhythmia rate were lower in group C, D compare with group B. CONCLUSIONS: Rosiglitazone may protect myocardium from I/R injury by enhancing T-SOD and GSH-Px concentration, inhibit inflammatory reaction, and improve endothelial function.

Comparison of Secondary Prevention Status between Percutaneous Coronary Intervention and Coronary Artery Bypass Patients / Comparação de Prevenção Secundária em Intervenção Coronária Percutânea e Cirurgia de Revascularização Miocárdica

Abstract Background: Data are scarce regarding disparities in cardiovascular risk factor management between patients treated with percutaneous coronary intervention (PCI) and those treated with coronary artery bypass grafting (CABG). Objective: Whether the goal achievement rates of cardiovascular risk factors were different between PCI and CABG patients. Methods: We retrospectively reviewed the data retrieved from a clinical record database of patients admitted to Beijing Anzhen Hospital between January 1, 2014, and December 31, 2014, who underwent PCI or CABG. Results: Compared with the CABG group, low-density lipoprotein cholesterol (LDL-C) < 1.8 mmol/L (28.6% vs. 24.7%; p < 0.01), LDL-C < 2.07 mmol/L (43.5% vs. 39.4%; p < 0.01) and blood pressure (BP) < 140/90 mm Hg (85.6% vs. 77.7%; p < 0.01) goal achievement rates were significantly higher in the PCI group. Compared with patients ≥ 60 years old: patients < 60 years old had better BP < 140/90 mm Hg goal achievement rates (87.7% vs. 84.4%; p < 0.01) in the PCI group, and better fasting blood-glucose (FBG) < 7 mmol/L (79.4% vs.72.0%; p < 0.01) and HbA1c < 7% (79.4% vs. 70.1%; p < 0.01) goal achievement rates in the CABG group. Compared with females: males had better LDL-C < 2.07 mmol/L (24.7% vs. 28.5%; p < 0.01), FBG < 7 mmol/L (71.8% vs.75.2%; p < 0.01) and HbA1c < 7% (70.4% vs. 74.1%; p < 0.01) goal achievement rates in the PCI group. Conclusion: Patients in the PCI group were generally more likely than those in the CABG group to achieve LDL-C < 1.8 mmol/L and BP goals. The control of cardiovascular risk factors differed between patients ≥ 60 years old and < 60 years old. Female patients were less likely to achieve LDL-C, FBG and HbA1c goals.

Resumo Fundamento: Há poucos dados referentes às disparidades no manejo de fatores de risco cardiovascular entre pacientes tratados com intervenção coronária percutânea (ICP) e aqueles tratados com cirurgia de revascularização miocárdica (CRM). Objetivo: Avaliar se as taxas de cumprimento de metas de fatores de risco cardiovascular diferiram entre pacientes submetidos a ICP ou a CRM. Métodos: Revisão retrospectiva de banco de dados de prontuários médicos de pacientes admitidos no Hospital Beijing Anzhen entre 1 de janeiro de 2014 e 31 de dezembro de 2014, submetidos a ICP ou a CRM. Resultados: Comparado ao grupo CRM, o grupo ICP apresentou taxas significativamente maiores de cumprimento de meta de colesterol da lipoproteína de baixa densidade (LDL-C) < 1,8 mmol/L (28,6% vs. 24,7%; p < 0,01), LDL-C < 2,07 mmol/L (43,5% vs. 39,4%; p < 0,01) e pressão arterial (PA) <140/90 mmHg (85,6% vs. 77,7%; p < 0,01). Comparados aos pacientes ≥ 60 anos de idade, aqueles < 60 anos de idade apresentaram melhor taxa de cumprimento de meta de PA < 140/90 mmHg (87,7% vs. 84,4%; p < 0,01) no grupo ICP, e melhores taxas de cumprimento de meta de glicemia de jejum (GJ) < 7 mmol/L (79.4% vs.72.0%; p < 0.01) e HbA1c < 7% (79.4% vs. 70.1%; p < 0.01) no grupo CRM. Comparados às mulheres, os homens apresentaram melhores taxas de cumprimento de meta de LDL-C < 2,07 mmol/L (24,7% vs. 28,5%; p < 0,01), GJ < 7 mmol/L (71,8% vs. 75,2%; p < 0,01) e HbA1c < 7% (70,4% vs. 74,1%; p < 0,01) no grupo ICP. Conclusão: Em geral, o grupo ICP apresentou maior probabilidade do que o grupo CRM de cumprir as metas de LDL-C < 1,8 mmol/L e PA. O controle dos fatores de risco cardiovascular diferiu entre pacientes ≥ 60 e < 60 anos de idade. As mulheres apresentaram menor probabilidade de cumprir as metas de LDL-C, GJ e HbA1c.