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1.
Immunopharmacol Immunotoxicol ; : 1-8, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34549685

RESUMO

OBJECTIVE: O-glycosylation is the most common post-translational modification of proteins, which is involved in many pathophysiological processes including inflammation. Acute liver injury is characterized by an excessive, uncontrolled inflammatory response, but the effects of aberrant O-glycosylation on acute liver injury are yet to explore. Here we aimed to investigate the role of defective O-glycosylation in D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced acute liver damage in mice. MATERIAL AND METHODS: Experimental mice were administrated with an O-glycosylation inhibitor (benzyl-a-GalNac, 5 mg/kg) at 24 h before administration of GalN/LPS. At 12 h after GalN/LPS administration, mice were sacrificed to collect blood and liver samples for further analysis. RESULTS: We found that benzyl-a-GalNac treatment-induced abundant expression of Tn antigen, which is an immature O-glycan representing abnormal O-glycosylation. Benzyl-a-GalNac pretreatment exacerbated considerably GalN/LPS-induced liver damage in mice, evidenced by significantly reduced survival rates, more severe histological alterations, and notable elevation of multiple inflammatory cytokines and chemokines. Mechanistically, benzyl-a-GalNac could trigger endoplasmic reticulum (ER) stress in the liver of mice, demonstrated by the elevated expression of glucose-regulated protein 78 (GRP78) and C/EBP-homologous protein (CHOP), both of which are hallmarks for ER stress. Inhibition of ER stress by 4-phenylbutyric acid (4-PBA) markedly abrogated benzyl-a-GalNac-mediated enhanced hepatotoxicity and systemic inflammation in GalN/LPS-treated mice. CONCLUSIONS: This study demonstrated that inhibition of O-glycosylation caused by benzyl-a-GalNac aggravated GalN/LPS-induced liver damage and systemic inflammation, which may be due to activation of ER stress.

2.
Int J Biol Macromol ; 188: 595-608, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34389388

RESUMO

Phosphate transporters (PHTs) mediate the uptake and translocation of phosphate in plants. A comprehensive analysis of the PHT family in aquatic plant is still lacking. In this study, we identified 73 PHT members of six major PHT families from four duckweed species. The phylogenetic analysis, gene structure and protein characteristics analysis revealed that PHT genes are highly conserved among duckweeds. Interaction network and miRNA target prediction showed that SpPHTs could interact with the important components of the nitrate/phosphate signaling pathway, and spo-miR399 might be a central regulator that mediates phosphate signal network in giant duckweed (Spirodela polyrhiza). The modeled 3D structure of SpPHT proteins shared a high level of homology with template structures, which provide information to understand their functions at proteomic level. The expression profiles derived from transcriptome data and quantitative real-time PCR revealed that SpPHT genes are respond to exogenous stimuli and remarkably induced by phosphate starvation, phosphate is absorbed from aquatic environment by the whole duckweed plant. This study lays the foundation for further functional studies on PHT genes for genetic improvement and the promotion of phosphate uptake efficiency in duckweeds.

3.
Eur J Med Chem ; 224: 113716, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34340042

RESUMO

5-C-Alkyl-DNJ and 5-C-alkyl-l-ido-DNJ derivatives have been designed and synthesized efficiently from an l-sorbose-derived cyclic nitrone. The DNJ and l-ido-DNJ derivatives with C-5 alkyl chains ranging from methyl to dodecyl were assayed against various glycosidases to study the effect of chain length on enzyme inhibition. Glycosidase inhibition study of DNJ derivatives showed potent and selective inhibitions of α-glucosidase; DNJ derivatives with methyl, pentyl to octyl, undecyl and dodecyl as C-5 branched chains showed significantly improved rat intestinal maltase inhibition. In contrast, most 5-C-alkyl-l-ido-DNJ derivatives were weak or moderate inhibitors of the enzymes tested, with only three compounds found to be potent α-glucosidase inhibitors. Docking studies showed different interaction modes of 5-C-ethyl-DNJ and 5-C-octyl-DNJ with ntMGAM and also different binding modes of 5-C-alkyl-DNJ and 5-C-alkyl-l-ido-DNJ derivatives; the importance of the degree of accommodation of the C-5 substituent in the hydrophobic groove and pocket may account for the variation of glycosidase inhibition in the two series of derivatives. The results reported herein are helpful in the design and development of α-glucosidase inhibitors; this may lead to novel agents for the treatment of viral infection and type II diabetes.

5.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203933

RESUMO

Natural resistance-associated macrophage proteins (Nramps) are specific metal transporters in plants with different functions among various species. The evolutionary and functional information of the Nramp gene family in Spirodela polyrhiza has not been previously reported in detail. To identify the Nramp genes in S. polyrhiza, we performed genome-wide identification, characterization, classification, and cis-elements analysis among 22 species with 138 amino acid sequences. We also conducted chromosomal localization and analyzed the synteny relationship, promoter, subcellular localization, and expression patterns in S. polyrhiza. ß-Glucuronidase staining indicated that SpNramp1 and SpNramp3 mainly accumulated in the root and joint between mother and daughter frond. Moreover, SpNramp1 was also widely displayed in the frond. SpNramp2 was intensively distributed in the root and frond. Quantitative real-time PCR results proved that the SpNramp gene expression level was influenced by Cd stress, especially in response to Fe or Mn deficiency. The study provides detailed information on the SpNramp gene family and their distribution and expression, laying a beneficial foundation for functional research.


Assuntos
Araceae/genética , Cádmio/toxicidade , Proteínas de Transporte de Cátions/genética , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Família Multigênica , Proteínas de Plantas/genética , Estresse Fisiológico/genética , Motivos de Aminoácidos , Sequência de Aminoácidos , Araceae/efeitos dos fármacos , Proteínas de Transporte de Cátions/química , Proteínas de Transporte de Cátions/metabolismo , Cromossomos de Plantas/genética , Sequência Conservada , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Estresse Fisiológico/efeitos dos fármacos , Sintenia/genética
6.
Talanta ; 232: 122451, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074435

RESUMO

The superior supramolecular recognition ability of macrocyclic compounds will enhance the sensitivity and selectivity of electrochemical detection, which has a great application potential in electrochemical sensing. Herein, we developed a novel electrochemical aptasensor based on the specific host-guest interactions between cucurbit [7]uril and ferrocene (Fc) for capture, determination and release of exosomes. Macrocyclic compounds, cucurbit [7]uril is modified on the surface of the gold nanoparticles composed electrode by self-assembling. CD63 aptamer linked ferrocene is introduced into this platform to capture exosomes specifically by CD63 protein on the exosomes. The dual specificity of macrocyclic compounds and aptamers enables highly selective and sensitive electrochemical detection of exosomes. The limit of detection (LOD) was 482 particles µL-1. In addition, the captured exosomes could be released on demand in a very mild manner through aminoferrocene (NH2-Fc) because of its higher affinity to cucurbit [7]uril. The proposed electrochemical aptasensor showed good performance in detecting exosomes even in plasma samples, thus demonstrating its great potential in early clinical diagnosis. Simultaneously, exosomes could be released undamaged by this protocol, exhibiting good applicability in comprehensive studies of exosomes. Moreover, this strategy can be applied to other target biomolecules by changing the recognition pairs.

7.
Drug Deliv ; 28(1): 943-956, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33988472

RESUMO

This study aimed to develop an effective therapy against M2 macrophages and to investigate the effects of imidazole and mannose modified carboxymethyl chitosan-nanoparticles (MIC-NPs) on tumor growth and antitumor immune responses. MIC-NPs were constructed and analyzed through 1H NMR, nano-laser particle size analyzer, and transmission electron microscopy. The nanoparticles were mainly distributed in 75-85 nm, and zeta potential was 1.5 mV. Cytotoxicity studies in vitro and in vivo indicated that MIC-NPs were safe. The targeting effect of MIC-NPs on M2 macrophages was observed through fluorescence microscope and microplate system. The results demonstrated the uptake of a large amount of FITC-loaded MIC-NPs by M2. Cell growth inhibition experiments showed that MIC-NPs significantly inhibited M2 through cell apoptosis. The evaluation of anti-tumor activity in vivo showed that MIC-NPs could accumulate in the tumor site to exert an anti-tumor effect. Flow cytometry showed that the proportion of M2 macrophages at the tumor site in the experimental group was significantly lower than that in the control group, while the Treg cells and cytotoxic T cells (CTL) were found to be increased. PCR detection showed that the cDNA of FIZZ, MR, TGF-ß, and arginase, closely related to M2 macrophages, in the experimental group, was significantly lower than that in the control group, but there was no significant difference in the cDNA of Treg cell characteristic Foxp3 between the two groups. These results suggest that MIC-NPs are expected to provide a new and effective treatment for tumor.

8.
Pediatr Rev ; 42(Suppl 1): S1-S3, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33386348
9.
Int J Mol Sci ; 22(2)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466729

RESUMO

Plants adapt to environmental changes by regulating their development and growth. As an important interface between plants and their environment, leaf morphogenesis varies between species, populations, or even shows plasticity within individuals. Leaf growth is dependent on many environmental factors, such as light, temperature, and submergence. Phytohormones play key functions in leaf development and can act as molecular regulatory elements in response to environmental signals. In this review, we discuss the current knowledge on the effects of different environmental factors and phytohormone pathways on morphological plasticity and intend to summarize the advances in leaf development. In addition, we detail the molecular mechanisms of heterophylly, the representative of leaf plasticity, providing novel insights into phytohormones and the environmental adaptation in plants.


Assuntos
Aclimatação , Reguladores de Crescimento de Plantas/metabolismo , Fenômenos Fisiológicos Vegetais , Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Desenvolvimento Vegetal , Reguladores de Crescimento de Plantas/genética , Folhas de Planta/anatomia & histologia , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/fisiologia , Plantas/anatomia & histologia , Plantas/genética
10.
Biomaterials ; 269: 120620, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33421709

RESUMO

Activated platelets can maintain tumor vessel integrity, thereby leading to limited tumor perfusion and suboptimal antitumor efficacy of nanoparticle-based drugs. Herein, to disrupt the tumor vascular endothelial barriers by inhibiting the transformation of resting platelets to activated platelets, a TM33 peptide-modified gelatin/oleic acid nanoparticle loaded with tanshinone IIA (TNA) was constructed (TM33-GON/TNA). TM33-GON/TNA could adhere to activated platelets by specifically binding their superficial P-selectin and release TNA into the extracellular space under matrix metalloproteinase-2 (MMP-2) stimulation, leading to local high TNA exposure. Thus, platelet activation, adhesion, and aggregation, which occur in the local environment around the activated platelets, were efficiently inhibited, leading to leaky tumor endothelial junctions. Accordingly, TM33-GON/TNA treatment resulted in a 3.2-, 4.0-, and 11.2-fold increase in tumor permeation of Evans blue (macromolecule marker), small-sized Nab-PTX (~10 nm), and large-sized DOX-Lip (~100 nm), respectively, without elevating drug delivery to normal tissues. Ultimately, TM33-GON/TNA plus Nab-PTX exhibited superior antitumor efficacy with minimal side effects in a murine pancreatic cancer model. In addition, the TM33-GON/TNA-induced disrupted endothelial junctions were reversibly restored after the treatment because the number of platelets was not reduced, which implies a low risk of the undesirable systemic bleeding. Hence, TM33-GON/TNA represents a clinically translational adjuvant therapy to magnify the antitumor efficacy of existing nanomedicines in pancreatic cancer and other tumors with tight endothelial lining.


Assuntos
Sistemas de Liberação de Medicamentos , Endotélio Vascular/patologia , Nanopartículas , Neoplasias/tratamento farmacológico , Preparações Farmacêuticas , Ativação Plaquetária/efeitos dos fármacos , Animais , Plaquetas , Metaloproteinase 2 da Matriz , Camundongos
11.
Front Microbiol ; 11: 1294, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32676056

RESUMO

Vibrio parahaemolyticus is the leading cause of seafood-borne bacterial poisoning in China and is a threat to human health worldwide. The aim of this study was to assess the antibiotic resistance profiles and distribution of heavy metal resistance of V. parahaemolyticus isolates from Penaeus vannamei from freshwater farms, seawater farms, and their corresponding markets in Zhejiang, China and to assess the relationship between multidrug resistance (MDR) and multi-heavy metal resistance (MHMR). Of the 360 P. vannamei samples that we tested, 90 (25.00%) were V. parahaemolyticus positive, but the occurrence of pathogenic isolates carrying the toxin genes tdh (4.44%) and trh (3.33%) was low. None of the tested isolates harbored both the tdh and trh genes. However, antibiotic resistance profiles varied among different sampling locations, levels of resistance to the antibiotics ampicillin (76.67%) and streptomycin (74.44%) were high overall, and MDR isolates were common (40.00% of all isolates). Heavy metal resistance patterns were similar among the different sampling locations. Overall, the majority of V. parahaemolyticus isolates displayed tolerance to Cd2+ (60.00%), and fewer were resistant to Cu2+ (40.00%), Zn2+ (38.89%), Ni2+ (24.44%), Cr3+ (14.44%), and Co2+ (8.89%). In addition, 34.44% (31/90) of isolates tested in this study were found to be MHMR. Using Pearson's correlation analysis, MDR and MHMR were found to be positively correlated (P = 0.004; R = 0.759). The 18 V. parahaemolyticus isolates that were both MDR and MHMR represented 18 sequence types, of which 12 were novel to the PubMLST database, and displayed a high level of genetic diversity, suggesting that dissemination may be affected by mobile genetic elements via horizontal gene transfer. However, a low percentage of class 1 integrons without gene cassettes and no class 2 or 3 integrons were detected in the 18 MDR and MHMR isolates or in the 90 V. parahaemolyticus isolates overall. Thus, we suggest that future research focus on elucidating the mechanisms that lead to a high prevalence of resistance determinants in V. parahaemolyticus. The results of this study provide data that will support aquatic animal health management and food safety risk assessments in the aquaculture industry.

12.
Hematol Oncol Clin North Am ; 34(3): 601-612, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32336423

RESUMO

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematological malignancy, derived from plasmacytoid dendritic cells. It mainly occurs in older adults, but has been reported across all age groups. Most patients present with skin lesions with or without marrow involvement and leukemic dissemination. Treatment with high-risk acute lymphoblastic leukemia therapy regimens with central nervous system prophylaxis is recommended in pediatric patients. Stem cell transplant in children is recommended for relapsed/refractory disease or high-risk disease at presentation. New targeted therapies including the recently FDA-approved anti-CD123 cytotoxin show great promise in improving the response rate.


Assuntos
Células Dendríticas/patologia , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/terapia , Fatores Etários , Biomarcadores , Criança , Terapia Combinada , Diagnóstico Diferencial , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Imunofenotipagem , Transtornos Mieloproliferativos/etiologia , Transtornos Mieloproliferativos/metabolismo , Fenótipo , Avaliação de Sintomas , Resultado do Tratamento
13.
Molecules ; 25(7)2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32218360

RESUMO

Ten pairs of pyrrolidine analogues of pochonicine and its stereoisomers have been synthesized from four enantiomeric pairs of polyhydroxylated cyclic nitrones. Among the ten N-acetylamino pyrrolidine analogues, only compounds with 2,5-dideoxy-2,5-imino-d-mannitol (DMDP) and pochonicine (1) configurations showed potent inhibition of ß-N-acetylhexosaminidases (ß-HexNAcases); while 1-amino analogues lost almost all their inhibitions towards the tested enzymes. The assay results reveal the importance of the N-acetylamino group and the possible right configurations of pyrrolidine ring required for this type of inhibitors.


Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Pirrolidinas/química , Alcaloides de Pirrolizidina/química , Alcaloides de Pirrolizidina/síntese química , beta-N-Acetil-Hexosaminidases/antagonistas & inibidores , Animais , Ciclização , Glicosídeo Hidrolases/antagonistas & inibidores , Glicosídeo Hidrolases/metabolismo , Ratos , Estereoisomerismo , beta-N-Acetil-Hexosaminidases/metabolismo
14.
Biomaterials ; 238: 119844, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32062148

RESUMO

Mitochondrial dysfunction is an early event of Alzheimer's disease (AD), contributes the onset and progression of AD, and may represent an effective therapeutic target for AD intervention. Since mitochondria in central neurons are more susceptible to oxidative damage than non-neuronal cells, the specific delivery of the antioxidants to the mitochondria of impaired central neurons is crucial for achieving the therapeutic effect on AD. Here, we prepare the neuronal mitochondria-targeted micelles (CT-NM) through co-decoration with neural cell adhesion molecule (NCAM) mimetic peptide C3 for brain neuron specific binding and the triphenylphosphonium (TPP) for mitochondrial targeting. CT-NM significantly increase the encapsulated resveratrol's concentration in the neuronal mitochondria compared to the micelles modified with C3 only or the resveratrol solution. The resveratrol-loaded CT-NM alleviate the oxidative stress in the neuronal cells, resulting in stabilization of the dynamic balance of mitochondrial fission and fusion. The targeted micelles restore the cognitive performance in APP/PS1 transgenic mice to the level of wild-type mice characterized by up-regulation of sirtuin 1 expression, reduction of amyloid deposition and tau hyperphosphorylation, protection of synapses and inhibition of microglia proliferation. The results demonstrate the delay of the progression of AD through reversing neuronal mitochondrial dysfunction by the targeted delivery of antioxidants.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Micelas , Mitocôndrias/metabolismo , Neurônios/metabolismo , Estresse Oxidativo
15.
Org Biomol Chem ; 18(5): 999-1011, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-31944194

RESUMO

N-Substituted derivatives of 1,4-dideoxy-1,4-imino-d-mannitol (DIM), the pyrrolidine core of swainsonine, have been synthesized efficiently and stereoselectively from d-mannose with 2,3:5,6-di-O-isopropylidene DIM (10) as a key intermediate. These N-substituted derivatives include N-alkylated, N-alkenylated, N-hydroxyalkylated and N-aralkylated DIMs with the carbon number of the alkyl chain ranging from one to nine. The obtained 33 N-substituted DIM derivatives were assayed against various glycosidases, which allowed a systematic evaluation of their glycosidase inhibition profiles. Though N-substitution of DIM decreased their α-mannosidase inhibitory activities, some of the derivatives showed significant inhibition of other glycosidases.


Assuntos
Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Glicosídeo Hidrolases/antagonistas & inibidores , Manitol/análogos & derivados , Animais , Inibidores Enzimáticos/química , Glicosídeo Hidrolases/metabolismo , Humanos , Imino Furanoses/síntese química , Imino Furanoses/química , Imino Furanoses/farmacologia , Concentração Inibidora 50 , Manitol/síntese química , Manitol/química , Manitol/farmacologia , Ratos , Swainsonina/química
16.
Molecules ; 24(20)2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31619020

RESUMO

Cross-metathesis (CM) and Keck asymmetric allylation, which allows access to defined stereochemistry of a remote side chain hydroxyl group, are the key steps in a versatile synthesis of broussonetine M (3) from the d-arabinose-derived cyclic nitrone 14. By a similar strategy, ent-broussonetine M (ent-3) and six other stereoisomers have been synthesized, respectively, starting from l-arabino-nitrone (ent-14), l-lyxo-nitrone (ent-3-epi-14), and l-xylo-nitrone (2-epi-14) in five steps, in 26%-31% overall yield. The natural product broussonetine M (3) and 10'-epi-3 were potent inhibitors of ß-glucosidase (IC50 = 6.3 µM and 0.8 µM, respectively) and ß-galactosidase (IC50 = 2.3 µM and 0.2 µM, respectively); while their enantiomers, ent-3 and ent-10'-epi-3, were selective and potent inhibitors of rice α-glucosidase (IC50 = 1.2 µM and 1.3 µM, respectively) and rat intestinal maltase (IC50 = 0.29 µM and 18 µM, respectively). Both the configuration of the polyhydroxylated pyrrolidine ring and C-10' hydroxyl on the alkyl side chain affect the specificity and potency of glycosidase inhibition.


Assuntos
Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Glicosídeo Hidrolases/antagonistas & inibidores , Glicosídeo Hidrolases/química , Pirrolidinas/síntese química , Pirrolidinas/farmacologia , Inibidores Enzimáticos/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Pirrolidinas/química , Relação Estrutura-Atividade
17.
Med Hypotheses ; 124: 84-86, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30798924

RESUMO

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection. Due to the lack of causative immune treatment, mortality of sepsis remains at a high level and represents one of the main disease burdens globally. Adenosine 5' triphosphate (ATP) levels in red blood cells (RBC) are modulated by various factors during sepsis, including a decrease in ATP production, an increase in ATP catabolism and alterations in ATP release. Therefore, we hypothesize that intracellular ATP levels in RBC can serve as potential biomarker for sepsis and support sepsis diagnosis. This will facilitate early treatment and could improve the outcome of this serious condition.


Assuntos
Trifosfato de Adenosina/metabolismo , Eritrócitos/metabolismo , Sepse/sangue , Sepse/diagnóstico , Biomarcadores/metabolismo , Hemoglobinas/metabolismo , Humanos , Hipóxia , Peroxidação de Lipídeos , Mitocôndrias/metabolismo , Modelos Teóricos , Óxido Nítrico/metabolismo
18.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 30(6): 558-563, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-30009731

RESUMO

OBJECTIVE: To investigate the accuracy of sequential organ failure assessment (SOFA) scoring in emergency physicians in Beijing. METHODS: Emergency physicians from 8 hospitals in Beijing in January 2018 were demanded to complete a SOFA questionnaire which was developed on "wenjuanxing" website and submit via cell phone. All participants were divided into urban center group (UC group) and no-urban center group (NUC group) based on the hospital's location. The accuracy rate of components and total score of SOFA along with the mistakes were evaluated, and the results of the two groups were compared. RESULTS: (1) The questionnaire was sent to 217 emergency physicians of the 8 hospitals, and 197 qualified questionnaires were received with 109 of NUC group and 88 of UC group, respectively, the total response rate was 90.8%. Compared with those from NUC group, UC physicians had older ages [years: 37 (32, 42) vs. 34 (29, 40), Z = -2.554, P = 0.011] and higher education level [postgraduate degree 76.1% (67/88) vs. 40.4% (44/109), χ2 = 25.327, P < 0.001], and more of them experienced SOFA scoring [62.5% (55/88) vs. 45.9% (50/109), χ2 = 5.409, P = 0.020]. Other baseline characteristics such as gender, working years, professional title and training experience were not different between the two groups. (2) The accuracy rate of total SOFA score was 62.4% (123/197) in the whole cohort, and UC group was lower than that of NUC group, but the difference was not significant [56.8% (50/88) vs. 67.0% (73/109), χ2 = 2.141, P = 0.143]. While comparing the accuracy of individual variable/system of SOFA, the accuracy rate of norepinephrine of UC group was much higher than NUC group [80.7% (71/88) vs. 66.1% (72/109), χ2 = 5.235, P = 0.022], but the accuracy of Glasgow coma scale (GCS) was much lower in NUC group [38.6% (27/70) vs. 81.6% (71/87), χ2 = 30.629, P < 0.001]. Other variables of SOFA were not different between the two groups. Based upon the results of all submitted questionnaires, 566 mistakes were identified. It was indicated that the mistakes per capital was 2.9 in the whole cohort and in the two groups. The first type mistakes which caused by carelessness (including calculating error, filling error, choosing error) were 233 times. The calculating error in norepinephrine from NUC physicians was higher than the UC group [33.9% (37/109) vs. 19.3% (17/88), χ2 = 5.235, P = 0.022], there was no significant difference in any other first type mistakes between the two groups. The total second type mistakes caused by misunderstanding of SOFA (including using wrong variables, not using the worst value within 24 hours, and incorrect GCS score) were 333 times in the whole cohort. GCS error [61.8% (42/88) vs. 16.9% (14/109), χ2 = 32.292, P < 0.001], and using urine output per hour instead of urine output per 24 hours [15.9% (14/88) vs. 4.6% (5/109), χ2 = 7.162, P = 0.007] were much higher in UC group than NUC group. CONCLUSIONS: The total accuracy of SOFA scoring in the investigated emergency physicians of 8 hospitals in Beijing was not good. Mistakes causing by carelessness or misunderstanding of score rules were similar. It is necessary to apply strict training in SOFA scoring.


Assuntos
Serviço Hospitalar de Emergência , Escala de Coma de Glasgow , Humanos , Unidades de Terapia Intensiva , Escores de Disfunção Orgânica , Médicos , Prognóstico
20.
BMC Cancer ; 17(1): 593, 2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28854900

RESUMO

BACKGROUND: Recent studies suggested that cancer stem-like cells contribute to tumor vasculogenesis by differentiating into endothelial cells. However, such process is governed by still undefined mechanism. METHODS: At varying differentiation levels, three representative colon cancer cells were cultured in endothelial-inducing conditioned medium: human colon cancer cells HCT116 (HCT116) (poorly differentiated), SW480 (moderately differentiated), and HT29 (well differentiated). We tested for expression of endothelial markers (cluster of differentiation (CD) 31, CD34, and vascular endothelial (VE)-cadherin and their ability to form tube-like structures in 3D culture. We also observed VEGF secretion and expressions of endothelial markers and VEGFRs in HCT116 cells under hypoxia to simulate physiological conditions. In in vitro and in xenotransplantation experiments, VE growth factor receptor 2 (VEGFR2) antagonist SKLB1002 was used to test effect of VEGFR2 in endothelial differentiation of HCT116 cells. Expression levels of VEGFR2 and VE-cadherin were assessed by immunohistochemistry of human colon cancer tissues to evaluate clinicopathological significance of VEGFR2. RESULTS: After culturing in endothelial-inducing conditioned medium, poorly differentiated HCT116 cells expressed endothelial markers and formed tube-like structure in vitro. HCT116 cells secreted more endogenous VEGF and expressed higher VEGFR2 under hypoxia. SKLB1002 impaired endothelial differentiation in vitro and xenotransplantation experiments, suggesting a VEGFR2-dependent mechanism. Increased expression of VEGFR2 correlated with differentiation, metastasis/recurrence, and poor prognosis in 203 human colon cancer samples. Positive correlation was observed between VEGFR2 and VE-cadherin expression. CONCLUSIONS: VEGFR2 regulates endothelial differentiation of colon cancer cell and may be potential platform for anti-angiogenesis cancer therapy.


Assuntos
Diferenciação Celular/fisiologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Antígenos CD/metabolismo , Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Células Endoteliais/patologia , Endotélio Vascular/patologia , Feminino , Células HCT116 , Células HT29 , Humanos , Camundongos , Camundongos Nus , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Transdução de Sinais/fisiologia
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