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1.
Anal Chem ; 96(2): 787-793, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38170819

RESUMO

In the clinic, small-molecule metabolites (SMMs) in blood are highly convincing indicators for disease diagnosis, such as cancer. However, challenges still exist for detection of SMMs due to their low concentration and complicated components in blood. In this work, we report the design of a novel "selenium signature" nanoprobe (Se nanoprobe) for efficient identification of multiple aldehyde metabolites in blood. This Se nanoprobe consists of magnetic nanoparticles that can enrich aldehyde metabolites from a complex environment, functionalized with photosensitive "selenium signature" hydrazide molecules that can react with aldehyde metabolites. Upon irradiation with UV, the aldehyde derivatives can be released from the Se nanoprobe and further sprayed by mass spectrometry through ambient ionization (AIMS). By quantifying the selenium isotope distribution (MS/MS) from the derivatization product, accurate detection of several aldehyde metabolites, including valeraldehyde (Val), heptaldehyde (Hep), 2-furaldehyde (2-Fur), 10-undecenal aldehyde (10-Und), and benzaldehyde (Ben), is realized. This strategy reveals a new solution for quick and accurate cancer diagnosis in the clinic.


Assuntos
Neoplasias , Selênio , Humanos , Espectrometria de Massas em Tandem/métodos , Aldeídos
2.
Proc Natl Acad Sci U S A ; 118(23)2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34074749

RESUMO

Ataxia telangiectasia and Rad3 related (ATR) activation after replication stress involves a cascade of reactions, including replication protein A (RPA) complex loading onto single-stranded DNA and ATR activator loading onto chromatin. The contribution of histone modifications to ATR activation, however, is unclear. Here, we report that H3K14 trimethylation responds to replication stress by enhancing ATR activation. First, we confirmed that H3K14 monomethylation, dimethylation, and trimethylation all exist in mammalian cells, and that both SUV39H1 and SETD2 methyltransferases can catalyze H3K14 trimethylation in vivo and in vitro. Interestingly, SETD2-mediated H3K14 trimethylation markedly increases in response to replication stress induced with hydroxyurea, a replication stress inducer. Under these conditions, SETD2-mediated H3K14me3 recruited the RPA complex to chromatin via a direct interaction with RPA70. The increase in H3K14me3 levels was abolished, and RPA loading was attenuated when SETD2 was depleted or H3K14 was mutated. Rather, the cells were sensitive to replication stress such that the replication forks failed to restart, and cell-cycle progression was delayed. These findings help us understand how H3K14 trimethylation links replication stress with ATR activation.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Replicação do DNA , DNA/biossíntese , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Proteína de Replicação A/metabolismo , Animais , Proteínas Mutadas de Ataxia Telangiectasia/química , Proteínas Mutadas de Ataxia Telangiectasia/genética , DNA/química , DNA/genética , Histona-Lisina N-Metiltransferase/química , Histona-Lisina N-Metiltransferase/genética , Histonas/química , Histonas/genética , Humanos , Metilação , Metiltransferases/química , Metiltransferases/genética , Metiltransferases/metabolismo , Proteína de Replicação A/química , Proteína de Replicação A/genética , Proteínas Repressoras/química , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
3.
J Assist Reprod Genet ; 41(2): 493-504, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38049704

RESUMO

BACKGROUND: Endometrial receptivity (ER), a pivotal event for successful embryo implantation, refers to the capacity of endometrium to allow the adhesion of the trophectoderm of the blastocyst to endometrial cells. In this paper, we set to elucidate whether the peptides encoded by lncRNAs could influence trophoblast cells' adhesion to endometrial cells. METHODS: WGCNA construction and bioinformatics were used to find out the ER-related lncRNAs with coding potential. Protein analysis was done by immunoblotting and immunofluorescence (IF) microscopy. CCK-8 and Calcein-AM/PI double staining assays were employed to evaluate cell viability. The effect of the peptide on trophoblast spheroids' adhesion to endometrial cells was evaluated. The RNA sequencing (RNA-seq) analysis was applied to identify downstream molecular processes. RESULTS: lncRNA LINC00339 was found to be related to ER development and it had been predicted to have protein-coding potential. LINC00339 had high occupancy of ribosomes and was confirmed to encode a 49-aa peptide (named LINC00339-205-49aa). LINC00339-205-49aa could promote the attachment of JAR trophoblast spheroids to Ishikawa endometrial cells in vitro. LINC00339-205-49aa also upregulated the expression of E-cadherin in Ishikawa cells. Mechanistically, MAPK and PI3K-Akt signaling pathways were involved in the modulation of LINC00339-205-49aa, which were activated by LINC00339-205-49aa in Ishikawa cells. CONCLUSION: These data demonstrate that a previously uncharacterized peptide encoded by lncRNA LINC00339 has the ability to enhance JAR trophoblast spheroids' adhesion to Ishikawa endometrial cells, highlighting a new opportunity for the development of drugs to improve ER.


Assuntos
RNA Longo não Codificante , Feminino , Humanos , RNA Longo não Codificante/genética , Proteínas Proto-Oncogênicas c-akt/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Endométrio/metabolismo , Implantação do Embrião/genética , Trofoblastos/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais/genética , Adesão Celular/genética , Peptídeos
4.
Anal Chem ; 95(50): 18426-18435, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38051938

RESUMO

Non-small cell lung cancer (NSCLC) accounts for a high proportion of lung cancer cases globally, but early detection remains challenging, and insufficient oxygen supply at tumor sites leads to suboptimal treatment outcomes. Therefore, the development of core-shell Au@Pt-Se nanoprobes (Au@Pt-Se NPs) with peptide chains linked through Pt-Se bonds was designed and synthesized for NSCLC biomarker protein calcium-activated neutral protease 2 (CAPN2) and photothermal therapy (PTT) enhancement. The NP can be specifically cleaved by CAPN2, resulting in fluorescence recovery to realize the detection. The Pt-Se bonds exhibit excellent resistance to biologically abundant thiols such as glutathione, thus avoiding "false-positive" results and enabling precise detection of NSCLC. Additionally, the platinum (Pt) shell possesses catalase-like properties that catalyze the generation of oxygen from endogenous hydrogen peroxide within the tumor, thereby reducing hypoxia-inducible factor-1α (HIF-1α) levels and alleviating the hypoxic environment at the tumor site. The Au@Pt-Se NPs exhibit strong absorption bands, enabling the possibility of PTT in the near-infrared II region (NIR II). This study presents an effective approach for the early detection of NSCLC while also serving as an oxygen supplier to alleviate the hypoxic environment and enhance NIR II PTT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nanopartículas , Neoplasias , Humanos , Terapia Fototérmica , Carcinoma Pulmonar de Células não Pequenas/terapia , Platina/química , Neoplasias Pulmonares/terapia , Neoplasias/patologia , Oxigênio , Linhagem Celular Tumoral , Nanopartículas/química
5.
Bioconjug Chem ; 33(6): 1131-1137, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35576584

RESUMO

Owing to the encouraging pharmacological action and acceptable toxicity profile, Au(I) complexes have attracted growing interest in the application of disease treatment. In order to investigate their potential target proteins and related bioinformation, herein, we screened four Au(I) complexes and explored the binding proteins utilizing a competitive activity-based protein profiling (ABPP) strategy, including identification experiments and reactivity classification experiments, which offers a simple and robust method to identify the target proteins of Au(I) complexes. We quantified the target proteins of the four Au(I) complexes and found that most of proteins were associated with cancer. In addition, the newly Au(I)-binding proteins and biological gold-protein interaction pathways were exhibited. Furthermore, we estimated the correlation between target proteins of Au(I) complexes and various cancers, which will promote the development of the gold anticancer drugs.


Assuntos
Ouro , Proteínas , Antineoplásicos/química , Ouro/química , Humanos , Neoplasias/tratamento farmacológico , Proteínas/metabolismo
6.
BMC Pediatr ; 22(1): 15, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980064

RESUMO

BACKGROUND: The prenatal diagnosis of foetal imperforate anus is difficult. Most previous studies have been case reports. To provide useful information for diagnosing foetal imperforate anus, a retrospective review of diagnostic approaches was conducted. Ultrasonography was performed in 19 cases of foetal imperforate anus from 2016 to 2019 at our prenatal diagnostic centre. The prenatal sonographic features and outcomes of each case were collected and evaluated. RESULT: The anal sphincter of a normal foetus shows the 'target sign' on cross-sectional observation. Of the 19 cases of imperforate anus, 16 cases were diagnosed by the ultrasound image feature called the 'line sign'. 1 case with tail degeneration was low type imperforate anus with the irregular 'target sign' not a real 'target sign'. There was two false-negative case, in which the 'target sign' was found, but irregular. CONCLUSION: In this study, we find that the anus of a foetus with imperforate anus presents a 'line sign' on sonographic observation. The absence of the 'target sign' and then the presence of the 'line sign' can assist in the diagnosis of imperforate anus. The 'line sign' can be used as a secondary assessment to determine the type of the malformation following non visualization of the 'target sign'. The higher the position of the imperforate anus is, the more obvious the 'line sign'. It is worth noting that the finding of the short 'line sign' and irregularr 'target sign' can not ignore the low type imperforate anus.


Assuntos
Anus Imperfurado , Canal Anal/anormalidades , Canal Anal/diagnóstico por imagem , Anus Imperfurado/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Gravidez , Ultrassonografia/métodos , Ultrassonografia Pré-Natal/métodos
7.
Angew Chem Int Ed Engl ; 61(9): e202113051, 2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-34881475

RESUMO

Accurate quantification of disease-signature microRNAs (miRNAs) in biomedical samples is in high demand for clinical diagnosis but still challenging because of the low abundance of miRNAs and complicating interferences in the milieus. Here, we report a multi-amplification strategy based on paper-spray mass spectrometry (PS MS) for the analysis of miRNAs in blood. A toehold-mediated DNA-strand-displacement reaction (TSD) is employed to amplify the signal chain and to ensure the specificity. The signal chain is then cleaved by UV light to release signal molecules for detection. Moreover, the paper spray method can efficiently filter out interfering substances in the blood and further enhance the sensitivity of detection. This concept is successfully demonstrated in the prototypical detection of the cancer biomarker miRNA-141 in blood and serum. The proposed TSD-PS MS approach provides an efficient method for the sensitive detection of oligonucleotides at low concentration in complicated milieus.


Assuntos
Biomarcadores Tumorais/sangue , DNA/química , MicroRNAs/sangue , Neoplasias/sangue , Técnicas de Amplificação de Ácido Nucleico , Papel , Técnicas Biossensoriais , Humanos , Espectrometria de Massas , Neoplasias/patologia
8.
Anal Chem ; 93(3): 1749-1756, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33351590

RESUMO

Significant efforts have been made to develop robust and reliable methods for simultaneous biothiols determination in different matrices, but there still exist the problems such as easy oxidation, tedious derivatization, and difficulty in discrimination, which brings unsatisfactory results in their accuracy and fast quantification in biological samples. To overcome these problems, a simultaneous biothiols detection method combining a "selenium signature" chemical probe and paper spray mass spectrometry (PS-MS) was proposed. In the strategy, the modified-paper substrate is used to enhance the analytical performance. Chemical probe Ebselen-NH2 that has a specific response to biothiols was designed and covalently fixed on the surface of an oxidized paper substrate. By the identification of derivatized product with distinctive selenium isotope distribution and employment of the optimized PS-MS method, qualitative and quantitative analysis of five biothiols including glutathione (GSH), cysteine (Cys), cysteinylglycine (CysGly), N-acetylcysteine (Nac), and homocysteine (Hcy) were realized. Biothiols in plasma and cell lysates were measured with satisfactory results. The established method not only provides a novel protocol for simultaneous determination of biothiols, but also is helpful for understanding the biological and clinical roles played by these bioactive small molecules.


Assuntos
Acetilcisteína/análise , Cisteína/análise , Dipeptídeos/análise , Corantes Fluorescentes/química , Glutationa/análise , Papel , Selênio/química , Técnicas Biossensoriais , Cisteína/análogos & derivados , Humanos , Espectrometria de Massas
9.
Ecotoxicol Environ Saf ; 224: 112676, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34419644

RESUMO

Chemical hazardous substances in teethers may migrate into infant's body through oral exposure, resulting in a potential health risk. In recent years, researchers have performed a series of studies for detecting target chemicals in teethers and other toys, but the presence of unknown chemicals has not been systematically investigated yet. This paper reports the non-targeted identification of unknown chemical hazards that may have migrated from teethers to infants based on gas chromatography-Orbitrap high resolution mass spectrometry. In view of the difficulties that may be encountered in the qualitative analysis of substances, several typical cases and the corresponding reliable solutions are given from the perspective of comprehensive score and retention index, isotope-aided qualitative analysis, chemical ionization identification formula, and fragment ion detail comparison for distinguishing isomers. Finally, 28 substances are identified in 10 teether samples. Among them, phenol, N-methylaniline, 1,6-dioxacyclododecane-7,12-dione and cyclohexanone have higher detection rates. This study not only has valuable reference for the identification of unknown substances, but also has positive guiding role in monitoring potential chemical hazards in toys and promoting the safety of products.

10.
BMC Med Inform Decis Mak ; 21(1): 284, 2021 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-34656109

RESUMO

Charging according to disease is an important way to effectively promote the reform of medical insurance mechanism, reasonably allocate medical resources and reduce the burden of patients, and it is also an important direction of medical development at home and abroad. The cost forecast of single disease can not only find the potential influence and driving factors, but also estimate the active cost, and tell the management and reasonable allocation of medical resources. In this paper, a method of Bayesian network combined with regression analysis is proposed to predict the cost of treatment based on the patient's electronic medical record when the amount of data is small. Firstly, a set of text-based medical record data conversion method is established, and in the clustering method, the missing value interpolation is carried out by weighted method according to the distance, which completes the data preparation and processing for the realization of data prediction. Then, aiming at the problem of low prediction accuracy of traditional regression model, this paper establishes a prediction model combined with local weight regression method after Bayesian network interpretation and classification of patients' treatment process. Finally, the model is verified with the medical record data provided by the hospital, and the results show that the model has higher prediction accuracy.


Assuntos
Registros Eletrônicos de Saúde , Custos de Cuidados de Saúde , Teorema de Bayes , Análise por Conglomerados , Humanos , Análise de Regressão
11.
Anal Chem ; 92(9): 6430-6436, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32268724

RESUMO

Compared with semiconductor quantum dots and organic chromophores, carbon dots (CDs)-based lysosome probe with strong emission, an intrinsic targeting ability, and easy synthesis procedure were urgently desired in visualization imaging studies. Herein, we showed that it was possible to produce CDs with the desired properties for lysosome imaging via a one-step hydrothermal treatment of commercial reagents, rose bengal (RB) and branched polyethylenimine (bPEI). The prepared bPEI-RB CDs (P-R CDs) had a high fluorescence quantum yield (FLQY) of 90.49%, a narrow emission band of 30 nm, negligible phototoxicity, and dark toxicity. Moreover, P-R CDs had an intrinsic lysosome targeting ability without any postmodification of the ligands. Long-term cell imaging displayed P-R CDs can anchor lysosomes for up to 48 h without leakage. In addition, experimental results confirmed that dehalogenation cross-linking and structural reorganization of the reactants were the main causes of the ultrahigh photoluminescence efficiency, low cytotoxicity, and passivated surface of the P-R CDs. This origin was attributed to the restricted intersystem crossing and nonradiative transition, the reduced production of singlet oxygen, and suitable -NH2 functional groups. Due to outstanding characteristics, P-R CDs may be developed for a promising tool in lysosome images. The concept of facile preparation will also pave a new avenue for developing ultrabright functional nanomaterial markers.

12.
Anal Chem ; 92(1): 1245-1251, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31820623

RESUMO

Drug-induced liver injury (DILI) can cause liver failure and even death in severe cases, gravely threatening human health. The treatment of DILI remains a clinical challenge, mainly due to the lack of efficient and accurate diagnosis. Therefore, developing an accurate diagnosis approach is imperative to boost the timely treatment for DILI. As the primary organ of iron storage, liver's functions are tightly linked to iron homeostasis. Thus, monitoring iron homeostasis is promising for the diagnosis and treatment of DILI. Hence, we reported a new near-infrared fluorescent probe (LCy7) that enables real-time and in vivo visualizing of Fe2+ in drug-induced liver injury. In this design, Fe2+ would bind to the N4O ligand in LCy7 and conduce to the C-O bond broken in the presence of O2, which restore the masked QCy7 emitting luminous near-infrared fluorescence. Utilizing LCy7, the increase in Fe2+ was distinctly witnessed in hepatocytes under endoplasmic reticulum stress by acetaminophen (APAP) stimulation. In vivo near-infrared fluorescence imaging revealed the conspicuous rise in Fe2+ in the liver of mice during APAP-induced liver injury. We further unprecedentedly disclosed that endoplasmic reticulum stress was accompanied by the overload of Fe2+ in injured liver of these mice. Collectively, this work will facilitate a greater understanding of the pathogenesis of DILI, and also provide a powerful new tool for DILI diagnosis and treatment.


Assuntos
Acetaminofen/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Compostos Ferrosos/metabolismo , Corantes Fluorescentes/química , Fígado/efeitos dos fármacos , Animais , Linhagem Celular , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Compostos Ferrosos/química , Corantes Fluorescentes/síntese química , Fígado/metabolismo , Fígado/patologia , Camundongos , Estrutura Molecular , Imagem Óptica
13.
Analyst ; 145(19): 6357-6362, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32724990

RESUMO

How to further improve the sensitivity of paper spray mass spectrometry (PS-MS) is very important for its application in low content substance detection. Covalent organic frameworks (COFs) are a kind of novel crystalline materials that exhibit tremendous potential for multifarious applications. Nevertheless, the applications of COFs in PS-MS are still unexplored. Herein, for the first time, a method that used COFs nanoparticles as a coated matrix of PS-MS coupled with solid phase microextraction (SPME) was developed, and as a proof of concept, it was applied for highly sensitive analysis of pollutant tetrabromobisphenol A (TBBPA) in environmental samples. In order to prepare the COFs-coated papers, a variety of factors, such as starch type and amount, loaded COFs amount and spray solvent, have been explored in detail. Compared with the naked paper substrates, a lower limit of quantitation of 1 nmol L-1 with 50-fold enhancement was achieved using COFs-based paper composites, which indicated that papers decorated with COFs might be a promising candidate for paper spray with high sensitivity in the analysis of environmental samples.

14.
BMC Pregnancy Childbirth ; 20(1): 387, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620086

RESUMO

BACKGROUND: The purpose of this research is to summarize the prenatal ultrasound characteristics of congenital duodenal obstruction (CDO), especially in the diagnosis of duodenal diaphragm and annular pancreas. At present, few researchers have summarized the specific ultrasound features of duodenal diaphragm and annular pancreas. METHODS: In this study, a retrospective analysis of 40 patients diagnosed with CDO between January 2016 and December 2019 was carried out. Data on the diagnosis, ultrasound images and outcomes of the patients were gathered, and the features of the patients were analyzed. RESULTS: The results showed that there were 17 patients (42.5%) of congenital duodenal diaphragm, all with a 'rat tail' sign on the ultrasound images. Moreover, there were 4 patients (10.0%) of CDO caused by annular pancreas, all with a 'pliers' sign on the ultrasound images. We summarized the imaging features of the 'rat tail' sign and the 'pliers' sign. CONCLUSION: The main conclusion of this study was that the 'rat tail' sign could be used as an indirect ultrasound feature to diagnose duodenal diaphragm. The 'pliers' sign could be used as a direct ultrasound feature in the diagnosis of annular pancreas in CDO.


Assuntos
Obstrução Duodenal/diagnóstico por imagem , Ultrassonografia Pré-Natal , Adulto , Obstrução Duodenal/congênito , Feminino , Idade Gestacional , Humanos , Masculino , Pâncreas/anormalidades , Pâncreas/diagnóstico por imagem , Pancreatopatias/diagnóstico por imagem , Gravidez , Estudos Retrospectivos
15.
BMC Pregnancy Childbirth ; 20(1): 614, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046002

RESUMO

BACKGROUND: Fetal double aortic arch (DAA) malformation is a rare congenital heart disease with few reported cases in the literature. We aimed to investigate the characteristics of prenatal ultrasound and postnatal computed tomography angiography (CTA) of DAA and to describe the associated anomalies and clinical outcomes to improve prenatal diagnosis and assist in perinatal management. METHODS: The obstetric ultrasound imaging databases of seven tertiary referral centers were reviewed retrospectively to identify fetuses with a prenatal diagnosis of DAA between January 2013 and December 2018. Ultrasonographic findings, associated anomalies, genetic abnormalities, postnatal CTA images, and long-term postnatal outcomes were evaluated. RESULTS: A total of 36 cases out of 40 prenatally diagnosed DAA fetuses were confirmed by postnatal diagnosis (fetal autopsy, CTA, and surgery). In this cohort of 36 confirmed cases, 24 (67%) were isolated anomalies, while 12 (33%) were associated with intracardiac or extracardiac anomalies, and 2 (6%) had a 22q11.2 chromosome deletion. Among nine cases of pregnancy termination with a fetal autopsy, 7 had other abnormalities. Among the remaining 27 live births, 16 (59%) were asymptomatic and 11 (41%) received surgical treatment due to tracheal or esophageal compression symptoms, all with satisfactory outcomes. Prenatal echocardiography showed that DAA was mainly characterized by a bifurcation of the ascending aorta into the right and left aortic arch and the formation of a complete O-shaped vascular ring around the trachea on the three-vessel tracheal view. A variant in the aortic arch branching pattern was found for the first time. The airway obstruction, branching pattern, and atretic arch of DAA were clearly shown by postnatal CTA. CONCLUSIONS: Fetal DAA has unique features on prenatal echocardiography and postnatal CTA, and systematic prenatal examination and timely postnatal CTA evaluation are required. A certain proportion of intracardiac and extracardiac abnormalities are associated with DAA, but the probability of chromosome abnormalities is low, especially for isolated DAA.The clinical outcomes of isolated DAA are favorable, even if surgery is performed due to symptoms. Determining whether other malformations or chromosomal anomalies exist is crucial for prognosis evaluation and prenatal counseling.


Assuntos
Obstrução das Vias Respiratórias/diagnóstico , Angiografia por Tomografia Computadorizada , Ecocardiografia Doppler em Cores , Ultrassonografia Pré-Natal/métodos , Anel Vascular/diagnóstico , Aborto Induzido/estatística & dados numéricos , Aborto Terapêutico , Adulto , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/cirurgia , Aorta/anormalidades , Aorta/diagnóstico por imagem , Erros de Diagnóstico/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Imageamento Tridimensional , Incidência , Recém-Nascido , Idade Materna , Cuidado Pós-Natal , Estudos Retrospectivos , Resultado do Tratamento , Anel Vascular/complicações , Anel Vascular/epidemiologia , Anel Vascular/cirurgia , Adulto Jovem
16.
Anal Chem ; 91(15): 9770-9776, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31288519

RESUMO

Macrophage foam cell formation mediated by CD36 receptor dependent internalization of oxidized low-density lipoprotein (oxLDL) is an important hallmark of early atherosclerosis. Activation of CD36 and its binding to oxLDL are the key points in foam cell formation. Herein, we develop a site-specific luminescence resonance energy transfer (LRET) system for the simultaneous imaging of CD36 activity and CD36-oxLDL binding on the cell surface. The system utilizes CD36-antibody-modified, SiO2-coated upconversion luminescent nanoparticles (UCNPs) as an energy donor to target the plasma membranes of macrophages, and DiI-oxLDL (energy acceptor) binds to CD36 and passes through the membrane during macrophage foam cell formation. Upon excitation at 980 nm, the LRET signal can be obtained because of the short distance between DiI-oxLDL and the nanoprobe. Additionally, the very specific fluorescence can be used to visualize distinct features of CD36. The nanoprobe also exhibits high sensitivity, good stability, simplicity, and low cost for the accurate detection and evaluation of macrophage foam cell formation. Moreover, using this novel nanoprobe, we also investigate the mechanism by which reactive oxygen species (ROS) signaling enhances the binding of oxLDL to CD36. ROS, especially O2·-, alter endothelial permeability and facilitate CD36 clustering, ultimately promoting the entry and internalization of oxLDL. Because of these advantages, this nanoprobe may provide a versatile platform for monitoring the progression of atherogenesis and elucidating atherogenesis signaling at the cellular level.


Assuntos
Aterosclerose/metabolismo , Antígenos CD36/metabolismo , Transferência de Energia , Lipoproteínas LDL/metabolismo , Substâncias Luminescentes/química , Nanoestruturas/química , Imagem Óptica/métodos , Animais , Antígenos CD36/química , Macrófagos/metabolismo , Camundongos , Ligação Proteica , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo
17.
Anal Chem ; 91(20): 12874-12881, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31518111

RESUMO

To achieve personalized healthcare, a quick, accurate, and high-throughput method to detect disease biomarkers is essential. In the traditional practice, mass spectrometry is one of the most powerful tools and is widely studied. However, the test of human serum usually requires complicated sample pretreatment, tedious operations, and precise condition control, especially for the detection of enzymes as biomarkers. As butyrylcholinesterase (BuChE) has an indicative significance in detecting degenerative disease, liver injury, and organophosphate poisoning, the quick quantification of BuChE is of vital importance to the clinic. In this paper, we report the design and fabrication of a portable 3D-printed enzyme reactor paper spray cartridge (3D ER-PS) with integrated functions: temperature control, enzyme reaction, analyte transfer, and paper spray ionization. Coupled with mass spectrometry, quantitative testing of BuChE activity in human serum was realized conveniently and accurately. While it only requires very simple sample preparation, the results from current 3D ER-PS approach are well consistent with those obtained using Ellman's method. This 3D ER-PS platform not only provides a novel solution for the liquid biopsy of BuChE in clinics but also contributes to the development of quick and targeted medical approaches for analyzing other types of serum biomarker molecules in the field of disease diagnosis.


Assuntos
Butirilcolinesterase/sangue , Espectrometria de Massas/métodos , Intoxicação por Organofosfatos/diagnóstico , Papel , Praguicidas/intoxicação , Impressão Tridimensional/instrumentação , Ouro/química , Humanos , Nanopartículas Metálicas/química , Intoxicação por Organofosfatos/enzimologia
18.
Anal Chem ; 91(1): 1150-1156, 2019 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-30497260

RESUMO

Inflammation triggered by oxidative stress is the main determinant of atherosclerotic plaque disruption, which is the leading cause of myocardial infarctions and strokes. Hence, noninvasive mapping of alterations in redox status in vivo is highly desirable for accurate assessment of plaque inflammatory activity and vulnerability. Herein, two types of near-infrared fluorescence probes, specific for glutathione (GSH)/hydrogen peroxide (H2O2) redox couple, were used to introduce the self-assembly of bovine serum albumin (BSA), forming a BSA-Cy-Mito nanoprobe for in vivo photoacoustic imaging of redox status. Such BSA-based self-assemblies on one hand processed good biocompatibility and long blood circulation for high EPR effect and plaque accumulation and on the other hand displayed strong GSH- and H2O2-dependent absorbance at 765 and 680 nm, which enabled simultaneous photoacoustic detection of GSH/H2O2 with high specificity and sensitivity. Using BSA-Cy-Mito as an in vivo GSH/H2O2 indicator, accurate detection of the redox-related inflammatory process was realized both in oxidized low-density lipoprotein (ox-LDL)-activated macrophages and high fat diet-fed apolipoprotein E-deficient (ApoE-/-) mice. Systemic administration of BSA-Cy-Mito further enabled differentiation of vulnerable plaques from stable ones based on their different redox states. Therefore, this sensitive redox-responsive PA nanoprobe may be a powerful tool for early identification of rupture-prone plaques and help in implementing successful preventative therapeutic strategies.


Assuntos
Corantes Fluorescentes/química , Inflamação/diagnóstico por imagem , Nanopartículas/química , Técnicas Fotoacústicas , Placa Aterosclerótica/diagnóstico por imagem , Animais , Apolipoproteínas E/análise , Apolipoproteínas E/deficiência , Corantes Fluorescentes/síntese química , Glutationa/química , Peróxido de Hidrogênio/química , Lipoproteínas LDL/análise , Camundongos , Camundongos Knockout , Oxirredução , Soroalbumina Bovina/química
19.
Anal Chem ; 90(13): 8116-8122, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-29879841

RESUMO

Previous studies proposed that sodium selenite (Na2SeO3) was reduced to hydrogen selenide (H2Se) and that H2Se subsequently reacted with oxygen to generate superoxide anion (O2•-), resulting in tumor cell oxidative stress and apoptosis. However, under the hypoxic conditions of a solid tumor, the anticancer mechanism of sodium selenite remains unclear. To reveal the exact anticancer mechanism of selenite in the real tumor microenvironment, we developed a mitochondria-targeting fluorescent nanosensor, Mito-N-D-MSN, which was fabricated from mesoporous silica nanoparticles (MSNs) loaded with two small-molecule fluorescent probes and a triphenylphosphonium ion as a mitochondria-targeting moiety. With Mito-N-D-MSN, the fluctuations in the contents of mitochondrial hydrogen selenide (H2Se) and superoxide anion (O2•-) in HepG2 cells induced by Na2SeO3 were investigated in detail under normoxic and hypoxic conditions. The results showed that the mitochondrial H2Se content increased gradually, while the O2•- content remained unchanged in HepG2 cells under hypoxic conditions, which indicated that the anticancer mechanism of selenite involves nonoxidative stress in the real tumor microenvironment.


Assuntos
Mitocôndrias/metabolismo , Imagem Óptica , Compostos de Selênio/metabolismo , Superóxidos/metabolismo , Hipóxia Celular , Corantes Fluorescentes/metabolismo , Células Hep G2 , Humanos , Fatores de Tempo
20.
Anal Chem ; 90(24): 14507-14513, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30477304

RESUMO

Effective and sensitive monitoring of arsenate in drinking water is significant for risk management of public health. Here, we demonstrated that a CeO2 nanowire acted as an efficient quencher for small fluorescent molecules with a phosphate group, BODIPY-adenosine triphosphate (BODIPY-ATP) and riboflavin-5'-phosphate (Rf-P), and developed a CeO2 nanowire-BODIPY-ATP platform for highly selective and sensitive detection of arsenate. The response strategy was based on the competitive coordination chemistry of CeO2 nanowire between arsenate and phosphate group of BODIPY-ATP. Arsenate displaced adsorbed BODIPY-ATP to enhance fluorescence, allowing detection of arsenate down to 7.8 nM, which is lower than the WHO-defined limit of 130 nM. An excellent linear range of 20-150 and 150-1000 nM was obtained. Importantly, this system was simple in design and convenient in operation. Also, the platform exhibited excellent selectivity for arsenate without the interference of phosphate ions. Finally, the proposed method had been successfully employed for determination of arsenate in real water samples.


Assuntos
Trifosfato de Adenosina/química , Arseniatos/análise , Compostos de Boro/química , Cério/química , Nanofios/química , Adsorção , Arseniatos/química , Corantes Fluorescentes/química , Limite de Detecção , Espectrometria de Fluorescência
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