2.Evaluation of dose-related effects of 2', 3', 5'-tri-O-acetyl-N6-(3-hydroxylaniline)adenosine using NMR-based metabolomics.
Zhao-Xia MIAO ; Liu YANG ; Chun-Ying JIANG ; Ying-Hong WANG ; Hai-Bo ZHU
Acta Pharmaceutica Sinica 2014;49(5):679-685
2', 3', 5'-Tri-O-acetyl-N6-(3-hydroxylaniline)adenosine (WS070117) is a derivative compound of natural product cordycepin. It has significant lipids regulating activity and low toxicity which has been proved by in vitro and in vivo experiments. In this study, 1H NMR-based metabolomics was used to investigate the dose-related effects of WS070117 on hyperlipidemia of high-fat-fed hamsters. The hyperlipidemic hamsters were administrated with six different doses of WS070117, including 3, 12, 50, 100, 200 and 400 mg x kg(-1) x d(-1). 1H NMR spectra of hamster serum were visually and statistically analyzed using two multivariate analyses: principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). As a result, WS070117-treated groups showed dose-related regulation of metabolites associated with lipid metabolism, choline metabolism and glucose metabolism. The dose of 3 mg x kg(-1) x d(-1) of WS070117 only exhibited a little lipids regulating activity. However, the doses of 12 and 50 mg x kg(-1) x d(-1) of WS070117 both regulated the contents of metabolites to reverse significantly toward normal levels. When the dose of WS070117 reached 100 mg x kg(-1) x d(-1), it was more effective than positive control drugs. The work suggested that NMR-based metabolomics might be a valuable approach to evaluate dose-related effects of lipids regulating compounds.
Adenosine
;
analogs & derivatives
;
pharmacology
;
Animals
;
Cricetinae
;
Hyperlipidemias
;
metabolism
;
Least-Squares Analysis
;
Lipid Metabolism
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drug effects
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Magnetic Resonance Spectroscopy
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Metabolomics
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Multivariate Analysis
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Principal Component Analysis
3.Analysis of a 452C/T single nucleotide polymorphism in γ-glutamyl hydrolase gene in children with acute leukemia.
Hong-hong ZHANG ; Li-jie YUE ; Xiao-wen CHEN ; Wei ZHAO ; Chun-yan HU ; Miao-miao ZHENG ; Chun-lan YANG ; Cai XIE
Chinese Journal of Medical Genetics 2012;29(3):352-355
OBJECTIVETo investigate the distribution of γ-glutamyl hydrolase gene (GGH) 452C/T genotype and allele frequency in children with acute leukemia (AL) and healthy children.
METHODSBone marrow samples from 92 children with AL and peripheral blood samples from 124 healthy children were obtained to prepare complementary DNAs (cDNAs). The cDNAs were analyzed for a GGH 452C/T polymorphism by reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis (RT-PCR-DGGE) and direct sequencing.
RESULTSThe frequencies of the AL patients with TT, CT and CC genotypes were 2.2%, 13.0% and 84.8%, and the frequencies of the control children were 1.6%, 16.9% and 81.5%, respectively. There was no significant difference in GGH genotype or T allele frequency between the two groups (P> 0.05). However, the T allele frequency in Han Chinese children was significantly different from those reported in Japanese, Mexican and African-American populations.
CONCLUSIONThe frequency of 452C/T polymorphism of GGH gene in Han Chinese children has been determined. The results suggested that an ethnic difference may exist.
Acute Disease ; Base Sequence ; Child ; Child, Preschool ; Female ; Gene Frequency ; Genotype ; Humans ; Infant ; Infant, Newborn ; Leukemia ; enzymology ; genetics ; Male ; Polymorphism, Single Nucleotide ; gamma-Glutamyl Hydrolase ; genetics
4.Treatment of constipation by intensive acupoints thread embedding combined with local anal operation.
Dong-bing LI ; Jing-fan TAN ; Chun-hong MIAO
Chinese Journal of Integrated Traditional and Western Medicine 2009;29(3):260-263
OBJECTIVETo search for the best therapy for slow transmission constipation (STC) or mixed constipation (MC) by intensive acupoints thread embedding (IATE).
METHODSA total of 310 patients with constipation were assigned to 5 groups using a stratification control method. The 62 patients of STC in the observation group I were treated by IATE at Dachangshu (BL 25), Tianshu (ST 25), Zhongji (CV 3) and Zusanli (ST 36) acupoints; the 62 of MC in the observation group II by IATE at the same acupoints and local anal operation; both the 62 of STC in the control group I and the 62 of MC in the control group 1I were treated by oral administration of Simo Decoction, while the 62 of MC in the control group III were treated by local anal operation alone. Conditions of defecation were recorded every day in the 6-month follow-up period. Gastrointestinal transit test (GITT) was carried out before and after treatment. One follow-up was conducted at the 1st, 3rd and 6th month.
RESULTSIn the 124 patients of the two observation groups, 52 (41.9%) were cured after treatment, they could normally discharge stool, 5 (4.0%) showed markedly effective with their constipation alleviated, but having occasional bowel slackened sensation. In the control group I and II, none was cured or effectively treated, while in the control group III, the efficacy in 8 patients were judged as marked effective, but none was cured.
CONCLUSIONIATE is a convenient and effective composite therapy. It shows favorable clinical efficacy for STC, and also for MC in case of combined with local anal operation.
Acupuncture Points ; Aged ; Anal Canal ; surgery ; Catgut ; Constipation ; therapy ; Female ; Humans ; Male ; Middle Aged ; Prosthesis Implantation ; methods
5.Effect of graded composite zirconia-hydroxyapatite on viability of rat osteoblast cells cultured in vitro
Ren-Fu QUAN ; Di-Sheng YANG ; Xu-Dong MIAO ; Wei LI ; Xiao-Chun WU ; Hong-Bin WANG
Chinese Journal of Trauma 2003;0(11):-
Objective To evaluate the effect of a novel orthopedic biomaterial,graded composite zireonia(ZrO2)hydroxyapatite(HAP)on activity of rat osteoblast ceils(OB)cultured in vitro. Methods The pure zirconia material was used as control to measure surface roughness of the composite material that was examined by using scanning electron microscope(SEM)and X-ray diffraetometer (XRD).The rat osteoblast cells were cultured on the two materials.Alkali phosphatase(ALP)of the two groups was measured and ELISA was used to detect IL-6 and TGF-?eoncentration of the supematant of OB cells.Tumor growth factor-?(TGF-?)mRNA was detected by RT-PCR.SEM was used to observe OB cells on the two materials.The extract of the composite material was used for a eytotoxicity test to cal- culate the relative proliferation rate(RGR)and classify the toxicity.Results The surface roughness of the gradual composite materials was significantly higher than that of the control materials(P<0.01). The ALP of the gradual material group was markedly higher than that of the control group at different in- tervals.There was significant difference of the IL-6 and TGF-?concentrations 2-4 days after culture be- tween two groups(P<0.05,P<0.01).The mRNA level of TGF-?of the two OB groups also showed marked statistical difference(P<0.01).The ossification of the OB cells on the composed material was marked after 14 days.The MTT color experiments showed no statistic significance between materials group and negative group,with the toxicity at levelⅠand 0(P<0.05).Conclusion Graded composite ZrO2 HAP can significantly promote proliferation and differentiation of OB cells cultured in vitro and has good biocompatibility.
6.Association of single nucleotide polymorphism of methylenetetrahydrofolate reductase gene with susceptibility to acute leukemia.
Miao-miao ZHENG ; Li-jie YUE ; Hong-hong ZHANG ; Chun-lan YANG ; Cai XIE
Chinese Journal of Medical Genetics 2013;30(4):451-455
OBJECTIVETo assess whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene is associated with susceptibility to acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) in Chinese Han children.
METHODSThe study has included 87 patients with ALL, 22 patients with AML and 120 healthy controls. All subjects were analyzed with reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis and sequencing.
RESULTSA 677CT genotype of the MTHFR gene was associated with decreased risk of ALL (OR=0.23, 95%CI: 0.07-0.79). However, MTHFR A1298C genotypes were not associated with the risk of either disease. 677TT/1298AA and 677CC/1298AC genotypes were associated with increased risk of ALL(OR=3.78, 95% CI: 1.38-10.40; OR=3.17, 95% CI: 1.18-8.53, respectively), whereas the genotype 677CT/1298AA was associated with susceptibility to AML (OR=0.23, 95% CI: 0.06-0.97).
CONCLUSIONOur data suggested that C677T polymorphism of MTHFR gene may increase the risk of childhood AML.
Acute Disease ; Base Sequence ; Child ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Infant ; Leukemia ; diagnosis ; enzymology ; genetics ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Molecular Sequence Data ; Polymorphism, Single Nucleotide
7.Methylation status of FHIT gene in plasma and expression of FHIT gene in cancer tissue of cervical cancer patients.
Chen-chun REN ; Xu-hong MIAO ; Bin YANG ; Lei ZHAO ; Rui SUN ; Wen-qin SONG
Chinese Journal of Medical Genetics 2006;23(5):565-567
OBJECTIVETo explore the methylation status of 5' CpG island of fragile histidine triad (FHIT) gene in plasma and the expression of FHIT protein in cancer tissue of cervical cancer patients.
METHODSMethylation-specific PCR (MS-PCR) was employed to examine methylation of FHIT gene in 151 plasma samples before treatment. The immunohistochemistry was used to the expression of FHIT protein in cancer tissues.
RESULTSCpG island methylation of FHIT was detected in 31.13% of plasma samples. The expression of FHIT protein was decreased or discarded in 59.60% of cervical cancer tissues. Among them 47.78% was included in methylation positive samples.
CONCLUSIONCpG island methylation of FHIT gene in plasma plays an important role on cervical cancer, which results in decreased expression of FHIT protein. It can be used to diagnose and evaluate the effect of treatment to cervical cancers.
Acid Anhydride Hydrolases ; blood ; genetics ; metabolism ; Adult ; Aged ; DNA Methylation ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Proteins ; blood ; genetics ; metabolism ; Polymerase Chain Reaction ; Uterine Cervical Neoplasms ; blood ; genetics ; metabolism
8.Candida infection in patients with acute necrotizing pancreatitis.
Xing-wu YANG ; Zhen-ming GAO ; Jian MIAO ; Hong-bo TANG ; Chun-ming YANG
Chinese Journal of Surgery 2003;41(10):726-728
OBJECTIVETo summarize our hospital's experience in the diagnosis and treatment of Candida infection in patients with acute necrotizing pancreatitis (ANP).
METHODSSeventy-eight cases with ANP were reviewed. There were diagnoses either by operative finding or by CT scanning. Sixty-two cases received prophylactic antibiotic treatment, other sixteen did not. For cultivation of Candida, blood, urine, stool, sputum and wound drainage fluid culture, and swabs were examined microbiologically for fungi.
RESULTSThe incidence of Candida infection in all patients with ANP was 17.9% (14/78) and mortality was 28.6% (4/14). The incidence of prophylactic antibiotic group was 19.4% (12/62) and mortality was 25.0% (3/12). Non prophylactic group was 12.5% (2/16) and 50.0%.
CONCLUSIONSOur data provide evidence for the clinical significance of Candida infection in patients with ANP. The current prophylactic antibiotic treatment can prevent a septic course of the ANP, but might lead to the evolution of Candida infection.
Adult ; Aged ; Aged, 80 and over ; Candidiasis ; drug therapy ; etiology ; Female ; Humans ; Male ; Middle Aged ; Pancreatitis, Acute Necrotizing ; complications ; drug therapy
9.Clinical features and prognosis analysis of different breast cancer molecular subtypes.
Qian YANG ; Jie CHEN ; Hong-Jiang LI ; Miao YU ; Chun-Xiang TIAN ; Qing LÜ
Chinese Journal of Oncology 2011;33(1):42-46
OBJECTIVETo investigate the clinical characteristics and prognosis of different breast cancer molecular subtypes.
METHODSClinicopathological and follow-up data of 1153 cases of operable breast cancer were analyzed retrospectively. Their molecular subtypes were categorized as luminal A, luminal B, Her-2 over-expressing and basal-like subtypes, based on detection of ER, PR, Her-2 expression. The correlation of prognosis of different molecular subtypes with age, tumor size, lymph node status and clinical staging was analyzed.
RESULTSAmong the 1153 cases, 791 cases (68.6%) were of luminal A subtype, 50 cases (4.3%) luminal B subtype, 53 cases (4.6%) Her-2(+)subtype, and 259 cases (22.5%) basal-like subtype. There were no statistically significant differences among different molecular subtypes regarding the age, tumor size, lymph node status, and clinical stage. 1006 cases had complete follow-up data and the analysis showed that distant metastasis of Her-2 over-expressing subtype was significantly higher than that in other subtypes (P = 0.005), but the differences of local recurrence rate in different molecular subtypes was not statistically significant (P > 0.05). Kaplan-Meier method was used to analyze the survival prognosis of different molecular subtypes, showing both DFS rate and OS rate of Her-2 over-expressing subtype were the lowest, with a statistically significant difference (Log rank test, P < 0.05). Univariate and multivariate analyses showed that molecular typing and lymph node status were independent prognostic factors affecting both DFS and OS.
CONCLUSIONSHer-2 over-expressing subtype has the worst prognosis. Molecular subtypes may provide important information to predict the prognosis of breast cancer and might be an important basis for individualized treatment of breast cancer in future.
Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; classification ; metabolism ; pathology ; therapy ; Carcinoma, Ductal, Breast ; classification ; metabolism ; pathology ; therapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Mastectomy ; methods ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Survival Rate ; Young Adult
10.Effect of intrathecal pumping tramadol on the immune function in rats with formalin pain.
Wang-yuan ZOU ; Qu-lian GUO ; Jin CAI ; E WANG ; Hong-wei YANG ; Dao-miao XU ; Yi-chun WANG
Journal of Central South University(Medical Sciences) 2008;33(5):404-409
OBJECTIVE:
To evaluate the effect of intrathecal pumping tramadol on cell-mediated immunity in rats with formalin inflammatory pain.
METHODS:
Thirty-two Sprague-Dawley adult male rats weighting 250 approximately 300 g were randomly divided into 4 groups (n=8 in each group):Saline group (NS) and 3 tramadol groups (T1,T2,and T3). The rats were anesthetized with intraperitoneal chloral hydrate (300 approximately 350)mg/kg. Microspinal catheter was inserted into the subarachnoid space at the lumber region according to modified Yaksh techniques. In the tramadol groups,after 5 days tramadol was continuously infused through the spinal catheter at 50 (T1),25 (T2), and 12.5 microg/h (T3) for 7 days. In the NS group normal saline was continuously infused instead of tramadol. On Day 7 formalin (5%, 50 microL) was injected into the plantar surface of the left hindpaw. The number of flinches, lickings and total time of licking was recorded for 60 min.Pain intensity scoring(PIS)(0 approximately 3;0= no pain, 3=severe pain) was used to assess the antinociceptive effect of intrathecal tramadol. The rats were killed after the evaluation of pain intensity. Body weight and spleen weight were measured and spleen index (spleen weight/body weight) was calculated. T-lymphocyte function was evaluated based on Concanavalin-A(ConA) induced splenocyte proliferation. A modified lactic acid dehydrogenase(LDH) release assay was done to assess the NK cell activity. Phenotypic expressions of cell surface markers of T lymphocyte subsets (CD3+, CD3+ CD4+, CD3+ CD8+, and CD4+/ CD8+) and NK cell(CD161+) in the spleen were analyzed by flow cytometry.
RESULTS:
The PIS scores were significantly lower in the T1,T2,and T3 groups than those in the NS group. The spleen index and splenocyte proliferation induced by ConA were significantly suppressed in the T1 group,and the phenotypes of T lymphocyte subsets were significantly changed,but no significant difference was found in the T2 and T3 groups compared with the NS group. There were no differences in NK cell activity in the 3 tramadol groups from the control group.
CONCLUSION
Intrathecal pumping tramadol has significantly antinociceptive effect. Intrathecal pumping higher dosage tramadol (50microg/h) suppresses T lymphocyte proliferation and alteres T lymphocyte subset phenotype but does not affect NK cell activity. General analgesic dosage tramadol (25 and 12.5 microg/h) has no effect on the immune function.
Analgesics, Opioid
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pharmacology
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Animals
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Dose-Response Relationship, Drug
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Formaldehyde
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Injections, Spinal
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Killer Cells, Natural
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immunology
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Male
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Pain
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chemically induced
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immunology
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Pain Measurement
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drug effects
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Rats
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Rats, Sprague-Dawley
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T-Lymphocyte Subsets
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immunology
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Tramadol
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administration & dosage
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pharmacology