Int J Med Sci
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In clinical cohort studies, high expression of long-chain acyl-coenzyme A synthetases 1 (ACSL1 gene) in peripheral white blood cells of patients with acute myocardial infarction (AMI) has been utilized as molecular markers of myocardial infarction diagnosis. The plasma triglyceride level of AMI patients is significantly higher than that of healthy individuals. We hypothesized that the high expression of ACSL1 increases the level of triglyceride, which is one of the pathogenesis of AMI promoted by ACSL1. ⋯ The expression level of fatty acid oxidation pathway PPARγ was significantly down-regulated compared with the control group, as were genes associated with fatty acid synthesis pathways: SREBP1, ACC, FAS, and SCD1. ACSL1 knockdown decreased the content of triglyceride whereas PPARγ was up-regulated and SREBP1, ACC, FAS, and SCD1 were down-regulated compared with the control group. In summary, high expression of ACSL1 reduced fatty acid β-oxidation through the PPARγ pathway, thereby increasing triglyceride levels.
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Breast cancer is the most common cancer type in females, and exploring the mechanisms of disease progression is playing a crucial role in the development of potential therapeutics. Pituitary tumor-transforming gene (PTTG) family members are well documented to be involved in cell-cycle regulation and mitosis, and contribute to cancer development by their involvement in cellular transformation in several tumor types. The critical roles of PTTG family members as crucial transcription factors in diverse types of cancers are recognized, but how they regulate breast cancer development still remains mostly unknown. ⋯ Meanwhile, through Cytoscape analyzed indicated that in addition to the metastasis markers AURKA, AURKB, and NDC80, many of the kinesin superfamily (KIF) members including KIFC1, KIF2C, KIF4A, KIF14, KIF20A, KIF23, were also correlated with PTTG family transcript expression. Finally, we revealed that high levels of PTTG1 and PTTG3 transcription predicted poor survival, which provided useful insights into prospective research of cancer associated with the PTTG family. Therefore, these members of the PTTG family would serve as distinct and essential prognostic biomarkers in breast cancer.
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Purpose: We aimed to determine whether biatrial enlargement could predict reablation of atrial fibrillation after first ablation. Methods: 519 consecutive patients with drug resistant atrial fibrillation [paroxysmal AF (PAF) 361, non-PAF 158] who underwent catheter ablation in Capital Medical University Xuanwu hospital between 2009 and 2014 were enrolled. Biatrial enlargement (BAE) was diagnosed according to trans-thoracic echocardiography (TTE). ⋯ Results: After 33.11±21.45months, 170 patients recurred atrial arrhythmia, and reablation were applied in 117 patients. Multivariate Cox regression analysis demonstrated that that biatrial enlargement (BAE, HR 1.755, 95%CI 1.153-2.670, P=0.009) was an independent predictor for reablation and was associated with reablation (Log rank P=0.007). Conclusion: Biatrial enlargement is an independent risk predictor for the reablation in atrial fibrillation patients after first ablation.
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Objective: Our study aimed to evaluate the association between prediabetes and renal dysfunction, and further assess which of glycemic indices of fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and hemoglobin A1c (HbA1c) has a higher risk of renal dysfunction. Methods: This was a community-based prospective cohort study, which included 7015 participants from Beijing and Taian between May and October in 2015. The outcome was the renal dysfunction defined as estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m2. ⋯ The similar results were obtained by performing the subgroup analysis. ROC analysis revealed the PPG had a higher predictive value for renal dysfunction. Conclusion: We found prediabetes was positively associated with the risk of renal dysfunction and PPG had a higher risk and predictive value of renal dysfunction than other glycemic indices of FPG and HbA1c.
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Sorafenib is the standard systemic treatment for advanced hepatocellular carcinoma (HCC), and improving its therapeutic effects is crucial for addressing cancer aggression. We previously reported that epalrestat, an aldo-keto reductase 1B10 inhibitor, enhanced sorafenib's inhibitory effects on HCC xenograft in nude mice. This study aimed to elucidate the mechanism of epalrestat's anti-tumour enhancing effects on sorafenib. ⋯ Treatment with a specific mTOR activator MHY-1485 increased mTOR phosphorylation, while suppressing apoptosis and autophagy. Consistent with in vitro results, data from the HCC-xenograft nude mouse model also indicated that combined treatment inhibited the mTOR pathway and promoted apoptosis and autophagy. In conclusion, epalrestat heightens sorafenib's anti-cancer effects via blocking the mTOR pathway, thus inducing cell cycle arrest, apoptosis, and autophagy.