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1.
J Am Chem Soc ; 144(5): 2179-2188, 2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35080388

RESUMO

The application of solid-state batteries (SSBs) is challenged by the inherently poor interfacial contact between the solid-state electrolyte (SSE) and the electrodes, typically a metallic lithium anode. Building artificial intermediate nanofilms is effective in tackling this roadblock, but their implementation largely relies on vapor-based techniques such as atomic layer deposition, which are expensive, energy-intensive, and time-consuming due to the monolayer deposited per cycle. Herein, an easy and low-cost wet-chemistry fabrication process is used to engineer the anode/solid electrolyte interface in SSBs with nanoscale precision. This coordination-assisted deposition is initiated with polyacrylate acid as a functional polymer to control the surface reaction, which modulates the distribution and decomposition of metal precursors to reliably form a uniform crack-free and flexible nanofilm of a large variety of metal oxides. For demonstration, artificial Al2O3 interfacial nanofilms were deposited on a ceramic SSE, typically garnet-structured Li6.5La3Zr1.5Ta0.5O12 (LLZT), that led to a significant decrease in the Li/LLZT interfacial resistance (from 2079.5 to 8.4 Ω cm2) as well as extraordinarily long cycle life of the assembled SSBs. This strategy enables the use of a nickel-rich LiNi0.83Co0.07Mn0.1O2 cathode to deliver a reversible capacity of 201.5 mAh g-1 at a considerable loading of 4.8 mg cm-2, featuring performance metrics for an SSB that is competitive with those of traditional Li-ion systems. Our study demonstrates the potential of solution-based routes as an affordable and scalable manufacturing alternative to vapor-based deposition techniques that can accelerate the development of SSBs for practical applications.

2.
BMC Cancer ; 20(1): 968, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028275

RESUMO

BACKGROUND: Colon adenocarcinoma (COAD) patients who develop recurrence have poor prognosis. Our study aimed to establish effective prognosis prediction model based on competing endogenous RNAs (ceRNAs) for recurrence of COAD. METHODS: COAD expression profilings downloaded from The Cancer Genome Atlas (TCGA) were used as training dataset, and expression profilings of GSE29623 retrieved from Gene Expression Omnibus (GEO) were set as validation dataset. Differentially expressed RNAs (DERs) between non-recurrent and recurrent specimens in training dataset were screened, and optimum prognostic signature DERs were revealed to establish prognostic score (PS) model. Kaplan-Meier survival analysis was conducted for PS model, and GEO dataset was used for validation. Prognosis prediction efficiencies were evaluated by area under curve (AUC) and C-index. Meanwhile, ceRNA regulatory network was constructed by using signature mRNAs, lncRNAs and miRNAs. RESULTS: We identified 562 DERs including 42 lncRNAs, 36 miRNAs, and 484 mRNAs. PS prediction model, consisting of 17 optimum prognostic signature DERs, showed that high risk group had significantly poorer prognosis (5-year AUC = 0.951, C-index = 0.788), which also validated in GSE29623. Prognosis prediction model incorporating multi-RNAs with pathologic distant metastasis (M) and pathologic primary tumor (T) (5-year AUC = 0.969, C-index = 0.812) had better efficiency than clinical prognosis prediction model (5-year AUC = 0.712, C-index = 0.680). In the constructed ceRNA regulatory network, lncRNA NCBP2-AS1 could interact with hsa-miR-34c and hsa-miR-363, and lncRNA LINC00115 could interact with hsa-miR-363 and hsa-miR-4709. SIX4, GRAP, NKAIN4, MMAA, and ERVMER34-1 are regulated by hsa-miR-4709. CONCLUSION: Prognosis prediction model incorporating multi-RNAs with pathologic M and pathologic T may have great value in COAD prognosis prediction.


Assuntos
Adenocarcinoma/genética , Neoplasias do Colo/genética , RNA/genética , Adenocarcinoma/patologia , Idoso , Neoplasias do Colo/patologia , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia , Prognóstico , Projetos de Pesquisa
3.
Molecules ; 25(19)2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32992833

RESUMO

Osteoarthritis (OA) is the most common joint disease type and is accompanied by varying degrees of functional limitation. Both hyaluronic acid (HA) joint injections and pain relievers are efficient treatments for early-stage osteoarthritis. However, for the decomposition by hyaluronidase and free radicals in the knee joint, HA injection treatment has limited effect time. The cerium oxide nanoparticles (CeO2) is a long time free radical scavenger. CeO2 combined with HA expected, may extend the HA decomposition time and have a positive effect on osteoarthritis therapy. In this study, CeO2 was successfully synthesized using the hydrothermal method with a particle size of about 120 nm, which possessed excellent dispersibility in the culture medium. The in vitro OA model was established by cell treated with H2O2 for 30 min. Our study found that the inhibition of chondrocyte proliferation dose-dependently increased with H2O2 concentration but was significantly decreased by supplementation of cerium oxide nanoparticles. COL2a1 and ACAN gene expression in chondrocytes was significantly decreased after H2O2 treatment; however, the tendency was changed after cerium oxide nanoparticles treatment, which suggested that damaged chondrocytes were protected against oxidative stress. These findings suggest that cerium oxide nanoparticles are potential therapeutic applications in the early stage of OA.


Assuntos
Antioxidantes , Cério , Condrócitos/metabolismo , Ácido Hialurônico , Peróxido de Hidrogênio/efeitos adversos , Modelos Biológicos , Nanopartículas/química , Osteoartrite/tratamento farmacológico , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Bovinos , Cério/química , Cério/farmacologia , Condrócitos/patologia , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Peróxido de Hidrogênio/farmacologia , Osteoartrite/induzido quimicamente , Osteoartrite/metabolismo , Osteoartrite/patologia
4.
Nanotechnology ; 29(37): 375101, 2018 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-29920184

RESUMO

HepG2 cell death with magnetic hyperthermia (MHT) using hydroxyapatite nanoparticles (mHAPs) and alternating magnetic fields (AMF) was investigated in vitro. The mHAPs were synthesized as thermo-seeds by co-precipitation with the addition of Fe2+. The grain size of the HAPs and iron oxide magnetic were 39.1 and 19.5 nm and were calculated by the Scherrer formula. The HepG2 cells were cultured with mHAPs and exposed to an AMF for 30 min yielding maximum temperatures of 43 ± 0.5 °C. After heating, the cell viability was reduced by 50% relative to controls, lactate dehydrogenase (LDH) concentrations measured in media were three-fold greater than those measured in all control groups. Readouts of toxicity by live/dead staining were consistent with cell viability and LDH assay results. Measured reactive oxygen species (ROS) in cells exposed to MHT were two-fold greater than in control groups. Results of cDNA microarray and Western blotting revealed tantalizing evidence of ATM and GADD45 downregulation with possible MKK3/MKK6 and ATF-2 of p38 MAPK inhibition upon exposure to mHAPs and AMF combinations. These results suggest that the combination of mHAPs and AMF can increase intracellular concentrations of ROS to cause DNA damage, which leads to cell death that complement heat stress related biological effects.


Assuntos
Durapatita/química , Hipertermia Induzida , Nanopartículas de Magnetita/química , Espécies Reativas de Oxigênio/metabolismo , Morte Celular , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Campos Magnéticos , Nanopartículas de Magnetita/ultraestrutura , Regulação para Cima/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
5.
Medicine (Baltimore) ; 102(48): e36230, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38050305

RESUMO

INTRODUCTION: Acute mitral regurgitation (MR) due to papillary muscle rupture (PMR) is a rare but lethal mechanical complication of acute myocardial infarction (MI). The treatment of patients with post-MI PMR, especially those with cardiogenic shock, presents great challenges due to the high surgical risk. PATIENT CONCERNS: We report an 80-year-old woman with a history of hypertension and diabetes mellitus, presented with chest pain. Despite an early percutaneous coronary intervention and transfer to the intensive care unit, her general condition and hemodynamic parameters continued to deteriorate rapidly. DIAGNOSIS: Evidenced by electrocardiogram, echocardiogram and coronary angiography, the patient was diagnosed with acute lateral and posterior ST-segment elevation MI, cardiogenic shock, PMR, severe MR, and pulmonary edema. INTERVENTIONS: The patient received percutaneous mitral valve repair with MitraClip (Abbott Vascular, Santa Clara, CA, USA) supported by extracorporeal membranous oxygenation and intra-aortic balloon pump. OUTCOMES: The patient was discharged with relief of heart failure symptoms, reduced MR, and recovery of cardiac function, remaining in a stable condition in New York Heart Association class I after 15-month outpatient follow up. CONCLUSION: Transcatheter edge-to-edge repair with MitraClip can serve as a viable alternative to surgery in reducing MR in post-MI PMR patients at high surgical risk.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Infarto do Miocárdio , Humanos , Feminino , Idoso de 80 Anos ou mais , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/cirurgia , Choque Cardiogênico/etiologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/cirurgia , Infarto do Miocárdio/diagnóstico , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ecocardiografia , Resultado do Tratamento , Implante de Prótese de Valva Cardíaca/efeitos adversos
6.
ACS Appl Mater Interfaces ; 15(1): 1495-1504, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36579462

RESUMO

An in-depth understanding of structure-property relationships and the construction of multifunctional stimuli-responsive materials are still difficult challenges. Herein, we discovered a 4,4'-bipyridinium derivative with both photochromism and dynamic afterglow at 77 K for the first time. A one-dimensional (1D) Cd(II) coordination polymer (1) assembled by only a 4,4'-bipyridinium derivative and cadmium chloride showed photochromism, room-temperature phosphorescence (RTP), and electrochromism. Interestingly, we found that 1 underwent single-crystal-to-single-crystal transformation during the anion exchange process, and the color of the crystal changed from colorless to yellow (1-SCN-) within 10 min. Complex 1 exhibited photochromism, whereas 1-SCN- did not. The difference in the photochromic behavior between the two complexes was ascribed to the electron transfer pathway between the carboxylate groups and viologen. The DFT calculation based on the crystal structure of 1-SCN- indicated that the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were mainly located on bipyridine and cadmium atoms, eliminating the possibility of electron transfer, whereas for complex 1, electron transfer was probable from O and Cl atoms to pyridinium N atoms in viologen as demonstrated by density of states (DOS) calculations. In addition, complex 1 was successfully made into test paper for the rapid detection of I- and SCN- and displayed potential applications in inkless printing, multiple encryption, and anticounterfeiting.

7.
ACS Appl Mater Interfaces ; 14(11): 13379-13387, 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35266694

RESUMO

The development of potassium-ion batteries (PIBs) is challenged by the shortage of stable cathode materials capable of reversibly hosting the large-sized K+ (1.38 Å), which is prone to cause severe structural degradation and complex phase evolution during the potassiation/depotassiation process. Here, we identified that anionic doping of the layered oxides for PIBs is effective to combat their capacity fading at high voltage (>4.0 V). Taking P2-type K2/3Mn7/9Ni1/9Ti1/9O17/9F1/9 (KMNTOF) as an example, we showed that the partial substitution of O2- by F- enlarged the interlayer distance of the K2/3Mn7/9Ni1/9Ti1/9O2 (KMNTO), which becomes more favorable for fast K+ transition without violent structural destruction. Meanwhile, based on the experimental data and theoretical results, we identified that the introduction of F- anions effectively increased the redox-active Mn cationic concentration by lowering the average valence of the Mn element, accordingly providing more reversible capacity derived from the Mn3+/4+ redox couple, rather than oxygen redox. This anionic doping strategy enables the KMNTOF cathode to deliver a high reversible capacity of 132.5 mAh g-1 with 0.53 K+ reversible (de)intercalation in the structure. We expect that the discovery provides new insights into structural engineering for pursuing stable cathodes to facilitate the future applications of high-performance PIBs.

8.
Orthop Surg ; 13(8): 2263-2270, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34672095

RESUMO

OBJECTIVE: Publications on hidden blood loss (HBL) after posterior lumbar interbody fusion (PLIF) for lumbar spine stenosis syndrome (LSS) have been reported, but the modified HBL (mHBL) was different from HBL obtained by classical formula and there are few studies on lumbar spine hemorrhage with rheumatoid arthritis (RA). Therefore, the aim of our study is to respectively evaluate the importance of hidden blood loss (HBL) and modified HBL (mHBL) after posterior lumbar interbody fusion (PLIF) in patients diagnosed with LSS and RA, to explore the correlation between RA activity and HBL as well as mHBL. METHODS: A total of 61 patients (nine males and 52 females) diagnosed with LSS and RA who underwent PLIF were included. Data contained demographics, RA-related parameters such as duration of RA, Steinbrocker classification (used to evaluated RA activity), the disease-modifying anti-rheumatic drugs (DMARDs), osteoporosis and total knee arthroplasty; operation and hemorrhage parameters. Then HBL and mHBL were calculated by Gross formula and modified formula, respectively. Subgroup analysis on HBL and mHBL was performed based on gender, age (≤60 years and ˃60 years), different number of surgical segments (single segment, double segment, and ≥3 segments), and taking DMARDs or not. ANOVA analysis was performed on HBL and mHBL in different surgery segment number and Steinbrocker classification of RA. Independent sample t-test was used in comparison of gender and age, as well as in comparison between HBL and mHBL based on whether the patient took DMARDs or not. Furthermore, paired t-test was used to compare the volume between HBL and mHBL. RESULTS: The mean age and duration of RA was 65.2 ± 9.3 years and 14.3 ± 10.7 years, respectively. There were 13 grade I cases, 34 grade II cases, and 14 grade III cases as assessed by Steinbrocker classification and the most common anti-RA drugs were DMARDs (57.4%). The mean intraoperative bleeding, drainage, and blood loss in drainage (DBL) was 453.3 ± 377.8 mL, 489.1 ± 253.8 mL, and 304.6 ± 156.3 mL, respectively. There was no difference on HBL and mHBL in gender. HBL and mHBL was larger in patients over 60 years (P = 0.040 and P = 0.023). There were differences in intraoperative blood loss, drainage, and DBL based on different number of segments but not in HBL and mHBL, or on Steinbrocker classification. DBL was lower in DMARDs group than non-drugged group (P = 0.03), while HBL and mHBL were both of no significance. The comparison of HBL and mHBL showed statistical difference (P < 0.001), suggesting that mHBL volume is larger than HBL. CONCLUSIONS: Patients diagnosed as LSS with RA have amounts of HBL or mHBL after PLIF. HBL or mHBL is not associated with RA activity, which may not increase in RA patients compared with common ones. Taking DMARDs may reduce postoperative DBL. The fact that mHBL is larger than HBL provides an all-round basis for measuring factual HBL.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Perda Sanguínea Cirúrgica , Vértebras Lombares/cirurgia , Hemorragia Pós-Operatória , Fusão Vertebral/métodos , Estenose Espinal/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
9.
Infect Drug Resist ; 14: 4157-4166, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675560

RESUMO

Disseminated infection caused by Nocardia farcinica with primary nephrotic syndrome is exceedingly rare. A 66-year-old female visited the outpatient department due to fever and fatigue who had been diagnosed as membranous nephropathy and with a long-term prednisone and immunosuppressive therapy. After lung biopsy for many times, culture from space-occupying lesion of the right lung and species identification by mass spectrometry-based methods (MALDI-TOF) revealed Nocardia farcinica. By imaging examination, space-occupying lesions from the lungs, brain, abdominal cavity and kidney were found. After 2 weeks of meropenem intravenous and up to 6 months of trimethoprim-sulfamethoxazole (TMP-SMX) therapy, our patient has remained relapse-free at that time of writing. Disseminated infection caused by Nocardia farcinica is usually subacute with complex clinical manifestations. In addition, it can be easily confused with diseases such as tumor and mycobacterial infection, and lead to fatal consequences. Therefore, we hope that we can remind clinicians considering by discussing common features of disseminated Nocardia farcinica infection.

10.
Indian Heart J ; 72(2): 93-100, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32534695

RESUMO

OBJECTIVES: The different etiology of HF has different prognostic risk factors. Prognosis assessment of ICM and NICM has important clinical value. This study is aimed to explore the predicting factors for ICM and NICM. METHODS: 1082 HFrEF patients were retrospectively enrolled from Jan. 01, 2016 to Dec. 31, 2017. On Jan. 31, 2019, 873 patients were enrolled for analysis excluding incomplete, unfollowed, and unexplained data. The patients were divided into ischemic and non-ischemic group. The differences in clinical characteristics and long-term prognosis between the two groups were analyzed, and multivariate Cox analysis was used to predict the respective all-cause mortality, SCD and rehospitalization of CHF. RESULTS: 873 patients aged 64(53,73) were divided into two groups: ICM (403, 46.16%) and NICM. At the end, 203 died (111 in ICM, 54.68%), of whom 87 had SCD (53 in ICM, 60.92%) and 269 had rehospitalization for HF(134 in ICM, 49.81%). Independent risk factors affecting all-cause mortality in ICM: DM, previous hospitalization of HF, age, eGFR, LVEF; for SCD: PVB, eGFR, Hb, revascularization; for readmission of HF: low T3 syndrome, PVB, DM, previous hospitalization of HF, eGFR. Otherwise; factors affecting all-cause mortality in NICM: NYHA III-IV, paroxysmal AF/AFL, previous hospitalization of HF, ß-blocker; for SCD: low T3 syndrome, PVB, nitrates, sodium, ß-blocker; for rehospitalization of HF: paroxysmal AF/AFL, previous admission of HF, LVEF. CONCLUSIONS: Both all-cause mortality and SCD in ICM is higher than that in NICM. Different etiologies of CHF have different risk factors affecting the prognosis.


Assuntos
Cardiomiopatias/diagnóstico , Isquemia Miocárdica/diagnóstico , Medição de Risco/métodos , Idoso , Cardiomiopatias/epidemiologia , China/epidemiologia , Progressão da Doença , Eletrocardiografia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Tomografia Computadorizada por Raios X
11.
Cytotechnology ; 71(6): 1095-1108, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31598888

RESUMO

Seleno-short-chain chitosan (SSCC) is a derivative of chitosan. In the present study, we sought to investigate the underlying antitumor mechanism of SSCC on human gastric cancer BGC-823 cells in vitro. MTT assay suggested that SSCC exhibited a dose-dependent inhibitory effect on the proliferation of BGC-823 cells. We found the SSCC-treated cells showed typical morphological characteristics of apoptosis in a dose dependent manner by observing on microscope. Annexin V-FITC/PI double staining and cell cycle assay identified that SSCC could induce BGC-823 cells apoptosis by triggering G2/M phase arrest. Our research provided the first evidence that SSCC could effectively induce the apoptosis of BGC-823 cells via an intrinsic mitochondrial pathway, as indicated by inducing the disruption of mitochondrial membrane potential (MMP), the excessive accumulation of reactive oxidative species (ROS), the increase of Bax/Bcl-2 ratio and the activation of caspase 3, caspase 9 and cytochrome C (Cyt-C) in BGC-823 cells. These combined results clearly indicated that SSCC could induce BGC-823 cells apoptosis by the involvement of mitochondrial signaling pathway, which provided precise experimental evidence for SSCC as a potential agent in the prevention and treatment of human gastric cancer.

12.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 36(3): 301-307, 2018 Jun 01.
Artigo em Zh | MEDLINE | ID: mdl-29984933

RESUMO

OBJECTIVE: This systematic review and Meta-analysis aimed to compare the efficacy of calcium sodium phos-phosilicate (CSPS) and potassium nitrate as desensitizing agents for the treatment of dentin hypersensitivity (DH). METHODS: A thorough search in The Cochrane Library, PubMed, Embase, Chinese WanFang Data, CBM, and CNKI were conducted for studies published up to June 2017. Randomized controlled trials (RCTs) of the treatment of DH with CSPS and potassium nitrate toothpaste were included. Quality assessment and data extraction were performed by two reviewers independently, and Meta-analysis was performed by using RevMan 5.3 software. RESULTS: Eight RCTs involving 411 patients were included. Experimental group comprised 203 and control group had 208 patients. The Meta-analysis indicated the superior effect of CSPS dentifrice on air blast sensitivity at 2, 4, 6, and 8 weeks of follow-up [SMD=-1.85, 95%CI (-2.89, 
-0.81), P=0.000 5, I²=93%], [SMD=-1.61, 95%CI (-1.96, -1.26), P<0.000 01, I²=49%], [SMD=-3.79, 95%CI (-7.18, -0.40), P=0.03, I²=98%], and [SMD=-2.13, 95%CI (-2.69, -1.58), P<0.000 01] , respectively. No significant effects were seen at 12 weeks [SMD=-0.63, 95%CI (-1.47, 0.20), P=0.14, I²=71%]. CSPS dentifrice showed a better desensitizing effect at 2, 4, 6, 8, and 12 weeks of follow-up on cold water sensitivity [SMD=-1.07, 95%CI (-1.48, -0.66), P<0.000 01, I²=69%], [SMD=
-1.29, 95%CI (-1.81, -0.76), P<0.000 01, I²=64%], [SMD=-1.20, 95%CI (-1.57, -0.83), P<0.000 01, I²=86%], [SMD=-1.30, 95%CI (-2.51, -0.08), P=0.04, I²=82%], and [SMD=-0.79, 95%CI (-1.27, -0.31), P=0.001], respectively. No significant effects at 1 week of follow-up [SMD=0.00, 95%CI (-0.62, 0.62), P=1]. The favorable effect of CSPS dentifrice on tactile sensitivity was more obvious than the control group at 2, 4, and 8 weeks of follow-up [SMD=-1.31, 95%CI (-2.00, -0.62), P=0.000 2, I²=67%], [SMD=-1.37, 95%CI (-1.74, -0.99), P<0.000 01, I²=23%], and [SMD=-1.33, 95%CI (-1.82,-0.84), P<0.000 01], respectively. No significant effects at 1 week of follow-up [SMD=-0.32, 95%CI (-0.94, 0.31), P=0.32] were observed. CONCLUSIONS: Current evidence indicated that CSPS was more effective than potassium nitrate at reducing DH. The evidence generated by this review was based on a small number of individuals. High-quality and large sample size as well as ideally-designed clinical trials are required in the future before definitive recommendations can be made.


Assuntos
Dessensibilizantes Dentinários , Sensibilidade da Dentina , Nitratos , Compostos de Potássio , Cremes Dentais , Cálcio , Dessensibilizantes Dentinários/uso terapêutico , Vidro , Humanos , Nitratos/uso terapêutico , Compostos de Potássio/uso terapêutico , Sódio
13.
J Am Coll Cardiol ; 68(12): 1281-93, 2016 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-27634119

RESUMO

BACKGROUND: Pathogenesis and diagnostic biomarkers for diseases can be discovered by metabolomic profiling of human fluids. If the various types of coronary artery disease (CAD) can be accurately characterized by metabolomics, effective treatment may be targeted without using unnecessary therapies and resources. OBJECTIVES: The authors studied disturbed metabolic pathways to assess the diagnostic value of metabolomics-based biomarkers in different types of CAD. METHODS: A cohort of 2,324 patients from 4 independent centers was studied. Patients underwent coronary angiography for suspected CAD. Groups were divided as follows: normal coronary artery (NCA), nonobstructive coronary atherosclerosis (NOCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). Plasma metabolomic profiles were determined by liquid chromatography-quadrupole time-of-flight mass spectrometry and were analyzed by multivariate statistics. RESULTS: We made 12 cross-comparisons to and within CAD to characterize metabolic disturbances. We focused on comparisons of NOCA versus NCA, SA versus NOCA, UA versus SA, and AMI versus UA. Other comparisons were made, including SA versus NCA, UA versus NCA, AMI versus NCA, UA versus NOCA, AMI versus NOCA, AMI versus SA, significant CAD (SA/UA/AMI) versus nonsignificant CAD (NCA/NOCA), and acute coronary syndrome (UA/AMI) versus SA. A total of 89 differential metabolites were identified. The altered metabolic pathways included reduced phospholipid catabolism, increased amino acid metabolism, increased short-chain acylcarnitines, decrease in tricarboxylic acid cycle, and less biosynthesis of primary bile acid. For differential diagnosis, 12 panels of specific metabolomics-based biomarkers provided areas under the curve of 0.938 to 0.996 in the discovery phase (n = 1,086), predictive values of 89.2% to 96.0% in the test phase (n = 933), and 85.3% to 96.4% in the 3-center external sets (n = 305). CONCLUSIONS: Plasma metabolomics are powerful for characterizing metabolic disturbances. Differences in small-molecule metabolites may reflect underlying CAD and serve as biomarkers for CAD progression.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/metabolismo , Metabolômica , Idoso , Doença da Artéria Coronariana/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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