4?,7-Dimethoxy-N-methylisoflavone-3?-sulfonamide(3) was synthesized by a two step synthesis method and characterized via IR and 1H NMR. Its chemical structure was determined by X-ray single-crystal diffraction. It cry...4?,7-Dimethoxy-N-methylisoflavone-3?-sulfonamide(3) was synthesized by a two step synthesis method and characterized via IR and 1H NMR. Its chemical structure was determined by X-ray single-crystal diffraction. It crystallizes in monoclinic, space group C2/c with a = 27.677(13), b = 10.490(5), c = 13.982(7) ?, β = 118.781(9)o, V = 3558(3) ?3, Z = 8, F(000) = 1568, Dc = 1.401 Mg/m3, Mr = 375.39, μ = 0.217 mm–1, λ = 0.71073 ?, the final R = 0.0436 and w R = 0.0910 for 3168 observed reflections with I > 2σ(I). The compound was studied subsequently for the potent neuroprotective activity, and showed effects against oxygen-glucose deprivation injury in PC12 cells in a dose-dependent manner(protection: 42.5% at 100 μg·m L-1, 35.1% at 10 μg·m L-1 and 22.5% at 1 μg·m L-1).展开更多
Background:Cerebrovascular accident has high morbidity,high disability,and high mortality,possibly causing several serious sequelae and bringing a heavy burden to the patient,the family,and the society.Buyang Huanwu d...Background:Cerebrovascular accident has high morbidity,high disability,and high mortality,possibly causing several serious sequelae and bringing a heavy burden to the patient,the family,and the society.Buyang Huanwu decoction,a classic ancient prescription of traditional Chinese medicine,and acupuncture are often used in combination to treat the sequelae of cerebrovascular accident.In the present study,we systematically evaluated the clinical efficacy and safety of acupuncture combined with Buyang Huanwu decoction in treating the sequelae of cerebrovascular accident.Methods:Relevant randomized controlled trials of acupuncture combined with Buyang Huanwu decoction in treating the sequelae of cerebrovascular accident were comprehensively retrieved from electronic databases from inception to May 8,2020,including PubMed,Embase,The Cochrane Library,China National Knowledge Infrastructure,WanFang Data,and China Science and Technology Journal Database.The main outcomes of clinical efficacy,degree of nerve function impairment,daily self-care capacity,Fugl-Meyer locomotor function score,life quality score,and occurrence of adverse reactions were subjected to meta-analysis.Results:The 28 randomized controlled trials included 2,341 patients with the sequelae of cerebrovascular accident.Systematic review and meta-analysis indicated that compared with acupuncture alone,its combined treatment with Buyang Huanwu decoction significantly increased clinical efficacy(RR=1.19,95%CI(1.14,1.23),P<0.001),improved nerve function impairment(WMD=−4.89,95%CI(−8.25,−1.53),P=0.004),promoted daily self-care capacity(WMD=15.87,95%CI(11.22,20.51),P<0.001),strengthened Fugl-Meyer locomotor function(WMD=20.89,95%CI(13.79,27.98),P<0.001),enhanced physical functioning(WMD=16.99,95%CI(6.01,27.96),P<0.001)and mental health(WMD=16.91,95%CI(9.14,24.69),P<0.001)in terms of life quality score(SF-36 scale)of patients with sequelae of cerebrovascular accident,with few adverse reactions.Conclusion:Compared with acupuncture alone,its combination with Buyang Huanwu decoction had better comprehensive effects on sequelae of cerebrovascular accident without obvious adverse reactions.展开更多
Polyphyllin I(PPI)and polyphyllin II(PII)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechani...Polyphyllin I(PPI)and polyphyllin II(PII)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPI and PII exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepatotoxicity of PPI and PII was associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the cholesterol synthesis,selected as the potential targets,were confirmed by the molecular docking,the overexpression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPI could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPI-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.展开更多
CircularRNAs(circRNAs)are a class of single-stranded,closedRNAmolecules with unique functions that are ubiquitously expressed in all eukaryotes.The biogenesis of circRNAs is regulated by specific cis-acting elements a...CircularRNAs(circRNAs)are a class of single-stranded,closedRNAmolecules with unique functions that are ubiquitously expressed in all eukaryotes.The biogenesis of circRNAs is regulated by specific cis-acting elements and trans-acting factors in humans and animals.circRNAs mainly exert their biological functions by acting as microRNA sponges,forming R-loops,interacting with RNA-binding proteins,or being translated into polypeptides or proteins in human and animal cells.Genome-wide identification of circRNAs has been performedin multiple plant species,and the results suggest that circRNAs are abundant and ubiquitously expressed in plants.There is emerging compelling evidence to suggest that circRNAs play essential roles during plant growthanddevelopment as well as inthe responses to bioticandabiotic stress.However,compared with recent advances in human and animal systems,the roles of most circRNAs in plants are unclear at present.Here we review the identification,biogenesis,function,and mechanism of action of plant circRNAs,which will provide a fundamental understanding of the characteristics and complexity of circRNAs in plants.展开更多
基金supported by grants from the project of the education department of Shaanxi Province(No.2013JK0839)
文摘4?,7-Dimethoxy-N-methylisoflavone-3?-sulfonamide(3) was synthesized by a two step synthesis method and characterized via IR and 1H NMR. Its chemical structure was determined by X-ray single-crystal diffraction. It crystallizes in monoclinic, space group C2/c with a = 27.677(13), b = 10.490(5), c = 13.982(7) ?, β = 118.781(9)o, V = 3558(3) ?3, Z = 8, F(000) = 1568, Dc = 1.401 Mg/m3, Mr = 375.39, μ = 0.217 mm–1, λ = 0.71073 ?, the final R = 0.0436 and w R = 0.0910 for 3168 observed reflections with I > 2σ(I). The compound was studied subsequently for the potent neuroprotective activity, and showed effects against oxygen-glucose deprivation injury in PC12 cells in a dose-dependent manner(protection: 42.5% at 100 μg·m L-1, 35.1% at 10 μg·m L-1 and 22.5% at 1 μg·m L-1).
基金This study was supported by Fundamental Research Funds for the Central University(No.GK202003050,GK202003048)the Innovation Training Program for University Student(No.cx2019013,s201910718084).
文摘Background:Cerebrovascular accident has high morbidity,high disability,and high mortality,possibly causing several serious sequelae and bringing a heavy burden to the patient,the family,and the society.Buyang Huanwu decoction,a classic ancient prescription of traditional Chinese medicine,and acupuncture are often used in combination to treat the sequelae of cerebrovascular accident.In the present study,we systematically evaluated the clinical efficacy and safety of acupuncture combined with Buyang Huanwu decoction in treating the sequelae of cerebrovascular accident.Methods:Relevant randomized controlled trials of acupuncture combined with Buyang Huanwu decoction in treating the sequelae of cerebrovascular accident were comprehensively retrieved from electronic databases from inception to May 8,2020,including PubMed,Embase,The Cochrane Library,China National Knowledge Infrastructure,WanFang Data,and China Science and Technology Journal Database.The main outcomes of clinical efficacy,degree of nerve function impairment,daily self-care capacity,Fugl-Meyer locomotor function score,life quality score,and occurrence of adverse reactions were subjected to meta-analysis.Results:The 28 randomized controlled trials included 2,341 patients with the sequelae of cerebrovascular accident.Systematic review and meta-analysis indicated that compared with acupuncture alone,its combined treatment with Buyang Huanwu decoction significantly increased clinical efficacy(RR=1.19,95%CI(1.14,1.23),P<0.001),improved nerve function impairment(WMD=−4.89,95%CI(−8.25,−1.53),P=0.004),promoted daily self-care capacity(WMD=15.87,95%CI(11.22,20.51),P<0.001),strengthened Fugl-Meyer locomotor function(WMD=20.89,95%CI(13.79,27.98),P<0.001),enhanced physical functioning(WMD=16.99,95%CI(6.01,27.96),P<0.001)and mental health(WMD=16.91,95%CI(9.14,24.69),P<0.001)in terms of life quality score(SF-36 scale)of patients with sequelae of cerebrovascular accident,with few adverse reactions.Conclusion:Compared with acupuncture alone,its combination with Buyang Huanwu decoction had better comprehensive effects on sequelae of cerebrovascular accident without obvious adverse reactions.
基金supported by the National Natural Science Foundation of China(Grant No.:82204753),the Scientific Research Staring Foundation for the New Teachers of Beijing University of Chinese Medicine(Grant No.:2020-JYB-XJSJJ-009),and Special Scientific Research for Traditional Chinese Medicine of State Administration of Traditional Chinese Medicine of China(Grant No.:201507004).The funders had no role in the study design,data collection,data analysis,interpretation,or writing of the report.
文摘Polyphyllin I(PPI)and polyphyllin II(PII)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPI and PII exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepatotoxicity of PPI and PII was associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the cholesterol synthesis,selected as the potential targets,were confirmed by the molecular docking,the overexpression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPI could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPI-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.
基金funded by the National Science Foundation of China(31770333 and 31370329)the Program for New Century Excellent Talents in University(NCET-12–0896)+1 种基金the Fundamental Research Funds for the Central Universities(GK202103067 and GK202202006)the Natural Science Foundation of Shaanxi Province,China(2022JQ-218).
文摘CircularRNAs(circRNAs)are a class of single-stranded,closedRNAmolecules with unique functions that are ubiquitously expressed in all eukaryotes.The biogenesis of circRNAs is regulated by specific cis-acting elements and trans-acting factors in humans and animals.circRNAs mainly exert their biological functions by acting as microRNA sponges,forming R-loops,interacting with RNA-binding proteins,or being translated into polypeptides or proteins in human and animal cells.Genome-wide identification of circRNAs has been performedin multiple plant species,and the results suggest that circRNAs are abundant and ubiquitously expressed in plants.There is emerging compelling evidence to suggest that circRNAs play essential roles during plant growthanddevelopment as well as inthe responses to bioticandabiotic stress.However,compared with recent advances in human and animal systems,the roles of most circRNAs in plants are unclear at present.Here we review the identification,biogenesis,function,and mechanism of action of plant circRNAs,which will provide a fundamental understanding of the characteristics and complexity of circRNAs in plants.
