1.Progress in anti-cancer research of American ginseng: with an example of colorectal cancer.
Chun-Hao YU ; Chong-Zhi WANG ; Chun-Su YUAN
Acta Pharmaceutica Sinica 2013;48(7):986-992
Cancer is a group of various diseases, all of which involve unregulated cell growth. Many currently used chemotherapeutic drugs are derived from botanicals. Thus, searching botanical sources for novel oncology medications, including identifying the lead compounds and their derivatives for chemoprevention, is an essential step in advancing cancer therapeutics. This article mainly focuses on the data from our previous American ginseng anti-colon cancer studies. In addition to the potential role of American ginseng on cancer, the herb as an adjuvant for cancer treatment is presented, including describing the attenuation of adverse events induced by chemotherapeutic agents and increasing of quality of cancer patient life. Since heat-treated American ginseng and ginsenoside gut microbiome metabolites showed significant increases in cancer chemopreventive effects, active constituents of the steamed herb and their gut metabolites should be clearly identified, and the structure-activity relationship should be further explored. Data obtained from herbal medicine studies and clinical trials will help develop useful anticancer agents.
Animals
;
Antineoplastic Agents, Phytogenic
;
isolation & purification
;
pharmacology
;
Apoptosis
;
drug effects
;
Cell Proliferation
;
drug effects
;
Colorectal Neoplasms
;
drug therapy
;
pathology
;
Ginsenosides
;
isolation & purification
;
metabolism
;
pharmacology
;
therapeutic use
;
Hot Temperature
;
Humans
;
Panax
;
chemistry
;
Phytotherapy
;
Plant Roots
;
chemistry
;
Plants, Medicinal
;
chemistry
;
Structure-Activity Relationship
2.Effects of Ginkgo biloba extract on biomarker expressions during aflatoxin B_1-induced hepatocarcinogenesis in Wistar rats
Yanrong HAO ; Chao OU ; Ji CAO ; Fang YANG ; Xiaoxian DUAN ; Chun YANG ; Yuan LI ; Jianjia SU
Tumor 2010;(1):1-5
Objective:To study the effect of Ginkgo biloba extract (EGb761) on metabolism of aflatoxin B_1(AFB_1) in Wistar rats. Methods:Seventy one Wistar rats were divided into three groups at random: group A (AFB_1 group), group B (AFB_1+EGb761 group), and group C (control group). The rats in groups A and B were given AFB_1(intraperitoneal injection, 100-200 μg/ kg body weight, 1-3 times/week). The rats in group B were fed the food containing EGb761 while the rats in groups A and C were given normal food. Blood samples were collected and liver biopsy was performed on the 14th, 28th and 42nd week. All the rats were sacrificed at the 64th week. The incidence of hepatoma was observed. The hepatic phase Ⅰ drug-metabolizing enzyme CYP450 and phase Ⅱ enzyme GST were detected by spectrometry. The serum AFB_1-lysine adduct was determined by high performance liquid chromatography (HPLC). The expression of 8-hydroxydeoxyguanosine(8-OHdG) was measured by immunohistochemistry. Results:The incidence of hepatocellular carcinoma (HCC) in group B was significantly lower than that in group A (26.92% vs 76.00%,P<0.001). No hepatocellular carcinoma developed in group C. EGb761 had no effects on the activities of CYP450 and GST in rat liver tissues. The level of AFB_1-lysine adduct reached the peak (4 356.01 pg/mg albumin) at the 14th week in group A. EGb761 significantly inhibited the formation of AFB_1-lysine adducts in serum by 13.07% at the 14th week (P=0.033), and 73.63% at the 42nd week (P=0.002). The expression of 8-OHdG protein in rat liver tissues in group B was significantly lower than that in group A at the 28th, 42nd, and 64th week (P<0.05). Conclusion:The main mechanism underlying the effect of EGb761 in blocking hepatogenesis induced by AFB_1 may not be fully related with its influence on the activity of liver phase Ⅰ and phase Ⅱ metabolizing enzymes. EGb761 inhibites the production of AFB_1-lysine addcuts, decreases the expression of 8-OHdG protein, and finally alleviates the DNA oxidative injury, which may be one of the mechanisms for the effects of EGb761 in inhibiting or delaying hepatogenesis induced by AFB_1.
3.Effects of RNA interference targeting CDC25a gene on proliferation of human liver cancer HepG2 cells
Wei LI ; Ji CAO ; Lingli ZHOU ; Wang LUO ; Chun YANG ; Chengpiao LUO ; Yuan LI ; Jianjia SU
Chinese Journal of Pathophysiology 2014;(12):2142-2147
[ ABSTRACT] AIM:To investigate the effect of silencing cell division cycle 25a ( CDC25a) gene on the prolifera-tion of human hepatoma HepG2 cells.METHODS:CDC25a gene in human hepatoma HepG2 cells was silenced by RNA interference.Real-time PCR was applied to detect the expression of CDC25a, cyclin E and CDK2 at mRNA levels in the HepG2 cells.Western blotting was applied to detect the expression of CDC25a at protein level.In addition, MTT assay, Giemsa staining and flow cytometry were used to measure the proliferation of human hepatoma HepG2 cells.RESULTS:The expression of CDC25a at mRNA and protein levels in RNA silence group was lower than those in negative control group and normal control group (P<0.05).The mRNA expression of cyclin E and CDK2 in silence group was lower than that in negative control group and normal control group (P<0.05).The cell proliferation in silence group was lower than that in negative control group and normal control group ( P<0.05) .The results of flow cytometry revealed that the cells in silence group were blocked in G1 phase.CONCLUSION:Infection of LV-CDC25a-RNAi recombinant to the HepG2 cells effec-tively inhibits the CDC25a gene expression and the proliferation of human hepatoma cells, and arrests the cells in G1 phase, suggesting that CDC25a gene may be a key target for the treatment of liver cancer.
4.Detection and significance of the main nutritional ingredients of tree shrew’ s milk
Chun YANG ; Chao OU ; Yuan LI ; Jianjia SU ; Chengpiao LUO ; Xiaoxu LU ; Lingqun ZHU ; Ji CAO
Chinese Journal of Comparative Medicine 2014;(9):44-47
Objective To explore the basic ingredients of the tree shrew’ s( Tupaia belangeri) milk and compare with the dairy ingredients of other milks.Methods We select ten seed tree shrews after delivery ( 1 ~21 ) d with lactation mother tree shrews, and use artificial passive breastfeeding method let the young tree shrews suck breast milk,we took the milk from the young tree shrews in the stomach, directly using aseptic operation with a syringe immediately, once every two days, for consecutive three to five times, and a total of 18 mL milk was taken from each seed tree shrew.Then the milk was detected according to the national standard method for component testing.Results The total solid content of the tree shrew’ s milk was 43.63%, including 26.01%of fat, 10.41%of protein, 0.45% of lactose and 0.99%of ash content.Compared with cow's milk, the tree shrew’ s milk contained 3.36 times of total solid contents, 1.24 times of ash, 2.74 times of protein, 6.67 times of fat, and 0.09 times of lactose.Compare with baby formula milk, the tree shrew’ s milk contained 1.44 times of total solid contents, 0.20 times of ash, 0.58 times of protein, 1.53 times of fat, and 0.06 times of lactose.The trace mineral composition of the tree shrew’ s milk showed that the calcium, phosphorus, potassium, sodium, magnesium, and iron contents were 1.83 times, 2.73 times, 1.25 times, 1.93 times, 1.28 times, and 1.48 times higher than those in the cow's milk, and were 0.66 times, 0.85 times, 0.34 times, 0.26 times, 0.85 times, 0.24 times lower than those in baby formula milk.Conclusions The main nutrients of tree shrew’ s milk is of high fat, high protein and low sugar, and it can provide a basis for tree shrews artificial brood and breeding work.
5.The expression and significance of MCM7 protein in hepatocellu-lar carcinoma tissues of human, rat and tree shrew
Lingqun ZHU ; Chun YANG ; Hong QIN ; Xiaoxu LU ; Yuan LI ; Chao OU ; Jianjia SU ; Ji CAO
Chinese Journal of Clinical Oncology 2013;(16):951-955
Objective:To test the expression of Minichromosome maintenance complex component 7(MCM7) protein in hepato-cellular carcinoma(HCC) of different species including human, rat and tree shrew (tupaia) by cross-species oncogenomics approach, and to investigate the relationship between the expression of MCM7 and the development of hepatocellular carcinoma and its clinical significance. Methods:Western blot and Immunohistochemistry were applied to detect the expression levels of MCM7 protein in HCC tissues,corresponding HCC-adjacent liver tissues and normal liver tissues collected from different species including human, rat and tree shrew, respectively. The clinicopathologic factors were also analyzed with the results of Immunohistochemistry. Results:Western blot analysis showed that the expression of MCM7 protein in HCC tissues of human and rat were higher than that in corresponding HCC-ad-jacent liver tissues and normal liver tissues, respectively and significantly (P<0.05). However, the expression of MCM7 protein in HCC tissues of tree shrew were also higher than that in corresponding HCC-adjacent liver tissues and normal liver tissues, but no significant difference was found among three types of tissues (P>0.05).There was also no significant difference between HCC-adjacent liver tis-sues and normal liver tissues in three species (P>0.05). Immunohistochemical analysis showed that MCM7 protein was mainly ex-pressed in nucleus of HCC cells, and the positive rate of MCM7 protein in HCC tissues of human, rat and tree shrew were significantly higher than that in corresponding HCC-adjacent liver tissues and normal liver tissues, respectively (P<0.05). However, no significant difference was found between HCC-adjacent liver tissues and normal liver tissues (P>0.05). Moreover, the protein level of MCM7 was intimately related to patient's HCC stage, extrahepatic metastases and postoperative recurrence (P<0.05). Conclusion:MCM7 protein might play a pivotal role in hepatocarcinogenesis. In addition, it was probably related to patient's HCC stage, extrahepatic metastases and postoperative recurrence. It seems very likely that MCM7 may be applied as a new molecular target in HCC prevention and treat-ment.
6.Study on the infection of primary tupaia hepatocytes with hepatitis B virus in vitro
Jingjing ZHANG ; Guang YANG ; Chun YANG ; Yanrong HAO ; Ji CAO ; Chao OU ; Yuan LI ; Kechen BAN ; E.blum HUBERT ; Jianjia SU
Chinese Journal of Microbiology and Immunology 2008;28(11):984-988
Objective To provide a better cell model of closely nature infectious state for further research of hepatitis B virus(HBV). Methods Primary tupaia hepatocytes were isolated by the two-step perfusion method. The hepatocytes were then infected with purified serum from patients with hepatitis B. DNA and RNA isolated from the hepatocytes were detected with Southern blot and Northern blot. HBsAg in supernatant was tested by immunohistochemical method. Results cccDNA, pgRNA and sgRNA could be detected by Southern blot and Northem blot, and strong signals could be seen from day 7 to day 14 post-in-fection. The S/CO value of HBsAg in supernatant decreased from day 1 to day 5 and then increased after 5 day. Conclusion Primary tupaia hepatocytes are competent for infection with HBV. HBV can stably repli-cate and express in HBV-infected tupaia hepatocytes.
7.Analysis of the Relationship Between Era and YggG in E.coli by Double-promoter Expression Vector pDH2-YggG-P_(tac)-Era
Yong HUANG ; Xiao-Nan ZHANG ; Bin ZHANG ; Tao WANG ; Li WANG ; Lu-Yuan GUAN ; Nan-Chun CHEN ; Su-Min CHEN ;
China Biotechnology 2006;0(03):-
yggG, a Era-binding protein gene, was isolated and cloned from the E.coli genomic DNA library. Previous studies indicated that the product of yggG gene, YggG294(amino acids 1-294), strongly inhibited the growth of host bacteria and caused the death of bacteria cells. To elucidate whether Era is related to the death of bacterial cells expressed YggG294,A double promoter expression vector that can express YggG294 and Era proteins controllably in cells was constructed. Using this vector to express YggG294 and Era protein in the same E.coli cells, then analyzed the relation between YggG294 and Era. The results showed that the ratio of Era proteins to total proteins increased with the increase of induction time in E.coli cells without YggG294 expression and with little YggG294 expression;the ratio of Era proteins to total proteins seemed to be a constant level in E.coli cells overexpressing YggG294;but we could not detect any Era hydrolyzate in E.coli cells overexpressed YggG294 could not be detected. The results also showed that pre-expression of Era protein did not produce any effect on the growth inhibition of E.coli cells caused by YggG294. These results indicate that YggG294 can not hydrolyze Era protein in E.coli cells, and that YggG-Era interaction is not associated with the death of bacteria expressed YggG294. It is thus reasonable to draw a conclusion that Era is not associated with the growth inhibition of E.coli cells caused by YggG294. YggG294 inhibits the growth of bacteria by other way.
8.Chest CT features and outcome of necrotizing pneumonia caused by Mycoplasma pneumoniae in children (report of 30 cases).
Su-rong LI ; Jing-hui MU ; Li CHANG ; Yu-chun YAN ; Xin-yu YUAN ; Hui-zhong CHEN
Chinese Journal of Pediatrics 2013;51(3):211-215
OBJECTIVETo summarize the chest CT features and outcome of necrotizing pneumonia (NP) caused by Mycoplasma pneumoniae in children and to review the changes of common inflammatory parameters in NP patients to help clinicians understand the proper timing of CT scan.
METHODThe imaging data from 30 cases of Mycoplasma pneumoniae pneumonia in NP group and 24 cases with non-necrotizing Mycoplasma penumoniae pneumonia (control group) were analyzed retrospectively. The changes of common inflammatory parameters in NP group and control group were compared.
RESULT(1) The chest CT findings of NP (30 cases): 28 cases showed unilateral pneumonia, and 20 cases showed single lobar consolidation, 10 cases had multiple lobes involvement; pulmonary cavities were seen in 27 cases. There were decreased enhancement areas in the consolidation (22 cases). (2) The dynamic changes of CT signs during follow-up: The CT scan performed during the 1 - 2 months after onset of disease (23 cases) showed that pulmonary consolidation in 2 cases (9%) were absorbed, 18 cases (78%)had cavities in lung, 16 cases (70%) had pleural thickening, 2 cases (9%) atelectasis and 1 case (4%) bronchopleural fistula;the CT scan performed during the 2 - 3 months after onset of disease (11 cases) showed pulmonary consolidation in 7 cases (64%) were absorbed, 10 cases (91%) pleural thickness, 7 cases (64%) with cavities in lung, 5 cases (45%) atelectasis, 2 cases (18%) pulmonary lobe cysts and 1 case bronchopleural fistula. The CT scan performed at 3.5 years of disease course (10 cases) showed that there were no pulmonary consolidation in any of the cases, 4 cases had atelectasis, 4 cases had pulmonary cysts, and 1 case had band-like scars. (3) There were significant differences between NP group and control group in the maximum peripheral blood WBC, proportion of neutrophil and C-reactive protein(CRP, mg/L) (P < 0.01, 0.01, 0.001, respectively), and there was significant difference between the 2 groups in the duration of fever, abnormal WBC(d) and CRP(d) (P < 0.001).
CONCLUSIONThe chest CT features of NP caused by Mycoplasma pneumoniae in children were single lobular consolidation in most cases, NP had decreased parenchymal enhancement and cavity in the consolidation, and recovery was slow, the outcome included recovery, atelectasis or lobar cystic degeneration. The clinicians should pay more attention to the common inflammatory parameters when they suspect the Mycoplasma pneumoniae pneumonia is progressing into necrosis and make correct decision for chest CT examination.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Leukocyte Count ; Lung ; diagnostic imaging ; pathology ; Male ; Mycoplasma pneumoniae ; Necrosis ; pathology ; Pleural Effusion ; diagnostic imaging ; pathology ; Pneumonia, Mycoplasma ; diagnostic imaging ; pathology ; Pulmonary Atelectasis ; diagnostic imaging ; pathology ; Radiography, Thoracic ; Retrospective Studies ; Sensitivity and Specificity ; Severity of Illness Index ; Tomography, X-Ray Computed
9.Hyperglycemia at admission and outcome in elderly patients with acute ST segment elevation myocardial infarction underwent primary percutaneous coronary intervention.
Hong-jie CHI ; Da-peng ZHANG ; Xin-chun YANG ; Zhong-su YANG ; Yuan XU
Chinese Journal of Cardiology 2009;37(7):595-598
OBJECTIVETo investigate the association between hyperglycemia and outcome in elderly patients with acute ST segment elevation myocardial infarction (STEMI) underwent primary percutaneous coronary intervention (PCI).
METHODSThis retrospective analysis was performed on 284 elderly patients (age > or = 60 years) with acute STEMI underwent primary PCI between January 2000 to April 2004 in our department. Patients were divided into 3 groups according to the level of blood glucose on admission: group A, < 7.8 mmol/L; group B, 7.8 - 10.9 mmol/L; group C, > or = 11.0 mmol/L.
RESULTS(1) The proportion of female in group B and group C was greater than that of group A (33.3% vs. 26.5%, P < 0.01; 40.2% vs. 26.5%, P < 0.01). The hospital stay time of group B and group C was significantly longer than that of group A (16.0 days vs. 13.9 days, P < 0.05; 16.6 days vs. 13.9 days, P < 0.05). There were more patients with history of hypertension in group C than that in group A (72.1% vs. 54.9%, P < 0.01). (2) After PCI, the proportion of patients with TIMI myocardial perfusion grade (TMPG) 0-1 in group B and C was greater than that of group A (22.6% vs. 13.3%, P < 0.05; 34.1% vs. 13.3%, P < 0.05). The proportion of patients with TMPG 3 in group B and C was less than that in group A (74.3% vs. 84.4%, P < 0.05; 57.6% vs. 84.4%, P < 0.05). The complication rate of PCI was significantly higher in group C than in group A (42.5% vs. 20.6%, P < 0.01) and group B (42.5% vs. 26.6%, P < 0.01). IABP use was significantly more in group C than that in group A (19.5% vs. 4.9%, P < 0.01) and group B (19.5% vs. 6.4%, P < 0.01). (3) There were more patients with grade of Killip class > or = 2 in group C than that in group A (44.8% vs. 23.5%, P < 0.01) and group B (44.8% vs. 27.7%, P < 0.01). The in-hospital mortality rate (8.0% vs. 1.1%, P < 0.05) and one-year mortality rate (18.7% vs. 3.4%, P < 0.05) of group C were significantly higher than those in group A.
CONCLUSIONHyperglycemia at admission was associated with poor tissue perfusion, cardiac function and prognosis in elderly patients with acute STEMI underwent primary PCI.
Aged ; Angioplasty, Balloon, Coronary ; Blood Glucose ; analysis ; Female ; Humans ; Hyperglycemia ; Male ; Middle Aged ; Myocardial Infarction ; blood ; physiopathology ; therapy ; Prognosis ; Retrospective Studies ; Treatment Outcome
10.Expression of epidermal fatty acid-binding protein in cross-species hepatocellular carcinoma.
Jun-lin SHI ; Ji CAO ; Jian-jia SU ; Chun YANG ; Chao OU ; Duo-ping WANG ; Yuan LI
Chinese Journal of Hepatology 2012;20(4):270-274
OBJECTIVETo evaluate the utility of the cross-species screening strategy for investigating key molecule(s) involved in onset and progression of hepatocellular carcinoma (HCC).
METHODSHCC-related molecule data from our previous studies and in the literature were collected to establish a cross-species dataset. Tissue samples of HCC, non-HCC surrounding liver (para-HCC), and normal liver that were collected from humans, tree shrews and rats. The genes reported to have the most differential expression in HCC were verified by analyzing the mRNA and protein levels by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively.
RESULTSThe cross-species dataset of HCC-related molecules included four genes: epidermal fatty acid-binding protein (E-FABP), liver (L)-FABP, tyrosine a-ketoglutarate transaminase (TKT), and cytokeratin (CK8). In humans, E-FABP mRNA expression was significantly higher (P less than 0.05) in HCC (0.87+/-0.14 vs. para-HCC: 0.64+/-0.12 and normal liver: 0.67+/-0.07; F=20.910). Similar results were obtained in tree shrew (HCC: 0.87 +/- 0.25 vs. para-HCC: 0.73 +/- 0.19 and normal liver: 0.68+/-0.19; F=3.807) and rat (HCC: 0.97+/-0.22 vs. para-HCC: 0.78+/-0.16 and normal liver: 0.80 +/- 0.13; F=4.482). The Western blotting analyses revealed a similar statistically significant trend.
CONCLUSIONThe cross-species screening strategy for tumor genes may represent a feasible and convenient process of identifying key molecule(s) for human HCC. E-FABP may be a particularly crucial molecule for hepatocarcinogenesis.
Adult ; Aged ; Animals ; Carcinoma, Hepatocellular ; metabolism ; Case-Control Studies ; Epidermis ; chemistry ; Fatty Acid-Binding Proteins ; metabolism ; Female ; Humans ; Liver ; metabolism ; Liver Neoplasms ; metabolism ; Male ; Middle Aged ; Rats ; Tupaiidae ; metabolism