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1.
J Neuroinflammation ; 17(1): 50, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024542

RESUMO

BACKGROUND: Astrocytes are the most abundant glial cells in a brain that mediate inflammatory responses and provide trophic support for neurons. We have previously disclosed that paroxetine, a common selective serotonin reuptake inhibitor, ameliorates LPS-induced microglia activation. However, it remains elusive for the role of paroxetine in astrocytic responses. METHODS: Isolated primary astrocytes were pretreated with paroxetine and stimulated with different stimuli, lipopolysaccharide (LPS) or microglia conditioned medium pre-activated with LPS (M/Lps). Inflammatory and neurotrophic responses, underlying mechanisms and the impact on neuronal survival were assessed. RESULTS: Paroxetine had no impact on LPS-stimulated iNOS, TNF-α, and IL-1ß expression, but inhibited M/Lps-induced TNF-α and IL-1ß expression in primary astrocytes. Paroxetine suppressed M/Lps- but not LPS-induced activation of NF-κB and had no impact on the activation of MAPKs and STAT3. Incubation with the resulted astrocyte conditioned media caused no change in the viability of SH-SY5Y cells. BDNF and MANF mRNA expressions were upregulated by M/Lps and paroxetine, respectively. However, M/Lps- or LPS-induced extracellular releases of NO, TNF-α, and/or BDNF in astrocytes were in minor amount compared to those by microglia. CONCLUSIONS: Paroxetine ameliorates the reactive microglia-mediated inflammatory responses in astrocytes partially via inhibition of the NF-κB pathway but has no impact on LPS-stimulated astrocyte activation. While the effects of paroxetine on secondary astrocytic responses are not robust compared to its effect on the innate immune responses of microglia, the results together may implicate a therapeutic potential of paroxetine against neuroinflammation-associated neurological disorders such as Parkinson's disease.

2.
ACS Appl Mater Interfaces ; 12(4): 4815-4820, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31898447

RESUMO

Taking the advantages of excellent optical properties, biocompatibility, and photostability of carbon dots, herein, we developed polarity-sensitive polymer carbon dots (PCDs) for visualizing of cellular polarity to real-time monitoring autophagy changes without perturbing the cellular status. The PCDs can be prepared by simply mixing dopamine (DA), H2O2, and o-phenylenediamine (o-PDA) in a common beaker without the need for any special equipment or external energy supply, and the preparation could be completed within 3 min at room temperature. Interestingly, the polarity-sensitive PCDs could emit various types of fluorescence and are insensitive to the excitation light when dispersed in different water/dioxane systems with different polarities. Based on the polarity-sensitive emission of the PCDs, the change of polarity during autophagy has been successfully monitored in living cells. Moreover, the change of polarity detected by PCDs is autophagy-specific (does not occur during apoptosis), occurs under different autophagy-inducing situations (starvation, rapamycin, and trehalose), and requires a normal autophagic flux, showing that PCDs rapidly prepared by polymerization cross-linking at room temperature can be functionally applied in the case of autophagy-related physiological or pathological processes.

3.
Front Neurol ; 10: 333, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31024427

RESUMO

Introduction: Level of serotonin is mainly regulated by the serotonin reuptake transporter encoded by SLC6A4. The promoter region of SLC6A4 bears a repeat polymorphism 5-HTTLPR and a single nucleotide polymorphism rs25531. We have previously studied the association between these two variants and sporadic PD. The objective of the current study was to determine whether the SLC6A4 polymorphisms were associated with key motor and non-motor symptoms of PD. Methods: A total of 370 PD patients of Han Chinese were included. Associations between the SLC6A4 polymorphisms and PD symptoms including depression, intellectual impairment, tremor and rigidity were analyzed. Results: 5-HTTLPR was associated with depression in PD patients and presence of the LL genotype was protective against the depression risk. The rs25531 was associated with rest tremor in PD and the A allele serves as a recessive risk allele. No associations were found in the two polymorphisms with respect to intellectual impairment and rigidity in the cohort. Conclusion: The current study reveals two PD symptoms associated with SLC6A4 polymorphisms, and provides new insight into how serotonergic system genetically participates in the symptomatic progression of PD. Further study is warranted in additional populations.

4.
Anal Chem ; 91(10): 6761-6768, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31020834

RESUMO

Nonalcoholic fatty liver disease (NAFLD) can progress gradually to liver failure, early warning of which is critical for improving the cure rate of NAFLD. In situ imaging and monitoring of overexpressed miR-21 is an advanced strategy for NAFLD diagnosis. However, this strategy usually suffers from the high background imaging in living cells owing to the complexity of the biological system. To overcome this problem, herein, we have developed a one-donor-two-acceptor nanoprobe by assembling gold nanoparticles (AuNPs) coupled with BHQ2 (AuBHQ) and quantum dots (QDs) through DNA hybridization for imaging of miR-21 in living cells. The fluorescence of QDs was quenched up to 82.8% simultaneously by the AuNPs and the BHQ2 via nanometal surface energy transfer and fluorescence resonance energy transfer, reducing the background signals for target imaging. This low background fluorescent nanoprobe was successfully applied for imaging the target miR-21 in nonalcoholic fatty liver cells by catalyzing the disassembly of QDs with the AuBHQ and the fluorescence recovery of QDs. In addition, the sensitivity of this nanoprobe has also been enhanced toward detecting miR-21 in the range of 2.0-15.0 nM with the detection limit (LOD, 3σ) of 0.22 nM, which was 13.5 times lower than that without BHQ2. The proposed approach provides a new way for early warning, treatments, and prognosis of NAFLD.

5.
Talanta ; 196: 100-108, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30683338

RESUMO

Carbon quantum dots (CQDs), prepared by one-step hydrothermal treatment of perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA) and triethylamine (TEA), could be exfoliated or delaminated into single-layered graphene quantum dots (s-GQDs) with methanol for the first time, with fluorescence (FL) emission at 500 nm when excited at 417 nm. The s-GQDs, with more sufficient carboxyl groups on the surface than CQDs, could be induced to be aggregated by metal ion dysprosium (Dy3+), resulting in aggregation-induced emission quenching effect subsequently. However, the presence of phosphate (PO43-) destroys the Dy3+-induced aggregates of s-GQDs owing to the strong coordination between Dy3+ and PO43-, inducing the FL emission recovery of the s-GQDs and providing selective detection method of PO43- in the artificial wetlands with the linear range of 0.2-30 µM and determination limit of 0.1 µM (3σ).

6.
Talanta ; 191: 443-448, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30262082

RESUMO

The highly sensitive detection of dipicolinic acid (DPA), a biomarker of the biological threat-agent anthrax, is strongly associated with the sensing of Bacillus anthracis (B. anthracis) in environmental and food samples. In this study, we developed a novel, ultrasensitive method for the detection of DPA by using a ratiometric fluorescent terbium ions modified carbon dots (CDs-Tb). The CDs-Tb showed two fluorescent emission bands at 459 nm and 495 nm when excited at the single wavelength of 260 nm. DPA could specifically bind with terbium ions on the surface of CDs through strong chelate-conjugation to produce antenna effect, resulting in significantly enhancement of the 495 nm emission peak without affecting the 459 nm emission peak. The fluorescence intensity ratio (I495/I459) of CDs-Tb was proportional to the concentration of DPA in the range of 0.5 nM to 2.5 µM with the limit of detection as low as 100 pM. This selective and ultrasensitive assay had a great application prospect in the complex matrixes owing to its simplicity and specificity for DPA. Meanwhile, the CDs-Tb-based paper sensor was successfully developed for sensitive and visual detection of DPA.

7.
Anal Chim Acta ; 1035: 203-210, 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30224140

RESUMO

Mercury ions (Hg2+) are one of the compulsory items in the quality control of herbal medicines for its serious toxicity to human health. Highly selective and sensitive Hg2+ detection, especially in complex real samples, is still challenging. In this work, Fluorescent (FL) carbon dots (CDs) with a core-shell structures composed of the crystalline core of stacked sp2-hybridized carbon layers and the shell of functional groups on the periphery of carbon layers are facilely prepared through a one-step hydrothermal synthetic route. They can specifically interact with Hg2+ in aqueous medium to form aggregates, during which coordination of carboxyl functional groups on the surface of CDs with Hg2+ occurred, which facilitated electron transfer from the CDs to Hg2+. As a result, fluorescence of the CDs was quenched with a high efficiency, making the detection of Hg2+ highly sensitive with the limit of determination (LOD) of 2.2 nM (3σ). With that, detection of Hg2+ in the complex compound herbal medicines samples with highly reproducible results has been successfully realized by using the as-prepared CDs, showing that fluorescent CDs-based probe may have great potential in the quality controls of heavy metals for pharmaceutical analysis.


Assuntos
Corantes Fluorescentes/química , Mercúrio/análise , Preparações de Plantas/análise , Pontos Quânticos/química , Espectrometria de Fluorescência/métodos , Carbono/química , Ácido Cítrico/química , Transporte de Elétrons , Mercúrio/metabolismo , Pontos Quânticos/metabolismo , Sensibilidade e Especificidade , Espermina/química
8.
Anal Chem ; 90(16): 9966-9974, 2018 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-30040384

RESUMO

Increasing demands for the sensitive, selective, visual, conveniently solid-phase-sensing film for disease-related biomarkers, electrospun nanofibrous films (ENFFs) are a novel sensing paltform because of the high surface area ratios, networked structures, and facile functionalization. In this research, carbon dots (CDs) and quantum dots (QDs) were doped inside and electrostatically assembled on electrospun nanofibers (ENFs), affording ratiometrically dual-emitting fluoresecent films. Because of the FRET process between CDs and QDs on NFs and the strong quenching response of QDs to Cu2+, the as-prepared NFs can visually detect Cu2+ with high sensitivity and selectivity based on ratiometric fluorescent signals. By exploiting the release of numerous Cu2+ from CuO nanoparticles (NPs) under acidic conditions, a sandwich-type immunoassay with CuO NPs-labeled antibody was developed for the detection of biomarker proteins via the response of dual-emitting and FRET-based NFs to different Cu2+ concentrations. Taking advantage of the ratiometrically fluorescent property of these ENFFs as well as the Cu2+-mediated signal amplification strategy, alpha fetoprotein can be detected with high sensitivity (detection limit of 8.3 pg/mL) and selectivity. This strategy demonstrates a promising candidate with a point-of-care assay for clinical diagnostics and biomedical research.


Assuntos
Biomarcadores/sangue , Cobre/química , Imunoensaio/métodos , alfa-Fetoproteínas/análise , Anticorpos/imunologia , Carbono/química , Fluorescência , Humanos , Limite de Detecção , Nanofibras/química , Nanopartículas/química , Pontos Quânticos/química , alfa-Fetoproteínas/imunologia
9.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(5): 633-639, 2017 05 20.
Artigo em Chinês | MEDLINE | ID: mdl-28539286

RESUMO

OBJECTIVE: To identify the functions of the proteins containing the GGDEF or EAL domain in Lactobacillus acidophilus for investigation of the regulatory mechanism of c-di-GMP in this strain. METHODS: The DNA fragments of NH13_07045-GGDEF, NH13_07050 and NH13_07055 from Lactobacillus acidophilus ATCC4356 were amplified by PCR and cloned into the expression vector pMAL-His-c2. After sequencing, the recombinant plasmids were transformed into competent Escherichia coli cells, which were induced by IPTG to express the recombinant proteins fused with maltose binding protein (MBP). The fusion proteins were purified using amylose resin column for diguanylate cyclase (DGC) or phosphodiesterase (PDE) activity assays in vitro followed by analysis with high-performance liquid chromatography (HPLC). RESULTS: The target DNA fragments were obtained by PCR, and their sequences were all identical to that in GenBank. The purified and concentrated fusion proteins, which were identified by SDS-PAGE and Western blotting, had relative molecular masses of 59 kD, 67 kD and 72 kD. HPLC analysis showed no DGC activity in NH13_07045-GGDEF, while PDE activity was found in NH13_07050 but not in NH13_07055. CONCLUSION: We obtained the protein encoded by NH13_07050 that possesses PDE activity in vitro. This protein may facilitate the evaluation of the regulatory function of c-di-GMP in Lactobacillus acidophilus.


Assuntos
Proteínas de Bactérias/metabolismo , GMP Cíclico/metabolismo , Lactobacillus acidophilus/metabolismo , Proteínas de Bactérias/genética , Escherichia coli , Lactobacillus acidophilus/genética , Proteínas Recombinantes de Fusão/biossíntese
10.
Mol Divers ; 19(4): 945-53, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26162532

RESUMO

Drug-induced myelotoxicity usually leads to decrease the production of platelets, red cells, and white cells. Thus, early identification and characterization of myelotoxicity hazard in drug development is very necessary. The purpose of this investigation was to develop a prediction model of drug-induced myelotoxicity by using a Naïve Bayes classifier. For comparison, other prediction models based on support vector machine and single-hidden-layer feed-forward neural network  methods were also established. Among all the prediction models, the Naïve Bayes classification model showed the best prediction performance, which offered an average overall prediction accuracy of [Formula: see text] for the training set and [Formula: see text] for the external test set. The significant contributions of this study are that we first developed a Naïve Bayes classification model of drug-induced myelotoxicity adverse effect using a larger scale dataset, which could be employed for the prediction of drug-induced myelotoxicity. In addition, several important molecular descriptors and substructures of myelotoxic compounds have been identified, which should be taken into consideration in the design of new candidate compounds to produce safer and more effective drugs, ultimately reducing the attrition rate in later stages of drug development.


Assuntos
Hematopoese/efeitos dos fármacos , Xenobióticos/efeitos adversos , Xenobióticos/química , Teorema de Bayes , Simulação por Computador , Desenho de Drogas , Modelos Químicos , Máquina de Vetores de Suporte
11.
Chin Med J (Engl) ; 122(15): 1755-8, 2009 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-19781320

RESUMO

BACKGROUND: The biofragmentable anastomosis ring (BAR) is a simple alternative device to create intestinal anastomosis. Our study was designed to evaluate the clinical value of BAR in intestinal anastomosis. METHODS: A total of 167 patients performed intestinal anastomosis from January 2002 to February 2006 were randomized to BAR group (n = 82) and manual suture group (n = 85) as control. They were equally allocated to the two groups regarding sex, age, site of anastomosis, emergent or elective surgery and contaminant diseases. The results of postoperative complications and recovery were recorded in each group. RESULTS: Eighty-seven intraperitoneal BAR anastomoses were completed in 82 patients. Two and one postoperative deaths were recorded in BAR and suture group, respectively, no deaths were directly related to anastomotic technique. In suture group, anastomotic leakage and early bleeding both occurred in two patients respectively, no anastomotic bleeding occurred in BAR group, one patient in BAR group developed enterocutaneous fistulae. Perioperative bleeding, operation time and length of hospitalization were similar in two groups (P > 0.05). Time for return of bowel function was significantly shortened in BAR group than that in suture group (P < 0.05). CONCLUSION: The BAR appears to be a standard, easy, safe and effective alternative either in elective or emergent intraperitoneal intestinal anastomotic surgery.


Assuntos
Anastomose Cirúrgica/instrumentação , Procedimentos Cirúrgicos do Sistema Digestório/instrumentação , Intestinos/cirurgia , Técnicas de Sutura/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Resultado do Tratamento , Adulto Jovem
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