RESUMO
This study aimed to identify whether there are elevations or declines in specific plasma lipids in intertrochanteric fracture (ITF) patients which might serve as potential biomarkers for assessing the severity of trauma, or therapeutic targets for controlling post-traumatic responses. Ten metal work removal patients were enrolled. Their preoperative blood samples served as the control group (C group). Their 24-hour postoperative blood samples served as the moderate trauma group (M group). The ITF group was composed of 12 intertrochanteric fracture patients. A total of 707 lipid species were identified from 32 plasma samples (10 controls, 10 moderate trauma and 12 ITF samples). We first identified 31 lipids that were elevated and 6 lipids that were decreased in the more severe trauma group in aged patients, with an especially strong relationship among 14 lipids that are candidates as markers for trauma severity evaluation. Fourteen lipids were identified as potential markers of bone trauma. The definition of important lipids in trauma may not only provide guidance for the formulation of optimum ITF operation time, but may also have importance in other traumatic models, and in further understanding the components of the systemic inflammatory response for new drug targets.
Assuntos
Lipídeos , Humanos , Idoso , Biomarcadores , Período Pós-OperatórioRESUMO
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an irreversible interstitial pulmonary disease featured by high mortality, chronic and progressive course, and poor prognosis with unclear etiology. Currently, more studies have been focusing on identifying biomarkers to predict the progression of IPF, such as genes, proteins, and lipids. Lipids comprise diverse classes of molecules and play a critical role in cellular energy storage, structure, and signaling. The role of lipids in respiratory diseases, including cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD) has been investigated intensely in the recent years. The human serum lipid profiles in IPF patients however, have not been thoroughly understood and it will be very helpful if there are available molecular biomarkers, which can be used to monitor the disease progression or provide prognostic information for IPF disease. METHODS: In this study, we performed the ultraperformance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-QTOF/MS) to detect the lipid variation and identify biomarker in plasma of IPF patients. The plasma were from 22 IPF patients before received treatment and 18 controls. RESULTS: A total of 507 individual blood lipid species were determined with lipidomics from the 40 plasma samples including 20 types of fatty acid, 159 types of glycerolipids, 221 types of glycerophospholipids, 47 types of sphingolipids, 46 types of sterol lipids, 7 types of prenol lipids, 3 types of saccharolipids, and 4 types of polyketides. By comparing the variations in the lipid metabolite levels in IPF patients, a total of 62 unique lipids were identified by statistical analysis including 24 kinds of glycerophoslipids, 30 kinds of glycerolipids, 3 kinds of sterol lipids, 4 kinds of sphingolipids and 1 kind of fatty acids. Finally, 6 out of 62 discriminating lipids were selected as the potential biomarkers, which are able to differentiate between IPF disease and controls with ROC analysis. CONCLUSIONS: Our results provided vital information regarding lipid metabolism in IPF patients and more importantly, a few potentially promising biomarkers were firstly identified which may have a predictive role in monitoring and diagnosing IPF disease.
Assuntos
Fibrose Pulmonar Idiopática/sangue , Lipídeos/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Cromatografia Líquida , Ácidos Graxos/sangue , Feminino , Glicerofosfolipídeos/sangue , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Metabolismo dos Lipídeos , Masculino , Espectrometria de Massas , Metabolômica , Policetídeos/sangue , Esfingolipídeos/sangueRESUMO
OBJECTIVE: To find new biomarkers for early diagnosis of breast cancer. RESULTS: 847 lipid species were identified from 78 plasma samples (37 breast cancer samples and 41 healthy controls) by ultra HPLC coupled with quadrupole time-of-flight tandem mass spectrometry. These include 321 glycerophospholipids (GPs), 265 glycerolipids (GLs), 91 sphingolipids (SPs), 77 fatty acyls (FAs), 68 sterol lipids (STs), 18 prenol lipids (PRs), 6 polyketides (PKs), and 1 saccharolipid (SL). Separation was observed from an orthogonal signal correction Partial Least Square Discrimination Analysis model. Based on this analysis, six differentiating lipids were identified: PC (20:2/20:5), PC (22:0/24:1), TG (12:0/14:1), and DG (18:1/18:2) had high levels, whereas PE (15:0/19:1) and N-palmitoyl proline had low levels in the breast cancer samples compared with the healthy controls. Furthermore, significant differences in metabolites were found among some clinical characteristics. CONCLUSIONS: Our results reveal that six specific lipids could serve as potential biomarkers for early diagnosis of breast cancer.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/patologia , Lipídeos/sangue , Adulto , Idoso , Biomarcadores Tumorais/análise , Neoplasias da Mama/sangue , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Análise dos Mínimos Quadrados , Lipídeos/análise , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Espectrometria de Massas em TandemRESUMO
BACKGROUND: microRNAs (miRNAs) are implicated in plant development processes and play pivotal roles in plant adaptation to environmental stresses. Salicornia europaea, a salt mash euhalophyte, is a suitable model plant to study salt adaptation mechanisms. S. europaea is also a vegetable, forage, and oilseed that can be used for saline land reclamation and biofuel precursor production on marginal lands. Despite its importance, no miRNA has been identified from S. europaea thus far. RESULTS: Deep sequencing was performed to investigate small RNA transcriptome of S. europaea. Two hundred and ten conserved miRNAs comprising 51 families and 31 novel miRNAs (including seven miRNA star sequences) belonging to 30 families were identified. About half (13 out of 31) of the novel miRNAs were only detected in salt-treated samples. The expression of 43 conserved and 13 novel miRNAs significantly changed in response to salinity. In addition, 53 conserved and 13 novel miRNAs were differentially expressed between the shoots and roots. Furthermore, 306 and 195 S. europaea unigenes were predicted to be targets of 41 conserved and 29 novel miRNA families, respectively. These targets encoded a wide range of proteins, and genes involved in transcription regulation constituted the largest category. Four of these genes encoding laccase, F-box family protein, SAC3/GANP family protein, and NADPH cytochrome P-450 reductase were validated using 5'-RACE. CONCLUSIONS: Our results indicate that specific miRNAs are tightly regulated by salinity in the shoots and/or roots of S. europaea, which may play important roles in salt tolerance of this euhalophyte. The S. europaea salt-responsive miRNAs and miRNAs that target transcription factors, nucleotide binding site-leucine-rich repeat proteins and enzymes involved in lignin biosynthesis as well as carbon and nitrogen metabolism may be applied in genetic engineering of crops with high stress tolerance, and genetic modification of biofuel crops with high biomass and regulatable lignin biosynthesis.
Assuntos
Chenopodiaceae/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , MicroRNAs/genética , RNA de Plantas/genética , Tolerância ao Sal/genética , Sequência de Bases , Chenopodiaceae/efeitos dos fármacos , Sequência Conservada/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Biblioteca Gênica , Redes Reguladoras de Genes/efeitos dos fármacos , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Dados de Sequência Molecular , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA de Plantas/metabolismo , Reprodutibilidade dos Testes , Tolerância ao Sal/efeitos dos fármacos , Cloreto de Sódio/farmacologia , Estatística como Assunto , Transcriptoma/genéticaRESUMO
γ-Aminobutyric acid (GABA) accumulates in many plant species in response to environmental stress. However, the physiological function of GABA or its metabolic pathway (GABA shunt) in plants remains largely unclear. Here, the genes, including glutamate decarboxylases (SlGADs), GABAâ transaminases (SlGABA-Ts) and succinic semialdehyde dehydrogenase (SlSSADH), controlling three steps of the metabolic pathway of GABA, were studied through virus-induced gene silencing approach in tomato. Silencing of SlGADs (GABA biosynthetic genes) and SlGABA-Ts (GABA catabolic genes) led to increased accumulation of reactive oxygen species (ROS) as well as salt sensitivity under 200 mm NaCl treatment. Targeted quantitative analysis of metabolites revealed that GABA decreased and increased in the SlGADs- and SlGABA-Ts-silenced plants, respectively, whereas succinate (the final product of GABA metabolism) decreased in both silenced plants. Contrarily, SlSSADH-silenced plants, also defective in GABA degradation process, showed dwarf phenotype, curled leaves and enhanced accumulation of ROS in normal conditions, suggesting the involvement of a bypath for succinic semialdehyde catabolism to γ-hydroxybutyrate as reported previously in Arabidopsis, were less sensitive to salt stress. These results suggest that GABA shunt is involved in salt tolerance of tomato, probably by affecting the homeostasis of metabolites such as succinate and γ-hydroxybutyrate and subsequent ROS accumulation under salt stress.
Assuntos
4-Aminobutirato Transaminase/genética , Glutamato Descarboxilase/genética , Espécies Reativas de Oxigênio/metabolismo , Solanum lycopersicum/fisiologia , Succinato-Semialdeído Desidrogenase/genética , 4-Aminobutirato Transaminase/metabolismo , Regulação da Expressão Gênica de Plantas , Inativação Gênica , Glutamato Descarboxilase/metabolismo , Solanum lycopersicum/efeitos dos fármacos , Solanum lycopersicum/enzimologia , Solanum lycopersicum/genética , Redes e Vias Metabólicas , Folhas de Planta/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Tolerância ao Sal , Cloreto de Sódio/farmacologia , Estresse Fisiológico , Succinato-Semialdeído Desidrogenase/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
High salinity and nitrogen (N) deficiency in soil are two key factors limiting crop productivity, and they usually occur simultaneously. Here we firstly found that H(+) -PPase is involved in salt-stimulated NO3 (-) uptake in the euhalophyte Salicornia europaea. Then, two genes (named SeVP1 and SeVP2) encoding H(+) -PPase from S. europaea were characterized. The expression of SeVP1 and SeVP2 was induced by salt stress and N starvation. Both SeVP1 or SeVP2 transgenic Arabidopsis and wheat plants outperformed the wild types (WTs) when high salt and low N occur simultaneously. The transgenic Arabidopsis plants maintained higher K(+) /Na(+) ratio in leaves and exhibited increased NO3 (-) uptake, inorganic pyrophosphate-dependent vacuolar nitrate efflux and assimilation capacity under this double stresses. Furthermore, they had more soluble sugars in shoots and roots and less starch accumulation in shoots than WT. These performances can be explained by the up-regulated expression of ion, nitrate and sugar transporter genes in transgenic plants. Taken together, our results suggest that up-regulation of H(+) -PPase favours the transport of photosynthates to root, which could promote root growth and integrate N and carbon metabolism in plant. This work provides potential strategies for improving crop yields challenged by increasing soil salinization and shrinking farmland.
Assuntos
Arabidopsis/fisiologia , Chenopodiaceae/genética , Pirofosfatase Inorgânica/fisiologia , Proteínas de Plantas/fisiologia , Triticum/fisiologia , Arabidopsis/genética , Metabolismo dos Carboidratos , Pirofosfatase Inorgânica/genética , Nitrogênio/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas/fisiologia , Potássio/metabolismo , Cloreto de Sódio/metabolismo , Estresse Fisiológico/genética , Triticum/genéticaRESUMO
Improving crop nitrogen (N) use efficiency under salinity is essential for the development of sustainable agriculture in marginal lands. Salicornia europaea is a succulent euhalophyte that can survive under high salinity and N-deficient habitat conditions, implying that a special N assimilation mechanism may exist in this plant. In this study, phenotypic and physiological changes of S. europaea were investigated under different nitrate and NaCl levels. The results showed that NaCl had a synergetic effect with nitrate on the growth of S. europaea. In addition, the shoot nitrate concentration and nitrate uptake rate of S. europaea were increased by NaCl treatment under both low N and high N conditions, suggesting that nitrate uptake in S. europaea was NaCl facilitated. Comparative proteomic analysis of root plasma membrane (PM) proteins revealed 81 proteins, whose abundance changed significantly in response to NaCl and nitrate. These proteins are involved in metabolism, cell signalling, transport, protein folding, membrane trafficking, and cell structure. Among them, eight proteins were calcium signalling components, and the accumulation of seven of the above-mentioned proteins was significantly elevated by NaCl treatment. Furthermore, cytosolic Ca(2+) concentration ([Ca(2+)]cyt) was significantly elevated in S. europaea under NaCl treatment. The application of the Ca(2+) channel blocker LaCl3 not only caused a decrease in nitrate uptake rate, but also attenuated the promoting effects of NaCl on nitrate uptake rates. Based on these results, a possible regulatory network of NaCl-facilitated nitrate uptake in S. europaea focusing on the involvement of Ca(2+) signalling was proposed.
Assuntos
Sinalização do Cálcio/efeitos dos fármacos , Chenopodiaceae/metabolismo , Proteínas de Membrana/metabolismo , Nitratos/metabolismo , Proteínas de Plantas/metabolismo , Proteômica , Cloreto de Sódio/farmacologia , Membrana Celular/metabolismo , Raízes de Plantas/metabolismo , Plantas Tolerantes a Sal/metabolismoRESUMO
Despite the importance of NHX1 (Na(+)/H(+) exchanger 1) in plant salt tolerance, little is known about its other functions. In this study, intriguingly, it was found that NHX1 participated in plant disease defence against Phytophthora parasitica var. nicotianae (Ppn) in Nicotiana benthamiana. NbNHX1 was originally isolated from N. benthamiana, and characterized. The subcellular localization of NbNHX1 with its C-terminus fused with green fluorescent protein indicated that NbNHX1 localized primarily to the tonoplast. Tobacco rattle virus-induced NbNHX1 silencing led to reduced H(+) efflux from the vacuole to cytoplasts, and decreased Ppn resistance in N. benthamiana. After attack by Ppn, NbNHX1-silenced plants exhibited impaired ability to scavenge reactive oxidative species (ROS) induced by the pathogen. Pea early browning virus-mediated ectopic expression of SeNHX1 (from Salicornia europaea) or AtNHX1 (from Arabidopsis thaliana) both conferred enhanced Ppn resistance to N. benthamiana, with a lower H2O2 concentration after Ppn inoculation. Further investigation of the role of NHX1 demonstrated that transient overexpression of NbNHX1 improved the vacuolar pH and cellular ROS level in N. benthamiana, which was coupled with an enlarged NAD(P) (H) pool and higher expression of ROS-responsive genes. In contrast, NbNHX1 silencing led to a lower pH in the vacuole and a lower cellular ROS level in N. benthamiana, which was coupled with a decreased NAD(P) (H) pool and decreased expression of ROS-responsive genes. These results suggest that NHX1 is involved in plant disease defence; and regulation of vacuolar pH by NHX1, affecting the cellular oxidation state, primes the antioxidative system which is associated with Ppn resistance in tobacco.
Assuntos
Resistência à Doença , Regulação da Expressão Gênica de Plantas , Nicotiana/imunologia , Phytophthora/fisiologia , Doenças das Plantas/imunologia , Trocadores de Sódio-Hidrogênio/metabolismo , Sequência de Aminoácidos , Antioxidantes/metabolismo , Genes Reporter , Peróxido de Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Dados de Sequência Molecular , Folhas de Planta , Alinhamento de Sequência , Trocadores de Sódio-Hidrogênio/genética , Nicotiana/citologia , Nicotiana/genética , Vacúolos/metabolismoRESUMO
The Arabidopsis genome contains seven members of Hsp90. Mutations in plastid AtHsp90.5 were reported to cause defects in chloroplast development and embryogenesis. However, the exact function of plastid AtHsp90.5 has not yet been defined. In this study, albino seedlings were found among AtHsp90.5 transformed Arabidopsis, which were revealed to be AtHsp90.5 co-suppressed plants. The accumulation of photosynthetic super-complexes in the albinos was decreased, and expression of genes involved in photosynthesis was significantly down-regulated. AtHsp90.5 T-DNA insertion mutants were embryo-lethal with embryo arrested at the heart stage. Further investigation showed AtHsp90.5 expression was up-regulated in the siliques at 4 days post anthesis (DPA). Confocal microscopy proved AtHsp90.5 was located in the chloroplasts. Plastid development in the AtHsp90.5 mutants and co-suppressed plants was seriously impaired, and few thylakoid membranes were observed, indicating the involvement of AtHsp90.5 in chloroplast biogenesis. AtHsp90.5 was found to interact with vesicle-inducing protein in plastids 1 (VIPP1) by bimolecular fluorescence complementation system. The ratio between VIPP1 oligomers and monomers in AtHsp90.5 co-suppressed plants drastically shifted toward the oligomeric state. Our study confirmed that AtHsp90.5 is vital for chloroplast biogenesis and embryogenesis. Further evidence also suggested that AtHsp90.5 may help in the disassembly of VIPP1 for thylakoid membrane formation and/or maintenance.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/embriologia , Arabidopsis/metabolismo , Cloroplastos/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Membrana/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Segregação de Cromossomos , DNA Bacteriano/genética , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Teste de Complementação Genética , Proteínas de Choque Térmico HSP90/genética , Proteínas de Membrana/genética , Mutagênese Insercional/genética , Fotossíntese , Plantas Geneticamente Modificadas , Ligação Proteica , Transporte Proteico , Protoplastos/metabolismo , Plântula/genética , Frações Subcelulares/metabolismo , Supressão Genética , Transformação GenéticaRESUMO
Introduction: Multiple system atrophy (MSA) is a rapidly progressing neurodegenerative disorder. Although diverse biomarkers have been established for Parkinson's disease (PD), no widely accepted markers have been identified in MSA. Pyruvate and lactate are the end-product of glycolysis and crucial for brain metabolism. However, their correlation with MSA remains unclear. Moreover, it is elusive how lifestyles modify these metabolites. Methods: To investigate the correlation and diagnostic value of plasma pyruvate and lactate levels in MSA and PD. Moreover, we explored how lifestyle-related metabolites interact with these metabolites in determining the disease risk. We assayed the 3 metabolites in pyruvate/lactate and 6 in the tea/coffee metabolic pathways by targeted mass spectrometry and evaluate their interactions and performance in diagnosis and differentiation between MSA and PD. Results: We found that 7 metabolites were significantly different between MSA, PD and healthy controls (HCs). Particularly, pyruvate was increased in PD while significantly decreased in MSA patients. Moreover, the tea/coffee metabolites were negatively associated with the pyruvate level in HCs, but not in MSA and PD patients. Using machine-learning models, we showed that the combination of pyruvate and tea/coffee metabolites diagnosed MSA (AUC = 0.878) and PD (AUC = 0.833) with good performance. Additionally, pyruvate had good performance in distinguishing MSA from PD (AUC = 0.860), and the differentiation increased (AUC = 0.922) when combined with theanine and 1,3-dimethyluric acid. Conclusions: This study demonstrates that pyruvate correlates reversely with MSA and PD, and may play distinct roles in their pathogenesis, which can be modified by lifestyle-related tea/coffee metabolites.
RESUMO
BACKGROUND: Identifying the risk factors associated with perioperative mortality is crucial, particularly in older patients. Predicting 6-month mortality risk in older patients based on large datasets can assist patients and surgeons in perioperative clinical decision-making. This study aimed to develop a risk prediction model of mortality within 6 months after noncardiac surgery using the clinical data from 11 894 older patients in China. MATERIALS AND METHODS: A multicentre, retrospective cohort study was conducted in 20 tertiary hospitals. The authors retrospectively included 11 894 patients (aged ≥65 years) who underwent noncardiac surgery between April 2020 and April 2022. The least absolute shrinkage and selection operator model based on linear regression was used to analyse and select risk factors, and various machine learning methods were used to build predictive models of 6-month mortality. RESULTS: The authors predicted 12 preoperative risk factors associated with 6-month mortality in older patients after noncardiac surgery. Including laboratory-associated risk factors such as mononuclear cell ratio and total blood cholesterol level, etc. Also including medical history associated risk factors such as stroke, history of chronic diseases, etc. By using a random forest model, the authors constructed a predictive model with a satisfactory accuracy (area under the receiver operating characteristic curve=0.97). CONCLUSION: The authors identified 12 preoperative risk factors associated with 6-month mortality in noncardiac surgery older patients. These preoperative risk factors may provide evidence for a comprehensive preoperative anaesthesia assessment as well as necessary information for clinical decision-making by anaesthesiologists.
Assuntos
Acidente Vascular Cerebral , Humanos , Idoso , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Tomada de Decisão ClínicaRESUMO
Hypoxic-ischemic encephalopathy (HIE) at high-altitudes leads to neonatal mortality and long-term neurological complications without effective treatment. Acer truncatum Bunge Seed extract (ASO) is reported to have effect on cognitive improvement, but its molecular mechanisms on HIE are unclear. In this study, ASO administration contributed to reduced neuronal cell edema and improved motor ability in HIE rats at a simulated 4500-meter altitude. Transcriptomics and WGCNA analysis showed genes associated with lipid biosynthesis, redox homeostasis, neuronal growth, and synaptic plasticity regulated in the ASO group. Targeted and untargeted-lipidomics revealed decreased free fatty acids and increased phospholipids with favorable ω-3/ω-6/ω-9 fatty acid ratios, as well as reduced oxidized glycerophospholipids (OxGPs) in the ASO group. Combining multi-omics analysis demonstrated FA to FA-CoA, phospholipids metabolism, and lipid peroxidation were regulated by ASO treatment. Our results illuminated preliminary metabolism mechanism of ASO ingesting in rats, implying ASO administration as potential intervention strategy for HIE under high-altitude.
Assuntos
Acer , Hipóxia-Isquemia Encefálica , Ratos , Animais , Neuroproteção , Altitude , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Hipóxia-Isquemia Encefálica/prevenção & controle , Hipóxia-Isquemia Encefálica/complicações , Multiômica , Extratos Vegetais/farmacologia , IsquemiaRESUMO
Objective: The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule (LTC) on ischemic stroke rats. Methods: Twenty-six rats were randomly divided into four groups, including sham group, sham + LTC group, MCAO group, and MCAO + LTC group. Ischemic stroke rats were simulated by middle cerebral artery occlusion (MCAO), and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days. LTC therapy was validated in terms of neurobehavioral abnormality evaluation, cerebral infarct area, and histological assessments. The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis, aiming to finding the molecules in respond to the surgery or LTC treatment. Results: Intragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats. The interstitial edema, atrophy, and pyknosis of glial and neuronal cells occurred in the infarcted area, core area, and marginal area of cerebral cortex were improved after LTC treatment. A total of 13 potential biomarkers were observed, and Youden index of 11 biomarkers such as LysoPC, SM, and PE were more than 0.7, which were involved in neuroprotective process. The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism, together with nicotinate and nicotinamide metabolism. Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC. Conclusion: The present study could provide evidence that metabolomics, as systematic approach, revealed its capacity to evaluate the holistic efficacy of TCM, and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.
RESUMO
Hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of acute neonatal death and chronic neurological damage, and severe HIE can have secondary sequelae such as cognitive impairment and cerebral palsy, for which effective interventions are lacking. In this study, we found that continuous 30-day intake of Acer truncatum Bunge seed oil (ASO) reduced brain damage and improved cognitive ability in HIE rats. Using lipidomic strategies, we observed that HIE rats had decreased unsaturated fatty acids and increased lysophospholipids in the brain. However, after 30 days of ASO treatment, phospholipids, plasmalogens, and unsaturated fatty acids increased, while lysophospholipids and oxidized glycerophospholipids decreased in both serum and the brain. Enrichment analysis showed that ASO intake mainly affected sphingolipid metabolism, fat digestion and absorption, glycerolipid metabolism and glycerophospholipid metabolic pathways in serum and the brain. Cluster, correlation, and confirmatory factor analyses showed that cognitive improvement after ASO administration was attributed to increased essential phospholipids and ω3/6/9 fatty acids, coupled with decreased oxidized glycerophospholipids in HIE rats. Our findings indicate that ASO has the potential to be developed as an effective food supplement for ischemic hypoxic newborns.
Assuntos
Acer , Hipóxia-Isquemia Encefálica , Ratos , Animais , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Hipóxia-Isquemia Encefálica/metabolismo , Lipidômica , Cognição , Glicerofosfolipídeos , Óleos de Plantas/farmacologiaRESUMO
BACKGROUND AND AIMS: Carotid atherosclerosis is an important cause of ischemic stroke. Lipids play a key role in the progression of atherosclerosis. To date, the spatial lipid profile of carotid atherosclerotic plaques related to histology has not been systematically investigated. METHODS: Carotid atherosclerosis samples from 12 patients were obtained and classified into four classical pathological stages (preatheroma, atheroma, fibroatheroma and complicated lesion) by histological staining. Desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) was used to investigate the lipid profile of carotid atherosclerosis, and correlated it with histological information. Bioinformatics technology was used to process MSI data among different pathological stages of atherosclerosis lesions. RESULTS: A total of 55 lipids (26 throughout cross-section regions [TCSRs], 13 in lipid-rich regions [LRRs], and 16 in collagen-rich regions [CRRs]) were initially identified in carotid plaque from one patient. Subsequently, 32 of 55 lipids (12 in TCSRs, eight in LRRs, and 12 in CRRs) were further screened in 11 patients. Pathway enrichment analysis showed that multiple metabolic pathways, such as fat digestion and absorption, cholesterol metabolism, lipid and atherosclerosis, were enriched in TCSRs; sphingolipid signaling pathway, necroptosis pathway were enriched in LRRs; and glycerophospholipid metabolism, ether lipid metabolism pathway were mainly enriched in CRRs. CONCLUSIONS: This study comprehensively showed the spatial lipid metabolism footprint in human carotid atherosclerotic plaques. The lipid profiles and related metabolism pathways in three regions of plaque with disease progression were different markedly, suggesting that the different metabolic mechanisms in these regions of carotid plaque may be critical in atherosclerosis progression.
Assuntos
Aterosclerose , Doenças das Artérias Carótidas , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/patologia , Doenças das Artérias Carótidas/patologia , Aterosclerose/patologia , Artérias Carótidas/patologia , Lipídeos/químicaRESUMO
BACKGROUND: The diagnosis of cerebral thrombosis origin is challenging and remains unclear. This study aims to identify thrombosis due to cardioembolism (CE) and large artery atherosclerosis (LAA) from a new perspective of distinct metabolites. METHODS: Distinct metabolites between 26 CE and 22 LAA origin thrombi, which were extracted after successful mechanical thrombectomy in patients with acute ischemic stroke in the anterior circulation, were analyzed with a ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) system. Enriched metabolic pathways related to the metabolites were identified. Least absolute shrinkage selection operator regression analyses and a filtering method were used to select potential predictors. Furthermore, four machine learning classifiers, including decision tree, logistic regression, random forest (RF), and k means unsupervised classification model, were used to evaluate the predictive ability of the selected metabolites. RESULTS: UPLC-QTOF-MS analysis revealed that levels of 88 and 55 metabolites were elevated in LAA and CE thrombi, respectively. Kyoto Encyclopedia of Genes and Genomes analysis revealed a significant difference between the pathways enriched in the two types of thrombi. Six metabolites (diglyceride (DG, 18:3/24:0), DG (22:0/24:0), phytosphingosine, galabiosylceramide (18:1/24:1), triglyceride (15:0/16:1/o-18:0), and glucosylceramide (18:1/24:0)) were finally selected to build a predictive model. The predictive RF model was confirmed to be the best, with a satisfactory stability and prediction capacity (area under the curve=0.889). CONCLUSIONS: Six metabolites as potential predictors for distinguishing between cerebral thrombi of CE and LAA origin were identified. The results are useful for understanding the pathogenesis and for secondary stroke prevention.
Assuntos
Aterosclerose , AVC Isquêmico , Acidente Vascular Cerebral , Trombose , Humanos , AVC Isquêmico/complicações , Aterosclerose/complicações , Aterosclerose/diagnóstico , Acidente Vascular Cerebral/complicações , Trombose/complicações , Artérias/patologiaRESUMO
In order to explore the details of the reaction mechanisms of Nb atoms with acetonitrile molecules, the sextet, quartet, and doublet spin state potential energy surfaces have been investigated. Density functional theory (DFT) with the relativistic zero-order regular approximation at the PW91/TZ2P level has been applied. The complicated minimum energy reaction path involves four transition states (TS), stationary states (1) to (5) and two intersystem crossings from spin sextets to quartets to doublets (indicated by â): (6)Nb + NCCH3â(6)Nb η(1)-NCCH3 ((6)1) â(6)TS1/2â(4)Nb η(2)-(NC)CH3 ((4)2) â(4)TS2/3â(4)NbH η(3)-(NCCH2) ((4)3) â(4)TS3/4â CNNbCH3 ((4)4) â(2)TS4/5â CN(NbH)CH2 ((2)5). The minimum energy crossing points were determined with the help of the DFT fractional-occupation-number approach. The first spin inversion leads from the sextet to an energetically low intermediate quartet ((4)2) with final insertion of Nb into the C-C bond. The second one from the quartet to the doublet state facilitates the activation of a C-H bond, lowering the rearrangement-barrier by 44 kJ mol(-1). The overall reaction is calculated to be exothermic by about 170-180 kJ mol(-1). All intermediate and product species were frequency and NBO analyzed. The species can be rationalized with the help of Lewis type formulas.
RESUMO
To explore the details of the reaction mechanisms of Zr atoms with acetonitrile molecules, the triplet and singlet spin-state potential energy surfaces have been investigated. Density functional theory (DFT) with the relativistic zero-order regular approximation at the PW91/TZ2P level has been applied. The complicated minimum energy reaction path involves four transition states (TS), stationary states 1-5 and one spin inversion (indicated by â): (3)Zr + NCCH(3) â (3)Zr-η(1)-NCCH(3) ((3)1) â (3)TS(1/2) â (3)Zr-η(2)-(NC)CH(3) ((3)2) â (3)TS(2/3) â (3)ZrH-η(3)-(NCCH(2)) ((3)3) â (3)TS(3/4) â CNZrCH(3) ((3)4) â (1)TS(4/5) â CN(ZrH)CH(2) ((1)5). The minimum energy crossing point was determined with the help of the DFT fractional-occupation-number approach. The spin inversion leading from the triplet to the singlet state facilitates the activation of a C-H bond, lowering the rearrangement-barrier by 78 kJ/mol. The overall reaction is calculated to be exothermic by about 296 kJ/mol. All intermediate and product species were frequency and NBO analyzed. The species can be rationalized with the help of Lewis type formulas.
RESUMO
BACKGROUND AND PURPOSE: Radiotherapy is a standard treatment for head and neck tumors that significantly increases patients' long-term survival rates. However, late cerebrovascular complications, especially carotid artery stenosis (CAS), have gained increasing attention. Investigation of biomarkers of radiation-induced CAS may help to elucidate the mechanism by which radiation induces damage to blood vessels and identify possible preventive measures against such damage. MATERIALS AND METHODS: In this study, we used lipidomics strategy to characterize the lipids present in 8 radiation-induced carotid plaques (RICPs) and 12 atherosclerotic carotid plaques (ASCPs). We also used desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) to map the spatial distribution of the screened lipids from 2 RICPs samples and 2 ASCPs samples. RESULTS: The results showed that 31 metabolites in RICPs were significantly higher than that in ASCPs, 24 of which were triglycerides (TGs). We used four machine learning models to select potential indicators from the 31 metabolites. Six TGs [TG(17:2/17:2/18:0), TG(17:1/17:2/18:0), TG(17:0/17:2/18:0), TG(17:2/17:2/20:0), TG(17:1/17:2/20:0), TG(15:0/22:0/22:2)] were found to be the potential markers for distinguishing RICPs and ASCPs (AUC = 0.83). The DESI-MSI results suggested that the 6 TGs were localized in the collagen fiber regions and confirmed the differences of these TGs between the two kinds of plaques. CONCLUSIONS: The 6 TGs primarily localized in the collagen fiber regions of plaques are likely to be potential indicators for the differentiation of RICPs from ASCPs which may have implications in the mechanisms and possible preventive measures against RICPs.
Assuntos
Lipídeos , Espectrometria de Massas por Ionização por Electrospray , Colágeno , Humanos , Lipídeos/análise , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
In this work, untargeted lipidomics was employed to analyze the effects of coal dust exposure on serum metabolite profiles. Furthermore, the potential of differential metabolites as novel biomarkers for diagnosis was investigated by binary logistic classification model. Nineteen differential metabolites were found among the three groups. The compounds were enriched in pathways associated with linoleic acid metabolism and pyrimidine metabolism. Fifty-three differential metabolites were found in coal dust-exposed people and CWP patients, and they were mainly enriched in glycerophospholipid metabolism. Three differential metabolites were correlated with lung function values. The diagnostic model, composed of lysoPI (16:0/0:0), bilirubin, and lysoPC (24:1/0:0), showed strong discrimination ability between dust-exposed people and CWP patients. The sensitivity, specificity, and AUC values of the model were 0.869, 0.600, and 0.750, respectively. The results suggest that coal worker's pneumoconiosis causes abnormal lipid metabolism in the body. A diagnostic model may aid current CWP diagnostic methods, and lysoPI (16:0/0:0), bilirubin, and lysoPC (24:1/0:0) can be used as potential CWP biomarkers. Further study is warranted to validate the findings in larger populations.