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1.
Int J Neurosci ; : 1-7, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31696761

RESUMO

Background and Purpose: Oxidative stress is involved in the development of infections. However, whether oxidative stress indicators can be used as markers of stroke-associated infection (SAI) is still unclear. The purpose of this study was to test the predictive values of superoxide dismutase (SOD) and malondialdehyde (MDA) levels for SAI incidence.Methods: A total of 45 consecutive patients with ischemic stroke who were admitted to our hospital were enrolled. A prospective study was carried out to observe the occurrence of SAI during the first 7 days after stroke. Accordingly, the patients were divided into SAI and non-SAI groups. The relationship between SOD and MDA serum levels and SAI was analyzed.Results: The patients in the SAI group had significantly higher serum SOD levels than those in the non-SAI group (41.638 ± 3.428 U/ml vs. 36.542 ± 9.114 U/ml, p = 0.033). However, there were no significant differences in MDA levels between the SAI and non-SAI group (p > 0.05). The discriminating ability of serum SOD level for SAI was measured using an ROC curve. Serum level of SOD >38.16 U/ml was useful in diagnosing SAI with a sensitivity of 88% and a specificity of 61%. Kaplan-Meier curves showed that the group with serum SOD level >38.16 U/ml had higher rates of SAI incidence (χ2 = 9.688, p = 0.002; log rank test). Furthermore, Cox regression analysis indicated that a serum SOD level >38.16 U/ml was an independent risk factor for SAI (hazard ratio = 5.836; 95% CI, 1.298-26.244; p = 0.021).Conclusions: Acute-phase serum SOD level could be a predictor of SAI.

2.
Plant Cell Physiol ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31693150

RESUMO

Although control of xylem ion loading is essential to confer salinity stress tolerance, specific details behind this process remain elusive. In this work, we compared kinetics of xylem Na+ and K+ loading between two halophytes (Atriplex lentiformis and quinoa) and two glycophyte (pea and beans) species, to understand the mechanistic basis of the above process. Halophyte plants had high initial amounts of Na+ in the leaf, even when grown in the absence of the salt stress. This was matched by 7-fold xylem sap Na+ concentration compared with glycophyte plants. Upon salinity exposure, the xylem sap Na+ concentration increased rapidly but transiently in halophytes, while in glycophytes this increase was much delayed. Electrophysiological experiments using the MIFE technique showed that glycophyte plants tend to re-absorb Na+ back into the stele, thus reducing xylem Na+ load at the early stages of salinity exposure. The halophyte plants, however, were capable to release Na+ even in the presence of high Na+ concentrations in the xylem. The presence of H2O2 (mimicking NaCl-stress induced ROS accumulation in the root) caused a massive Na+ and Ca2+ uptake into the root stele, while triggering a substantial K+ efflux from the cytosol into apoplast in glycophyte but not halophytes species. The peak in H2O2 production was achieved faster in halophytes (30 min vs 4 h) and was attributed to the increased transcript levels of RbohE. Pharmacological data suggested that non-selective cation channels are unlikely play a major role in ROS-mediated xylem Na+ loading.

3.
Fish Physiol Biochem ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31709461

RESUMO

The full-length cDNA coding IGF-I was cloned from the liver of Yellow catfish Pelteobagrus fulvidraco. The tissue distributions of IGF-I in adults were then analyzed by using real-time PCR. The effects of starvation (3 weeks) and subsequent refeeding (3 weeks) on the compensatory growth performance in juvenile fish weighing 3.80 ± 0.78 g and hepatic IGF-I mRNA expressions were also investigated. The cDNA obtained covered 884 bp with an open reading frame of 480 bp encoding 159 amino acids. It is composed of a signal peptide with 41 amino acids (AAs), a mature peptide comprising the B, C, A, and D domains (71 AAs) and E domain of 47 AAs. Sequence alignment and phylogenetic analysis revealed a high degree of conservation (71-87%) among the species of Siluriformes and some closely related species. In adults, the highest IGF-I expression was observed in the liver, followed by the brain, whereas relatively low expressions were detected in muscle and stomach. Both body weight and length increased significantly in fish fed to satiation continuously. Body weight, body length, condition factor, and hepatic IGF-I expressions were all decreased remarkably with increasing starvation times, but increased significantly after refeeding. The results showed that the expression of IGF-I was positively correlated with feed intakes and IGF-I may play a key regulatory role for somatic growth induced by compensatory growth in Yellow catfish.

4.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(9): 1122-1126, 2019 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-31640954

RESUMO

Previous studies have shown that postoperative cognitive dysfunction (POCD) is related to multiple factors including age, postoperative trauma, inflammation, postoperative pain, and anesthesia, among which postoperative pain is thought to play an important role in the development of POCD. This review summarizes the recent findings in the study of the role of postoperative pain in the pathogenesis of POCD in light of nerve injuries, neural remodeling and stress, and the progress in the prevention and treatment of POCD in elderly patients. It is of vital important to assess the postoperative pain and formulate adequate analgesic regimens for effective prevention and management of POCD to protect the brain functions of elderly patients.


Assuntos
Disfunção Cognitiva/etiologia , Dor Pós-Operatória/complicações , Complicações Pós-Operatórias , Idoso , Humanos , Inflamação , Dor Pós-Operatória/terapia
5.
Chemosphere ; 235: 1050-1058, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31561294

RESUMO

Lead (Pb) is one of the most toxic heavy metals and has aroused widespread concern as it can cause severe impairments in the developing nervous system. Autophagy has been proposed as an injury factor in Pb-induced neurotoxicity. In this study, we used zebrafish embryo as a model, measured the general toxic effects of Pb, and investigated the effect of Pb exposure on autophagy, and its role in Pb-induced developmental neurotoxicity. Zebrafish embryos were exposed to Pb at concentrations of 0, 0.1, 1 or 10 µM until 4 days post-fertilization. Our data showed that exposure to 10 µM Pb significantly reduced survival rates and impaired locomotor activity. Uptake of Pb was enhanced as the concentration and duration of exposure increased. Inhibition of lysosomal degradation with bafilomycin A1 treatment abolished the suppression of Lc3-II protein expression by Pb. Furthermore, autophagosome formation was inhibited by Pb in the brain. In addition, mRNA expression of beclin1, one of the critical genes in autophagy, were decreased in Pb exposure groups at 72 h post-fertilization. Whole-mount in situ hybridization assay showed that beclin1 gene expression in the brain was reduced by Pb. Rapamycin, an autophagy inducer, partly resolved developmental neurotoxicity induced by Pb exposure. Our results suggest that autophagy plays a protective role in the developmental neurotoxicity of Pb in zebrafish embryos and larvae.


Assuntos
Autofagia/efeitos dos fármacos , Intoxicação do Sistema Nervoso por Chumbo/prevenção & controle , Chumbo/toxicidade , Peixe-Zebra/embriologia , Animais , Expressão Gênica , Larva/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo
6.
Artigo em Inglês | MEDLINE | ID: mdl-31480157

RESUMO

Objective: We investigated the temporal expression profiles of long noncoding RNA (lncRNA) and mRNA in the peripheral blood of pigs during development and identified the lncRNAs that are related to the blood-based immune system. Methods: Peripheral blood samples were obtained from the pigs at 0, 7, 28 and 180 days and 2 years of age. RNA sequencing was performed to survey the lncRNA and mRNA transcriptomes in the samples. Short time-series expression miner (STEM) was used to show temporal expression patterns in the mRNAs and lncRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to assess the genes' biological relevance. To predict the functions of the identified lncRNAs, we extracted mRNAs that were nearby loci and highly correlated with the lncRNAs. Results: In total of 5,946 lncRNA and 12,354 mRNA transcripts were identified among the samples. STEM showed that most lncRNAs and mRNAs had similar temporal expression patterns during development, indicating the expressional correlation and functional relatedness between them. The five stages were divided into two classes: the suckling period and the late developmental stage. Most genes were expressed at low level during the suckling period, but at higher level during the late stages. Expression of several T-cell-related genes increased continuously during the suckling period, indicating that these genes are crucial for establishing the adaptive immune system in piglets at this stage. Notably, lncRNA TCONS-00086451 may promote blood-based immune system development by upregulating nuclear factor of activated T-cells cytoplasmic 2 (NFATC2) expression. Conclusion: This study provides a catalog of porcine peripheral blood-related lncRNAs and mRNAs and reveals the characteristics and temporal expression profiles of these lncRNAs and mRNAs during peripheral blood development from the newborn to adult stages in pigs.

7.
Int J Cardiol ; 295: 7-13, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31399301

RESUMO

BACKGROUND: Vascular aging has profound effects on cardiovascular diseases. Endothelial to mesenchymal transition (EndMT) is defined as the acquisition of mesenchymal characteristics by endothelial cells (ECs) and has been found induced in a model of ECs aging. However, whether EndMT occurs during aging in vivo, the functional significance of EndMT on vascular biology and the underlying mechanisms remain unknown. METHODS AND RESULTS: In this study, we examined the vascular ECs from young (2 months old) and old (18 months old) mice, and demonstrated that aged ECs underwent EndMT. Moreover, the transwell assay showed that EndMT process was accompanied by increased endothelial permeability. It was found that sirtuin 6 (SIRT6), a nicotinamide adenine dinucleotide+ (NAD+)-dependent histone deacetylase, was down-regulated during ECs aging. Knockdown of SIRT6 in young ECs could induce EndMT. Next, we identified five long non-coding RNAs that are enriched in ECs for downstream effector of SIRT6; only metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was significantly up-regulated in aged ECs. Knockdown of SIRT6 could increase MALAT1 levels. Furthermore, the ChIP assay and luciferase reporter gene assay confirmed that SIRT6 bound directly to the promoter region of MALAT1 and suppressed MALAT1 expression. Finally, we demonstrated that MALAT1 mediated aging-induced EndMT through increasing Snail expression. CONCLUSION: Our study provides in vivo evidence that ECs undergo EndMT during vascular aging, which increases endothelial permeability. SIRT6-mediated transcriptional suppression of MALAT1 is a key mechanism for EndMT. Manipulating EndMT may be considered as a new therapeutic strategy for retarding aging-associated vascular diseases.

8.
Int J Mol Med ; 44(4): 1594, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432126

RESUMO

Subsequently to the publication of the article, the authors have realized that the second and third author affiliations were presented the wrong way around, and should have been reversed. Therefore, the author affiliations in this paper should have appeared as follows: Faqing Tian1, Yong Zhan2, Wei Zhu3, Juheng Li1, Meiqin Tang1, Xiaohui Chen1 and Jian Jiang1. Departments of 1Hematology and 2Radiology, Longgang District People's Hospital of Shenzhen, Shenzhen, Guangdong 518172; 3Department of Pathology, School of Basic Medicine, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China. The authors regret that these errors and omissions were not corrected prior to the publication of the paper, and apologize to the readership for the inconvenience caused. [the original article was published in International Journal of Molecular Medicine 43: 1058­1066, 2019; DOI: 10.3892/ijmm.2018.4019].

9.
Int J Mol Sci ; 20(17)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443572

RESUMO

In this work, the effect of drought on K+ uptake in root and its translocation from root to shoot was investigated using six barley genotypes contrasting in drought tolerance. Results showed that drought conditions caused significant changes in K+ uptake and translocation in a time- and genotype-specific manner, which consequently resulted in a significant difference in tissue K+ contents and drought tolerance levels between the contrasting barley genotypes. The role of K+ transporters and channels and plasma membrane (PM) H+-ATPase in barley's adaptive response to drought stress was further investigated at the transcript level. The expression of genes conferring K+ uptake (HvHAK1, HvHAK5, HvKUP1, HvKUP2 and HvAKT1) and xylem loading (HvSKOR) in roots were all affected by drought stress in a time- and genotype-specific manner, indicating that the regulation of these K+ transporters and channels is critical for root K+ uptake and root to shoot K+ translocation in barley under drought stress. Furthermore, the barley genotypes showed a strong correlation between H+ efflux and K+ influx under drought stress, which was further confirmed by the significant up-regulation of HvHA1 and HvHA2. These results suggested an important role of plasma membrane H+-ATPase activity and/or expression in regulating the activity of K+ transporters and channels under drought stress. Taken together, it may be concluded that the genotypic difference in drought stress tolerance in barley is conferred by the difference in the ability to regulate K+ transporters and channels in root epidermis and stele.

10.
J Exp Clin Cancer Res ; 38(1): 316, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31319849

RESUMO

BACKGROUND: Sorafenib is the first-line treatment for advanced-stage hepatocellular carcinoma (HCC). Several studies have shown that the up-regulation of ß-catenin plays a role in sorafenib resistance in HCC; however, the mechanism associated with this phenomenon remains elusive. METHODS: Western blotting, flow cytometry, and an evaluation of IC50 values were used to confirm the role of ß-catenin in HCC sorafenib resistance. Immunoprecipitation and western blotting were then performed to identify regulatory interactions between ß-catenin and Nek2. Further, western blotting, flow cytometry, and an in vivo xenograft model were used to evaluate the function of Nek2 in HCC sorafenib resistance, whereas rescue experiments were performed to confirm that Nek2 induces sorafenib resistance via ß-catenin. Finally, western blotting and immunohistochemistry were used to evaluate the expression level of Nek2 in paired HCC and non-tumor tissues. RESULTS: We showed that ß-catenin could suppress sorafenib-induced apoptosis and cell growth inhibition in HCC cell lines. By screening ß-catenin-interacting proteins, we found that Nek2 could bind ß-catenin in sorafenib-treated HCC cell lines. Our results also showed that Nek2 stabilizes ß-catenin and promotes its translocation to the nucleus, consequently activating the transcription of downstream target genes. We further confirmed that Nek2 could induce sorafenib resistance in HCC cell lines, and that ß-catenin was the key element involved in this process. Further, a xenograft tumor model showed that Nek2 knockdown could improve the anti-tumor effect of sorafenib, whereas an analysis of tumor proteins showed that Nek2 regulates ß-catenin protein levels and its nuclear translocation in vivo. In addition, Nek2 was found to be up-regulated in HCC tissue, and especially in advanced-stage disease. CONCLUSIONS: Our study proves that Nek2 induces HCC sorafenib resistance via ß-catenin and suggests a novel therapeutic strategy to improve the anti-tumor effects of sorafenib in HCC.

12.
Ann Surg Oncol ; 26(9): 2890-2898, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31183641

RESUMO

BACKGROUND: Effective tools evaluating the prognosis for patients with esophageal cancer undergoing surgery is lacking. The current study aimed to develop a nomogram to predict overall survival (OS) and provide evidence for adjuvant therapy for patients with esophageal carcinoma after esophagectomy. METHODS: The study retrospectively reviewed patients with pathologic T1N +/T2-4aN0-3, M0 thoracic esophageal squamous cell carcinoma after radical esophagectomy, with or without adjuvant therapy, in one institution as the training cohort (n = 2281). A nomogram was established using Cox proportional hazard regression to identify prognostic factors for OS, which were validated in an independent validation cohort (n = 1437). Area under curve (AUC) values of receiver operating characteristic curves were calculated to evaluate prognostic efficacy. RESULTS: In the training cohort, the median OS was 50.46 months, and the 5-year OS rate was 47.08%. Adjuvant therapy, sex, tumor location, grade, lymphovascular invasion, removed lymph nodes, and T and N categories were identified as predictive factors for OS. The nomogram showed favorable prognostic efficacy in the training and validation cohorts (5-year OS AUC: 0.685 and 0.744, respectively), which was significantly higher than that of the American Joint Committee on Cancer (AJCC) staging system. The nomogram distinguished OS rates among six risk groups, whereas AJCC could not separate the OS of 2A and 1B, 3C and 3B, or 3A and 2B. Patients with a nomogram score of 72 to 227 were predicted to achieve a 5-year OS increase of 10% or more from adjuvant therapy. CONCLUSION: The nomogram could effectively predict OS and aided decision making in adjuvant therapy for patients with thoracic esophageal squamous cell carcinoma after esophagectomy.

13.
Arterioscler Thromb Vasc Biol ; 39(8): 1629-1644, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31189430

RESUMO

OBJECTIVE: Periaortic arch adipose tissue (PAAT) plays critical roles in regulating vascular homeostasis; however, its anatomic features, developmental processes, and origins remain unclear. Approach and Results: Anatomic analysis and genetic lineage tracing of Wnt1 (wingless-type MMTV [mouse mammary tumor virus] integration site family member 1)-Cre+;Rosa26RFP/+ mice, Myf5 (myogenic factor 5)-Cre+;Rosa26RFP/+ mice, and SM22α-Cre+;Rosa26RFP/+ mice are performed, and the results show that PAAT has unique anatomic features, and the developmental processes of PAAT are independent of the others periaortic adipose tissues. PAAT adipocytes are mainly derived from neural crest cells (NCCs) rather than from Myf5+ progenitors. Most PAAT adipocyte progenitors expressed SM22α+ (smooth muscle protein 22-alpha) during development. Using Wnt1-Cre+;PPARγflox/flox mice, we found that knockout of PPAR (peroxisome proliferator-activated receptor)-γ in NCCs results in PAAT developmental delay and dysplasia, further confirming that NCCs contribute to PAAT formation. And we further indicated PAAT dysplasia aggravates Ang II (angiotensin II)-induced inflammation and remodeling of the common carotid artery close to aorta arch. We also found that NCCs can be differentiated into both brown and white adipocytes in vivo and in vitro. RNA sequencing results suggested NCC-derived adipose tissue displays a distinct transcriptional profile compared with the non-NCC-derived adipose tissue in PAAT. CONCLUSIONS: PAAT has distinctive anatomic features and developmental processes. Most PAAT adipocytes are originated from NCCs which derive from ectoderm. NCCs are progenitors not only of white adipocytes but also of brown adipocytes. This study indicates that the PAAT is derived from multiple cell lineages, the adipocytes derived from different origins have distinct transcriptional profiles, and PAAT plays a critical role in Ang II-induced common carotid artery inflammation and remodeling.Visual OvervieW: An online visual overview is available for this article.

14.
Anal Chim Acta ; 1072: 54-60, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31146865

RESUMO

In this work, we reported a novel electrochemical sensor for enantiorecognition of electrochemically inactive aspartic acid (Asp) enantiomers. By combining sol-gel processing with molecular imprinting technology, an enantioselective interface of molecularly imprinted sol-gel (MIS) films with imprinted cavities was prepared on the surface of a glassy carbon electrode (GCE). In order to obtain the electrochemical responses of electrochemically inactive Asp, the ternary derivative of L-aspartic, (l-aspartic acid)Cu2+(N-carbobenzoxy-l-aspartic acid), was used as the template for fabrication of MIS. The stripping currents of target molecules could be detected by square-wave stripping voltammetry due to the reduction of cupric ion on the modified electrode. The resulted sensor showed good adsorbability to L-Asp derivative, and the recognition efficiency was obtained as 2.1. Meanwhile, the L-Asp was quantitatively determined by the MIS sensor. As a result, the proposed electrochemical sensor could be regarded as a potential platform for enantiorecognition of electrochemically inactive chiral compounds.


Assuntos
Ácido Aspártico/análise , Complexos de Coordenação/química , Cobre/química , Técnicas Eletroquímicas , Impressão Molecular , Géis/química , Conformação Molecular , Tamanho da Partícula , Estereoisomerismo , Propriedades de Superfície
15.
BMC Plant Biol ; 19(1): 231, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159735

RESUMO

BACKGROUND: Four-Coumarate:CoA ligase gene (4CL) plays multiple important roles in plant growth and development by catalyzing the formation of CoA ester. 4CL belongs to the plant phenylpropane derivative, which is related to the synthesis of flavonoids and lignin and is a key enzyme in the biosynthetic pathway. RESULTS: In this study, 12 4CL genes of Fraxinus mandschurica were identified and named Fm4CL1-Fm4CL12, respectively. The analysis of the expression pattern of Fm4CL genes indicate that Fm4CL-like 1 gene may play a role in the lignin synthesis pathway. Our study indicate that overexpression of Fm4CL-like 1 increases the lignin content of transgenic tobacco by 39.5% compared to WT, and the S/G ratio of transgenic tobacco increased by 19.7% compared with WT. The xylem cell layer of transgenic line is increased by 40% compared to WT, the xylem cell wall thickness increased by 21.6% compared to the WT. Under mannitol-simulated drought stress, the root length of transgenic tobacco is 64% longer than WT, and the seed germination rate of the transgenic lines is 47% higher than that of WT. In addition, the H2O2 content in the transgenic tobacco was 22% lower than that of WT, while the POD and SOD content was higher than WT by 30 and 24% respectively, which showed Fm4CL-like 1 affect the accumulation of reactive oxygen species (ROS). The MDA content and relative conductivity was 25 and 15% lower than WT, respectively. The water loss rate is 16.7% lower than that of WT. The relative expression levels of stress-related genes NtHAK, NtAPX, NtCAT, NtABF2, and NtZFP were higher than those of WT under stress treatment. The stomatal apertures of OE (Overexpression) were 30% smaller than those of WT, and the photosynthetic rate of OE was 48% higher than that of WT. These results showed that the overexpression line exhibited stronger adaptability to osmotic stress than WT. CONCLUSIONS: Our results indicate that Fm4CL-like 1 is involved in secondary cell wall development and lignin synthesis. Fm4CL-like 1 play an important role in osmotic stress by affecting cell wall and stomatal development.


Assuntos
Secas , Proteínas de Plantas/genética , Tabaco/fisiologia , Clonagem Molecular , Fraxinus/genética , Fraxinus/metabolismo , Expressão Gênica , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/fisiologia , Estresse Fisiológico/genética , Tabaco/genética
16.
Aging (Albany NY) ; 11(11): 3768-3784, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182679

RESUMO

Myocyte enhancer factor 2A (MEF2A) dysfunction is closely related to the occurrence of senile diseases such as cardiocerebrovascular diseases, but the underlying molecular mechanism is unclear. Here, we studied the effects of MEF2A on the senescent phenotype of vascular endothelial cells (VEC) and downstream signaling pathway, and the association between plasma MEF2A levels and coronary artery disease (CAD). Results showed that MEF2A silencing promoted cell senescence and down-regulated PI3K/p-AKT/Sirtuin 1 (SIRT1) expression. MEF2A overexpression delayed cell senescence and up-regulated PI3K/p-AKT/SIRT1. Hydrogen peroxide (H2O2) treatment induced cellular senescence and down-regulated the expression of MEF2A and PI3K/p-AKT/SIRT1. MEF2A overexpression inhibited cellular senescence and the down-regulation of PI3K/p-AKT/SIRT1 induced by H2O2. Further study revealed that MEF2A directly up-regulated the expression of PIK3CA and PIK3CG through MEF2 binding sites in the promoter region. Pearson correlation and logistic regression analysis showed that the plasma level of MEF2A was negatively correlated with CAD, and with age in the controls. These results suggested that MEF2A can directly up-regulate PI3K gene expression, and one of the molecular mechanisms of delaying effect of MEF2A on VEC cell senescence was SIRT1-expression activation through the PI3K/p-Akt pathway. Moreover, the plasma MEF2A levels may be a potential biomarker for CAD risk prediction.

17.
Colloids Surf B Biointerfaces ; 181: 94-101, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31125923

RESUMO

A cross-linkable gemcitabine (GEM)-containing reduction-sensitive polymeric micelles based on the copolymer poly(PEG-co-CMA-co-GEM) was successfully fabricated. The copolymer which synthesized by one-step radical copolymerization of poly(ethylene glycol) methacrylate (PEGMA), 7-(2-Methylacryloylethoxy)-4-methylcoumarin (CMA), and 2-((2-hydroxyethyl)disulfanyl)ethyl acrylate (HSEA-GEM), endowed the micelles with "stealth" surface in circulation, photo cross-linkable property, and reduction-sensitivity. The designed micelles were fabricated by self-assembly of the copolymer in aqueous solution followed by UV-light induced cross-linking of coumarin moieties to enhance stability, which would not disassemble even below critical micelle concentration (CMC) or in non-selective solvent (DMSO/H2O 1:1). In vitro drug release curve demonstrated that the intracellular-mimicking reductive microenvironment could accelerated the GEM release of the prodrug micelles. These micelles could be effectively internalized by BxPC-3 pancreatic cancer cells according to confocal laser scanning microscopy (CLSM) detection and flow cytometry analysis. Meanwhile, methyl thiazolyl tetrazolium (MTT) assay demonstrated that the cross-linked prodrug micelles could efficiently inhibit the proliferation of BxPC-3 cells.

18.
Anal Sci ; 35(8): 929-934, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31061243

RESUMO

In this work, the electrochemiluminscence system of nitrogen-doped graphene quantum dots (N-GQDs) and K2S2O8 was built for the determination of crystal violet (CV). Meanwhile, a carboxylic carbon nanotubes modified glassy carbon electrode (CCNTs/GCE) was used as an ECL sensor. Thanks to the excellent electron transfer ability and large surface area of CCNTs, the ECL signal of N-GQDs@S2O82- was remarkablely amplified. With the presence of a low concentration of CV, a distinct decrease of the ECL signal was observed due to a quenching effect of CV on the ECL emission. Moreover, the quenched ECL intensity responded linearly to the logarithm of CV concentration within the range of 0.05 - 5 µmol/L, with a LOD of 45 nmol/L (S/N = 3). The proposed ECL system exhibited high sensitivity and specificity to CV, which was successfully applied in the practical detection of CV in real water samples from a local fishpond farm.

19.
J Stroke Cerebrovasc Dis ; 28(7): 1824-1831, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31078388

RESUMO

OBJECTIVE: To assess the reproducibility of 3.0T high-resolution magnetic resonance imaging for the identification and quantification of atherosclerotic plaques in the middle cerebral artery. METHODS: Sixty-nine consecutive patients with ischemic stroke or asymptomatic stenosis (>30%) of the middle cerebral artery underwent 3.0T high-resolution magnetic resonance imaging examinations. Two independent investigators reviewed all images with 1 investigator re-evaluating all images 4 weeks later. Wall characteristics of the middle cerebral artery, including plaque surface morphology, plaque location, plaque components, and burden were identified and measured. RESULTS: Intraobserver and interobserver agreement were all substantial in identifying plaque surface irregularity (k = 0.741, 0.555-0.897; k = 0.685, 0.490-0.843; respectively) and intraplaque hemorrhage (k = 0.654, 0.446-0.838; k = 0.605, 0.369-0.792; respectively). Intraobserver agreement was substantial (k = 0.654) and interobserver agreement was moderate (k = 0.553) for the identification of plaque fibrous caps. The total intraobserver and interobserver reproducibility was almost excellent for the identification of plaque position. With regards to vessel area measurement at the site of maximal lumen narrowing, intraobserver and interobserver reproducibility was excellent (intraclass correlation coefficient was 0.886 and 0.885, respectively) and moderate for lumen area at the site of maximal lumen narrowing (intraclass correlation coefficient was 0.695 and 0.558, respectively). In addition, intraobserver and interobserver reproducibility was excellent for vessel area and lumen area measurements at the reference sites. CONCLUSIONS: The reproducibility of 3.0T high-resolution magnetic resonance imaging for the identification and quantification of artery wall characteristics was overall acceptable. However, the reliability for lumen area measurement at the maximum narrowing site and identification of the fibrous cap needs to be improved.


Assuntos
Angiografia Cerebral/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Arteriosclerose Intracraniana/diagnóstico por imagem , Ataque Isquêmico Transitório/diagnóstico por imagem , Angiografia por Ressonância Magnética/métodos , Artéria Cerebral Média/diagnóstico por imagem , Placa Aterosclerótica , Idoso , Feminino , Fibrose , Humanos , Infarto da Artéria Cerebral Média/patologia , Arteriosclerose Intracraniana/patologia , Ataque Isquêmico Transitório/patologia , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/patologia , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
20.
Hematology ; 24(1): 446-454, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31072235

RESUMO

BACKGROUND: Various subsets of diffuse large B-cell lymphoma(DLBCL) are distinguished based on molecular and immunohistochemical features. As we know, CD5 is a pan-T-cell surface marker and is seldom expressed in DLBCL. Large-scale studies of de novo CD5+ DLBCL are lacking in Chinese patients. METHOD: A total of 139 patients with DLBCL (30 CD5+ DLBCL and 109 CD5- DLBCL) who were immunophenotyped and treated with chemotherapy were subjected to this analysis. There were 85 males and 54 females. Their age ranged from 17 to 84 years old, and the median age was 58 years old. RESULTS: In this study CD5+ DLBCL was associated with higher IPI scores (>2), bone marrow involvement, higher probability of >1 ECOG performance status, non-germinal center B-cell like(non-GCB), BCL2 overexpression, whereas seldom expressed CD10 or BCL6, and unconspicuous higher expression of Ki67. With standard chemotherapy, CD5+ DLBCL patients had significantly worse overall survival (OS, median, 29.5 months vs. not reached, P = 0.0004) and progression-free survival (PFS, median, 18.0 months vs. not reached, P = 0.0002) than CD5- DLBCL patients, which had independent prognostic significance of the International Prognostic Index (IPI), and subtype of the non-GCB DLBCL. For CD5+ DLBCL, the addition of rituximab to chemotherapy may not significantly improve the OS (median, 14 months vs. 29.5 months, P = 0.72) and PFS (median, 10 months vs. 12 months, P = 0.92). CONCLUSION: CD5+ DLBCL patients have the distinctive clinical and biological features, they should be provided with clinic individualized treatment and important pathways with therapeutic implications should be underscored.


Assuntos
Antígenos CD5/genética , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
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