The effectiveness of supermicrosurgical lymphovenous anastomosis(LVA)for lymphedema treatment remains controversial.Currently,no evidence has been summarized.This study aimed to review the published literature on supe...The effectiveness of supermicrosurgical lymphovenous anastomosis(LVA)for lymphedema treatment remains controversial.Currently,no evidence has been summarized.This study aimed to review the published literature on supermicrosurgical LVAs in the treatment of peripheral lymphedema and to analyze the surgical outcomes.Studies from databases(PubMed/MEDLINE,Cochrane Controlled Trial Data,and Embase)were collected to determine the effectiveness of supermicrosugrical LVAs for lymphedema.A systematic review was performed using individual patient data.Fifteen studies,including 578 patients(482 female,72 male,and 24 unknown)with a mean age of 51 years,satisfied the needs of the study requirements.Supermicrosurgical LVAs for peripheral lymphedema have demonstrated substantial improvements in both objective and subjective findings in many patients.Moreover,in the long-term follow-up,the effectiveness of this treatment modality maintained a high efficacy of LVA in lymphedema cases.However,most studies provided low-quality evidence,and the conclusion is still not finalized.展开更多
Metabolites of microorganisms have long been considered as potential sources for drug discovery.In this study,fve new depsidone derivatives,talaronins A-E(1-5)and three new xanthone derivatives,talaronins F-H(6-8),tog...Metabolites of microorganisms have long been considered as potential sources for drug discovery.In this study,fve new depsidone derivatives,talaronins A-E(1-5)and three new xanthone derivatives,talaronins F-H(6-8),together with 16 known compounds(9-24),were isolated from the ethyl acetate extract of the mangrove-derived fungus Talaromyces species WHUF0362.The structures were elucidated by analysis of spectroscopic data and chemical methods including alkaline hydrolysis and Mosher’s method.Compounds 1 and 2 each attached a dimethyl acetal group at the aromatic ring.A putative biogenetic relationship of the isolated metabolites was presented and suggested that the depsidones and the xanthones probably had the same biosynthetic precursors such as chrysophanol or rheochrysidin.The antimicrobial activity assay indicated that compounds 5,9,10,and 14 showed potent activity against Helicobacter pylori with minimum inhibitory concentration(MIC)values in the range of 2.42-36.04μmol/L.While secalonic acid D(19)demonstrated signifcant antimicrobial activity against four strains of H.pylori with MIC values in the range of 0.20 to 1.57μmol/L.Furthermore,secalonic acid D(19)exhibited cytotoxicity against cancer cell lines Bel-7402 and HCT-116 with IC_(50) values of 0.15 and 0.19μmol/L,respectively.The structure–activity relationship of depsidone derivatives revealed that the presence of the lactone ring and the hydroxyl at C-10 was crucial to the antimicrobial activity against H.pylori.The depsidone derivatives are promising leads to inhibit H.pylori and provide an avenue for further development of novel antibiotics.展开更多
A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase(XOD) inhibitor by previous in vitro study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperu...A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase(XOD) inhibitor by previous in vitro study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7 th day to induce hyperuricemia. Meanwhile, J99745(3, 10, and 30 mg/kg), allopurinol(20 mg/kg) or benzbromarone(20 mg/kg) were orally administered to mice for 7 days. On the 7 th day,uric acid and creatinine in serum and urine, blood urea nitrogen(BUN), malondialdehyde(MDA) content and XOD activities in serum and liver were determined. Morphological changes in kidney were observed using hematoxylin and eosin(H&E) staining. Hepatic XOD, renal urate transporter 1(URAT1), glucose transporter type 9(GLUT9), organic anion transporter 1(OAT1) and ATP-binding cassette transporter G2(ABCG2) were detected by Western blot and real time polymerase chain reaction(PCR). The results showed that J99745 at doses of 10 and 30 mg/kg significantly reduced serum urate, and enhanced fractional excretion of uric acid(FEUA). H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and benzbromarone. Moreover, serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia mice. In consistence with the ability to inhibit XOD, J99745 lowered serum MDA content in hyperuricemia mice. Our resultssuggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression, thus representing a promising candidate as an anti-hyperuricemia agent.展开更多
The purpose of this study was to investigate the effects of salvianolic acid A(SAA) in systemic lupus erythematosus(SLE) induced by pristane in BALB/c mice.Lupus mice were established by confirming elevated levels of ...The purpose of this study was to investigate the effects of salvianolic acid A(SAA) in systemic lupus erythematosus(SLE) induced by pristane in BALB/c mice.Lupus mice were established by confirming elevated levels of autoantibodies and IL-6 after intraperitoneal injection of pristane.Mice were then treated with daily oral doses of SAA for 5 months in parallel with mice treated with prednisone and aspirin as positive controls.The levels of autoantibodies were monitored at monthly intervals and nephritic symptoms observed by hematoxylin and eosin(H&E) and periodic acid-Schiff(PAS) staining.Western blot analysis of renal tissue was also employed.SAA treatment caused a significant reduction in the levels of anti-Sm autoantibodies and reduced renal histopathological changes and pathological effects.SAA treatment also significantly inhibited the phosphorylation of IKK,IκB and NFκB in renal tissues of lupus mice.In conclusion,the results suggest that SAA alleviates renal injury in pristane-induced SLE in BALB/c mice through inhibition of phosphorylation of IKK,IκB and NFκB.展开更多
Little attention has been paid to the effect of Rho-kinase inhibitor on the vascular dysfunction of nitric oxide-deficient hypertension.We aimed to investigate whether the Rho-kinase inhibitor fasudil showed beneficia...Little attention has been paid to the effect of Rho-kinase inhibitor on the vascular dysfunction of nitric oxide-deficient hypertension.We aimed to investigate whether the Rho-kinase inhibitor fasudil showed beneficial effect on the vascular dysfunction of the N^(G)-nitro-L-arginine methyl ester(L-NAME)treated rat,as well as to compare the differential effects of fasudil and angiotensin Ⅱ receptor antagonist valsartan on vascular function.In the present study,both valsartan and fasudil exerted antihypertensive action on the L-NAME-treated rats,while only va lsartan attenuated the cardiac hypertrophy.Treatment with valsartan showed improvement on vascular reactivity to norepinephrine,KCl and CaCl_(2),whereas fasudil therapy showed little effect on vasoconstriction.Endothelium-dependent vasodilation to acetylcholine was reduced in the NO-deficient group but was normalized by the fasudil therapy.The increased expression of RhoA and Rho-kinase(ROCK)in the vasculature was corrected well to normal level by either valsartan or fasudil administration,which seemed to be at least partially responsi ble for the beneficial effect of the drug infusion.These findings suggest that the angiotensin Ⅱ receptor antagonist interferes more with the contractile response than Rho-kinase inhibitor,whereas inhibition of Rho-kinase activity exhibits a better improvement on vasorelaxation than blockade of angiotensin Ⅱ receptor.展开更多
Salvianolic acids,including salvianolic acid A(SAA)and salvianolic acid B(SAB),are.the main water-soluble bioactive compounds isolated from the Chinese medicinal herb Danshen and have been shown to exert in vitro and ...Salvianolic acids,including salvianolic acid A(SAA)and salvianolic acid B(SAB),are.the main water-soluble bioactive compounds isolated from the Chinese medicinal herb Danshen and have been shown to exert in vitro and in vivo cardiovascular protection.Recent studies suggest that epoxyeicosatrienoic acids(EETs),the primary cytochrome P4502J(CYP2J)epoxygenase metabolites of arachidonic acid,are involved in the progression of ischemic injury in diverse organs.Here,we investigated the relation between the protective effects of salvianolic acids and EETs/sEH as well as MAPK signaling pathway.In the present study,the rat acute myocardial infarction(AMI)model was established by the left anterior descending coronary artery occlusion.Our results showed that salvianolic acids significantly reduced ST-segment elevation and serum levels of CK-MB,LDH,and ALT in AMI rats,and significantly attenuated the caspase 3 expression and reduced the ratio of Bax/Bcl-2.ELISA measurement showed that salvianolic acids significantly increased the 14,15-EET levels in blood and heart,and attenuated hydrolase activity of sEH in heart of AMI rat.Western blotting analysis suggested that salvianolic acids significantly attenuated the phosphorylation of JNK and p38,and increased phosphorylation of ERK in heart.In conclusion,these results indicate that EETs/sEH and MAPK signaling pathways are important processes in cardioprotection of salvianolic acids.展开更多
文摘The effectiveness of supermicrosurgical lymphovenous anastomosis(LVA)for lymphedema treatment remains controversial.Currently,no evidence has been summarized.This study aimed to review the published literature on supermicrosurgical LVAs in the treatment of peripheral lymphedema and to analyze the surgical outcomes.Studies from databases(PubMed/MEDLINE,Cochrane Controlled Trial Data,and Embase)were collected to determine the effectiveness of supermicrosugrical LVAs for lymphedema.A systematic review was performed using individual patient data.Fifteen studies,including 578 patients(482 female,72 male,and 24 unknown)with a mean age of 51 years,satisfied the needs of the study requirements.Supermicrosurgical LVAs for peripheral lymphedema have demonstrated substantial improvements in both objective and subjective findings in many patients.Moreover,in the long-term follow-up,the effectiveness of this treatment modality maintained a high efficacy of LVA in lymphedema cases.However,most studies provided low-quality evidence,and the conclusion is still not finalized.
基金This research was funded by grants from National Key Research and Development Program of China(2018YFC0311002)High-Level Talent Special Support Plan of Zhejiang Province(2019R52009).
文摘Metabolites of microorganisms have long been considered as potential sources for drug discovery.In this study,fve new depsidone derivatives,talaronins A-E(1-5)and three new xanthone derivatives,talaronins F-H(6-8),together with 16 known compounds(9-24),were isolated from the ethyl acetate extract of the mangrove-derived fungus Talaromyces species WHUF0362.The structures were elucidated by analysis of spectroscopic data and chemical methods including alkaline hydrolysis and Mosher’s method.Compounds 1 and 2 each attached a dimethyl acetal group at the aromatic ring.A putative biogenetic relationship of the isolated metabolites was presented and suggested that the depsidones and the xanthones probably had the same biosynthetic precursors such as chrysophanol or rheochrysidin.The antimicrobial activity assay indicated that compounds 5,9,10,and 14 showed potent activity against Helicobacter pylori with minimum inhibitory concentration(MIC)values in the range of 2.42-36.04μmol/L.While secalonic acid D(19)demonstrated signifcant antimicrobial activity against four strains of H.pylori with MIC values in the range of 0.20 to 1.57μmol/L.Furthermore,secalonic acid D(19)exhibited cytotoxicity against cancer cell lines Bel-7402 and HCT-116 with IC_(50) values of 0.15 and 0.19μmol/L,respectively.The structure–activity relationship of depsidone derivatives revealed that the presence of the lactone ring and the hydroxyl at C-10 was crucial to the antimicrobial activity against H.pylori.The depsidone derivatives are promising leads to inhibit H.pylori and provide an avenue for further development of novel antibiotics.
基金supported by National Natural Science Foundation of China(81573645,81202538 and 81673422)CAMS Innovation Fund for Medical Sciences(CIFMS,2016-I2M-3-007)National Science and Technology Major Projects for "Major New Drugs Innovation and Development"(2013ZX09508104and 2013ZX09402203)
文摘A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase(XOD) inhibitor by previous in vitro study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7 th day to induce hyperuricemia. Meanwhile, J99745(3, 10, and 30 mg/kg), allopurinol(20 mg/kg) or benzbromarone(20 mg/kg) were orally administered to mice for 7 days. On the 7 th day,uric acid and creatinine in serum and urine, blood urea nitrogen(BUN), malondialdehyde(MDA) content and XOD activities in serum and liver were determined. Morphological changes in kidney were observed using hematoxylin and eosin(H&E) staining. Hepatic XOD, renal urate transporter 1(URAT1), glucose transporter type 9(GLUT9), organic anion transporter 1(OAT1) and ATP-binding cassette transporter G2(ABCG2) were detected by Western blot and real time polymerase chain reaction(PCR). The results showed that J99745 at doses of 10 and 30 mg/kg significantly reduced serum urate, and enhanced fractional excretion of uric acid(FEUA). H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and benzbromarone. Moreover, serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia mice. In consistence with the ability to inhibit XOD, J99745 lowered serum MDA content in hyperuricemia mice. Our resultssuggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression, thus representing a promising candidate as an anti-hyperuricemia agent.
基金supported by the National Natural Science Foundation of China(Nos.81573645 and 81473383)National Scientific&Technological Major Special Project“Significant Creation of New Drugs”(Nos.2013ZX09103001-008,2012ZX09103101-078 and2013ZX09508104)
文摘The purpose of this study was to investigate the effects of salvianolic acid A(SAA) in systemic lupus erythematosus(SLE) induced by pristane in BALB/c mice.Lupus mice were established by confirming elevated levels of autoantibodies and IL-6 after intraperitoneal injection of pristane.Mice were then treated with daily oral doses of SAA for 5 months in parallel with mice treated with prednisone and aspirin as positive controls.The levels of autoantibodies were monitored at monthly intervals and nephritic symptoms observed by hematoxylin and eosin(H&E) and periodic acid-Schiff(PAS) staining.Western blot analysis of renal tissue was also employed.SAA treatment caused a significant reduction in the levels of anti-Sm autoantibodies and reduced renal histopathological changes and pathological effects.SAA treatment also significantly inhibited the phosphorylation of IKK,IκB and NFκB in renal tissues of lupus mice.In conclusion,the results suggest that SAA alleviates renal injury in pristane-induced SLE in BALB/c mice through inhibition of phosphorylation of IKK,IκB and NFκB.
基金This study was supported by the National Natural Science Foundation of China(No.30572182)National Scientific&Technological Major Special Project-“Significant Creation of New Drugs”(Nos.2009ZX09302-003 and 2009ZX09501-021).
文摘Little attention has been paid to the effect of Rho-kinase inhibitor on the vascular dysfunction of nitric oxide-deficient hypertension.We aimed to investigate whether the Rho-kinase inhibitor fasudil showed beneficial effect on the vascular dysfunction of the N^(G)-nitro-L-arginine methyl ester(L-NAME)treated rat,as well as to compare the differential effects of fasudil and angiotensin Ⅱ receptor antagonist valsartan on vascular function.In the present study,both valsartan and fasudil exerted antihypertensive action on the L-NAME-treated rats,while only va lsartan attenuated the cardiac hypertrophy.Treatment with valsartan showed improvement on vascular reactivity to norepinephrine,KCl and CaCl_(2),whereas fasudil therapy showed little effect on vasoconstriction.Endothelium-dependent vasodilation to acetylcholine was reduced in the NO-deficient group but was normalized by the fasudil therapy.The increased expression of RhoA and Rho-kinase(ROCK)in the vasculature was corrected well to normal level by either valsartan or fasudil administration,which seemed to be at least partially responsi ble for the beneficial effect of the drug infusion.These findings suggest that the angiotensin Ⅱ receptor antagonist interferes more with the contractile response than Rho-kinase inhibitor,whereas inhibition of Rho-kinase activity exhibits a better improvement on vasorelaxation than blockade of angiotensin Ⅱ receptor.
基金The study was supported by the National Science Foundation for Young Scholars of China(Grant No.81202538).
文摘Salvianolic acids,including salvianolic acid A(SAA)and salvianolic acid B(SAB),are.the main water-soluble bioactive compounds isolated from the Chinese medicinal herb Danshen and have been shown to exert in vitro and in vivo cardiovascular protection.Recent studies suggest that epoxyeicosatrienoic acids(EETs),the primary cytochrome P4502J(CYP2J)epoxygenase metabolites of arachidonic acid,are involved in the progression of ischemic injury in diverse organs.Here,we investigated the relation between the protective effects of salvianolic acids and EETs/sEH as well as MAPK signaling pathway.In the present study,the rat acute myocardial infarction(AMI)model was established by the left anterior descending coronary artery occlusion.Our results showed that salvianolic acids significantly reduced ST-segment elevation and serum levels of CK-MB,LDH,and ALT in AMI rats,and significantly attenuated the caspase 3 expression and reduced the ratio of Bax/Bcl-2.ELISA measurement showed that salvianolic acids significantly increased the 14,15-EET levels in blood and heart,and attenuated hydrolase activity of sEH in heart of AMI rat.Western blotting analysis suggested that salvianolic acids significantly attenuated the phosphorylation of JNK and p38,and increased phosphorylation of ERK in heart.In conclusion,these results indicate that EETs/sEH and MAPK signaling pathways are important processes in cardioprotection of salvianolic acids.