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1.
IEEE Trans Automat Contr ; 67(4): 2027-2032, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35480236

RESUMEN

This paper considers identification of sparse Volterra systems. A method based on the almost orthogonal matching pursuit (AOMP) is proposed. The AOMP algorithm allows one to estimate one non-zero coefficient at a time until all non-zero coefficients are found without losing the optimality and the sparsity, thus avoiding the curse of dimensionality often encountered in Volterra system identification.

2.
Automatica (Oxf) ; 1372022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35095107

RESUMEN

This paper investigates the uniqueness of parameters via persistence of excitation for switched linear systems. The main contribution is a much weaker sufficient condition on the regressors to be persistently exciting that guarantees the uniqueness of the parameter sets and also provides new insights in understanding the relation among different subsystems. It is found that for uniquely determining the parameters of switched linear systems, the needed minimum number of samples derived from our sufficient condition is much smaller than that reported in the literature.

3.
Int J Mol Sci ; 23(18)2022 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-36142796

RESUMEN

Amyloid aggregation is associated with many neurodegenerative diseases such as Alzheimer's disease (AD). The current technologies using phototherapy for amyloid inhibition are usually photodynamic approaches based on evidence that reactive oxygen species can inhibit Aß aggregation. Herein, we report a novel combinational photothermally assisted photo-oxygenation treatment based on a nano-platform of the brain-targeting peptide RVG conjugated with the 2D porphyrinic PCN-222 metal-organic framework and indocyanine green (PCN-222@ICG@RVG) with enhanced photo-inhibition in Alzheimer's Aß aggregation. A photothermally assisted photo-oxygenation treatment based on PCN@ICG could largely enhance the photo-inhibition effect on Aß42 aggregation and lead to much lower neurotoxicity upon near-infrared (NIR) irradiation at 808 nm compared with a single modality of photo-treatment in both cell-free and in vitro experiments. Generally, local photothermal heat increases the instability of Aß aggregates and keeps Aß in the status of monomers, which facilitates the photo-oxygenation process of generating oxidized Aß monomers with low aggregation capability. In addition, combined with the brain-targeting peptide RVG, the PCN-222@ICG@RVG nanoprobe shows high permeability of the human blood-brain barrier (BBB) on a human brain-on-a-chip platform. The ex vivo study also demonstrates that NIR-activated PCN-222@ICG@RVG could efficiently dissemble Aß plaques. Our work suggests that the combination of photothermal treatment with photo-oxygenation can synergistically enhance the inhibition of Aß aggregation, which may boost NIR-based combinational phototherapy of AD in the future.


Asunto(s)
Enfermedad de Alzheimer , Estructuras Metalorgánicas , Humanos , Enfermedad de Alzheimer/terapia , Amiloide , Péptidos beta-Amiloides , Verde de Indocianina , Rayos Infrarrojos , Especies Reactivas de Oxígeno
4.
Analyst ; 145(3): 797-804, 2020 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-31894762

RESUMEN

Detecting trace amounts of copper ions (Cu2+) is of high importance since copper is an essential element in the environment and the human body. Despite the recent advances in Cu2+ detection, the current approaches still suffer from insensitivity and lack of in situ detection in living cells. In the present work, a fluorescent nanosensor based on porphyrinic metal-organic framework nanoparticles (MOF-525 NPs) is proposed for sensitive and selective monitoring of Cu2+ in aqueous solution and living cells. The MOF-525 NPs with attractive properties, including ultrasmall size, good water dispersity and intense red fluorescence, are prepared via a facile and environment-friendly hydrothermal route. The fluorescence signal of MOF-525 NPs could be quenched statically by Cu2+ with high selectivity due to the strong affinity of Cu2+ to the porphyrin ligand in MOF-525. The proposed fluorescent nanosensor has a linear response in the range of 1.0-250 nM with a low detection limit of 220 pM. Furthermore, it is successfully employed for the detection of Cu2+ in water samples and the intracellular imaging of Cu2+ in living cells, demonstrating its great potential in the sensing and biological fields.


Asunto(s)
Cobre/análisis , Estructuras Metalorgánicas/química , Microscopía Fluorescente , Nanopartículas/química , Espectrometría de Fluorescencia , Supervivencia Celular/efectos de los fármacos , Colorantes Fluorescentes/química , Células HeLa , Humanos , Iones/química , Límite de Detección , Nanopartículas/toxicidad , Agua/química
5.
Am J Med Genet B Neuropsychiatr Genet ; 177(8): 709-716, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30350918

RESUMEN

No biologically based diagnostic criteria are in clinical use today for obsessive-compulsive disorder (OCD), schizophrenia, and major depressive disorder (MDD), which are defined with reference to Diagnostic and Statistical Manual clinical symptoms alone. However, these disorders cannot always be well distinguished on clinical grounds and may also be comorbid. A biological blood-based dynamic genomic signature that can differentiate among OCD, MDD, and schizophrenia would therefore be of great utility. This study enrolled 77 patients with OCD, 67 controls with no psychiatric illness, 39 patients with MDD, and 40 with schizophrenia. An OCD-specific gene signature was identified using blood gene expression analysis to construct a predictive model of OCD that can differentiate this disorder from healthy controls, MDD, and schizophrenia using a logistic regression algorithm. To verify that the genes selected were not derived as a result of chance, the algorithm was tested twice. First, the algorithm was used to predict the cohort with true disease/control status and second, the algorithm predicted the cohort with disease/control status randomly reassigned (null set). A six-gene panel (COPS7A, FKBP1A, FIBP, TP73-AS1, SDF4, and GOLGA8A) discriminated patients with OCD from healthy controls, MDD, and schizophrenia in the training set (with an area under the receiver-operating-characteristic curve of 0.938; accuracy, 86%; sensitivity, 88%; and specificity, 85%). Our findings indicate that a blood transcriptomic signature can distinguish OCD from healthy controls, MDD, and schizophrenia. This finding further confirms the feasibility of using dynamic blood-based genomic signatures in psychiatric disorders and may provide a useful tool for clinical staff engaged in OCD diagnosis and decision making.


Asunto(s)
Trastorno Obsesivo Compulsivo/sangre , Trastorno Obsesivo Compulsivo/genética , Adulto , Complejo del Señalosoma COP9/genética , Proteínas de Unión al Calcio/genética , Proteínas Portadoras/genética , Estudios de Cohortes , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Glicoproteínas/genética , Humanos , Masculino , Proteínas de la Membrana/genética , Trastorno Obsesivo Compulsivo/diagnóstico , Sensibilidad y Especificidad , Proteínas de Unión a Tacrolimus/genética , Factores de Transcripción/genética , Transcriptoma , Proteínas Supresoras de Tumor/genética
6.
Electrophoresis ; 37(20): 2657-2662, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27346878

RESUMEN

In this study, in-column fiber-optic (ICFO) laser-induced fluorescence (LIF) detection technique is coupled with capillary electrophoresis (CE) for the rapid separation of neodymium for the first time. The effects of buffer concentration, buffer pH, and separation voltage on the CE behaviors, including electrophoretic efficiency and detection sensitivity, are investigated in detail. Under the optimal condition determined in this study (15 mM borate buffer, pH 10.50, separation voltage 24 kV), neodymium could be separated effectively from the neighboring lanthanides (praseodymium and samarium) within several minutes, and the limit of detection for neodymium is estimated to be at the ppt level. The ICFO-LIF-CE system assembled in this study exhibits unique performance characteristics such as low cost and flexibility. Meanwhile, the separation efficiency and detection sensitivity of the assembled CE system are comparable to or somewhat better than those obtained in the previous traditional CE systems, indicating the potential of the assembled CE system for practical applications in the fields of spent nuclear fuel analysis, nuclear waste disposal/treatment, and nuclear forensics.


Asunto(s)
Electroforesis Capilar/métodos , Tecnología de Fibra Óptica/métodos , Neodimio/aislamiento & purificación , Límite de Detección , Neodimio/análisis , Neodimio/química , Reproducibilidad de los Resultados
7.
Chem Commun (Camb) ; 60(12): 1619-1622, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38230677

RESUMEN

In this study, we intricately designed and synthesized two isoreticular two-dimensional covalent organic framework nanosheets, namely TAPA-COF-1 and TAPA-COF-2, distinguished by their unique spatial arrangement of hydroxyl groups. These precisely engineered nanosheets were employed as a tailored platform for the selective capture of uranium, due to their tunable chelating sites and characteristic sheet-like morphology. Notably, TAPA-COF-1, featuring ortho-hydroxyl groups, demonstrated a significantly enhanced adsorption capacity for uranium capture originating from the additional oriented adjacent phenolic hydroxyl chelating sites in comparison to TAPA-COF-2 with para-hydroxyl groups, which was proved by theoretical calculation. The impressive features of TAPA-COF-1, including its notable selectivity, rapid adsorption kinetics, and high uptake capacity (657.2 mg g-1), endow it as a highly promising candidate for uranium capture.

8.
Anal Chem ; 85(5): 2601-5, 2013 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-23373468

RESUMEN

In this paper, the anodic electrogenerated chemiluminescence (ECL) behavior of graphite-like carbon nitride (g-C3N4) is studied using cyclic voltammetry with triethanolamine (TEA) as a coreactant. The possible anodic ECL response mechanism of the g-C3N4/TEA system is proposed. Furthermore, it is observed that the anodic ECL signal can be quenched efficiently in the presence of rutin, on the basis of which a facile anodic ECL senor for the determination of rutin is developed. This ECL sensor is found to have a linear response in the range of 0.20-45.0 µM and a low detection limit of 0.14 µM (at signal-to-noise of 3). These results suggest that semiconductor g-C3N4 has great potential in extending the application in the ECL field as an efficient luminophore.


Asunto(s)
Técnicas de Química Analítica/instrumentación , Grafito/química , Mediciones Luminiscentes , Nitrilos/química , Rutina/análisis , Rutina/química , Electroquímica , Electrodos , Transferencia de Energía
9.
Anal Biochem ; 434(1): 34-8, 2013 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-23142428

RESUMEN

The detection of rare mutations is particularly essential in many areas of biomedical research. Here, we report an ultrasensitive method to detect extremely rare point mutations based on electrochemiluminescent assay. The point mutation among large excess wild-type alleles is exclusively amplified through ligase detection reaction. The products corresponding to the amplification of mutant alleles are selectively captured by magnetic beads and then labeled with electrochemiluminescent substrates. Thus, point mutations with a percentage as small as 0.01% in the DNA population can be detected by electrochemiluminescent assay. Moreover, because the electrochemiluminescent signal of the mutation is proportional to the percentage of mutant alleles in the DNA population, the percentage of mutant alleles can be roughly accessed.


Asunto(s)
ADN/análisis , Técnicas Electroquímicas/métodos , Ligasas/metabolismo , Mediciones Luminiscentes/métodos , 2,2'-Dipiridil/análogos & derivados , 2,2'-Dipiridil/química , Alelos , Línea Celular Tumoral , ADN/aislamiento & purificación , Células Hep G2 , Humanos , Separación Inmunomagnética , Compuestos Organometálicos/química , Polimorfismo de Nucleótido Simple
10.
Analyst ; 138(7): 2073-9, 2013 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-23435198

RESUMEN

In this research, quantities of carbon nanospheres (CNSs) were prepared with a convenient and low cost method at atmospheric pressure and functionalized with the xanthate group in a simple way. The materials were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), Fourier transform infrared spectra (FT-IR), and X-ray photoelectron spectroscopy (XPS). In addition, the carbon nanospheres (CNSs) xanthate was applied to fabricate a modified carbon paste electrode (CPE) for the selective and sensitive determination of Cu(2+). Also, the xanthate with a -CS2 group was applied as a chelating agent to enrich Cu(2+) in the determination of Cu(2+) ions. In square wave stripping voltammetry (SWSV), the carbon nanospheres xanthate-modified CPE displayed linear response to Cu(2+) in the concentration range of 8.0 × 10(-8) M to 2.2 × 10(-6) M with a detection limit (S/N = 3) of 3.55 × 10(-8) M. The modified electrode exhibited excellent analytical performance in terms of high repeatability. Finally, it was applied to detect Cu(2+) in the wastewater samples with high accuracy and good recovery, indicating its promising application in the routine analysis of metal ions.

11.
Anal Chem ; 84(11): 4754-9, 2012 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-22583002

RESUMEN

This paper reports for the first time the electrogenerated chemiluminescence (ECL) behavior of graphite-like carbon nitride (g-C(3)N(4)) with K(2)S(2)O(8) as the coreactant. The possible ECL reaction mechanisms are proposed. The spectral features of the ECL emission and photoluminescence (PL) of g-C(3)N(4) are compared, and their resemblance demonstrates that the excited states of g-C(3)N(4) from both ECL and photoexcitation are the same. The effects of K(2)S(2)O(8) concentration, pH, g-C(3)N(4)/carbon powder ratio, and scan rate on the ECL intensity have been studied in detail. Furthermore, it is observed that the ECL intensity is efficiently quenched by trace amounts of Cu(2+). g-C(3)N(4) is thus employed to fabricate an ECL sensor which shows high selectivity to Cu(2+) determination. The limit of detection is determined as 0.9 nM. It is anticipated that g-C(3)N(4) could be a new class of promising material for fabricating ECL sensors.

12.
Chemphyschem ; 13(1): 336-41, 2012 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-22095763

RESUMEN

Magnetic iron oxide particles are widely used as contrast agents to improve the sensitivity of magnetic resonance imaging (MRI). Their efficiency in MRI is usually quantified by transverse relaxivity (r(2)) in solution. Herein, we synthesized a series of magnetite nanocrystal clusters (MNCs) with ultra-high transverse relaxivity by a polyol process and studied the relationship between r(2) and size of the MNCs. The sizes of MNCs can be tuned over a wide range from 13 to 179 nm. The r(2) of MNC suspensions as a function of the size of the cluster was analyzed and compared with a theoretical model. We found that MNCs of 64 nm had an r(2) value of 650 mM(-1) s(-1), which was more than three times that of the commercial contrast agent and was among the highest reported for iron oxide materials. Compared with the theoretical model, the r(2) value of the MNC suspension is approximately 0.93 of the theoretical prediction. Imaging of the MNC suspensions was performed in a clinical 1.5 T MRI instrument and a comparison was made between MNCs and commercial contrast agents. MRI indicated that the decrease of signal intensity induced by MNCs was in proportion to the r(2) value, which was in accordance with theoretical predictions. These results demonstrate that MNCs with ultra-high transverse relaxivity and tunable size are promising candidates for molecular imaging and clinical diagnosis in MRI.


Asunto(s)
Imagen por Resonancia Magnética , Nanopartículas de Magnetita/química , Compuestos Férricos/química , Modelos Teóricos , Polímeros/química
13.
J Huazhong Univ Sci Technolog Med Sci ; 32(4): 534-539, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22886966

RESUMEN

The changes of plasma myostatin levels in patients with type 2 diabetes mellitus (T2D) and their clinical correlation were investigated. We recruited 43 T2D patients and 20 age-matched healthy subjects. Plasma myostatin, lipid and glucose, and serum insulin were determined. T2D patients showed significantly higher fasting plasma glucose (FPG), serum insulin and triglyceride levels, and lower high-density lipoprotein levels than normal control subjects (P<0.01). Mean plasma myostatin level in T2D patients and health controls was (66.5±17.8) and (46.2±13.8) ng/mL, respectively. An unpaired t test showed that the increase of myostatin in the T2D patients was significant (P<0.001). In both healthy control and T2D groups, the female subjects showed higher myostatin levels than the male subjects. In the T2D patients, plasma level of myostatin was negatively correlated with body mass index (BMI, r=-0.42, P<0.01) and FPG (r=-0.51, P[Symbol: see text]0.01), but positively correlated with insulin resistance index (HOMA-IR, r=0.48, P<0.01). Up-regulation of plasma myostatin in the T2D patients and its correlation with BMI, FPG and blood insulin sensitivity suggests that plasma myostatin may be implicated in the pathogenesis of T2D and thus presented as a therapeutic target for treating the disease. Furthermore, circulating myostatin levels may be used as a biomarker for the disease.


Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Miostatina/sangre , Glucemia , Femenino , Humanos , Insulina/sangre , Lípidos/sangre , Masculino , Persona de Mediana Edad
14.
Artículo en Inglés | MEDLINE | ID: mdl-36497551

RESUMEN

Agriculture has the dual effect of contributing to both carbon emissions and sequestration, and thus plays a critical role in mitigating global climate change and achieving carbon neutrality. Agricultural eco-efficiency (AEE) is an important measurement through which we can assess the efforts toward reduced emissions and increased sequestration. The purpose of this study was to understand the relationship between China's target of carbon neutrality and AEE through an evaluative model, so as to improve AEE and ultimately achieve sustainable agricultural development. The Super-SBM model scientifically measures the AEE based on provincial panel data collected between 2000 and 2020. We selected kernel density function and spatial distribution to explore the spatial and temporal evolutionary trends, and used a Tobit model to identify the drivers of AEE. The research shows that (1) China's agricultural system functions as a net carbon sink, with all provinces' agricultural carbon sequestration levels recorded as higher than their carbon emissions from 2000 to 2020. (2) Despite sequestration levels, the level of AEE in China is not high enough, and the average efficiency level from 2000 to 2020 is 0.7726, showing an overall trend where AEE decreased at first and then increased. (3) The AEE of each province is clearly polarized; there are obvious core-periphery characteristics and spatial distribution of clustered contiguous areas. Central provinces generally have lower efficiency, eastern and northeastern provinces have higher efficiency, and northeastern provinces always remain in the high-efficiency group. (4) Influencing factors show that urbanization, upgrading of industrial structure, financial support for agriculture, and mechanization have a significant positive impact on AEE. These findings have important implications for the promotion of the low-carbon green development of Chinese agriculture.


Asunto(s)
Agricultura , Carbono , Carbono/análisis , Urbanización , Eficiencia , Industrias , China , Desarrollo Económico
15.
Front Pharmacol ; 12: 639382, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34168557

RESUMEN

Tripterygii Radix exhibits good clinical efficacy and safety in rheumatoid arthritis (RA) patients, but its effective components and mechanism of action are still unclear. The purpose of this study was to explore and verify the major ingredients and molecular targets of Tripterygii Radix in RA using drug-compounds-biotargets-diseases network and protein-protein interaction (PPI) network analyses. The processes and pathways were derived from Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The most important compounds and biotargets were determined based on the degree values. RA fibroblast-like synoviocytes (RA-FLS) were separated from RA patients and identified by hematoxylin and eosin (HE) staining and immunohistochemistry. The purity of RA-FLS was acquired by flow cytometry marked with CD90 or VCAM-1. RA-FLS were subjected to control, dimethyl sulfoxide (control), kaempferol, or lenalidomide treatment. Cell migration was evaluated by the transwell assay. The relative expression of biotarget proteins and cytokines was analyzed by western blotting and flow cytometry. In total, 144 chemical components were identified from Tripterygii Radix; kaempferol was the most active ingredient among 33 other components. Fourteen proteins were found to be affected in RA from 285 common biotargets. The tumor necrosis factor (TNF) signaling pathway was predicted to be one of the most latent treatment pathways. Migration of RA-FLS was inhibited and the expression of protein kinase B (AKT1), JUN, caspase 3 (CASP3), TNF receptor 1 and 2 (TNFR1 and TNFR2), interleukin-6 (IL-6), and TNF-α was significantly affected by kaempferol. Thus, this study confirmed kaempferol as the effective component of Tripterygii Radix against RA-FLS and TNF signaling pathway and its involvement in the regulation of AKT1, JUN, CASP3, TNFR1, TNFR2, IL-6, and TNF-α expression.

16.
Oncol Lett ; 22(1): 543, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34079596

RESUMEN

The immune system is crucial in regulating colorectal cancer (CRC) tumorigenesis. Identification of immune-related transcriptomic signatures derived from the peripheral blood of patients with CRC would provide insights into CRC pathogenesis, and suggest novel clues to potential immunotherapy strategies for the disease. The present study collected blood samples from 59 patients with CRC and 62 healthy control patients and performed whole blood gene expression profiling using microarray hybridization. Immune-related gene expression signatures for CRC were identified from immune gene datasets, and an algorithmic predictive model was constructed for distinguishing CRC from controls. Model performance was characterized using an area under the receiver operating characteristic curve (ROC AUC). Functional categories for CRC-specific gene expression signatures were determined using gene set enrichment analyses. A Kaplan-Meier plotter survival analysis was also performed for CRC-specific immune genes in order to characterize the association between gene expression and CRC prognosis. The present study identified five CRC-specific immune genes [protein phosphatase 3 regulatory subunit Bα (PPP3R1), amyloid ß precursor protein, cathepsin H, proteasome activator subunit 4 and DEAD-Box Helicase 3 X-Linked]. A predictive model based on this five-gene panel showed good discriminatory power (independent test set sensitivity, 83.3%; specificity, 94.7%, accuracy, 89.2%; ROC AUC, 0.96). The candidate genes were involved in pathways associated with 'adaptive immune responses', 'innate immune responses' and 'cytokine signaling'. The survival analysis found that a high level of PPP3R1 expression was associated with a poor CRC prognosis. The present study identified five CRC-specific immune genes that were potential diagnostic biomarkers for CRC. The biological function analysis indicated a close association between CRC pathogenesis and the immune system, and may reveal more information about the immunogenic and pathogenic mechanisms driving CRC in the future. Overall, the association between PPP3R1 expression and survival of patients with CRC revealed potential new targets for CRC immunotherapy.

17.
ACS Appl Mater Interfaces ; 12(23): 26391-26398, 2020 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-32395978

RESUMEN

Herein, a dual-modal fluorescent/colorimetric "Signal-On" nanoprobe based on PCN-222 nanorods (NRs) toward phosphate was proposed for the first time. Due to the high affinity of the zirconium node in PCN-222 NRs for phosphate, the structure collapse of PCN-222 NRs was triggered by phosphate, resulting in the release of the tetrakis(4-carboxyphenyl)porphyrin (TCPP) ligand from PCN-222 NRs as well as the enhancement of fluorescence and absorbance signals. The PCN-222 NR-based nanoprobe could be employed for phosphate detection over a wide concentration range with a detection limit down to 23 nM. The practical application of the PCN-222 NR-based nanoprobe in real samples was evaluated. Moreover, benefitting from the good biocompatibility and water dispersibility of PCN-222 NRs, this nanoprobe was successfully employed in the intracellular imaging of phosphate, revealing its promising application in the biological science. The present work would greatly extend the potential of nanostructured MOFs in the sensing and biological fields.


Asunto(s)
Colorantes Fluorescentes/química , Estructuras Metalorgánicas/química , Nanotubos/química , Fosfatos/análisis , Porfirinas/química , Colorimetría/métodos , Colorantes Fluorescentes/toxicidad , Células HeLa , Humanos , Límite de Detección , Estructuras Metalorgánicas/toxicidad , Microscopía Confocal , Microscopía Fluorescente , Nanotubos/toxicidad , Fosfatos/química , Porfirinas/toxicidad , Circonio/química , Circonio/toxicidad
18.
PLoS One ; 15(6): e0233713, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32497068

RESUMEN

BACKGROUND: Peripheral blood transcriptome profiling is a potentially important tool for disease detection. We utilize this technique in a case-control study to identify candidate transcriptomic biomarkers able to differentiate women with breast lesions from normal controls. METHODS: Whole blood samples were collected from 50 women with high-risk breast lesions, 57 with breast cancers and 44 controls (151 samples). Blood gene expression profiling was carried out using microarray hybridization. We identified blood gene expression signatures using AdaBoost, and constructed a predictive model differentiating breast lesions from controls. Model performance was then characterized by AUC sensitivity, specificity and accuracy. Biomarker biological processes and functions were analyzed for clues to the pathogenesis of breast lesions. RESULTS: Ten gene biomarkers were identified (YWHAQ, BCLAF1, WSB1, PBX2, DDIT4, LUC7L3, FKBP1A, APP, HERC2P2, FAM126B). A ten-gene panel predictive model showed discriminatory power in the test set (sensitivity: 100%, specificity: 84.2%, accuracy: 93.5%, AUC: 0.99). These biomarkers were involved in apoptosis, TGF-beta signaling, adaptive immune system regulation, gene transcription and post-transcriptional protein modification. CONCLUSION: A promising method for the detection of breast lesions is reported. This study also sheds light on breast cancer/immune system interactions, providing clues to new targets for breast cancer immune therapy.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Detección Precoz del Cáncer/métodos , Modelos Genéticos , Transcriptoma , Adulto , Anciano , Área Bajo la Curva , Biomarcadores de Tumor/genética , Neoplasias de la Mama/sangre , Estudios de Casos y Controles , Exactitud de los Datos , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto Joven
19.
Oncol Lett ; 20(3): 2280-2290, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32765790

RESUMEN

It is crucial to classify cervical lesions into high-grade squamous intraepithelial lesions (HSILs) and low-grade SILs (LSILs), as LSILs are conservatively treated by observation, based on an expectation of natural regression, whereas HSILs usually require electrosurgical excision. In the present study, peripheral blood gene expression profiles were analyzed to identify transcriptomic biomarkers distinguishing HSILs from LSILs. A total of 102 blood samples were collected from women with cervical SILs (66 HSIL and 36 LSIL) for microarray hybridization. Candidate gene signatures were identified using AdaBoost algorithms, and a predictive model was constructed using logistic regression to differentiate HSILs from LSILs. To correct for possible bias as a result of the limited sample size and to verify the stability of the predictive model, a two-fold cross validation and null set analysis was conducted over 1,000 iterations. The functions of the transcriptomic biomarkers were then analyzed to elucidate the pathogenesis of cervical SIL. A total of 10 transcriptomic genes (STMN3, TRPC4AP, DYRK2, AGK, KIAA0319L, GRPEL1, ZFC3H1, LYL1, ITGB1 and ARHGAP18) were identified. The predictive model based on the 10-gene panel exhibited well-discriminated power. A cross validation process using known disease status exhibited almost the same performance as that of the predictive model, whereas null-set analysis with randomly reassigned disease status exhibited much lower predictive performance for distinguishing HSILs from LSILs. These biomarkers were involved in the 'Rho GTPase cycle', 'mitochondrial protein import', 'oncogenic MAPK signaling', 'integrin cell surface interaction' and 'signaling by BRAF and RAF fusions'. In conclusion, peripheral blood gene expression analysis is a promising method for distinguishing HSILs from LSILs. The present study proposes 10 candidate genes that could be used in the future as diagnostic biomarkers and potential therapeutic targets for cervical SILs. A simple, non-invasive blood test would be clinically useful in the diagnosis and classification of patients with cervical SILs.

20.
Nanotechnology ; 20(40): 405102, 2009 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-19752494

RESUMEN

Silica coated, PEI and citric acid hybrid superparamagnetic magnetite nanocrystal clusters (SMNC) were synthesized using either a mini-emulsion/sol-gel method or a polyol technique. After careful characterization of the size, structure, composition, and magnetic properties, the as-synthesized SMNC were used for cell labeling while the MR detection sensitivity of cells labeled with silica SMNC was performed with a 3 T whole body MR scanner. TEM investigations revealed that the sizes of the SMNC were about 200 nm and the SMNC mainly consisted of magnetite nanoparticles imbedded in a PEI, citric acid or polystyrene scaffold. Silica and citric acid SMNC were highly negatively charged and PEI SMNC were positively charged. Relaxometry measurements revealed that these SMNC possessed a very high MR sensitivity (silica SMNC: r(2) = 299 s(-1) mM(-1), PEI SMNC: r(2) = 124 s(-1) mM(-1)), especially for the citric acid SMNC (r(2) = 360 s(-1) mM(-1)). Furthermore, when used for cell (RAW264.7 cells) labeling, the SMNC had no adverse effect on cell viability, and the cell uptake of the SMNC show a dose- and time-dependent feature. MR imaging of cells labeled with silica SMNC indicated that cells with a concentration as low as 10 x 10(3) cells ml(-1) could be detected with a 3 T MRI scanner. Our study demonstrated that superparamagnetic magnetite nanocrystal clusters are a sensitive tool for cell imaging.


Asunto(s)
Imagen por Resonancia Magnética/instrumentación , Imagen por Resonancia Magnética/métodos , Magnetismo , Nanopartículas/química , Animales , Línea Celular , Ácido Cítrico/química , Ratones , Microscopía Electrónica de Transmisión , Nanopartículas/ultraestructura , Polietileneimina/química , Dióxido de Silicio/química , Espectroscopía Infrarroja por Transformada de Fourier
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