1.The mechanisms of apoptosis induced by curcumin in gastric cancer cells
Xiao-Ping TAN ; San-Ping XU ; Chang-Hua HE ; Yan-Ni ZHU ; Hong-An WU ; Bo HU
Cancer Research and Clinic 2001;0(04):-
Objective To study the mechanisms of Curcumin-induced apoptosis on human gastric cancer cell line SGC-7901.Methods SC,C-7901 cells were treated with various concentrations of Curcumin and the growth inhibition rates of it were accessed by MTT method.Apoptosis of gastric cancer cells were in- spected by flow cytometry.The expression of Fas and survivin in gastric cancer cells were evaluated by west- ern blot.Results Curcumin could effectively inhibit the growth of gastric cancer cells in dose-dependent and time-dependent manners,the sub-peak appeared and the apoptotic rate was increased.The expressions of Fas was higher in Western blot,meanwhile,the expressions of survivin was decreased.Conclusion Curcumin could significantly inhibit the growth and induce apoptosis of gastric cancer cells(SGC-7901),Curcumin could probably through up-regulating Fas and down-regulating surviving to induce apoptosis.
2.Clinical observation of gefitinib in treatment of female patients with adenocarcinoma of lung WU
Xiao-Ping WU ; Ying-Zhi ZHUANG ; Hao JIANG ; You-Hua WU ; Wen-Xiang DAI ; Xiao-Hong AI ; San-Yuan TANG ;
Cancer Research and Clinic 2006;0(12):-
Objective To evaluate the efficacy and adverse effects of gefitinib in the treatment of fe- male patients with advanced adenocarcinoma of lung who had failed to previous chemotherapy.Methods These patients received 250mg of gefitinib orally,once daily until disease progression or development of intol- erable toxic reaction.They were evaluated one month after treatment and every other month thereafter.Results Among the 27 evaluable patients,there were 1 CR(3.7%),11 PR(40.8%),10 SD(37.0%)and 5 PD(18.5%). The overall response rate was 44.5%(95% CI 29%~68%);and 22 patients(81.5%)gained profit(CR+PR+ SD)from the clinical therapy(95% CI 62%~94%);the mean TTP was 7.2 months.Symptomatic improvement rate was 80.0%.The main adverse effects were mild rash and diarrhea.Conclusion gefitinib has significant efficacy in the treatment of female patients with advanced tung cancer who had failed to previous chemother- apy.Adverse effects are mild.gefitinib is a suitable therapy for these patients.
3.Cysteinyl leukotriene receptor 1 antagonist pranlukast modulates differentiation of SK-N-SH cells.
Fang PENG ; San-Hua FANG ; Xiao-Liang ZHENG ; Wei-Ping ZHANG ; Yun-Bi LU ; Er-Qing WEI
Journal of Zhejiang University. Medical sciences 2007;36(2):123-128
OBJECTIVETo determine whether cysteinyl leukotriene receptor agonist LTD(4) and cysteinyl leukotriene receptor 1 (CysLT(1)) antagonist pranlukast affect the differentiation of human neuroblastoma SK-N-SH cells.
METHODSSK-N-SH cell morphological changes induced by LTD(4), pranlukast and LTD(4) + pranlukast were observed with retinoid acid (RA) as the positive control. The expressions of CysLT(1) and CysLT(2) receptors were detected by immunoblotting analysis, and the expression of microtubule-associated protein-2 (MAP-2), a neuron marker, was detected by fluorescent immunostaining.
RESULTThe immunoblotting results showed that SK-N-SH cells expressed CysLT(1) receptor moderately, and CysLT(2) receptor highly. The morphological results showed that RA, pranlukast and LTD(4) + pranlukast induced the compaction of the cell bodies and the outgrowth of neurites, while LTD(4) had no significant effect. The immunostaining results showed that MAP-2 was distributed in the cell bodies in control or pranlukast-treated cells; it was distributed in cell bodies and neuritis in RA-treated cells. Pranlukast increased the numbers of MAP-2-positive cells.
CONCLUSIONThe CysLT(1)receptor antagonist pranlukast modulates the differentiation of SK-N-SH cells.
Cell Differentiation ; drug effects ; Cell Line, Tumor ; Chromones ; pharmacology ; Humans ; Immunoblotting ; Immunohistochemistry ; Leukotriene Antagonists ; pharmacology ; Leukotriene D4 ; pharmacology ; Membrane Proteins ; metabolism ; Microtubule-Associated Proteins ; metabolism ; Neuroblastoma ; metabolism ; pathology ; Receptors, Leukotriene ; metabolism
4.Effects of Cigu Xiaozhi Pills on Lipotoxicity and Oxidative Stress in Rats with Non-alcoholic Steatohepatitis
hua Yan MA ; jun Shao YANG ; Xia SHI ; qing Xiao QIU ; peng San XU
Chinese Journal of Information on Traditional Chinese Medicine 2018;25(1):48-53
Objective To explore the effects of Cigu Xiaozhi Pills on lipotoxicity and oxidative stress in rats with non-alcoholic steatohepatitis (NASH); To discuss relevant mechanism of action. Methods SD rats were divided into six groups randomly:normal control group,model group,positive medicine group,Cigu Xiaozhi Pills high-,medium-, and low-dose groups. NASH model was established by feeding rats with high fat diet for 12 weeks. At the same time, the model rats were given medicine intervention. At the end of 12 weeks, all the experimental animals were killed and the liver and serum were taken. Serum samples were taken for detection of ALT, AST, TG, TC, T-SOD, LDL-C, MDA, GSH-Px and FFA. Liver tissues were taken for detection of T-SOD, MDA, GSH-Px and FFA. The liver histopathological changes were observed under microscope with HE staining. The ultrastructure of liver cells was observed by transmission electron microscope. The fatty degeneration of liver cells was observed by oil red O staining. Results Liver histopathological examination showed that the liver tissue of model group showed moderate to severe steatosis and inflammatory cell infiltration. Compared with normal control group, rat liver wet weight, liver index, ALT, AST, TG, TC, LDL-C, MDA and FFA in serum, and FFA and MDA in liver homogenate in model group significantly increased (P<0.05, P<0.01), while T-SOD and GSH-Px activity in serum and liver homogenate significantly decreased (P<0.05, P<0.01). Compared with model group, Cigu Xiaozhi Pills high-dose group could significantly decrease the elevation of serum ALT, AST, TG, TC, LDL-C, MDA and FFA (P<0.05, P<0.01), but increase T-SOD and GSH-Px activity in serum and liver tissue (P<0.01). The pathological section showed that:compared with model group, the hepatic lobule vacuolar degeneration and fatty degeneration were significantly reduced in Cigu Xiaozhi Pills high-, medium- and low-dose groups, and the inflammatory cell infiltration was improved. Conclusion Cigu Xiaozhi Pills can obviously improve liver function and blood lipid of NASH rat model induced by high-fat diet, enhance antioxidant capacity, reduce lipid peroxidation and achieve the purpose of prevention and treatment of NASH.
5.Expression of IFN-γ,IL-4 and IL-17A in asthmatic mice vaccinated with BCG and HepB in neonatal period
Xue-Yan SHEN ; San-Mei CHEN ; Xiao-Ping CHEN ; Hai-Yan XING ; Wei-Ying ZHAO ; Zhi-Hua CHEN
Chinese Journal of Pathophysiology 2018;34(3):515-520
AIM:To investigate the expression of IFN-γ,IL-4 and IL-17A in asthmatic mice vaccinated with bacillus Calmette-Guérin(BCG)and hepatitis B(HepB)in the neonatal period.METHODS: BALB/c mice were ran-domly divided into BGG+HepB+ovalbumin(OVA)group(B/H/O group),B/O group,H/O group,B/H group,OVA group,BCG group,HepB group and normal saline(NS)group(n=6).The mice in B/H/O group and B/H group at 0, 7 and 14 d received subcutaneous injection of 1×105CFU BCG for 3 times,while at 0 and 28 d received intramuscular in-jection of 1.5 μg HepB on the hindlimb twice.The mice in other groups were individually vaccinated with BCG or HepB. OVA sensitization and aerosol inhalation were performed to establish the asthma model.The lung tissues were collected for HE staining.Bronchoalveolar lavage fluid(BALF)and peripheral blood(PB)were collected,and the number of eosino-phils(EOS)in BALF was counted.The serum levels of IFN-γand IL-4,and the level of IL-17A in lung tissue homoge-nate were measured by ELISA.RESULTS: The pathological changes of the lung in OVA group, B/O group, B/H/O group and H/O group were observed.There were extensive inflammatory cell infiltration around the bronchus,and epithe-lial cell hypertrophy.Those in B/H/O group and H/O group were worse than those in OVA group, while those in B/O group was better than those in OVA group.Total BALF cell counts in B/H/O group,B/O group and H/O group were de-creased(P<0.05)as compared with OVA group.The BALF EOS count in B/H/O group was higher than that in B/H group,that in B/O group was higher than that in BCG group,and that in H/O group was higher than that in HepB groups (P<0.05).Compared with H/O group, OVA group and NS group, the serum IFN-γ/IL-4 ratio in HepB group was in-creased(P<0.05),and compared with B/H/O group,B/O group,OVA group and NS group,that in B/H group was al-so increased(P<0.05).Compared with OVA group, the level of IL-17A in the lung tissues of B/H/O group and B/O group was decreased(P <0.05), and compared with B/O group, that in B/H/O group was further decreased(P <0.05).CONCLUSION:Combined vaccination of BCG and HepB reduces the inflammotory responses in the lung tissues of asthmatic mice.The mechanism may be related with the decrease in the release of IL-4, the increase in IFN-γ/IL-4, and the inhibition of IL-17A expression.
6.Comparison of the effect between insulin lispro 75/25 and humulin 70/30 on the postprandial blood glucose excursion in patients with diabetes
Yu-Fang BI ; Song-Hua WU ; Xiao-Hui GUO ; Guang NING ; Kun-San XIANG ; Yan GAO ; Yi-Fei ZHANG ; Ming LI ; Jun-qing ZHANG ; Xin-yin SUN ; Xiao-jing ZHOU ; Phillipa Clarke ; Caroline Markey ; Yi-man ZHENG ; Jia-lun CHEN ;
Chinese Journal of Endocrinology and Metabolism 1985;0(02):-
The effects of human insulin 70/30 and insulin lispro 75/25 were compared in improving postprandial blood glucose excursions in 106 patients with type 1 or 2 diabetes in a one-month,open-labelled,self- controlled trial .The results showed that treatment of diabetic patients with insulin lispro 75/25 significantly improved 2 h postprandial blood glucose excursion compared to pre-study with human insulin 70/30 (baseline) without any significant adverse events or sustained hypoglycemic episodes.These physiological benefits were associated with a patient preference for insulin lispro 75/25.
7.Advanced glycation end products promote differentiation of CD4(+) T helper cells toward pro-inflammatory response.
Xiao-qun HAN ; Zuo-jiong GONG ; San-qing XU ; Xun LI ; Li-kun WANG ; Shi-min WU ; Jian-hong WU ; Hua-fen YANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2014;34(1):10-17
This study investigated the effect of advanced glycation end products (AGEs) on differentiation of naïve CD4(+) T cells and the role of the receptor of AGEs (RAGE) and peroxisome proliferator-activated receptors (PPARs) activity in the process in order to gain insight into the mechanism of immunological disorders in diabetes. AGEs were prepared by the reaction of bovine serum albumin (BSA) with glucose. Human naïve CD4(+) T cells, enriched from blood of healthy adult volunteers with negative selection assay, were cultured in vitro and treated with various agents including AGEs, BSA, high glucose, PGJ2 and PD68235 for indicated time. In short hairpin (sh) RNA knock-down experiment, naïve CD4(+) T cells were transduced with media containing shRNA-lentivirus generated from lentiviral packaging cell line, Lent-X(TM) 293 T cells. Surface and intracellular cytokine stainings were used for examination of CD4(+) T cell phenotypes, and real-time PCR and Western blotting for detection of transcription factor mRNA and protein expression, respectively. The suppressive function of regulatory T (Treg) cells was determined by a [(3)H]-thymidine incorporation assay. The results showed that AGEs induced higher pro-inflammatory Th1/Th17 cells differentiated from naïve CD4(+) T cells than the controls, whereas did not affect anti-inflammatory Treg cells. However, AGEs eliminated suppressive function of Treg cells. In addition, AGEs increased RAGE mRNA expression in naïve CD4(+) T cells, and RAGE knock-down by shRNA eliminated the effect of AGEs on the differentiation of CD4(+) T cells and the reduction of suppressive function of Treg cells. Furthermore, AGEs inhibited the mRNA expression of PPARγ, not PPARα PPARγ agonist, PGJ2, inhibited the effect of AGEs on naïve CD4(+) T cell differentiation and reversed the AGE-reduced suppressive function of Treg cells; on the other hand, PPARγ antagonist, PD68235, attenuated the blocking effect of RAGE shRNA on the role of AGEs. It was concluded that AGEs may promote CD4(+) T cells development toward pro-inflammatory state, which is associated with increased RAGE mRNA expression and reduced PPARγ activity.
Adult
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Animals
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Blotting, Western
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CD4-Positive T-Lymphocytes
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drug effects
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metabolism
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Cattle
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Cell Differentiation
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drug effects
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Cells, Cultured
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Glucose
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pharmacology
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Glycation End Products, Advanced
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pharmacology
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HEK293 Cells
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Humans
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Interferon-gamma
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metabolism
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Interleukin-17
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metabolism
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PPAR gamma
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agonists
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genetics
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metabolism
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Prostaglandin D2
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analogs & derivatives
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pharmacology
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RNA Interference
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Receptor for Advanced Glycation End Products
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Receptors, Immunologic
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genetics
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metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Serum Albumin, Bovine
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pharmacology
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T-Lymphocytes, Regulatory
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drug effects
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metabolism
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Th1 Cells
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drug effects
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metabolism
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Th17 Cells
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drug effects
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metabolism
8.Comparison of endocrine therapy and chemotherapy for bone metastasis of breast cancer.
Min YAN ; San-Tai SONG ; Ze-Fei JIANG ; Shao-Hua ZHANG ; Xiao-Qing LIU ; Jian-Ming XU ; Tao WANG ; Wei-Dong LUO
Chinese Journal of Oncology 2004;26(3):177-180
OBJECTIVETo compare the efficacy of endocrine therapy with chemotherapy for bone metastasis of breast cancer.
METHODSA total of 138 breast cancer patients with bone metastasis, but without visceral metastasis as retrospectively reviewed.
RESULTSThe response rates of endocrine therapy and chemotherapy as the first-line therapy were 35.4% and 31.7% (P = 0.687), and the total response rates were 27.1% and 25.0% (P = 0.690). The clinical benefit rates of endocrine therapy and chemotherapy as first-line were 43.9% and 36.6% (P = 0.437), as second-line were 47.8% and 24.2% (P = 0.033), in total treatments were 47.5% and 27.7% (P = 0.001). The median interval to treatment failure (TTF) was 5 months and 2 months (P < 0.001), and that to progression (TTP) was 5 and 2.5 months (P < 0.001) in endocrine therapy and chemotherapy group, respectively.
CONCLUSIONEndocrine therapy is superior to chemotherapy for bone metastasis of breast cancer.
Antineoplastic Agents ; therapeutic use ; Bone Neoplasms ; secondary ; therapy ; Breast Neoplasms ; mortality ; therapy ; Female ; Humans ; Prognosis ; Retrospective Studies ; Survival Rate ; Treatment Failure
9.Effects of berberine on expression of hepatocyte nuclear factor 4alpha and glucokinase activity in mouse primary hepatocytes.
Zhong-Qing YAN ; San-Hua LENG ; Fu-Er LU ; Xiao-Hong LU ; Hui DONG ; Zhi-Qiang GAO
China Journal of Chinese Materia Medica 2008;33(18):2105-2109
OBJECTIVETo observe the expression of hepatocyte nuclear factor 4alpha (HNF4alpha) and the activity of key enzyme glucokinase (GK) in glucose metabolism, and further to investigate the possible mechanism of berberine in treating type 2 diabetes.
METHODMouse primary hepatocytes were isolated by an improved single two-step perfusion method. The murine hepatocytes were cultured and incubated with berberine (0, 1, 3, 10, 30, 100 micromol x L(-1)) and 1 mmol x L(-1) metformin for 24 h respectively. The mRNA expression of HNF4alpha were quantified by RT-PCR and the protein expression of HNF4alpha were quantified by Western-blot. And the activity of GK were detected with enzyme kinetics method.
RESULTAs compared with the negative control group, at a certain concentration range, the expression of HNF4alpha mRNA and protein and the activity of GK were promoted by berberine. Both of them reached the top at the concentration of 30 micromol x L(-1) (P<0.01). But the metformin made no difference with the negative control group on the expression of HNF4alpha and the activity of GK.
CONCLUSIONIt is suggested that the effects of berberine on improving glucose metabolism can be mechanically associated with its up-regulating the HNF4a expression and inducing the activity of hepatic glucokinase.
Animals ; Berberine ; pharmacology ; Cell Survival ; drug effects ; Cells, Cultured ; Gene Expression Regulation ; drug effects ; Glucokinase ; genetics ; metabolism ; Hepatocyte Nuclear Factor 4 ; genetics ; metabolism ; Hepatocytes ; cytology ; drug effects ; metabolism ; Male ; Mice ; Plant Extracts ; pharmacology
10.Protective effects of Huanglian Jiedu decoction on vascular endothelial function in type 2 diabetic rats.
Yan-ling XIAO ; Fu-er LU ; Li-jun XU ; San-hua LENG ; Kai-fu WANG
China Journal of Chinese Materia Medica 2005;30(22):1767-1770
OBJECTIVETo investigate the effects of Huanglian Jiedu (HLJD) decoction on vascular endothelial function in type 2 diabetic rats and explore the prophylactic and therapeutic significance and pharmacological mechanism of HLJD decoction in type 2 diabetic angiopathic complication.
METHODThe murine type 2 diabetes models were induced by the intravenous injection of a small dose of streptozotocin plus high fat and high caloric laboratory chow. Then modeled diabetic animals were divided into model group, HLJD group, and aspirin group. Normal ratsfed with routine chow were designated as normal group. The oral glucose tolerance test (OGTT) were performed in all animals, 9 weeks after treatment, the changes of murine body weights and levels of fasting blood glucose (FBG), serum total cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol(HDL-C), fasting serum insulin (FINS), serum nitric oxide, plasma endothelin, angiotensin II and von Willebrand Factor (vWF) were determined 10 weeks after treatment.
RESULTCompared with model group, the result of OGTT of HLJD group was improved. The levels of the body weights, TC, TG and ET in HLJD group weredecreased (P < 0.05). The levels of FBG,INS, AngII and vWFwere significantly decreased (P < 0.01), and the levels of HDL-C and NO were obviously increased (P < 0.05), as compared with those in model group. Furthermore. The levels of FBG was lower in HLJD group than in aspirin group (P < 0.05), and the improvement of TG, HDL-C,NO, AngII, vWF levels in HLJD group was more greatly than that in aspirin group, but there was not significant difference between two groups (P > 0.05).
CONCLUSIONIt is suggested by the present results that HLJD decoction could protect vascular endothelium from early damage in type 2 diabetes. The protective effects of HLJD on endothelium might be related to its ability of reducing the blood glucose, adjusting plasma lipids profiles, improving insulin resistance, antagonizing inflammatory mediators and inducing endothelium-dependent vascular relaxation.
Angiotensin II ; blood ; Animals ; Blood Glucose ; metabolism ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Coptis ; chemistry ; Diabetes Mellitus, Experimental ; blood ; physiopathology ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Endothelium, Vascular ; physiopathology ; Glucose Tolerance Test ; Hypoglycemic Agents ; pharmacology ; Insulin ; blood ; Male ; Nitric Oxide ; blood ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar ; Triglycerides ; blood ; von Willebrand Factor ; metabolism