Baicalin enhances the chemotherapy sensitivity of oxaliplatin-resistant gastric cancer cells by activating p53-mediated ferroptosis.

Gastric cancer is one of the most common malignant tumors, and chemotherapy is the main treatment for advanced gastric cancer. However, chemotherapy resistance leads to treatment failure and poor prognosis in patients with gastric cancer. Multidrug resistance (MDR) is a major challenge that needs to be overcome in chemotherapy. According to recent research, ferroptosis activation is crucial for tumor therapeutic strategies. In this work, we explored the solution to chemoresistance in gastric cancer by investigating the effects of the Chinese medicine monomer baicalin on ferroptosis. Baicalin with different concentrations was used to treat the parent HGC27 and drug-resistant HGC27/L cells of gastric cancer. Cell viability was measured by CCK8, and synergistic effects of baicalin combined with oxaliplatin were evaluated using Synergy Finder software. The effects of baicalin on organelles and cell morphology were investigated using projective electron microscopy. Iron concentration, MDA production and GSH inhibition rate were measured by colorimetry. ROS accumulation was detected by flow cytometry. The ferroptosis-related genes (IREB2, TfR, GPX4, FTH1), P53, and SLC7A11 were analysed by Western blot, and the expression differences of the above proteins between pretreatment and pretreatment of different concentrations of baicalin, were assayed in both parental HGC27 cells and Oxaliplatin-resistant HGC27/L cells. Mechanically, Baicalin disrupted iron homeostasis and inhibits antioxidant defense, resulting in iron accumulation, lipid peroxide aggregation, and specifically targeted and activated ferroptosis by upregulating the expression of tumor suppressor gene p53, thereby activating the SLC7A11/GPX4/ROS pathway mediated by it. Baicalin activates ferroptosis through multiple pathways and targets, thereby inhibiting the viability of oxaliplatin-resistant gastric cancer HGC27/L cells and enhancing the sensitivity to oxaliplatin chemotherapy.

EMT-related gene risk model establishment for prognosis and drug treatment efficiency prediction in hepatocellular carcinoma.

This study was designed to evaluate the prognosis and pharmacological therapy sensitivity of epithelial mesenchymal transition-related genes (EMTRGs) that obtained from the EMTome database in hepatocellular carcinoma (HCC) using bioinformatical method. The expression status of EMTRGs were also investigated using the clinical information of HCC patients supported by TCGA database and the ICGC database to establish the TCGA cohort as the training set and the ICGC cohort as the validation set. Analyze the EMTRGs between HCC tissue and liver tissue in the TCGA cohort in the order of univariate COX regression, LASSO regression, and multivariate COX regression, and construct a risk model for EMTRGs. In addition, enrichment pathways, gene mutation status, immune infiltration, and response to drugs were also analyzed in the high-risk and low-risk groups of the TCGA cohort, and the protein expression status of EMTRGs was verified. The results showed a total of 286 differentially expressed EMTRGs in the TCGA cohort, and EZH2, S100A9, TNFRSF11B, SPINK5, and CCL21 were used for modeling. The TCGA cohort was found to have a worse outcome in the high-risk group of HCC patients, and the ICGC cohort confirmed this finding. In addition, EMTRGs risk score was shown to be an independent prognostic factor in both cohorts by univariate and multivariate COX regression. The results of GSEA analysis showed that most of the enriched pathways in the high-risk group were associated with tumor, and the pathways enriched in the low-risk group were mainly associated with metabolism. Patients in various risk groups had varying immunological conditions, and the high-risk group might benefit more from targeted treatments. To sum up, the EMTRGs risk model was developed to forecast the prognosis for HCC patients, and the model might be useful in assisting in the choice of treatment drugs for HCC patients.

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.

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.

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.

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.

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.

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.