Dear Editor,Ferroptosis,an iron-dependent form of cell death driven by overwhelming lipid peroxidation,represents a vulnerability in cancers,and therapeutic strategies to further potentiate ferroptosis hold great pote...Dear Editor,Ferroptosis,an iron-dependent form of cell death driven by overwhelming lipid peroxidation,represents a vulnerability in cancers,and therapeutic strategies to further potentiate ferroptosis hold great potential for melanoma treatment.展开更多
Quantitative structure activity relationship （QSAR） studies were performed on 45 anthranilic acid derivatives for their potent allosteric inhibition activities of HCV NSSB polymerase. Genetic algorithm based genetic...Quantitative structure activity relationship （QSAR） studies were performed on 45 anthranilic acid derivatives for their potent allosteric inhibition activities of HCV NSSB polymerase. Genetic algorithm based genetic function approximation （GFA） method of variable selection was used to generate the model. Highly statistically significant model with r^2 = 0.966 and r^2cv = 0.951 was obtained when the number of descriptors in the equation was set to 5. High r^2pred value of 0.884 indicates the good predictive power of the best model. Spatial descriptors of radius of gyration （RadOfGration）, molecular volume （Vm）, length of molecule in the z dimension （Shadow-Zlength）, thermodynamic descriptors of the octanol/water partition coefficient （LogP） and molecular refractivity index （MR） showed enormous contributions to HCV NS5B polymerase inhibition. The validation of the model was done by leave-one-out （LOO） test, randomization tests and external test set prediction. The model gives insight on indispensable structural requirements for the activity and can be used to design more potent analogs against HCV NSSB polymerase.展开更多
A serials of novel 5-substituted benzyl-2,4-diamino pyrimidine derivatives have been synthesized and evaluated as inhibitors of c-Fms kinase by the standard MTT method.The results showed that compound 15,5-[3-methoxy...A serials of novel 5-substituted benzyl-2,4-diamino pyrimidine derivatives have been synthesized and evaluated as inhibitors of c-Fms kinase by the standard MTT method.The results showed that compound 15,5-[3-methoxy-4-（pyridine-3-yl）benzyl]-2,4-diamino pyrimidine,had an IC50 of 1.45μmol/L in inhibiting the proliferation of M-CSF-dependent myeloid leukemia cells in mice （NFS-60）,which was similar with GW2580,a selective inhibitor of c-Fms kinase.展开更多
Objectives: To evaluate the influence of meals on the pharmacokinetics of omeprazole and rabeprazole and to investigate these PPIs with reference to CYP2C19 genotypes in healthy Japanese men. Methods: This was a rando...Objectives: To evaluate the influence of meals on the pharmacokinetics of omeprazole and rabeprazole and to investigate these PPIs with reference to CYP2C19 genotypes in healthy Japanese men. Methods: This was a randomized, open label, four-way crossover study. Twelve healthy Japanese male volunteers received a single oral dose of either 20 mg omeprazole or 10 mg rabeprazole, in the fasted state and after a standardized breakfast. Results: Between the administration of omeprazole in the fasted state and after breakfast, there were no significant differences in Cmax, AUC, Tmax, and half-life. Between the administration of rabeprazole in the fasted state and after breakfast, there were no significant differences in Cmax, AUC and half-life, whereas the Tmax of rabeprazole after breakfast was significantly delayed (2.8 ± 1.0 vs 5.3 ± 1.8 h, respectively;p = 0.006). PMs demonstrated the highest Cmax and AUC after drug intake under the fasting state and after breakfast, and homo EMs showed a significantly delayed Tmax. Conclusion: When a single dose of either PPI was administered, the pharmacokinetics of omeprazole was not affected by the meal, whereas the Tmax of rabeprazole after the meal was significantly delayed.展开更多
Objective:To explore the new treatment strategies for radiation proctitis,which is the most common complication of pelvic tumor malignancies.Methods:Four cases of patients with severe radiation proctitis were treated ...Objective:To explore the new treatment strategies for radiation proctitis,which is the most common complication of pelvic tumor malignancies.Methods:Four cases of patients with severe radiation proctitis were treated with high-dosage vitamin C(VC,12–24 g/d,iv)combined with cyclooxygenase-2(cyclooxygenase-2,COX-2)inhibitors.Results:For these four cases,the diarrhea,hematochezia,tenesmus,pain,and other symptoms were significantly improved.The edema of the rectal wall is also significantly improved in the imaging review.Conclusion:The high-dosage VC combined with the treatment of severe radiation proctitis is safe and effective.展开更多
AIM: To evaluate the effect of first line esomeprazole(EPZ)-based triple therapy on Helicobacter pylori(H. pylori) eradication.METHODS: A total of 80 Japanese patients with gastritis who were diagnosed as positive for...AIM: To evaluate the effect of first line esomeprazole(EPZ)-based triple therapy on Helicobacter pylori(H. pylori) eradication.METHODS: A total of 80 Japanese patients with gastritis who were diagnosed as positive for H. pylori infection by endoscopic biopsy-based or ^(13)C-urea breath tests were included in this study. The average age of the patients was 57.2 years(male/female, 42/38). These patients were treated by first-line eradication therapy with EPZ 40 mg/d, amoxicillin 1500 mg/d, and clarithromycin 400 mg/d for 7 d. All drugs were given twice per day. Correlations between H. pylori eradication, CYP2C19 genotype, and serum pepsinogen(PG) level were analyzed. This study was registered with the UMIN Clinical Trials Registry(UMIN000009642).RESULTS: The H. pylori eradication rates by EPZbased triple therapy evaluated by intention-to-treat and per protocol were 67.5% and 68.4%, respectively, which were similar to triple therapies with other first-generation proton pump inhibitors(PPIs). The eradication rates in three different CYP2C19 genotypes, described as extensive metabolizer(EM), intermediate metabolizer, and poor metabolizer, were 52.2%, 72.1%, and 84.6%, respectively. The H. pylori eradication rate was significantly lower in EM than non-EM(P < 0.05). The serum PG?Ⅰ?level and PG?Ⅰ/Ⅱ ratio were significantly increased after eradication of H. pylori(P < 0.01), suggesting that gastric atrophy was improved by H. pylori eradication. Thus, first-line eradication by EPZbased triple therapy for patients with H. pylori-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was on the same level with other firstgeneration PPIs in the Japanese population.CONCLUSION: The results from this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication compared to other firstgeneration PPIs.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(82103183,82102803,82272849)the Natural Science Foundation of Hunan Province(2022JJ40767,2021JJ40976)+1 种基金the Natural Science Fund for Outstanding Youths in Hunan Province(2023JJ20093)the National Key Research and Development Program(2022YFC2504700).
文摘Dear Editor,Ferroptosis,an iron-dependent form of cell death driven by overwhelming lipid peroxidation,represents a vulnerability in cancers,and therapeutic strategies to further potentiate ferroptosis hold great potential for melanoma treatment.
基金supported by the National Natural Science Foundation of China (No. 30500339)Natural Science Foundation of Zhejiang Province (NO.Y407308)the Sprout Talented Project Program of Zhejiang Province (No. 2008R40G2020019)
文摘Quantitative structure activity relationship （QSAR） studies were performed on 45 anthranilic acid derivatives for their potent allosteric inhibition activities of HCV NSSB polymerase. Genetic algorithm based genetic function approximation （GFA） method of variable selection was used to generate the model. Highly statistically significant model with r^2 = 0.966 and r^2cv = 0.951 was obtained when the number of descriptors in the equation was set to 5. High r^2pred value of 0.884 indicates the good predictive power of the best model. Spatial descriptors of radius of gyration （RadOfGration）, molecular volume （Vm）, length of molecule in the z dimension （Shadow-Zlength）, thermodynamic descriptors of the octanol/water partition coefficient （LogP） and molecular refractivity index （MR） showed enormous contributions to HCV NS5B polymerase inhibition. The validation of the model was done by leave-one-out （LOO） test, randomization tests and external test set prediction. The model gives insight on indispensable structural requirements for the activity and can be used to design more potent analogs against HCV NSSB polymerase.
基金financially supported by the National High-Tech Research and Development Program of China(863 Program)(No.2006AA10A201)National Natural Science Foundation(No.30472093)
文摘A serials of novel 5-substituted benzyl-2,4-diamino pyrimidine derivatives have been synthesized and evaluated as inhibitors of c-Fms kinase by the standard MTT method.The results showed that compound 15,5-[3-methoxy-4-（pyridine-3-yl）benzyl]-2,4-diamino pyrimidine,had an IC50 of 1.45μmol/L in inhibiting the proliferation of M-CSF-dependent myeloid leukemia cells in mice （NFS-60）,which was similar with GW2580,a selective inhibitor of c-Fms kinase.
文摘Objectives: To evaluate the influence of meals on the pharmacokinetics of omeprazole and rabeprazole and to investigate these PPIs with reference to CYP2C19 genotypes in healthy Japanese men. Methods: This was a randomized, open label, four-way crossover study. Twelve healthy Japanese male volunteers received a single oral dose of either 20 mg omeprazole or 10 mg rabeprazole, in the fasted state and after a standardized breakfast. Results: Between the administration of omeprazole in the fasted state and after breakfast, there were no significant differences in Cmax, AUC, Tmax, and half-life. Between the administration of rabeprazole in the fasted state and after breakfast, there were no significant differences in Cmax, AUC and half-life, whereas the Tmax of rabeprazole after breakfast was significantly delayed (2.8 ± 1.0 vs 5.3 ± 1.8 h, respectively;p = 0.006). PMs demonstrated the highest Cmax and AUC after drug intake under the fasting state and after breakfast, and homo EMs showed a significantly delayed Tmax. Conclusion: When a single dose of either PPI was administered, the pharmacokinetics of omeprazole was not affected by the meal, whereas the Tmax of rabeprazole after the meal was significantly delayed.
基金Leading Discipline Construction Support Project(Oncology),Zhongnan Hospital of Wuhan University(XKJS202005),China.
文摘Objective:To explore the new treatment strategies for radiation proctitis,which is the most common complication of pelvic tumor malignancies.Methods:Four cases of patients with severe radiation proctitis were treated with high-dosage vitamin C(VC,12–24 g/d,iv)combined with cyclooxygenase-2(cyclooxygenase-2,COX-2)inhibitors.Results:For these four cases,the diarrhea,hematochezia,tenesmus,pain,and other symptoms were significantly improved.The edema of the rectal wall is also significantly improved in the imaging review.Conclusion:The high-dosage VC combined with the treatment of severe radiation proctitis is safe and effective.
基金Supported by Research Grant of Kitasato Institute Hospital
文摘AIM: To evaluate the effect of first line esomeprazole(EPZ)-based triple therapy on Helicobacter pylori(H. pylori) eradication.METHODS: A total of 80 Japanese patients with gastritis who were diagnosed as positive for H. pylori infection by endoscopic biopsy-based or ^(13)C-urea breath tests were included in this study. The average age of the patients was 57.2 years(male/female, 42/38). These patients were treated by first-line eradication therapy with EPZ 40 mg/d, amoxicillin 1500 mg/d, and clarithromycin 400 mg/d for 7 d. All drugs were given twice per day. Correlations between H. pylori eradication, CYP2C19 genotype, and serum pepsinogen(PG) level were analyzed. This study was registered with the UMIN Clinical Trials Registry(UMIN000009642).RESULTS: The H. pylori eradication rates by EPZbased triple therapy evaluated by intention-to-treat and per protocol were 67.5% and 68.4%, respectively, which were similar to triple therapies with other first-generation proton pump inhibitors(PPIs). The eradication rates in three different CYP2C19 genotypes, described as extensive metabolizer(EM), intermediate metabolizer, and poor metabolizer, were 52.2%, 72.1%, and 84.6%, respectively. The H. pylori eradication rate was significantly lower in EM than non-EM(P < 0.05). The serum PG?Ⅰ?level and PG?Ⅰ/Ⅱ ratio were significantly increased after eradication of H. pylori(P < 0.01), suggesting that gastric atrophy was improved by H. pylori eradication. Thus, first-line eradication by EPZbased triple therapy for patients with H. pylori-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was on the same level with other firstgeneration PPIs in the Japanese population.CONCLUSION: The results from this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication compared to other firstgeneration PPIs.
