Aim To investigate the effect of curcumin on induction of glutathione S-transferases (GST), NADP(H):quinone oxidoreductase (NQO) and explore their possible molecular mechanism. Methods The activity of GST, NQO and cel...Aim To investigate the effect of curcumin on induction of glutathione S-transferases (GST), NADP(H):quinone oxidoreductase (NQO) and explore their possible molecular mechanism. Methods The activity of GST, NQO and cellular reduced glutathione (GSH) content were measured by spectrophotometrical methods. Cellular changes in the distribution of NF-E2 related factor 2 (Nrf2) was detected by western blotting analysis. Nrf2-AREs (antioxidant-responsive elements) binding activity was examined by electrophoretic mobility shift assay (EMSA). Results Curcumin caused a significant increase in GST and NQO activity, with a maximal value being observed at 20, 25 μmol/L, respectively. At concentration higher than 30 μmol/L, curcumin appeared to be less effective in stimulating GST and NQO activity. Treatment of HT-29 with curcumin caused a modest increase in the cellular GSH content at 3 h (P<0.05). All concentrations of curcumin continued to increase GSH content during the next 9 h. No significant change in the GSH content was observed at either 1 or 2 h after curcumin exposure. Upon treatment of cells with 20 μmol/L curcumin, Nrf2 protein accumulated rapidly (3 h) in the nucleus. This data suggested that curcumin mediate an increase of Nrf2 in the nuclear, a common component of ARE binding complexes. The retarded Nrf2-AREs complexes progressively formed upon treatment with curcumin at the concentration of 20 μmol/L for indicated time. Conclusion These results demonstrated that induction of GST and NQO activity by curcumin may be mediated by translocation of transcription factor Nrf2 from cytoplasm to nuclear and increased binding activity of Nrf2-ARE complexes.It is possible that this effect efficiently protects cells from oxidative stress and should be evaluated as a new therapeutic approach in oxidative stress-mediated damage.展开更多
To explore the relation of angiotensin-converting enzyme (ACE) and angiotensin Ⅱ type 1 receptor (AT1R) gene polymorphism with coronary heart disease (CHD) and the severity of coronary artery stenosis, 130 CHD ...To explore the relation of angiotensin-converting enzyme (ACE) and angiotensin Ⅱ type 1 receptor (AT1R) gene polymorphism with coronary heart disease (CHD) and the severity of coronary artery stenosis, 130 CHD patients who underwent coronary angiography were examined for the number of affected coronary vessels (≥75% stenosis) and coronary Jeopardy score. The insertion/deletion of ACE gene polymorphism and AT1R gene polymorphism (an A→C transversion at nucleotide position 1166) were detected by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) in CHD patients and 90 healthy serving as controls. The resuits showed that DD genotype and of ACE were more frequent in CHD patients than that in control group (38.5% vs 14.4%, P〈0.001). The frequency of the ATIR A/C genotypes did not differ between the patients and the controls (10% vs 13.1%, P〉0.05). The relative risk associated with the ACE-DD was increased by AT1R-AC genotype. Neither the number of affected coronary vessels nor the coronary score differed among the ACE I/D genotypes (P〉0.05). But the number of affected coronary vessels and the coronary score were significantly greater in the patients with the AT1R-AC genotype than in those with the AA genotype (P〈0.05). In conclusion, DD genotype may be risk factor for CHD and MI in Chinese people, and is not responsible for the development of the coronary artery stenosis. The AT1R-C allele may increase the relative risk associated with the ACE-DD genotype, and may be involved in the development of the stenosis of coronary artery.展开更多
Objective The increasing recognition of the role for oxidative stress in hepatic disorders has led to extensive investigation on the protection by exogenous antioxidants against hepatic injury.In this study,we choose ...Objective The increasing recognition of the role for oxidative stress in hepatic disorders has led to extensive investigation on the protection by exogenous antioxidants against hepatic injury.In this study,we choose two typical polyphenol,quercetin and rutin,to investigate the mechanism of induction of cellular antioxidants and phase 2 enzymes in human HepG2 cells.Methods The HepG2 cells were treated with various concentrations of quercetin and rutin for 6 h and 24 h.The activities of NAD(P)H:quinone oxidoreductase(NQO1)in HepG2 cells were measured by 2,6-dichloroindophenol reduction method.The content of superoxide dismutase(SOD)was determined with the method of chemical colorimetry.The protein expressions of NQO1 and NF-E2-related factor 2(Nrf2)in HepG2 cells were detected by Western blotting.Results Incubation of HepG2 cells with quercetin and rutin resulted in a marked concentration-and time-dependent induction of a number of cellular antioxidants and phase 2 enzymes,including NQO1,SOD.Quercetin and rutin treatment of HepG2 cells also caused increase in protein expressions of NQO1 and Nrf2.Conclusions This study demonstrates that a series of phase 2 enzymes in HepG2 cells can be induced by quercetin and rutin in a concentration-and time-dependent fashion by upregulation the protein expression of nrf2.展开更多
The synthesis of dipeptide AcPheLeuNH2 catalyzed by immobilized pancreatic lipase was carried out in a two- liquid-phase hollow-fiber membrane reactor, operated in a batch mode. Kinetic properties of free and immobili...The synthesis of dipeptide AcPheLeuNH2 catalyzed by immobilized pancreatic lipase was carried out in a two- liquid-phase hollow-fiber membrane reactor, operated in a batch mode. Kinetic properties of free and immobilized enzyme, partition behavior between aqueous buffer phase and organic solvent phase, and effective diffusion coefficients of substrates and products through the membrane were investigated respectively. Based on the preliminary experimental results, the performance of the enzyme membrane reactor, which is evaluated by the purity and the yield, is discussed.展开更多
Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In ...Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In an earlier phase I study, a novel form of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) that is currently in clinical development for the treatment of hematologic malignancies, i.e., circularly permuted TRAIL(CPT), was well tolerated at a dose of 2.5 mg/kg per day and showed promising preliminary activity in patients with RRMM. This phase II, open-label, multicenter study further investigated the eicacy and safety of 2.5-mg/kg per day CPT as single-agent therapy for patients with RRMM.Methods: Patients with RRMM were treated once daily with CPT(2.5 mg/kg, intravenously) for 14 consecutive days for each 21-day cycle. Clinical response and toxicity were assessed after each treatment cycle.Results: Twenty-seven patients received CPT. Using the European Group for Blood and Marrow Transplantation criteria, we calculated the overall response rate of 33.3% with 1 near-complete response(n CR) and 8 partial responses(PRs). The clinical beneit rate(48.1%) included 1 nCR, 8 PRs, and 4 minimal responses. The most common treatmentrelated adverse events(TRAEs) were fever, aspartate aminotransferase elevation, alanine aminotransferase elevation, leucopenia, rash, neutropenia, and thrombocytopenia. We graded toxicity using the Common Toxicity Criteria for Adverse Events, version 3.0, and determined that 37.0% of patients had at least 1 grade 3–4 TRAE.Conclusions: CPT as a single agent can elicit a response in patients with RRMM and is well tolerated. Further clinical investigation is warranted.展开更多
The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a...The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues,including the liver,pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme(ACE)-angiotensin(Ang) Ⅱ-Ang type 1(AT1) receptor mediates pro-inflammatory,pro-thrombotic,and pro-fibrotic processes. On the other hand,the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang Ⅱ action. Chronic hepatitis B(CHB) is one of the leading causes of liver fibrosis,accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However,the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36 th issue of the World Journal of Gastroenterology,Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate,non-invasive,widely available,and easy method to evaluate fibrosis related to CHB. Moreover,therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis.展开更多
AIM To evaluate the efficacy and safety of modified FOLFIRINOX as a second-line treatment for gemcitabine(GEM)-refractory unresectable pancreatic cancer(PC).METHODS This study was a prospective, multicenter, one-arm, ...AIM To evaluate the efficacy and safety of modified FOLFIRINOX as a second-line treatment for gemcitabine(GEM)-refractory unresectable pancreatic cancer(PC).METHODS This study was a prospective, multicenter, one-arm, open-label, phase Ⅱ trial. Patients with unresectable PC, who showed disease progression during GEMbased chemotherapy were enrolled. All patients were administered FOLFIRINOX with reduced irinotecan and oxaliplatin(RIO; irinotecan 120 mg/m^2 and oxaliplatin 60 mg/m^2), which was set according to the phase Ⅰ study of FOLFIRINOX. The objective response rate(ORR), disease control rate(DCR), progressionfree survival(PFS), overall survival(OS), adverse events were evaluated. Additionally, changes in quality of life(QoL) were assessed using a questionnaire on QoL.RESULTS Between August 2015 and May 2016, a total of 48 patients were enrolled. The median follow-up time was 259 d with a median of 8.5 cycles. The ORR and DCR were 18.8% and 62.5%, respectively, including one patient who showed complete remission. The median PFS was 5.8 mo [95% confidence interval(CI): 3.7-7.9] and median OS was 9.0 mo(95%CI: 6.4-11.6). Neutropenia(64.6%) was the most common grade 3-4 adverse event, followed by febrile neutropenia(16.7%). Although 14.6% of patients experienced grade 3 fatigue, most non-hematologic AEs were under grade 2. In the QoL analysis, the global health status score before treatment was not different from the score at the last visit after treatment(45.43 ± 22.88 vs 48.66 ± 24.14, P = 0.548).CONCLUSION FOLFIRINOX with RIO showed acceptable toxicity and promising efficacy for GEM-refractory unresectable PC. However, this treatment requires careful observation of treatment-related hematologic toxicities.展开更多
Human urotension-Ⅱ was synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy. Disulphide bridge was formed on solid phase with the irradiation of microwave, t...Human urotension-Ⅱ was synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy. Disulphide bridge was formed on solid phase with the irradiation of microwave, then the whole peptide was cleaved from the resin. The purity of crude peptide cyclized under microwave irradiation was higher than that under room temperature.展开更多
Iron(Ⅱ) tetrasulfophthalocyanine(FeTSPc) ,as a novel mimetic enzyme of peroxidase,was used in the synthesis of a conducting polyaniline(PANI) /sodium dodecylsulfate(SDS) complex in SDS aqueous micellar solutions. The...Iron(Ⅱ) tetrasulfophthalocyanine(FeTSPc) ,as a novel mimetic enzyme of peroxidase,was used in the synthesis of a conducting polyaniline(PANI) /sodium dodecylsulfate(SDS) complex in SDS aqueous micellar solutions. The effects of pH,concentrations of aniline,SDS and H2O2,and reaction time on polymerization of aniline were studied in this case as shown by UV-Vis absorption spectroscopy. The results show that a wide range of pH(0.5-4.0) is required to produce the conducting PANI,and the optimal pH is 1.0 in SDS micelle. The optimal concentrations of aniline,SDS and H2O2 in feed,and reaction time in this case for the production of conducting PANI are respectively 10 mmol/L,10 mmol/L,25 mmol/L,and 15 h. FT-IR spectrum,elemental analysis,conductivity,cyclic voltammetry and thermogravimetric analysis confirm the thermal stability and electroactive form of PANI.展开更多
Objective To evaluate the anti-tumor effect and toxicity of gemcitabine combined with platinum chemotherapy on recurrent epithelial ovarian cancer. Methods Phase Ⅱ study of gemcitabine combined with platinum chemothe...Objective To evaluate the anti-tumor effect and toxicity of gemcitabine combined with platinum chemotherapy on recurrent epithelial ovarian cancer. Methods Phase Ⅱ study of gemcitabine combined with platinum chemotherapy was carried out in 22 patients with recurrent epithelial ovarian cancer. Median age of patients was 50. 5 years old. Seven patients were platinum-sensitive and 15 patients were platinum-resistant or -refractory. All patients received gemcitabine combined with carboplatin or oxa/iplatin chemotherapy. Patients' response rate (RR) and toxicity of gemcitabine combined with platinum chemotherapy were evaluated. Results A total of 98 gemcitabine-based chemotherapy cycles were performed. Total RR was 36. 4%, RR of platinum-sensitive patients was 4/7 and platinum-resistant and -refractory patients was 4/15. The estimated median survival time was 10.0 months (95% CI. 7.0-13.0) after initiation of gemcitabine combined with platinum chemotherapy. There was no significant difference in survival time between platinum-resistant/refractory group and platinum-sensitive group (P = 0. 061 ). Side effects of gemcitabine combined with platinum chemotherapy were observed in 81.8% of patients. Grade Ⅱ/Ⅲ anemia (54. 5% ) and grade Ⅲ/Ⅳ neutropenia (54. 5% ) were most common toxicities. Ten (45.5%) patients had to delay their chemotherapy cycles or reduce the dose of chemotherapeutic drugs because of the severe side effects. Fourteen (63.6%) patients received granulocyte colony-stimulating factor to relieve neutropenia, and 8 ( 36. 4% ) patients received component blood transfusion to treat anemia or thrombocytopenia. There was no treatment-associated death. Conclusion Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.展开更多
Broccoli sprout (BS) supplements have been marketed for over a decade for the promising health beneficial effects of sulforaphane (SFN), which induces Nrf2 signaling and downstream chemoprotective genes, including pha...Broccoli sprout (BS) supplements have been marketed for over a decade for the promising health beneficial effects of sulforaphane (SFN), which induces Nrf2 signaling and downstream chemoprotective genes, including phase 2 enzymes. Most commercially available BS supplements encapsulate heat-processed BS containing glucoraphanin (GR), which is hydrolyzed to SFN by the intestinal microbiota. However, the absorption behavior of SFN following the intake of such BS supplements is still unclear. Additionally, the GR dose (around 30 mg) recommended by many manufacturers of BS supplements is relatively lower than the effective dose determined in previous intervention studies. The aims of this study were to assess the effects of a single administration of a typical BS supplement containing lower doses of GR (30 or 60 mg from 3 or 6 capsules, respectively) on SFN absorption, and also to assess the serum activities of phase 2 enzymes as possible surrogate markers of the beneficial effects of SFN. Urinary excreted isothiocyanates and dithiocarbamates showed that the SFN absorption following administration of BS supplement was prolonged and varied among individuals, which conforms to the well-known characteristics of intestinal microbiota-mediated SFN absorption. The amount of SFN absorbed increased dose-dependently but not linear fashion (9.27 μmol and 13.5 μmol for 3 and 6 capsules, respectively). There was no significant difference in SFN bioavailability and the number of capsules consumed. Serum activities of phase 2 enzymes glutathione S-transferase (GST) and NAD(P)H: quinone oxidoreductase 1 (NQO1), which have been reported to display “chemoprotected states” in organs such as the liver, were dose-dependently and synchronously elevated (p < 0.05) following BS supplement intake. This suggests that a low dose of GR (30 mg) exerts chemoprotective effects in humans. In conclusion, our findings will be useful in future clinical studies investigating the chemoprotective effects of SFN, and for the development of BS supplement products.展开更多
This article mainly describes the self-reliance and innovation of Qinshan nuclear power project of phase II,in-between it contains new reactor core design,as well as related experimental and calculation analysis,espec...This article mainly describes the self-reliance and innovation of Qinshan nuclear power project of phase II,in-between it contains new reactor core design,as well as related experimental and calculation analysis,especially for new reactor design produced fluid-induced vibration model test,theoretical analysis and testing in-built reactor;aiming at two-loop NSSS a series improvement made for safety systems and related safety analysis to enhance their reliability and redundancy;according to specialty of two-loop NSSS an optimization made for NPP parameters and design of related equipments,for the purpose to make the output of NPP maximal;design of main reactor building and T-G building also improved according to characteristics of two-loop NSSS and site conditions.CRDM and refueling machine are researched and manufactured on base of self-reliance,their performance are better than design requirements,large portion of key equipments are localized through different way.In construction first time realized the integrated erection of containment dome.During the commissioning non-nuclear steam driving of T-G set,as well as 500 kV high voltage rising using emergent diesel generator,etc.are carried out.In period of operation still continuous innovation and improvement are made,so that to keep the good record of operation.展开更多
A new method for determination of Cu(Ⅱ) by DDCT chelating resin preconcentration and thin layer resin phase spectrophotometry was developed. The method has a high sensitivity (ε455= 3.6×10^5L/mol·cm), ...A new method for determination of Cu(Ⅱ) by DDCT chelating resin preconcentration and thin layer resin phase spectrophotometry was developed. The method has a high sensitivity (ε455= 3.6×10^5L/mol·cm), which is 33 times higher than that of liquid phase spectrophotometry. It has a good selectivity (most coexisting ions could not influence determination) and an ideal precision [30μg Cu(Ⅱ), n=6, RSD= l.67%]. The content of Cu(Ⅱ) in water, high purity rare earth and its oxide was determined. The detection limit of Cu(Ⅱ) is 5.3μg/L , and the linear range is 0-7.2μg/ml. The result is satisfactory.展开更多
Changes in the bacterial communities inhabiting Agaricus bisporus compost during Phase Ⅱ treatment were monitored using amplified rDNA restriction analysis(ARDRA).Sequence analysis data indicated that the bacterial c...Changes in the bacterial communities inhabiting Agaricus bisporus compost during Phase Ⅱ treatment were monitored using amplified rDNA restriction analysis(ARDRA).Sequence analysis data indicated that the bacterial communities associated with the compost samples were far richer in composition when determined by ARDRA compared with traditional methods based on bacterial isolation.Furthermore,the composition of the communities,especially in terms of the dominant bacteria during each of the four treatment stages(beginning of Phase Ⅱ,after pasteurization,5 days aeration,end of Phase Ⅱ,respectively),were very different.Restriction endonuclease digestion of mainly bacterial clones from four 16S rDNA libraries,C1,C3,C6 and C7,previously constructed on the basis of 16S rDNA fragments amplified from the four different stages of the Phase Ⅱ composting process,revealed the presence of unique microbial types.Thermophilic bacteria belonging to the Bacilli,and previously unreported strains of Trichococcus,Planococcus,Caryophanon,and subclass γ-Proteobacteria,were identified among the clones from the compost sampled during the aeration period(C6).Bacteria belonging to Thermus thermophilus and subclass α-Proteobacteria were detected in C1 and C7 composts sampled at the beginning and the end of Phase Ⅱ,respectively.Clones of some uncultured bacteria were also scored.展开更多
文摘Aim To investigate the effect of curcumin on induction of glutathione S-transferases (GST), NADP(H):quinone oxidoreductase (NQO) and explore their possible molecular mechanism. Methods The activity of GST, NQO and cellular reduced glutathione (GSH) content were measured by spectrophotometrical methods. Cellular changes in the distribution of NF-E2 related factor 2 (Nrf2) was detected by western blotting analysis. Nrf2-AREs (antioxidant-responsive elements) binding activity was examined by electrophoretic mobility shift assay (EMSA). Results Curcumin caused a significant increase in GST and NQO activity, with a maximal value being observed at 20, 25 μmol/L, respectively. At concentration higher than 30 μmol/L, curcumin appeared to be less effective in stimulating GST and NQO activity. Treatment of HT-29 with curcumin caused a modest increase in the cellular GSH content at 3 h (P<0.05). All concentrations of curcumin continued to increase GSH content during the next 9 h. No significant change in the GSH content was observed at either 1 or 2 h after curcumin exposure. Upon treatment of cells with 20 μmol/L curcumin, Nrf2 protein accumulated rapidly (3 h) in the nucleus. This data suggested that curcumin mediate an increase of Nrf2 in the nuclear, a common component of ARE binding complexes. The retarded Nrf2-AREs complexes progressively formed upon treatment with curcumin at the concentration of 20 μmol/L for indicated time. Conclusion These results demonstrated that induction of GST and NQO activity by curcumin may be mediated by translocation of transcription factor Nrf2 from cytoplasm to nuclear and increased binding activity of Nrf2-ARE complexes.It is possible that this effect efficiently protects cells from oxidative stress and should be evaluated as a new therapeutic approach in oxidative stress-mediated damage.
文摘To explore the relation of angiotensin-converting enzyme (ACE) and angiotensin Ⅱ type 1 receptor (AT1R) gene polymorphism with coronary heart disease (CHD) and the severity of coronary artery stenosis, 130 CHD patients who underwent coronary angiography were examined for the number of affected coronary vessels (≥75% stenosis) and coronary Jeopardy score. The insertion/deletion of ACE gene polymorphism and AT1R gene polymorphism (an A→C transversion at nucleotide position 1166) were detected by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) in CHD patients and 90 healthy serving as controls. The resuits showed that DD genotype and of ACE were more frequent in CHD patients than that in control group (38.5% vs 14.4%, P〈0.001). The frequency of the ATIR A/C genotypes did not differ between the patients and the controls (10% vs 13.1%, P〉0.05). The relative risk associated with the ACE-DD was increased by AT1R-AC genotype. Neither the number of affected coronary vessels nor the coronary score differed among the ACE I/D genotypes (P〉0.05). But the number of affected coronary vessels and the coronary score were significantly greater in the patients with the AT1R-AC genotype than in those with the AA genotype (P〈0.05). In conclusion, DD genotype may be risk factor for CHD and MI in Chinese people, and is not responsible for the development of the coronary artery stenosis. The AT1R-C allele may increase the relative risk associated with the ACE-DD genotype, and may be involved in the development of the stenosis of coronary artery.
文摘Objective The increasing recognition of the role for oxidative stress in hepatic disorders has led to extensive investigation on the protection by exogenous antioxidants against hepatic injury.In this study,we choose two typical polyphenol,quercetin and rutin,to investigate the mechanism of induction of cellular antioxidants and phase 2 enzymes in human HepG2 cells.Methods The HepG2 cells were treated with various concentrations of quercetin and rutin for 6 h and 24 h.The activities of NAD(P)H:quinone oxidoreductase(NQO1)in HepG2 cells were measured by 2,6-dichloroindophenol reduction method.The content of superoxide dismutase(SOD)was determined with the method of chemical colorimetry.The protein expressions of NQO1 and NF-E2-related factor 2(Nrf2)in HepG2 cells were detected by Western blotting.Results Incubation of HepG2 cells with quercetin and rutin resulted in a marked concentration-and time-dependent induction of a number of cellular antioxidants and phase 2 enzymes,including NQO1,SOD.Quercetin and rutin treatment of HepG2 cells also caused increase in protein expressions of NQO1 and Nrf2.Conclusions This study demonstrates that a series of phase 2 enzymes in HepG2 cells can be induced by quercetin and rutin in a concentration-and time-dependent fashion by upregulation the protein expression of nrf2.
基金Supported by the National Natural Science Foundation of China andExtraction Separation branch of United Chemical Engineeing
文摘The synthesis of dipeptide AcPheLeuNH2 catalyzed by immobilized pancreatic lipase was carried out in a two- liquid-phase hollow-fiber membrane reactor, operated in a batch mode. Kinetic properties of free and immobilized enzyme, partition behavior between aqueous buffer phase and organic solvent phase, and effective diffusion coefficients of substrates and products through the membrane were investigated respectively. Based on the preliminary experimental results, the performance of the enzyme membrane reactor, which is evaluated by the purity and the yield, is discussed.
文摘Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In an earlier phase I study, a novel form of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) that is currently in clinical development for the treatment of hematologic malignancies, i.e., circularly permuted TRAIL(CPT), was well tolerated at a dose of 2.5 mg/kg per day and showed promising preliminary activity in patients with RRMM. This phase II, open-label, multicenter study further investigated the eicacy and safety of 2.5-mg/kg per day CPT as single-agent therapy for patients with RRMM.Methods: Patients with RRMM were treated once daily with CPT(2.5 mg/kg, intravenously) for 14 consecutive days for each 21-day cycle. Clinical response and toxicity were assessed after each treatment cycle.Results: Twenty-seven patients received CPT. Using the European Group for Blood and Marrow Transplantation criteria, we calculated the overall response rate of 33.3% with 1 near-complete response(n CR) and 8 partial responses(PRs). The clinical beneit rate(48.1%) included 1 nCR, 8 PRs, and 4 minimal responses. The most common treatmentrelated adverse events(TRAEs) were fever, aspartate aminotransferase elevation, alanine aminotransferase elevation, leucopenia, rash, neutropenia, and thrombocytopenia. We graded toxicity using the Common Toxicity Criteria for Adverse Events, version 3.0, and determined that 37.0% of patients had at least 1 grade 3–4 TRAE.Conclusions: CPT as a single agent can elicit a response in patients with RRMM and is well tolerated. Further clinical investigation is warranted.
基金Supported by CNPq,No.460334/2014-0FAPEMIG,No.CDS-PPM-00555-15(to Simoes e Silva AC)2016 NARSAD Young Investigator Grant Awardee from the Brain and Behavior Research Foundation,No.25414(to Miranda AS)
文摘The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues,including the liver,pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme(ACE)-angiotensin(Ang) Ⅱ-Ang type 1(AT1) receptor mediates pro-inflammatory,pro-thrombotic,and pro-fibrotic processes. On the other hand,the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang Ⅱ action. Chronic hepatitis B(CHB) is one of the leading causes of liver fibrosis,accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However,the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36 th issue of the World Journal of Gastroenterology,Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate,non-invasive,widely available,and easy method to evaluate fibrosis related to CHB. Moreover,therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis.
文摘AIM To evaluate the efficacy and safety of modified FOLFIRINOX as a second-line treatment for gemcitabine(GEM)-refractory unresectable pancreatic cancer(PC).METHODS This study was a prospective, multicenter, one-arm, open-label, phase Ⅱ trial. Patients with unresectable PC, who showed disease progression during GEMbased chemotherapy were enrolled. All patients were administered FOLFIRINOX with reduced irinotecan and oxaliplatin(RIO; irinotecan 120 mg/m^2 and oxaliplatin 60 mg/m^2), which was set according to the phase Ⅰ study of FOLFIRINOX. The objective response rate(ORR), disease control rate(DCR), progressionfree survival(PFS), overall survival(OS), adverse events were evaluated. Additionally, changes in quality of life(QoL) were assessed using a questionnaire on QoL.RESULTS Between August 2015 and May 2016, a total of 48 patients were enrolled. The median follow-up time was 259 d with a median of 8.5 cycles. The ORR and DCR were 18.8% and 62.5%, respectively, including one patient who showed complete remission. The median PFS was 5.8 mo [95% confidence interval(CI): 3.7-7.9] and median OS was 9.0 mo(95%CI: 6.4-11.6). Neutropenia(64.6%) was the most common grade 3-4 adverse event, followed by febrile neutropenia(16.7%). Although 14.6% of patients experienced grade 3 fatigue, most non-hematologic AEs were under grade 2. In the QoL analysis, the global health status score before treatment was not different from the score at the last visit after treatment(45.43 ± 22.88 vs 48.66 ± 24.14, P = 0.548).CONCLUSION FOLFIRINOX with RIO showed acceptable toxicity and promising efficacy for GEM-refractory unresectable PC. However, this treatment requires careful observation of treatment-related hematologic toxicities.
文摘Human urotension-Ⅱ was synthesized efficiently on Wang resin under microwave irradiation using Fmoc/tBu orthogonal protection strategy. Disulphide bridge was formed on solid phase with the irradiation of microwave, then the whole peptide was cleaved from the resin. The purity of crude peptide cyclized under microwave irradiation was higher than that under room temperature.
基金Project(07JJ6020) supported by the Hunan Provincial Natural Science Foundation of ChinaProject(2007-24-3) supported by the Huaihua Key Science and Technology Program, China
文摘Iron(Ⅱ) tetrasulfophthalocyanine(FeTSPc) ,as a novel mimetic enzyme of peroxidase,was used in the synthesis of a conducting polyaniline(PANI) /sodium dodecylsulfate(SDS) complex in SDS aqueous micellar solutions. The effects of pH,concentrations of aniline,SDS and H2O2,and reaction time on polymerization of aniline were studied in this case as shown by UV-Vis absorption spectroscopy. The results show that a wide range of pH(0.5-4.0) is required to produce the conducting PANI,and the optimal pH is 1.0 in SDS micelle. The optimal concentrations of aniline,SDS and H2O2 in feed,and reaction time in this case for the production of conducting PANI are respectively 10 mmol/L,10 mmol/L,25 mmol/L,and 15 h. FT-IR spectrum,elemental analysis,conductivity,cyclic voltammetry and thermogravimetric analysis confirm the thermal stability and electroactive form of PANI.
文摘Objective To evaluate the anti-tumor effect and toxicity of gemcitabine combined with platinum chemotherapy on recurrent epithelial ovarian cancer. Methods Phase Ⅱ study of gemcitabine combined with platinum chemotherapy was carried out in 22 patients with recurrent epithelial ovarian cancer. Median age of patients was 50. 5 years old. Seven patients were platinum-sensitive and 15 patients were platinum-resistant or -refractory. All patients received gemcitabine combined with carboplatin or oxa/iplatin chemotherapy. Patients' response rate (RR) and toxicity of gemcitabine combined with platinum chemotherapy were evaluated. Results A total of 98 gemcitabine-based chemotherapy cycles were performed. Total RR was 36. 4%, RR of platinum-sensitive patients was 4/7 and platinum-resistant and -refractory patients was 4/15. The estimated median survival time was 10.0 months (95% CI. 7.0-13.0) after initiation of gemcitabine combined with platinum chemotherapy. There was no significant difference in survival time between platinum-resistant/refractory group and platinum-sensitive group (P = 0. 061 ). Side effects of gemcitabine combined with platinum chemotherapy were observed in 81.8% of patients. Grade Ⅱ/Ⅲ anemia (54. 5% ) and grade Ⅲ/Ⅳ neutropenia (54. 5% ) were most common toxicities. Ten (45.5%) patients had to delay their chemotherapy cycles or reduce the dose of chemotherapeutic drugs because of the severe side effects. Fourteen (63.6%) patients received granulocyte colony-stimulating factor to relieve neutropenia, and 8 ( 36. 4% ) patients received component blood transfusion to treat anemia or thrombocytopenia. There was no treatment-associated death. Conclusion Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.
文摘Broccoli sprout (BS) supplements have been marketed for over a decade for the promising health beneficial effects of sulforaphane (SFN), which induces Nrf2 signaling and downstream chemoprotective genes, including phase 2 enzymes. Most commercially available BS supplements encapsulate heat-processed BS containing glucoraphanin (GR), which is hydrolyzed to SFN by the intestinal microbiota. However, the absorption behavior of SFN following the intake of such BS supplements is still unclear. Additionally, the GR dose (around 30 mg) recommended by many manufacturers of BS supplements is relatively lower than the effective dose determined in previous intervention studies. The aims of this study were to assess the effects of a single administration of a typical BS supplement containing lower doses of GR (30 or 60 mg from 3 or 6 capsules, respectively) on SFN absorption, and also to assess the serum activities of phase 2 enzymes as possible surrogate markers of the beneficial effects of SFN. Urinary excreted isothiocyanates and dithiocarbamates showed that the SFN absorption following administration of BS supplement was prolonged and varied among individuals, which conforms to the well-known characteristics of intestinal microbiota-mediated SFN absorption. The amount of SFN absorbed increased dose-dependently but not linear fashion (9.27 μmol and 13.5 μmol for 3 and 6 capsules, respectively). There was no significant difference in SFN bioavailability and the number of capsules consumed. Serum activities of phase 2 enzymes glutathione S-transferase (GST) and NAD(P)H: quinone oxidoreductase 1 (NQO1), which have been reported to display “chemoprotected states” in organs such as the liver, were dose-dependently and synchronously elevated (p < 0.05) following BS supplement intake. This suggests that a low dose of GR (30 mg) exerts chemoprotective effects in humans. In conclusion, our findings will be useful in future clinical studies investigating the chemoprotective effects of SFN, and for the development of BS supplement products.
文摘This article mainly describes the self-reliance and innovation of Qinshan nuclear power project of phase II,in-between it contains new reactor core design,as well as related experimental and calculation analysis,especially for new reactor design produced fluid-induced vibration model test,theoretical analysis and testing in-built reactor;aiming at two-loop NSSS a series improvement made for safety systems and related safety analysis to enhance their reliability and redundancy;according to specialty of two-loop NSSS an optimization made for NPP parameters and design of related equipments,for the purpose to make the output of NPP maximal;design of main reactor building and T-G building also improved according to characteristics of two-loop NSSS and site conditions.CRDM and refueling machine are researched and manufactured on base of self-reliance,their performance are better than design requirements,large portion of key equipments are localized through different way.In construction first time realized the integrated erection of containment dome.During the commissioning non-nuclear steam driving of T-G set,as well as 500 kV high voltage rising using emergent diesel generator,etc.are carried out.In period of operation still continuous innovation and improvement are made,so that to keep the good record of operation.
文摘A new method for determination of Cu(Ⅱ) by DDCT chelating resin preconcentration and thin layer resin phase spectrophotometry was developed. The method has a high sensitivity (ε455= 3.6×10^5L/mol·cm), which is 33 times higher than that of liquid phase spectrophotometry. It has a good selectivity (most coexisting ions could not influence determination) and an ideal precision [30μg Cu(Ⅱ), n=6, RSD= l.67%]. The content of Cu(Ⅱ) in water, high purity rare earth and its oxide was determined. The detection limit of Cu(Ⅱ) is 5.3μg/L , and the linear range is 0-7.2μg/ml. The result is satisfactory.
基金Supported by project of China Agricultural Ministry(No.nyhyzx-07-008)
文摘Changes in the bacterial communities inhabiting Agaricus bisporus compost during Phase Ⅱ treatment were monitored using amplified rDNA restriction analysis(ARDRA).Sequence analysis data indicated that the bacterial communities associated with the compost samples were far richer in composition when determined by ARDRA compared with traditional methods based on bacterial isolation.Furthermore,the composition of the communities,especially in terms of the dominant bacteria during each of the four treatment stages(beginning of Phase Ⅱ,after pasteurization,5 days aeration,end of Phase Ⅱ,respectively),were very different.Restriction endonuclease digestion of mainly bacterial clones from four 16S rDNA libraries,C1,C3,C6 and C7,previously constructed on the basis of 16S rDNA fragments amplified from the four different stages of the Phase Ⅱ composting process,revealed the presence of unique microbial types.Thermophilic bacteria belonging to the Bacilli,and previously unreported strains of Trichococcus,Planococcus,Caryophanon,and subclass γ-Proteobacteria,were identified among the clones from the compost sampled during the aeration period(C6).Bacteria belonging to Thermus thermophilus and subclass α-Proteobacteria were detected in C1 and C7 composts sampled at the beginning and the end of Phase Ⅱ,respectively.Clones of some uncultured bacteria were also scored.