Background:Diethylnitrosamine,one of food additives,possessed a strong carcinogenic effect in human.Rhizoma paridis saponins,as the main active components of Paris polyphylla,have a good anti-cancer effect in our prev...Background:Diethylnitrosamine,one of food additives,possessed a strong carcinogenic effect in human.Rhizoma paridis saponins,as the main active components of Paris polyphylla,have a good anti-cancer effect in our previous research.To verify their inhibitory effect on diethylnitrosamine-induced liver cancer,we carried out this study.Methods:We established diethylnitrosamine-induced mouse hepatocarcinoma models to evaluate antitumor of Rhizoma paridis saponins.Subsequently,gas chromatography-mass spectrometry was applied to analyze the metabolites in the urine and serum samples.Results:Rhizoma paridis saponins alleviated diethylnitrosamine-induced hepatocarcinogenesis.On the one hand,Rhizoma paridis saponins down-regulated the levels of liver function markers,such as alanine aminotransferase,aspartate transaminase and alpha fetoprotein.On the other hand,Rhizoma paridis saponins reduced metabolic disorders by increasing fructose and mannose metabolism,and decreasing pentose and glucuronate interconversion,inositol phosphate metabolism,and the process of saturated fatty acids transforming to unsaturated fatty acids,which based on the regulating mRNA expression of glucose transporter type 4,lactate dehydrogenase A,fatty acid synthetas,acetyl-CoA carboxylase and apolipoprotein A-I.Conclusion:Rhizoma paridis saponins has the potential application to inhibit chemical-induced hepatocarcinogenesis in the future.展开更多
目的探讨敲低星形细胞上调基因-1(astrocyte elevated gene-1,AEG-1)表达对二乙基亚硝胺(diethylnitrosamine,DEN)诱导的原发性肝癌的调控。方法将60只大鼠随机分成Control组、DEN组、AEG-1 NC KO DEN组及AEG-1 KO DEN组,每组15只。除Co...目的探讨敲低星形细胞上调基因-1(astrocyte elevated gene-1,AEG-1)表达对二乙基亚硝胺(diethylnitrosamine,DEN)诱导的原发性肝癌的调控。方法将60只大鼠随机分成Control组、DEN组、AEG-1 NC KO DEN组及AEG-1 KO DEN组,每组15只。除Control组外,其余组均以DEN灌胃构建大鼠原发性肝癌模型,Control组和DEN组大鼠每日灌胃等体积生理盐水。AEG-1 KO DEN组和AEG-1 NC KO DEN组分别经腹腔注射稳定转染AEG-1shRNA或shRNA-NC慢病毒表达载体的HCCLM6。比较各组肝脏细胞损伤、凋亡、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)和谷肽甘肽(glutathione peroxidase,GSH)、肝功能,血清IL-6、TNF-α含量,肝脏组织半胱氨酸蛋白酶3(caspase-3,Cas-3)、半胱氨酸蛋白酶9(caspase-9,Cas-9)表达及P65蛋白表达。结果DEN组AEG-1的表达水平明显高于Control组(P<0.05),AEG-1 KO DEN组的大鼠死亡率及腹水发生率低于DEN组(P<0.05);AEG-1 KO DEN组血清AST、ALT、IL-6和TNF-α水平低于DEN组(P<0.05),SOD活性高于DEN组(P<0.05),GSH和MDA含量低于DEN组(P<0.05),cleaved cas9/cas9、cleaved cas3/cas3和p-P65/P65蛋白表达低于DEN组(P<0.05)。结论AEG-1敲除可降低DEN诱导的大鼠的氧化应激水平以及炎症因子水平,减轻对肝脏组织的损伤,改善肝脏功能。展开更多
AIM:To investigate whether carnitine deficiency is a risk factor during the development of diethylnitrosamine (DENA)-induced hepatic carcinogenesis. METHODS:A total of 60 male Wistar albino rats were divided into six ...AIM:To investigate whether carnitine deficiency is a risk factor during the development of diethylnitrosamine (DENA)-induced hepatic carcinogenesis. METHODS:A total of 60 male Wistar albino rats were divided into six groups with 10 animals in each group.Rats in group 1(control group)received a single intraperitoneal(i.p.)injection of normal saline. Animals in group 2(carnitine-supplemented group) were given L-carnitine(200 mg/kg per day)in drinking water for 8 wk.Animals in group 3(carnitine-depleted group)were given D-carnitine(200 mg/kg per day)and mildronate(200 mg/kg per day)in drinking water for 8 wk.Rats in group 4(DENA group)were injected with a single dose of DENA(200 mg/kg,i.p.)and 2 wk later received a single dose of carbon tetrachloride(2 mL/kg) by gavage as 1:1 dilution in corn oil.Animals in group 5(DENA-carnitine depleted group)received the same treatment as group 3 and group 4.Rats in group 6 (DENA-carnitine supplemented group)received the same treatment as group 2 and group 4.RESULTS:Administration of DENA resulted in a significant increase in alanine transaminase(ALT), gamma-glutamyl transferase(G-GT),alkaline phosphatase(ALP),total bilirubin,thiobarbituric acid reactive substances(TBARS)and total nitrate/ nitrite(NOx)and a significant decrease in reduced glutathione(GSH),glutathione peroxidase(GSHPx), catalase(CAT)and total carnitine content in liver tissues.In the carnitine-depleted rat model,DENA induced a dramatic increase in serum ALT,G-GT,ALP and total bilirubin,as well as a progressive reduction in total carnitine content in liver tissues.Interestingly, L-carnitine supplementation resulted in a complete reversal of the increase in liver enzymes,TBARS and NOx,and a decrease in total carnitine,GSH,GSHPx, and CAT induced by DENA,compared with the control values.Histopathological examination of liver tissues confirmed the biochemical data,where L-carnitine prevented DENA-induced hepatic carcinogenesis while D-carnitine-mildronate aggravated DENA-induced hepatic damage. CONCLUSION:Data from this study suggest for the first time that:(1)carnitine deficiency is a risk factor and should be viewed as a mechanism in DENA- induced hepatic carcinogenesis;(2)oxidative stress plays an important role but is not the only cause of DENA-induced hepatic carcinogenesis;and(3) long-term L-carnitine supplementation prevents the development of DENA-induced liver cancer.展开更多
Dena Fault is one of the fundamental and main structures with more than 130 km. One of the most important structural properties of this fault is changing in its trend so that at least three structural trends are detec...Dena Fault is one of the fundamental and main structures with more than 130 km. One of the most important structural properties of this fault is changing in its trend so that at least three structural trends are detectable along this fault. Some continental transpression evidences along fault Dena are checked. These evidences are: Fold’s axis has configuration step and mutual desire. Fold’s axis average preferred orientation makes angles less than 45 degrees with preferred orientation of the boundary faults. Strike-slip faults are arranged overlapping and territory. P harmonic sections are more than harmonic sections R. In the central and southern parts the type is transpression Trust and in the northern part the type is transpression shear. In the present strike-slip component right lateral of this fault is dominant to its trust component and Fault function in the present era, is right lateral reverse.展开更多
BACKGROUND Diethylnitrosamine(DEN)induces hepatic neoplastic lesions over a prolonged period.AIM To investigate the promotive action of 2-acetylaminofluorene(2-AAF)when combined with DEN in order to develop a rat mode...BACKGROUND Diethylnitrosamine(DEN)induces hepatic neoplastic lesions over a prolonged period.AIM To investigate the promotive action of 2-acetylaminofluorene(2-AAF)when combined with DEN in order to develop a rat model for induction of precancerous lesion and investigate the molecular mechanism underlying the activity of 2-AAF.METHODS The pre-precancerous lesions were initiated by intraperitoneal injection of DEN for three weeks consecutively,followed by one intraperitoneal injection of 2-AAF at three different doses(100,200 and 300 mg/kg).Rats were separated into naïve,DEN,DEN+100 mg 2-AAF,DEN+200 mg 2-AAF,and DEN+300 mg 2-AAF groups.Rats were sacrificed after 10 wk and 16 wk.Liver functions,level of alpha-fetoprotein,glutathione S-transferase-P and proliferating cell nuclear antigen staining of liver tissues were performed.The mRNA level of RAB11A,BAX,p53,and Cyclin E and epigenetic regulation by long-noncoding RNA(lncRNA)RP11-513I15.6,miR-1262(microRNA),and miR-1298 were assessed in the sera and liver tissues of the rats.RESULTS 2-AAF administration significantly increased the percent area of the precancerous foci and cell proliferation along with a significant decrease in RAB11A,BAX,and p53 mRNA,and the increase in Cyclin E mRNA was associated with a marked decrease in lncRNA RP11-513I15.6 expression with a significant increase in both miR-1262 and miR-1298.CONCLUSION 2-AFF promoted hepatic precancerous lesions initiated through DEN by decreasing autophagy,apoptosis,and tumor suppression genes,along with increased cell proliferation,in a time-and dose-dependent manner.These actions were mediated under the epigenetic regulation of lncRNA RP11-513I15.6/miR-1262/miR-1298.展开更多
Pomegranate （Punica granatum L.） has strong anti-inflammatory, antioxidant, anti obesity, and anticancer effects. The effect of different pomegranate extracts, PE （peel extract）, SOE （seed oil extract）, and PJ ...Pomegranate （Punica granatum L.） has strong anti-inflammatory, antioxidant, anti obesity, and anticancer effects. The effect of different pomegranate extracts, PE （peel extract）, SOE （seed oil extract）, and PJ （pomegranate juice） extract on levels of kidney caspase-3, DNAF （DNA fragmentation） and kidney function tests in rats treated and untreated with DEN （diethyl nitrosamine） and PB （Phenobarbital） during short （35 days） and long （154 days） period was studied. Injected of rats with DEN and PB caused an increased in the levels ofDNAF, caspase-3 and kidney function tests, compared to the control in both period of study. Treatment of rats with PE, SOE, PJ pre, during, and post DEN and PB administration improved kidney function and decreased the levels of DNAF, and caspase-3 activities compared to the DEN group in both period of study, indicates that PE, SOE, PJ reduced and treatment apoptosis induced by DEN and PB. Treatment of healthy rats with PE, SOE, and PJ only for 35 days not increased kidney function or induced apoptosis for kidney tissues. Treatment with PJ alone in healthy kidney induced apoptosis which was higher than that induced by SOE and PE in case of long period study, this mean that fresh fruit or pomegranate juice safe for healthy in general at harvesting season only.展开更多
The present study aimed at clarifying whether Chinese green tea, coffee and levamisole (LMS) have similar Inhibitory effect on hepatocarclnogenesis induced by diethylnltrosamine (DEN) as they had been proved in our pr...The present study aimed at clarifying whether Chinese green tea, coffee and levamisole (LMS) have similar Inhibitory effect on hepatocarclnogenesis induced by diethylnltrosamine (DEN) as they had been proved in our previous aflatoxin B1 (AFB1) experiments. Male Wistar rates were divided into control (A), green tea (B), coffee (C) and levamisole (D) groups. All rats received the same basic DEN treatment according to the program originally designed by Solt and Farber. During the two weeks before and one week after i. p. injection of DEN, the group B, C and D were given 2. 5% green tea, 5% coffee and 0. 1% LMS diet, respectively. The results demonstrated that coffee, LMS and , in particular,green tea showed Inhibitory effect against DEN-induced hepatocarcinogenesis, indicating that green tea can be used as chemopreventive agent for DEN-, as well as for AFB1-induced hepatocarcinogenesis.展开更多
This work presents an approach to build a high-performance, low-viscous and replaceable separation matrix, semi-crosslinked polyacrylamide （semi-CPA） capillary gel electrophoresis. Non- denatured basic proteins, suc...This work presents an approach to build a high-performance, low-viscous and replaceable separation matrix, semi-crosslinked polyacrylamide （semi-CPA） capillary gel electrophoresis. Non- denatured basic proteins, such as lysozyme, cytochrome C, ribonuclease A and trypsin were separa- ted. The impacts of monomer and cross-linker concentrations on protein separation were studied, and the ability of dynamic capillary inner wall coating was demonstrated. The UV absorption interfer- ence by semi-CPA gel matrix was successfully overcome by a partial filling technique, which results in sensitivity 20 times higher than other protein separation method. The excellent separation ability, reproducibility and dynamic coating ability made semi-CPA an ideal separation media in both capillar- y electrophoresis and microfluidic chip separation scheme.展开更多
文摘Background:Diethylnitrosamine,one of food additives,possessed a strong carcinogenic effect in human.Rhizoma paridis saponins,as the main active components of Paris polyphylla,have a good anti-cancer effect in our previous research.To verify their inhibitory effect on diethylnitrosamine-induced liver cancer,we carried out this study.Methods:We established diethylnitrosamine-induced mouse hepatocarcinoma models to evaluate antitumor of Rhizoma paridis saponins.Subsequently,gas chromatography-mass spectrometry was applied to analyze the metabolites in the urine and serum samples.Results:Rhizoma paridis saponins alleviated diethylnitrosamine-induced hepatocarcinogenesis.On the one hand,Rhizoma paridis saponins down-regulated the levels of liver function markers,such as alanine aminotransferase,aspartate transaminase and alpha fetoprotein.On the other hand,Rhizoma paridis saponins reduced metabolic disorders by increasing fructose and mannose metabolism,and decreasing pentose and glucuronate interconversion,inositol phosphate metabolism,and the process of saturated fatty acids transforming to unsaturated fatty acids,which based on the regulating mRNA expression of glucose transporter type 4,lactate dehydrogenase A,fatty acid synthetas,acetyl-CoA carboxylase and apolipoprotein A-I.Conclusion:Rhizoma paridis saponins has the potential application to inhibit chemical-induced hepatocarcinogenesis in the future.
文摘目的探讨敲低星形细胞上调基因-1(astrocyte elevated gene-1,AEG-1)表达对二乙基亚硝胺(diethylnitrosamine,DEN)诱导的原发性肝癌的调控。方法将60只大鼠随机分成Control组、DEN组、AEG-1 NC KO DEN组及AEG-1 KO DEN组,每组15只。除Control组外,其余组均以DEN灌胃构建大鼠原发性肝癌模型,Control组和DEN组大鼠每日灌胃等体积生理盐水。AEG-1 KO DEN组和AEG-1 NC KO DEN组分别经腹腔注射稳定转染AEG-1shRNA或shRNA-NC慢病毒表达载体的HCCLM6。比较各组肝脏细胞损伤、凋亡、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)和谷肽甘肽(glutathione peroxidase,GSH)、肝功能,血清IL-6、TNF-α含量,肝脏组织半胱氨酸蛋白酶3(caspase-3,Cas-3)、半胱氨酸蛋白酶9(caspase-9,Cas-9)表达及P65蛋白表达。结果DEN组AEG-1的表达水平明显高于Control组(P<0.05),AEG-1 KO DEN组的大鼠死亡率及腹水发生率低于DEN组(P<0.05);AEG-1 KO DEN组血清AST、ALT、IL-6和TNF-α水平低于DEN组(P<0.05),SOD活性高于DEN组(P<0.05),GSH和MDA含量低于DEN组(P<0.05),cleaved cas9/cas9、cleaved cas3/cas3和p-P65/P65蛋白表达低于DEN组(P<0.05)。结论AEG-1敲除可降低DEN诱导的大鼠的氧化应激水平以及炎症因子水平,减轻对肝脏组织的损伤,改善肝脏功能。
基金Supported by Operating grant from Research Center,Collegeof Pharmacy,King Saud University(CPRC 207)
文摘AIM:To investigate whether carnitine deficiency is a risk factor during the development of diethylnitrosamine (DENA)-induced hepatic carcinogenesis. METHODS:A total of 60 male Wistar albino rats were divided into six groups with 10 animals in each group.Rats in group 1(control group)received a single intraperitoneal(i.p.)injection of normal saline. Animals in group 2(carnitine-supplemented group) were given L-carnitine(200 mg/kg per day)in drinking water for 8 wk.Animals in group 3(carnitine-depleted group)were given D-carnitine(200 mg/kg per day)and mildronate(200 mg/kg per day)in drinking water for 8 wk.Rats in group 4(DENA group)were injected with a single dose of DENA(200 mg/kg,i.p.)and 2 wk later received a single dose of carbon tetrachloride(2 mL/kg) by gavage as 1:1 dilution in corn oil.Animals in group 5(DENA-carnitine depleted group)received the same treatment as group 3 and group 4.Rats in group 6 (DENA-carnitine supplemented group)received the same treatment as group 2 and group 4.RESULTS:Administration of DENA resulted in a significant increase in alanine transaminase(ALT), gamma-glutamyl transferase(G-GT),alkaline phosphatase(ALP),total bilirubin,thiobarbituric acid reactive substances(TBARS)and total nitrate/ nitrite(NOx)and a significant decrease in reduced glutathione(GSH),glutathione peroxidase(GSHPx), catalase(CAT)and total carnitine content in liver tissues.In the carnitine-depleted rat model,DENA induced a dramatic increase in serum ALT,G-GT,ALP and total bilirubin,as well as a progressive reduction in total carnitine content in liver tissues.Interestingly, L-carnitine supplementation resulted in a complete reversal of the increase in liver enzymes,TBARS and NOx,and a decrease in total carnitine,GSH,GSHPx, and CAT induced by DENA,compared with the control values.Histopathological examination of liver tissues confirmed the biochemical data,where L-carnitine prevented DENA-induced hepatic carcinogenesis while D-carnitine-mildronate aggravated DENA-induced hepatic damage. CONCLUSION:Data from this study suggest for the first time that:(1)carnitine deficiency is a risk factor and should be viewed as a mechanism in DENA- induced hepatic carcinogenesis;(2)oxidative stress plays an important role but is not the only cause of DENA-induced hepatic carcinogenesis;and(3) long-term L-carnitine supplementation prevents the development of DENA-induced liver cancer.
文摘Dena Fault is one of the fundamental and main structures with more than 130 km. One of the most important structural properties of this fault is changing in its trend so that at least three structural trends are detectable along this fault. Some continental transpression evidences along fault Dena are checked. These evidences are: Fold’s axis has configuration step and mutual desire. Fold’s axis average preferred orientation makes angles less than 45 degrees with preferred orientation of the boundary faults. Strike-slip faults are arranged overlapping and territory. P harmonic sections are more than harmonic sections R. In the central and southern parts the type is transpression Trust and in the northern part the type is transpression shear. In the present strike-slip component right lateral of this fault is dominant to its trust component and Fault function in the present era, is right lateral reverse.
文摘BACKGROUND Diethylnitrosamine(DEN)induces hepatic neoplastic lesions over a prolonged period.AIM To investigate the promotive action of 2-acetylaminofluorene(2-AAF)when combined with DEN in order to develop a rat model for induction of precancerous lesion and investigate the molecular mechanism underlying the activity of 2-AAF.METHODS The pre-precancerous lesions were initiated by intraperitoneal injection of DEN for three weeks consecutively,followed by one intraperitoneal injection of 2-AAF at three different doses(100,200 and 300 mg/kg).Rats were separated into naïve,DEN,DEN+100 mg 2-AAF,DEN+200 mg 2-AAF,and DEN+300 mg 2-AAF groups.Rats were sacrificed after 10 wk and 16 wk.Liver functions,level of alpha-fetoprotein,glutathione S-transferase-P and proliferating cell nuclear antigen staining of liver tissues were performed.The mRNA level of RAB11A,BAX,p53,and Cyclin E and epigenetic regulation by long-noncoding RNA(lncRNA)RP11-513I15.6,miR-1262(microRNA),and miR-1298 were assessed in the sera and liver tissues of the rats.RESULTS 2-AAF administration significantly increased the percent area of the precancerous foci and cell proliferation along with a significant decrease in RAB11A,BAX,and p53 mRNA,and the increase in Cyclin E mRNA was associated with a marked decrease in lncRNA RP11-513I15.6 expression with a significant increase in both miR-1262 and miR-1298.CONCLUSION 2-AFF promoted hepatic precancerous lesions initiated through DEN by decreasing autophagy,apoptosis,and tumor suppression genes,along with increased cell proliferation,in a time-and dose-dependent manner.These actions were mediated under the epigenetic regulation of lncRNA RP11-513I15.6/miR-1262/miR-1298.
文摘Pomegranate （Punica granatum L.） has strong anti-inflammatory, antioxidant, anti obesity, and anticancer effects. The effect of different pomegranate extracts, PE （peel extract）, SOE （seed oil extract）, and PJ （pomegranate juice） extract on levels of kidney caspase-3, DNAF （DNA fragmentation） and kidney function tests in rats treated and untreated with DEN （diethyl nitrosamine） and PB （Phenobarbital） during short （35 days） and long （154 days） period was studied. Injected of rats with DEN and PB caused an increased in the levels ofDNAF, caspase-3 and kidney function tests, compared to the control in both period of study. Treatment of rats with PE, SOE, PJ pre, during, and post DEN and PB administration improved kidney function and decreased the levels of DNAF, and caspase-3 activities compared to the DEN group in both period of study, indicates that PE, SOE, PJ reduced and treatment apoptosis induced by DEN and PB. Treatment of healthy rats with PE, SOE, and PJ only for 35 days not increased kidney function or induced apoptosis for kidney tissues. Treatment with PJ alone in healthy kidney induced apoptosis which was higher than that induced by SOE and PE in case of long period study, this mean that fresh fruit or pomegranate juice safe for healthy in general at harvesting season only.
文摘The present study aimed at clarifying whether Chinese green tea, coffee and levamisole (LMS) have similar Inhibitory effect on hepatocarclnogenesis induced by diethylnltrosamine (DEN) as they had been proved in our previous aflatoxin B1 (AFB1) experiments. Male Wistar rates were divided into control (A), green tea (B), coffee (C) and levamisole (D) groups. All rats received the same basic DEN treatment according to the program originally designed by Solt and Farber. During the two weeks before and one week after i. p. injection of DEN, the group B, C and D were given 2. 5% green tea, 5% coffee and 0. 1% LMS diet, respectively. The results demonstrated that coffee, LMS and , in particular,green tea showed Inhibitory effect against DEN-induced hepatocarcinogenesis, indicating that green tea can be used as chemopreventive agent for DEN-, as well as for AFB1-induced hepatocarcinogenesis.
基金Supported by the Key Project in the National Science ＆ Tech- nology Pillar Program During the Eleventh Five-Year Plan Pe- riod （2009BAK59B02）
文摘This work presents an approach to build a high-performance, low-viscous and replaceable separation matrix, semi-crosslinked polyacrylamide （semi-CPA） capillary gel electrophoresis. Non- denatured basic proteins, such as lysozyme, cytochrome C, ribonuclease A and trypsin were separa- ted. The impacts of monomer and cross-linker concentrations on protein separation were studied, and the ability of dynamic capillary inner wall coating was demonstrated. The UV absorption interfer- ence by semi-CPA gel matrix was successfully overcome by a partial filling technique, which results in sensitivity 20 times higher than other protein separation method. The excellent separation ability, reproducibility and dynamic coating ability made semi-CPA an ideal separation media in both capillar- y electrophoresis and microfluidic chip separation scheme.
