It is first demonstrated that dipyridamole (DP) and radiation were capable of significantly inhibiting, independently and synerglcally, clonogenlc growth in the two kinds of K562 cell lines, adriamycin (ADM) -sensitiv...It is first demonstrated that dipyridamole (DP) and radiation were capable of significantly inhibiting, independently and synerglcally, clonogenlc growth in the two kinds of K562 cell lines, adriamycin (ADM) -sensitive and ADM- resistant. DP or radiation alone Increased clonogenlc Inhibition rate (CIR) in the two kinds of cell lines in a dose- dependent fashion. DP potentiated radiosensitivity and radiation increased inhibition of DP in the two kinds of cell lines. K562/ ADM cell lines were higher sensitive to DP. radiation and combination of them than K562 cell lines (P【0. 01). There was stronger synergic inhibition of clonogenlc growth in the two kinds of cell lines when pretreated with DP than when posttreated with DP (P【0. 01).展开更多
Objective: It was known that neutrophils play an important role in ischemic-reperfusion injury. In this study we tested the effect and its mechanism of dipyridamole on neutrophils. Methods:Hydrogen peroxide(H2O2) prod...Objective: It was known that neutrophils play an important role in ischemic-reperfusion injury. In this study we tested the effect and its mechanism of dipyridamole on neutrophils. Methods:Hydrogen peroxide(H2O2) production by neutrophils was determined using luminol amplified chemiluminescence and the percentage of activity was calculated by observing the uninhibited peak height. Results: Dipyridamole per se produced a concentration-dependent inhibition of H2O2 by formyl-MetleuPhe(fMLP)-stimulated neutrophils. Dipy-ridamole at a low concentration(0.3μmol·L-1) that per se affected neutrophils only slightly, enhanced markedly the effects of adenosine on neutrophils. On the other hand, dipyridamole did not alter the inhibitory effect of NECA(5'-N-ethylcarboxamidoadenosine) on neutrophils. However, propentofylline, a known inhibitor of adenosine uptake, also gotten the same result. Conclusion:Dipy-ridamole inhibited the production of H2O2 by fMLP-stimulated neutrophils. Dipyridamole at a low concentration enhanced the inhibi-tory effect of adenosine on neutrophils. The mechanism involved is probably due to the effect of dipyridamole on adenosine uptake.展开更多
Using dipyridamole stress test to evaluate cerebral blood flow reserve in cerebrovascular disease (CVD). Dipyridamole stress tests were performed first, the baseline SPECT images were obtained under similar conditions...Using dipyridamole stress test to evaluate cerebral blood flow reserve in cerebrovascular disease (CVD). Dipyridamole stress tests were performed first, the baseline SPECT images were obtained under similar conditions 2-5 days later. By visual and semiquantitative analysis, the responses of cerebral blood flow to dipyridamole were divided into the following four patterns: A: The dipyridamole SPECT showed an expanded area of hypoperfusion, Asymmetry Index(AI) and Uptake Rate(UR) were all decreased; B: Rest images was normal but new hypoperfused areas appeared on stress test with decreased Al and UR; C: Hypoperfused areas were decreased in size or disappeared after stress test with increased Al and UR; D: No changes showed in cerebral perfusion imaging patterns, and in Al and UR between stress and rest studies. Dipyridarnole brain perfusion imaging may be helpful to the diagnosis of CVD, to the decision the therapeutic plan, and to predicting the therapeutic effect.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical pro...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis.In an analysis of a randomly collected cohort of 124 patients with COVID-19,we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity.By virtual screening of a U.S.FDA approved drug library,we identified an anticoagulation agent dipyridamole(DIP)in silico,which suppressed SARS-CoV-2 replication in vitro.In a proof-of-concept trial involving 31 patients with COVID-19,DIP supplementation was associated with significantly decreased concentrations of D-dimers(P<0.05),increased lymphocyte and platelet recovery in the circulation,and markedly improved clinical outcomes in comparison to the control patients.In particular,all 8 of the DIP-treated severely ill patients showed remarkable improvement:7 patients(87.5%)achieved clinical cure and were discharged from the hospitals while the remaining 1 patient(12.5%)was in clinical remission.展开更多
目的探讨低分子肝素钙/磺达肝癸钠序贯联合双嘧达莫预防性抗凝在原发性肾病综合征(PNS)中的应用效果及安全性。方法回顾性选取2020年3月至2022年12月期间四川省凉山彝族自治州第一人民医院收治的188例PNS患者,根据肾穿刺活检病理结果及...目的探讨低分子肝素钙/磺达肝癸钠序贯联合双嘧达莫预防性抗凝在原发性肾病综合征(PNS)中的应用效果及安全性。方法回顾性选取2020年3月至2022年12月期间四川省凉山彝族自治州第一人民医院收治的188例PNS患者,根据肾穿刺活检病理结果及磷脂酶A2受体抗体分为膜性肾病组(n=73)与非膜性肾病组(n=115)。两组患者均根据血清白蛋白水平,采用低分子肝素钙或磺达肝癸钠序贯联合双嘧达莫抗凝。比较两组患者治疗前及治疗后4周、治疗后6个月的肾功能指标[白蛋白、尿素氮、血肌酐、肾小球滤过率(eGFR)和24 h尿蛋白定量(24 h PRO)],治疗前及治疗后4周的血栓弹力图指标[反应指数(R时间)、凝血时间(K时间)、血栓最大弹力度(MA)、凝血指数(CI)和α角],以及随访6个月记录血栓事件、出血事件。结果治疗后4周、6个月,两组的白蛋白、eGFR均较治疗前明显升高,尿素氮、血肌酐、24 h PRO均较治疗前明显降低,差异均有统计学意义(P<0.05),但两组治疗后各肾功能指标比较,差异均无统计学意义(P>0.05)。治疗后4周,两组患者的R时间、K时间均较治疗前明显延长,MA、CI值和α角均较治疗前明显降低,差异均有统计学意义(P<0.05),但两组患者治疗后4周的R时间、K时间、MA、CI值和α角比较,差异均无统计学意义(P>0.05)。膜性肾病组患者的血栓、出血事件发生率分别为6.85%、10.96%,均高于非膜性肾病组(0.87%、3.48%),但两组间血栓事件总发生率、出血事件发生率比较,差异均无统计学意义(P>0.05)。结论低分子肝素钙/磺达肝癸钠序贯联合双嘧达莫预防性抗凝有利于改善PNS患者的肾功能,缓解高凝状态,降低血栓栓塞事件发生率,且非膜性肾病患者获益较膜性肾病患者更明显,安全性更高。展开更多
Herbal bioactives have been shown to influence the pathogenesis of homocysteine associated vascular complications.However,there are no simple cellular models to study their role in preventing angiogenesis impairment b...Herbal bioactives have been shown to influence the pathogenesis of homocysteine associated vascular complications.However,there are no simple cellular models to study their role in preventing angiogenesis impairment by homocysteine and adenosine.Using dipyridamole,an inhibitor for nucleoside transport,we examined its mechanism of action on impaired展开更多
Objective: To provide information about the effectiveness and safety of Ginkgo Leaf Extract and Dipyridamole Injection(GD) as one adjuvant therapy for treating angina pectoris(AP) and to evaluate the relevant randomiz...Objective: To provide information about the effectiveness and safety of Ginkgo Leaf Extract and Dipyridamole Injection(GD) as one adjuvant therapy for treating angina pectoris(AP) and to evaluate the relevant randomized controlled trials(RCTs) with meta-analysis. Methods: RCTs concerning AP treated by GD were searched in China Biology Medicine Disc(SinoMed), PubMed, the China National Knowledge Infrastructure Database(CNKI), the Chinese Scientific Journals Database(VIP), Wanfang Database, Embase, and the Cochrane Library, from inception to February, 2017. The Cochrane Risk Assessment Tool was adopted to assess the methodological quality of the RCTs. The Review Manager 5.3 software was utilized to conduct the meta-analysis. Results: A total of 41 RCTs involving 4,462 patients were included in the meta-analysis. The results indicated that the combined use of GD and Western medicine(WM) against AP was associated with a higher total effective rate [risk ratio(RR)=1.25, 95% confidence interval(CI): 1.21–1.29, P<0.01], total effective rate of electrocardiogram(RR=1.29, 95% CI: 1.21–1.36, P<0.01). Additional, GD combined with WM could decrease the level of plasma viscosity [mean difference(MD)=–0.56, 95% CI: –0,81 to –0.30, P<0.01], fibrinogen [MD=–1.02, 95% CI: –1.50 to –0.54, P<0.01], whole blood low shear viscosity [MD=–2.27, 95% CI: –3.04 to –1.49, P<0.01], and whole blood high shear viscosity(MD=–0.90, 95% CI: 1.37 to –0.44, P<0.01). Conclusions: Comparing with receiving WM only, the combine use of GD and WM was associated with a better curative effect for patients with AP. Nevertheless, limited by the methodological quality of included RCTs more large-sample, multi-center RCTs were needed to confirm our findings and provide further evidence for the clinical utility of GD.展开更多
Helicobacter pylori is a risk factor for the development of peptic ulcers with autophagy dysfunction.Omeprazole was widely known as the first-line regimen for H.pylori-associated gastritis.Objectives:The objective of ...Helicobacter pylori is a risk factor for the development of peptic ulcers with autophagy dysfunction.Omeprazole was widely known as the first-line regimen for H.pylori-associated gastritis.Objectives:The objective of this work was to assess the role of omeprazole on cell pyroptosis and autophagy.Methods:The clinical samples were collected.Quantitative polymerase chain reaction,western blotting,enzyme linked immunosorbent assay,and immunofluorescence(IF)analysis were conducted to reveal the mechanism of omeprazole on cell pyroptosis and autophagy.Results:The results revealed that omeprazole could decrease cell pyroptosis,which was attributed to the downregulation of cleaved caspase-1 expression,resulting in the inhibition of gasdermin E and interleukin-18/1βmaturation and secretion as well as the resolution of inflammation.Mechanistically,omeprazole treatment led to drastic downregulation of mammalian target of rapamycin(mTOR)activity was observed in BGC823 cells,leading to enhanced autophagy characterized by increased LC3II expression,which further reduced cell pyroptosis.This omeprazole-mediated phenomenon was enhanced after phosphodiesterase-4(PDE4)inhibitor dipyridamole(DIP)treatment.In addition,activation of mTOR by MHY1485 could rescue the suppression of cell pyroptosis induced by omeprazole.Most importantly,IF analysis suggested that phosphorylation of mTOR and PDE4 activity and caspase-1 were enhanced in H.pylori-infected gastric mucosa.Conclusion:These findings indicate that omeprazole suppresses cell pyroptosis through PDE4-mediated autophagy in gastric epithelial cells,and DIP enhanced the omeprazole-mediated inhibition of cell pyroptosis,implying that DIP is an alternative combined therapy strategy in improving the treatment of patients with H.pylori infection.展开更多
文摘It is first demonstrated that dipyridamole (DP) and radiation were capable of significantly inhibiting, independently and synerglcally, clonogenlc growth in the two kinds of K562 cell lines, adriamycin (ADM) -sensitive and ADM- resistant. DP or radiation alone Increased clonogenlc Inhibition rate (CIR) in the two kinds of cell lines in a dose- dependent fashion. DP potentiated radiosensitivity and radiation increased inhibition of DP in the two kinds of cell lines. K562/ ADM cell lines were higher sensitive to DP. radiation and combination of them than K562 cell lines (P【0. 01). There was stronger synergic inhibition of clonogenlc growth in the two kinds of cell lines when pretreated with DP than when posttreated with DP (P【0. 01).
文摘Objective: It was known that neutrophils play an important role in ischemic-reperfusion injury. In this study we tested the effect and its mechanism of dipyridamole on neutrophils. Methods:Hydrogen peroxide(H2O2) production by neutrophils was determined using luminol amplified chemiluminescence and the percentage of activity was calculated by observing the uninhibited peak height. Results: Dipyridamole per se produced a concentration-dependent inhibition of H2O2 by formyl-MetleuPhe(fMLP)-stimulated neutrophils. Dipy-ridamole at a low concentration(0.3μmol·L-1) that per se affected neutrophils only slightly, enhanced markedly the effects of adenosine on neutrophils. On the other hand, dipyridamole did not alter the inhibitory effect of NECA(5'-N-ethylcarboxamidoadenosine) on neutrophils. However, propentofylline, a known inhibitor of adenosine uptake, also gotten the same result. Conclusion:Dipy-ridamole inhibited the production of H2O2 by fMLP-stimulated neutrophils. Dipyridamole at a low concentration enhanced the inhibi-tory effect of adenosine on neutrophils. The mechanism involved is probably due to the effect of dipyridamole on adenosine uptake.
文摘Using dipyridamole stress test to evaluate cerebral blood flow reserve in cerebrovascular disease (CVD). Dipyridamole stress tests were performed first, the baseline SPECT images were obtained under similar conditions 2-5 days later. By visual and semiquantitative analysis, the responses of cerebral blood flow to dipyridamole were divided into the following four patterns: A: The dipyridamole SPECT showed an expanded area of hypoperfusion, Asymmetry Index(AI) and Uptake Rate(UR) were all decreased; B: Rest images was normal but new hypoperfused areas appeared on stress test with decreased Al and UR; C: Hypoperfused areas were decreased in size or disappeared after stress test with increased Al and UR; D: No changes showed in cerebral perfusion imaging patterns, and in Al and UR between stress and rest studies. Dipyridarnole brain perfusion imaging may be helpful to the diagnosis of CVD, to the decision the therapeutic plan, and to predicting the therapeutic effect.
基金National Key R&D Program of China(2017YFB0202600 and 2020YFC0841400)National Natural Science Foundation of China(91742109,8152204,31770978,81773674,and 21877134)+8 种基金National Health&Medical Research of Australia(1080321,1143976 and 1150425)Science Foundation of Guangzhou City(201904020023,China)Guangdong Province Higher Vocational Colleges and Schools Pearl River Scholar Funded Scheme(2016 and 2019,China)Guangdong Provincial Key Laboratory of Construction Foundation(2017B030314030,China)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y093,China)Zhejiang University special scientific research fund for COVID-19 prevention and control(China)National Health&Medical Research of Australia(1080321,1143976,and 1150425)Taikang Insurance Group Co.,Ltd.Beijing Taikang Yicai Foundation(Beijing,China)
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis.In an analysis of a randomly collected cohort of 124 patients with COVID-19,we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity.By virtual screening of a U.S.FDA approved drug library,we identified an anticoagulation agent dipyridamole(DIP)in silico,which suppressed SARS-CoV-2 replication in vitro.In a proof-of-concept trial involving 31 patients with COVID-19,DIP supplementation was associated with significantly decreased concentrations of D-dimers(P<0.05),increased lymphocyte and platelet recovery in the circulation,and markedly improved clinical outcomes in comparison to the control patients.In particular,all 8 of the DIP-treated severely ill patients showed remarkable improvement:7 patients(87.5%)achieved clinical cure and were discharged from the hospitals while the remaining 1 patient(12.5%)was in clinical remission.
文摘目的探讨低分子肝素钙/磺达肝癸钠序贯联合双嘧达莫预防性抗凝在原发性肾病综合征(PNS)中的应用效果及安全性。方法回顾性选取2020年3月至2022年12月期间四川省凉山彝族自治州第一人民医院收治的188例PNS患者,根据肾穿刺活检病理结果及磷脂酶A2受体抗体分为膜性肾病组(n=73)与非膜性肾病组(n=115)。两组患者均根据血清白蛋白水平,采用低分子肝素钙或磺达肝癸钠序贯联合双嘧达莫抗凝。比较两组患者治疗前及治疗后4周、治疗后6个月的肾功能指标[白蛋白、尿素氮、血肌酐、肾小球滤过率(eGFR)和24 h尿蛋白定量(24 h PRO)],治疗前及治疗后4周的血栓弹力图指标[反应指数(R时间)、凝血时间(K时间)、血栓最大弹力度(MA)、凝血指数(CI)和α角],以及随访6个月记录血栓事件、出血事件。结果治疗后4周、6个月,两组的白蛋白、eGFR均较治疗前明显升高,尿素氮、血肌酐、24 h PRO均较治疗前明显降低,差异均有统计学意义(P<0.05),但两组治疗后各肾功能指标比较,差异均无统计学意义(P>0.05)。治疗后4周,两组患者的R时间、K时间均较治疗前明显延长,MA、CI值和α角均较治疗前明显降低,差异均有统计学意义(P<0.05),但两组患者治疗后4周的R时间、K时间、MA、CI值和α角比较,差异均无统计学意义(P>0.05)。膜性肾病组患者的血栓、出血事件发生率分别为6.85%、10.96%,均高于非膜性肾病组(0.87%、3.48%),但两组间血栓事件总发生率、出血事件发生率比较,差异均无统计学意义(P>0.05)。结论低分子肝素钙/磺达肝癸钠序贯联合双嘧达莫预防性抗凝有利于改善PNS患者的肾功能,缓解高凝状态,降低血栓栓塞事件发生率,且非膜性肾病患者获益较膜性肾病患者更明显,安全性更高。
文摘Herbal bioactives have been shown to influence the pathogenesis of homocysteine associated vascular complications.However,there are no simple cellular models to study their role in preventing angiogenesis impairment by homocysteine and adenosine.Using dipyridamole,an inhibitor for nucleoside transport,we examined its mechanism of action on impaired
基金Supported by the National Natural Science Foundation of China(No.81473547 and No.81673829)
文摘Objective: To provide information about the effectiveness and safety of Ginkgo Leaf Extract and Dipyridamole Injection(GD) as one adjuvant therapy for treating angina pectoris(AP) and to evaluate the relevant randomized controlled trials(RCTs) with meta-analysis. Methods: RCTs concerning AP treated by GD were searched in China Biology Medicine Disc(SinoMed), PubMed, the China National Knowledge Infrastructure Database(CNKI), the Chinese Scientific Journals Database(VIP), Wanfang Database, Embase, and the Cochrane Library, from inception to February, 2017. The Cochrane Risk Assessment Tool was adopted to assess the methodological quality of the RCTs. The Review Manager 5.3 software was utilized to conduct the meta-analysis. Results: A total of 41 RCTs involving 4,462 patients were included in the meta-analysis. The results indicated that the combined use of GD and Western medicine(WM) against AP was associated with a higher total effective rate [risk ratio(RR)=1.25, 95% confidence interval(CI): 1.21–1.29, P<0.01], total effective rate of electrocardiogram(RR=1.29, 95% CI: 1.21–1.36, P<0.01). Additional, GD combined with WM could decrease the level of plasma viscosity [mean difference(MD)=–0.56, 95% CI: –0,81 to –0.30, P<0.01], fibrinogen [MD=–1.02, 95% CI: –1.50 to –0.54, P<0.01], whole blood low shear viscosity [MD=–2.27, 95% CI: –3.04 to –1.49, P<0.01], and whole blood high shear viscosity(MD=–0.90, 95% CI: 1.37 to –0.44, P<0.01). Conclusions: Comparing with receiving WM only, the combine use of GD and WM was associated with a better curative effect for patients with AP. Nevertheless, limited by the methodological quality of included RCTs more large-sample, multi-center RCTs were needed to confirm our findings and provide further evidence for the clinical utility of GD.
基金supported by National Natural Science Foundation of China(No.82200607)Guangdong Basic and Applied Basic Research Foundation(Nos.2020A1515110109,2021A1515012194,2023A1515030064)+3 种基金Basic and Applied Research Project of Guangzhou Municipal Science and Technology Project(No.202201020631)Guangzhou Medical Key Disciplines and Specialties(No.011006003)Guangzhou Key Laboratory of Pediatric Inflammatory Bowel Disease(No.2023A03J0866)National Health Commission Key Laboratory of Tropical Disease Prevention and Control(2022NHCTDCKFKT21001).
文摘Helicobacter pylori is a risk factor for the development of peptic ulcers with autophagy dysfunction.Omeprazole was widely known as the first-line regimen for H.pylori-associated gastritis.Objectives:The objective of this work was to assess the role of omeprazole on cell pyroptosis and autophagy.Methods:The clinical samples were collected.Quantitative polymerase chain reaction,western blotting,enzyme linked immunosorbent assay,and immunofluorescence(IF)analysis were conducted to reveal the mechanism of omeprazole on cell pyroptosis and autophagy.Results:The results revealed that omeprazole could decrease cell pyroptosis,which was attributed to the downregulation of cleaved caspase-1 expression,resulting in the inhibition of gasdermin E and interleukin-18/1βmaturation and secretion as well as the resolution of inflammation.Mechanistically,omeprazole treatment led to drastic downregulation of mammalian target of rapamycin(mTOR)activity was observed in BGC823 cells,leading to enhanced autophagy characterized by increased LC3II expression,which further reduced cell pyroptosis.This omeprazole-mediated phenomenon was enhanced after phosphodiesterase-4(PDE4)inhibitor dipyridamole(DIP)treatment.In addition,activation of mTOR by MHY1485 could rescue the suppression of cell pyroptosis induced by omeprazole.Most importantly,IF analysis suggested that phosphorylation of mTOR and PDE4 activity and caspase-1 were enhanced in H.pylori-infected gastric mucosa.Conclusion:These findings indicate that omeprazole suppresses cell pyroptosis through PDE4-mediated autophagy in gastric epithelial cells,and DIP enhanced the omeprazole-mediated inhibition of cell pyroptosis,implying that DIP is an alternative combined therapy strategy in improving the treatment of patients with H.pylori infection.
