Objective:To investigate the mechanisms underlying the renoprotective effects of celastrol,a bioactive compound extracted from the traditional Chinese medicinal plant Tripterygium wilfordii in diabetic kidney disease(...Objective:To investigate the mechanisms underlying the renoprotective effects of celastrol,a bioactive compound extracted from the traditional Chinese medicinal plant Tripterygium wilfordii in diabetic kidney disease(DKD).Methods:We established a DKD model using db/db mice and investigated the protective mechanisms of celastrol against DKD progression using integrated analysis of 16S rRNA sequencing and transcriptome analysis.We evaluated colon tissue damage using hematoxylin and eosin and immunofluorescence staining.In addition,16S rRNA sequencing and transcriptomic analyses were performed to explore the potential mechanisms of celastrol.Immunofluorescence staining,Western blotting and real-time quantitative polymerase chain reaction analysis were performed to confirm the PPAR signaling pathway related proteins in kidney tissues.Results:Celastrol alleviated colon injury and increased the expression of mucosal barrier markers,particularly occludin and zonula occludens-1.The 16S rRNA gene sequencing analysis demonstrated that treatment with celastrol altered the diversity and abundance of the gut microbiota.Spearman’s correlation analysis further revealed significant associations among gut microbial,renal injury markers,and serum lipid profiles.A subsequent renal transcriptome analysis revealed that celastrol significantly modulated the renal transcriptional landscape,primarily by regulating genes associated with the PPAR signaling pathway and lipid metabolism.Further investigations demonstrated that celastrol significantly downregulated adipose differentiation-related protein expression and attenuated DKD progression by activating the PPAR pathway.Conclusions:This study demonstrates that celastrol alleviates both colonic and renal injuries by modulating the gut-kidney axis through PPAR-mediated lipid metabolism regulation,indicating its potential as a therapeutic approach for DKD management.展开更多
Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the m...Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.展开更多
Cattle encephalon glycoside and ignotin(CEGI)injection is a compound preparation formed by a combination of muscle extract from hea lthy rabbits and brain gangliosides from cattle,and it is generally used as a neuropr...Cattle encephalon glycoside and ignotin(CEGI)injection is a compound preparation formed by a combination of muscle extract from hea lthy rabbits and brain gangliosides from cattle,and it is generally used as a neuroprotectant in the treatment of central and peripheral nerve injuries.However,there is still a need for high-level clinical evidence from large samples to support the use of CEGI.We therefore carried out a prospective,multicenter,randomized,double-blind,parallel-group,placebo-controlled study in which we recruited 319 patients with acute cerebral infarction from 16 centers in China from October 2013 to May 2016.The patients were randomized at a 3:1 ratio into CEGI(n=239;155 male,84 female;61.2±9.2 years old)and placebo(n=80;46 male,34 female;63.2±8.28 years old)groups.All patients were given standard care once daily for 14 days,including a 200 mg aspirin enteric-coated tablet and 20 mg atorvastatin calcium,both taken orally,and intravenous infusion of 250–500 mL 0.9%sodium chloride containing 40 mg sodium tanshinone IIA sulfonate.Based on conventional treatment,patients in the CEGI and placebo groups were given 12 mL CEGI or 12 mL sterile water,respectively,in an intravenous drip of 250 mL 0.9%sodium chloride(2 mL/min)once daily for 14 days.According to baseline National Institutes of Health Stroke Scale scores,patients in the two groups were divided into mild and moderate subgroups.Based on the modified Rankin Scale results,the rate of patients with good outcomes in the CEGI group was higher than that in the placebo group,and the rate of disability in the CEGI group was lower than that in the placebo group on day 90 after treatment.In the CEGI group,neurological deficits were decreased on days 14 and 90 after treatment,as measured by the National Institutes of Health Stroke Scale and the Barthel Index.Subgroup analysis revealed that CEGI led to more significant improvements in moderate stroke patients.No drug-related adverse events occurred in the CEGI or placebo groups.In conclusion,CEGI may be a safe and effective treatment for acute cerebral infarction patients,especially for moderate stroke patients.This study was approved by the Ethical Committee of Peking University Third Hospital,China(approval No.2013-068-2)on May 20,2013,and registered in the Chinese Clinical Trial Registry(registration No.ChiCTR1800017937).展开更多
Self-nitrogen-doped porous biochar derived from kapok fibers possesses unique structure and excel- lent electrochemical performance. In this study, one-step pyrolysis method was introduced to prepare porous biochar fr...Self-nitrogen-doped porous biochar derived from kapok fibers possesses unique structure and excel- lent electrochemical performance. In this study, one-step pyrolysis method was introduced to prepare porous biochar from kapok fibers, and effect of pyrolysis temperature on structure and electrochemical performance of the porous biochar was investigated. It was found that pyrolysis temperature played an important role in determining microstructure of the biochar. At the pyrolysis temperature of 750 ℃, the as-prepared biochar （CKF-750） represented a largest specific surface area of 1125.7 m^2 g^-1 and pore vol- ume of 0.7130 m^3 g^-1, and hence brings CKF-750 a highest specific capacitance of 283 F g^-1 at a current density of I A g^-1 in a 6 mol L^-1 KOH electrolyte. Furthermore, the cycle stability of CKF-750 was wonderful, and the specific capacitance retained almost constant after 10000 cycles. Therefore, the pyrolysis tem- perature of 750 ℃ is optimal for the preparation of porous hiochar as an outstanding electrode material for supercapacitor.展开更多
Co-delivery of anti-cancer drugs is promising to improve the efficacy of cancer treatment.This study was aiming to investigate the potential of concurrent delivery of resveratrol(RES)and docetaxel(DTX)via polymeric na...Co-delivery of anti-cancer drugs is promising to improve the efficacy of cancer treatment.This study was aiming to investigate the potential of concurrent delivery of resveratrol(RES)and docetaxel(DTX)via polymeric nanocarriers to treat breast cancer.To this end,methoxyl poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PDLA)was prepared and characterized using FTIR and 1H NMR,and their molecular weights were determined by GPC.Isobologram analysis and combination index calculation were performed to find the optimal ratio between RES and DTX to against human breast adenocarcinoma cell line(MCF-7 cells).Subsequently,RES and DTX were loaded in the mPEG-PDLA micelles simultaneously,and the morphology,particle size distribution,in vitro release,pharmacokinetic profiles,as well as cytotoxicity to the MCF-7 cells were characterized.IC50 of RES and DTX in MCF-7 cells were determined to be 23.0μg/ml and 10.4μg/ml,respectively,while a lower IC50 of 4.8μg/ml of the combination of RES and DTX was obtained.The combination of RES and DTX at a ratio of 1:1(w/w)generated stronger synergistic effect than other ratios in the MCF-7 cells.RES and DTX loaded mPEG-PDLA micelles exhibited prolonged release profiles,and enhanced cytotoxicity in vitro against MCF-7 cells.The AUC(0→t)of DTX and RES in mPEG-PDLA micelles after i.v.administration to rats were 3.0-fold and 1.6-fold higher than that of i.v.injections of the individual drugs.These findings indicated that the co-delivery of RES and DTX using mPEG-PDLA micelles could have better treatment of tumors.展开更多
基金Hangzhou Municipal Health Commission Project(A20231278)Zhejiang Province Medical and Health Technology Plan Project(2024KY219)+1 种基金Zhejiang Traditional Medicine and Technology Program,China(2024ZR114)Peak Discipline Nephrology of Hangzhou(Integrated Traditional and Western Medicine,2025HZGF12).
文摘Objective:To investigate the mechanisms underlying the renoprotective effects of celastrol,a bioactive compound extracted from the traditional Chinese medicinal plant Tripterygium wilfordii in diabetic kidney disease(DKD).Methods:We established a DKD model using db/db mice and investigated the protective mechanisms of celastrol against DKD progression using integrated analysis of 16S rRNA sequencing and transcriptome analysis.We evaluated colon tissue damage using hematoxylin and eosin and immunofluorescence staining.In addition,16S rRNA sequencing and transcriptomic analyses were performed to explore the potential mechanisms of celastrol.Immunofluorescence staining,Western blotting and real-time quantitative polymerase chain reaction analysis were performed to confirm the PPAR signaling pathway related proteins in kidney tissues.Results:Celastrol alleviated colon injury and increased the expression of mucosal barrier markers,particularly occludin and zonula occludens-1.The 16S rRNA gene sequencing analysis demonstrated that treatment with celastrol altered the diversity and abundance of the gut microbiota.Spearman’s correlation analysis further revealed significant associations among gut microbial,renal injury markers,and serum lipid profiles.A subsequent renal transcriptome analysis revealed that celastrol significantly modulated the renal transcriptional landscape,primarily by regulating genes associated with the PPAR signaling pathway and lipid metabolism.Further investigations demonstrated that celastrol significantly downregulated adipose differentiation-related protein expression and attenuated DKD progression by activating the PPAR pathway.Conclusions:This study demonstrates that celastrol alleviates both colonic and renal injuries by modulating the gut-kidney axis through PPAR-mediated lipid metabolism regulation,indicating its potential as a therapeutic approach for DKD management.
基金funded by the National Natural Science Foundation of China(82003879)Project of Science and Technology Department of Sichuan Province(2023NSFSC1928,2023NSFSC1992)+3 种基金Young Elite Scientists Sponsorship Program China Association for Science and Technology(CACM-2020-QNRC1-01)Project of State Administration of Traditional Chinese Medicine of China(ZYYCXTD-D-202209)Project of Undergraduate Training Programs for Innovation and Entrepreneurship(S202310610637)the Open Research Fund of State Key Laboratory of Southwestern Chinese Medicine Resources(SKLTCM202205).
文摘Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.
文摘Cattle encephalon glycoside and ignotin(CEGI)injection is a compound preparation formed by a combination of muscle extract from hea lthy rabbits and brain gangliosides from cattle,and it is generally used as a neuroprotectant in the treatment of central and peripheral nerve injuries.However,there is still a need for high-level clinical evidence from large samples to support the use of CEGI.We therefore carried out a prospective,multicenter,randomized,double-blind,parallel-group,placebo-controlled study in which we recruited 319 patients with acute cerebral infarction from 16 centers in China from October 2013 to May 2016.The patients were randomized at a 3:1 ratio into CEGI(n=239;155 male,84 female;61.2±9.2 years old)and placebo(n=80;46 male,34 female;63.2±8.28 years old)groups.All patients were given standard care once daily for 14 days,including a 200 mg aspirin enteric-coated tablet and 20 mg atorvastatin calcium,both taken orally,and intravenous infusion of 250–500 mL 0.9%sodium chloride containing 40 mg sodium tanshinone IIA sulfonate.Based on conventional treatment,patients in the CEGI and placebo groups were given 12 mL CEGI or 12 mL sterile water,respectively,in an intravenous drip of 250 mL 0.9%sodium chloride(2 mL/min)once daily for 14 days.According to baseline National Institutes of Health Stroke Scale scores,patients in the two groups were divided into mild and moderate subgroups.Based on the modified Rankin Scale results,the rate of patients with good outcomes in the CEGI group was higher than that in the placebo group,and the rate of disability in the CEGI group was lower than that in the placebo group on day 90 after treatment.In the CEGI group,neurological deficits were decreased on days 14 and 90 after treatment,as measured by the National Institutes of Health Stroke Scale and the Barthel Index.Subgroup analysis revealed that CEGI led to more significant improvements in moderate stroke patients.No drug-related adverse events occurred in the CEGI or placebo groups.In conclusion,CEGI may be a safe and effective treatment for acute cerebral infarction patients,especially for moderate stroke patients.This study was approved by the Ethical Committee of Peking University Third Hospital,China(approval No.2013-068-2)on May 20,2013,and registered in the Chinese Clinical Trial Registry(registration No.ChiCTR1800017937).
基金supported financially by the Natural Science Foundation of Fujian Province,China(No.2016J01729)the Key Program of Youth Natural Science Foundation of Fujian Province University,China(No.JZ160413)
文摘Self-nitrogen-doped porous biochar derived from kapok fibers possesses unique structure and excel- lent electrochemical performance. In this study, one-step pyrolysis method was introduced to prepare porous biochar from kapok fibers, and effect of pyrolysis temperature on structure and electrochemical performance of the porous biochar was investigated. It was found that pyrolysis temperature played an important role in determining microstructure of the biochar. At the pyrolysis temperature of 750 ℃, the as-prepared biochar （CKF-750） represented a largest specific surface area of 1125.7 m^2 g^-1 and pore vol- ume of 0.7130 m^3 g^-1, and hence brings CKF-750 a highest specific capacitance of 283 F g^-1 at a current density of I A g^-1 in a 6 mol L^-1 KOH electrolyte. Furthermore, the cycle stability of CKF-750 was wonderful, and the specific capacitance retained almost constant after 10000 cycles. Therefore, the pyrolysis tem- perature of 750 ℃ is optimal for the preparation of porous hiochar as an outstanding electrode material for supercapacitor.
基金the Liaoning Province Pan Deng Xue Zhe Grant(M.Yang)Liaoning Provincial Education officer’s Excellent Talents Supporting Plan(D.Cun)National Natural Science Foundation of China(No.81302720 and 81573380)for financial support。
文摘Co-delivery of anti-cancer drugs is promising to improve the efficacy of cancer treatment.This study was aiming to investigate the potential of concurrent delivery of resveratrol(RES)and docetaxel(DTX)via polymeric nanocarriers to treat breast cancer.To this end,methoxyl poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PDLA)was prepared and characterized using FTIR and 1H NMR,and their molecular weights were determined by GPC.Isobologram analysis and combination index calculation were performed to find the optimal ratio between RES and DTX to against human breast adenocarcinoma cell line(MCF-7 cells).Subsequently,RES and DTX were loaded in the mPEG-PDLA micelles simultaneously,and the morphology,particle size distribution,in vitro release,pharmacokinetic profiles,as well as cytotoxicity to the MCF-7 cells were characterized.IC50 of RES and DTX in MCF-7 cells were determined to be 23.0μg/ml and 10.4μg/ml,respectively,while a lower IC50 of 4.8μg/ml of the combination of RES and DTX was obtained.The combination of RES and DTX at a ratio of 1:1(w/w)generated stronger synergistic effect than other ratios in the MCF-7 cells.RES and DTX loaded mPEG-PDLA micelles exhibited prolonged release profiles,and enhanced cytotoxicity in vitro against MCF-7 cells.The AUC(0→t)of DTX and RES in mPEG-PDLA micelles after i.v.administration to rats were 3.0-fold and 1.6-fold higher than that of i.v.injections of the individual drugs.These findings indicated that the co-delivery of RES and DTX using mPEG-PDLA micelles could have better treatment of tumors.
