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Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively.
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Purpose To explore the difference of expression and prognostic significance of SP1,KLF4 and p21 in low grade ovarian serous carcinoma (LGSC) and high grade ovarian serous carcinoma (HGSC).Methods The expression of SP1,KLF4 and p21 protein was examined with immunohistochemistry EliVision method in cases with LGSC and HGSC.Kaplan-Meier analysis and Cox multivariate survival analysis were used to assess the impact of SP1,KLF4 and p21 expression on prognosis of LGSC and HGSC.Results SP1,KLF4 and p21 expression were detected respectively in 74.5％,17.0％ and 11.7％ HG-SC cases,and in 65.2％,34.8％ and 26.1％ LGSC cases.Compared to control group,the expression level of SP1 was significantly higher (P ＜ 0.05),but the expression level of KLF4 and p21 were significantly lower (P ＜0.05).There was no significant difference of SP1,KLF4 and p21 expression between HGSC and LGSC (P ＞ 0.05).The expression of SP1,KLF4 and p21 were associated with FIGO stage,meanwhile SP1 associated with residual tumor size in HGSC (P ＜ 0.05).There was a significant negative correlation between SP1 and KLF4,p21 proteins in HGSC (P ＜ 0.05).Kaplan-Meier analysis revealed that there were significantly poor overall survival (OS) of 5 years for patients with HGSC displaying high expression of SP1,or low expression of KLF4 and p21 (P ＜0.05),but no significantly improved OS for patients with LGSC (P ＞ 0.05).Cox analysis showed that SP1 overexpression is an independent prognosis factor for HGSC.Conclusion Overexpression of SP1 and low expresion of KLF4 and p21 contribute to carcinogenesis of HGSC and LGSC.They are associated with a poor prognosis of HGSC,but not LGSC,meanwhile SP1 is an independant prognosis factor for HGSC.
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Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract fromthat is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ and the target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.
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Objective To construct the uniform electron density couch model (model A ED =0.25) and two components non uniform electron density couch model (model B FD =0.5and foam core=0.1) in the Monaco treatment planning system for the iBEAM(R) evo Extension 415,and to compare which model can better quantify the treatment couch influence on radiation dose.Methods Phantom was positioned in the center of the couch,the attenuation of the couch was evaluated with 6 MV for a field size of 10 cm× 10 cm.Dose measurements of couch attenuation were performed at gantry angles from 180.0° to 122.8°,using a 0.125cc semiflex ionization chamber (PTW),isocentrically placed in the center of a homogeneous cylindrical phantom.Each experimental setup was first measured on the linear accelerator and then reproduced in the TPS.By adjusting the relative-to water electron density (ED) values of the couch,the measured attenuation was replicated.The model accuracies of the model A and model B were evaluated by comparing the measured and calculated results at the minimum computational grid (2 mm) and maximum computing grid (5 mm),respectively.Results The maximum measured and calculated percentage deviation for the central phantom position was 4.01％.The couch model was included in the TPS with a uniform ED of 0.25 or a 2 component model with a fiber ED=0.5 and foam core ED=0.1.For model A and B under 2 and 5 mm voxel grid size,the mean absorbed dose with couch was reduced to 0.61％,0.84％,0.71％ and 0.92％from 2.8％ without couch.Conclusions Model A has a good agreement between measured and calculated dose distributions for all different voxel grid sizes and gantry angles.It can accurately describes the dose perturbations due to the presence of the couch and should therefore be used during treatment planning.
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Aim To detect the role of sirtuin1 ( SIRT1 ) in hepatotoxity caused by valproic acid ( VPA) . Methods The changes of SIRT1 expression of HepG2 cells were detected by Western blot. And then SIRT1 plasmid or siRNA was transfected to con-struct SIRT1 overexpressed or knocked-down HepG2 cells. Furthermore, SRB assays were taken to observe the changes of viability of these cells exposed to VPA. Results VPA suppressed SIRT1 expression in a time and dose-dependent manner. SIRT1 overexpression showed a protective effect to the cytotoxicity caused by VPA, and the IC50 before and after transfection was (4. 025 ± 0. 47) and (10. 87 ± 1. 50) mmol·L-1 re-spectively. Moreover, transfection of SIRT1 siRNA sensitized HepG2 cells to VPA, and the IC50 before and after transfection was (1. 938 ± 0. 16) and (0. 663 ± 0. 05) mmol·L-1 respectively. Conclusion VPA suppressed SIRT1 expression in HepG2 cells and over-expression of SIRT1 could reduce cytotoxicity induced by VPA.
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Objective To investigate the correlation of XRCC1 Arg194Trp Arg399Gln Single nucleotide polymor-phism (SNP) with radiotherapy response of squamous cell carcinoma of cervix. Methods Patients with exogenous type cer-vical squamous cell carcinoma confirmed by histopathology were selected for our study. These include:patients in stageⅠ(4 cases), patients in stageⅡ(36 cases), patients in stageⅢ(30 cases), patients in stageⅣ (3 cases). There are 30 patients with tumor diameter less than 4 cm and 43 patients with tumor diameter over 4 cm in our test. There are 36 cases with dose point A less than 80 Gy and 37 cases with dose point A over 80 Gy . Radiotherapy outcomes showed 47 cases of complete re-mission and 26 cases of part remission. Polymorphisms Arg194Trp, Arg399Gln of XRCC1 gene in 73 cervical cancer pa-tients were analyzed by mismatch amplification polymerase chain reaction (MAMA-PCR). Results Arg/Arg, Arg/Trp, TrP/Trp of Arg194Trp genotype distribution were 31 (42.5%), 37 (50.7%), 5 (6.8%) respectively. Arg/Arg, Arg/Gln, Gln/Gln of Arg399Gln distribution were 6 (35.6%), 39 (53.4%), 8 (11.0%) respectively. The response to radiotherapy was not statistical-ly significant in three genotypes, Arg/Arg, Arg/Trp, TrP/Trp of XRCC1 at codon 194(P>0.05). Neither was XRCC1 at codon 399. Multivariate analysis showed that late clinical stage was a risk factor of part remission. Conclusion SNP of XRCC1 gene at codon 194 and codon 399 could not predict clinical response of patients with squamous cell carcinoma of cervix to ra-diotherapy. The patients with advanced cervical cancer had poor response to radiotherapy.
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Objective Comparing the dosimetric characteristics of volumetric modulated arc therapy (VMAT) and constant dose rate intensity modulated arc therapy (IMAT) in esophagus cancer to evaluate the performance of the two different arc therapy delivery techniques.Methods 22 cases of esophageal cancer patients were selected for the planning comparison study.All plans were done for IMAT and VMAT treatment plans on Oncentra 4.1 treatment planning system,prescription dose of 2 Gy in total 30 fractions.Planning objectives for PTV were at least 95％ reached the prescription dose and V110 no more than 10％.The maximum dose of spinalcord below 45 Gy and double lung dose V20 ≤ 28％,V30 ≤ 18％ were constrained.Plans were evaluated based on the ability to meet the dose volume histogram.The dose homogeneity index (HI),radiation conformity index (CI),radiation delivery time,monitor units and γ pass rate were also compared.SPSS 19.0 software paired ttest analysis was carried out on the two sets of data.Results The results showed that the IMAT plans in terms of the PTV's CI (t =3.35,P=0.003),D2(t =-2.27,P=0.034) lung's V30(t =-2.46,P=0.023) were better than that of VMAT group.But the VMAT plans spinal's V40 (t =2.37,P =0.027),lung's V5 (t =2.43,P =0.024) were superior to that of IMAT plans.There were no significant differences between IMAT and VMAT plans in the average dose of PTV,CTV,GTV,heart,spinal cord,double lung and the γpass rate.Conclusion IMAT presents a slight improvement in the OAR sparing in high dose with shorter treatment time when compared to VMAT.While in terms of delivered MU and tissue of low dose irradiated area is higher than that of in VMAT.These two treatment methods all can meet the clinical demand,which should be selected according to the actual situation of the patient.
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AIM: To investigate the CE fingerprint of the compound Shengmai Powder(Radix et Rhizoma Ginseng rubra,Radix Ophiopogonis,Fructus Schisandrae chinensis). METHODS: Sequential uniform design was used to optimize the separation conditions. A CE fingerprint for Shengmai Powder was established using buffer comprising 44 mmol/L borate and 34 mmol/L SDS at pH 9. 5,a running voltage of 25 kV,a capillary temperature of 25 ?C and a wavelength of 200 nm. The sample was injected at a pressure of 50 mbar for 100 s. RESULTS: From the fingerprints of eleven batches of sample solutions,twenty main common peaks were determined. four peaks came from Radix et Rhizoma Ginseng,six peaks from Radix Ophiopogonis,thirteen peaks from Fructus Schisandrae chinensis,three peaks shared by Radix et Rhizoma Ginseng and Radix Ophiopogonis,one peak shared by Radix Ophiopogonis and Fructus Schisandrae chinensis and one new constituent. CONCLUSION: The developed method is accurate and reliable,and the fingerprint analysis can be used for the quality assessment and control of compound Shengmai Powder.