Objective:To profile the secondary metabolites and to evaluate the antidiabetic potential of hydroethanolic leaf extracts of Conocarpus lancifolius.Methods:The various hydroethanolic extracts of Conocarpus lancifolius...Objective:To profile the secondary metabolites and to evaluate the antidiabetic potential of hydroethanolic leaf extracts of Conocarpus lancifolius.Methods:The various hydroethanolic extracts of Conocarpus lancifolius leaf were prepared by ultrasonication assisted freezedrying.Total phenolic contents,flavonoid contents,antioxidant activity,α-glucosidase andα-amylase inhibitions of leaf extracts were determined.The metabolite profiling was accomplished by UHPLC-Q-TOF-MS/MS analysis.The antidiabetic assessment of the most potent extract was carried out by measuring the hypoglycemic and hypolipidemic effect in the high fat diet-fed diabetic albino mice.The blood glucose level,haemoglobin,total cholesterol,high-density lipoproteins(HDL)and low-density lipoproteins(LDL)were determined.Results:The 60%ethanolic extract exhibited the highest phenolic and flavonoid contents of(349.39±2.13)mg GAE/g dry extract and(116.95±2.34)mg RE/g dry extracts,respectively,and the highest DPPH scavenging activity with an IC50 value of(32.87±1.11)μg/mL.The IC50 values forα-glucosidase andα-amylase inhibitions were(38.64±0.93)μg/mL and(44.80±1.57)μg/mL,respectively.UHPLC-Q-TOF-MS/MS analysis confirmed the presence of gallic acid,ellagic acid,corilagin,kaempherol-3-O-rutinoside,caffeic acid derivative,isorhamnetin and galloyl derivatives in the 60%ethanolic extract.Plant extract at a dose of 450 mg/kg body weight reduced blood glucose level,total cholesterol,LDL and HDL,and increased haemoglobin in alloxan-induced diabetic mice,Conclusions:Conocarpus lancifolius leaves are proved as a good source of biologically functional metabolites and possess antidiabetic activity which may be further explored to treat diabetes.展开更多
In this work,a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry(LC-MS)method was developed for metabolite profiling of the glutathione anabolic pathway(GAP)in cancer tissues and cells.The p...In this work,a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry(LC-MS)method was developed for metabolite profiling of the glutathione anabolic pathway(GAP)in cancer tissues and cells.The pyrylium salt of 6,7-dimethoxy-3-methyl isochromenylium tetrafluoroborate(DMMIC)was used to label the amino group of metabolites,and a reductant of dithiothreitol(DTT)was employed to stabilize the thiol group.By combining DMMIC derivatization with LC-MS,it was feasible to quantify the 13 main metabolites on the GAP in complex biological samples,which had good linearity(R^(2)=0.99810.9999),precision(interday precision of 1.6%e19.0%and intraday precision of 1.4%e19.8%)and accuracy(83.4%-115.7%).Moreover,the recovery assessments in tissues(82.5%e107.3%)and in cells(98.1%e118.9%)with GSH-^(13)C2,^(15)N,and Cys-^(15)N demonstrated the reliability of the method in detecting tissues and cells.Following a methodological evaluation,the method was applied successfully to investigate difference in the GAP between the carcinoma and para-carcinoma tissues of esophageal squamous cell carcinoma(ESCC)and the effect of p-hydroxycinnamaldehyde(CMSP)on the GAP in KYSE150 esophageal cancer cells.The results demonstrate that the developed method provides a promising new tool to elucidate the roles of GAP in physiological and pathological processes,which can contribute to research on drugs and diseases.展开更多
Objective:To evaluate the antioxidant potential and pancreatic lipase inhibitory action of optimized hydroethanolic extracts of Solanum nigrum.Methods:Optimized extraction for maximum recovery of metabolites was perfo...Objective:To evaluate the antioxidant potential and pancreatic lipase inhibitory action of optimized hydroethanolic extracts of Solanum nigrum.Methods:Optimized extraction for maximum recovery of metabolites was performed using a combination of freeze-drying and ultrasonication followed by determination of antioxidant and antiobesity properties.The ultra-high performance liquid chromatography equipped with mass spectrometry was used to analyze metabolite profiling of Solanum nigrum.Computational studies were performed using molecular docking and electrostatic potential analysis for individual compounds.The hypolipidemic potential of the most potent extract was assessed in the obese mice fed on fat rich diet.Results:The 80%hydroethanolic extract exhibited the highest extract yield,total phenolic contents,total flavonoid contents along with the strongest 2,2-diphenyl-1-picrylhydrazyl scavenging activity,total antioxidant power,and pancreatic lipase inhibitory properties.The 80%hydroethanolic extract not only regulated the lipid profile of obese mice but also restricted the weight gain in the liver,kidney,and heart.The 80%hydroethanolic extract also reduced alanine transaminase and aspartate transaminase concentrations in serum.The effects of plant extract at 300 mg/kg body weight were quite comparable with the standard drug orlistat.Conclusions:Solanum nigrum is proved as an excellent and potent source of secondary metabolites that might be responsible for obesity mitigation.展开更多
Chang-Kang-Fang(CKF)formula,a Traditional Chinese Medicine(TCM)prescription,has been widely used for the treatment of irritable bowel syndrome(IBS).However,its potential material basis and underlying mechanism remain ...Chang-Kang-Fang(CKF)formula,a Traditional Chinese Medicine(TCM)prescription,has been widely used for the treatment of irritable bowel syndrome(IBS).However,its potential material basis and underlying mechanism remain elusive.Therefore,this study employed an integrated approach that combined ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS)with network pharmacology to systematically characterize the phytochemical components and metabolites of CKF,as well as elucidating its underlying mechanism.Through this comprehensive analysis,a total of 150 components were identified or tentatively characterized within the CKF formula.Notably,six N-acetyldopamine oligomers from Cicadae Periostracum and eight resin glycosides from Cuscutae Semen were characterized in this formula for the first time.Meanwhile,149 xenobiotics(58 prototypes and 91 metabolites)were detected in plasma,urine,feces,brain,and intestinal contents,and the in vivo metabolic pathways of resin glycosides were elaborated for the first time.Furthermore,network pharmacology and molecular docking analyses revealed that alkaloids,flavonoids,chromones,monoterpenes,N-acetyldopamine dimers,p-hydroxycinnamic acid,and Cus-3/isomer might be responsible for the beneficial effects of CKF in treating IBS,and CASP8,MARK14,PIK3C,PIK3R1,TLR4,and TNF may be its potential targets.These discoveries offer a comprehensive understanding of the potential material basis and clarify the underlying mechanism of the CKF formula in treating IBS,facilitating the broader application of CKF in the field of medicine.展开更多
Objective:The absorbed prototypes and metabolites of traditional Chinese medicines in vivo are crucial for identifying their biological functions.However,comprehensive profiling of constituents in vivo is difficult ow...Objective:The absorbed prototypes and metabolites of traditional Chinese medicines in vivo are crucial for identifying their biological functions.However,comprehensive profiling of constituents in vivo is difficult owing to endogenous interference and low metabolite abundance.Therefore,a systematic strategy was proposed for screening and profiling exogenous components in biological matrices based on the mass differences between prototypes and the products of their metabolic reactions.Materials and Methods:Two hundred and forty-seven previously reported metabolic reactions were collected from the relevant literature on the Huangqi-Danshen(HD)herb pair,and a metabolic reaction-based mass difference database was created.The preprocessed data from experimental MS1based on ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry were automatically calculated mass differences by R programming and matched with the database to screen potential constituents.Finally,the components were annotated across the MS2data.Results:A total of 164 components were annotated in the plasma samples from the rats after oral administration of HD,of which 20 were confirmed using the reference standards.The major metabolic pathways include methylation,dehydration,cysteine S-binding,glucuronidation,sulfation,and multistep reactions.Conclusions:This study revealed the metabolic characteristics and biotransformation regulation of HD and laid the foundation for elucidating its therapeutic effects.The proposed approach provides advantageous resources for evaluating the metabolites in the complex systems.展开更多
Piper sarmentosum Roxb.(Piperaceae)is a traditional medicinal and food plant widely distributed in the tropical and subtropical regions of Asia,offering both health and culinary benefits.In this study the secondary me...Piper sarmentosum Roxb.(Piperaceae)is a traditional medicinal and food plant widely distributed in the tropical and subtropical regions of Asia,offering both health and culinary benefits.In this study the secondary metabolites in different organs of P.sarmentosum were identified and their relative abundances were characterized.The metabolic profiles of leaves,roots,stems and fruits were comprehensively investigated by liquid chromatography high-resolution mass spectrometry(LC-HR-MS)and the data subsequently analyzed using multivariate statistical methods.Manual interpretation of the tandem mass spectrometric(MS/MS)fragmentation patterns revealed the presence of 154 tentatively identified metabolites,mostly represented by alkaloids and flavonoids.Principle component analysis and hierarchical clustering indicated the predominant occurrence of flavonoids,lignans and phenyl propanoids in leaves,aporphines in stems,piperamides in fruits and lignan-amides in roots.Overall,this study provides extensive data on the metabolite composition of P.sarmentosum,supplying useful information for bioactive compounds discovery and patterns of their preferential biosynthesis or storage in specific organs.This can be used to optimize production and harvesting as well as to maximize the plant’s economic value as herbal medicine or in food applications.展开更多
The physiological properties of rice grains are immediately obvious to consumers. High-coverage metabolomic characterization of the rice diversity research set predicted a negative correlation between fatty acid and l...The physiological properties of rice grains are immediately obvious to consumers. High-coverage metabolomic characterization of the rice diversity research set predicted a negative correlation between fatty acid and lipid levels and amylose/total starch ratio （amylose ratio）, but the reason for this is unclear. To obtain new insight into the relationships among the visual phenotypes of rice kernels, starch granule structures, amylose ratios, and metabolite changes, we investigated the metabolite changes of five Japonica cultivars with various amylose ratios and two knockout mutants （e 1, a Starch synthase Ilia （SSIIla）-deficient mutant and the SSIIla/starch branching enzyme （BE） double-knockout mutant 4019） by using mass spectrometry-based metabolomics techniques. Scanning electron microscopy clearly showed that the two mutants had unusual starch granule structures. The metabolomic compositions of two cultivars with high amylose ratios （Hoshiyutaka and Yumetoiro） exhibited similar patterns, while that of the double-knockout mutant, which has an extremely high amylose ratio, differed. Rice pedigree network analysis of the cultivars and the mutants provided insight into the association between metabolic-trait properties and their underlying genetic basis in rice breeding in Japan. Multidimensional scaling analysis revealed that the Hoshiyutaka and Yumetoiro cultivars were Indica-like, yet they are classified as Japonica subpopulations. Exploring metabolomic traits is a powerful way to follow rice genetic traces and breeding history.展开更多
Tissue culture techniques were used to produce large amounts of bioactive compounds with medicinal potential, overcoming space and time constraints for cancer prevention. Rice callus suspension cultures(RCSC) and seed...Tissue culture techniques were used to produce large amounts of bioactive compounds with medicinal potential, overcoming space and time constraints for cancer prevention. Rice callus suspension cultures(RCSC) and seed extracts prepared from aromatic rice varieties were used to evaluate the cytotoxic impact on human colon and lung cancer cell lines, as well as a normal control cell line, using Taxol as a positive control. RCSC and seed extracts from two Indian aromatic rice varieties were applied at different concentrations to treat the cancer cell lines and normal lung fibroblasts over varying time intervals. Apoptosis was assessed in 1:5 dilutions of the A549 and HT-29 cell lines treated with RCSC for 72 h, using propidium iodide staining and flow cytometry. RCSC showed a more potent cytotoxic effect than seed extracts with minimal effect on the normal cell line, in contrast to Taxol. Confocal microscopy and flow cytometry further confirmed the apoptotic effect of RCSC. Gas chromatography-mass spectrometry-based metabolic profiling identified metabolites involved in cytotoxicity and highlighted altered pathways. RCSC is proposed as an alternative source for the development of novel anticancer drugs with reduced side effects.展开更多
More than 30 species of benthic Prorocentrum have been identified,some of which produce okadaic acid(OA)and its derivatives,dinophysistoxins(DTXs),which cause diarrhetic shellfish poisoning(DSP).Increasing numbers of ...More than 30 species of benthic Prorocentrum have been identified,some of which produce okadaic acid(OA)and its derivatives,dinophysistoxins(DTXs),which cause diarrhetic shellfish poisoning(DSP).Increasing numbers of benthic Prorocentrum species have been reported in tropical and subtropical waters of China.In contrast,only a few benthic Prorocentrum species have been reported in temperate waters.In this study,morphological descriptions obtained using light microscopy,scanning electron microscopy and molecular characterization of one Prorocentrum clipeus strain isolated from the Yellow Sea are presented.Prorocentrum clipeus cells were nearly circular in shape,with a collar,ridge,and one protrusion.The periflagellar area was wide U-shaped,with two curved projections on platelet 1a.Nine periflagellar platelets of different sizes were observed.The morphology closely fits that of the species isolated from other locations.Phylogenetic analysis based on the molecular sequences of the small subunit(SSU)rDNA,internal transcribed spacer(ITS),and large subunit(LSU)rDNA was performed.A comprehensive metabolomic analysis incorporating target,suspect and non-target screenings was first applied to investigate the intracellular and extracellular metabolite profiles of the current isolate of P.clipeus.According to the results of the target and suspect screenings,179 metabolites or toxins produced by DSP-related algal species,including OA,dinophysistoxin-1(DTX1),dinophysistoxin-2(DTX2)and pectenotoxin-2(PTX2),were not detected.Non-target screening involving feature-based molecular networking(FBMN)provided a global view of major metabolites produced by the P.clipeus DF128 strain and revealed 23 clusters belonging to at least 13 compound classes,with organometallic compounds,lipids and lipid-like molecules,phenylpropanoids and polyketides,and benzenoids as major types.To date,this is the first record of the characterization of P.clipeus in samples from Chinese waters.Our results support the wide distribution of epibenthic Prorocentrum species.展开更多
Background:Diabetic peripheral neuropathy(DPN)is a prevalent and debilitating complication of diabetes mellitus,lacking effective treatment options.Despite unclear underlying mechanisms,electroacupuncture(EA)shows pro...Background:Diabetic peripheral neuropathy(DPN)is a prevalent and debilitating complication of diabetes mellitus,lacking effective treatment options.Despite unclear underlying mechanisms,electroacupuncture(EA)shows promise in relieving DPN symptoms.Neurotransmitter dysregulation is central to DPN pathophysiology.This study aimed to investigate EA’s effects on DPN via targeted neurotransmitter metabolomics.Methods:A streptozotocin-induced mouse model of DPN was developed,and EA treatment was administered for two weeks to assess the therapeutic potential of EA.Following the collection of sciatic nerve samples,LC-MS-based targeted metabolomics analyses investigations were performed to examine alterations in DPN-associated neurotransmitter metabolism brought on by EA therapy.Multivariate statistical analyses were employed to assess metabolite expression patterns,using cluster heatmaps to display neurotransmitter expression results.KEGG pathway analyses were also used to explore the functional classifications of these neurotransmitters and associated metabolic pathways.Results:Targeted neurotransmitter-focused metabolomics analyses led to the identification of 34 putative biomarkers associated with EA treatment,of which 5 showed significant changes,such as beta-alanine(increased by 80.37%,P=0.0004)and kynurenine(decreased by 29.36%,P=0.0163).KEGG pathway analysis indicated that changes in the abundance of these metabolites were associated with the cAMP signaling pathway,neuroactive ligand-receptor interactions,the synaptic vesicle cycle,and other pathways.Conclusion:The results indicate that EA can efficiently regulate neurotransmitter metabolism and restore peripheral nerve function,suggesting a feasible non-pharmacological strategy for DPN treatment and warranting clinical translation.展开更多
Ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry （UPLC-Q-TOF/MS） was developed to identify the absorbed parent components and metabolites in rat bile, plasma an...Ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry （UPLC-Q-TOF/MS） was developed to identify the absorbed parent components and metabolites in rat bile, plasma and urine after oral administration of Radix Paeoniae Alba extract （RPAE）. A total of 65 compounds were detected in rat bile, plasma and urine samples, including 11 parent compounds and 54 metabolites. The results indicated that glucuronidation, hydroxylation and methylation were the major metabolic pathways of the components of RPAE. Furthermore, the results of this work demonstrated that UPLC-Q-TOF/MS combined with MetaboLynx？ software and mass defect filtering （MDF） could provide unique high throughput capabilities for drug metabolism study, with excellent MS mass accuracy and enhanced MSE data acquisition. With the MSE technique, both precursor and fragment mass spectra can be simultaneously acquired by alternating between high and low collision energy during a single chromatographic run.展开更多
Mud crab(Scylla paramamosain)is one of the most consumed crabs in China.Generally,it is believed that dead mud crabs are not edible.Herein,we investigated the postmortem metabolite profile changes of the muscle and he...Mud crab(Scylla paramamosain)is one of the most consumed crabs in China.Generally,it is believed that dead mud crabs are not edible.Herein,we investigated the postmortem metabolite profile changes of the muscle and hepatopancreas of mud crab associated with storage method using nuclear magnetic resonance-based metabolomics coupled with multivariate data analysis.Our results showed that postmortem changes of trimethylamine,organic acids(lactate,formate,and succinate),as well as ATP and its breakdown products are closely affected by the storage method.These metabolites can be used as indicators for monitoring loss of crab freshness.Furthermore,dead mud crabs preserved an edible quality at least for 4 h at room temperature,12h on ice,and 16 d at−20℃,strongly suggesting that dead crab consumption quality should be determined by freshness.They shouldn’t be discarded without considering the effects of different storage conditions on their freshness.展开更多
Cotton fibers elongate rapidly after initiation of elongation, eventually leading to the deposit of a large amount of cellulose. To reveal features of cotton fiber cells at the fast elongation and the secondary cell w...Cotton fibers elongate rapidly after initiation of elongation, eventually leading to the deposit of a large amount of cellulose. To reveal features of cotton fiber cells at the fast elongation and the secondary cell wall synthesis stages, we compared the respective transcriptomes and metabolite profiles. Comparative analysis of transcriptomes by cDNA array identified 633 genes that were differentially regulated during fiber development. Principal component analysis （PCA） using expressed genes as variables divided fiber samples into four groups, which are diagnostic of developmental stages. Similar grouping results are also found if we use non-polar or polar metabolites as variables for PCA of developing fibers. Auxin signaling, wall-loosening and lipid metabolism are highly active during fiber elongation, whereas cellulose biosynthesis is predominant and many other metabolic pathways are downregulated at the secondary cell wall synthesis stage. Transcript and metabolite profiles and enzyme activities are consistent in demonstrating a specialization process of cotton fiber development toward cellulose synthesis. These data demonstrate that cotton fiber cell at a certain stage has its own unique feature, and developmental stages of cotton fiber cells can be distinguished by their transcript and metabolite profiles. During the secondary cell wall synthesis stage, metabolic pathways are streamed into cellulose synthesis.展开更多
Soil salinity is known to improve cadmium(Cd)mobility,especially in arid soils.However,the mechanisms involved in how salt stress-associated metabolic profiles participate in mediating Cd transport in the soil-plant s...Soil salinity is known to improve cadmium(Cd)mobility,especially in arid soils.However,the mechanisms involved in how salt stress-associated metabolic profiles participate in mediating Cd transport in the soil-plant system remain poorly understood.This study was designed to investigate the effects of salinity-induced changes in soil metabolites on Cd bioavailability.Sodium salts in different combinations according to molar ratio(NaCl:Na_(2)SO_(4)=1:1;NaCl:Na_(2)SO_(4):NaHCO_(3)=1:2:1;NaCl:Na_(2)SO_(4):NaHCO_(3):Na_(2)CO_(3)=1:9:9:1;NaCl:Na_(2)SO_(4):NaHCO_(3):Na_(2)CO_(3)=1:1:1:1)were applied to the Cd-contaminated soils,which increased soil Cd availability by 22.36%and the Cd content in wheat grains by 36.61%,compared to the control.Salt stress resulted in soil metabolic reprogramming,which might explain the decreased growth of wheat plants and increased Cd transport from the soil into wheat tissues.For example,down-regulation of starch and sucrose metabolism reduced the production of sugars,which adversely affected growth;up-regulation of fatty acid metabolism allowed wheat plants to maintain a normal intracellular environment under saline conditions;up-regulation of the tricarboxylic acid(TCA)cycle was triggered,causing an increase in organic acid synthesis and the accumulation of organic acids,which facilitated the migration of soil Cd into wheat tissues.In summary,salt stress can facilitate Cd transport into wheat tissues by the direct effect of salt-based ions and the combined effect of altered soil physicochemical properties and soil metabolic profiles in Cd-contaminated soils.展开更多
The evaluation of plant-based feedstocks is an important aspect of biorefining.Nicotiana glauca is a solanaceous,non-food crop that produces large amounts of biomass and is well adapted to grow in suboptimal condition...The evaluation of plant-based feedstocks is an important aspect of biorefining.Nicotiana glauca is a solanaceous,non-food crop that produces large amounts of biomass and is well adapted to grow in suboptimal conditions.In the present article,compatible sequential solvent extractions were applied to N.glauca leaves to enable the generation of enriched extracts containing higher metabolite content comparing to direct leaf extracts.Typically,between 60 to 100 metabolite components were identified within the fractions.The occurrence of plant fatty acids,fatty acid alcohols,alkanes,sterols and terpenoids was detected by gas liquid chromatography-mass spectrometry(GC-MS)and metabolite identification was confirmed by comparison of physico-chemical properties displayed by available authentic standards.Collectively,co-products such waxes,oils,fermentable sugars,and terpenoids were all identified and quantified.The enriched fractions of N.glauca revealed a high level of readily extractable hydrocarbons,oils and high value co-products.In addition,the saccharification yield and cell wall composition analyses in the stems revealed the potential of the residue material as a promising lignocellulosic substrate for the production of fermentable sugars.In conclusion a multifractional cascade for valuable compounds/commodities has been development,that uses N.glauca biomass.These data have enabled the evaluation of N.glauca material as a potential feedstock for biorefining.展开更多
Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal m...Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota.Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq.Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336–0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34–0.55),which were mainly involved in neurodevelopment.Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.展开更多
Four extracts of the marine-derived fungus Penicillium velutinum J.F.H.Beyma were obtained via metal ions stress conditions based on the OSMAC(One Strain Many Compounds)strategy.Using a combination of modern approache...Four extracts of the marine-derived fungus Penicillium velutinum J.F.H.Beyma were obtained via metal ions stress conditions based on the OSMAC(One Strain Many Compounds)strategy.Using a combination of modern approaches such as LC/UV,LC/MS and bioactivity data analysis,as well as in silico calculations,influence metal stress factors to change metabolite profiles Penicillium velutinum were analyzed.From the ethyl acetate extract of the P.velutinum were isolated two new piperazine derivatives helvamides B(1)and C(2)together with known saroclazin A(3)(4S,5R,7S)-4,11-dihydroxy-guaia-1(2),9(10)-dien(4).Their structures were established based on spectroscopic methods.The absolute configuration of helvamide B(1)as 2R,5R was determined by a combination of the X-ray analysis and by time-dependent density functional theory(TD-DFT)calculations of electronic circular dichroism(ECD)spectra.The cytotoxic activity of the isolated compounds against human prostate cancer PC-3 and human embryonic kidney HEK-293 cells and growth inhibition activity against yeast-like fungi Candida albicans were assayed.展开更多
Development of a novel in vivo lung perfusion(IVLP)procedure allows localized delivery of high-dose doxorubicin(DOX)for targeting residual micrometastatic disease in the lungs.However,DOX delivery via IVLP requires ca...Development of a novel in vivo lung perfusion(IVLP)procedure allows localized delivery of high-dose doxorubicin(DOX)for targeting residual micrometastatic disease in the lungs.However,DOX delivery via IVLP requires careful monitoring of drug level to ensure tissue concentrations of this agent remain in the therapeutic window.A small dimension nitinol wire coated with a sorbent of biocompatible morphology(Bio-SPME)has been clinically evaluated for in vivo lung tissue extraction and determination of DOX and its key metabolites.The in vivo Bio-SPME-IVLP experiments were performed on pig model over various(150 and 225 mg/m^(2))drug doses,and during human clinical trial.Two patients with metastatic osteosarcoma were treated with a single 5 and 7 μg/mL(respectively)dose of DOX during a 3-h IVLP.In both pig and human cases,DOX tissue levels presented similar trends during IVLP.Human lung tissue concentrations of drug ranged between 15 and 293 μg/g over the course of the IVLP procedure.In addition to DOX levels,Bio-SPME followed by liquid chromatography-mass spectrometry analysis generated 64 metabolic features during endogenous metabolite screening,providing information about lung status during drug administration.Real-time monitoring of DOX levels in the lungs can be performed effectively throughout the IVLP procedure by in vivo Bio-SPME chemical biopsy approach.Bio-SPME also extracted various endogenous molecules,thus providing a real-time snapshot of the physiology of the cells,which might assist in the tailoring of personalized treatment strategy.展开更多
Drought is a common abiotic stress that considerably limits crop production. The objective of this study is to explore the influence of water deficiency on the yield, physiologic and metabolomic attributes in upland c...Drought is a common abiotic stress that considerably limits crop production. The objective of this study is to explore the influence of water deficiency on the yield, physiologic and metabolomic attributes in upland cotton cultivars（Gossypium hirsutum L）. Cotton cultivars, ＇Ishonch＇ and ＇Tashkent-6＇ were selected to study the relationships among their physiologic, metabolomic and yield attributes during water deficiency. Deficit irrigation was designed by modifying the traditional watering protocol to reduce water use. Results indicate that cotton cultivars respond differently to water deficit stress. Water deficit significantly influenced plant height, the number of internodes, and sympodial branches in both cultivars. However, yield components such as the number of bolls, boll seed, lint mass, and individual plant yield were significantly reduced only in ＇Tashkent-6＇. The leaf area decreased and the specific leaf weight increased in ＇Ishonch＇ under deficit irrigation conditions. However, ＇Tashkent-6＇ demonstrated significant water loss compared to ＇Ishonch＇, and both cultivars showed reduced transpiration rates. Untargeted metabolite profiles of leaves showed clear separation in ＇Ishonch＇, but not in ＇Tashkent-6＇ under deficit irrigation compared to full irrigation. The individual metabolites such as proline and galactinol showed strong association with yield under water deficit stress. Moreover, this study indicates that leaf area and transpiration intensity influence yield during water deficiency. In summary, the correlation among morpho-physiologic, metabolic, and yield components significantly varied between the two cultivars under water deficiency. The flowering stage was sensitive to water stress for both cultivars. The direct relationship between physiology, metabolism, and yield may be a useful selection criterion for determining candidate parents for cotton drought tolerance breeding.展开更多
Objective: To undertake metabolite profiling of various plant parts of Citrullus colocynthis, and assess antioxidant and wound healing activities of fractions for therapeutical applications. Methods: Extracts from lea...Objective: To undertake metabolite profiling of various plant parts of Citrullus colocynthis, and assess antioxidant and wound healing activities of fractions for therapeutical applications. Methods: Extracts from leaves, stem, root, fruit pulp and seeds were analyzed using gas chromatography-mass spectrometry and high performance liquid chromatography. Variation in antioxidant potential was assayed by 1,1-diphenyl-2-picrylhydrazyl(DPPH) free radical scavenging assay. The extract with highest antioxidant potential was subjected on in-vivo wound healing activity using excision wound model. Results: Metabolite profiling of Citrullus colocynthis identified 70 chemically diverse metabolites from different plant parts by using a combination of GC-MS and HPLC. Concentration of colocynthin, a principal active secondary metabolite, ranged from 3.15 mg/g dry weight to 242.00 mg/g dry weight, the lowest being in leaves and highest in fruit pulp. DPPH radical scavenging activity of free radical(IC50) ranged from 196.44 μg/mL in fruit pulp to 413.33 μg/mL in leaves tissues. Significant wound contraction and increase in hydroxyproline content of granulation tissue were observed with ointment formulated from methanolic extract of fruit pulp. Conclusions: The study indicates that the methanol extract of Citrullus colocynthis fruit pulp when applied topically may promote wound contraction in rat model attributable to the accumulation of colocynthin. The high quantity of colocynthin(242.00 mg/g dry weight) and substantial concentration of 2,4-di-tert butyl phenol(3.2%), squalene(4.2%) and δ-tocopherol(2.5%) make this plant to provide new opportunities for development of medicinal, nutraceutical and dietary supplements with optimized functionality.展开更多
文摘Objective:To profile the secondary metabolites and to evaluate the antidiabetic potential of hydroethanolic leaf extracts of Conocarpus lancifolius.Methods:The various hydroethanolic extracts of Conocarpus lancifolius leaf were prepared by ultrasonication assisted freezedrying.Total phenolic contents,flavonoid contents,antioxidant activity,α-glucosidase andα-amylase inhibitions of leaf extracts were determined.The metabolite profiling was accomplished by UHPLC-Q-TOF-MS/MS analysis.The antidiabetic assessment of the most potent extract was carried out by measuring the hypoglycemic and hypolipidemic effect in the high fat diet-fed diabetic albino mice.The blood glucose level,haemoglobin,total cholesterol,high-density lipoproteins(HDL)and low-density lipoproteins(LDL)were determined.Results:The 60%ethanolic extract exhibited the highest phenolic and flavonoid contents of(349.39±2.13)mg GAE/g dry extract and(116.95±2.34)mg RE/g dry extracts,respectively,and the highest DPPH scavenging activity with an IC50 value of(32.87±1.11)μg/mL.The IC50 values forα-glucosidase andα-amylase inhibitions were(38.64±0.93)μg/mL and(44.80±1.57)μg/mL,respectively.UHPLC-Q-TOF-MS/MS analysis confirmed the presence of gallic acid,ellagic acid,corilagin,kaempherol-3-O-rutinoside,caffeic acid derivative,isorhamnetin and galloyl derivatives in the 60%ethanolic extract.Plant extract at a dose of 450 mg/kg body weight reduced blood glucose level,total cholesterol,LDL and HDL,and increased haemoglobin in alloxan-induced diabetic mice,Conclusions:Conocarpus lancifolius leaves are proved as a good source of biologically functional metabolites and possess antidiabetic activity which may be further explored to treat diabetes.
基金We thank the Shanghai Municipal Committee of Science and Technology(Grant Nos.:20XD1423400,23ZR1460900 and 20DZ2201100)Shanghai Municipal Health Commission/Shanghai Municipal Administration of Traditional Chinese Medicine(Grant No.:ZY(2021e2023)-0501)+2 种基金Shanghai Science and Technology Development Fund from Central Leading Local Government(Grant No.:YDZX20223100001004)National Natural Science Foundation of China(Grant No.:21672249)Expenditure Budget Program of Shanghai University of Traditional Chinese Medicine(Grant Nos.:2020LK051,and 2021LK001).
文摘In this work,a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry(LC-MS)method was developed for metabolite profiling of the glutathione anabolic pathway(GAP)in cancer tissues and cells.The pyrylium salt of 6,7-dimethoxy-3-methyl isochromenylium tetrafluoroborate(DMMIC)was used to label the amino group of metabolites,and a reductant of dithiothreitol(DTT)was employed to stabilize the thiol group.By combining DMMIC derivatization with LC-MS,it was feasible to quantify the 13 main metabolites on the GAP in complex biological samples,which had good linearity(R^(2)=0.99810.9999),precision(interday precision of 1.6%e19.0%and intraday precision of 1.4%e19.8%)and accuracy(83.4%-115.7%).Moreover,the recovery assessments in tissues(82.5%e107.3%)and in cells(98.1%e118.9%)with GSH-^(13)C2,^(15)N,and Cys-^(15)N demonstrated the reliability of the method in detecting tissues and cells.Following a methodological evaluation,the method was applied successfully to investigate difference in the GAP between the carcinoma and para-carcinoma tissues of esophageal squamous cell carcinoma(ESCC)and the effect of p-hydroxycinnamaldehyde(CMSP)on the GAP in KYSE150 esophageal cancer cells.The results demonstrate that the developed method provides a promising new tool to elucidate the roles of GAP in physiological and pathological processes,which can contribute to research on drugs and diseases.
文摘Objective:To evaluate the antioxidant potential and pancreatic lipase inhibitory action of optimized hydroethanolic extracts of Solanum nigrum.Methods:Optimized extraction for maximum recovery of metabolites was performed using a combination of freeze-drying and ultrasonication followed by determination of antioxidant and antiobesity properties.The ultra-high performance liquid chromatography equipped with mass spectrometry was used to analyze metabolite profiling of Solanum nigrum.Computational studies were performed using molecular docking and electrostatic potential analysis for individual compounds.The hypolipidemic potential of the most potent extract was assessed in the obese mice fed on fat rich diet.Results:The 80%hydroethanolic extract exhibited the highest extract yield,total phenolic contents,total flavonoid contents along with the strongest 2,2-diphenyl-1-picrylhydrazyl scavenging activity,total antioxidant power,and pancreatic lipase inhibitory properties.The 80%hydroethanolic extract not only regulated the lipid profile of obese mice but also restricted the weight gain in the liver,kidney,and heart.The 80%hydroethanolic extract also reduced alanine transaminase and aspartate transaminase concentrations in serum.The effects of plant extract at 300 mg/kg body weight were quite comparable with the standard drug orlistat.Conclusions:Solanum nigrum is proved as an excellent and potent source of secondary metabolites that might be responsible for obesity mitigation.
基金supported by National Key Research and Development Program of China(No.2017ZX 09301005).
文摘Chang-Kang-Fang(CKF)formula,a Traditional Chinese Medicine(TCM)prescription,has been widely used for the treatment of irritable bowel syndrome(IBS).However,its potential material basis and underlying mechanism remain elusive.Therefore,this study employed an integrated approach that combined ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS)with network pharmacology to systematically characterize the phytochemical components and metabolites of CKF,as well as elucidating its underlying mechanism.Through this comprehensive analysis,a total of 150 components were identified or tentatively characterized within the CKF formula.Notably,six N-acetyldopamine oligomers from Cicadae Periostracum and eight resin glycosides from Cuscutae Semen were characterized in this formula for the first time.Meanwhile,149 xenobiotics(58 prototypes and 91 metabolites)were detected in plasma,urine,feces,brain,and intestinal contents,and the in vivo metabolic pathways of resin glycosides were elaborated for the first time.Furthermore,network pharmacology and molecular docking analyses revealed that alkaloids,flavonoids,chromones,monoterpenes,N-acetyldopamine dimers,p-hydroxycinnamic acid,and Cus-3/isomer might be responsible for the beneficial effects of CKF in treating IBS,and CASP8,MARK14,PIK3C,PIK3R1,TLR4,and TNF may be its potential targets.These discoveries offer a comprehensive understanding of the potential material basis and clarify the underlying mechanism of the CKF formula in treating IBS,facilitating the broader application of CKF in the field of medicine.
基金supported by the National Natural Science Foundation of China(Grant No.82173963)。
文摘Objective:The absorbed prototypes and metabolites of traditional Chinese medicines in vivo are crucial for identifying their biological functions.However,comprehensive profiling of constituents in vivo is difficult owing to endogenous interference and low metabolite abundance.Therefore,a systematic strategy was proposed for screening and profiling exogenous components in biological matrices based on the mass differences between prototypes and the products of their metabolic reactions.Materials and Methods:Two hundred and forty-seven previously reported metabolic reactions were collected from the relevant literature on the Huangqi-Danshen(HD)herb pair,and a metabolic reaction-based mass difference database was created.The preprocessed data from experimental MS1based on ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry were automatically calculated mass differences by R programming and matched with the database to screen potential constituents.Finally,the components were annotated across the MS2data.Results:A total of 164 components were annotated in the plasma samples from the rats after oral administration of HD,of which 20 were confirmed using the reference standards.The major metabolic pathways include methylation,dehydration,cysteine S-binding,glucuronidation,sulfation,and multistep reactions.Conclusions:This study revealed the metabolic characteristics and biotransformation regulation of HD and laid the foundation for elucidating its therapeutic effects.The proposed approach provides advantageous resources for evaluating the metabolites in the complex systems.
基金supported by the German Academic Exchange Service(DAAD)as a grant scholarship and part of the Ph.D.thesis of IW.Funding program/-ID:Research Grants-Doctoral Programs in Germany,2017/18(57299294),ST34.
文摘Piper sarmentosum Roxb.(Piperaceae)is a traditional medicinal and food plant widely distributed in the tropical and subtropical regions of Asia,offering both health and culinary benefits.In this study the secondary metabolites in different organs of P.sarmentosum were identified and their relative abundances were characterized.The metabolic profiles of leaves,roots,stems and fruits were comprehensively investigated by liquid chromatography high-resolution mass spectrometry(LC-HR-MS)and the data subsequently analyzed using multivariate statistical methods.Manual interpretation of the tandem mass spectrometric(MS/MS)fragmentation patterns revealed the presence of 154 tentatively identified metabolites,mostly represented by alkaloids and flavonoids.Principle component analysis and hierarchical clustering indicated the predominant occurrence of flavonoids,lignans and phenyl propanoids in leaves,aporphines in stems,piperamides in fruits and lignan-amides in roots.Overall,this study provides extensive data on the metabolite composition of P.sarmentosum,supplying useful information for bioactive compounds discovery and patterns of their preferential biosynthesis or storage in specific organs.This can be used to optimize production and harvesting as well as to maximize the plant’s economic value as herbal medicine or in food applications.
文摘The physiological properties of rice grains are immediately obvious to consumers. High-coverage metabolomic characterization of the rice diversity research set predicted a negative correlation between fatty acid and lipid levels and amylose/total starch ratio （amylose ratio）, but the reason for this is unclear. To obtain new insight into the relationships among the visual phenotypes of rice kernels, starch granule structures, amylose ratios, and metabolite changes, we investigated the metabolite changes of five Japonica cultivars with various amylose ratios and two knockout mutants （e 1, a Starch synthase Ilia （SSIIla）-deficient mutant and the SSIIla/starch branching enzyme （BE） double-knockout mutant 4019） by using mass spectrometry-based metabolomics techniques. Scanning electron microscopy clearly showed that the two mutants had unusual starch granule structures. The metabolomic compositions of two cultivars with high amylose ratios （Hoshiyutaka and Yumetoiro） exhibited similar patterns, while that of the double-knockout mutant, which has an extremely high amylose ratio, differed. Rice pedigree network analysis of the cultivars and the mutants provided insight into the association between metabolic-trait properties and their underlying genetic basis in rice breeding in Japan. Multidimensional scaling analysis revealed that the Hoshiyutaka and Yumetoiro cultivars were Indica-like, yet they are classified as Japonica subpopulations. Exploring metabolomic traits is a powerful way to follow rice genetic traces and breeding history.
基金partly funded by the Department of Science and Technology Fund for Improvement of S&T Infrastructure (Grant No. SR/FST/LS-I/2018/125)。
文摘Tissue culture techniques were used to produce large amounts of bioactive compounds with medicinal potential, overcoming space and time constraints for cancer prevention. Rice callus suspension cultures(RCSC) and seed extracts prepared from aromatic rice varieties were used to evaluate the cytotoxic impact on human colon and lung cancer cell lines, as well as a normal control cell line, using Taxol as a positive control. RCSC and seed extracts from two Indian aromatic rice varieties were applied at different concentrations to treat the cancer cell lines and normal lung fibroblasts over varying time intervals. Apoptosis was assessed in 1:5 dilutions of the A549 and HT-29 cell lines treated with RCSC for 72 h, using propidium iodide staining and flow cytometry. RCSC showed a more potent cytotoxic effect than seed extracts with minimal effect on the normal cell line, in contrast to Taxol. Confocal microscopy and flow cytometry further confirmed the apoptotic effect of RCSC. Gas chromatography-mass spectrometry-based metabolic profiling identified metabolites involved in cytotoxicity and highlighted altered pathways. RCSC is proposed as an alternative source for the development of novel anticancer drugs with reduced side effects.
基金The National Natural Science Foundation of China under contract Nos 41706191 and 41961144013the Natural Science Foundation of Zhejiang Province under contract No.LY20D060004+2 种基金the National Natural Science Foundation of China under contract Nos 41676111,41876139 and 41906140the Program of Bureau of Science and Technology of Zhoushan Grant under contract No.2019C81031the Basic Public Welfare Research Project of Zhejiang Province under contract No.LGC22B050032.
文摘More than 30 species of benthic Prorocentrum have been identified,some of which produce okadaic acid(OA)and its derivatives,dinophysistoxins(DTXs),which cause diarrhetic shellfish poisoning(DSP).Increasing numbers of benthic Prorocentrum species have been reported in tropical and subtropical waters of China.In contrast,only a few benthic Prorocentrum species have been reported in temperate waters.In this study,morphological descriptions obtained using light microscopy,scanning electron microscopy and molecular characterization of one Prorocentrum clipeus strain isolated from the Yellow Sea are presented.Prorocentrum clipeus cells were nearly circular in shape,with a collar,ridge,and one protrusion.The periflagellar area was wide U-shaped,with two curved projections on platelet 1a.Nine periflagellar platelets of different sizes were observed.The morphology closely fits that of the species isolated from other locations.Phylogenetic analysis based on the molecular sequences of the small subunit(SSU)rDNA,internal transcribed spacer(ITS),and large subunit(LSU)rDNA was performed.A comprehensive metabolomic analysis incorporating target,suspect and non-target screenings was first applied to investigate the intracellular and extracellular metabolite profiles of the current isolate of P.clipeus.According to the results of the target and suspect screenings,179 metabolites or toxins produced by DSP-related algal species,including OA,dinophysistoxin-1(DTX1),dinophysistoxin-2(DTX2)and pectenotoxin-2(PTX2),were not detected.Non-target screening involving feature-based molecular networking(FBMN)provided a global view of major metabolites produced by the P.clipeus DF128 strain and revealed 23 clusters belonging to at least 13 compound classes,with organometallic compounds,lipids and lipid-like molecules,phenylpropanoids and polyketides,and benzenoids as major types.To date,this is the first record of the characterization of P.clipeus in samples from Chinese waters.Our results support the wide distribution of epibenthic Prorocentrum species.
基金supported by Pudong New Area Science and Technology Development Fund Special Research Project on the Livelihood of Institutions(No.PKJ2023-Y03)Pudong New Area Chinese Medicine Senior Teacher Training Program(No.PDZY-2023-0801)Talents Training Program of the Seventh People’s Hospital,Shanghai University of Traditional Chinese Medicine(No.JY2024-08).
文摘Background:Diabetic peripheral neuropathy(DPN)is a prevalent and debilitating complication of diabetes mellitus,lacking effective treatment options.Despite unclear underlying mechanisms,electroacupuncture(EA)shows promise in relieving DPN symptoms.Neurotransmitter dysregulation is central to DPN pathophysiology.This study aimed to investigate EA’s effects on DPN via targeted neurotransmitter metabolomics.Methods:A streptozotocin-induced mouse model of DPN was developed,and EA treatment was administered for two weeks to assess the therapeutic potential of EA.Following the collection of sciatic nerve samples,LC-MS-based targeted metabolomics analyses investigations were performed to examine alterations in DPN-associated neurotransmitter metabolism brought on by EA therapy.Multivariate statistical analyses were employed to assess metabolite expression patterns,using cluster heatmaps to display neurotransmitter expression results.KEGG pathway analyses were also used to explore the functional classifications of these neurotransmitters and associated metabolic pathways.Results:Targeted neurotransmitter-focused metabolomics analyses led to the identification of 34 putative biomarkers associated with EA treatment,of which 5 showed significant changes,such as beta-alanine(increased by 80.37%,P=0.0004)and kynurenine(decreased by 29.36%,P=0.0163).KEGG pathway analysis indicated that changes in the abundance of these metabolites were associated with the cAMP signaling pathway,neuroactive ligand-receptor interactions,the synaptic vesicle cycle,and other pathways.Conclusion:The results indicate that EA can efficiently regulate neurotransmitter metabolism and restore peripheral nerve function,suggesting a feasible non-pharmacological strategy for DPN treatment and warranting clinical translation.
文摘Ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry （UPLC-Q-TOF/MS） was developed to identify the absorbed parent components and metabolites in rat bile, plasma and urine after oral administration of Radix Paeoniae Alba extract （RPAE）. A total of 65 compounds were detected in rat bile, plasma and urine samples, including 11 parent compounds and 54 metabolites. The results indicated that glucuronidation, hydroxylation and methylation were the major metabolic pathways of the components of RPAE. Furthermore, the results of this work demonstrated that UPLC-Q-TOF/MS combined with MetaboLynx？ software and mass defect filtering （MDF） could provide unique high throughput capabilities for drug metabolism study, with excellent MS mass accuracy and enhanced MSE data acquisition. With the MSE technique, both precursor and fragment mass spectra can be simultaneously acquired by alternating between high and low collision energy during a single chromatographic run.
基金Financial support from the 2025 Technological Innova-tion for Ningbo(No.2019B10010)China Agriculture Re-search System-CARS48+1 种基金K.C.Wong Magna Fund in Ningbo Universitythe Special research funding from the Marine Biotechnology and Marine Engineering Dis cipline Group in Ningbo University(No.422004582)are greatly acknowledged.
文摘Mud crab(Scylla paramamosain)is one of the most consumed crabs in China.Generally,it is believed that dead mud crabs are not edible.Herein,we investigated the postmortem metabolite profile changes of the muscle and hepatopancreas of mud crab associated with storage method using nuclear magnetic resonance-based metabolomics coupled with multivariate data analysis.Our results showed that postmortem changes of trimethylamine,organic acids(lactate,formate,and succinate),as well as ATP and its breakdown products are closely affected by the storage method.These metabolites can be used as indicators for monitoring loss of crab freshness.Furthermore,dead mud crabs preserved an edible quality at least for 4 h at room temperature,12h on ice,and 16 d at−20℃,strongly suggesting that dead crab consumption quality should be determined by freshness.They shouldn’t be discarded without considering the effects of different storage conditions on their freshness.
文摘Cotton fibers elongate rapidly after initiation of elongation, eventually leading to the deposit of a large amount of cellulose. To reveal features of cotton fiber cells at the fast elongation and the secondary cell wall synthesis stages, we compared the respective transcriptomes and metabolite profiles. Comparative analysis of transcriptomes by cDNA array identified 633 genes that were differentially regulated during fiber development. Principal component analysis （PCA） using expressed genes as variables divided fiber samples into four groups, which are diagnostic of developmental stages. Similar grouping results are also found if we use non-polar or polar metabolites as variables for PCA of developing fibers. Auxin signaling, wall-loosening and lipid metabolism are highly active during fiber elongation, whereas cellulose biosynthesis is predominant and many other metabolic pathways are downregulated at the secondary cell wall synthesis stage. Transcript and metabolite profiles and enzyme activities are consistent in demonstrating a specialization process of cotton fiber development toward cellulose synthesis. These data demonstrate that cotton fiber cell at a certain stage has its own unique feature, and developmental stages of cotton fiber cells can be distinguished by their transcript and metabolite profiles. During the secondary cell wall synthesis stage, metabolic pathways are streamed into cellulose synthesis.
基金supported by the National Natural Science Foundation of China(Nos.42177010 and 41877387)Fundamental Research Funds for Central Non-profit Scientific Institution(No.1610132021008).
文摘Soil salinity is known to improve cadmium(Cd)mobility,especially in arid soils.However,the mechanisms involved in how salt stress-associated metabolic profiles participate in mediating Cd transport in the soil-plant system remain poorly understood.This study was designed to investigate the effects of salinity-induced changes in soil metabolites on Cd bioavailability.Sodium salts in different combinations according to molar ratio(NaCl:Na_(2)SO_(4)=1:1;NaCl:Na_(2)SO_(4):NaHCO_(3)=1:2:1;NaCl:Na_(2)SO_(4):NaHCO_(3):Na_(2)CO_(3)=1:9:9:1;NaCl:Na_(2)SO_(4):NaHCO_(3):Na_(2)CO_(3)=1:1:1:1)were applied to the Cd-contaminated soils,which increased soil Cd availability by 22.36%and the Cd content in wheat grains by 36.61%,compared to the control.Salt stress resulted in soil metabolic reprogramming,which might explain the decreased growth of wheat plants and increased Cd transport from the soil into wheat tissues.For example,down-regulation of starch and sucrose metabolism reduced the production of sugars,which adversely affected growth;up-regulation of fatty acid metabolism allowed wheat plants to maintain a normal intracellular environment under saline conditions;up-regulation of the tricarboxylic acid(TCA)cycle was triggered,causing an increase in organic acid synthesis and the accumulation of organic acids,which facilitated the migration of soil Cd into wheat tissues.In summary,salt stress can facilitate Cd transport into wheat tissues by the direct effect of salt-based ions and the combined effect of altered soil physicochemical properties and soil metabolic profiles in Cd-contaminated soils.
基金Open Access funding enabled and organized by Projekt DEALThe research from the MultiBioPro project leading to these results has received funding from the European Union’s Seventh Framework Programme for research,technological development and demonstration under grant agreement 311804Further funding from the BBSRC 21EBTA-Celfacto project is acknowledged by PDF.
文摘The evaluation of plant-based feedstocks is an important aspect of biorefining.Nicotiana glauca is a solanaceous,non-food crop that produces large amounts of biomass and is well adapted to grow in suboptimal conditions.In the present article,compatible sequential solvent extractions were applied to N.glauca leaves to enable the generation of enriched extracts containing higher metabolite content comparing to direct leaf extracts.Typically,between 60 to 100 metabolite components were identified within the fractions.The occurrence of plant fatty acids,fatty acid alcohols,alkanes,sterols and terpenoids was detected by gas liquid chromatography-mass spectrometry(GC-MS)and metabolite identification was confirmed by comparison of physico-chemical properties displayed by available authentic standards.Collectively,co-products such waxes,oils,fermentable sugars,and terpenoids were all identified and quantified.The enriched fractions of N.glauca revealed a high level of readily extractable hydrocarbons,oils and high value co-products.In addition,the saccharification yield and cell wall composition analyses in the stems revealed the potential of the residue material as a promising lignocellulosic substrate for the production of fermentable sugars.In conclusion a multifractional cascade for valuable compounds/commodities has been development,that uses N.glauca biomass.These data have enabled the evaluation of N.glauca material as a potential feedstock for biorefining.
基金partly supported by grants from the National Natural Science Foundation of China(No:81372955)BiosTime Maternal and Infant Nutrition and Health Research Fund(2017FYH008)+1 种基金the Projects of Medical and Health Technology Development Program in Shandong Province(No:2016WS0309)Qingdao Outstanding Health Professional Development Fund(2020-2022,2022-2024)。
文摘Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota.Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq.Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336–0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34–0.55),which were mainly involved in neurodevelopment.Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.
基金funded by Russian Science Foundation,grant number№22-73-00190,https://rscf.ru/en/project/22-73-00190/.
文摘Four extracts of the marine-derived fungus Penicillium velutinum J.F.H.Beyma were obtained via metal ions stress conditions based on the OSMAC(One Strain Many Compounds)strategy.Using a combination of modern approaches such as LC/UV,LC/MS and bioactivity data analysis,as well as in silico calculations,influence metal stress factors to change metabolite profiles Penicillium velutinum were analyzed.From the ethyl acetate extract of the P.velutinum were isolated two new piperazine derivatives helvamides B(1)and C(2)together with known saroclazin A(3)(4S,5R,7S)-4,11-dihydroxy-guaia-1(2),9(10)-dien(4).Their structures were established based on spectroscopic methods.The absolute configuration of helvamide B(1)as 2R,5R was determined by a combination of the X-ray analysis and by time-dependent density functional theory(TD-DFT)calculations of electronic circular dichroism(ECD)spectra.The cytotoxic activity of the isolated compounds against human prostate cancer PC-3 and human embryonic kidney HEK-293 cells and growth inhibition activity against yeast-like fungi Candida albicans were assayed.
文摘Development of a novel in vivo lung perfusion(IVLP)procedure allows localized delivery of high-dose doxorubicin(DOX)for targeting residual micrometastatic disease in the lungs.However,DOX delivery via IVLP requires careful monitoring of drug level to ensure tissue concentrations of this agent remain in the therapeutic window.A small dimension nitinol wire coated with a sorbent of biocompatible morphology(Bio-SPME)has been clinically evaluated for in vivo lung tissue extraction and determination of DOX and its key metabolites.The in vivo Bio-SPME-IVLP experiments were performed on pig model over various(150 and 225 mg/m^(2))drug doses,and during human clinical trial.Two patients with metastatic osteosarcoma were treated with a single 5 and 7 μg/mL(respectively)dose of DOX during a 3-h IVLP.In both pig and human cases,DOX tissue levels presented similar trends during IVLP.Human lung tissue concentrations of drug ranged between 15 and 293 μg/g over the course of the IVLP procedure.In addition to DOX levels,Bio-SPME followed by liquid chromatography-mass spectrometry analysis generated 64 metabolic features during endogenous metabolite screening,providing information about lung status during drug administration.Real-time monitoring of DOX levels in the lungs can be performed effectively throughout the IVLP procedure by in vivo Bio-SPME chemical biopsy approach.Bio-SPME also extracted various endogenous molecules,thus providing a real-time snapshot of the physiology of the cells,which might assist in the tailoring of personalized treatment strategy.
基金supported by Committee of Science and Technology of Uzbekistan (F5-T025)CAS PIFI fellowships (2017PB0051,2017VBA0017)the High Technology Research and Development Program of Xinjiang Uygur Autonomous Region (201411104)
文摘Drought is a common abiotic stress that considerably limits crop production. The objective of this study is to explore the influence of water deficiency on the yield, physiologic and metabolomic attributes in upland cotton cultivars（Gossypium hirsutum L）. Cotton cultivars, ＇Ishonch＇ and ＇Tashkent-6＇ were selected to study the relationships among their physiologic, metabolomic and yield attributes during water deficiency. Deficit irrigation was designed by modifying the traditional watering protocol to reduce water use. Results indicate that cotton cultivars respond differently to water deficit stress. Water deficit significantly influenced plant height, the number of internodes, and sympodial branches in both cultivars. However, yield components such as the number of bolls, boll seed, lint mass, and individual plant yield were significantly reduced only in ＇Tashkent-6＇. The leaf area decreased and the specific leaf weight increased in ＇Ishonch＇ under deficit irrigation conditions. However, ＇Tashkent-6＇ demonstrated significant water loss compared to ＇Ishonch＇, and both cultivars showed reduced transpiration rates. Untargeted metabolite profiles of leaves showed clear separation in ＇Ishonch＇, but not in ＇Tashkent-6＇ under deficit irrigation compared to full irrigation. The individual metabolites such as proline and galactinol showed strong association with yield under water deficit stress. Moreover, this study indicates that leaf area and transpiration intensity influence yield during water deficiency. In summary, the correlation among morpho-physiologic, metabolic, and yield components significantly varied between the two cultivars under water deficiency. The flowering stage was sensitive to water stress for both cultivars. The direct relationship between physiology, metabolism, and yield may be a useful selection criterion for determining candidate parents for cotton drought tolerance breeding.
基金supported by Council of Scientific and Industrial Research(CSIR),New Delhi
文摘Objective: To undertake metabolite profiling of various plant parts of Citrullus colocynthis, and assess antioxidant and wound healing activities of fractions for therapeutical applications. Methods: Extracts from leaves, stem, root, fruit pulp and seeds were analyzed using gas chromatography-mass spectrometry and high performance liquid chromatography. Variation in antioxidant potential was assayed by 1,1-diphenyl-2-picrylhydrazyl(DPPH) free radical scavenging assay. The extract with highest antioxidant potential was subjected on in-vivo wound healing activity using excision wound model. Results: Metabolite profiling of Citrullus colocynthis identified 70 chemically diverse metabolites from different plant parts by using a combination of GC-MS and HPLC. Concentration of colocynthin, a principal active secondary metabolite, ranged from 3.15 mg/g dry weight to 242.00 mg/g dry weight, the lowest being in leaves and highest in fruit pulp. DPPH radical scavenging activity of free radical(IC50) ranged from 196.44 μg/mL in fruit pulp to 413.33 μg/mL in leaves tissues. Significant wound contraction and increase in hydroxyproline content of granulation tissue were observed with ointment formulated from methanolic extract of fruit pulp. Conclusions: The study indicates that the methanol extract of Citrullus colocynthis fruit pulp when applied topically may promote wound contraction in rat model attributable to the accumulation of colocynthin. The high quantity of colocynthin(242.00 mg/g dry weight) and substantial concentration of 2,4-di-tert butyl phenol(3.2%), squalene(4.2%) and δ-tocopherol(2.5%) make this plant to provide new opportunities for development of medicinal, nutraceutical and dietary supplements with optimized functionality.
