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Multidrug resistance of tumors has been a severe obstacle to the success of cancer chemotherapy. The study wants to investigate the reversal effects of imperatorin (IMP) on doxorubicin (DOX) resistance in K562/DOX leukemia cells, A2780/Taxol cells and in NOD/SCID mice, to explore the possible molecular mechanisms. K562/ DOX and A2780/Taxol cells were treated with various concentrations of DOX and Taol with or without different concentrations of IMP, respectively. K562/DOX xenograft model was used to assess anti-tumor effect of IMP combined with DOX. MTT assay, Rhodamine 123 efflux assay, RT-PCR, and Western blot analysis were determined in vivo and in vitro. Results showed that IMP significantly enhanced the cytotoxicity of DOX and Taxol toward corresponding resistance cells. In vivo results illustrated both the tumor volume and tumor weight were significantly decreased after 2-week treatment with IMP combined with DOX compared to the DOX alone group. Western blotting and RT-PCR analyses indicated that IMP downregulated the expression of P-gp in K562/DOX xenograft tumors in NOD/SCID mice. We also evaluated glycolysis and glutamine metabolism in K562/DOX cells by measuring glucose consumption and lactate production. The results revealed that IMP could significantly reduce the glucose consumption and lactate production of K562/DOX cells. Furthermore, IMP could also remarkably repress the glutamine consumption, α-KG and ATP production of K562/DOX cells. Thus, IMP may sensitize K562/DOX cells to DOX and enhance the antitumor effect of DOX in K562/DOX xenograft tumors in NOD/SCID mice. IMP may be an adjuvant therapy to mitigate the multidrug resistance in leukemia chemotherapy.
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Objective: Astragalus Radix (AR, Huangqi in Chinese) has been widely used as a qi (energy) restoring herb that is thought to act through reinvigorating the spleen and lung. Aconite is used to rebalance the body temperature during illness and played an irreplaceable role in disease control since ancient times, but it is limited by its strong neuro and cardiotoxicity. Since the Song Dynasty (1227), the two herbs have been commonly used as herbal pairs including in the famous Qifu Decotion, from the “Wei's Family Prescription”. However, many ancient texts also record that they are not compatible using together, suggesting they can have negative outcomes when mixed. This study investigated whether Astragali Radix had either positive or negative effects on absorption of six different active alkaloids derived from aconite. Methods: Single intestinal perfusion model was used to study the effects of Astragali Radix on aconite alkaloids absorption. Response of ABC transporters and distribution of three tight junction proteins on the surface of intestinal enothelium were assessed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blot and immunofluorescence microscopy, respectively. Results: The results showed that aconite alkaloids absorption could be inhibited, and different concentrations of Astragali Radix considerably increased the expression levels of the ABC transporters and tight junction proteins with Astragali Radix treatment. Conclusion: These results suggest that Astragali Radix can block absorption of aconite alkaloids through the upregulation expression of ATP-binding cassette transporters (ABC transporters) and tight junction proteins. It demonstrates that co-administration of Astragali Radix with other drugs might change the absorption profile of the second drug which is important to know in clinic therapy.
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OBJECTIVE:To observe the effects of dexmedetomidine (Dex) on postoperative agitation of Wilson's disease patients with secondary hypersplenism after genernl anesthesia of splenectomy.METHODS:A total of 60 Wilson's disease patients with secondary hypersplenism underwent general anesthesia of splenectomy duning Jan.-Dec.2016 were divided into control group and observation group according to random number table,with 30 cases in each group.Observation group was given intravenous pump of Dex 0.4 μg/kg at constant speed 15 min before anesthesia induction,and then maintained at 0.4 tg/(kg·h)till splenectomy completed.Control group was given constant volume of normal saline.Other anesthesia plans were same in 2 groups.Mean arterial pressure (MAP),heart rate (HR) and pulse oxygen saturation (SpO2) of 2 groups were observed before pumping (T0),before intubation (T1),1 min after intubation (T2),before extubation (T3),3 min after extubation (T4).Riker sedation-agitation score (SAS) were recorded in 2 groups at T3 and T4.The duration of stay in postanesthesia intensive care unit (PACU) and the occurrence of bradycardia were compared between 2 groups.RESULTS:At T0,there was no statistical significance in MAP,HR or SpO2 levels between 2 groups (P＞0.05).At T1,T2,T3 and T4,MAP and HR levels of 2 groups were decreased significantly,and the observation group was significantly lower than the control group,with statistical significance (P＜0.05).SpO2 were 100％ at each time point,there was no statistical significance between 2 groups (P＞0.05).Riker SAS scores of observation group was significantly lower than that of control group,with statistical significance (P＜0.05).The incidence of bradycardia in observation group was 26.67％,which was significantly higher than 3.33％ of control group,with statistical significance (P＜0.05).But this symptom was corrected after intravenous injection of atropine.The duration of stay in PACU in observation group was significantly shorter than control group,with statistical significance (P＜0.05).CONCLUSIONS:Dex can keep postoperative hemodynamics stable in Wilson's disease patients with secondary hypersplenism,reduce agitation and shorten the time of the patients transferring from PACU.
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@#ObjectiveTo study the hemoprotective effects of rotating and stationary magnetic field(RSMF) in mice treated with 5-Fluorouracil(5-FU).MethodsThe BalB/C mice were randomly divided into control group and RSMF-treated group.The mice were injected with 5-FU,the dose were 150,180,210,250 mg/kg respectively. RSMF-treated group was exposed to RSMF for 1 h a time,twice a day during 30 consecutive days,and the magnetic intensity was 0.6 T.The survival rate and survival days during the 30 days were observed.7,10,14,21,28 days after injection,the peripheral blood cells were counted.On day 8,10 and 14,the number of bone marrow mononuclear cells(BMNC) and the forming ability of colony-forming unit-granulocyte/macrophage(CFU-GM) were measured.The pathological section of femur and the expression level of bone morphogenic proteins(BMPs) in bone marrow were evaluated.ResultsRSMF could increase the survival rate and survival days of mice treated with 5-FU,and induce an increase in hemoglobin concentration,white blood cell count(WBC),red blood cell count(RBC) and platelet number.Also,RSMF could increase the number of BMNC and improve the forming ability of CFU-GM on days 8～14.Furthermore,RSMF could improve the bone marrow angiogenesis and the expression level of BMPs.ConclusionRSMF have an obvious protective effect against chemotherapeutic injury,and it can accelerate the recovery of hematopoiesis and hematopoietic microenvironment in mouse bone marrow.
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Objective To study the hemoprotective effects of a rotary magnetic field(RMF)with radiation- injured mice.Methods C57 BL6/J mice were randomly divided into a control group and a magnetic treatment group.The mice received total body irradiation with 7.0 Gy and 6.5 Gy ~(137)Cs?rays.The treatment group was trea- ted with a RMF for one hour at a time,twice a day.The intensity of the RMF was 0.6T.The survival rate was ob- served for 30 days.On day 7,10,14,21,28 after irradiation,the subjects' peripheral blood cells were counted.On day 12 and 16,the number of bone marrow mononuelear cells(BMNCs)was measured and their ability to form granu- locyte-macruphage colony-forming unit(CFU-GM)was assessed.The pathological sectioning of the femur was per- formed and the expression level of bone morphogenetic proteins(BMPs)in the bone marrow were evaluated.Re- sults The RMF treatment increased the survival rate and duration among the irradiated mice and the number of blood cells in their peripheral blood.Also,RMF treatment could increase the number of BMNCs and improve their ability to form CFU-GM on days 12-16.Furthermore,RMF could improve angiogenesis and the expression level of BMPs. Conclusion The RMF treatment had an obvious protective effect against the effects of irradiation,and it accelerated the recovery of hematopoiesis and the hematopoietic microenviroment in mouse bone marrow.
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<p><b>OBJECTIVE</b>To analyze the frequency of beta-fibrinogen (beta-Fg) gene -455G/A, -148C/T and 448G/A polymorphism, fibrinogen molecular reactivity and their association with plasma fibrinogen levels in health adults, myocardial infarction and cerebral infarction disease.</p><p><b>METHODS</b>The beta-Fg gene -455G/A, -148C/T and 448G/A polymorphisms were analyzed by restriction fragment length polymorphism (RFLP). Fibrinogen molecular reactivity was analyzed for the conversion kinetics of fibrinogen into fibrin by a computer assistant procedure. Plasma fibrinogen levels were determined by Clauss method.</p><p><b>RESULTS</b>The frequencies of -455A, -148T, 448A allele in health adults were 0.185, 0.194 and 0.192, in myocardial infarction disease 0.295, 0.318 and 0.307, in cerebral infarction disease 0.177, 0.193 and 0.182, respectively. The frequencies of -455A, -148T, 448A alleles in myocardial infarction disease were apparently higher than that of health adults. There were close linkage between -455G, -148C and 448G or -455A, -148T and 448A, the correspondence was over 98%. There are no differences in the plasma fibrinogen levels of the three polymorphisms in two genotype groups. The fibrinogen molecular reactivity was significantly increased in cardiocerebral vascular disease and related with plasma fibrinogen level.</p><p><b>CONCLUSION</b>The three polymorphisms loci are strong linkage disequilibrium. There are no significant differences in the plasma fibrinogen levels of the three polymorphisms in two genotype groups. The frequencies of -455A, -148T, 448A alleles in myocardial infarction disease were apparently higher than that of health adults. It suggest that there was no association between beta-Fg gene -455G/A, -148C/T and 448G/A polymorphisms and plasma fibrinogen levels, but did in myocardial infarction disease. The fibrinogen molecular reactivity was significantly increased in cardiocerebral vascular disease and related with plasma fibrinogen level.</p>