Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 321
Filtrar
1.
Food Funct ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674605

RESUMO

The development of a new generation antioxidant peptides with high free radical scavenging rates is highly desirable, but remains a great challenge. Herein, a new dual-peptide development strategy based on plant and animal proteins has been proposed to enhance the antioxidant activity of peptides. Sea cucumber peptide and pine nut peptide were selected to assemble the dual-peptides, namely, VTPYKDHCH and VTPYQDHCH. The in vitro antioxidant activity of the dual-peptides was confirmed to be much higher than that of the individual peptides VTPY, KDHCH, and QDHCH according to the DPPH and ABTS radical scavenging and EPR experiments. The antioxidant activity of the dual-peptides was also further confirmed via cell experiments. Moreover, circular dichroism (CD), Raman spectrum and 1H NMR spectrum were recorded to determine the enhancement mechanism, which showed that the enhancement activity was derived from the increase in the random crimp degree of the secondary structure after the two different proteins were bound together. Our findings are expected to establish a new dual-peptide strategy for the enhancement of antioxidant activity based on plant and animal sources and encourage the further exploration of dual-peptides for functional applications.

3.
Radiol Med ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31605354

RESUMO

AIMS: The aim of the study was to predict and assess treatment response by histogram analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to patients with locally advanced esophageal squamous cell carcinoma receiving chemoradiotherapy (CRT). MATERIALS AND METHODS: Seventy-two patients with locally advanced esophageal squamous cell carcinoma who underwent DCE-MRI before and after chemoradiotherapy were enrolled and divided into the complete response (CR) group and the non-CR group based on RECIST. The histogram parameters (10th percentile, 90th percentile, median, mean, standard deviation, skewness, and kurtosis) of pre-CRT and post-CRT were compared using a paired Student's t test in the CR and non-CR groups, respectively. The histogram parameter differences between the CR and the non-CR groups were compared using an unpaired Student's t test. A receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance. RESULTS: The histogram parameters of Ktrans values were observed to have significantly decreased after chemoradiotherapy in the CR group. The CR responders showed significantly higher median, mean, and 10th and 90th percentile of pre-Ktrans values than those of the non-CR group. The histogram analysis indicated the decreased heterogeneity in the CR group after CRT. Esophageal cancer with higher pre-Ktrans and lower post-Ktrans values indicated a good treatment response to CRT. Pre-Ktrans-10th showed the best diagnostic performance in predicting the chemoradiotherapy response. CONCLUSIONS: The histogram parameters of Ktrans are useful in the assessment and prediction of the chemoradiotherapy response in patients with advanced esophageal squamous cell carcinoma. DCE-MRI could serve as an adjunctive imaging technique for treatment planning.

4.
J Agric Food Chem ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31610118

RESUMO

In this study, the binding mechanism, morphological, and conformational analysis of the complex of a sea cucumber ovum derived octapeptide (EDLAALEK) with Ca2+ as well as its calcium delivery behavior via the gastrointestinal (GI) tract were investigated. The Ca2+ specifically bound to two carboxyl oxygen atoms of C-terminal Glu and Asp on the EDLAALEK peptide at a stoichiometric ratio of 1:1. Calcium coordination induced the self-assembly of the EDLAALEK peptide, resulting in the formation of a nanocomposite with a crystal structure. Furthermore, the formed nanocomposite went through dissociation and self-assembly during in vitro GI digestion, accompanied by the release and rechelation of Ca2+, which was related to changes in their secondary structure. Nevertheless, the GI digests of the EDLAALEK-calcium complex could significantly enhance Ca2+ absorption across Caco-2 cell monolayers. The findings suggest that the sea cucumber ovum derived peptide has the potential as an efficient nanocarrier to transport calcium through the GI system.

6.
Chemistry ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31574171

RESUMO

Development of Pt-group metal free catalysts for low-temperature CO oxidation remains critical. In this work, an active and stable mesoporous Cu-Ce-O x  solid solution is presented by spray pyrolysis. The specific surface areas and pore volumes reach as high as ~170 m 2 /g and 0.24 cm 3 /g, respectively. The results of CO oxidation study suggest that (1) the catalyst obtained by the spray pyrolysis possess much higher activity than co-precipitation, sol-gel and hydrothermal methods; (2) the optimal Cu 0.2 -Ce 0.8 -O x  solid solution presents a reactivity over 28 times of both single-component CuO and CeO 2  at 70 o C. Based on the study of pure phase Cu-Ce-O x  solid solution by selective leaching of segregated CuO x  species, the active center for CO oxidation is confirmed as bimetallic Cu-Ce-O site, while the individual CuO x  particles not only act as spectators but also block the active Cu-Ce-O sites. A low apparent activation energy of ~48 KJ/mol is detected for CO oxidation at Cu-Ce-O site, making Cu-Ce-O x  solid solutions sufficient to present high activity at low temperature. Furthermore, the Cu-Ce-O x  catalysts exhibit excellent stability and thermal-tolerance toward CO oxidation.

7.
ACS Appl Mater Interfaces ; 11(43): 39586-39593, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31577122

RESUMO

Extreme rarity and inherent heterogeneity of circulating tumor cells (CTCs) result in a tremendous challenge for the CTC isolation from patient blood samples with high efficiency and purity. Current CTC isolation approaches mainly rely on the epithelial cell adhesion molecule (EpCAM), which may significantly reduce the ability to capture CTCs when the expression of EpCAM is lost or down-regulated in epithelial-mesenchymal transition. Here, a rapid and highly efficient method is developed to isolate and identify heterogeneous CTCs with high efficiency from patient blood samples using the fluorescent-magnetic nanoparticles (F-MNPs). A dual-antibody interface targeting EpCAM and N-cadherin is fabricated onto the F-MNPs to capture epithelial CTCs as well as mesenchymal CTCs from whole blood samples. The poly(carboxybetaine methacrylate) brushes of excellent antifouling properties are employed to decrease nonspecific cell adhesion. Moreover, the F-MNPs provide a prompt identification strategy for heterogeneous CTCs (F-MNPs+, Hoechst 33342+, and CD45-) that can directly identify CTCs in a gentle one-step processing within 1 h after isolation from patient blood samples. This has been demonstrated through artificial samples as well as patient samples in details.

8.
Sci Signal ; 12(604)2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641080

RESUMO

Transitional B cells must actively undergo selection for self-tolerance before maturing into their resting follicular B cell successors. We found that metabolic quiescence was acquired at the follicular B cell stage in both humans and mice. In follicular B cells, the expression of genes involved in ribosome biogenesis, aerobic respiration, and mammalian target of rapamycin complex 1 (mTORC1) signaling was reduced when compared to that in transitional B cells. Functional metabolism studies, profiling of whole-cell metabolites, and analysis of cell surface proteins in human B cells suggested that this transition was also associated with increased extracellular adenosine salvage. Follicular B cells increased the abundance of the cell surface ectonucleotidase CD73, which coincided with adenosine 5'-monophosphate-activated protein kinase (AMPK) activation. Differentiation to the follicular B cell stage in vitro correlated with surface acquisition of CD73 on human transitional B cells and was augmented with the AMPK agonist, AICAR. Last, individuals with gain-of-function PIK3CD (PI3Kδ) mutations and increased pS6 activation exhibited a near absence of circulating follicular B cells. Together, our data suggest that mTORC1 attenuation may be necessary for human follicular B cell development. These data identify a distinct metabolic switch during human B cell development at the transitional to follicular stages, which is characterized by an induction of extracellular adenosine salvage, AMPK activation, and the acquisition of metabolic quiescence.

9.
Clin Chem ; 65(10): 1276-1286, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31492715

RESUMO

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumor with variable prognosis even within the same tumor stage. Cancer-related sex hormones and their sulfated metabolites in body fluids can be used as tumor markers. The role of steroid sulfation in ACC has not yet been studied. MALDI mass spectrometry imaging (MALDI-MSI) is a novel tool for tissue-based chemical phenotyping. METHODS: We performed phenotyping of formalin-fixed, paraffin-embedded tissue samples from 72 ACC by MALDI-MSI at a metabolomics level. RESULTS: Tumoral steroid hormone metabolites-estradiol sulfate [hazard ratio (HR) 0.26; 95% CI, 0.10-0.69; P = 0.005] and estrone 3-sulfate (HR 0.22; 95% CI, 0.07-0.63; P = 0.003)-were significantly associated with prognosis in Kaplan-Meier analyses and after multivariable adjustment for age, tumor stage, and sex (HR 0.29; 95% CI, 0.11-0.79; P = 0.015 and HR 0.30; 95% CI, 0.10-0.91; P = 0.033, respectively). Expression of sulfotransferase SULT2A1 was associated with prognosis to a similar extent and was validated to be a prognostic factor in two published data sets. We discovered the presence of estradiol-17ß 3,17-disulfate (E2S2) in a subset of tumors with particularly poor overall survival. Electron microscopy revealed novel membrane-delimited organelles in only these tumors. By applying cluster analyses of metabolomic data, 3 sulfation-related phenotypes exhibited specific metabolic features unrelated to steroid metabolism. CONCLUSIONS: MALDI-MSI provides novel insights into the pathophysiology of ACC. Steroid hormone sulfation may be used for prognostication and treatment stratification. Sulfation-related metabolic reprogramming may be of relevance also in conditions beyond the rare ACC and can be directly investigated by the use of MALDI-MSI.

10.
J Ethn Subst Abuse ; : 1-13, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31510870

RESUMO

Previous studies have reported controversial results about the association between rs6296 and alcoholism. Thus, a meta-analysis was performed to further explore this association. A comprehensive search was conducted to identify relevant case-control or cohort studies (up to December 1, 2017). A fixed- or random-effect model was selected as a pooling method depending on the heterogeneity among studies. The heterogeneity was measured by Q test and I2 statistic. The Harbord and Peters test was used to estimate publication bias. Fifteen English articles with 16 outcomes and 5,429 participants were included in this meta-analysis. A fixed-effect model was chosen, and the pooled result showed that rs6296 was not related to alcoholism (z = 1.93, p = .053). The Harbord and Peters test showed that there was no publication bias. This meta-analysis indicated that rs6296 may be not be significantly associated with alcoholism, which needs to be further confirmed by future research.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31512998

RESUMO

Chronic pain is a common condition that seriously affects the quality of human life with variable etiology and complicated symptoms; people who suffer from chronic pain may experience anxiety, depression, insomnia, and other harmful emotions. Currently, chronic pain treatments are nonsteroidal anti-inflammatory drugs and opioids; these drugs are demonstrated to be insufficient and cause severe side effects. Therefore, research into new therapeutic strategies for chronic pain is a top priority. In recent years, stem cell transplantation has been demonstrated to be a potent alternative for the treatment of chronic pain. Mesenchymal stem cells (MSCs), a type of pluripotent stem cell, exhibit multi-directional differentiation, promotion of stem cell implantation, and immune regulation; they have also been shown to exert analgesic effects in several chronic pain models. Exosomes produced by MSCs have been demonstrated to relieve painful symptoms with fewer side effects. In this review, we summarize the therapeutic use of MSCs in various chronic pain studies. We also discuss ways to enhance the treatment effect of MSCs. We predict in the future, cell-free therapies for chronic pain will develop from exosomes secreted by MSCs.

12.
J Nat Med ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31493217

RESUMO

One novel neoligan glucoside, Ginkgoside B (1), and one new glucose ester, 6-O-(4-hydroxyhydrocinnamoyl)-D-glucopyranose (2), along with nine known compounds (3-11) were isolated from the ethanol extract of Ginkgo biloba leaves. Their structures were elucidated by combination of spectroscopic analyses and alkaline methanolysis. The absolute configuration of compound 1 was determined by single-crystal X-ray diffraction. All the isolated compounds were evaluated for their cytotoxicity activities, and compound 11 exhibited IC50 values of 36.20 and 58.95 µM against 5637 and HeLa cell lines, respectively.

13.
Phytochemistry ; 168: 112113, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31494343

RESUMO

Sixteen diterpenoids including nine undescribed ones, named rhodoauriculatols A-I, were isolated from the leaves of Rhododendron auriculatum Hemsl. Sixteen diterpenoids belong to seven diverse carbon skeletons, which were classified into 1,10-seco-grayanane, 1,10:2,3-diseco-grayanane, A-homo-B-nor-ent-kaurane, ent-kaurane, 4,5-seco-ent-kaurane, leucothane, and grayanane, respectively. Their structures were determined by the detailed HRESIMS, 1D and 2D NMR, UV, and IR data analysis, and their absolute configurations were established by single crystal X-ray diffraction analysis, electronic circular dichroism (ECD) data analysis, ECD calculation, as well as chemical methods. Rhodoauriculatols A-C possess a rare 1,10-seco-grayanane diterpene skeleton. Rhodoauriculatol D is the second example of the 1,10:2,3-diseco-grayanane diterpenoids, and rhodoauriculatol E is the fourth example of the A-homo-B-nor-ent-kaurane diterpenoids. Rhodomicranone E was reported as a natural product for the first time. All the isolated sixteen diterpenoids showed analgesic activities in the acetic acid-induced writhing test. Rhodoauriculatols B, E-G, rhodomicranone E, pierisformoside F, and micranthanoside A showed significant analgesic activities with the inhibition rates over 40%, and their preliminary structures-activity relationships were studied.

14.
Eur J Pharmacol ; 863: 172679, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31542483

RESUMO

BACKGROUND: Increased expression levels of bone morphogenetic protein 7 (BMP7) are associated with poor prognosis in pulmonary hypertension patients. However, whether BMP7 signaling conspire to involve in the proliferation of pulmonary artery smooth muscle cells (PASMC) underlying monocrotaline (MCT) induced pulmonary arterial hypertension (PAH) remain unclear. METHODS AND RESULTS: Western blot experiments found BMP7 was increased in pulmonary arteries isolated from MCT-PAH rat. In addition, monocrotaline pyrrole (MCTP), the putative toxic metabolite of the MCT, increases the expression of BMP7, proliferating cell nuclear antigen (PCNA) and activin A receptor type 2A, but decreases bone morphogenetic protein receptor type 2 in cultured pulmonary artery smooth muscle cells (PASMC). In PASMCs, exogenous BMP7 leads to the decreasing expression of activin A receptor type 2, increasing phosphorylation of p38MAPK and elevation of P21. However, BMP7 treatment results in the increasing expression of activin A receptor type 2A, p38MAPK, and PCNA in bone morphogenetic protein receptor type 2 knockdown PASMCs. Knockdown of activin A receptor type 2A abrogated the MCTP-induced PCNA and cell cycle progression. CONCLUSIONS: MCTP treatment lead to the expression of BMP7, suppression of bone morphogenetic protein receptor type 2 but increasing expression of activin A receptor type 2A, the BMP7 mediated PASMC proliferation via preferential activation of an activin A receptor type 2A signaling axis.

15.
Food Funct ; 10(10): 6711-6719, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31560353

RESUMO

Food-borne nanoparticles (FNs) produced during thermal processing of food may have potential as nanocarriers for Fe(ii) supplements. In this paper, the FNs in beef patties roasted for different times (15, 30, and 45 minutes) and the binding between FNs and ferrous ions were studied. The size of FNs decreased from 7.5 to 3.0 nm with the increase of baking time, and the FNs emitted bright blue fluorescence under ultraviolet light irradiation. The combination of FNs with ferrous ions was by means of the amino, hydroxyl and carboxyl functional groups on the particles. Cell viability study showed that the Fe(ii)-FNs increased the apoptotic rate, but significantly decreased the necrosis rate, which led to an increase in the number of living cells. In addition, the Fe(ii)-FNs can easily enter the Caco-2 cytoplasm, but not the cellular nucleus. The FNs derived from beef patties with an ultra-small size, high water solubility and plenty of functional groups might be good candidates as nanocarriers for Fe(ii) delivery.

16.
JCI Insight ; 4(17)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31484828

RESUMO

Recent genetic examinations and multisteroid profiles have provided the basis for subclassification of aldosterone-producing adenomas (APAs). The objective of the current study was to produce a comprehensive, high-resolution mass spectrometry imaging (MSI) map of APAs in relation to morphometry, immunohistochemical profiles, mutational status, and clinical outcome. The study cohort comprised 136 patients with unilateral primary aldosteronism. Matrix-assisted laser desorption/ionization-Fourier transform-ion cyclotron resonance MSI was conducted, and metabolite profiles were analyzed with genotype/phenotype information, including digital image analysis from morphometry and IHC of steroidogenic enzymes. Distinct molecular signatures between KCNJ5- and CACNA1D-mutated APAs with significant differences of 137 metabolites, including metabolites of purine metabolism and steroidogenesis, were observed. Intratumor concentration of 18-oxocortisol and 18-hydroxycortisol were inversely correlated with the staining intensity of CYP11B1. Lower staining intensity of CYP11B1 and higher levels of 18-oxocortisol were associated with a higher probability of complete clinical success after surgery. The present study demonstrates distinct metabolomic profiles of APAs in relation to tumor genotype. In addition, we reveal an inverse correlation between cortisol derivatives and CYP11B1 and the impact of 18-oxocortisol and CYP11B1 on clinical outcome, which provides unprecedented insights into the pathophysiology, clinical features, and steroidogenesis of APAs.

17.
Transbound Emerg Dis ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31433123

RESUMO

Malignant catarrhal fever (MCF) is a fatal lymphoproliferative disease that represents a serious problem in the deer-rearing industry. To better understand an MCF-like disease that has emerged in northern China since 2015, we investigated ten cases by documenting clinical and epidemiological data and analysing causative agents and histopathological changes. In addition, a retrospective screen for Macavirus DNA and a questionnaire-based survey were conducted. Epizootic MCF in Chinese sika deer herds has emerged with a low morbidity of 3.8% (95% CI: 2.5%-5.1%) and a high mortality of 93.2% (95% CI: 86.6%-99.9%). The disease course varied from 3 to 12 days. Aetiologically, OvHV-2 was predominant in the MCFV, accounting for most MCF cases (21/23). In contrast, only two CpHV-2 isolates were phylogenetically closely related to CpHV-2. Diarrhoea and nasal discharges were the most frequent manifestations, although clinical signs varied in some cases. Pathologically typical lesions of haemorrhage, necrosis and lymphoid cell infiltration were readily observed in a variety of organs. Vasculitis caused by vascular and perivascular lymphoid cell infiltration was common. The retrospective survey suggested a low positive rate (3/275) of MCFV DNA in peripheral blood lymphocytes (PBL). The questionnaire-based survey suggested the disease was neglected by local veterinarians, who did not acknowledge the risk of co-rearing deer with reservoir species. Collectively, the emerging epizootic MCF in Chinese sika deer herds remains neglected, emphasizing the urgency of initiating full-field diagnoses and control strategies.

18.
Int J Biol Macromol ; 140: 1249-1259, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31465800

RESUMO

The therapeutics having ability to target cancer cells specifically and exhibit nominal cytopathic effect on normal healthy cells are highly significant for cancer therapeutic applications. Recombinant porcine natural killer lysin (rpNK-lysin) has proven cationic anti-bacterial and anti-tumor peptide. Herein, we report its anti-invasion and anti-metastasis effects on hepatocellular carcinoma (HCC) cells in vitro. We first investigate the maximum non-toxic concentration (MNTC) of rpNK-lysin for the normal hepato cells (L-02). Using MNTC rpNK-lysin, we explore anti-proliferative, anti-adhesive, anti-invasive and anti-metastatic effect of rpNK-lysin on three different HCC cells lines (SMMC-7721, 97-H and HepG2) through MTT, wound-healing, adhesion and invasion assay along with mRNA and protein expression. The results reveal that rpNK-lysin has potential to specifically inhibit HCC cells growth in a dose and time-dependent manner with a little cytopathic effect on the L-02 cells, effectively reduce migration, adhesion and invasion ability of HCC cells. rpNK-lysin significantly reduce Fascin1 expression, which subsequently decrease ß-catenin expression and metaloproteinases (MMP-2 and MMP9). This study suggest that MNTC rpNK-lysin has an anti-invasion and anti-metastasis effect on HCC cells in vitro through inhibition of Fascin 1 expression which regulates Wnt/ß-catenin signaling pathway by inducing ß-catenin degradation and subsequently results in suppression of MMP-2 and MMP9 expression.

19.
Food Funct ; 10(9): 5605-5615, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31432849

RESUMO

The effects of amino acids Gln and Lys on the antioxidant ability of peptides were investigated in this study. The identified peptides Lys-Met-Asp-Asp-Lys (KMDDK), Lys-Met-Asp-Asp-Gln (KMDDQ), Gln-Met-Asp-Asp-Lys (QMDDK), and Gln-Met-Asp-Asp-Gln (QMDDQ) were used to investigate their antioxidant activity and the structure-activity relationship by using UPLC-Q-TOF-MS, flow cytometry, laser scanning confocal microscopy and 1H NMR spectroscopy. The results indicated that the four pentapeptides significantly increased the viability of PC12 cells and inhibited cell apoptosis and that QMDDQ possessed a stronger survival activity than the others in cell apoptosis. Moreover, the four peptides significantly decreased the scopolamine-induced ROS and LDH content in PC12 cells, and upregulated the SOD activity to the level of the scopolamine group. The DPPH and hydroxyl radical scavenging of QMDDQ were higher than those of the other peptides at 0.5 mg mL-1 and 1.0 mg mL-1 (P < 0.05). 1H NMR spectra revealed that the prominent antioxidant ability of QMDDQ might be attributed to more active hydrogen sites and functional groups. The carboxyl active hydrogen atoms and amino active hydrogen atoms as active sites play a critical role in the antioxidant capacity.

20.
Chem Commun (Camb) ; 55(66): 9861-9864, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31364622

RESUMO

Single-tailed and gemini-type supra-gelators were facilely fabricated via the conjugation of the d- or l-enantiomeric dihydrazide TDH with single-tailed achiral aldehyde C12BAD through dynamic acylhydrazone bonding. Chirality transfer from small molecules to supramolecules was successfully achieved via the spontaneous assembly of the formed supra-gelators into supramolecular chiral hydrogels.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA