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1.
Chem Commun (Camb) ; 55(81): 12192-12195, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31544919

RESUMO

A fast (down to 1 min), power-saving (watt) and green strategy was proposed for preparing diverse and fine-tuned metal-organic frameworks (MOFs) and MOFs-based composites in either DMF or ethanol, catalyzed by liquid-phase plasma generated via dielectric barrier discharge (DBD).

2.
Angew Chem Int Ed Engl ; 58(36): 12519-12523, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269315

RESUMO

A light-responsive system constructed from hydrogen-bonded azo-macrocycles demonstrates precisely controlled propensity in molecular encapsulation and release process. A significant decrease in the size of the cavity is observed in the course of the E→Z photoisomerization based on the results from DFT calculations and traveling wave ion mobility mass spectrometry. These macrocyclic hosts exhibit a rare 2:1 host-guest stoichiometry and guest-dependent slow or fast exchange on the NMR timescale. With the slow host-guest exchange and switchable shape change of the cavity, quantitative release and capture of bipyridinium guests is achieved with the maximum release of 68 %. This work underscores the importance of slow host-guest exchange on realizing accurate release of organic cations in a stepwise manner under light irradiation. The light-responsive system established here could advance further design of novel photoresponsive molecular switches and mechanically interlocked molecules.

3.
Asia Pac J Clin Nutr ; 28(2): 411-418, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31192571

RESUMO

BACKGROUND AND OBJECTIVES: By combining the techniques of metabolomics and computational biology, this research aims to explore the mechanism of metabolic dynamics in critically injured patients and develop a new early warning method for mortality. METHODS AND STUDY DESIGN: A prospective cohort study was conducted, group plasma samples of critically injured patients were collected for 1H-NMR metabolomics analysis. The data was processed with partial least squares regression, to explore the role of enzyme-gene network regulatory mechanism in critically injured metabolic network regulation and to build a quantitative prediction model for early warning of fast death. RESULTS: In total, 60 patients were enrolled. There were significant differences in plasma metabolome between the surviving patients and the deceased ones. Compared to the surviving patients, 112 enzymes and genes regulating the 6 key metabolic marker disturbances of neopterin, corticosterone, 3-methylhistidine, homocysteine, Serine, tyrosine, prostaglandin E2, tryptophan, testosterone and estriol, were observed in the plasmas of deceased ones. Among patients of different injury stages, there were significant differences in plasma metabolome. Progressing from T0 to T50 stages of injury, increased levels of neopterin, corticosterone, prostaglandin E2, tryptophan and testosterone, together with decreased levels of homocysteine, and estriol, were observed. Eventually, the quantitative prediction model of death warning was established. Cross-validation results showed that the predictive effect was good (RMSE=0.18408, R2=0.87 p=0.036). CONCLUSIONS: Metabolomics approaches can be used to quantify the metabolic dynamics of patients with critically injuries and to predict death of critically injured patients by plasma 1H-NMR metabolomics.

4.
Chem Commun (Camb) ; 55(33): 4869-4872, 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-30951049

RESUMO

Three new hydrogen-bonded aromatic amide macrocycles with eight residues were synthesized. The first single crystal structure of this class of larger macrocycles was obtained, which reveals a saddle-like conformation. Interestingly, in sharp contrast to previous negative cooperativity in binding paraquat with cyclo[6]aramide, strong positive allosteric cooperativity in ternary complexes was observed. This may open an avenue for the construction of mechanically interlocked molecules with these larger H-bonded macrocycles.

5.
Org Lett ; 21(3): 652-655, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30638017

RESUMO

A supramolecular approach to catalyzing the Ritter reaction by utilizing enhanced anion-binding affinity in the presence of alkali metal cations was developed with ditopic hydrogen-bonded amide macrocycles. With prebound cations in the macrocycle, particularly Li+ ion, their metal complexes exhibit greatly enhanced catalytic activities. The catalysis is switchable by removal or addition of the bound cation. The method described in this work may be generalized for use in other anion-triggered organic reactions involving heteroditopic receptors capable of ion pairing.


Assuntos
Compostos Macrocíclicos/química , Metais Alcalinos/química , Amidas/química , Catálise , Ligações de Hidrogênio
7.
Cell Death Discov ; 4: 24, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30109143

RESUMO

To better understand the resistance mechanism of non-small cell lung cancers (NSCLCs) to gefitinib, the metabolic profiles of gefitinib-resistant A549 cells and gefitinib-sensitive PC-9 cells were analyzed with a metabolomics analytical platform. A549 and PC-9 cells exhibited significant differences in the levels of glutamine-related metabolites. After gefitinib treatment, the glutamine level decreased in A549 cells but showed no change in PC-9 cells. The glutamine consumed by A549 cells was used to generate ATP and glutathione (GSH). As glutamine utilization was suppressed in gefitinib-treated PC-9 cells, the resulting ATP shortage and ROS accumulation led to cell death. The difference in glutamine metabolism was caused by differential changes in the levels of glutamine synthetase (GS, encoded by glutamate-ammonia ligase (GLUL)). GLUL expression was upregulated in gefitinib-sensitive cells, but it was either absent from gefitinib-resistant cells or no significant change was observed in the gefitinib-treated cells. GLUL overexpression in A549 cells significant sensitized them to gefitinib and decreased their invasive capacity. Conversely, knockout GS in PC-9 cells reduced gefitinib sensitivity and enhanced metastasis. Furthermore, the continuous exposure of gefitinib-sensitive HCC827 cells to gefitinib created gefitinib-resistant (GR) HCC827 cells, which exhibited a GLUL deletion and resistance to gefitinib. Thus, GLUL plays a vital role in determining the sensitivity of NSCLCs to gefitinib. Elevated GS levels mediate increased glutamine anabolism, and this novel mechanism sensitizes NSCLCs to gefitinib. The inhibition of glutamine utilization may serve as a potential therapeutic strategy to overcome gefitinib resistance in the clinic.

8.
Phys Chem Chem Phys ; 20(35): 23013-23024, 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30159576

RESUMO

It is important to investigate the phase transition mechanism of stimuli-sensitive hydrogels due to its great guiding significance for the application of stimuli-sensitive hydrogels in biomedical applications. In this work, the novel thermo-sensitive poly(N-vinylcaprolactam-co-hydroxyethyl methacrylate) (PVCL-co-HEMA) hydrogel was successfully synthesized via free radical polymerization, and then temperature-dependent FTIR spectra combined with the newly developed scaling moving-window two-dimensional (scaling-MW2D) correlation spectroscopy and generalized two-dimensional correlation analysis were utilized to investigate its volume phase transition (VPT) mechanism upon heating. Conventional 1D FTIR spectra and Boltzmann fitting results revealed that the PVCL-co-HEMA hydrogel exhibited a distinct VPT behavior from the neat PVCL hydrogel due to the incorporation of PHEMA. The essential reason is that some water molecules were still confined in the PVCL-co-HEMA network after phase transition at high temperature, rather than continuously being expelled out of the gel with the increase of temperature. Scaling-MW2D spectra revealed that the phase transition of the PVCL-co-HEMA hydrogel could be divided into two steps (I and II), and further confirmed that the transition regions of these two steps were 25.0-32.3 °C and 32.3-46.8 °C, respectively. The transition regions of both these steps were obviously lower than those of the neat PVCL hydrogel. According to the generalized 2D correlation analysis of step I, we concluded that the dissociation of the hydrogen bonds between the incorporated PHEMA moieties and water molecules is the driving force for the local hydrophobic domain formation process (step I), and its occurrence at a lower temperature is the main reason for the decrease of the VPTT of the PVCL segments. Furthermore, we found that the dissociation of the hydrogen bonds between the C[double bond, length as m-dash]OVCL groups and water molecules is the driving force for the chain collapse (step II), and the driving effect of the PVCL segments on PHEMA during the phase transition was confirmed. Combined with the obtained sequential order of steps I and II, an unusual two-step VPT mechanism for the PVCL-co-HEMA hydrogel upon heating was proposed.

9.
Exp Neurol ; 307: 52-61, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29753648

RESUMO

Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis in mammals, converts nicotinamide into nicotinamide mononucleotide (NMN). NMN is subsequently converted to NAD, a component that is critical for cell energy metabolism and survival. Sirtuin 1 (SIRT1), an NAD-dependent histone deacetylase, plays an important role in mediating memory and synaptic plasticity. Here, we found that NAMPT was significantly upregulated in the ventral tegmental area (VTA) of cocaine-conditioned mice. Intraperitoneal or intra-VTA injection of FK866, a specific inhibitor of NAMPT, significantly attenuated cocaine reward. However, such effects were clearly repressed by intra-VTA expression of NAMPT or supplementation with NMN. Using 1H-nuclear magnetic resonance metabolomic analysis, we found that the content of NAD and NMN were increased in the VTA of cocaine-conditioned mice; moreover, the expression of SIRT1 was also upregulated. Interestingly, the inhibitory effect of FK866 on cocaine reward was significantly weakened in Sirt1 midbrain conditional knockout mice. Our results suggest that NAMPT-mediated NAD biosynthesis may modify cocaine behavioral effects through SIRT1. Moreover, our findings reveal that the interplay between NAD biosynthesis and SIRT1 regulation may comprise a novel regulatory pathway that responds to chronic cocaine stimuli.

10.
Toxicol Lett ; 294: 166-176, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29758358

RESUMO

Alcohol abuse and its related diseases are the major risk factors for human health. Although the mechanism of alcohol-related disorders has been widely investigated, serum metabolites associated with long-term alcohol intake have not been well explored. In this study, we aimed to investigate the profiles of serum metabolites and lipid species of rats chronically exposed to alcohol, which may be involved in the pathogenesis of alcohol-associated disease. An 1H NMR-based metabolomics and Q-TOF/MS-based lipidomics approach were applied to investigate the profile of serum metabolites and lipid species of rats administrated daily with alcohol (12% vol/vol, 10 ml/kg per day, i.g.) for one year continuously. The rats administered with sterile water (10 ml/kg per day, i.g.) were used as control. We found that alcohol affected mostly the lipid species rather than small molecule metabolites in the serum of both female and male rats. Among the modified lipids, glycerophospholipid, sphingolipid and glycerolipids metabolism pathways were profoundly altered. The prominent changes in lipid profiles included diacylglycerol (DG), lysophosphatidylcholine (LysoPC), phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE) and triacylglycerol (TG). Moreover, fatty-acyl profile of lipids and total degree of unsaturation of fatty acid were also significantly altered by alcohol. The modified lipidomic profile may help to understand the pathogenesis of alcohol-associated diseases and also be of value for clinical evaluation of alcohol abuse, alcohol-associated disease diagnosis.


Assuntos
Alcoolismo/fisiopatologia , Modelos Animais de Doenças , Dislipidemias/etiologia , Lipídeos/sangue , Alcoolismo/sangue , Animais , Colesterol/sangue , Colesterol/química , Análise Discriminante , Ácidos Graxos/análise , Ácidos Graxos/sangue , Ácidos Graxos/química , Feminino , Glicerídeos/sangue , Glicerídeos/química , Glicerofosfolipídeos/sangue , Glicerofosfolipídeos/química , Análise dos Mínimos Quadrados , Lipídeos/química , Espectroscopia de Ressonância Magnética , Masculino , Metabolômica/métodos , Estrutura Molecular , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Caracteres Sexuais , Espectrometria de Massas por Ionização por Electrospray , Esfingolipídeos/sangue , Esfingolipídeos/química
11.
Talanta ; 178: 538-544, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29136859

RESUMO

The chemical shifts of several important endogenous phosphorus compounds under different pH conditions were explored, including adenosine-5'-triphosphate, adenosine-5'-diphosphate, adenosine-5'-monophosphate, phosphorylcholine and phosphorylethanolamine. Their 31P NMR and 1H NMR chemical shifts were all pH-sensitive in the similar pH range. Two dimensional (2D) 1H-31P NMR spectra were found helpful to identify these endogenous phosphorus markers in biological samples from rather complicated NMR spectra. Herein, for the first time, a pH sensor based on 2D 1H-31P NMR was established and applied to biological samples analysis with pH values determined in good agreement with those by potentiometric method. Apart from being simple, green, rapid and less sample-consuming, information concerning both the endogenous phosphorus markers and pH status could be attained in a single NMR run, which demonstrated the great potential of this method in rare sample analysis and even disease diagnosis.


Assuntos
Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética/métodos , Difosfato de Adenosina/análise , Difosfato de Adenosina/urina , Monofosfato de Adenosina/análise , Monofosfato de Adenosina/urina , Trifosfato de Adenosina/análise , Trifosfato de Adenosina/urina , Etanolaminas/análise , Etanolaminas/urina , Sucos de Frutas e Vegetais/análise , Células Hep G2 , Humanos , Malus , Fosforilcolina/análise , Fosforilcolina/urina
12.
Neuropharmacology ; 2017 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-28987936

RESUMO

The brain is a high energy-consuming organ that typically utilizes glucose as the main energy source for cerebral activity. When glucose becomes scarce under conditions of stress, ketone bodies, such as ß-hydroxybutyrate, acetoacetate and acetone, become extremely important. Alterations in brain energy metabolism have been observed in psychostimulant abusers; however, the mode of brain metabolic programming in cocaine dependence remains largely unknown. Here, we profiled the metabolites and metabolic enzymes from brain nucleus accumbens (NAc) of mice exposed to cocaine. We found that cocaine modified energy metabolism and markedly activated ketogenesis pathway in the NAc. The expression of HMG-CoA synthase 2 (HMGCS2), a critical rate-limiting ketogenesis enzyme, was markedly up-regulated. After switching metabolic pathways from ketogenesis to glycolysis through activation of glucokinase, cocaine-evoked metabolic reprogramming regained homeostasis, and the cocaine effect was attenuated. Importantly, both the pharmacological and genetic inhibition of HMGCS2 significantly suppressed cocaine-induced ketogenesis and behavior. In conclusion, cocaine induces a remarkable energy reprogramming in the NAc, which is characterized by HMGCS2-driven ketogenesis. Such effect may facilitate adaptations to cocaine-induced energy stress in the brain. Our findings establish an important link between drug-induced energy reprogramming and cocaine effect, and may have implication in the treatment of cocaine addiction.

13.
Oncol Rep ; 38(5): 3044-3054, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28901465

RESUMO

Lung metastasis is an important cause for the low 5-year survival rate of colorectal cancer patients. Understanding the metabolic profile of lung metastasis of colorectal cancer is important for developing molecular diagnostic and therapeutic approaches. We carried out the metabonomic profiling of lung tissue samples on a mouse lung metastasis model of colorectal cancer using 1H-nuclear magnetic resonance (1H-NMR). The lung tissues of mice were collected at different intervals after marine colon cancer cell line CT-26 was intravenously injected into BALB/c mice. The distinguishing metabolites of lung tissue were investigated using 1H-NMR-based metabonomic assay, which is a highly sensitive and non-destructive method for biomarker identification. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were applied to analyze 1H-NMR profiling data to seek potential biomarkers. All of the 3 analyses achieved excellent separations between the normal and metastasis groups. A total of 42 metabolites were identified, ~12 of which were closely correlated with the process of metastasis from colon to lung. These altered metabolites indicated the disturbance of metabolism in metastatic tumors including glycolysis, TCA cycle, glutaminolysis, choline metabolism and serine biosynthesis. Our findings firstly identified the distinguishing metabolites in mouse colorectal cancer lung metastasis models, and indicated that the metabolite disturbance may be associated with the progression of lung metastasis from colon cancer. The altered metabolites may be potential biomarkers that provide a promising molecular approach for clinical diagnosis and mechanistic study of colorectal cancer with lung metastasis.


Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Metabolômica/métodos , Animais , Linhagem Celular Tumoral , Progressão da Doença , Glicólise , Neoplasias Pulmonares/diagnóstico por imagem , Camundongos , Transplante de Neoplasias , Análise de Componente Principal , Espectroscopia de Prótons por Ressonância Magnética/métodos
14.
Nanoscale ; 9(29): 10167-10172, 2017 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-28702587

RESUMO

As acidic pH plays essential roles in several organelles, development of pH sensors for extreme acidity is of vital importance. Herein, on the basis of the inner filter effect (IFE) between ascorbic acid (AA) and Au nano-clusters (AuNCs), a simple extreme acidity fluorescence sensor was developed without complex organic synthesis. The as-prepared probe can be used to detect acidity within the pH range of 2.4-4.6. Moreover, the probe possesses high selectivity, good photostability, and excellent reversibility for monitoring extreme acidity in bacterial cells without the influence of autofluorescence.

15.
Chem Sci ; 8(3): 2091-2100, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28451329

RESUMO

Examples of using two-dimensional shape-persistent macrocycles, i.e. those having noncollapsible and geometrically well-defined skeletons, for constructing mechanically interlocked molecules are scarce, which contrasts the many applications of these macrocycles in molecular recognition and functional self-assembly. Herein, we report the crucial role played by macrocyclic shape-persistency in enhancing multipoint recognition for the highly efficient template-directed synthesis of rotaxanes. Cyclo[6]aramides, with a near-planar conformation, are found to act as powerful hosts that bind bipyridinium salts with high affinities. This unique recognition module, composed of two macrocyclic molecules with one bipyridinium ion thread through the cavity, is observed both in the solid state and in solution, with unusually high binding constants ranging from ∼1013 M-2 to ∼1015 M-2 in acetone. The high efficacy of this recognition motif is embodied by the formation of compact [3]rotaxanes in excellent yields based on either a "click-capping" (91%) or "facile one-pot" (85%) approach, underscoring the great advantage of using H-bonded aromatic amide macrocycles for the highly efficient template-directed synthesis of mechanically interlocked structures. Furthermore, three cyclo[6]aramides bearing different peripheral chains 1-3 demonstrate high specificity in the synthesis of a [3]rotaxane from 1 and 2, and a [2]rotaxane from 3via a "facile one-pot" approach, in each case as the only isolated product. Analysis of the crystal structure of the [3]rotaxane reveals a highly compact binding mode that would be difficult to access using other macrocycles with a flexible backbone. Leveraging this unique recognition motif, resulting from the shape-persistency of these oligoamide macrocycles, in the template-directed synthesis of compact rotaxanes may open up new opportunities for the development of higher order interlocked molecules and artificial molecular machines.

16.
J Trauma Acute Care Surg ; 83(2): 296-304, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28452885

RESUMO

BACKGROUND: Therapeutic hypothermia is widely used to treat traumatic brain injuries (TBIs). However, determining the best hypothermia therapy strategy remains a challenge. We hypothesized that reducing the metabolic rate, rather than reaching a fixed body temperature, would be an appropriate target because optimizing metabolic conditions especially the brain metabolic environment may enhance neurologic protection. A pilot single-blind randomized controlled trial was designed to test this hypothesis, and a nested metabolomics study was conducted to explore the mechanics thereof. METHODS: Severe TBI patients (Glasgow Coma Scale score, 3-8) were randomly divided into the metabolic-targeted hypothermia treatment (MTHT) group, 50% to 60% rest metabolic ratio as the hypothermia therapy target, and the body temperature-targeted hypothermia treatment (BTHT) control group, hypothermia therapy target of 32°C to 35°C body temperature. Brain and circulatory metabolic pool blood samples were collected at baseline and on days 1, 3, and 7 during the hypothermia treatment, which were selected randomly from a subgroup of MTHT and BTHT groups. The primary outcome was mortality. Using H nuclear magnetic resonance technology, we tracked and located the disturbances of metabolic networks. RESULTS: Eighty-eight severe TBI patients were recruited and analyzed from December 2013 to December 2014, 44 each were assigned in the MTHT and BTHT groups (median age, 42 years; 69.32% men; mean Glasgow Coma Scale score, 6.17 ± 1.02). The mortality was significantly lower in the MTHT than the BTHT group (15.91% vs. 34.09%; p = 0.049). From these, eight cases of MTHT and six cases from BTHT group were enrolled for metabolomics analysis, which showed a significant difference between the brain and circulatory metabolic patterns in MTHT group on day 7 based on the model parameters and scores plots. Finally, metabolites representing potential neuroprotective monitoring parameters for hypothermia treatment were identified through H nuclear magnetic resonance metabolomics. CONCLUSION: MTHT can significantly reduce the mortality of severe TBI patients. Metabolomics research showed that this strategy could effectively improve brain metabolism, suggesting that reducing the metabolic rate to 50% to 60% should be set as the hypothermia therapy target. LEVEL OF EVIDENCE: Therapeutic study, Level I.


Assuntos
Metabolismo Basal/fisiologia , Lesões Encefálicas Traumáticas/mortalidade , Lesões Encefálicas Traumáticas/terapia , Encéfalo/metabolismo , Hipotermia Induzida/métodos , Adulto , Temperatura Corporal , Lesões Encefálicas Traumáticas/fisiopatologia , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Tomografia Computadorizada de Emissão de Fóton Único
17.
Genes Dis ; 4(1): 28-36, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30258906

RESUMO

Cancer is one of the most serious diseases that cause an enormous number of deaths all over the world. Tumor metabolism has great discrimination from that of normal tissues. Exploring the tumor metabolism may be one of the best ways to find biomarkers for cancer detection, diagnosis and to provide novel insights into internal physiological state where subtle changes may happen in metabolite concentrations. Nuclear Magnetic Resonance (NMR) technique nowadays is a popular tool to analyze cell extracts, tissues and biological fluids, etc, since it is a relatively fast and an accurate technique to supply abundant biochemical information at molecular levels for tumor research. In this review, approaches in tumor metabolism are discussed, including sample collection, data profiling and multivariate data analysis methods etc. Some typical applications of NMR are also summarized in tumor metabolism.

18.
BMC Cancer ; 16: 371, 2016 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-27356757

RESUMO

BACKGROUND: Gastric cancer is the fourth most common cancer and the second most deadly cancer worldwide. Study on molecular mechanisms of carcinogenesis will play a significant role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to identify the potential biomarkers for the early diagnosis of gastric cancer. METHODS: In this study, we reported the metabolic profiling of tissue samples on a large cohort of human gastric cancer subjects (n = 125) and normal controls (n = 54) based on (1)H nuclear magnetic resonance ((1)H NMR) together with multivariate statistical analyses (PCA, PLS-DA, OPLS-DA and ROC curve). RESULTS: The OPLS-DA model showed adequate discrimination between cancer tissues and normal controls, and meanwhile, the model excellently discriminated the stage-related of tissue samples (stage I, 30; stage II, 46; stage III, 37; stage IV, 12) and normal controls. A total of 48 endogenous distinguishing metabolites (VIP > 1 and p < 0.05) were identified, 13 of which were changed with the progression of gastric cancer. These modified metabolites revealed disturbance of glycolysis, glutaminolysis, TCA, amino acids and choline metabolism, which were correlated with the occurrence and development of human gastric cancer. The receiver operating characteristic diagnostic AUC of OPLS-DA model between cancer tissues and normal controls was 0.945. And the ROC curves among different stages cancer subjects and normal controls were gradually improved, the corresponding AUC values were 0.952, 0.994, 0.998 and 0.999, demonstrating the robust diagnostic power of this metabolic profiling approach. CONCLUSION: As far as we know, the present study firstly identified the differential metabolites in various stages of gastric cancer tissues. And the AUC values were relatively high. So these results suggest that the metabolic profiling of gastric cancer tissues has great potential in detecting this disease and helping to understand its underlying metabolic mechanisms.


Assuntos
Biomarcadores Tumorais/metabolismo , Metabolômica/métodos , Espectroscopia de Prótons por Ressonância Magnética/métodos , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Curva ROC , Neoplasias Gástricas/metabolismo
19.
Talanta ; 150: 485-92, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26838434

RESUMO

ATP, ADP and AMP are energy substances with vital biological significance. Based on the structural differences, a simple, rapid and comprehensive method has been established by (1)H and (31)P Nuclear Magnetic Resonance ((1)H-NMR and (31)P-NMR) spectroscopies. Sodium 3-(trimethylsilyl) propionate-2,2,3,3-d4 (TMSP) and anhydrous disodium hydrogen phosphate (Na2HPO4) were selected as internal standards for (1)H-NMR and (31)P-NMR, respectively. Those three compounds and corresponding internal standards can be easily distinguished both by (1)H-NMR and (31)P-NMR. In addition, they all have perfect linearity in a certain range: 0.1-100mM for (1)H-NMR and 1-75 mM for (31)P-NMR. To validate the precision of this method, mixed samples of different concentrations were measured. Recovery experiments were conducted in serum (91-113% by (1)H-NMR and 89-113% by (31)P-NMR).


Assuntos
Difosfato de Adenosina/análise , Monofosfato de Adenosina/análise , Trifosfato de Adenosina/análise , Espectroscopia de Ressonância Magnética/métodos , Soro/metabolismo , Humanos , Limite de Detecção , Controle de Qualidade , Reprodutibilidade dos Testes , Soro/química
20.
Neurotox Res ; 28(4): 290-301, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26233726

RESUMO

Sorafenib, an active multi-kinase inhibitor, has been widely used as a chemotherapy drug to treat advanced clear-cell renal cell carcinoma patients. In spite of the relative safety, sorafenib has been shown to exert a negative impact on cognitive functioning in cancer patients, specifically on learning and memory; however, the underlying mechanism remains unclear. In this study, an NMR-based metabolomics approach was applied to investigate the neurochemical effects of sorafenib in rats. Male rats were once daily administrated with 120 mg/kg sorafenib by gavage for 3, 7, and 28 days, respectively. NMR-based metabolomics coupled with histopathology examinations for hippocampus, prefrontal cortex (PFC), and striatum were performed. The (1)H NMR spectra data were analyzed by using multivariate pattern recognition techniques to show the time-dependent biochemical variations induced by sorafenib. Excellent separation was obtained and distinguishing metabolites were observed between sorafenib-treated and control rats. A total of 36 differential metabolites in hippocampus of rats treated with sorafenib were identified, some of which were significantly changed. Furthermore, these modified metabolites mainly reflected the disturbances in neurotransmitters, energy metabolism, membrane, and amino acids. However, only a few metabolites in PFC and striatum were altered by sorafenib. Additionally, no apparent histological changes in these three brain regions were observed in sorafenib-treated rats. Together, our findings demonstrate the disturbed metabonomics pathways, especially, in hippocampus, which may underlie the sorafenib-induced cognitive deficits in patients. This work also shows the advantage of NMR-based metabolomics over traditional approach on the study of biochemical effects of drugs.


Assuntos
Encéfalo/metabolismo , Metabolômica , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Aminoácidos/metabolismo , Animais , Antioxidantes/metabolismo , Membrana Celular/metabolismo , Metabolismo Energético , Imagem por Ressonância Magnética , Masculino , Niacinamida/administração & dosagem , Ratos , Ratos Sprague-Dawley , Sorafenibe
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