2.ZO-1 gene methylation status and its clinical significance in children with non-Hodgkin lymphoma.
Yu-Qiao DIAO ; Fan QU ; Ming-Juan YANG ; Jian-Hui MENG ; Xiu-Li ZHU ; Jian CHEN
Chinese Journal of Contemporary Pediatrics 2014;16(6):619-623
OBJECTIVETo investigate the methylation status of zonula occludens-1 (ZO-1) gene promoter and its clinical significance in children with stage IV non-Hodgkin lymphoma (NHL) and to provide a basis for further etiological study and early diagnosis of this disease.
METHODSFifty-five children with a confirmed diagnosis of stage IV NHL (40 cases of T-NHL and 15 cases of B-NHL) were selected as the case group, and 20 children with diseases other than hematologic malignancies were selected as the control group. Bone marrow samples were collected from these subjects. Methylation-specific PCR (MS-PCR) was applied to evaluate the methylation status of ZO-1 gene promoter, and the integrated optical density (IOD) was determined. RT-PCR was used to measure the mRNA expression of ZO-1.
RESULTSMS-PCR showed that the methylated bands of ZO-1 gene promoter were found in 39 (70.9%) of 55 patients in the case group before treatment, while no ZO-1 gene promoter methylation was detected in the control group. With close tracking of 47 cases in the study group, consisting of 32 cases of T-NHL and 15 cases of B-NHL, the rates of ZO-1 gene promoter methylation prior to treatment were 72% and 67%, respectively, (P>0.572). The cases of T-NHL and B-NHL showed no significant changes in methylation rate in the early and middle phases of chemotherapy (P>0.05), but they showed significant changes in methylation rate in the late phase of chemotherapy (P<0.05). RT-PCR showed that the NHL cases carrying methylated ZO-1 gene had no mRNA expression of ZO-1, while all children in the control group had mRNA expression of ZO-1. There was no linear relationship between the total number of peripheral blood leukocytes and ZO-1 gene IOD (r=0.093, P=0.575); a positive correlation was found between the number of malignant cells in bone marrow and ZO-1 gene IOD (r=0.669, P<0.001).
CONCLUSIONSZO-1 gene shows a hypermethylation status in children with NHL, and the methylation level is positively correlated with the number of malignant cells in bone marrow. ZO-1 may be used as a novel molecular marker in early diagnosis, outcome assessment, prognostic evaluation, and detection of minimal residual disease.
Adolescent ; Child ; Child, Preschool ; DNA Methylation ; Female ; Humans ; Infant ; Lymphoma, Non-Hodgkin ; genetics ; Male ; Promoter Regions, Genetic ; Zonula Occludens-1 Protein ; genetics
4.Recent advances in natural product induced DNA damage response in cancer cells.
Guo-wen REN ; Ya-nan NIU ; Jin-jian LU ; Yi-tao WANG ; Xiu-ping CHEN
China Journal of Chinese Materia Medica 2015;40(24):4797-4804
The DNA structures could be altered or even damaged by exogeous or endogenous factors during cell proliferation. Failure of effective and timely repair will lead to cell cycle arrest or apoptosis. By taking the advantage of the quick proliferation of cancer cells, DNA damage induction, cell cycle arrest and apoptosis promotion have become important strategies for ant-cancer chemotherapy. Previous reports showed that an array of natural compounds inhibit cancer cell proliferation by inducing DNA damage, which have therapeutic potentials for anti-cancer drug research and development.
Animals
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Biological Products
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pharmacology
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therapeutic use
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DNA Damage
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Drugs, Chinese Herbal
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therapeutic use
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Humans
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Neoplasms
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drug therapy
5.Antitussive constituents of Disporum cantoniense.
Xiu-Hai GAN ; Chao ZHAO ; Zhi-Yuan LIANG ; Xiao-Jian GONG ; Hua-Guo CHEN ; Xin ZHOU
China Journal of Chinese Materia Medica 2013;38(23):4099-4103
The antitussive activity assay for the root extraction of Disporum cantoniense was carried out with coughing mice induced by ammonia liquor. The results showed that the ethanol and water extractions of D. cantoniense possess strong antitussive activity, and the high dose of the former was better than positive control, and then the constituents of the ethanol extraction were separated and purified by various modern chromatographic techniques. Their structures were identified by physico-chemical properties and spectroscopic data. As a result, eight compounds were isolated and identified as stigmast-4-en-3-one(1), (22E, 24R)-ergosta-5, 7, 22-trien-3beta-ol(2), obtucarbamate A(3), obtucarbamate B(4), neotigogenin(5), azo-2, 2'-bis[Z-(2,3-dihydroxy-4-methyl-5-methoxy) phenyl ethylene] (6),dimethyl {[carbonylbis (azanediyl)] bis( 2-methyl-5, 1-phenylene) j dicarbamate (7) , and quercetin-3-O-pB-D-glucopyranoside(8). All compounds were isolated from this plant for the first time, and the result of bioactivity-directed isolation showed that compounds 3, 4, and 6 had obvious effect on antitussive activity, and compound 6 had the same level as positive control.
Animals
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Antitussive Agents
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chemistry
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isolation & purification
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pharmacology
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Drugs, Chinese Herbal
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chemistry
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isolation & purification
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pharmacology
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Ethanol
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chemistry
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Female
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Liliaceae
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chemistry
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Male
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Mice
6.Effects of ischemic postconditioning on myocardial infarction sizes and protein kinase C expression in aged rats with post-ischemia reperfusion injury
Min LI ; Jian ZHANG ; Yanhong LIANG ; Yanrong CHEN ; Mengran WANG ; Yao XIAO ; Hui XIU
Chinese Journal of Geriatrics 2010;29(5):420-423
Objective To observe the effects of ischemic postconditioning (IPTC) on myocardial infarction sizes (IS) and protein kinase Cα (PKCα) expression in aged rats with post-ischemia reperfusion injury,and to explore the mechanism.Methods A total of 120 male Wistar rats were divided into aged group and adult group.The aged group was randomly divided into control group (n=12,30-min ischemia and 3-h reperfusion),5 s,10 s,30 s and 60 s IPTC groups [n= 12,each;after 30 min occlusion of left coronary artery (LCA),three cycles of 5 s,10 s,30 s,60 s reperfusion respectively followed by the same interval LCA re-occlusion were applied at the beginning of reperfusion].The IS was measured with TTC dye,and PKC expression was investigated by immunohistochemistry.Results Different IPTC intervals had different effects on IS and PKC expression,10 s and 30 s IPTC could reduce IS both in aged rats and adult rats [(55.9±6.0)% and (47.4±5.5)%],IS in 10 s IPTC group in aged rats was (48.1±5.3)%,in adult rats was (39.2±5.7) %;IS in 30 s IPTC group in aged rats was (48.8 ± 6.8) %,in adult rats was (40.2 ± 6.1 ) %.PKCα expression increased in aged and adult rats (all P<0.05).5 s IPTC could increase IS [IS in 5 s IPTC group in aged rats was (63.5±5.4)%,and PKCα expression reduced in aged rats (all P<0.05)].Conclusions IPTC has cardio-protective effect in aged rats suffering from acute myocardial injury during reperfusion,the effect of IPTC is related to reperfusion-reocclusion interval.
7.Effect of knockdown microRNA-214 on drug resistance of different lymphoma cell types
The Chinese Journal of Clinical Pharmacology 2017;33(10):905-908
Objective To explore the function of microRNA-214 on the drug resistance of different lymphoma cell types.Methods The Jurkat cells,OCI-Ly3 cells and Raji cells were selec-ted as the experimental groups.The healthy peripheral blood lymphocytes (Scr) were selected as the control group.The cells were miR-214 knockdown and stimulated with different drugs.The expression of miR-214 in different types of lymphoma ceils was detected by real-time PCR.The cell viability of lymphoma cells after knockdown miR-214 was detected by CCK-8.The drug sensitivity was detected by methyl thiazolyl tetrazolium colorimetric method(MTT) assay.The BCL11B protein levels was detected by Western blot.The luciferase reporter assay was used to detect whether BCL11B was the target gene of miR-214.Results The miR-214 expression in the experimental groups of Jurkat,Oci-ly3 and Raji cells were 27.21 ± 1.37,17.13 ±2.11,19.31± 2.46,which were significantly higher than those in control group of 1.17 ± 0.28,the difference was statistical significance (P < 0.05).After knockout miR-214,compared with the cell viability in control group (86 ± 12)%,the cell viability of Jurkat,OCI-Ly3 and Raji were (42 ± 13)%,(65 ± 11)%,(58 ± 7)%,the difference were significantly decreased (P < 0.05).The drug sensitivity of Scr cells (control group) to doxorubicin,cyclophosphamide,daunorubicin,mito-mycin C and vincristine were 0.46 ± 0.11,1.96 ± 0.13,1.15 ± 0.22,3.90 ± 0.52,0.52 ± 0.15,respectively.The drug sensitivity of Jurkat cells to five drugs were 0.32 ±0.07,0.76 ±0.16,0.73-±0.13,2.36 ±0.16,0.37 ±0.06.The drug sensitivity of OCI-Ly3 cells to the five drugs were 0.28 ±0.06,0.91 ±0.12,0.55 ±0.09,2.01 ±0.36,0.23 ± 0.07,respectively.The drug sensitivity of Raji cells to five drugs were 0.36 ± 0.04,0.82 ± 0.08,0.64 ± 0.07,3.31 ±0.21,0.35 ±0.05,respectively.Which indicated that the drug sensitivity of lymphoma cells to various drugs was significantly decreased after the inhibition of miR-214 expression.The BCL11B was the direct target of miR-214.Conclusion Inhibition of miR-214 expression could decrease the cell viability of lymphoma cells and decrease the multidrug resistance of leukemia lymphocytes,which may be related to the miR-214 knockdown on the expression of BCL11 B.
8.Antiviral effects of the combination of glycyrrhizin and ribavirin against influenza A H1N1 virus infection in vivo.
Xiu-xiu CHEN ; Hong-xia ZHOU ; Wen-bao QI ; Zhang-yong NING ; Yong-jiang MA ; Yao-lan LI ; Guo-cai WANG ; Jian-xin CHEN
Acta Pharmaceutica Sinica 2015;50(8):966-972
Ribavirin is a broad-spectrum antiviral agent and glycyrrhizin has activities of anti-inflammation, immunoregulation and anti-viral infections. To enhance antiviral efficacy and weaken side-effects of ribavirin, antiviral effects of the combination of glycyrrhizin and ribavirin were studied in the present study. Firstly, a mouse model of viral pneumonia was established by inoculation of influenza H1N1 virus. Protective effects of glycyrrhizin and ribavirin used alone or in combination against H1N1 virus infection in mice were evaluated based on the survival rate, lung index and virus titer in lungs of mice. Results showed that the combination of glycyrrhizin and ribavirin significantly inhibited the lung consolidation with a 36% inhibition ratio on the lung swell of infected mice. The combination of the two drugs exhibited synergetic effects on survival of infected mice. The combination of 50 mg · kg(-1) · d(-1) glycyrrhizin and 40 mg · kg(-1) · d(-1) ribavirin resulted a 100% protection for infected mice with a synergetic value of 36, which was significantly higher than the control group and each drug alone. This combination also resulted a significant drop of lung virus titer (P < 0.01), as well as inhibition on the production of proinflammatory cytokines IL-6 (P < 0.01), TNF-α (P < 0.01) and IL-1β (P < 0.05) induced by virus infection compared to the control. The treatment of ribavirin plus glycyrrhizin was more effective in influenza A infection in mice than either compound used alone, which suggested a potential clinical value of the combination of the two agents.
Animals
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Antiviral Agents
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pharmacology
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Disease Models, Animal
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Drug Synergism
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Drug Therapy, Combination
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Glycyrrhizic Acid
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pharmacology
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Inflammation
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immunology
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Influenza A Virus, H1N1 Subtype
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drug effects
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Interleukin-1beta
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immunology
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Interleukin-6
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immunology
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Lung
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immunology
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virology
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Mice
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Orthomyxoviridae Infections
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drug therapy
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Pneumonia, Viral
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drug therapy
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Ribavirin
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pharmacology
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Tumor Necrosis Factor-alpha
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immunology
9.Effects of guizhi fuling capsule on sex hormone levels and breast issue morphology of mammary gland hyperplasia model rats.
Xiu-juan CHANG ; Jun ZHOU ; Shuai ZHANG ; Jian CHEN ; Chun-miao CHEN ; Zhen-zhong WANG ; Wei XIAO
China Journal of Chinese Materia Medica 2014;39(21):4139-4142
OBJECTIVETo research the effects of Guizhi Fuling capsule on sex hormones levels in blood serum and breast issue morphology of hyperplasia of mammary glands model rats.
METHODThe unpregnancy SD rat models of hyperplasia of mammary glands were established by injecting 0.5 mg x kg(-1) benzoate estradiol. After five weeks doses,the effects of Guizhi Fuling capsule 2.0, 1.0, 0.5 g x kg(-1) and Rupixiao tablet 0.5 g x kg(-1) on the changes of papilla diameter, height and breast issue morphology of the naimal models were explored, and sex hormones levels in blood serum were measured.
RESULTGuizhi Fuling capsule can inhibitnipple swell, improve breast tissue morphology pathological profiles of the animal models, and decrease oestradiol (E2) level and increase progesterone (P) level in blood serum.
CONCLUSIONThese results suggested that Guizhi Fuling capsule could, improve mammary gland pathological profiles. Regulating sex hormone levels may be its important mechanism for treatment of hyperplasia of mammary glands.
Animals ; Capsules ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gonadal Steroid Hormones ; blood ; Hyperplasia ; Mammary Glands, Animal ; drug effects ; pathology ; Rats
10.Current topics on cancer biology and research strategies for anti-cancer traditional Chinese medicine.
Xiu-ping CHEN ; Zheng-hai TANG ; Zhe SHI ; Jin-jian LU ; Huan-xing SU ; Xin CHEN ; Yi-tao WANG
China Journal of Chinese Materia Medica 2015;40(17):3416-3422
Cancer, an abnormal cell proliferation resulted from multi-factors,has the highest morbidity and mortality among all the serious diseases. Considerable progress has been made in cancer biology in recent years. Tumor immunology, cancer stem cells (CSCs), autophagy, and epithelial-mesenchymal transition (EMT) have become hot topics of interests in this area. Detailed dissection of these biological processes will provide novel directions, targets, and strategies for the pharmacological evaluation, mechanism elucidation, and new drug development of traditional Chinese medicine.
Animals
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Antineoplastic Agents, Phytogenic
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administration & dosage
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Drugs, Chinese Herbal
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administration & dosage
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chemistry
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Humans
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Neoplasms
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drug therapy
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genetics
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immunology
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physiopathology