Three new secoiridoids, swertiakoulactone (1) and swertiakosides A and B (2 and 3), were isolated from Swertia kouitchensis. Their structures were elucidated by comprehensive spectroscopic analyses including MS, IR, 1...Three new secoiridoids, swertiakoulactone (1) and swertiakosides A and B (2 and 3), were isolated from Swertia kouitchensis. Their structures were elucidated by comprehensive spectroscopic analyses including MS, IR, 1D and 2D NMR data. By the anti-hepatitis B virus (HBV) assay on Hep G 2.2.15 cells line in vitro, compound 1 showed moderate activities inhibiting the HBsAg secretion (IC50 = 1.10 mM, SI = 4.39) and HBV DNA replication (IC50 = 1.16 mM, SI = 4.12).展开更多
Colorectal carcinoma(CRC) is a common cause of morbidity and mortality worldwide. Two pathogenic pathways are involved in the development of adenoma to CRC. The first pathway involves APC/β-catenin characterized by c...Colorectal carcinoma(CRC) is a common cause of morbidity and mortality worldwide. Two pathogenic pathways are involved in the development of adenoma to CRC. The first pathway involves APC/β-catenin characterized by chromosomal instability resulting in the accumulation of mutations. The second pathway is characterized by lesions in DNA mismatch repair genes.Aberrant DNA methylation in selected gene promoters has emerged as a new epigenetic pathway in CRC development. CRC screening is the most efficient strategy to reduce death. Specific DNA methylation events occur in multistep carcinogenesis.Epigenetic gene silencing is a causative factor of CRC development. DNA methylations have been extensively examined in stool from CRC and precursor lesions. Many methylated genes have been described in CRC and adenoma, although no definite DNA methylation biomarkers panel has been established. Multiple DNA methylation biomarkers, including secreted frizzled-related protein 2, secreted frizzled-related protein 1, tissue factor pathway inhibitor 2, vimentin, and methylguanine DNA methyltransferase, have been further investigated, and observations have revealed that DNA methylation biomarkers exhibit with high sensitivity and specificity. These markers may also be used to diagnose CRC and adenoma in early stages. Real time polymerase chain reaction(q PCR) is sensitive, scalable, specific, reliable, time saving, and cost effective. Stool exfoliated markers provide advantages, including sensitivity and specificity. A stool q PCR methylation test may also be an enhanced tool for CRC and adenoma screening.展开更多
Eleven new secoiridoid aglycones involving unusual C9-skeleton:swerimilegenins A-F(1-6);bis-C9-skeleton:swerimilegenin G(7);and C_(10)-skeleton:swerimilegenins H−K(8−11),as well as six known ones,were isolated from th...Eleven new secoiridoid aglycones involving unusual C9-skeleton:swerimilegenins A-F(1-6);bis-C9-skeleton:swerimilegenin G(7);and C_(10)-skeleton:swerimilegenins H−K(8−11),as well as six known ones,were isolated from the low-polarity part of the traditional Chinese herb medicine Swertia mileensis.Their structures were determined by extensive spectroscopic data and X-ray diffraction.Biogenetically,swerimilegenin A(1)belonged to 10-nor-secoiridoid,and swerimilegenins B-F(2-6)were 1-nor-secoiridoids.Erythrocentaurin(12)and gentiogenal(15)showed moderate anti-HBV activity on HepG 2.2.15 cell line in vitro.展开更多
Mentha haplocalyx(Mentha canadensis)is widely used as a medicinal plant in traditional Chinese medicine,and the extracts of its aerial parts are found to signifcantly inhibit the activity ofα-glucosidase with an IC_(...Mentha haplocalyx(Mentha canadensis)is widely used as a medicinal plant in traditional Chinese medicine,and the extracts of its aerial parts are found to signifcantly inhibit the activity ofα-glucosidase with an IC_(50) value of 21.0μg/mL.Bioactivity-guided isolation of the extracts aforded two new compounds(1 and 2),together with 23 known ones(3-25).Their structures were established by extensive spectroscopic analyses(1D and 2D NMR,MS,IR and UV).Compounds 1-17 and 21-25 were evaluated for theirα-glucosidase inhibitory activities.Compound 11 was the most active ones with an IC_(50) values of 83.4μM.These results verify theα-glucosidase inhibitory activity of M.haplocalyx(M.canadensis)and specify its active compounds for the frst time.展开更多
Hepatitis B virus(HBV)infection causing acute and chronic hepatitis is a serious problem worldwide,whereas the current treatment methods are unsatisfactory.Traditional Chinese herbs that have long been used for medici...Hepatitis B virus(HBV)infection causing acute and chronic hepatitis is a serious problem worldwide,whereas the current treatment methods are unsatisfactory.Traditional Chinese herbs that have long been used for medicinal purposes are fascinating sources for novel anti-HBV candidates.This paper summarizes the progress of anti-HBV constituents from diverse medicinal plants in China to provide information for searching new anti-HBV drugs from natural sources.展开更多
A new favane,bropapyriferol(1),and eleven known ones were isolated from the EtOAc part of Broussonetia papyrifera under the guidance of bioassay.The structure of compound 1 was determined by extensive 1D and 2D NMR,[...A new favane,bropapyriferol(1),and eleven known ones were isolated from the EtOAc part of Broussonetia papyrifera under the guidance of bioassay.The structure of compound 1 was determined by extensive 1D and 2D NMR,[α]_(D) spectroscopic data and quantum computation.Daphnegiravan F(2)and 5,7,3′,4′-tetrahydroxy-3-methoxy-8,5′-diprenylfavone(3)showed signifcantly anti-oral microbial activity against fve Gram-positive strains and three Gram-negative strains in vitro.Especially,compound 3 was more potent in suppressing Actinomyces naeslundii and Porphyromonas gingivalis(MIC=1.95 ppm)than the positive control,triclosan.展开更多
Two new sesquiterpenoids,artemlavanins A(1)and B(3),together with fifteen known compounds(2 and 4−17)were iso-lated from the EtOH extract of Artemisia lavandulaefolia.The structures of new compounds were elucidated by...Two new sesquiterpenoids,artemlavanins A(1)and B(3),together with fifteen known compounds(2 and 4−17)were iso-lated from the EtOH extract of Artemisia lavandulaefolia.The structures of new compounds were elucidated by extensive spectroscopic analyses(HRESIMS,1D and 2D NMR)and ECD calculations.Compound 1 was a sesquiterpenoid lactone possessing a rearranged eudesmane skeleton;compounds 2-5,6-8,9 and 10-12 belonged to the eudesmane,guaiane,oppositane and farnesane sesquiterpenoids,respectively;compounds 13-17 were the phenyl derivatives with a 4-hydroxy-acetophenone moiety.Twelve compounds(1-3,5-7,10-12,14,15 and 17)displayed cytotoxicity against hepatic stellate cell line LX2(HSC-LX2)with IC50 values ranging from 35.1 to 370.3μM.Compounds 2,7,10-12 and 17 exhibited the stronger cytotoxicity than silybin(IC50,169.6μM)with IC50 values of 82.1,35.1,95.0,83.8,81.6 and 90.1μM.Compound 7 as the most active one showed significant inhibition on the deposition of human collagen type I(Col I),human hyaluronic acid(HA)and human laminin(HL)with IC50 values of 10.7,24.5 and 13.3μM.展开更多
Four new sesquiterpenoids,artemyrianins A-D(1-4),and three new norlignans,artemyrianins E-G(5-7),together with five known compounds(8-12),were isolated from the aerial parts of Artemisia myriantha(Asteraceae).The new ...Four new sesquiterpenoids,artemyrianins A-D(1-4),and three new norlignans,artemyrianins E-G(5-7),together with five known compounds(8-12),were isolated from the aerial parts of Artemisia myriantha(Asteraceae).The new compounds were established by spectroscopic data analyses(HRMS,IR,1D and 2D NMR),and their absolute configurations were confirmed by the single-crystal X-ray diffraction or ECD calculations.The isolates showed cytotoxicity against HepG2 cells with IC50 values ranging from 33.3 to 145.2μM.展开更多
Uncariae Ramulus Cum Uncis(Gou-Teng),the dried hook-bearing stems of several Uncaria plants(Rubiaceae),is a wellknown herbal medicine in China.The clinical application of Gou-Teng is bewildered for the morphological a...Uncariae Ramulus Cum Uncis(Gou-Teng),the dried hook-bearing stems of several Uncaria plants(Rubiaceae),is a wellknown herbal medicine in China.The clinical application of Gou-Teng is bewildered for the morphological and chemical similarity between diferent species.In order to discern their chemical and biological diference,an ultra-fast liquid chromatography equipped with ion trap time-of-fight mass spectrometry(UFLC-IT/TOF-MS)combining with melatonin(MT1 and MT2)and 5-hydroxytryptamine(5-HT1A and 5-HT2C)receptors agonistic assay in vitro was conducted on seven Uncaria species.As a result,57 compounds including 35 indole alkaloids,ten favonoids,fve triterpenoids,fve chlorogenic analogues,and two other compounds were characterized based on their MS/MS patterns and UV absorptions.Specifcally,cadambine-type and corynanthein-type alkaloids were exclusively present in U.rhynchophylla and U.scandens,whereas corynoxine-type alkaloids were commonly detected in all the seven Uncaria plants.Three Uncaria species,U.rhynchophylla,U.macrophylla,and U.yunnanensis showed obviously agnostic activity on four neurotransmitter receptors(MT1,MT2,5-HT1A,and 5-HT_(2C)).This frst-time UFLCMS-IT-TOF analyses integrated with biological assay on seven Uncaria plants will provide scientifc viewpoints for the clinical application of Gou-Teng.展开更多
Swerilactones H–K(1–4)as four unprecedented secoiridoid trimers represent a new type of natural product,which has attracted much interest of natural chemists due to their novel skeletons and promising bioactivity.In...Swerilactones H–K(1–4)as four unprecedented secoiridoid trimers represent a new type of natural product,which has attracted much interest of natural chemists due to their novel skeletons and promising bioactivity.In order to well understand their MS fragmentation behaviors,they were investigated by electrospray ionization ion-trap time-of-flight multistage product ion mass spectrometry(ESI-IT-TOF-MSn)for the first time.The protonated molecules([M?H]?)of swerilactones J and K,and deprotonated molecules([M-H]-)of swerilactones H,J and K were readily observed in the conventional single-stage mass spectra(MS);however only the[M?Cl]-ion for swerilactone I was obtained in negative mode.Based on the MSn study,the fragmentation pathways of swerilactones H and I in negative mode,and swerilactones J and K in both positive and negative modes were proposed.The neutral losses of H_(2)O,CO,CO_(2)and C_(2)H_(4)O moieties are the particular elimination from the precursor ions due to the presence of hydroxyl,d-lactone and 1-O-ethyl moieties in their structures,of which the retro-Diels–Alder cleavage was the most particular dissociation.The fragment ions at m/z 341 and 291 in negative mode can be considered as the diagnostic ions for secoiridoid trimers.This investigation will provide valuable information for their fast characterization from complicated natural mixtures and extensive understanding their structural architectures.展开更多
Ten 3,5-dimethylcoumarins(1-6 and 8‒11)involving six new ones(1-6),together with a known 3-methylcoumarin(7),were isolated from the aerial parts of three Chelonopsis plants,C.praecox,C.odontochila,and C.pseudobracteat...Ten 3,5-dimethylcoumarins(1-6 and 8‒11)involving six new ones(1-6),together with a known 3-methylcoumarin(7),were isolated from the aerial parts of three Chelonopsis plants,C.praecox,C.odontochila,and C.pseudobracteata.The struc-tures of the new compounds were determined by extensive HRESIMS,1D and 2D NMR spectroscopic analyses.According to the substitution at C-5,these coumarins were classified into 5-methyl,5-hydroxymethyl,5-formyl,and 5-nor types.All the isolates were assayed for their inhibition onα-glucosidase,protein tyrosine phosphatase 1B,and T-cell protein tyrosine phosphatase in vitro.展开更多
Sixteen tropinone derivatives were prepared,and their antitumor activities against five human cancer cells(HL-60,A-549,SMMC-7721,MCF-7 and SW480)were evaluated with MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy methox...Sixteen tropinone derivatives were prepared,and their antitumor activities against five human cancer cells(HL-60,A-549,SMMC-7721,MCF-7 and SW480)were evaluated with MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy methoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium]assay.Most of the derivatives exhibited better activities compared with tropinone at the concentration of 40 pM.Particularly,derivative 6 showed significant activities with IC50 values of 3.39,13.59,6.65,13.09 and 12.38 pM respectively against HL-60,A-549,SMMC-7721,MCF-7 and SW480 cells,which suggested more potent activities than that of cis-dichlorodiamineplatinum(DDP).展开更多
28 Derivatives of panaxadiol(PD)and panaxatriol were synthesized and evaluated for their anti-HBV activity on HepG 2.2.15 cells,of which 17 derivatives inhibited HBV DNA replication.Compounds 4,9,10,14,and 15 showed m...28 Derivatives of panaxadiol(PD)and panaxatriol were synthesized and evaluated for their anti-HBV activity on HepG 2.2.15 cells,of which 17 derivatives inhibited HBV DNA replication.Compounds 4,9,10,14,and 15 showed moderate activity against HBV DNA replication with IC50 values ranged from 7.27 to 28.21 lM compared with PD.In particular,3-O-20-thenoyl panaxadiol(4)inhibited not only HBV DNA replication(IC50=16.5 lM,SI[115.7)but also HBsAg(IC50=30.8 lM,SI[62.0)and HBeAg(IC50=18.2 lM,SI[105.14)secretions.Their structure–activity relationships were discussed for guiding future research toward the discovery of new anti-HBV agents.展开更多
Ten new germacrane-type sesquiterpenoids,artemyrianosins A-J(1-10),were isolated from the aerial parts of Arte-misia myriantha.Their structures were elucidated by spectral analyses including UV,IR,HRESIMS,1D and 2D NM...Ten new germacrane-type sesquiterpenoids,artemyrianosins A-J(1-10),were isolated from the aerial parts of Arte-misia myriantha.Their structures were elucidated by spectral analyses including UV,IR,HRESIMS,1D and 2D NMR,ECD and the absolute configurations of compounds 1 and 7-9 were characterized using X-ray crystallography.All isolates were tested their cytotoxicity against three human hepatoma cell lines(HepG2,Huh7,and SK-Hep-1),and com-pounds 1-3,7,and 10 showed cytotoxicity with IC50 values ranging from 43.7 to 89.3μM.Among them,the most active compound 3 exhibited activity against three human hepatoma cell lines with IC50 values of 43.7μM(HepG2),47.9μM(Huh7),and 44.9μM(SK-Hep-1).展开更多
Eight new guaiane-type sesquiterpenoid trimers,artemsieverolactones A—H,possessing unprecedented scaffolds via biocatalyzed[4+2]Diels−Alder cycloaddition reactions were identified from Artemisia sieversiana.Their str...Eight new guaiane-type sesquiterpenoid trimers,artemsieverolactones A—H,possessing unprecedented scaffolds via biocatalyzed[4+2]Diels−Alder cycloaddition reactions were identified from Artemisia sieversiana.Their structures were determined by comprehensive spectroscopic data,single-crystal X-ray diffraction analyses,and ECD calculations.In terms of structure,artemsieverolactones A—H are first examples of sesquiterpenoid trimers from guaiane-type sesquiterpenoid through four different[4+2]Diels−Alder cycloaddition models.Antihepatic fibrosis assay suggested that five compounds exhibited activity against HSC-LX2 with IC_(50)values ranging from 37.8 to 117.1μmol/L.The most active artemsieverolactone B(2)displayed significant inhibitory activity against HSC-LX2 with IC_(50)value of 37.8μmol/L,which was 3 times more active than the positive drug silybin(IC_(50),139.7μmol/L).Preliminary mechanism study revealed that artemsieverolactone B could inhibit the deposition of human collagen typeⅠ(ColⅠ),human hyaluronic acid(HA),and human laminin(HL)with IC_(50)values of 40.4μmol/L(Col I),55.1μmol/L(HL),47.3μmol/L(HA),which was 2 to 3-fold more potent than silybin.展开更多
Nineteen new cadinane-involving sesquiterpenoid dimers,artemordins A-S(1-—19),together with 13 known SDs(20-32)were isolated from Artemisia ordosica.Their structures and absolute configurations were established by co...Nineteen new cadinane-involving sesquiterpenoid dimers,artemordins A-S(1-—19),together with 13 known SDs(20-32)were isolated from Artemisia ordosica.Their structures and absolute configurations were established by comprehensive spectral analyses,X-ray single crystal diffraction,theoretical ECD,and NMR calculations.Chemically,artemordins A-F(1—6)were the first examples of two cadinane units constructed by unprecedented C-3−C-15′or C-3−C-13′single bond with an oxido-rearranged 6/5/6/6 fused ring system;artemordins G-K(7-11)were biogenetically connected by[4+2]cycloaddition reaction and artemordins G-J(7-10)possessed a novel 5/6/6/6/6/6/5-heptacyclic fused ring system.Artemordins L-S(12-19)were formed by esterification,which involved three different types of sesquiterpenoids.Antihepatoma assay suggested that the most active compounds,artemordins B and H(2 and 8),exhibited inhibitory activities on three hepatoma cell lines with IC50 values of 26.9 and 25.1μmol/L(HepG2),29.5 and 18.3μmol/L(Huh7),19.7 and 15.7μmol/L(SK-Hep-1).展开更多
Ten novel isocoumarins,including four pairs of enantiomers,were isolated from Artemisia dubia var.subdigitata(Asteraceae).Compounds 1,2 and 3a/3b possessed a unique 6/6/6-tricyclic system comprising an unusual 1-(2-me...Ten novel isocoumarins,including four pairs of enantiomers,were isolated from Artemisia dubia var.subdigitata(Asteraceae).Compounds 1,2 and 3a/3b possessed a unique 6/6/6-tricyclic system comprising an unusual 1-(2-methylcyclohexyl)propan-1-one moiety fused with isocoumarin core skeleton.Compounds 4a/4b were characterized as an unexpected 2,5-dimethylcyclohexan-1-one scaffold,and compounds 5a/5b and 6a/6b were rare 1,2-seco-isocoumarin.Their structures and absolute configurations were elucidated through spectroscopic data,X-ray crystallography,ECD and NMR calculations with DP4+analyses.Plausible biosynthetic pathways were proposed from the naturally occurring isocoumarin.Network pharmacological analysis suggested that the targets of compound 1 were significantly enriched in the cell cycle and Pl3K-Akt signaling pathway.The molecular docking revealed that compound 1 had high binding affinity with CDK2(total score:6.8717).Furthermore,compounds 1 and 2 exhibited inhibitory activity on three human hepatoma cell lines,with inhibitory ratios of 85.1% and 84.5%(HepG2),88.2% and 87.3%(Huh7),and 69.2% and 69.1%(SK-Hep-1)at 200μmol·L^(-1),respectively.展开更多
Background Surgery plays an important role in the treatment of neuroblastoma.Perioperative complications may impact the course of neuroblastoma treatment.To date,comprehensive analyses of complications and risk factor...Background Surgery plays an important role in the treatment of neuroblastoma.Perioperative complications may impact the course of neuroblastoma treatment.To date,comprehensive analyses of complications and risk factors have been lacking.Methods Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and 2021.The data collected included clinical characteristics,operative details,operative complications and postopera-tive outcomes.Risk factors for perioperative complications of retroperitoneal neuroblastoma were analyzed.Results A total of 571 patients were enrolled in this study.Perioperative complications were observed in 255(44.7%)patients.Lymphatic leakage(28.4%),diarrhea(13.5%),and injury(vascular,nerve and organ;7.5%)were the most frequent compli-cations.There were three operation-related deaths(0.53%):massive hemorrhage(n=1),biliary tract perforation(n=1)and intestinal necrosis(n=1).The presence of image-defined risk factors(IDRFs)[odds ratio(OR)=2.09,P<0.01],high stage of the International Neuroblastoma Risk Group staging system(INRGSS)(OR=0.454,P=0.04),retroperitoneal lymph node metastasis(OR=2.433,P=0.026),superior mesenteric artery encasement(OR=3.346,P=0.003),and inferior mesenteric artery encasement(OR=2.218,P=0.019)were identified as independent risk factors for perioperative complications.Conclusions Despite the high incidence of perioperative complications,the associated mortality rate was quite low.Perio-perative complications of retroperitoneal neuroblastoma were associated with IDRFs,INRGSS,retroperitoneal lymph node metastasis and vascular encasement.Patients with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma.展开更多
The asymmetric radical carboamination of 1,1-disubstituted alkenes from readily available alkyl halides and arylamines provides expedient access to valueadded chiralα-tertiary N-arylamines but has been less recognize...The asymmetric radical carboamination of 1,1-disubstituted alkenes from readily available alkyl halides and arylamines provides expedient access to valueadded chiralα-tertiary N-arylamines but has been less recognized.A challenge arises mainly from the difficult reaction initiation inherent in alkyl halides and the construction of fully substituted chiral C–N bonds from sterically congested tertiary alkyl radicals.Herein,we report a copper-catalyzed asymmetric three-component radical carboamination of acrylamides utilizing an anionic chiral N,N,N-ligand under mild conditions.This ligand was essential for the reaction initiation by enhancing the reducing capability of copper and enabling the enantiocontrol over tertiary alkyl radicals.The substrate scope was broad,covering an array of acrylamides,aryl-and heteroaryl-amines,as well as alkyl halides and sulfonyl chlorides,enabling good functional group tolerance.When combined with the follow-up transformation,this strategy provides a versatile platform for accessing structurally diverse chiralα-tertiary N-arylamine building blocks of interest in organic synthesis.展开更多
Leading by cytotoxicity against HepG2 cells,bioactivity-guided fractionation of the EtOAc fraction from Artemisia atrovirens led to the isolation of 18 new guaianolide dimers,artematrolides A-R and lavandiolides A,B,C...Leading by cytotoxicity against HepG2 cells,bioactivity-guided fractionation of the EtOAc fraction from Artemisia atrovirens led to the isolation of 18 new guaianolide dimers,artematrolides A-R and lavandiolides A,B,C,H,and J.Eight compounds(1,4,10,12,13,and 19-21) were unambiguously confirmed by the single-crystal X-ray diffraction analyses,and the others were elucidated based on IR,UV,HRESIMS,1 D and 2 D NMR experiments,and comparison of the experimental and calculated ECD data.Structurally,all of them were [4+2] Diels-Alder adducts of two monomeric guaianolides.The isolates were evaluated for their cytotoxicity against three human hepatoma cell lines,and 19 compounds demonstrated cytotoxicity against HepG2,SMMC-7721,and Huh7 cell lines.Especially,compounds 1,12,14,and 15 exhibited cytotoxicity with IC50 values of 4.4,3.8,7.6,and 6.7 μmol/L(HepG2),9.6,4.6,6.6,and 6.0 μmol/L(SMMC-7721),and 7.6,4.5,6.9,and 5.6 μmol/L(Huh7),respectively.Notably,compound 12 showed the most promising activity against three human hepatoma cell lines and dose-dependently inhibited cell migration and invasion,induced G2/M cell cycle arrest and cell apoptosis in HepG2 cells,down-regulated the expression of BCL-2 and PARP-1,and activated PARP-1 to up-regulate the expression of cleaved-PARP-1.展开更多
基金This work was financially supported by the National Natural Sciences Foundation of China for Distinguished Young Scholar(No.81025023)The authors are grateful to the staff of the analytical group of the State Key Laboratory of Phytochemistry and Plant Resources in West China,Kunming Institute of Botany,Chinese Academy of Sciences,for the measurements of all spectra.
文摘Three new secoiridoids, swertiakoulactone (1) and swertiakosides A and B (2 and 3), were isolated from Swertia kouitchensis. Their structures were elucidated by comprehensive spectroscopic analyses including MS, IR, 1D and 2D NMR data. By the anti-hepatitis B virus (HBV) assay on Hep G 2.2.15 cells line in vitro, compound 1 showed moderate activities inhibiting the HBsAg secretion (IC50 = 1.10 mM, SI = 4.39) and HBV DNA replication (IC50 = 1.16 mM, SI = 4.12).
文摘Colorectal carcinoma(CRC) is a common cause of morbidity and mortality worldwide. Two pathogenic pathways are involved in the development of adenoma to CRC. The first pathway involves APC/β-catenin characterized by chromosomal instability resulting in the accumulation of mutations. The second pathway is characterized by lesions in DNA mismatch repair genes.Aberrant DNA methylation in selected gene promoters has emerged as a new epigenetic pathway in CRC development. CRC screening is the most efficient strategy to reduce death. Specific DNA methylation events occur in multistep carcinogenesis.Epigenetic gene silencing is a causative factor of CRC development. DNA methylations have been extensively examined in stool from CRC and precursor lesions. Many methylated genes have been described in CRC and adenoma, although no definite DNA methylation biomarkers panel has been established. Multiple DNA methylation biomarkers, including secreted frizzled-related protein 2, secreted frizzled-related protein 1, tissue factor pathway inhibitor 2, vimentin, and methylguanine DNA methyltransferase, have been further investigated, and observations have revealed that DNA methylation biomarkers exhibit with high sensitivity and specificity. These markers may also be used to diagnose CRC and adenoma in early stages. Real time polymerase chain reaction(q PCR) is sensitive, scalable, specific, reliable, time saving, and cost effective. Stool exfoliated markers provide advantages, including sensitivity and specificity. A stool q PCR methylation test may also be an enhanced tool for CRC and adenoma screening.
基金This work was funded by the National Natural Science Foundation of China and Yunnan Province(U0832603)the National Science Foundation of China for Distinguished Young Scholars(81025023)+1 种基金the West Light Foundation of the Chinese Academy of Sciences,the International Foundation for Science(No.F/5202-1)the Youth Innovation Promotion Association,CAS.
文摘Eleven new secoiridoid aglycones involving unusual C9-skeleton:swerimilegenins A-F(1-6);bis-C9-skeleton:swerimilegenin G(7);and C_(10)-skeleton:swerimilegenins H−K(8−11),as well as six known ones,were isolated from the low-polarity part of the traditional Chinese herb medicine Swertia mileensis.Their structures were determined by extensive spectroscopic data and X-ray diffraction.Biogenetically,swerimilegenin A(1)belonged to 10-nor-secoiridoid,and swerimilegenins B-F(2-6)were 1-nor-secoiridoids.Erythrocentaurin(12)and gentiogenal(15)showed moderate anti-HBV activity on HepG 2.2.15 cell line in vitro.
基金supported by the CAS Hundred Talents Program,the Youth Innovation Promotion Association of the Chinese Academy of Sciences(CN),and Southeast Asia Biodiversity Research Institute,CAS(2017CASSEABRIQG003).
文摘Mentha haplocalyx(Mentha canadensis)is widely used as a medicinal plant in traditional Chinese medicine,and the extracts of its aerial parts are found to signifcantly inhibit the activity ofα-glucosidase with an IC_(50) value of 21.0μg/mL.Bioactivity-guided isolation of the extracts aforded two new compounds(1 and 2),together with 23 known ones(3-25).Their structures were established by extensive spectroscopic analyses(1D and 2D NMR,MS,IR and UV).Compounds 1-17 and 21-25 were evaluated for theirα-glucosidase inhibitory activities.Compound 11 was the most active ones with an IC_(50) values of 83.4μM.These results verify theα-glucosidase inhibitory activity of M.haplocalyx(M.canadensis)and specify its active compounds for the frst time.
基金This work was financially supported by the Program of Yunling Scholarship,the Youth Innovation Promotion Association,CAS,the Applied Basic Research Programs of Yunnan Province(2017FB137)the CAS Hundred Talents Program,and the CAS"Light of West China"Program(Western Youth Scholars"A").
文摘Hepatitis B virus(HBV)infection causing acute and chronic hepatitis is a serious problem worldwide,whereas the current treatment methods are unsatisfactory.Traditional Chinese herbs that have long been used for medicinal purposes are fascinating sources for novel anti-HBV candidates.This paper summarizes the progress of anti-HBV constituents from diverse medicinal plants in China to provide information for searching new anti-HBV drugs from natural sources.
基金supported by the Program of Yunling Scholarship,the CAS“Light of West China”Program(Western Youth Scholars“A”),the Youth Innovation Promotion Association CAS(2013252)the Applied Basic Research Programs of Yunnan Province(2017FB137).
文摘A new favane,bropapyriferol(1),and eleven known ones were isolated from the EtOAc part of Broussonetia papyrifera under the guidance of bioassay.The structure of compound 1 was determined by extensive 1D and 2D NMR,[α]_(D) spectroscopic data and quantum computation.Daphnegiravan F(2)and 5,7,3′,4′-tetrahydroxy-3-methoxy-8,5′-diprenylfavone(3)showed signifcantly anti-oral microbial activity against fve Gram-positive strains and three Gram-negative strains in vitro.Especially,compound 3 was more potent in suppressing Actinomyces naeslundii and Porphyromonas gingivalis(MIC=1.95 ppm)than the positive control,triclosan.
基金supported by the Yunnan Wanren Project(YNWR-KJLJ-2019-002)the Program of Yunling Scholarship,the Reserve Talents of Young and Middle-aged Academic and Technical Leaders in Yunnan Province,and the Youth Innovation Promotion Association,CAS(2013252).
文摘Two new sesquiterpenoids,artemlavanins A(1)and B(3),together with fifteen known compounds(2 and 4−17)were iso-lated from the EtOH extract of Artemisia lavandulaefolia.The structures of new compounds were elucidated by extensive spectroscopic analyses(HRESIMS,1D and 2D NMR)and ECD calculations.Compound 1 was a sesquiterpenoid lactone possessing a rearranged eudesmane skeleton;compounds 2-5,6-8,9 and 10-12 belonged to the eudesmane,guaiane,oppositane and farnesane sesquiterpenoids,respectively;compounds 13-17 were the phenyl derivatives with a 4-hydroxy-acetophenone moiety.Twelve compounds(1-3,5-7,10-12,14,15 and 17)displayed cytotoxicity against hepatic stellate cell line LX2(HSC-LX2)with IC50 values ranging from 35.1 to 370.3μM.Compounds 2,7,10-12 and 17 exhibited the stronger cytotoxicity than silybin(IC50,169.6μM)with IC50 values of 82.1,35.1,95.0,83.8,81.6 and 90.1μM.Compound 7 as the most active one showed significant inhibition on the deposition of human collagen type I(Col I),human hyaluronic acid(HA)and human laminin(HL)with IC50 values of 10.7,24.5 and 13.3μM.
基金supported by the Yunnan Wanren Project(YNWR-KJLJ-2019-002)the Program of Yunling Scholarship,the Reserve Talents of Young and Middle-aged Academic and Technical Leaders in Yunnan Province,and the Youth Innovation Promotion Association,CAS(2013252).
文摘Four new sesquiterpenoids,artemyrianins A-D(1-4),and three new norlignans,artemyrianins E-G(5-7),together with five known compounds(8-12),were isolated from the aerial parts of Artemisia myriantha(Asteraceae).The new compounds were established by spectroscopic data analyses(HRMS,IR,1D and 2D NMR),and their absolute configurations were confirmed by the single-crystal X-ray diffraction or ECD calculations.The isolates showed cytotoxicity against HepG2 cells with IC50 values ranging from 33.3 to 145.2μM.
基金supported by the National Natural Science Foundation of China(81573322)the Yunnan Wanren Project(YNWR-QNBJ-2018-061)+1 种基金the Youth Innovation Promotion Association,CAS(2013252)the Program of Yunling Scholarship,the Yunnan Science Fund for Excellent Young Scholars(2019FI017)。
文摘Uncariae Ramulus Cum Uncis(Gou-Teng),the dried hook-bearing stems of several Uncaria plants(Rubiaceae),is a wellknown herbal medicine in China.The clinical application of Gou-Teng is bewildered for the morphological and chemical similarity between diferent species.In order to discern their chemical and biological diference,an ultra-fast liquid chromatography equipped with ion trap time-of-fight mass spectrometry(UFLC-IT/TOF-MS)combining with melatonin(MT1 and MT2)and 5-hydroxytryptamine(5-HT1A and 5-HT2C)receptors agonistic assay in vitro was conducted on seven Uncaria species.As a result,57 compounds including 35 indole alkaloids,ten favonoids,fve triterpenoids,fve chlorogenic analogues,and two other compounds were characterized based on their MS/MS patterns and UV absorptions.Specifcally,cadambine-type and corynanthein-type alkaloids were exclusively present in U.rhynchophylla and U.scandens,whereas corynoxine-type alkaloids were commonly detected in all the seven Uncaria plants.Three Uncaria species,U.rhynchophylla,U.macrophylla,and U.yunnanensis showed obviously agnostic activity on four neurotransmitter receptors(MT1,MT2,5-HT1A,and 5-HT_(2C)).This frst-time UFLCMS-IT-TOF analyses integrated with biological assay on seven Uncaria plants will provide scientifc viewpoints for the clinical application of Gou-Teng.
文摘Swerilactones H–K(1–4)as four unprecedented secoiridoid trimers represent a new type of natural product,which has attracted much interest of natural chemists due to their novel skeletons and promising bioactivity.In order to well understand their MS fragmentation behaviors,they were investigated by electrospray ionization ion-trap time-of-flight multistage product ion mass spectrometry(ESI-IT-TOF-MSn)for the first time.The protonated molecules([M?H]?)of swerilactones J and K,and deprotonated molecules([M-H]-)of swerilactones H,J and K were readily observed in the conventional single-stage mass spectra(MS);however only the[M?Cl]-ion for swerilactone I was obtained in negative mode.Based on the MSn study,the fragmentation pathways of swerilactones H and I in negative mode,and swerilactones J and K in both positive and negative modes were proposed.The neutral losses of H_(2)O,CO,CO_(2)and C_(2)H_(4)O moieties are the particular elimination from the precursor ions due to the presence of hydroxyl,d-lactone and 1-O-ethyl moieties in their structures,of which the retro-Diels–Alder cleavage was the most particular dissociation.The fragment ions at m/z 341 and 291 in negative mode can be considered as the diagnostic ions for secoiridoid trimers.This investigation will provide valuable information for their fast characterization from complicated natural mixtures and extensive understanding their structural architectures.
基金the Yunnan Wanren Project(YNWR-QNBJ-2018-061)the Natural Science Foundation of Yunnan Province(2019FI017)the Reserve Talents of Young and Middle-Aged Academic and Technical Leaders in Yunnan Province.
文摘Ten 3,5-dimethylcoumarins(1-6 and 8‒11)involving six new ones(1-6),together with a known 3-methylcoumarin(7),were isolated from the aerial parts of three Chelonopsis plants,C.praecox,C.odontochila,and C.pseudobracteata.The struc-tures of the new compounds were determined by extensive HRESIMS,1D and 2D NMR spectroscopic analyses.According to the substitution at C-5,these coumarins were classified into 5-methyl,5-hydroxymethyl,5-formyl,and 5-nor types.All the isolates were assayed for their inhibition onα-glucosidase,protein tyrosine phosphatase 1B,and T-cell protein tyrosine phosphatase in vitro.
基金supported by the Hundred Talents Program of the Chinese Academy of Sciences(CAS),the Youth Innovation Promotion Association,CAS and the Program of Yunling Scholarship.
文摘Sixteen tropinone derivatives were prepared,and their antitumor activities against five human cancer cells(HL-60,A-549,SMMC-7721,MCF-7 and SW480)were evaluated with MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy methoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium]assay.Most of the derivatives exhibited better activities compared with tropinone at the concentration of 40 pM.Particularly,derivative 6 showed significant activities with IC50 values of 3.39,13.59,6.65,13.09 and 12.38 pM respectively against HL-60,A-549,SMMC-7721,MCF-7 and SW480 cells,which suggested more potent activities than that of cis-dichlorodiamineplatinum(DDP).
基金the National Natural Science Foundation of China for Distinguished Young Scholars(No.81025023)the National Natural Science Foundation of China(81202436)the West Light Foundation of the Chinese Academy of Sciences,and the Youth Innovation Promotion Association,CAS.
文摘28 Derivatives of panaxadiol(PD)and panaxatriol were synthesized and evaluated for their anti-HBV activity on HepG 2.2.15 cells,of which 17 derivatives inhibited HBV DNA replication.Compounds 4,9,10,14,and 15 showed moderate activity against HBV DNA replication with IC50 values ranged from 7.27 to 28.21 lM compared with PD.In particular,3-O-20-thenoyl panaxadiol(4)inhibited not only HBV DNA replication(IC50=16.5 lM,SI[115.7)but also HBsAg(IC50=30.8 lM,SI[62.0)and HBeAg(IC50=18.2 lM,SI[105.14)secretions.Their structure–activity relationships were discussed for guiding future research toward the discovery of new anti-HBV agents.
基金supported by the Key Program of the National Natural Science Foundation of China (22137008)the Yunnan Wanren Project (YNWR-KJLJ-2019-002).
文摘Ten new germacrane-type sesquiterpenoids,artemyrianosins A-J(1-10),were isolated from the aerial parts of Arte-misia myriantha.Their structures were elucidated by spectral analyses including UV,IR,HRESIMS,1D and 2D NMR,ECD and the absolute configurations of compounds 1 and 7-9 were characterized using X-ray crystallography.All isolates were tested their cytotoxicity against three human hepatoma cell lines(HepG2,Huh7,and SK-Hep-1),and com-pounds 1-3,7,and 10 showed cytotoxicity with IC50 values ranging from 43.7 to 89.3μM.Among them,the most active compound 3 exhibited activity against three human hepatoma cell lines with IC50 values of 43.7μM(HepG2),47.9μM(Huh7),and 44.9μM(SK-Hep-1).
基金supported by the Key Program of National Natural Science Foundation of China(22137008)the Xingdian Yingcai Project(YNWR-KJLJ-2019-002)+1 种基金the Youth Innovation Promotion Association,CAS(2020386)the Reserve Talents of Young and Middle-aged Academic and Technical Leaders in Yunnan Province(202105AC160021).
文摘Eight new guaiane-type sesquiterpenoid trimers,artemsieverolactones A—H,possessing unprecedented scaffolds via biocatalyzed[4+2]Diels−Alder cycloaddition reactions were identified from Artemisia sieversiana.Their structures were determined by comprehensive spectroscopic data,single-crystal X-ray diffraction analyses,and ECD calculations.In terms of structure,artemsieverolactones A—H are first examples of sesquiterpenoid trimers from guaiane-type sesquiterpenoid through four different[4+2]Diels−Alder cycloaddition models.Antihepatic fibrosis assay suggested that five compounds exhibited activity against HSC-LX2 with IC_(50)values ranging from 37.8 to 117.1μmol/L.The most active artemsieverolactone B(2)displayed significant inhibitory activity against HSC-LX2 with IC_(50)value of 37.8μmol/L,which was 3 times more active than the positive drug silybin(IC_(50),139.7μmol/L).Preliminary mechanism study revealed that artemsieverolactone B could inhibit the deposition of human collagen typeⅠ(ColⅠ),human hyaluronic acid(HA),and human laminin(HL)with IC_(50)values of 40.4μmol/L(Col I),55.1μmol/L(HL),47.3μmol/L(HA),which was 2 to 3-fold more potent than silybin.
基金This work was financially supported by the Key Program of National Natural Science Foundation of China(22137008)the Xingdian Yingcai Project(YNWR-KJLJ-2019-002)+4 种基金the Youth Innovation Promotion Association,CAS(2020386)the Reserve Talents of Young and Middle-aged Academic and Technical Leaders in Yunnan Province(202105AC160021)the High-Level Talent Program of Yunnan Province(YNQR-QNRC-2020-125)the Science and Technology Plan Projects in Yunnan Province(202201AT070143)State Key Laboratory of Phytochemistry and Plant Resources in West China(P2021-ZZ06).
文摘Nineteen new cadinane-involving sesquiterpenoid dimers,artemordins A-S(1-—19),together with 13 known SDs(20-32)were isolated from Artemisia ordosica.Their structures and absolute configurations were established by comprehensive spectral analyses,X-ray single crystal diffraction,theoretical ECD,and NMR calculations.Chemically,artemordins A-F(1—6)were the first examples of two cadinane units constructed by unprecedented C-3−C-15′or C-3−C-13′single bond with an oxido-rearranged 6/5/6/6 fused ring system;artemordins G-K(7-11)were biogenetically connected by[4+2]cycloaddition reaction and artemordins G-J(7-10)possessed a novel 5/6/6/6/6/6/5-heptacyclic fused ring system.Artemordins L-S(12-19)were formed by esterification,which involved three different types of sesquiterpenoids.Antihepatoma assay suggested that the most active compounds,artemordins B and H(2 and 8),exhibited inhibitory activities on three hepatoma cell lines with IC50 values of 26.9 and 25.1μmol/L(HepG2),29.5 and 18.3μmol/L(Huh7),19.7 and 15.7μmol/L(SK-Hep-1).
基金financially supported by the Key Program of the National Natural Science Foundation of China(22137008)the Xingdian Yingcai Project(YNWR-KJLJ-2019-002)+1 种基金the Youth Innovation Promotion Association,CAs(2020386)the Reserve Talents of Young and Middle-aged Academic and Technical Leaders in Yunnan Province(202105AC160021).
文摘Ten novel isocoumarins,including four pairs of enantiomers,were isolated from Artemisia dubia var.subdigitata(Asteraceae).Compounds 1,2 and 3a/3b possessed a unique 6/6/6-tricyclic system comprising an unusual 1-(2-methylcyclohexyl)propan-1-one moiety fused with isocoumarin core skeleton.Compounds 4a/4b were characterized as an unexpected 2,5-dimethylcyclohexan-1-one scaffold,and compounds 5a/5b and 6a/6b were rare 1,2-seco-isocoumarin.Their structures and absolute configurations were elucidated through spectroscopic data,X-ray crystallography,ECD and NMR calculations with DP4+analyses.Plausible biosynthetic pathways were proposed from the naturally occurring isocoumarin.Network pharmacological analysis suggested that the targets of compound 1 were significantly enriched in the cell cycle and Pl3K-Akt signaling pathway.The molecular docking revealed that compound 1 had high binding affinity with CDK2(total score:6.8717).Furthermore,compounds 1 and 2 exhibited inhibitory activity on three human hepatoma cell lines,with inhibitory ratios of 85.1% and 84.5%(HepG2),88.2% and 87.3%(Huh7),and 69.2% and 69.1%(SK-Hep-1)at 200μmol·L^(-1),respectively.
基金supported by General Program of National Natural Science Foundation of China(No.32270853)Key Program of Natural Science Foundation of Zhejiang Province(No.HDMZ23H160029).
文摘Background Surgery plays an important role in the treatment of neuroblastoma.Perioperative complications may impact the course of neuroblastoma treatment.To date,comprehensive analyses of complications and risk factors have been lacking.Methods Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and 2021.The data collected included clinical characteristics,operative details,operative complications and postopera-tive outcomes.Risk factors for perioperative complications of retroperitoneal neuroblastoma were analyzed.Results A total of 571 patients were enrolled in this study.Perioperative complications were observed in 255(44.7%)patients.Lymphatic leakage(28.4%),diarrhea(13.5%),and injury(vascular,nerve and organ;7.5%)were the most frequent compli-cations.There were three operation-related deaths(0.53%):massive hemorrhage(n=1),biliary tract perforation(n=1)and intestinal necrosis(n=1).The presence of image-defined risk factors(IDRFs)[odds ratio(OR)=2.09,P<0.01],high stage of the International Neuroblastoma Risk Group staging system(INRGSS)(OR=0.454,P=0.04),retroperitoneal lymph node metastasis(OR=2.433,P=0.026),superior mesenteric artery encasement(OR=3.346,P=0.003),and inferior mesenteric artery encasement(OR=2.218,P=0.019)were identified as independent risk factors for perioperative complications.Conclusions Despite the high incidence of perioperative complications,the associated mortality rate was quite low.Perio-perative complications of retroperitoneal neuroblastoma were associated with IDRFs,INRGSS,retroperitoneal lymph node metastasis and vascular encasement.Patients with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma.
基金Financial supports were obtained from the National Natural Science Foundation of China(NSFC,grant nos.22025103,22331006,92256301,22371112,and 22101122)the National Key R&D Program of China(grant nos.2021YFF0701604 and 2021YFF0701704)+5 种基金Guangdong Major Project of Basic and Applied Basic Research,China(grant no.2023B0303000020)Guangdong Basic and Applied Basic Research Foundation,China(grant no.2023A1515140088)Shenzhen Science and Technology Program,China(grant nos.JCYJ20220818100600001,JCYJ202205300115409020,and 20220814231741002)the Shenzhen Key Laboratory of Cross-Coupling Reactions,China(grant no.ZDSYS20220328104200001)Dongguan Key Laboratory of Interdisciplinary Science for Advanced Materials and Large-Scale Scientific Facilities,China(grant no.2023KSYS014)Also,the New Cornerstone Science Foundation through the XPLORER PRIZE is gratefully acknowledged.
文摘The asymmetric radical carboamination of 1,1-disubstituted alkenes from readily available alkyl halides and arylamines provides expedient access to valueadded chiralα-tertiary N-arylamines but has been less recognized.A challenge arises mainly from the difficult reaction initiation inherent in alkyl halides and the construction of fully substituted chiral C–N bonds from sterically congested tertiary alkyl radicals.Herein,we report a copper-catalyzed asymmetric three-component radical carboamination of acrylamides utilizing an anionic chiral N,N,N-ligand under mild conditions.This ligand was essential for the reaction initiation by enhancing the reducing capability of copper and enabling the enantiocontrol over tertiary alkyl radicals.The substrate scope was broad,covering an array of acrylamides,aryl-and heteroaryl-amines,as well as alkyl halides and sulfonyl chlorides,enabling good functional group tolerance.When combined with the follow-up transformation,this strategy provides a versatile platform for accessing structurally diverse chiralα-tertiary N-arylamine building blocks of interest in organic synthesis.
基金supported by the Yunnan Wanren Project (YNWRKJLJ-2019-002)the Program of Yunling Scholarship (Ji-Jun, Chen)the Reserve Talents of Young and Middle-aged Academic and Technical Leaders in Yunnan Province (Changan, Geng)。
文摘Leading by cytotoxicity against HepG2 cells,bioactivity-guided fractionation of the EtOAc fraction from Artemisia atrovirens led to the isolation of 18 new guaianolide dimers,artematrolides A-R and lavandiolides A,B,C,H,and J.Eight compounds(1,4,10,12,13,and 19-21) were unambiguously confirmed by the single-crystal X-ray diffraction analyses,and the others were elucidated based on IR,UV,HRESIMS,1 D and 2 D NMR experiments,and comparison of the experimental and calculated ECD data.Structurally,all of them were [4+2] Diels-Alder adducts of two monomeric guaianolides.The isolates were evaluated for their cytotoxicity against three human hepatoma cell lines,and 19 compounds demonstrated cytotoxicity against HepG2,SMMC-7721,and Huh7 cell lines.Especially,compounds 1,12,14,and 15 exhibited cytotoxicity with IC50 values of 4.4,3.8,7.6,and 6.7 μmol/L(HepG2),9.6,4.6,6.6,and 6.0 μmol/L(SMMC-7721),and 7.6,4.5,6.9,and 5.6 μmol/L(Huh7),respectively.Notably,compound 12 showed the most promising activity against three human hepatoma cell lines and dose-dependently inhibited cell migration and invasion,induced G2/M cell cycle arrest and cell apoptosis in HepG2 cells,down-regulated the expression of BCL-2 and PARP-1,and activated PARP-1 to up-regulate the expression of cleaved-PARP-1.
