1.Expression and prognostic significance of interleukin-36α in colorectal cancers
Xutao LIN ; Dejun FAN ; Yifeng ZOU ; Xiaosheng HE ; Xiaobin ZHENG ; Xuanhui LIU ; Ping LAN
Journal of Chinese Physician 2015;17(5):652-657
Objective To investigate the expression and prognostic significance of Interleukin-36α (IL-36α) in colorectal cancer.Methods The expression of IL-36α was tested by immunohistochemical staining in 329 cases of colorectal cancer.According to the intensity and the proportion of positive tumor cells,all the patients were divided into IL-36α low and high expression groups.The clinicopathological factors and prognosis of patients between IL-36α low high expression groups were compared.Results Significant differences were observed in the number of patients in tumor differentiation and pM classification between patients in the IL-36α low and high expression groups (P < 0.05).The 5-year overall and tumorfree survival rates of patients were 79.3% and 77.2% in IL-36α low expression group,and 66.3% and 65.3% in IL-36α high expression group (P <0.05).COX proportional hazard regression model revealed that high expression of IL-36α was associated with short overall survival time and tumor-free survival time of colorectal cancer patients (P < 0.05).Multivariate analysis identified IL-36α expression in colorectal cancer as an independent prognosticator (P < 0.05).Conclusions High expression of IL-36α was correlated with tumor differentiation and pM classification of colorectal cancers,and it is an independent predictor of poor survival for patients with colorectal cancer.
2.Effect of the chelator Zn-DTPA on the excretion of lead in lead intoxication mice detected with ICP-MS.
Chen LI ; Kaizhi LU ; Qi ZHOU ; Qiong WANG ; Yuliang ZENG ; Hongjun YIN ; Xuanhui HE ; Ying TIAN ; Junxing DONG
Acta Pharmaceutica Sinica 2014;49(11):1588-92
To study the lead excretion effect of the chelator Zn-DTPA on the lead intoxication mice, inductively coupled plasma mass spectrometry (ICP-MS) was applied to detect the lead content of biological samples. The acute lead intoxication mice model was established by injecting lead acetate intraperitoneally with the dose of 1 mg. Zn-DTPA was administered intraperitoneally to mice once daily for five consecutive days 4 h after intoxication. Control group, model group, combination of Zn-DTPA and Ca-DTPA group were evaluated at the same time. The urine was collected every day. The mice were sacrificed in batches in the 2rd, 4th, 6th day. Biological samples including urine, whole blood, femur and brain were prepared and nitrated. Lead concentration was detected by ICP-MS. The result showed that Zn-DTPA could increase lead content in urine markedly and reduce lead content in blood, femur and brain.
3.Xuefu Zhuyu Capsules Ameliorate Atherosclerosis in Mice by Regulating Sirt3/EPAC1 Signaling Pathway
Bo YAO ; Hengwen CHEN ; Jiyu GONG ; Xuanhui HE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):31-41
ObjectiveTo observe the effects of Xuefu Zhuyu capsules (XFZY) on blood lipid levels and aortic plaques in the mouse model of atherosclerosis (AS) induced by a high-fat diet by regulating the silencing regulatory factor 2-like protein 3 (Sirt3)/exchange protein directly activated by cAMP 1 (EPAC1) signaling pathway and explore the mechanism of XFZY in ameliorating AS. MethodMice were assigned into normal, model, blank, rosuvastatin (0.05 g·kg-1·d-1), and low-, medium-, and high-dose (0.3, 0.6, 1.2 g·kg-1·d-1, respectively) XFZY groups. The normal group consisted of normal C57BL/6J mice, while the other groups consisted of ApoE-/- C57BL/6J mice. The normal group and blank group were fed routinely, and the rest groups were fed with a high-fat diet for 24 consecutive weeks for the modeling of AS. The drug intervention groups were administrated with corresponding drugs by gavage, and model group and blank group with an equal volume of deionized water for 6 consecutive weeks. The small animal B-ultrasound was used to evaluate the mouse heart function and aortic plaque condition. A fully automated biochemical analyzer was used to measure the levels of blood lipids such as total cholesterol (CHOL), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and extremely low-density lipoprotein (VLDL) in mice. Oil red O staining was employed to observe lipid deposition in the aorta. Hematoxylin-eosin staining and Masson staining were employed to observe the pathological changes and collagen deposition in mouse blood vessels. Transmission electron microscopy was employed to observe the mitochondrial damage in mouse aorta. The levels of adrenocorticotropic hormone (ACTH), adenosine triphosphate (ATP), and nicotinic choline receptor α1 (CHRNα1), and total superoxide dismutase (T-SOD) were measured by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were performed to determine the mRNA and protein levels, respectively, of Sirt3, EPAC1, Caspase-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the mouse aorta and heart. ResultMultiple AS plaques were observed in the aortic arch, indicating that the model was successfully established. Compared with the model group, the XFZY groups showed reduced and narrowed plaques. Compared with the normal group, the model group showed elevated CHOL level (P<0.01). Compared with the model group, rosuvastatin and low-dose XFZY lowered the CHOL and TG levels (P<0.01). Compared with the normal group, the model group presented a large number of protruding red lipid plaques on the aortic wall and increased percentage of AS plaque area to total tissue area (P<0.01). Compared with the model group, low-dose XFZY reduced the plaque load (P<0.05). Compared with the model group, XFZY at different doses reduced the lipid plaques and collagen deposition. Compared with the normal group, the model group showed decreased or disappeared mitochondrial cristae and presented severe damage of the membrane structure in endothelial cells. The mitochondria of endothelial cells in each treatment group approached the normal structure, with mitochondrial cristae faintly visible. Compared with the normal group, the model group showcased reduced myocardial mitochondrial ATP activity (P<0.01), which were rescored in the drug intervention groups (P<0.01). Compared with the normal group, the modeling inhibited the expression of Sirt3 (P<0.01) and promoted the expression of EPAC1 (P<0.01). Compared with the model group, low-dose XFZY increased the Sirt3 content (P<0.01) and medium-dose XFZY increased the EPAC1 content (P<0.01), which indicated that XFZY treatment upregulated the mRNA and protein levels of Sirt3 and downregulated the mRNA and protein levels of EPAC1. ConclusionXFZY can alleviate the aortic lipid deposition, reduce the AS plaque area, improve the mitochondrial morphology and functions in endothelial cells, increase the ATP activity, upregulate the expression of Sirt3, and downregulate the expression of EPAC1 in AS mice by regulating mitochondrial energy metabolism via the Sirt3/EPAC1 signaling pathway.