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1.
Carbohydr Polym ; 227: 115314, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590844

RESUMO

The physicochemical properties, structural features and immunomodulatory effects of the white asparagus (Asparagus officinalis L.) skin polysaccharides (WASP) were systematically studied. WASP showed a pectic-like structure with a relatively low degree of esterification (DE, 18%); the weight-average molecular weight (Mw) and intrinsic viscosity were 76.1 kDa and 13 mL/g, respectively. Structurally, the dominated sugar residue of WASP was 4-α-D-GalpA (39.7 mol%), while other residues including α-L-Araf, 3-α-L-Rhap, 2,4-α-L-Rhap, and 4-ß-D-Galp were also detected with a comparable amount. A proposed structure of WASP was also presented. Physiologically, WASP could modulate the immune response of RAW 264.7 macrophages through increasing the release of immune factors (IL-6, TNF-α and IL-10) and improving the expression of mRNA. To conclude, the pectic-like polysaccharides from white asparagus (Asparagus officinalis L.) skin could be potentially used as an immunomodulatory agent in functional food.

2.
J Neurosci Methods ; 328: 108438, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31542346

RESUMO

BACKGROUND: Positron emission tomography (PET) imaging techniques of tau retention in the human brain are important for mechanistic studies of Alzheimer's disease (AD). However, the method for effectively conducting voxel-wise analysis on tau PET images still needs to be improved. In the present study, we introduced a tau PET template for the human brain in Montreal Neurological Institute (MNI) space for the convenient and reliable voxel-wise analysis of tau PET images in AD studies. NEW METHOD: Twenty-four AD patients and 22 controls were used to construct the tau PET template, and an additional 22 subjects (11 AD patients and 11 controls) were enrolled to evaluate the performance of the template. Thirty regions (28 cortical and 2 subcortical regions) throughout the brain were used to evaluate the accuracy of the tau PET template. RESULTS: A significant relationship (R2 = 0.848, P < 0.001) was found between the standardized uptake value ratios (SUVRs) obtained by the tau PET template and magnetic resonance imaging (MRI)-aided approach, and the paired-sample t-test showed no significant difference (P = 0.62) between the values. These two approaches revealed consistent brain regions with high tau retention. COMPARISON WITH EXISTING METHODS: The tau PET template was comparable with the traditional MRI-aided strategy. Furthermore, compared to the MRI-aided approach, the tau PET template was more convenient and easier to use. More importantly, in most clinical settings, AD patients who underwent PET/computed tomography (CT) typically do not have MR images, in which case the traditional MRI-aided approach would not be applicable. Our tau PET template overcame this deficiency and may serve as a useful tool in AD research. CONCLUSIONS: This tau PET template performed well and may serve as a useful tool in future AD studies.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31526292

RESUMO

In the context of hepatic insulin resistance, hepatic gluconeogenesis is abnormally increased, which results in increased hepatic glucose production and hyperglycemia but the underlying mechanisms remain to be fully elucidated. MicroRNAs (miRNAs) have been identified as critical regulators of diabetes and other metabolic disorders. In this study, we found that the expressions of miRNA-27 family members, miRNA-27a and miRNA-27b (miR-27a/b) decreased significantly in the livers of diabetic mice. Moreover, the levels of miR-27a/b increased in the serum of patients with type 2 diabetes (T2D). Our present results showed that inhibition of miR-27a/b expression led to increased hepatic protein levels of G6pase and PEPCK and enhanced hepatic gluconeogenesis in vitro and in vivo. Overexpression of miR-27a/b suppressed hepatic glucose production and alleviated hyperglycemia in diabetic mice. Further study revealed that FOXO1 was a downstream target of miR-27a/b. Taken together, we found novel evidence suggesting that miR-27a/b contributes to hepatic gluconeogenesis through the targeting FOXO1 and provide novel mechanistic insight into the pathophysiology of insulin resistance.

4.
Int J Mol Sci ; 20(17)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31454889

RESUMO

In order to rapidly and efficiently excavate antihypertensive ingredients in Todarodes pacificus, its myosin heavy chain was hydrolyzed in silico and the angiotensin-converting enzyme (ACE) inhibitory peptides were predicted using integrated bioinformatics tools. The results showed the degree of hydrolysis (DH) theoretically achieved 56.8% when digested with papain, ficin, and prolyl endopeptidase (PREP), producing 126 ACE inhibitory peptides. By predicting the toxicity, allergenicity, gastrointestinal stability, and intestinal epithelial permeability, 30 peptides were finally screened, of which 21 had been reported and 9 were new. Moreover, the newly discovered peptides were synthesized to evaluate their in vitro ACE inhibition, showing Ile-Ile-Tyr and Asn-Pro-Pro-Lys had strong effects with a pIC50 of 4.58 and 4.41, respectively. Further, their interaction mechanisms and bonding configurations with ACE were explored by molecular simulation. The preferred conformation of Ile-Ile-Tyr and Asn-Pro-Pro-Lys located in ACE were successfully predicted using the appropriate docking parameters. The molecular dynamics (MD) result indicated that they bound tightly to the active site of ACE by means of coordination with Zn(II) and hydrogen bonding and hydrophobic interaction with the residues in the pockets of S1 and S2, resulting in stable complexes. In summary, this work proposed a strategy for screening and identifying antihypertensive peptides from Todarodes pacificus.

5.
ACS Appl Mater Interfaces ; 11(35): 31693-31699, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31339687

RESUMO

Fluorescent detection of glutathione (GSH) in the living system has attracted much attention, but current fluorescent probes are usually exposed to the exterior environment, leading to photobleaching and premature leakage and subsequently limiting the sensitivity and photostability. Herein, luminescent metal-organic frameworks [Ru(bpy)32+ encapsulated in UiO-66] coated with manganese dioxide nanosheets [MnO2 NS@Ru(bpy)32+-UiO-66] were prepared by an in situ growth method and further explored to construct a GSH-switched fluorescent sensing platform. Because of the splendid fluorescence quenching ability, special probe leakage blocking role and distinguished recognition of the MnO2 NS, and the improved fluorescence of Ru(bpy)32+ by UiO-66, a low background, highly sensitive and selective detection of GSH with a low limit of detection as 0.28 µM was realized. At the same time, the preparation of MnO2 NS@Ru(bpy)32+-UiO-66 nanocomposites is simple and less toxic, and there was no notable loss of cell survivability after being exposed to MnO2 NS@Ru(bpy)32+-UiO-66 below the concentrations of 120 µg mL-1 for 24 h. Consequently, the results coming from this effort suggest that the new sensing platform will have a great potential in the detection of GSH in living cells.

6.
EMBO Rep ; 20(7): e47563, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31267712

RESUMO

Monoubiquitination of histone H2B on lysine 120 (H2Bub1) is an epigenetic mark generally associated with transcriptional activation, yet the global functions of H2Bub1 remain poorly understood. Ferroptosis is a form of non-apoptotic cell death characterized by the iron-dependent overproduction of lipid hydroperoxides, which can be inhibited by the antioxidant activity of the solute carrier family member 11 (SLC7A11/xCT), a component of the cystine/glutamate antiporter. Whether nuclear events participate in the regulation of ferroptosis is largely unknown. Here, we show that the levels of H2Bub1 are decreased during erastin-induced ferroptosis and that loss of H2Bub1 increases the cellular sensitivity to ferroptosis. H2Bub1 epigenetically activates the expression of SLC7A11. Additionally, we show that the tumor suppressor p53 negatively regulates H2Bub1 levels independently of p53's transcription factor activity by promoting the nuclear translocation of the deubiquitinase USP7. Moreover, our studies reveal that p53 decreases H2Bub1 occupancy on the SLC7A11 gene regulatory region and represses the expression of SLC7A11 during erastin treatment. These data not only suggest a noncanonical role of p53 in chromatin regulation but also link p53 to ferroptosis via an H2Bub1-mediated epigenetic pathway. Overall, our work uncovers a previously unappreciated epigenetic mechanism for the regulation of ferroptosis.

7.
Fish Shellfish Immunol ; 92: 300-307, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31202968

RESUMO

Outbreaks of mass mortalities occurred in Macrobrachium rosenbergii farms in Gaoyou county, Jiangsu Province of China. The bacterial isolates from M. rosenbergii exhibited the same phenotypic traits and biochemical characteristics, and were identified as non-O1/O139 Vibrio cholerae according to biochemical characteristics and molecular identification. In challenge test, M. rosenbergii infected with non-O1/O139 V. cholerae GXFL1-4 developed similar pathological signs to the naturally diseased prawns, and LD50 of the strain to M. rosenbergii was 4.5 × 106 CFU/mL at 96 h post-infection. Histopathological analysis revealed that hepatopancreas and intestines of diseased M. rosenbergii exhibited obvious inflammatory responses to non-O1/O139 V. cholerae infection. Detection virulence factors of the strain GXFL1-4 showed that the bacteria produced caseinase, lipase, amylase, lecithinase and hemolysin, and carried toxR, hlyA, ompW, ompU, hap, rtxA and rtxC virulence related genes, supporting the strong virulence to M. rosenbergii. Additionally, the immune related gene expression in M. rosenbergii evaluated by qRT-PCR analysis showed that HSP70, Crustin, Lysozyme, TRL1, ALF1, Lectin, Peroxinectin, proPO and SOD immune related genes were significantly up-regulated at 6 and 12 h after infection with GXFL1-4. The results of our study suggested that non-O1/O139 V. cholerae was an etiological element in the mass mortalities of M. rosenbergii and this study provided preliminary insights into the diversity in the immune response of M. rosenbergii to the bacterial invasion.

8.
ACS Sens ; 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31244011

RESUMO

Surface plasmon-enhanced electrochemiluminescence (SPEECL) with excellent sensitivity and simplicity has attracted increasing attention. In this work, we reported a novel SPEECL with DNA templated silver nanoclusters (DNA-AgNCs) as ECL emitters and gold nanoparticles (AuNPs) as localized surface plasmon resonance (LSPR) source. The SPEECL with DNA-AgNCs as ECL luminophores possessed low toxicity and avoided the labeling process, which is favorable for its further sensing application. In addition, by investigation of the SPEECL under different distances between DNA-AgNCs and AuNPs, it was demonstrated that the SPEECL was distance dependent. Meanwhile, the SPEECL intensity changed with the sizes and interdistance of AuNPs under different electrodeposition time. Furthermore, by the combination of a cyclic amplification process with enzyme-free catalytic hairpin DNA, a sensitive SPEECL biosensor was proposed for the detection of microRNA (miRNA-21) successfully with a wide linear range from 1 aM to 104 fM and a relatively low detection limit of 0.96 aM, which was applied in the detection of miRNA-21 in real samples with satisfying results. This novel, simple, sensitive, and selective SPEECL with label-free and low-toxic ECL emitters displayed a great potential for bioassay application.

9.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(5): 654-657, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31198159

RESUMO

OBJECTIVE: Acute respiratory distress syndrome (ARDS) is considered to be a pulmonary manifestation of systemic inflammatory response syndrome (SIRS), often occurring as a complication of disease, and worsening the prognosis of patients. In recent years, the incidence of trauma has increased year by year. Severe trauma can lead to SIRS, which is one of the common risk factors of ARDS. The spleen is the largest peripheral immune organ of the body, containing a large number of immune cells and secreting inflammatory factors. The inflammatory factors play an important role in the formation of traumatic ARDS. In recent years, the benefits of treating ARDS by inhibiting spleen-induced inflammatory response have gradually been discovered, providing new ideas for the treatment of ARDS. Therefore, the research status of spleen-mediated inflammatory response in traumatic ARDS is of great significance for the prevention and treatment of traumatic ARDS. This article reports the spleen-mediated systemic inflammatory response, the role of inflammatory mediators in the development of ARDS, and the current state of research on ARDS treatment to explore new approaches to the prevention and treatment of traumatic ARDS.


Assuntos
Síndrome do Desconforto Respiratório do Adulto/etiologia , Baço/metabolismo , Síndrome de Resposta Inflamatória Sistêmica , Ferimentos e Lesões/complicações , Humanos , Síndrome do Desconforto Respiratório do Adulto/terapia
10.
Biochem Biophys Res Commun ; 516(1): 270-277, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31248593

RESUMO

Nuclear factor-erythroid 2 related factor 2 (Nrf2) plays critical roles in attenuating various inflammation- and oxidative stress-induced diseases, including acute lung injury (ALI). Bardoxolone (Bard), a synthetic triterpenoid based on natural product oleanolic acid, is one of the most potent Nrf2 activator. However, if Bard could prevent lipopolysaccharide (LPS)-induced ALI by inducing Nrf2 activation and its down-streaming signals, is still poorly understood. In this study, we attempted to explore the protective effect of Bard on ALI and the underlying molecular mechanisms. The results indicated that Bard significantly attenuated ALI through reducing the lung wet/dry weight ratio and protein concentration, neutrophil infiltration, malondialdehyde (MDA) and myeloperoxidase (MPO) levels, and improving superoxide dismutase (SOD) and glutathione (GSH) activities. In addition, Bard effectively ameliorated histopathological alterations, reactive oxygen species (ROS) production, pro-inflammatory cytokines release, and the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX2) and high mobility group box 1 (HMGB1). Moreover, the inhibitory role of Bard in inflammation was also attributed to its suppression of nuclear factor-κB (NF-κB) signaling. Furthermore, the activation of mitogen-activated protein kinases (MAPKs) signaling, including p38, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK), induced by LPS was substantially ameliorated by Bard. The beneficial effects of Bard on ALI were confirmed in LPS-incubated cells in vitro. Meanwhile, the in vitro studies also demonstrated that Bard-improved ALI was largely due to its role in inducing Nrf2 signaling through a dose-dependent manner. Importantly, we found that Bard-attenuated histological changes, inflammation, ROS production, NF-κB and MAPKs signaling in Nrf2+/+ mice were significantly abolished in mice with Nrf2 knockout. Therefore, our study for the first time provided evidence that Bard could effectively ameliorate LPS-induced ALI by reducing oxidative stress and inflammation mainly through the activation of Nrf2 signaling.

11.
Gene ; 709: 1-7, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31108165

RESUMO

Diabetes mellitus (DM) is a chronic, multifactorial metabolic disease whereby insulin deficiency or resistance results in hyperglycemia. A sustained high glucose environment results in inflammation and endothelial cell dysfunction. However, the underlying mechanisms are still not entirely clear. Circular RNAs (circRNAs) are recognized as functional non-coding RNAs involved in diverse biological processes, including DM. Previous studies have found that hsa_circ_0068087 is increased in DM patients. In order to identify whether hsa_circ_0068087 plays a role in high glucose (HG)-induced inflammation and endothelial cell dysfunction Human Umbilical Vein Endothelial Cell (HUVECs), quantitative reverse transcription PCR (qRTPCR), tube formation assay, enzyme-linked immunosorbent assay (ELISA) and bifluorescein reporter experiments were employed in this study. The results showed that the expression of hsa_circ_0068087 was upregulated in HUVECs following increases in glucose. Knockdown of hsa_circ_0068087 suppressed HG-induced HUVEC dysfunction and inflammation by suppression of the TLR4/NF-κB/NLRP3 inflammasome signaling pathway. Downregulation of miR-197 reversed hsa_circ_0068087 silence-induced HUVEC dysfunction and inflammation in the HG condition. It was found that TLR4 was the target of miR-197 and that overexpression of TLR4 ameliorated miR-197-induced HUVEC dysfunction and inhibited inflammation in the HG condition. Bifluorescein report experiments confirmed that miR-197 is a potential target of hsa_circ_0068087 and that TLR4 is a potential miR-197 target. Taken together, these results suggest that downregulation of hsa_circ_0068087 ameliorates TLR4/NF-κB/NLRP3 inflammasome-mediated inflammation and endothelial cell dysfunction in the high glucose condition by sponging miR-197.


Assuntos
Glucose/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Inflamassomos/fisiologia , Inflamação/genética , MicroRNAs/metabolismo , RNA/genética , Células Cultivadas , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Técnicas de Silenciamento de Genes , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/genética , Inflamassomos/metabolismo , Inflamação/metabolismo , MicroRNAs/efeitos dos fármacos , MicroRNAs/genética , RNA/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
12.
J Mol Neurosci ; 68(2): 251-260, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30949957

RESUMO

The present meta-analysis aimed to evaluate the interaction between type 2 diabetes mellitus (T2DM) and the risk of cognitive impairment. The studies that fulfilled certain inclusion criteria were selected from online databases including PubMed, Embase, and the Cochrane Library. Data extraction and quality assessment were conducted, and subgroup analysis was performed according to the study area, population sources, and types of cognitive impairment. Publication bias and sensitivity analysis were evaluated. In total, 30 studies from 25 articles, including 2 case-control studies, 9 cohort studies, and 19 cross-sectional studies, were included. Subgroup analysis showed that despite the presence of hospital-based and multi-center subgroups in the cohort studies, the association between T2DM and cognitive impairment risk was statistically significant in all other subgroups (P < 0.05). Furthermore, the sensitivity and publication bias analysis showed good stability in all enrolled studies. T2DM might be associated with the risk of cognitive impairment. Further studies on early detection and appropriate management of cognitive impairment might be required in T2DM patients of different regions.


Assuntos
Disfunção Cognitiva/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
J Phys Chem A ; 123(16): 3592-3598, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-30978022

RESUMO

Measurement of distances between spectroscopic labels (e.g., spin labels, fluorophores) attached to specific sites of biomolecules is an important method for studying biomolecular complexes. ALLNOX (Addition of Labels and Linkers) has been developed as a program to model interlabel distances based on an input macromolecule structure. Here, we report validation of ALLNOX using measured distances between nitroxide spin labels attached to specific sites of a protein-DNA complex. The results demonstrate that ALLNOX predicts average interspin distances that matched with values measured with pairs of labels attached at the protein and/or DNA. This establishes a solid foundation for using spin labeling in conjunction with ALLNOX to investigate complexes without high-resolution structures. With its high degree of flexibility for the label or the target biomolecule, ALLNOX provides a useful tool for investigating the structure-function relationship in a large variety of biological molecules.


Assuntos
Ácidos Nucleicos/química , Proteínas/química , Software , Cristalografia por Raios X , Espectroscopia de Ressonância de Spin Eletrônica , Modelos Moleculares , Estrutura Molecular , Mutagênese Sítio-Dirigida , Marcadores de Spin
14.
Int Immunopharmacol ; 72: 437-444, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31030100

RESUMO

BACKGROUND: Immune thrombocytopenia (ITP) is an immune-mediated acquired autoimmune hemorrhagic disease. About one-third of patients are unresponsive to first-line therapies. Thalidomide (THD) as an immunomodulatory agent is now used to treat several autoimmune disorders. Therefore, we assessed the safety and efficacy of THD in corticosteroid-resistant or relapsed ITP patients, and preliminarily explore its mechanism. METHODS: 50 newly-diagnosed ITP patients and 47 healthy volunteers were enrolled in this study. Additionally, 17 corticosteroid-resistant or relapsed ITP patients were recruited, with 7 cases in the rhTPO + THD group and 10 cases in the THD monotherapy group. Overall response rate at 6, 12, and 24 months were assessed. Levels of Neuropilin-1(NRP-1), regulatory T cells (Tregs) and regulatory B cells (Bregs) were detected. RESULTS: Expression of NRP-1, Tregs and Bregs were reduced in newly-diagnosed ITP patients. In vitro, THD treatment upregulated expression of NRP-1and Tregs only in ITP patients. As for corticosteroid-resistant or relapsed ITP patients, overall response rate at 6, 12, and 24 months was 85.7%, 57.1% and 100% in the rhTPO + THD group and 60%, 75% and 83.3% in the THD group, respectively. Additionally, rhTPO plus THD or THD therapy significantly increased the levels of NRP-1, Tregs and Bregs in responders. CONCLUSIONS: Our study shows for the first time that NRP-1 is involved in the pathogenesis of ITP, THD could induce response in ITP patients by upregulating NRP-1 expression and restoring the proportion of Tregs and Bregs. THD might be served as a novel therapeutic agent in corticosteroid-resistant or relapsed ITP patients.

15.
J Microbiol Biotechnol ; 29(4): 633-644, 2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-30939635

RESUMO

An advanced anaerobic expanded granular sludge bed (AnaEG) and an internal circulation (IC) reactor, which were adopted to treat starch processing wastewater (SPW) and ethanol processing wastewater (EPW), were comprehensively analyzed to determine the key factors that affected the granules and microbial communities in the bioreactors. The granule size of 900 µm in the AnaEG reactor was smaller than that in the IC reactor, and the internal and external morphological structures of the granular sludge were also significantly different between the two types of reactors. The biodiversity, which was higher in the AnaEG reactor, was mainly affected by reactor type. However, the specific microbial community structure was determined by the type of wastewater. Furthermore, the dominant methanogens of EPW were mainly Methanosaeta and Methanobacterium, but only Methanosaeta was a major constituent in SPW. Compared with the IC reactor, characteristics common to the AnaEG reactor were smaller granules, higher biodiversity and larger proportion of unknown species. The comparison of characteristics between these two reactors not only aids in understanding the novel AnaEG reactor type, but also elucidates the effects of reactor type and wastewater type on the microbial community and sludge structure. This information would be helpful in the application of the novel AnaEG reactor.


Assuntos
Reatores Biológicos/microbiologia , Microbiota , Esgotos/microbiologia , Águas Residuárias/microbiologia , Anaerobiose , Archaea/classificação , Archaea/genética , Archaea/metabolismo , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Biodiversidade , Biologia Computacional , DNA Bacteriano , Etanol/metabolismo , Methanobacterium , Methanosarcinales , Microbiota/genética , RNA Ribossômico 16S/genética , Eliminação de Resíduos Líquidos
16.
J Labelled Comp Radiopharm ; 62(8): 425-437, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-30991462

RESUMO

We report the design, synthesis, and evaluation of a new series of benzylpiperazine derivatives as selective σ1 receptor ligands. All seven ligands possessed low nanomolar affinity for σ1 receptors (Ki (σ1 ) = 0.31-4.19 nM) and high subtype selectivity (Ki (σ2 )/Ki (σ1 ) = 50-2448). The fluoroethoxy analogues also exhibited high selectivity toward the vesicular acetylcholine transporter (Ki (VAChT)/Ki (σ1 ) = 99-18252). The corresponding radiotracers [18 F]13, [18 F]14, and [18 F]16 with high selectivity (Ki (σ2 )/Ki (σ1 ) > 100, Ki (VAChT)/Ki (σ1 ) > 1000) were prepared in 42% to 55% radiochemical yields (corrected for decay), greater than 99% radiochemical purity (RCP), and molar activity of about 120 GBq/µmol at the end of synthesis (EOS). All three radiotracers showed high initial brain uptake in mouse (8.37-11.48% ID/g at 2 min), which was not affected by pretreatment with cyclosporine A, suggesting that they are not substrates for permeability-glycoprotein (P-gp). Pretreatment with SA4503 or haloperidol resulted in significantly reduced brain uptake (35%-62% decrease at 30 min). In particular, [18 F]16 displayed high brain-to-blood ratios and high in vivo metabolic stability. Although it may not be an optimal neuroimaging agent because of its slow kinetics in the mouse brain, [18 F]16 can serve as a lead compound for further structural modifications to explore new potential radiotracers for σ1 receptors.

17.
Cancer Sci ; 110(6): 1829-1841, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30950146

RESUMO

The present study aimed to select anti-tumor-associated antigen (TAA) autoantibodies as biomarkers in the immunodiagnosis of gastric adenocarcinoma (GAC) by the recursive partitioning approach (RPA) and further construct and evaluate a predictive model. A case-control study was designed including 407 GAC patients as the case group and 407 normal controls. In addition, 67 serial serum samples from 25 GAC patients were collected at different time points before and after gastrectomy treatment. Autoantibodies against 14 TAA were measured in sera from all subjects by enzyme immunoassay. Finally, RPA resulted in the selection of nine-panel TAA (c-Myc, p16, HSPD1, PTEN, p53, NPM1, ENO1, p62, HCC1.4) from all detected TAA in the case-control study; the classification tree based on this nine-TAA panel had area under curve (AUC) of 0.857, sensitivity of 71.5% and specificity of 71.3%; The optimal panel also can identify GAC patients at an early stage from normal individuals, with AUC of 0.737, sensitivity of 64.9% and specificity of 70.5%. However, frequencies of the nine autoantibodies showed no correlation with GAC stage, tumor size, lymphatic metastasis or differentiation. GAC patients positive for more than two autoantibodies in the nine-TAA panel had a worse prognosis than that of the GAC patients positive for no or one antibody. Titers of 10 autoantibodies in serial serum samples were significantly higher in GAC patients after surgical resection than before. In conclusion, this study showed that the panel of nine multiple TAAs could enhance the detection of anti-TAA antibodies in GAC, and may be potential prognostic biomarkers in GAC.


Assuntos
Adenocarcinoma/diagnóstico , Antígenos de Neoplasias/sangue , Testes Imunológicos/métodos , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC , Neoplasias Gástricas/imunologia , Adulto Jovem
19.
Mikrochim Acta ; 186(5): 269, 2019 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-30955099

RESUMO

A fluorescent probe for H2O2 is described. It is composed of MnO2 nanosheets and 5-carboxyfluorescein and was characterized by fluorescence, transmission electron microscopy, ultraviolet-visible absorption spectra, energy dispersive X-ray and Fourier transform infrared spectroscopy. The probe, with fluorescence excitation/emission maxima at 490/518 nm, responds to H2O2 in the 1 to 200 µM concentration range and has a 0.33 µM detection limit. The probe was used in enzymatic assays for glucose and cholesterol by using the respective oxidases which produce H2O2. Responses are linear in the concentration range from 0.5 to 200 µM in case of glucose, and from 1 to 300 µM in case of cholesterol. The method was applied to quantify glucose and cholesterol in (spiked) serum samples. Graphical abstract Schematic presentation of the principle based on hydrogen peroxide-induced degradation of MnO2 nanosheet-FAM complex for detection of H2O2 (a), glucose and cholesterol (b).

20.
Planta ; 250(1): 129-143, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30944981

RESUMO

MAIN CONCLUSION: In wheat, a QTL QTrl.saw-2D.2 associated with the total root length was identified, presumably containing genes closely related to root development. A mapping population of 184 recombinant inbred lines derived from the cross SY95-71 × CH7034 was used to map QTL for seedling root characteristics in hydroponic culture (HC) and in soil-filled pot (SP) methods. Four traits, including maximum root length (MRL), root number (RN), total length (TRL), and root diameter (RD) were measured and used in QTL analyses. A total of 33 QTL for the four root traits were detected, 17 QTLs for TRL, six for RN, seven for MRL, and three for RD. Seven QTL were detected in both HC and SP methods, which explained 7-18% phenotypic variation. One QTL QTrl.saw-2D.2 detected in both HC and SP methods was also validated in another population comprised of 215 diverse lines. This QTL is a novel QTL that explained the highest phenotypic variation 18% in all QTL identified in the present study. Based on candidate gene and comparative genomics analyses, the QTL QTrl.saw-2D.2 may contain genes closely related to root development in wheat (Triticum aestivum L.). The two candidate genes were proposed to explore in future studies.


Assuntos
Locos de Características Quantitativas/genética , Triticum/genética , Mapeamento Cromossômico , Secas , Ligação Genética , Estudo de Associação Genômica Ampla , Fenótipo , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/fisiologia , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/fisiologia , Triticum/crescimento & desenvolvimento , Triticum/fisiologia
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