1.Effects of curcumin derivatives C085 on K562 cells and its mechanism
Ying WU ; Ruijia CHEN ; Lixian WU ; Jianhua XU
Chinese Pharmacological Bulletin 2015;(6):870-875
Aim To explore the anti-proliferation and apoptotic effects of C085, a curcumin derivative, on K562 cells and its mechanism. Methods MTT assay and flow cytometry were used to examine cell prolifera-tion and apoptosis, respectively. The phosphorylation levels of Bcr-Abl initiated signaling proteins were ana-lyzed using Western blot. Results The results showed that C085 suppressed the growth of K562 cells and the IC50 value was about 5-fold lower than that of Cur. C085 also induced significant apoptosis on K562 cells in 24 hours when compared with imatinib. Western blot results demonstrated that C085 down-regulated the phosphorylation of Bcr-Abl in K562 cells in a dose-de-pendent manner. The phosphorylation of Stat 5 and
Crkl, which were downstream signaling proteins of Bcr-Abl kinase, was also inhibited by C085. C085 caused the opening of mitochondrial PT holes as detected by JC-1 fluorescent, which inhibited Bcl-2 and enhanced Bax , then induced apoptosis. Conclusion C085 in-hibited BCR-ABL+ K562 cells through inhibiting BCR-ABL kinase activity and down-regulating its down-stream signal proteins. Directly acting on mitochondrial PT hole and then activating apoptosis- associated pro-teins are also involved in the pro-apoptotic effect of C085 .
2.The therapeutic effects of survivin antisense nucleic acid combined with paclitaxel on subcutaneous xenograft mouse model of Balb/c
Lixian WU ; Lisen HUANG ; Ruijia CHEN ; Jue TIAN ; Fang KE
Journal of Xi'an Jiaotong University(Medical Sciences) 2015;(4):467-471
Objective To explore the therapeutic effects of combined application of survivin antisense nucleic acid and taxol in subcutaneous xenograft mouse model of Balb/c and to preliminarily investigate the mechanism of the anticancer effects.Methods The model of subcutaneous tumor was established by hypodermic injection of C26 cells into Bal b/c mice.The mice were then randomly divided into five groups through the internal tumor injection:the blank group (C),lipo2000 group (L),paclitaxel group (T),survivin antisense nucleic acid group (A),and survivin antisense nucleic acid combined with paclitaxel group (A+T).We observed tumor growth,determined cell apoptosis by TUNEL method,and detected the expression of survivin by Western blot.Results ① All treatment groups had T/C<60%,which was significantly different from that of group L (P <0.05);the intervention was proved effective in vivo .The tumor inhibition rate of mice tumor weight showed that there were significantly curative effects in groups T,A and A+ T compared with that in group C (P < 0.05 ).The antitumor activity of paclitaxel (tumor inhibition rate of 21.82%±0.84%)could be improved by more than 59% through combination therapy (tumor inhibition rate of 54.1 6% ± 0.32%)concerning inhibition of tumor weight growth.② TUNEL method detected apoptotic cells:The tumor cells hardly had apoptosis in the blank group while T group and A group had a certain number of apoptotic cells.The experiment results suggested that PTX could promote tumor cell apoptosis,and that not only A+T strengthened the effect in killing tumor cells,but also the synergy of both could influence tumor resistance and ultimately make the effect in promoting tumor cell apoptosis conspicuous.③ The expression of survivin protein:The results showed that the expression of survivin protein in group A + T was obviously decreased without the expression of β-actin affected;it did not change significantly in group C compared with group L.The ratio of the A-value in groups T,A and A+T was 0.895 ±0.01 1,0.704 ±0.121 and 0.345 ± 0.01 9,respectively.Analysis of variance t-test showed that the expression level in group A+T obviously differed from that in groups C,L,A and T (P <0.05).Conclusion The combined therapy of survivin antisense nucleic acid and taxol can promote tumor cell apoptosis by downregulating the expression of survivin protein,reduce the body’s resistance to drugs and create synergetic effects.
3.The experimental research about relationship between neuropeptides and mast cell in allergic rhinitis.
Jinxiang CHEN ; Ruijia YANG ; Zhichun HUANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2007;21(20):947-949
OBJECTIVE:
To explore the relationship between neuropeptides and mast cell in the initiation and development of allergic rhinitis.
METHOD:
Thirty healthy rats were randomly divided into three groups. The rat model of allergic rhinitis was established by using ovalbumin intraperitoneal immunization and nasal antigen challenge. After treating with capsaicin for two weeks, the counts of mast cells and the density of SP distribution were observed routinely in the nasal mucosa obtained from each models by HE, toluidine blue and immunohistochemical staining.
RESULT:
The counts of mast cells in AR were greatly more than them in normal controls (P < 0.01). After treating with capsaicin the mast cells were rare and significantly fewer than the normals (P < 0.01); The expression of SP was lower than the AR (P < 0.01), but no difference between the capsaicin group and normal group (P > 0.05).
CONCLUSION
Capsaicin can decrease the infiltration of mast cells, down regulate the SP expression, and improve the symptoms of AR greatly.
Animals
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Capsaicin
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therapeutic use
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Mast Cells
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metabolism
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Nasal Mucosa
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pathology
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Neuropeptides
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biosynthesis
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Rats
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Rats, Sprague-Dawley
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Rhinitis, Allergic, Perennial
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drug therapy
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metabolism
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pathology
4.DUOX2 mutations are frequently associated with congenital hypothyroidism in a Chinese Patients
Feng SUN ; Junxiu ZHANG ; Changyi YANG ; Keyi SONG ; Gang CHEN ; Wenbin ZHU ; Shuangxia ZHAO ; Yueyue WAN ; Ruijia ZHANG ; Manman ZHANG ; Huaidong SONG
Chinese Journal of Endocrinology and Metabolism 2017;33(7):567-573
Objective To investigate the prevalence of DUOX2 mutations in Chinese patients with congenital hypothyroidism (CH) and to discuss the inheritance pattern of DUOX2 gene.Methods Blood samples were collected from 91 CH children and their genomic DNA was extracted from peripheral blood leukocytes.All exons and exon-intron boundaries of DUOX2 were analyzed by target next-generation sequencing and family trios was established to study the inheritance pattern of DUOX2 gene.Results Fifty-four out of 91 children with CH carried DUOX2 mutation, with a prevalence of 59.34%.Of the 54 CH children, 36 carried DUOX2 biallelic mutations.In all 12 family trios with probands carrying biallelic DUOX2 mutations, the parents carried heterozygous DUOX2 mutations while still showing normal thyroid function, suggesting that CH caused by DUOX2 mutations is inherited in an autosomal recessive manner.Conclusion DUOX2 gene is one of the most frequently mutated genes in Chinese CH patients and its inheritance pattern is an autosomal recessive one.
5.Clinical study of correlation between syncope and risk of death in patients with cardiovascular emergencies
Jianbin MA ; Yun WANG ; Dong WANG ; Yan HUANG ; Hongli LIU ; Li BAI ; Ruijia XU ; Yongliang CHEN ; Qi WANG
Chinese Journal of Emergency Medicine 2018;27(5):541-547
Objective To explore the relationship between syncope and risk of death in patients with cardiovascular emergencies including acute myocardial infarction(AMI), arrhythmia, acute heart failure(AHF), pulmonary thromboembolism(PTE) and aortic dissection(AD) rupture. Methods Data from 2 789 patients with cardiovascular emergency admitted from June 2010 to June 2016 in the Emergency Department, Air Force General Hospital, PLA was retrospectively analyzed. Difference in gender, age and motality were compared between patients with syncope and those without syncope. Among fi ve kinds of cardiovascular emergency events with syncope, difference in mortality were compared. Difference in mortality were also analyzed by the CHM corrected chi square test when difference of disease, gender and age were taken into consideration. Syncope, the type of cardiovascular emergency, gender and age were analyzed as potential risk/protective factors for death by the multiple logistic regression analysis. Results The mortalities of the fi ve diseases accompanied with syncope were 50%, 30.43%, 26.53%, 20% and 7.04% respectively in arterial dissection, pulmonary embolism, acute myocardial infarction, acute heart failure and arrhythmia.There was a statistically signifi cant difference in mortality among the fi ve kinds of cardiovascular emergencies accompanied with syncope(P<0.05).The mortalities of patients with syncope were significantly higher than those without syncopein AMI patients(26.53% vs.11.20%,P<0.05) and cardiac arrhythmias patients(7.04% vs.0.36%,P<0.05).The results of the CHM corrected chi square test showed that there was signifi cant difference in mortality between the syncope group and non-syncope group, when the differences in disease type, age and gender were adjusted (χ2=35.876, P<0.01). The mortality of syncope group was higher than that of non-syncope group.When age, gender and disease type were considered as covariates, the multiple logistic regression analysis showed that syncope signifi cantly increased the risk of mortality(OR=3.876,95% CI:2.362-6.359,P<0.01).Conclusion Syncope is an independent risk factor of death in patients with cardiovascular emergencies.
6.Construction of a porcine model of ischemia with non-obstructive coronary artery and assessment by CT myocardial perfusion imaging combined with coronary CT angiography
Zilong REN ; Didi WEN ; Jingji XU ; Shuangxin LI ; Ruijia XUE ; Jing WANG ; Mai CHEN ; Jian XU ; Minwen ZHENG
Chinese Journal of Radiology 2023;57(7):797-803
Objective:To construct a porcine model of ischemia with non-obstructive coronary artery (INOCA) and explore the diagnostic value of a one-stop noninvasive method including CT myocardial perfusion imaging (CT-MPI) and coronary CT angiography (CCTA).Methods:Twelve swines were divided into the experimental group (9) and the normal group (3). Coronary microvascular dysfunction (CMD) porcine model was constructed in the experimental group by inducing diabetes mellitus, chronic kidney disease, and hypercholesterolemia. Invasive coronary angiography (ICA) and functional examination were performed on all 7+3 trial swines to clarify the INOCA diagnosis after completion of the modeling. Then, CT-MPI and CCTA were performed on all individuals to explore the CT-MPI and CCTA characteristics of INOCA porcine models. CT-MPI parameters, including myocardial blood flow (MBF), and myocardial blood volume (MBV) in rest and stress conditions, and CCTA parameters, including severity of stenosis and CAD-RADS, were analyzed.Results:ICA and functional tests showed that all swines in the experimental group met the diagnostic criteria for INOCA, which meant that INOCA porcine model was constructed successfully. CCTA results confirmed that there was no obstructive coronary stenosis in all 10 swines which were examined, which was consistent with ICA findings. CT-MPI results demonstrated that the mean MBF values, as well as the mean MBV values, in the rest and stress condition of each swines in the experimental group were lower than those of the control group. In contrast to the control group, the mean MBF and MBV values of swines in the experimental group in stress condition were generally lower than those in resting condition.Conclusions:In this study, a porcine model of CMD is successfully constructed by inducing hypercholesterolemia+diabetes mellitus+chronic kidney disease. ICA and invasive functional tests show that this CMD model meet the diagnostic criteria for INOCA. It has been confirmed that one-stop CT multimodality examination including CT-MPI and CCTA can be used for the diagnosis of INOCA as a noninvasive diagnostic method.