1. Angelica polysaccharides improve hepatic endoplasmic reticulum stress by inhibiting the expression of GRP78, p-PERK and p-Eif2α in diabetic KK-Ay mice
Xiankang MA ; Yangyang CUI ; Lixia YANG ; Denghai MI
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(8):926-936
AIM: To investigate the regulatory mechanism of Angelica polysaccharide on hepatic endoplasmic reticulum stress in diabetic KK-Ay mice. MEHTODS: Forty diabetic KK-Ay mice were randomly divided into model group, metformin group, and angelica polysaccharide high, medium, and low dose groups, with 8 mice in each group. 8 C57BL/6J mice were used as blank control group. The mice were gavaged with 400 mg/kg, 200 mg/ kg and 100 mg/kg of angelica polysaccharide in the high, medium and low dose groups, respectively, and 200 mg/kg of metformin hydrochloride in the metformin group, while the normal and model groups were gavaged with equal volume of saline, and fasting blood glucose and body weight were measured weekly. After 4 weeks of gavage, triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were measured in mice serum; RT-PCR was performed to observe the expression of glucose-regulated protein 78 (GRP78), phosphorylated pancreatic endoplasmic reticulum kinase (p-PERK) and phosphorylated α-subunit eukaryotic initiation factor 2 (p-Eif2α) in liver tissues. mRNA expression; Western blot, immunohistochemistry to detect the protein expression of GRP78, p-PERK, p-Eif2α in mouse liver tissues. HE staining: to observe the histopathological changes in the liver. RESULT: Compared with the blank group, the levels of TC, TG and LDL-C were significantly increased (P<0.01) and the levels of HDL-C were significantly decreased (P<0.01) in the model group; compared with the model group, the levels of TC, TG and LDL-C were significantly decreased (P <0.05, P<0.01) and the levels of HDL-C were significantly increased in the metformin group, angelica polysaccharide high and medium dose groups. Compared with the blank group, the expression of GRP78, p-PERK and p-Eif2α in the model group was significantly upregulated (P<0.01), and the expression of GRP78, p-PERK and p-Eif2α in the angelica polysaccharide high, medium and low dose groups was significantly downregulated (P<0.05, P<0.01), and the high dose group had the best effect compared with the model group. Compared with the model group, the mice in the angelica polysaccharide group showed dense liver tissue, reduced vacuole-like degeneration, reduced liver steatosis, gradually aligned hepatocytes, and clear hepatic sinusoidal structure, and the effect was dose-dependent. CONCLUSION: Angelica polysaccharide significantly improved liver injury in diabetic KK-Ay mice, and its mechanism of action may be related to the inhibition of endoplasmic reticulum stress-related proteins and factors GRP78, p-PERK and p-Eif2α expression by Angelica polysaccharide and improvement of endoplasmic reticulum stress.
2.Effects of Angelica sinensis polysaccharide on the apoptosis of cardiomyocytes in diabetic KK-Ay mice
Yangyang CUI ; Lixia YANG ; Denghai MI ; Ruixian WEI
China Pharmacy 2023;34(10):1211-1215
OBJECTIVE To investigate the effects of Angelica sinensis polysaccharide on the apoptosis of cardiomyocytes in diabetic KK-Ay mice. METHODS KK-Ay mice were randomly divided into model group, metformin group (200 mg/kg) and A. sinensis polysaccharide high-dose, medium-dose and low-dose groups (400, 200 and 100 mg/kg); C57BL/6J mice were included in blank group, with 8 mice in each group. Each group was given relevant medicine intragastrically or normal saline, once a day, for consecutive 4 weeks. After the final administration, the levels of fasting glucose, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and insulin (INS) were detected; the protein expressions of B-cell lymphoma 2 (Bcl-2), cleaved- caspase-3, apoptosis signal-regulated kinase 1 (ASK1), phosphorylated c-Jun N-terminal kinase (p-JNK), phosphorylated inositol- requiring enzyme 1α (p-IRE1α) in myocardium, and apoptosis in cardiomyocytes were also detected. RESULTS Compared with model group, the fasting glucose, TC and LDL-C content, apoptotic rate of cardiomyocyte, protein expressions of p-JNK and p- IRE1α, ASK1, cleaved-caspase-3 were significantly lower in the metformin group and A. sinensis polysaccharide medium-dose, high-dose groups; INS level and relative expression of Bcl-2 protein were significantly increased (P<0.05 or P<0.01). CONCLUSIONS A. sinensis polysaccharide can improve the levels of blood glucose and blood lipid and inhibit cardiomyocyte apoptosis in diabetic KK-Ay mice, and the mechanism may be related to the inhibition of IRE1/ASK1/JNK signaling pathway.
3.The progress of magnetic nanomaterials in application of biomedicine.
Journal of Biomedical Engineering 2014;31(2):472-476
Magnetic nanomaterials is widely used in medical diagnosis, drug delivery, biomedical and other fields due to their unique structure and excellent properties. The magnetic nanometer material in biomedical applications, such as biological separation and purification, application of controlled drug release and magnetic resonance imaging are reviewed in the present paper, and the development trend of magnetic nanomaterials is also forecasted.
Drug Delivery Systems
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Humans
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Magnetic Resonance Imaging
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Magnetics
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Nanostructures
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chemistry
4.Relationship between serum cortisol level and cancer-related fatigue
Zhongxing LI ; Denghai MI ; Fang YANG ; Zhizhen WEN ; Xiaorong LIU ; Yongxiang WANG ; Weiwei REN ; Zheng LI
Chinese Journal of Clinical Oncology 2014;(17):1089-1093
Objective:To investigate the relationship between cancer-related fatigue and cortisol in cancer patients and elucidate the underlying mechanism. Methods:A total of 80 cancer cases were divided into two groups:fatigue group (50 cases with cancer-related fatigue) and non-fatigue group (30 cases without fatigue). The scores were evaluated through the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) and the Fatigue Symptom Inventory (FSI) report. Serum specimens were examined through electrochemiluminesence immunoassay and enzyme-linked immunosorbent assay. Serum cholesterol was examined through the CHOD-PAP method, and serum total protein and albumin were determined via the Biuret method. Agarose gel electrophoresis was conducted to determine alpha 2 globulin ratio and to calculate serum alpha 2 globulin concentration. Results: The cortisol level in the fatigue group was significantly lower than that in the non-fatigue group[(119.68±5.34) nmol/L vs. (163.45± 31.49) nmol/L, P<0.05], and the adrenocorticotropic hormone (ACTH) level in the fatigue group was significantly higher than that in the non-fatigue group [(104.50 ± 17.15) ng/L vs. (51.43±13.24) ng/L, P<0.05]. Cortisol negatively correlated with MFSI-SF (r=-0.867, P<0.001) but positively correlated with ACTH (r=0.809, P<0.001). Furthermore, cortisol negatively correlated with FSI (r=-0.747, P<0.001) but positively correlated with ACTH (r=0.70, P<0.001). The levels of serum cholesterol [(1.25±0.70) mmol/L vs. (3.28±0.73) mmol/L, P<0.05], albumin[(18.24 ± 7.03) g/L vs. (37.40 ± 8.05) g/L, P<0.05], and alpha-2 globulin [(2.25±1.07) g/L vs. (5.36±1.09) g/L, P<0.05]were significantly lower in the fatigue group than in the non-fatigue group. Conclusion:The patients with cancer-related fatigue exhibited increased MFSI-SF score, decreased serum cortisol level, and enhanced ACTH level. The low serum cortisol levels caused a disorder in the serum ACTH and cancer-related fatigue of malignant tumor patients. The mechanism underlying the reduction in serum cortisol level correlated with the insufficient amounts of serum cholesterol, the composite material of cortisols, and of serum albumin, particularly alpha-2 globulin, the carrier protein of serum cholesterol.
5.Molecular targeting therapy of gastric cancer
Denghai MI ; Zhongxin LI ; Ning GAO
Journal of International Oncology 2011;38(5):377-380
It has been demonstrated that surgery is currently still the most effective approach to completely cure gastric cancer. However, while only 30%-40% of gastric cancer can obtain curative outcome through pure surgery, most of patients with gastric cancer would died of recurrence or distant metastasis of the tumor. It appears to be more critical to search for other therapeutic strategies for gastric cancer other than surgery. Molecular targeting therapy has become the focus and hotspot of comprehensive treatment of gastric cancer.
6.Cytokines correlated to cancer-related fatigue
Denghai MI ; Xiaorong LIU ; Zhongxin LI ; Zhizhen WEN
Journal of International Oncology 2011;38(8):577-579
Cancer-related fatigue is one of the most common and refractory clinical sympotoms in patients with cancer. Investigators have tried to study the molecular pathogenesis of cancer-related fatigue, and the cytokine has become a research focus. At present, a number of cytokines, including transformation growth factor, tumor necrosis factor, interleukin, proteolytic inducing factors, inflammatory cytokine are proved to be correlated to cancer-related fatigue.
7.Role of platelet in tumor thrombosis
Journal of International Oncology 2010;37(8):623-625
Through various mechanisms, malignant tumors can cause thrombosis, which in turn facilirates the growth and metastasis of tumors. Platelets interact with tumor cells to form tumor thrombosis and assist the metastasis of malignant tumors by mechanisms such as protecting tumor cells from immune surveillance and facilitating tumor cell growth and adhesion to vascular endothelial cells.
8.Prevention and treatment of aspirin on tumor
Journal of International Oncology 2010;37(6):435-438
It has been suggested that aspirin may have anti-tumor effect based on animal experiments and epidemiological investigation, however, it remains controversial whether aspirin has certain effects on prostatic cancer, bladder cancer, ovarian cancer and pancreatic cancer whereas it has been well documented that long-term regular use of aspirin can significantly reduce risks of colorectal cancer, esophageal cancer and gastric cancer.
9.Efficacy and safety of postoperative non-steroidal antiinflammatory drugs therapy in patients following total hip arthroplasty:A Meta analysis
Hongwu MA ; Genyuan CHEN ; Denghai MI ; Long HU ; Weihua HOU ; Guoxin QU
Chinese Journal of Tissue Engineering Research 2009;13(52):10223-10226
BACKGROUND:The non-steroidal antiinflammatory drugs (NSAIDs) were widely used to prevent heterotopic bone formation following total hip arthroplasty (THA),however,its efficacy and safety is poorly understood.OBJECTIVE:To determine the efficacy and safety of postoperative NSAIDs therapy in patients undergoing THA using Meta analysis.METHODS:The databases of PubMed,Embase,Cochrane Library,Chinese biomedical literature,CNKI,VIP as well as bibliographies of retrieved articles were researched for randomized controlled trials comparing NSAID versus control after THA,and the data were analyzed using Review Manager 5.0.RESULTS AND CONCLUSION:A total of 13 randomized controlled trials totaling 4706 participants were included.The result of meta analysis showed that low dose aspirin did not significantly affect the incidence of heterotopic bone formation (HBF) [RR=0.99,95% CI (0.87,1.14) rather than medium to high dose NSAIDs [RR=0.44,95% CI(0.30,0.64),there was no significant difference between two group in hip pain and physical function,the incidence of HBF was 16.0% in NSAID-group and 11.1% in 7 Gy group.Apart from low dose aspirin,medium to high doses of postoperative NSAIDs produce a substantial reduction in the incidence of HBF at the cost of minor high gastrointestinal side effect.Limited evidence showed there were no significant differences between the groups for improvements in hip pain and physical function,7 Gy fraction is more effective than use of NSAID.
10.Relationsip between PTEN and VEGF expression and clinicopathological characteristics in HCC.
Denghai, MI ; Jilin, YI ; Enyu, LIU ; Xingrui, LI
Journal of Huazhong University of Science and Technology (Medical Sciences) 2006;26(6):682-5
To investigate the expressions and significance of the tumor suppressor gene phosphatase and tensin homlog deleted on chromosome ten protein (PTEN) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC), and to analyze the relationship between their expressions and the tumor's invasion and their pericarcinomatous tissues, the correlation of their expressions with the tumor's clinicopathological characteristics and invasion potential were studied. Our study showed that the expression level of PTEN in HCC was remarkably lower than that in pericarcinomatous liver tissues, while the expressions of both VEGF and MVD were higher than that in pericarcinomatous liver tissues. Correlation analysis revealed that the expression of PTEN was negatively related to the progression of the pathological differentiation and invasion of tumor, whereas the expressions of VEGF and MVD were positively related. Moreover, there was a negative relationship between the expression of PTEN and the expressions of VEGF and MVD, and a positive one between VEGF and MVD. The expressions of PTEN and VEGF may reveal the degree of differentiation and the invasive potential of HCC tissues. The mechanism by which the lack of PTEN expression probably induces abnormal hyperexpression of VEGF may play an important role in the invasion and metastasis of HCC.

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