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1.
J Magn Reson Imaging ; 59(3): 998-1007, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37334908

RESUMO

BACKGROUND: Carotid stenosis, even in the clinically asymptomatic stage, causes cognitive impairment, silent lesions, and hemispheric changes. The corpus callosum (CC) is crucial for hemispheric cortical integration and specialization. PURPOSE: To examine if CC morphology and connectivity relate to cognitive decline and lesion burden in asymptomatic carotid stenosis (ACS). STUDY TYPE: Retrospective, cross-sectional. POPULATION: 33 patients with unilaterally severe (70%) ACS and 28 demographically and comorbidity-matched controls. A publicly available healthy adult lifespan (ages between 18 and 80; n = 483) MRI dataset was also included. FIELD STRENGTH/SEQUENCE: A 3.0 T; T1 MPRAGE and diffusion weighted gradient echo-planar imaging sequences. ASSESSMENT: Structural MRI and multidomain cognitive data were obtained. Midsagittal CC area, circularity, thickness, integrity, and probabilistic tractography were calculated and correlated with cognitive tests and white matter hyperintensity. Fractional anisotropy, mean diffusivity (MD), and radial diffusivity were determined from DTI. STATISTICAL TESTS: Independent two-sample t-tests, χ2 tests, Mann-Whitney U, locally weighted scatterplot smoothing (LOWESS) curve fit, and Pearson correlation. A P value < 0.05 was considered statistically significant. RESULTS: Patients with ACS demonstrated significant reductions in callosal area, circularity, and thickness compared to controls. The callosal atrophy was significantly correlated with white matter hyperintensity size (r = -0.629, P < 0.001). Voxel-wise analysis of diffusion measures in the volumetric CC showed that ACS patients exhibited significantly lower fractional anisotropy and higher MD and radial diffusivity in the genu and splenium of the CC than controls. Further lifespan trajectory analysis showed that although the midsagittal callosal area, circularity, and thickness exhibited age-related decreases, the values in the ACS patients were significantly lower in all age groups. DATA CONCLUSION: Midsagittal callosal atrophy and connectivity reflect the load of silent lesions and the severity of cognitive decline, respectively, suggesting that CC degeneration has potential to serve as an early marker in ACS. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.


Assuntos
Estenose das Carótidas , Adulto , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estenose das Carótidas/patologia , Estudos Transversais , Estudos Retrospectivos , Corpo Caloso , Atrofia/patologia
2.
Eur Radiol ; 31(11): 8197-8207, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33914116

RESUMO

OBJECTIVE: To evaluate the potential of diffusional variance decomposition (DIVIDE) for grading, molecular feature classification, and microstructural characterization of gliomas. MATERIALS AND METHODS: Participants with suspected gliomas underwent DIVIDE imaging, yielding parameter maps of fractional anisotropy (FA), mean diffusivity (MD), anisotropic mean kurtosis (MKA), isotropic mean kurtosis (MKI), total mean kurtosis (MKT), MKA/MKT, and microscopic fractional anisotropy (µFA). Tumor type and grade, isocitrate dehydrogenase (IDH) 1/2 mutant status, and the Ki-67 labeling index (Ki-67 LI) were determined after surgery. Statistical analysis included 33 high-grade gliomas (HGG) and 17 low-grade gliomas (LGG). Tumor diffusion metrics were compared between HGG and LGG, among grades, and between wild and mutated IDH types using appropriate tests according to normality assessment results. Receiver operating characteristic and Spearman correlation analysis were also used for statistical evaluations. RESULTS: FA, MD, MKA, MKI, MKT, µFA, and MKA/MKT differed between HGG and LGG (FA: p = 0.047; MD: p = 0.037, others p < 0.001), and among glioma grade II, III, and IV (FA: p = 0.048; MD: p = 0.038, others p < 0.001). All diffusion metrics differed between wild-type and mutated IDH tumors (MKI: p = 0.003; others: p < 0.001). The metrics that best discriminated between HGG and LGGs and between wild-type and mutated IDH tumors were MKT and FA respectively (area under the curve 0.866 and 0.881). All diffusion metrics except FA showed significant correlation with Ki-67 LI, and MKI had the highest correlation coefficient (rs = 0.618). CONCLUSION: DIVIDE is a promising technique for glioma characterization and diagnosis. KEY POINTS: • DIVIDE metrics MKI is related to cell density heterogeneity while MKA and µFA are related to cell eccentricity. • DIVIDE metrics can effectively differentiate LGG from HGG and IDH mutation from wild-type tumor, and showed significant correlation with the Ki-67 labeling index. • MKI was larger than MKA which indicates predominant cell density heterogeneity in gliomas. • MKA and MKI increased with grade or degree of malignancy, however with a relatively larger increase in the cell eccentricity metric MKA in relation to the cell density heterogeneity metric MKI.


Assuntos
Neoplasias Encefálicas , Glioma , Anisotropia , Neoplasias Encefálicas/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Glioma/diagnóstico por imagem , Glioma/genética , Humanos , Gradação de Tumores
3.
J Sep Sci ; 44(9): 1852-1865, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33646615

RESUMO

Low-dose methotrexate is the first-line therapy for juvenile idiopathic arthritis. In vivo, methotrexate is converted into a series of methotrexate polyglutamates whose intracellular levels contribute significantly to its efficacy and toxicity. In this study, a novel high-performance liquid chromatography-tandem mass spectrometry method was developed and validated to simultaneously determine erythrocyte methotrexate polyglutamates using stable isotope-labeled internal standards. Erythrocyte samples were precipitated by perchloric acid and then determined on an XBridge BEH C18 column with an XP vanguard precolumn in 12 min. The mobile phase consisted of 10 nM ammonium acetate (pH 10) and methanol under gradient elution. The detection was carried out in multiple reaction monitoring mode via an electrospray ionization source in positive ionization mode. The calibration curve for each metabolite was linear from 2.0 to 500.0 nmol/L (r2  > 0.99). The intraday and interday accuracies were between 93.0 and 107.0%, and the corresponding precisions were between 0.8 and 5.2%. The relative recovery ranged from 82.7 to 105.1%, and the relative matrix effect varied from 96.5 to 104.4%. The erythrocyte metabolites were stable for 30 days at -80°C. This simple and accurate method is applicable to routine monitoring of the concentration of erythrocyte methotrexate polyglutamates in patients to achieve individualized treatment.


Assuntos
Eritrócitos/química , Metotrexato/análogos & derivados , Ácido Poliglutâmico/análogos & derivados , Cromatografia Líquida de Alta Pressão , Humanos , Marcação por Isótopo , Metotrexato/análise , Ácido Poliglutâmico/análise , Espectrometria de Massas em Tandem
4.
Mol Med ; 26(1): 55, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32517686

RESUMO

BACKGROUND: With the advance of antibiotics and life support therapy, the mortality of sepsis has been decreasing in recent years. However, the incidence of sepsis-associated encephalopathy (SAE), a common complication of sepsis, is still high. There are few effective therapies to treat clinical SAE. We previously found that ethyl pyruvate (EP), a metabolite derivative, is able to effectively inhibit the NLRP3 inflammasome activation. Administration of ethyl pyruvate protects mice against polymicrobial sepsis in cecal ligation and puncture (CLP) model. The aim of present study is to investigate if ethyl pyruvate is able to attenuate SAE. METHODS: After CLP, C57BL/6 mice were intraperitoneally or intrathecally injected with saline or ethyl pyruvate using the sham-operated mice as control. New Object Recognition (NOR) and Morris Water Maze (MWM) were conducted to determine the cognitive function. Brain pathology was assessed via immunohistochemistry. To investigate the mechanisms by which ethyl pyruvate prevent SAE, the activation of NLRP3 in the hippocampus and the microglia were determined using western blotting, and cognitive function, microglia activation, and neurogenesis were assessed using WT, Nlrp3-/- and Asc-/- mice in the sublethal CLP model. In addition, Nlrp3-/- and Asc-/- mice treated with saline or ethyl pyruvate were subjected to CLP. RESULTS: Ethyl pyruvate treatment significantly attenuated CLP-induced cognitive decline, microglia activation, and impaired neurogenesis. In addition, EP significantly decreased the NLRP3 level in the hippocampus of the CLP mice, and inhibited the cleavage of IL-1ß induced by NLRP3 inflammsome in microglia. NLRP3 and ASC deficiency demonstrated similar protective effects against SAE. Nlrp3-/- and Asc-/- mice significantly improved cognitive function and brain pathology when compared with WT mice in the CLP models. Moreover, ethyl pyruvate did not have additional effects against SAE in Nlrp3-/- and Asc-/- mice. CONCLUSION: The results demonstrated that ethyl pyruvate confers protection against SAE through inhibiting the NLRP3 inflammasome.


Assuntos
Inflamassomos/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Substâncias Protetoras/farmacologia , Piruvatos/farmacologia , Encefalopatia Associada a Sepse/metabolismo , Encefalopatia Associada a Sepse/prevenção & controle , Animais , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Injeções Espinhais , Masculino , Camundongos , Microglia/efeitos dos fármacos , Microglia/imunologia , Microglia/metabolismo , Neurônios/imunologia , Neurônios/metabolismo , Neurônios/patologia , Substâncias Protetoras/administração & dosagem , Piruvatos/administração & dosagem , Encefalopatia Associada a Sepse/diagnóstico , Encefalopatia Associada a Sepse/etiologia
5.
Biochem Biophys Res Commun ; 533(4): 1519-1526, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33158480

RESUMO

Cognitive impairment, acute or long-term, is a common complication in patients with severe bacterial infection. However, the underlying mechanisms are not fully verified and effective medicine is not available in clinics. Interferon gamma (IFNγ) is a pivotal cytokine against infection and is believed to be a tune in homeostasis of cognitive function. Here, we collected blood and cerebrospinal fluid (CF) from human subjects and mice, and found that plasma and CF levels of IFNγ were significantly increased in septic patients and endotoxin-challenged mice when compared with healthy controls. IFNγ signaling was boosted in the hippocampus of mice after a challenge of lipopolysaccharide (LPS), which was accompanied with cognitive impairment and decline of neurogenesis. Deficiency of IFNγ or its receptor (IFNγR) dramatically attenuated microglia-induced A1 astrocytes and consequently restored neurogenesis and cognitive function in endotoxemia mice model. Using primary microglia, astrocytes and neurons, we found that IFNγ remarkably increased LPS-mediated release of TNFα and IL-1α in microglia and consequently induced the transformation of astrocyte to A1 subtype, which ultimately resulted in neuron damage. Thus, IFNγ promotes cognitive impairment in endotoxemia by enhancing microglia-induced A1 astrocytes. Targeting IFNγ would be a novel strategy for preventing or treating cognitive dysfunction in patients with Gram-negative infection.


Assuntos
Astrócitos/fisiologia , Disfunção Cognitiva/fisiopatologia , Endotoxemia/fisiopatologia , Interferon gama/antagonistas & inibidores , Neurogênese/fisiologia , Animais , Astrócitos/patologia , Estudos de Casos e Controles , Células Cultivadas , Disfunção Cognitiva/genética , Disfunção Cognitiva/terapia , Modelos Animais de Doenças , Endotoxemia/genética , Endotoxemia/psicologia , Inativação Gênica , Humanos , Interferon gama/deficiência , Interferon gama/genética , Interferon gama/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/patologia , Microglia/fisiologia , Neurogênese/genética , Terapêutica com RNAi , Receptores de Interferon/deficiência , Receptores de Interferon/genética , Receptores de Interferon/fisiologia , Receptor de Interferon gama
6.
J Acoust Soc Am ; 148(1): EL14, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32752752

RESUMO

This study compares event-related potentials (ERPs) elicited by variations of sound location in free and reverberant fields. The virtual sound sources located at azimuths 0°-40° were synthesized with head-related transfer functions and binaural room impulse responses for free and reverberant fields, respectively. The sound stimulus at 0° was assigned as standard in the oddball paradigm. Results show that the P3 amplitude is larger in the free field and acoustical conditions have no significant effect on the amplitudes of N2 and mismatch negativity. Moreover, a linear relationship between sound angle and amplitude of ERP components is observed.


Assuntos
Localização de Som , Estimulação Acústica , Eletroencefalografia , Potenciais Evocados , Potenciais Evocados Auditivos , Som
7.
Anal Chem ; 91(10): 6487-6497, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31037939

RESUMO

This study reports a novel and convenient bimodal method for label-free and signal-off detection of arsenate in environmental samples. Cobalt oxyhydroxide (CoOOH) nanoflakes with facile preparation and intrinsic peroxidase-like activity as nanozyme can efficiently catalyze the conversion of chromogenic substrate such as 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) with the presence of H2O2 into green-colored oxidation products. CoOOH nanoflakes can specifically bind with arsenate via electrostatic attraction and As-O bond interaction, which gives rise to inhibition of the peroxidase-like activity of CoOOH. Thus, through arsenate specific inhibition of CoOOH nanozyme toward ABTS catalysis, a simple colorimetric method was developed for arsenate detection with a detection limit of 3.72 ppb. Based on the system of CoOOH nanozyme and ABTS substrate, this colorimetric method can be converted into an electrochemical sensor for arsenate assay by the utilization of CoOOH nanoflake-modified electrode. The electrochemical measurement can be realized by chronoamperometry, which showed more sensitive and a lower limit of detection as low as 56.1 ppt. The applicability of this bimodal method was demonstrated by measuring arsenate and total arsenic in different real samples such as natural waters and soil extracted solutions, and the results are of satisfactory accuracy as confirmed by inductively coupled plasma mass spectrometry analysis. The bimodal strategy offers obvious advantages including a label-free step, convenient operation, on-site assay, low cost, and high sensitivity, which is promising for reliable detection of arsenate and total arsenic in environmental samples.


Assuntos
Arseniatos/química , Cobalto/química , Colorimetria/métodos , Óxidos/química , China , Técnicas Eletroquímicas , Poluentes Ambientais/química , Poluição Ambiental , Nanoestruturas , Poluição da Água
8.
J Sep Sci ; 42(4): 816-825, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30580494

RESUMO

An ultra high performance liquid chromatography with triple quadrupole mass spectrometry method for the determination of free and bound phenolic acids in tobacco plant and soil was developed. A simple solid-phase extraction, which used Polar Enhanced Polymer column as stationary phase and methanol as mobile phase, was used for the clean-up of bound phenolic acids, and a liquid-phase extraction using chloroform as solvent was used to purify free phenolic acids. With our method, 18 phenolic acids in rhizosphere soil of continuous cropping flue-cured cultivar k326 were separated and determined within 6 min with recoveries of 82-107% and relative standard deviations (n = 5) of 1.1-4.8%. Results showed that free phenolic acids accounted for 0-9, 92-100, and 69-100% of total phenolic acids in rhizosphere soil, cultivar k326 roots and leaves, respectively. Results also revealed that p-hydroxybenzoic acid, p-coumaric acid, vanillic acid, ferulic acid, and syringic acid were the predominant phenolic acids in rhizosphere soil of cultivar k326, and continuous cropping of cultivar k326 in the same farmland could lead to the accumulation of these phenolic acids in soil except syringic acid. The determination of phenolic acids provided detailed information for evaluating their source and characteristics in continuous cropping tobacco plant and soil.


Assuntos
Hidroxibenzoatos/análise , Nicotiana/química , Solo/química , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Rizosfera
9.
Mikrochim Acta ; 186(11): 732, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31667627

RESUMO

The authors describe an electrochemical and an optical method for the determination of As(V) by using iron oxyhydroxide (FeOOH) nanorods that display peroxidase-mimicking activity. The nanorods catalyze the oxidation of substrate ABTS by H2O2 to form a green product with an absorption maximum at 418 nm. If, however, As(V) is electrostatically adsorbed on the nanorods, the oxidation is gradually inhibited. A colorimetric assay was worked out based on these findings. Response is linear in the 0 to 8 ppb and 8 to 200 ppb As(V) concentration range, and the detection limit is 0.1 ppb. Even higher sensitivity is achieved in an electrochemical method which is based on the excellent electrical conductivity of FeOOH nanorods. Electrochemical analysis of As(V) was achieved by first adsorbing As(V) on the nanorods. This inhibits the ABTS reduction current signal, best measured at a potential of 150 mV (vs. Ag/AgCl). The linear range extends from 0.04 to 200 ppb, and the detection limit is as low as 12 ppt. Graphical abstract Schematic representation of FeOOH nanorod-based colorimetric and electrochemical assays for arsenate (As(V)). As(V) adsorbed on FeOOH nanorods inhibits the peroxidase-mimicking activity of nanorods, and a colorimetric and electrochemical dual-signal assay was constructed to achieve sensitive determination of As(V).


Assuntos
Arseniatos/análise , Colorimetria/métodos , Técnicas Eletroquímicas/métodos , Compostos Férricos/química , Nanotubos/química , Poluentes Químicos da Água/análise , Benzotiazóis/química , Materiais Biomiméticos/química , Catálise , Água Potável/análise , Peróxido de Hidrogênio/química , Lagos/análise , Limite de Detecção , Peroxidase/química , Rios/química , Ácidos Sulfônicos/química
10.
Mikrochim Acta ; 186(4): 241, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30868262

RESUMO

The activity of terminal deoxynucleotidyl transferase (TdTase) is a biomarker for routine diagnosis of acute leukemia. A method has been developed for the determination of TdTase activity. It is based on the use of silver nanoclusters (AgNCs) whose yellow fluorescence is enhanced by an in-situ grown DNA tail of TdTase-polymerized and guanine-rich DNA at the 3' end of a hairpin DNA. The fluorescence, best measured at excitation/emission peaks of 530/585 nm, increases linearly in the 1 to 35 mU mL-1 TdTase activity range. The detection limit is 0.8 mU mL-1. The method is cost-efficient, selective and convenient. It integrates enhancement of the fluorescence of AgNCs and target recognition into a single process. Graphical abstract Schematic presentation of a method for determination of TdTase activity. It is based on AgNCs fluorescence enhanced by in-situ grown TdTase-polymerized G-rich DNA tail. The method integrates AgNCs fluorescence enhancement and the target recognition into a single process.


Assuntos
DNA Nucleotidilexotransferase/sangue , DNA/química , Ensaios Enzimáticos/métodos , Nanopartículas Metálicas/química , Sequência de Bases , Biomarcadores/sangue , Técnicas Biossensoriais/métodos , DNA/genética , Fluorescência , Humanos , Sequências Repetidas Invertidas , Leucemia/diagnóstico , Limite de Detecção , Prata/química , Espectrometria de Fluorescência/métodos
11.
Mol Cancer ; 17(1): 78, 2018 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-29625565

RESUMO

BACKGROUND: SALL1 is a multi-zinc finger transcription factor that regulates organogenesis and stem cell development, but the role of SALL1 in tumor biology and tumorigenesis remains largely unknown. METHODS: We analyzed SALL1 expression levels in human and murine breast cancer cells as well as cancer tissues from different types of breast cancer patients. Using both in vitro co-culture system and in vivo breast tumor models, we investigated how SALL1 expression in breast cancer cells affects tumor cell growth and proliferation, metastasis, and cell fate. Using the gain-of function and loss-of-function strategies, we dissected the molecular mechanism responsible for SALL1 tumor suppressor functions. RESULTS: We demonstrated that SALL1 functions as a tumor suppressor in breast cancer, which is significantly down-regulated in the basal like breast cancer and in estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2) triple negative breast cancer patients. SALL1 expression in human and murine breast cancer cells inhibited cancer cell growth and proliferation, metastasis, and promoted cell cycle arrest. Knockdown of SALL1 in breast cancer cells promoted cancer cell growth, proliferation, and colony formation. Our studies revealed that tumor suppression was mediated by recruitment of the Nucleosome Remodeling and Deacetylase (NuRD) complex by SALL1, which promoted cancer cell senescence. We further demonstrated that the mechanism of inhibition of breast cancer cell growth and invasion by SALL1-NuRD depends on the p38 MAPK, ERK1/2, and mTOR signaling pathways. CONCLUSION: Our studies indicate that the developmental control gene SALL1 plays a critical role in tumor suppression by recruiting the NuRD complex and thereby inducing cell senescence in breast cancer cells.


Assuntos
Regulação para Baixo , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Senescência Celular , Técnicas de Cocultura , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Camundongos , Metástase Neoplásica , Transplante de Neoplasias , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo
13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(6): 1740-4, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-30052383

RESUMO

Surface-enhanced Raman scattering (SERS) is spectroscopic technique with ultra-sensitivity and high selectivity and has attracted great attention because of the potential applications in various fields. P-aminothiophenol (PATP) is often used as SERS probe molecule because it is easy to adsorb on SERS substrates and produce high-quality SERS signals. TiO2 is extensively used as photocatalyst although its photocatalytic efficiency is still needed to be improved. Noble metal-modified TiO2 is one of current important techniques for maximizing the efficiency of photocatalytic efficiency. In this article, a kind of bifunctional SERS substrates, Ag/TiO2 nanotubes, with photocatalysis property were prepared, the TiO2 NTs were prepared by anodic oxidation and noble metal Ag nanoparticles were deposited on the surface of TiO2 NTs by photoreduction method. The photocatalysis of PATP on Ag/TiO2 NTs and on Ag mirror substrates were studied. The SERS signals of PATP were decreased with the ultraviolet irradiation time, however, on Ag mirror substrates, SERS intensity of PATP was slightly changed, which indicated the photocatalysis reaction of PATP on Ag/TiO2 NTs substrates. The kinetics analysis results indicate that the kinetics of the photocatalysis follows the first order of the dynamical reaction.

14.
J Biol Chem ; 289(52): 36101-15, 2014 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-25371200

RESUMO

Ascl2, a basic helix-loop-helix transcription factor, is a downstream target of WNT signaling that controls the fate of intestinal cryptic stem cells and colon cancer progenitor cells. However, its involvement in colon cancer and downstream molecular events is largely undefined; in particular, the mechanism by which Ascl2 regulates the plasticity of epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) programs in colon cancer cells remains unknown. In this study, we systematically demonstrate that Ascl2 loss of function in colon cancer cells promotes MET by derepressing the expression of microRNA (miR)-200s (i.e. miR-200b, miR-200a, miR-429, miR-200c, and miR-141) and further activating their expression through a transcriptional mechanism that involves direct binding to the most proximal E-box (E-box2) in the miR-200b-a-429 promoter. Activation of miR-200s due to Ascl2 deficiency led to the inhibition of ZEB1/2 expression and the alteration of epithelial and mesenchymal features. Transfection of miR-200b, miR-200a, and miR-429 inhibitors into Ascl2-deficient colon cancer cells promoted the epithelial-mesenchymal transition in a reversible manner. Transfection of miR-200a or miR-429 inhibitors into Ascl2-deficient colon cancer cells increased cellular proliferation and migration. Ascl2 mRNA levels and the miR-200a, miR-200b, miR-200c, miR-141, or miR-429 levels in the colon cancerous samples were inversely correlated. These results provide the first evidence of a link between Ascl2 and miR-200s in the regulation of EMT-MET plasticity in colon cancer.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Neoplasias do Colo/metabolismo , Transição Epitelial-Mesenquimal , MicroRNAs/genética , Idoso , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células HT29 , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Metástase Linfática , Masculino , MicroRNAs/biossíntese , Pessoa de Meia-Idade , Família Multigênica , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica , Homeobox 2 de Ligação a E-box com Dedos de Zinco , Homeobox 1 de Ligação a E-box em Dedo de Zinco
15.
Dig Dis Sci ; 60(7): 1977-90, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25701318

RESUMO

BACKGROUND AND AIM: The roles of host glycosylation in interactions with EPEC and EHEC O157:H7 are largely unclear; this study examined whether O-glycans are involved in EPEC and EHEC O157:H7 adherence to HT-29 cells. METHODS: Bacterial adherence to the cultured cells was determined using the direct co-staining of adherent bacteria and host cells, the adherent bacteria plating, and/or the direct fluorescent observation of the adherent GFP-labeled bacteria. RESULTS: A comparison of the adherence of EPEC and EHEC O157:H7 to HT-29-Gal and HT-29 cells indicated that the differentiation of HT-29 cells led to a reduction in the adherence of EPEC and EHEC O157:H7. EPEC and EHEC O157:H7 adhesion decreased after the abrogation of O-glycan biosynthesis mediated by benzyl-α-GalNAc treatment. Core 2 O-glycan-deficient HT-29 cells induced by C2GnT2 knockdown had a significant reduction in EPEC and EHEC O157:H7 adhesion in C2GnT2-sh2/HT-29 cells compared with HT-29 and shRNA-Ctr/HT-29 cells. MUC2 expression in benzyl-α-GalNAc-treated HT-29 cells was significantly reduced but unchanged in C2GnT2-deficient HT-29 cells. EPEC or EHEC O157:H7 infection in C2GnT2-deficient HT-29 cells deteriorated the epithelial barrier function. The occludin expression in the shRNA-Ctr/HT-29 and C2GnT2-sh2/HT-29 cells after infection with EPEC or EHEC O157:H7 was pyknic and discontinuous at the cell surface compared with its continuous distribution of control cells. These data indicate that EPEC and EHEC O157:H7 adherence to HT-29 cells is related to mucin-type core 2 O-glycan. CONCLUSIONS: This study provides the concepts toward the design of carbohydrate-dependent inhibition of EPEC and EHEC O157:H7 adhesion to human intestinal epithelial cells.


Assuntos
Aderência Bacteriana/fisiologia , Escherichia coli Êntero-Hemorrágica/metabolismo , Escherichia coli Enteropatogênica/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Acetilgalactosamina/análogos & derivados , Acetilgalactosamina/farmacologia , Anticorpos , Compostos de Benzil/farmacologia , Escherichia coli Êntero-Hemorrágica/genética , Escherichia coli Enteropatogênica/genética , Células HT29 , Humanos , Mucina-2/genética , Mucina-2/metabolismo , N-Acetilglucosaminiltransferases/genética , Interferência de RNA
16.
Anal Methods ; 16(18): 2850-2856, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38644726

RESUMO

Early diagnostics and therapies for diseases such as cancer are limited by the fact that the inducing factors for the development of cytopathies are not clear. The stable polarity of lipid droplets is a potential biomarker for tumor cells; however, the complex intracellular biological environment poses great difficulties for specific detection of the polarity. Therefore, to meet this pressing challenge, we designed a highly selective fluorescent probe, DCI-Cou-polar, which used the ICT mechanism to differentiate normal cells and tumor cells in tissue sections by detecting changes in the polarities of intracellular lipid droplets. The introduction of a cyclic amine at the 7-position of coumarin (benzoquinolizine coumarin) reduced its ability to donate electrons compared with the diethylamino group, which increased the probe selectivity while retaining the sensitivity to polarity. With NIR emission and large Stokes shifts, DCI-Cou-polar has high sensitivity to polarity, excellent photostability, and biocompatibility, and it tracks lipid droplets with high fidelity. Therefore, we believe that this polarity-sensitive probe provides information on the connection between the polarity of lipid droplets and tumors while improving the development of highly selective polarity probes.


Assuntos
Cumarínicos , Corantes Fluorescentes , Corantes Fluorescentes/química , Humanos , Cumarínicos/química , Animais , Gotículas Lipídicas/química , Neoplasias/patologia , Camundongos , Polaridade Celular , Linhagem Celular Tumoral
17.
Front Psychol ; 15: 1347249, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38356774

RESUMO

Background: Nurses are the largest occupational group in the health field, with inestimable value in realizing universal health coverage, and nurses' physical and mental health has become an ordinary global reality. Compared with explicit absence, nurses' presenteeism has a more lasting impact and significant harm and loss. It has become an essential factor affecting nurses' physical and mental health, declining quality of healthcare services, and elevated healthcare-related risks. There is a lack of research exploring whether occupational coping self-efficacy influences nurses' presenteeism behavior, especially in less-developed regions of China. Objective: This study aimed to investigate the current status of ICU nurses' occupational coping self-efficacy and presenteeism in public hospitals in western China and to explore the impact of ICU nurses' occupational coping self-efficacy on presenteeism. Methods: A cross-sectional research design selected 722 ICU nurses in western China from January to February 2023 as survey respondents. A general information questionnaire, Occupational Coping Self-Efficacy Scale (OCSE-N), and Stanford Presenteeism Scale (SPS-6) were used. SPSS 21.0 software was used for statistical analysis. Pearson correlation analysis and multivariate hierarchical regression were used to explore the influence of ICU nurses' occupational coping self-efficacy on presenteeism. Results: A total of 722 ICU nurses completed the questionnaire. The OCSE-N score of ICU nurses was (22.24 ± 6.15), and the SPS-6 score was (16.83 ± 4.24). The high presenteeism was 67.23%. Correlation analysis showed that in ICU nurses, OCSE-N total score was negatively correlated with SPS-6 total score (r = -0.421, p < 0.05), indicating that the higher the level of occupational coping self-efficacy, the lower the presenteeism. Multiple hierarchical regression analysis showed that occupational coping self-efficacy strongly predicted presenteeism, accounting for approximately 18.35% of the total variance. Conclusion: There is a correlation between ICU nurses' occupational coping self-efficacy and presenteeism, and nurses' occupational coping self-efficacy affects presenteeism differently. Managers should pay attention to nurses' occupational coping self-efficacy to promote nurses' presenteeism reduction.

18.
Brain Imaging Behav ; 18(1): 192-206, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37985612

RESUMO

Advanced carotid stenosis is a known risk factor for ischemic stroke and vascular dementia, and it is associated with multidomain cognitive impairment as well as asymmetric alterations in hemispheric structure and function. Here we introduced a novel measure-the asymmetry index of amplitude of low-frequency fluctuations (ALFF_AI)-derived from resting-state functional magnetic resonance imaging. This measure captures the hemispheric asymmetry of intrinsic brain activity using high-dimensional registration. We aimed to investigate functional brain asymmetric alterations in patients with severe asymptomatic carotid stenosis (SACS). Furthermore, we extended the analyses of ALFF_AI to different frequencies to detect frequency-specific alterations. Finally, we examined the coupling between hemispheric asymmetric structure and function and the relationship between these results and cognitive tests, as well as the white matter hyperintensity burden. SACS patients presented significantly decreased ALFF_AI in several clusters, including the visual, auditory, parahippocampal, Rolandic, and superior parietal regions. At low frequencies (0.01-0.25 Hz), the ALFF_AI exhibited prominent group differences as frequency increased. Further structure-function coupling analysis indicated that SACS patients had lower coupling in the lateral prefrontal, superior medial frontal, middle temporal, superior parietal, and striatum regions but higher coupling in the lateral occipital regions. These findings suggest that, under potential hemodynamic burden, SACS patients demonstrate asymmetric hemispheric configurations of intrinsic activity patterns and a decoupling between structural and functional asymmetries.


Assuntos
Estenose das Carótidas , Disfunção Cognitiva , Humanos , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/patologia , Imageamento por Ressonância Magnética/métodos , Encéfalo/patologia , Mapeamento Encefálico
19.
J Pharm Anal ; 14(4): 100915, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38634065

RESUMO

Pien Tze Huang (PZH), a class I nationally protected traditional Chinese medicine (TCM), has been used to treat liver diseases such as hepatitis; however, the effect of PZH on the progression of sepsis is unknown. Here, we reported that PZH attenuated lipopolysaccharide (LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signalling. Mechanistically, PZH stimulated signal transducer and activator of transcription 3 (STAT3) phosphorylation to induce the expression of A20, which could inhibit the activation of NF-κB and MAPK signalling. Knockdown of the bile acid (BA) receptor G protein-coupled bile acid receptor 1 (TGR5) in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction, as well as the LPS-induced inflammatory response, suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5. Consistently, deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20, the activation of NF-κB and MAPK signalling, and the production of proinflammatory cytokines, whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines. Overall, our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

20.
Front Psychol ; 14: 1259333, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023026

RESUMO

Background: Presenteeism is a significant global public health problem, and nurses are a high-prevalence group of presenteeism, affecting not only nurses' physical and mental health, work efficiency, and quality of work but even poses a serious threat to patient safety. Objective: The categorization of presenteeism among ICU nurses is unclear. Our research aims to explore the subtypes of presenteeism among ICU nurses based on latent profile analysis, analyze the influencing factors of different subtypes, and provide a reference basis for developing targeted interventions to reduce the presenteeism rate. Methods: From January to February 2023, 509 ICU nurses in Sichuan Province, China, were selected as respondents and surveyed using the general information questionnaire, the presenteeism scale, and the perceived social support scale. Potential categories of presenteeism among ICU nurses were explored using potential profile analysis, and factors influencing the potential types of presenteeism among ICU nurses were investigated using the chi-square test and multivariate logistic regression analysis. Results: The best model was suggested to consist of three profiles: low presenteeism-normal coping group (18.3%), moderate presenteeism group (47.9%), and high presenteeism-work limitation group (33.8%). Multiple logistic regression results showed that secondary hospitals (OR = 0.116, p = 0.015), good physical health (OR = 0.084, p = 0.023), general physical health (OR = 0.016, p = 0.037), ICU human resource allocation = 1:2.5 to 3 (OR = 0.315, p = 0.007), and higher social support scores (OR = 0.975, p = 0.047) were more likely to be grouped into low presenteeism-normal coping group; married with no children (OR = 24.554, p = 0.005) were more likely to be grouped into moderate presenteeism group; and having experienced workplace violence in the past year (OR = 1.182, p = 0.049) were more likely to be grouped into high presenteeism-work limitation group. Conclusion: There is group heterogeneity in the presenteeism of ICU nurses, and nursing managers should develop targeted interventions to reduce the presenteeism rate of ICU nurses according to the characteristics and influencing factors of each type of presenteeism of ICU nurses.

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