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1.
BMC Genomics ; 25(1): 485, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755540

RESUMO

BACKGROUND: Indigenous chickens were developed through a combination of natural and artificial selection; essentially, changes in genomes led to the formation of these modern breeds via admixture events. However, their confusing genetic backgrounds include a genomic footprint regulating complex traits, which is not conducive to modern animal breeding. RESULTS: To better evaluate the candidate regions under domestication in indigenous chickens, we considered both runs of homozygosity (ROHs) and selective signatures in 13 indigenous chickens. The genomes of Silkie feather chickens presented the highest heterozygosity, whereas the highest inbreeding status and ROH number were found in Luhua chickens. Short ROH (< 1 Mb), were the principal type in all chickens. A total of 291 ROH islands were detected, and QTLdb mapping results indicated that body weight and carcass traits were the most important traits. An ROH on chromosome 2 covering VSTM2A gene was detected in 12 populations. Combined analysis with the Tajima's D index revealed that 18 genes (e.g., VSTM2A, BBOX1, and RYR2) were under selection and covered by ROH islands. Transcriptional analysis results showed that RYR2 and BBOX1 were specifically expressed in the heart and muscle tissue, respectively. CONCLUSION: Based on genome-wide scanning for ROH and selective signatures, we evaluated the genomic characteristics and detected significant candidate genes covered by ROH islands and selective signatures. The findings in this study facilitated the understanding of genetic diversity and provided valuable insights for chicken breeding and conservation strategies.


Assuntos
Galinhas , Domesticação , Homozigoto , Animais , Galinhas/genética , Seleção Genética , Locos de Características Quantitativas , Genoma , Genômica/métodos , Polimorfismo de Nucleotídeo Único
2.
Br J Cancer ; 129(5): 884-894, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37474721

RESUMO

BACKGROUND: It is imperative to develop novel therapeutics to overcome chemoresistance, a significant obstacle in the clinical management of prostate cancer (PCa) and other cancers. METHODS: A phenotypic screen was performed to identify novel inhibitors of chemoresistant PCa cells. The mechanism of action of potential candidate(s) was investigated using in silico docking, and molecular and cellular assays in chemoresistant PCa cells. The in vivo efficacy was evaluated in mouse xenograft models of chemoresistant PCa. RESULTS: Nicardipine exhibited high selectivity and potency against chemoresistant PCa cells via inducing apoptosis and cell cycle arrest. Computational, molecular, and cellular studies identified nicardipine as a putative inhibitor of embryonic ectoderm development (EED) protein, and the results are consistent with a proposed mechanism of action that nicardipine destabilised enhancer of zeste homologue 2 (EZH2) and inhibited key components of noncanonical EZH2 signalling, including transducer and activator of transcription 3, S-phase kinase-associated protein 2, ATP binding cassette B1, and survivin. As a monotherapy, nicardipine effectively inhibited the skeletal growth of chemoresistant C4-2B-TaxR tumours. As a combination regimen, nicardipine synergistically enhanced the in vivo efficacy of docetaxel against C4-2 xenografts. CONCLUSION: Our findings provided the first preclinical evidence supporting nicardipine as a novel EED inhibitor that has the potential to be promptly tested in PCa patients to overcome chemoresistance and improve clinical outcomes.


Assuntos
Nicardipino , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Apoptose , Linhagem Celular Tumoral , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Nicardipino/farmacologia , Nicardipino/uso terapêutico , Complexo Repressor Polycomb 2 , Neoplasias da Próstata/tratamento farmacológico
3.
Mikrochim Acta ; 190(11): 445, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37851156

RESUMO

Ni-Zn bimetallic organic framework nanosheets (NiZn-MOF NSs) were modified onto PEI-functionalized MXene for the first time. The combination of the two kinds of nanosheets forms a sensing platform with superior conductivity and biocompatibility. On this basis, a highly sensitive biosensor was developed for the determination of sulfadimethoxine (SDM). Furthermore, Au and Mn nanoparticles decorated reduced graphene oxide (Au-Mn/rGO) was introduced as a signal hindering molecule under the target-induced amplification strategy. When the Au-Mn/rGO-labelled SDM-binding aptamer (Au-Mn/rGO-SBA) specifically bound to target SDM, it detached from the electrode, thereby further amplifying the electrochemical signal of [Fe(CN)6]3-/4-. The developed aptasensor for SDM showed excellent response signals in the range 1 pg mL-1 to 100 ng mL-1, with a limit of detection (LOD) as low as 0.22 pg mL-1. Significantly, the proposed sensor also showed satisfactory results in milk samples with recoveries ranging from 87.0 to 96.4% and RSD from 1.5 to 5.1%, which is believed to be useful in food safety assays.


Assuntos
Grafite , Nanocompostos , Sulfadimetoxina , Grafite/química , Nanocompostos/química
4.
Geriatr Nurs ; 54: 129-134, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37782975

RESUMO

The aim of this study was to explore effects of palliative care (PC) on patients with different heart function. Patients with NYHA (New York Heart Association) class II, III, IV were divided into separate groups. The KCCQ (Kansas City Cardiomyopathy Questionnaire) and HADS (Hospital Anxiety and Depression Scale) scores were compared before and 3 months after PC intervention. After 3 months, compared with the control group, PC could further significantly improve the KCCQ, HADS-depression and -anxiety scores of patients in NYHA class IV (P < 0.05); PC could significantly improve the HADS-depression and -anxiety scores of patients with NYHA class III (P < 0.05), and had an improvement tendency on KCCQ score. The study revealed that PC can significantly improve anxiety and depression of patients with NYHA class III or IV, and significantly improve the quality of life of patients with NYHA class IV, but had no effects on patients with NYHA class II.


Assuntos
Insuficiência Cardíaca , Qualidade de Vida , Humanos , Cuidados Paliativos , Projetos Piloto , Ansiedade/terapia , Inquéritos e Questionários
5.
Org Biomol Chem ; 20(47): 9392-9396, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-36398442

RESUMO

A novel palladium catalyzed homodimerization of ortho-hydroxyphenyl substituted p-QMs has been developed via [4 + 2] cycloaddition/oxidative dehydrogenation coupling domino reactions. An interesting palladium catalyzed intramolecular benzyl C-H oxidation dehydrogenation to form a transannular C(sp3)-O bond was found. This protocol provided an efficient method to construct various dibenzodioxo[3.3.1]nonanes bearing spirocyclohexadienones.


Assuntos
Paládio
6.
Analyst ; 146(23): 7284-7293, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34749389

RESUMO

Graphdiyne oxide (GDYO) is a novel type of two-dimensional carbon allotrope nanomaterial consisting of a large conjugated system and excellent chemical stability. To date, application of GDYO as a nanozyme in biosensing has been rarely reported. In this study, a novel ultrasensitive colorimetric bioassay was constructed using a hemin/GDYO nanocomposite (H/GDYO) as a new nanozyme with superior peroxidase-like activity for the detection of H2O2 and glucose. It was discovered that H/GDYO exhibited 6-fold higher peroxidase-like activity than pure hemin. Catalytic kinetic analysis showed that H/GDYO had a much higher affinity for H2O2 and glucose than that of hemin. The designed colorimetric bioassay displayed excellent sensitivity for H2O2 and glucose detection with a wide linear range of 0.015-0.5 mM and 0.1-10 mM, respectively, while the limit of detection (LOD) was as low as 4.39 µM and 38 µM, respectively. Moreover, it was successfully applied for the analysis of H2O2 in milk and glucose in real human serum samples with acceptable recoveries. Importantly, the developed colorimetric bioassay shows good agreement with the results obtained from a commercial blood glucose meter. We believe that the proposed method could provide a promising prospect for medical diagnosis and biotechnology.


Assuntos
Técnicas Biossensoriais , Nanocompostos , Bioensaio , Biomimética , Colorimetria , Grafite , Hemina , Humanos , Peróxido de Hidrogênio , Cinética , Óxidos , Peroxidase/metabolismo
7.
Mikrochim Acta ; 188(11): 404, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34731314

RESUMO

A label-free electrochemical aptasensor is reported for sensitive detection of the 6-kDa early secreted antigenic target (ESAT-6). For the first time, the bimetallic organic framework (b-MOF) of Zr-MOF-on-Ce-MOF was decorated with nitrogen-doped graphene (NG) and applied as the matrix for electroactive toluidine blue (Tb) to form the NG@Zr-MOF-on-Ce-MOF@Tb nanohybrid. The prepared nanohybrid with excellent hydrophilicity, dispersibility, and large specific surface exhibited significant electrochemical response. This nanohybrid could be directly used for anchoring ESAT-6 binding aptamers (EBA) through the interaction between the 5'-phosphate group (PO43-) of EBA and Zr4+ of Zr-MOF. The signal response before and after incubating the ESAT-6 antigen has been evaluated by cyclic voltammetry at a scan rate of 100 mV s-1 from - 0.7 to 0.3 V (vs. SCE). Under optimal conditions, the proposed aptasensor displayed a wide linear range from 100 fg mL-1 to 10 ng mL-1 with a limit of detection (LOD) of 12 fg mL-1. The developed method showed good reproducibility with a relative standard deviation (RSD) of 2.27%. The aptasensor showed favorable results in the analysis of the real samples. With these merits, the aptasensor has exceptional potential as a diagnostic tool for tuberculosis in clinical practice.


Assuntos
Antígenos de Bactérias/sangue , Aptâmeros de Nucleotídeos/química , Proteínas de Bactérias/sangue , Técnicas Biossensoriais/métodos , Estruturas Metalorgânicas/química , Mycobacterium tuberculosis/química , Antígenos de Bactérias/química , Proteínas de Bactérias/química , Cério/química , Técnicas Eletroquímicas/métodos , Humanos , Limite de Detecção , Nanocompostos/química , Reprodutibilidade dos Testes , Zircônio/química
8.
Mikrochim Acta ; 188(2): 31, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33415459

RESUMO

A novel and relatively simple signal-off electrochemical aptasensor was constructed for highly sensitive detection of lipopolysaccharide (LPS). For the first time, silver nanoparticles (AgNPs) decorated titanium dioxide nanotube (TNT) was conjugated with polydiallyldimethylammonium chloride (PDDA) functionalized reduced graphene oxide (rGO) to form a new nanohybrid of Ag-TNT/P-rGO. This nanohybrid with a large specific surface area exhibited excellent electrochemical activity, which not only served as the sensing platform to immobilize LPS binding aptamer (LBA) but was also employed as the redox probe to monitor the change of the electrochemical signal. The electrochemical signal responses were measured by cyclic voltammetry (CV) in the potential range -0.3 to 0.5 V at a scan rate of 0.1 V/s. The proposed aptasensor exhibited acceptable stability, reproducibility, and specificity for LPS detection with a wide linear range from 17 fg/mL to 100 ng/mL. The limit of detection (LOD) was 5 fg/mL. Furthermore, the prepared aptasensor showed acceptable recovery ranging from 96% to 103%, and the RSD varied between 1.4% and 8.5% for determining LPS in real samples.Graphical abstract.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Lipopolissacarídeos/análise , Nanopartículas Metálicas/química , Nanotubos/química , Sequência de Bases , DNA/química , Grafite/química , Ácidos Nucleicos Imobilizados/química , Limite de Detecção , Lipopolissacarídeos/química , Oxirredução , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/química , Polietilenos/química , Compostos de Amônio Quaternário/química , Reprodutibilidade dos Testes , Prata/química , Titânio/química
9.
Molecules ; 26(18)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34577150

RESUMO

Photoactivated chemotherapy (PACT) is a novel cancer treatment method that has drawn increasing attention due to its high selectivity and low side effects by spatio-temporal control of irradiation. Compared with photodynamic therapy (PDT), oxygen-independent PACT is more suitable for treating hypoxic tumors. By finely tuning ligand structures and coordination configurations, many Ru(II) complexes can undergo photoinduced ligand dissociation, and the resulting Ru(II) aqua species and/or free ligands may have anticancer activity, showing their potential as PACT agents. In this mini-review, we summarized the progress in Ru(II)-based PACT agents, as well as challenges that researchers in this field still face.


Assuntos
Antineoplásicos , Complexos de Coordenação , Rutênio , Humanos , Fotoquimioterapia
10.
Cancer Cell Int ; 20(1): 592, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33298057

RESUMO

BACKGROUND: The ability to treat glioblastoma (GBM) using the chemotherapeutic agent temozolomide (TMZ) has been hampered by the development of therapeutic resistance. In this study, we assessed the ability of the isoquinoline alkaloid berberine to alter GBM TMZ resistance using two different TMZ-resistant cell lines to mimic a physiologically relevant GBM experimental system. METHODS: By treating these resistant cell lines with berberine followed by TMZ, we were able to assess the chemosensitivity of these cells and their parental strains, based on their performance in the MTT and colony formation assays, as well as on the degree of detectable apoptosis that was detected in the strains. Furthermore, we used Western blotting to assess autophagic responses in these cell lines, and we extended this work into a xenograft mouse model to assess the in vivo efficacy of berberine. RESULTS: Through these experiments, our findings indicated that berberine enhanced autophagy and apoptosis in TMZ-resistant cells upon TMZ treatment in a manner that was linked with ERK1/2 signaling. Similarly, when used in vivo, berberine increased GBM sensitivity to TMZ through ERK1/2 signaling pathways. CONCLUSIONS: These findings demonstrate that berberine is an effective method of increasing the sensitization of GBM cells to TMZ treatment in a manner that is dependent upon the ERK1/2-mediated induction of autophagy, thus making berberine a potentially viable therapeutic agent for GBM treatment.

11.
Org Biomol Chem ; 18(14): 2641-2645, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32196054

RESUMO

A novel organocatalytic asymmetric cascade 1,6-addition/hemiketalization/retro-Henry reaction of ortho-hydroxyphenyl-substituted p-QMs with α-nitroketones is described. A variety of novel chiral 2-(1-(4-hydroxyphenyl)ethyl)phenols are constructed for the first time with high yields (up to 92%) and excellent enantioselectivities (up to >99% ee) under mild reaction conditions. A gram-scale experiment of this process is also presented.

12.
Biochem Biophys Res Commun ; 514(1): 157-165, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31029427

RESUMO

FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression. FOXA1 was reported to facilitate or reprogram ERα binding, thus playing a key function in breast cancer progression. Our previous results indicated that the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1 plays a potentially significant role in the ERα transcription network. However, further investigations are needed to identify the specific mechanism of modification and the specific glycosylation sites on FOXA1. In this study, we first suggested that FOXA1 could be O-GalNAcylated by ppGalNAc-T2 in vitro. By dividing and expressing recombinant FOXA1 as three segments, two O-GalNAcylation sites were found on FOXA1, both located at the C-terminal of the protein. Then, synthesized peptides, including the predicted O-GalNAc sites in the C-terminus of FOXA1, were used in a vitro reaction, and peptides mutated at the predicted O-GalNAc sites were employed as controls. Through an ESI-MS assay, S354 and S355 were identified as probable O-GalNAcylation sites on FOXA1. Additionally, we performed ESI-ETD-MS/MS analysis of the full-length O-GalNAcylated FOXA1 protein and identified S355 as the O-GalNAc modification site on FOXA1, consistent with the peptide reaction. In conclusion, our results demonstrated that FOXA1 can be O-GalNAcylated by ppGalNAc-T2 at S355 in vitro. These results will provide new insights for studying the role of O-GalNAcylation in the development of breast cancer.


Assuntos
Fator 3-alfa Nuclear de Hepatócito/metabolismo , N-Acetilgalactosaminiltransferases/metabolismo , Acetilgalactosamina/metabolismo , Acilação , Glicosilação , Células HEK293 , Fator 3-alfa Nuclear de Hepatócito/genética , Humanos , Serina/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Uridina Difosfato N-Acetilgalactosamina/metabolismo , Polipeptídeo N-Acetilgalactosaminiltransferase
13.
J Transl Med ; 17(1): 191, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171000

RESUMO

BACKGROUND: Elevated protein expressions of CD markers such as IL2RA/CD25, CXCR4/CD184, CD34 and CD56 are associated with adverse prognosis in acute myeloid leukemia (AML). However, the prognostic value of mRNA expressions of these CD markers in AML remains unclear. Through our pilot evaluation, IL2RA mRNA expression appeared to be the best candidate as a prognostic biomarker. Therefore, the aim of this study is to characterize the prognostic value of IL2RA mRNA expression and evaluate its potential to refine prognostification in AML. METHODS: In a cohort of 239 newly diagnosed AML patients, IL2RA mRNA expression were measured by TaqMan realtime quantitative PCR. Morphological, cytogenetics and mutational analyses were also performed. In an intermediate-risk AML cohort with 66 patients, the mRNA expression of prognostic biomarkers (BAALC, CDKN1B, ERG, MECOM/EVI1, FLT3, ID1, IL2RA, MN1 and WT1) were quantified by NanoString technology. A TCGA cohort was analyzed to validate the prognostic value of IL2RA. For statistical analysis, Mann-Whitney U test, Fisher exact test, logistic regression, Kaplan-Meier and Cox regression analyses were used. RESULTS: In AML cohort of 239 patients, high IL2RA mRNA expression independently predicted shorter relapse free survival (RFS, p < 0.001) and overall survival (OS, p < 0.001) irrespective of age, cytogenetics, FLT3-ITD or c-KIT D816V mutational status. In core binding factor (CBF) AML, high IL2RA mRNA expression correlated with FLT3-ITD status (p = 0.023). Multivariable analyses revealed that high IL2RA expression (p = 0.002), along with c-KIT D816V status (p = 0.013) significantly predicted shorter RFS, whereas only high IL2RA mRNA expression (p = 0.014) significantly predicted shorter OS in CBF AML. In intermediate-risk AML in which multiple gene expression markers were tested by NanoString, IL2RA significantly correlated with ID1 (p = 0.006), FLT3 (p = 0.007), CDKN1B (p = 0.033) and ERG (p = 0.030) expressions. IL2RA (p < 0.001) and FLT3 (p = 0.008) expressions remained significant in predicting shorter RFS, whereas ERG (p = 0.008) and IL2RA (p = 0.044) remained significant in predicting shorter OS. Similar analyses in TCGA intermediate-risk AML showed the independent prognostic role of IL2RA in predicting event free survival (p < 0.001) and OS (p < 0.001). CONCLUSIONS: High IL2RA mRNA expression is an independent and adverse prognostic factor in AML and specifically stratifies patients to worse prognosis in both CBF and intermediate-risk AML.


Assuntos
Biomarcadores Tumorais/genética , Subunidade alfa de Receptor de Interleucina-2/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Adolescente , Adulto , Idoso , Estudos de Coortes , Fatores de Ligação ao Core/genética , Feminino , Perfilação da Expressão Gênica , Regulação Leucêmica da Expressão Gênica , Humanos , Cariotipagem , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Projetos Piloto , Prognóstico , Fatores de Risco , Adulto Jovem
15.
Analyst ; 144(4): 1253-1259, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30542691

RESUMO

Lipopolysaccharides (LPS), known as endotoxins, can cause a strong inflammatory response and lead to multiple organ failure in severe cases. This work reports a simple label-free voltammetric aptasensor for highly sensitive determination of LPS using a polyethyleneimine (PEI) functionalized reduced graphene oxide (rGO) and molybdenum disulfide (MoS2) composite (PEI-rGO-MoS2) as a new nanocarrier for electroactive toluidine blue (TB). The PEI-rGO-MoS2 nanocomposite with high electrical conductivity and large specific surface area can greatly increase the loading of TB and facilitate electron transfer from TB to an electrode. Then gold nanoparticles (AuNPs) were utilized to immobilize a thiolated LPS binding aptamer (LBA), which not only exhibited excellent biocompatibility, but also significantly amplified the electrochemical signal of TB. The proposed aptasensor exhibited high sensitivity for LPS and showed a wide linear range from 5.0 × 10-5 ng mL-1 to 2.0 × 102 ng mL-1 with a low limit of detection (LOD) of 3.01 × 10-5 ng mL-1, which overcame the shortcomings of traditional detection methods and achieved fast and accurate detection of LPS. Moreover, it exhibited excellent recovery and specificity upon spiking LPS in serum samples, indicating that this method has promising application in the field of trace analysis of LPS in clinical detection.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Dissulfetos/química , Técnicas Eletroquímicas/métodos , Grafite/química , Lipopolissacarídeos/análise , Molibdênio/química , Nanocompostos/química , Limite de Detecção , Lipopolissacarídeos/sangue , Propriedades de Superfície
16.
Cell Immunol ; 323: 19-32, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29111157

RESUMO

Angiogenesis is an organized series of events, beginning with vessel destabilization, followed by endothelial cell re-organization, and ending with vessel maturation. The formation of a mature vascular network requires precise spatial and temporal regulation of a large number of angiogenic factors, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor (PDGF). VEGF aids in vascular permeability and endothelial cell recruitment, FGF-2 activates endothelial cell proliferation and migration while PDGF stimulates vascular stability. Accordingly, VEGF may inhibit vessel stabilization while PDGF may inhibit endothelial cell recruitment. Therefore, a new polymeric system was prepared by the supercritical carbon dioxide foaming technology, which realized sequential delivery of two or more growth factors with the controlled dose and rate. Increased release of VEGF (71.10%) and FGF-2 (69.76%) compared to PDGF (43.17%) was observed for the first 7 days. Thereafter, up till 21 days, an increased rate of release of BMP-2 compared to VEGF 165 was observed. The effects of PDGF-PLAms/VEGF-FGF-2-PLGA scaffolds on angiogenesis were investigated by human umbilical vein endothelial cells (HUVECs) angiogenic differentiation in vitro and chorioallantoic membrane (CAM) angiogenesis in vivo. Sequential delivery of VEGF, FGF-2 and PDGF from structural polymer scaffolds with distinct kinetics resulted in significant angiogenic differentiation of HUVECs and rapid formation of mature vascular networks in chorioallantoic membrane. This study reported a composite scaffold with distinct release kinetics, and these results clearly indicated the importance of sequential delivery of multiple growth factors in tissue regeneration and engineering.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Neovascularização Fisiológica/efeitos dos fármacos , Fator de Crescimento Derivado de Plaquetas/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Indutores da Angiogênese/administração & dosagem , Indutores da Angiogênese/metabolismo , Proteína Morfogenética Óssea 2/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Membrana Corioalantoide , Preparações de Ação Retardada , Fator 2 de Crescimento de Fibroblastos/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Fator de Crescimento Derivado de Plaquetas/metabolismo , Poliésteres/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Mikrochim Acta ; 185(8): 379, 2018 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-30019137

RESUMO

The 6-kDa early secretory antigenic target referred to as ESAT-6 is a virulence factor secreted by Mycobacterium tuberculosis (MTB). This work describes a voltammetric aptasensor for ultrasensitive detection of ESAT-6. Reduced graphene oxide doped with metal-organic framework (MOF-rGO) was deposited on a glassy carbon electrode (GCE). This increases the immobilization of electroactive Toluidine Blue (TB) and facilitates the electron transfer from TB to the modified GCE. Platinum/gold core/shell (Pt@Au) nanoparticles were used to assemble thiolated ESAT-6 binding aptamer (EBA) on a modified electrode and to further amplify the response to TB. The modified GCE, typically operated at -0.36 V (vs. SCE), has a linear response in 1.0 × 10-4 to 2.0 × 102 ng⋅mL-1 ESAT-6 concentration range, and the limit of detection (LOD) for ESAT-6 is as low as 3.3 × 10-5 ng⋅mL-1. It exhibits satisfactory specificity and reproducibility when analyzing spiked human serum. Graphical abstract Schematic presentation of a voltammetric aptasensor for Mycobacterium tuberculosis antigen ESAT-6 using a glassy carbon electrode modified with reduced graphene oxide (rGO) and a metal-organic framework (MOF). The limit of detection for ESAT-6 is as low as 3.3 × 10-5 ng/mL.


Assuntos
Antígenos de Bactérias/sangue , Aptâmeros de Nucleotídeos/química , Proteínas de Bactérias/sangue , Técnicas Biossensoriais , Técnicas Eletroquímicas/métodos , Grafite/química , Estruturas Metalorgânicas/química , Carbono/química , Eletrodos , Ouro/química , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Nanocompostos/química , Oxirredução , Tamanho da Partícula , Platina/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Propriedades de Superfície
18.
Mikrochim Acta ; 186(1): 1, 2018 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-30515617

RESUMO

This work describes a voltammetric and ultrasensitive aptasensor for sulfadimethoxine (SDM). It is based on signal amplification by making use of a multifunctional fullerene-doped reduced graphene oxide nanohybrid. The nanohybrid was coated with poly(diallyldimethylammonium chloride) to obtain a material (P-C60-rGO) with large specific surface area and a unique adsorption ability for loading it with glucose oxidase (GOx). The coating also facilitates the direct electron transfer between the active site of GOx and the glassy carbon electrode (GCE). The P-C60-rGO were then modified with Pt@Au nanoparticles, and the thiolated SDM-binding aptamer was immobilized on the nanoparticles. On exposure of the modified GCE to a solution containing SDM, it binds to the aptamer. The results were recorded through the signal responses generated from the redox center of GOx (FAD/FADH2) by cyclic voltammetry at a scan rate of 100 mV·s-1 from -0.25 to -0.65 V. Accordingly, The sensor has good specificity and stability, and response is linear in the 10 fg·mL-1 to 50 ng·mL-1 SDM concentration range with a detection limit of 8.7 fg·mL-1. Graphical abstract Schematic presentation of an electrochemical aptasensor for sulfadimethoxine (SDM) using multifunctional fullerene-doped graphene (C60-rGO) nanohybrids for amplification. The limit of detection for SDM is as low as 8.7 fg·mL-1.


Assuntos
Fulerenos/química , Glucose Oxidase/química , Grafite/química , Nanoestruturas/química , Polietilenos/química , Compostos de Amônio Quaternário/química , Sulfadimetoxina/análise , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Domínio Catalítico , Técnicas Eletroquímicas/métodos , Eletrodos , Transporte de Elétrons , Ouro/química , Limite de Detecção , Oxirredução , Tamanho da Partícula , Platina/química , Propriedades de Superfície
19.
Mol Carcinog ; 56(12): 2692-2705, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28833571

RESUMO

Epithelial-mesenchymal transition (EMT) has emerged as an important determinant role in colorectal cancer (CRC) metastasis. It has been reported that aquaporin 5 (AQP5) is closely linked to CRC metastasis. However, the effect of AQP5 on the EMT process of CRC remains unknown. The current study showed that overexpression of AQP5 activated EMT in CRC cells. Cairicoside E (CE), a natural resin glycoside compound isolated from Ipomoea cairica, showed promising cytotoxic activity in our previous report. Further investigation found that CE inhibited the expression of AQP5 and the EMT process. Moreover, the inhibitory effect of CE on EMT was reversed by overexpression of AQP5. Importantly, CE also suppressed the EMT and p-Smad2/3 induced by TGF-ß1. On the other hand, overexpression of AQP5 up-regulated the p-Smad2/3, which resulted in the activation of EMT. After silencing of AQP5, CE had no significant effect on EMT markers and p-Smad2/3 induced by TGF-ß1, indicating that CE inhibited the EMT through down-regulation of AQP5 and suppression of p-Smad2/3. CE also inhibited the AQP5 expression in the lung metastatic nodules of HCT-116 cells in vivo. Our findings suggested that CE may serve as a promising drug for the treatment of CRC metastasis.


Assuntos
Aquaporina 5/genética , Produtos Biológicos/farmacologia , Neoplasias Colorretais/genética , Regulação para Baixo/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glicolipídeos/farmacologia , Animais , Aquaporina 5/metabolismo , Produtos Biológicos/química , Western Blotting , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicolipídeos/química , Células HCT116 , Células HEK293 , Células HT29 , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Metástase Neoplásica , Interferência de RNA , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Small ; 10(9): 1857-65, 2014 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-24554632

RESUMO

A novel functionalized material is synthesized using surface-decorated fullerene (C60) to encapsulate hollow and porous palladium nanocages (PdNCs), and is applied to fabricate an electrochemiluminescence (ECL) immunosensor for the detection of Streptococcus suis Serotype 2 (SS2). PdNCs with hollow interiors and porous walls are prepared using a galvanic replacement reaction between silver nanocubes and metal precursor salts. Then, C60 reacts with L-cysteine (L-Cys) to form L-Cys functionalized C60 (C60-L-Cys), which has a better biocompatibility, conductivity, and hydrophilicity compared to C60 and possesses abundant -SH groups on the surface. Because of the special interaction between -SH and PdNCs, the obtained C60-L-Cys is adsorbed around the PdNCs to form an interesting structure with multiple spheres encapsulating the cage. The resultant functionalized material (C60 -L-Cys-PdNCs) has a high specific surface area, good electrocatalytic ability, and efficient photocatalytic activity, and is used to construct an ECL immunosensor for the detection of SS2. The ECL signal amplified strategy is performed by using the novel coreactant (C60-L-Cys) and in situ generation of O2 thus creating the S2O8(2-)-O2 ECL system. As a result, a wide linear detection range of 0.1 pg mL(-1) to 100 ng mL(-1) is acquired with a relatively low detection limit of 33.3 fg mL(-1).


Assuntos
Técnicas Biossensoriais/instrumentação , Fulerenos/química , Imunoensaio/instrumentação , Medições Luminescentes/instrumentação , Nanopartículas/química , Paládio/química , Streptococcus suis/isolamento & purificação , Glucose/análise , Humanos , Microscopia de Força Atômica , Nanopartículas/ultraestrutura , Espectroscopia Fotoeletrônica , Reprodutibilidade dos Testes , Sorogrupo
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