Atherosclerosis (AS) is an age‑related inflammatory disease. Globule‑epidermal growth factor‑8 (MFG‑E8) and transforming growth factor-β1 (TGF‑β1) are involved in the pathogenesis of AS. However, age‑related changes in circulating levels of MFG‑E8 and TGF‑β1, and their correlation with the severity of AS is not well‑characterized. In this study, we investigated age‑related changes in serum levels of MFG‑E8, TGF‑β1 and examined their association with the severity of AS. Sixty healthy volunteers were divided into young, middle‑age and old‑age groups. In addition, carotid ultrasound examination was performed to assess the intima‑media thickness (IMT) of carotid artery. Sixty‑seven patients with carotid AS and 30 age‑matched healthy persons were divided into IMT increased group, plaque group and control group. Serum levels of MFG‑E8, TGF‑β1, tumor necrosis factor-α (TNF‑α) and intercellular adhesion molecule‑1 were measured in all subjects. A positive association between serum MFG‑E8 levels and age was observed in healthy volunteers, while a significant negative association was observed between TGF‑β1 levels and age. Serum levels of MFG‑E8 and TNF‑α showed a positive correlation while those of TGF‑β1 showed a negative correlation with Crouse scores for carotid artery IMT (P<0.05 for both). Both MFG‑E8 and TGF‑β1 were age‑related inflammatory factors. MFG‑E8 showed a positive correlation, while TGF‑β1 showed a negative correlation with the severity of AS. Our findings suggest that both MFG‑E8 and TGF‑β1 are age‑related inflammatory factors and are related to the degree of AS. In conclusion, both MFG‑E8 and TGF‑β1 may serve as potential markers of the severity of AS.
Investigating the determinants and dynamics of atherosclerotic plaque instability is a key area of current cardiovascular research. Extracellular matrix degradation from excessive proteolysis induced by enzymes such as cathepsin K (Cat K) is implicated in the pathogenesis of unstable plaques. The current study assessed the expression of Cat K in human unstable atherosclerotic plaques. Specimens of popliteal arteries with atherosclerotic plaques were classified as stable (<40% lipid core plaque area; n=6) or unstable (≥40% lipid core plaque area; n=14) based on histopathological examinations of hematoxylin and eosin stained sections. The expression of Cat K and cystatin C (Cys C) were assessed by immunohistochemical examination and levels of Cat K mRNA were detected by semi-quantitative reverse transcriptase polymerase chain reaction. Morphological changes including a larger lipid core, endothelial proliferation with foam cells and destruction of internal elastic lamina were observed in unstable atherosclerotic plaques. In unstable plaques, the expression of Cat K protein and mRNA was upregulated, whereas Cys C protein expression was downregulated. The interplay between Cat K and Cys C may underlie the progression of plaques from stable to unstable and the current study indicated that Cat K and Cys C are potential targets for preventing and treating vulnerable atherosclerotic plaque ruptures.
Abstract. Zebrafish (Danio rerio) is becoming an increasingly popular vertebrate cancer model. In this study, we established a xenotransplanted zebrafish embryo glioma model to further investigate the molecular mechanisms of tumor angiogenesis. We find that the glioma cell line U87 can survive, proliferate and induce additional SIV branches in zebrafish embryos. In addition, by the means of in situ hybridization and quantitive RT-PCR analyses we find that the transplanted U87 cells can induce the ectopic zebrafish vascular endothelial growth factor A (VEGF A) and its receptor VEGFR2/KDR mRNA expression and increase their expression levels, resulting in additional SIV branches. IntroductionGlioma is the most common primary brain tumor in adults and the median survival for patients without therapy is up to 3 months (1). Currently the traditional treatment such as resection, chemotherapy and radiotherapy has not greatly improved the median survival for patients. Malignant glioma is notorious for its behavior of rapid proliferation, great invasion and metastasis and it is also among the best vascularized tumors in humans. It is well known that angiogenesis plays a critical role in tumor progression. Therefore new anti-angiogenic treatment strategies are required (2-6). Revealing of various signaling pathways that lead to activation of angiogenesis will provide molecular insight into developing therapeutic agents to treat glioma. In the past decades, researchers have discovered many molecular mechanisms related to tumor angiogenesis (7-9).Traditional rodent cancer models have disadvantages, e.g., the high cost, long developmental phase, and limited availability for high-throughput assays (10), which limited effective ways to find the new molecular mechanisms and monitor the tumor in vivo in real time.The teleost zebrafish (Danio rerio), a promising alternative vertebrate cancer model has attracted considerable attention in recent years because of compelling advantages of transparency of the embryo, rapid development, fecundity, tractable genetics, great screening efficiency, high levels of physiologic and genetic homology with higher vertebrates (11-13). Moreover, the zebrafish embryo within 1 week is immune-free, and showed no immunosuppression to transplanted human glioma cells (14). The transgenic zebrafish strains, e.g., casper transparent mutant line (15), and VEGFR2:G-RCFP line with green fluorescence specifically in blood vessels (16), offered new tools for cancer research.In this study, we microinjected human U87 glioma cells into zebrafish embryos and developed a xenograft zebrafish glioma model. The U87 cells are first labeled with a red fluorescence protein and then microinjected into perivitelline space of VEGFR2:G-RCFP transgenic zebrafish embryos at 48 h post-fertilization. Then in order to investigate the angiogenesis mechanisms in details, we make use of the staining of endogenous alkaline phosphatase, fluorescent microscopy monitoring, in situ hybridization and quantitive RT-PCR to investigate the ch...
This study explored the efficacy and safety of rivaroxaban in elderly patients, at different doses and age of patients, and analyzed risk factors of bleeding. A retrospective analysis was conducted of 299 patients aged 60 years or older who were admitted to the First Hospital of Jilin University between January 2016 and August 2018. It was found that the rate of bleeding events (but not embolism) significantly increased as the dose of oral rivaroxaban increased ( P < .001), and with age, especially in patients aged ≥80 years ( P = .001, both). The multivariate logistic regression analysis indicated that age (odds ratio [OR]: 2.963, 95% CI: 1.627-5.396) and the daily dose of rivaroxaban (OR: 2.325, 95% CI: 1.483-3.645) were independent risk factors for bleeding. The study determined that rivaroxaban anticoagulant therapy is effective in the elderly patients, but the risk of bleeding increases with age, and is a concern especially in the most old patients. The recommended daily dose of rivaroxaban is effective, but a lower dose is safer for the elderly patients.
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