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1.
Aging (Albany NY) ; 12(2): 1808-1827, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32003757

RESUMO

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies and lacks reliable biomarkers for diagnosis and prognosis, which results in high incidence and mortality rates of ccRCC. In this study, ISG20, HJURP, and FOXM1 were identified as hub genes via weighted gene co-expression network analysis (WGCNA) and Cox regression analysis. Samples validation showed that only ISG20 was up-regulated in ccRCC. Therefore, ISG20 was selected for further study. High ISG20 expression was associated with poor overall survival and disease-free survival. Furthermore, the expression of ISG20 could effectively differentiate ccRCC from normal tissues and was positively correlated to clinical stages. Functional experiments proved that knockdown of ISG20 expression could obviously inhibit cell growth, migration, and invasion in ccRCC cells. To find the potential mechanisms of ISG20, gene set enrichment analysis (GSEA) was performed and revealed that high expression of ISG20 was significantly involved in metastasis and cell cycle pathways. In addition, we found that ISG20 could regulate the expression of MMP9 and CCND1. In conclusion, these findings suggested that ISG20 promoted cell proliferation and metastasis via regulating MMP9/CCND1 expression and might serve as a potential biomarker and therapeutic target in ccRCC.

2.
ACS Omega ; 4(23): 20223-20229, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31815223

RESUMO

The ability to research individual cells is important for various biological studies. Currently reported biointerfaces for single-cell analysis can only trap individual cells in random morphologies. Cell polarity is a key factor in cellular functions, and the study of single-cell polarity can facilitate an understanding of cancer metastasis and stem-cell differentiation. For single polar cell trapping, anisotropic honeycomb-structured films were prepared. Elastic poly(1,2-butadiene) honeycomb films with ordered hexagonal pores were first prepared via the breath figure method. Subsequently, the films were subjected to mechanical stretching and fixed via photo-cross-linking under UV light irradiation. This stretched honeycomb structure was then transferred to a polystyrene surface. The resultant anisotropic porous films exhibited excellent capacity for single-cell trapping. Besides contributing to the physical spatial confinement of cells, the trapped single cells exhibited orientation in different polarities. The single polar cell array provided a novel platform for fundamental biological research.

3.
Zhongguo Zhong Yao Za Zhi ; 44(19): 4129-4133, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31872689

RESUMO

Traditional Chinese medicine is planted in mountainous areas with suitable natural conditions. The planting area is complex in terrain,and the planting plots are mostly irregularly shaped. It is difficult to accurately calculate the planting area by traditional survey methods. The method of extracting Chinese herbal medicine planting area combined with remote sensing and GIS technology is of great significance for the rational development and utilization of traditional Chinese medicine resources. Taking Bletilla striata planting in Ningshan county of Shaanxi province as an example,the extraction method of planting area of traditional Chinese medicine in county was studied. High-resolution ZY-3 and GF-1 multi-spectral multi-temporal remote sensing images were used as data sources. Through field sampling,samples such as B. striata,cultivated land,forest land,water body,artificial surface,alpine meadow,etc. are collected. The spectral features,texture features and shape features of remotely identifiable objects in different planting areas and cultivated land,vegetable sheds were analyzed,confusing ground objects were eliminated and interpretation marks were establish. The method of visual interpretation is used to realize the extraction of B. striata planting areas,and the B. striata planting area are calculated by combining GIS technology. The results showed that the method of visual interpretation,using high-resolution ZY-3 and GF-1 multi-spectral multi-temporal remote sensing image data extracted the planting area of 403.05 mu. It can effectively extract the B. striata planting area in research region.


Assuntos
Medicina Tradicional Chinesa , Orchidaceae , Tecnologia de Sensoriamento Remoto , Florestas
4.
Blood Adv ; 3(21): 3406-3418, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714962

RESUMO

Thrombocytopenia is associated with life-threatening bleeding and is common in myelodysplastic syndromes (MDS). Robust molecular prognostic biomarkers need to be developed to improve clinical decision making for patients with MDS with thrombocytopenia. Wilms tumor 1 (WT1) and preferentially expressed antigen in melanoma (PRAME) are promising immunogenic antigen candidates for immunotherapy, and their clinical effects on patients with MDS with thrombocytopenia are still not well understood. We performed a multicenter observational study of adult patients with MDS with thrombocytopenia from 7 different tertiary medical centers in China. We examined bone marrow samples collected at diagnosis for WT1 and PRAME transcript levels and then analyzed their prognostic effect for patients with MDS with thrombocytopenia. In total, we enrolled 1110 patients diagnosed with MDS with thrombocytopenia. Overexpression of WT1 and PRAME was associated with elevated blast percentage, worse cytogenetics, and higher Revised International Prognostic Scoring System (IPSS-R) risk. Further, both WT1 and PRAME overexpression were independent poor prognostic factors for acute myeloid leukemia evolution, overall survival, and progression-free survival. Together, the 2 genes overexpression identified a population of patients with MDS with substantially worse survival. On the basis of WT1 and PRAME transcript levels, patients with MDS with IPSS-R low risk were classified into 2 significantly divergent prognostic risk groups: a low-favorable group and a low-adverse group. The low-adverse group had survival similar to that of patients in the intermediate-risk group. Our study demonstrates that the evaluation of WT1/PRAME transcript analysis may improve the prognostication precision and better risk-stratify the patients.

5.
Biomed Pharmacother ; 118: 109268, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545239

RESUMO

Danshen (salvia miltiorrhiza) and honghua(Carthamus tinctorius) were traditional herb pair with promoting blood circulation and removing blood stasis actions, in China. Both were widely used to treat cardiovascular diseases (CVD) for hundreds years, especially shown definite advantage in the treatment of ischemic heart disease (IHD). However, the mechanism of danshen-honghua herb pair (DHHP) in the treatment of IHD was still unclear. This study was focused on examining the effects and possible mechanisms of DHHP in rats with acute myocardial ischemia induced by isoproterenol (ISO). The results suggested that DHHP significantly ameliorated the myocardial tissue abnormalities, notablely inhibited the elevation of lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST), creatinekinase isoenzyme (CK-MB) and cardiac troponin T (CTn-T) in plasma, obviously decreased the plasma levels of Tumor Necrosis Factor α (TNF-α), outstandingly inhibited the reduction of superoxide dismutase (SOD), catalase (CAT) caused by ISO, significantly inhibited the high expression of Bcl-2 assaciated X protein (Bax) and nuclear transcriptionfactor-κBP65 (NF-κBP65) protein, significantly induced the low expression of B-cell lymphoma-2 (Bcl-2) protein in acute myocardial ischemia rats. DHHP can obviously ameliorate hemodynamic parameters. In summary, DHHP can significantly improve myocardial ischemia in acute myocardial ischemia model rats caused by ISO. Anti-free radicals, anti-peroxidation, inhibition of cell apoptosis and anti- inflammation maybe are the potential mechanisms of DHHP anti-myocardial ischemia in acute myocardial ischemia rats in duced by ISO.

6.
Chem Commun (Camb) ; 55(79): 11888-11891, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31528874

RESUMO

A novel type of oxime phosphonate was synthesized and used in the intermolecular cascade radical addition reaction of alkenes to access ß-aminophosphonates via visible-light-driven N-centered iminyl radical-mediated and redox-neutral selective C-P single-bond cleavage in an active phosphorus radical route. The procedure is characterized by its ability to achieve the construction of Csp3-P and Csp3-N bonds without the requirement for oxidants and bases.

7.
HLA ; 94(6): 519-521, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31523929

RESUMO

HLA-A*24:02:78 differs from HLA-A*24:02:01:01 in exon 3 by a single nucleotide.

8.
J Hematol Oncol ; 12(1): 87, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477147

RESUMO

BACKGROUND: Haploidentical transplantation has been proposed as an effective treatment for severe aplastic anemia (SAA). The majority of patients have more than one HLA-haploidentical donor. Herein, we compared the outcomes between different donor-recipient relationships for optimal haploidentical donor selection in acquired SAA. METHODS: We conducted a multicenter study based on a registered database of 392 patients with SAA treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) between 2006 and 2018. In total, 223 patients received grafts from father donors, 47 from mother donors, 91 from siblings, 29 from children, and 2 from collateral donors. RESULTS: Of the 381 patients who survived more than 28 days, 379 (99.5%) recipients were engrafted. The 2-year overall survival (OS) was 86.6 ± 2.5%, 87.1 ± 4.9%, 84.3 ± 3.9%, and 92.2 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.706). The 2-year failure-free survival (FFS) was 82.8 ± 2.7%, 86.7 ± 5.1%, 80.8 ± 4.2%, and 92.5 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.508). There was no difference in the incidence of either acute or chronic graft-versus-host disease (GVHD) among the different donor sources in multivariate analyses. There were also no differences in the OS or FFS among the different donor sources in the Cox regression analysis. However, OS was significantly better in the patients with a shorter history of aplastic anemia (< 12 months), better performance status (ECOG scores 0-1), or moderate graft mononuclear cell (MNC) counts (6-10 × 108/kg), and in female recipients with male donors. The FFS was also higher in patients with a shorter history of aplastic anemia (< 12 months) and better performance status (ECOG scores 0-1). CONCLUSIONS: Fathers, mothers, siblings, and children are all suitable haploidentical donors for patients with SAA.

9.
Biomater Sci ; 7(10): 4027-4035, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31389406

RESUMO

The efficient recognition and isolation of rare cancer cells from blood has great significance for early cancer diagnosis and monitoring prognosis. In this paper, we propose a cell-imprinted biomimetic interface for highly efficient capture of circulating tumor cells (CTCs) through the use of target cells as an imprint template. The cell-morphology topologies and residual biomolecular receptors on the cell-imprinted interface recognize template cells by mimicking the specific immunoaffinity of the antibody-antigen (known as plastic antibody). Furthermore, we introduced a natural antibody (anti-EpCAM) to accelerate the CTC-material interaction. Due to the synergistic contribution of natural and plastic antibodies, the imprinted surface exhibited high performances in CTC detection on an artificial blood sample, with a capture efficiency higher than 55%. In addition to the experiment, we conducted a systematic analysis of the biochemical recognition (real antibody anti-EpCAM and plastic receptor) and topographic interaction to gain insight into the cell-biointerface interaction. The results of this study provide new prospects for designing cell-material interaction interfaces for future cell-based biological research and clinical applications.

10.
J Biol Chem ; 294(36): 13366-13377, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31324719

RESUMO

The peptide hormone adropin regulates energy metabolism in skeletal muscle and plays important roles in the regulation of metabolic homeostasis. Besides muscle, the liver has an essential role in regulating glucose homeostasis. Previous studies have reported that treatment of diet-induced obese (DIO) male mice with adropin34-76 (the putative secreted domain) reduces fasting blood glucose independently of body weight changes, suggesting that adropin suppresses glucose production in the liver. Here, we explored the molecular mechanisms underlying adropin's effects on hepatic glucose metabolism in DIO mice. Male DIO B6 mice maintained on a high-fat diet received five intraperitoneal injections of adropin34-76 (450 nmol/kg/injection) over a 48-h period. We found that adropin34-76 enhances major intracellular signaling activities in the liver that are involved in insulin-mediated regulation of glucose homeostasis. Moreover, treatment with adropin34-76 alleviated endoplasmic reticulum stress responses and reduced activity of c-Jun N-terminal kinase in the liver, explaining the enhanced activities of hepatic insulin signaling pathways observed with adropin34-76 treatment. Furthermore, adropin34-76 suppressed cAMP activated protein kinase A (PKA) activities, resulting in reduced phosphorylation of inositol trisphosphate receptor, which mediates endoplasmic reticulum calcium efflux, and of cAMP-responsive element-binding protein, a key transcription factor in hepatic regulation of glucose metabolism. Adropin34-76 directly affected liver metabolism, decreasing glucose production and reducing PKA-mediated phosphorylation in primary mouse hepatocytes in vitro Our findings indicate that major hepatic signaling pathways contribute to the improved glycemic control achieved with adropin34-76 treatment in situations of obesity.

11.
Metabolism ; 98: 37-48, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31202835

RESUMO

BACKGROUND: Impaired cardiac insulin signalling and high cardiac fatty acid oxidation rates are characteristics of conditions of insulin resistance and diabetic cardiomyopathies. The potential role of liver-derived peptides such as adropin in mediating these changes in cardiac energy metabolism is unclear, despite the fact that in skeletal muscle adropin can preferentially promote glucose metabolism and improve insulin sensitivity. OBJECTIVES: To determine the influence of adropin on cardiac energy metabolism, insulin signalling and cardiac efficiency. METHODS: C57Bl/6 mice were injected with either vehicle or a secretable form of adropin (450 nmol/kg, i.p.) three times over a 24-h period. The mice were fasted to accentuate the differences between animals in adropin plasma levels before their hearts were isolated and perfused using a working heart system. In addition, direct addition of adropin to the perfusate of ex vivo hearts isolated from non-fasting mice was utilized to investigate the acute effects of the peptide on heart metabolism and ex vivo function. RESULTS: In contrast to the observed fasting-induced predominance of fatty acid oxidation as a source of ATP production in control hearts, insulin inhibition of fatty acid oxidation was preserved by adropin treatment. Adropin-treated mouse hearts also showed a higher cardiac work, which was accompanied by improved cardiac efficiency and enhanced insulin signalling compared to control hearts. Interestingly, acute adropin administration to isolated working hearts also resulted in an inhibition of fatty acid oxidation, accompanied by a robust stimulation of glucose oxidation compared to vehicle-treated hearts. Adropin also increased activation of downstream cardiac insulin signalling. Moreover, both in vivo and ex vivo treatment protocols induced a reduction in the inhibitory phosphorylation of pyruvate dehydrogenase (PDH), the major enzyme of glucose oxidation, and the protein levels of the responsible kinase PDH kinase 4 and the insulin-signalling inhibitory phosphorylation of JNK (p-T183/Y185) and IRS-1 (p-S307), suggesting acute receptor- and/or post-translational modification-mediated mechanisms. CONCLUSIONS: These results demonstrate that adropin has important effects on energy metabolism in the heart and may be a putative candidate for the treatment of cardiac disease associated with impaired insulin sensitivity.

12.
Ann Hematol ; 98(7): 1641-1646, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31041512

RESUMO

The aim of this study was to explore the clinical features and prognostic significance of CSF3R mutations in AML patients with CEBPA double mutations (CEBPAdm). One hundred one AML patients with CEBPAdm were retrospectively analyzed in this study. Mutation status of CSF3R gene, clinical features, and long-term outcomes were analyzed. The frequency of CSF3R mutations in patients with CEBPAdm was 19.80% (20/101). Patients with CSF3R mutations were associated with a lower platelet (u = 2.728, P = 0.006) and higher leukocytes (u = 3.178, P = 0.001) compared with those with wide-type CSF3R gene. The 5-year relapse-free survival (RFS) was 18.7% in patients with CSF3R mutations, which was significantly lower than those with wide-type CSF3R (31.8%) (P = 0.015). The 5-year overall survival (OS) was also significantly different between patients with and without CSF3R mutations (17.5% versus 57.4%, P = 0.019). The prevalence of CSF3R mutations was high in AML patients with CEBPAdm, which indicated a poor prognosis, and CSF3R mutations may be a new potential candidate for prognostically re-stratifying AML patients with CEBPAdm.


Assuntos
Proteínas Estimuladoras de Ligação a CCAAT/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Proteínas de Neoplasias/genética , Receptores de Fator Estimulador de Colônias/genética , Adolescente , Adulto , Idoso , Criança , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prevalência , Taxa de Sobrevida
13.
J Zhejiang Univ Sci B ; 20(6): 467-475, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31090272

RESUMO

The stem/progenitor cell has long been regarded as a central cell type in development, homeostasis, and regeneration, largely owing to its robust self-renewal and multilineage differentiation abilities. The balance between self-renewal and stem/progenitor cell differentiation requires the coordinated regulation of cell cycle progression and cell fate determination. Extensive studies have demonstrated that cell cycle states determine cell fates, because cells in different cell cycle states are characterized by distinct molecular features and functional outputs. Recent advances in high-resolution epigenome profiling, single-cell transcriptomics, and cell cycle reporter systems have provided novel insights into the cell cycle regulation of cell fate determination. Here, we review recent advances in cell cycle-dependent cell fate determination and functional heterogeneity, and the application of cell cycle manipulation for cell fate conversion. These findings will provide insight into our understanding of cell cycle regulation of cell fate determination in this field, and may facilitate its potential application in translational medicine.


Assuntos
Ciclo Celular , Fenômenos Fisiológicos Celulares , Animais , Epigenômica , Fase G1 , Fase G2 , Humanos , Pesquisa Médica Translacional
14.
Neuroscience ; 406: 389-404, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30926548

RESUMO

The over-activation of N-methyl-D-aspartate receptors (NMDARs) is the main cause of neuronal death in brain ischemia. Both the NMDAR and the Acid-sensing ion channel 1a (ASIC1a) are present in the postsynaptic membrane of the central nervous system (CNS) and participate in physiological and pathological processes. However, the specific role played by ASIC1a in these processes remains elusive. We hypothesize that NMDARs are the primary mediators of normal synaptic transmission and excitatory neuronal death, while ASIC1a plays a modulatory role in facilitating NMDAR function. Using various experimental approaches including patch-clamp recordings on hippocampal slices and CHO cells, primary cultures of hippocampal neurons, calcium imaging, Western blot, cDNA transfection studies, and transient middle cerebral artery occlusion (tMCAO) mouse models, we demonstrate that stimulation of ASIC1a facilitates NMDAR function and inhibition of ASIC1a suppresses NMDAR over-activation. One of our key findings is that activation of ASIC1a selectively facilitates the NR1/NR2A/NR2B triheteromeric subtype of NMDAR currents. In accordance, inhibition of ASIC1a profoundly reduced the NMDAR-mediated EPSCs in older mouse brains, which are known to express much higher levels of triheteromeric NMDARs than younger brains. Furthermore, brain infarct sizes were reduced by a greater degree in older mice compared to younger ones when ASIC1a activity was suppressed. These data suggest that ASIC1a activity selectively enhances the function of triheteromeric NMDARs and exacerbates ischemic neuronal death especially in older animal brains. We propose ASIC1a as a novel therapeutic target for preventing and reducing the detrimental effect of brain ischemia in humans.


Assuntos
Bloqueadores do Canal Iônico Sensível a Ácido/administração & dosagem , Canais Iônicos Sensíveis a Ácido/fisiologia , Agonistas de Aminoácidos Excitatórios/administração & dosagem , Proteínas do Tecido Nervoso/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Animais , Células CHO , Células Cultivadas , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos/métodos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/agonistas , Técnicas de Cultura de Órgãos , Receptores de N-Metil-D-Aspartato/agonistas
15.
Langmuir ; 35(4): 1040-1046, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30605340

RESUMO

Antibodies of epithelial cell-adhesion molecule (anti-EpCAM)-based interfaces have proven to be highly efficient at capturing circulating tumor cells (CTCs). To achieve the bonding of anti-EpCAM to the interface, biotin and streptavidin are used to modify the surface. These processes are critical to subsequent cell-capture efficiencies. However, quantitative research on the interactions between biotin, streptavidin, and biotinylated anti-EpCAM on the interface is lacking. In this work, the thermodynamics and kinetics of biomolecular interactions were determined by using surface plasmon resonance. The equilibrium binding affinities for biotinylated anti-EpCAM to streptavidin and streptavidin to biotin (illustrated by biotin-PEG400-thiol) were found to be 2.75 × 106 and 8.82 × 106 M-1, respectively. Each streptavidin can bind up to 2.30 biotinylated anti-EpCAM under thermodynamic equilibrium. The findings provide useful information to optimize the modification of anti-EpCAM and improve the capture efficiency of CTCs.


Assuntos
Anticorpos/imunologia , Molécula de Adesão da Célula Epitelial/imunologia , Células Neoplásicas Circulantes/imunologia , Ressonância de Plasmônio de Superfície , Biotina/química , Biotina/imunologia , Humanos , Cinética , Células MCF-7 , Células Neoplásicas Circulantes/química , Células Neoplásicas Circulantes/patologia , Estreptavidina/química , Estreptavidina/imunologia , Termodinâmica , Fatores de Tempo
16.
Int J Mol Sci ; 20(1)2018 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-30583543

RESUMO

SBP-box (Squamosa-promoter binding protein) genes are a type of plant-specific transcription factor and play important roles in plant growth, signal transduction and stress response. However, little is known about the SBP-box genes in pepper (CaSBP), especially in the process of Phytophthora capsici infection. In this study, a novel gene (CaSBP12) was selected from the CaSBP gene family, which was isolated from the pepper genome database in our previous study. The CaSBP12 gene was located in the nucleus of the cell and its silencing in the pepper plant enhanced the defense response against Phytophthora capsici infection. After inoculation with Phytophthora capsici, the root activity of the CaSBP12-silenced plants is compared to control plants, while malondialdehyde (MDA) content is compared viceversa. Additionally, the expression of defense related genes (CaPO1, CaSAR8.2, CaBPR1, and CaDEF1) in the silenced plants were induced to different degrees and the peak of CaSAR8.2 and CaBPR1 were higher than that of CaDEF1. The CaSBP12 over-expressed Nicotiana benthamiana plants were more susceptible to Phytophthora capsici infection with higher EC (electrical conductivity) and MDA contents as compared to the wild-type. The relative expression of defense related genes (NbDEF, NbNPR1, NbPR1a, and NbPR1b) in transgenic and wild-type Nicotiana benthamiana plants were induced, especially the NbPR1a and NbPR1b. In conclusion, these results indicate that CaSBP12 gene negative regulates the defense response against Phytophthora capsici infection which suggests their potentially significant role in plant defense. To our knowledge, this is the first report on CaSBP gene which negative regulate defense response.


Assuntos
Capsicum/fisiologia , Resistência à Doença/fisiologia , Regulação da Expressão Gênica de Plantas/fisiologia , Phytophthora/patogenicidade , Doenças das Plantas/imunologia , Doenças das Plantas/parasitologia , Fatores de Transcrição/metabolismo , Acetatos/farmacologia , Capsicum/efeitos dos fármacos , Capsicum/genética , Ciclopentanos/farmacologia , Resistência à Doença/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Oxilipinas/farmacologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/parasitologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/parasitologia , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/fisiologia , Ácido Salicílico/farmacologia , Fatores de Transcrição/genética
17.
Huan Jing Ke Xue ; 39(5): 2174-2183, 2018 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965517

RESUMO

To investigate the whole-reach nitrate (NO3--N) uptake dynamics in a headwater agricultural stream, we performed five pulse tracer additions of a reactive solute (as KNO3) and a conservative solute (as NaBr) in an agricultural drainage ditch in Hefei district, Chaohu Lake basin, from October 2016 to April 2017. The TASCC (tracer additions for spiraling curve characterization) approach and Michaelis-Menten (M-M) method were applied for the simulation of NO3--N uptake dynamics. Results showed that the ambient areal rate of total NO3--N uptake Uamb varied from 11.40 to 69.13 µg ·(m2 ·s)-1 with an average of 34.45 µg ·(m2 ·s)-1, and the ambient uptake velocity Vf-amb averaged 0.24 mm ·s-1 and varied from 0.07 to 0.43 mm ·s-1 across three well-mixed sub-reaches in the study. The ambient uptake length Sw-amb averaged 199.06 m with a range from 92.51 to 405.74 m, which was much smaller than the length of the drainage ditch (about 2.5 km), suggesting that the agricultural drainage ditch had a high potential for NO3--N retention. Generally, the M-M model fit the NO3--N uptake dynamics well, and the maximum uptake Umax ranged from 158 to 1280 µg ·(m2 ·s)-1 with a mean of 631.13 µg ·(m2 ·s)-1. The half saturation constant Km ranged from 0.16 to 5.52 mg ·L-1 with a mean of 1.46 mg ·L-1. According to correlation analysis, Sw-amb was negatively correlated with NO3--Namb, and Uambwas significantly positively correlated with NO3--Namb, while other nutrient spiraling metrics were not correlated with the NO3--N ambient concentration. Hydrological conditions had no distinct effect on the NO3--N retention, but both the width variability Фw and variability in cross-sectional area ФA were significantly correlated with most of the nutrient spiraling metrics, indicating that geomorphic features in the drainage ditch evidently impacted NO3--N uptake.

18.
ACS Appl Mater Interfaces ; 10(31): 25983-25993, 2018 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30014692

RESUMO

Traditional drug delivery systems suffer from low drug-loading and relatively weak therapeutic efficacy, therefore, development of new drug delivery systems with high-efficiency has become more urgent. In this report, a novel-innovative drug delivery strategy, namely drug self-framed delivery system (DSFDS), is prepared via using anticancer drugs as polymer frame without using any carriers. The drug molecules (exemplified by doxorubicin) containing more than two nucleophilic functional groups (diols/diamines) directly reacted with hexachlorocyclotriphosphazene via mild precipitation polycondensation under ambient conditions, forming biocompatible drug self-framed delivery nanoparticles. Because of the covalent bonding of the drug molecules, DSFD nanoparticles (DSFDs) with super high drug-loading were stable in the circulation during delivery. However, sustained release of drug in the acidic environment within cells endowed DSFDs with long-term anticancer therapeutic efficacy. This strategy is applicable for diverse hydrophilic and hydrophobic drugs and may be a new platform for designing high drug-loading and release-controllable drug delivery systems.


Assuntos
Nanopartículas , Antineoplásicos , Doxorrubicina , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Compostos Organofosforados , Polímeros
19.
Oncol Lett ; 15(6): 9101-9109, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29928331

RESUMO

MicroRNAs (miRNAs) are important regulators of tumor formation, progression and metastasis. The present study characterized a novel miRNA (miR)-888, as a potent oncomiR in human colorectal cancer (CRC). The clinicopathological investigation on 126 cases of CRC patients demonstrated that the expression level of miR-888 was significantly upregulated in tumors compared with adjacent healthy tissue, and was associated with tumor stage and histological differentiation. A Kaplan-Meier analysis and log-rank test demonstrated that CRC patients with increased miR-888 expression exhibited a decreased overall survival (OS) and disease-free survival (DFS) compared with patients with low miR-888 expression. Further univariate and multivariate analyses identified miR-888 as an independent prognostic factor for poor survival outcome in CRC patients. To determine the biological role of miR-888 in human CRC, in vitro Cell Counting kit-8, wound healing and transwell assays were performed and demonstrated that miR-888 contributed greatly to CRC cell proliferation, invasion and metastasis. Furthermore, potential targets of miR-888 were investigated using a luciferase reporter assay, followed by polymerase chain reaction and western blot analysis. The findings revealed that miR-888 directly bound to the 3'-untranslated region of mothers against decapentaplegic-4 and thus inhibited its expression and promoted the tumor growth factor-1-induced cancer metastasis signaling. The results of the present study identified miR-888 as an oncogenic miRNA in CRC and provide a foundation for promising research in the future regarding this predictive and prognostic biomarker.

20.
Oncotarget ; 9(38): 24970-24979, 2018 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-29861846

RESUMO

The aim of this study was to profile the spectrum of genetic mutations in acute myeloid leukemia (AML) patients co-occurring with CEBPA double mutation (CEBPAdm). Between January 1, 2012, and June 30, 2017, 553 consecutive patients with de novo AML were screened for CEBPA mutations. Out of these, 81 patients classified as CEBPAdm were analyzed further by a sensitive next-generation sequencing assay for mutations in 112 candidate genes. Within the CEBPA gene itself, we found 164 mutations. The most common mutated sites were c.936_937insGAG (n = 11/164, 6.71%) and c.939_940insAAG (n = 11/164, 6.71%), followed by c.68dupC (n = 10/164, 6.10%). The most common co-occurring mutations were found in the CSF3R (n = 16/81, 19.75%), WT1 (n = 15/81, 18.52%), and GATA2 (n = 13/81, 16.05%) genes. Patients with CSF3R mutations had an inferior four-year relapse-free survival (RFS) than those with the wild-type gene (15.3% versus 46.8%, respectively; P = 0.021). Patients with WT1 mutations had an inferior five-year RFS compared with those without such mutations (0% versus 26.6%, respectively, P = 0.003). However, GATA2, CSF3R, WT1 mutations had no significant influence on the overall survival. There were some differences in the location of mutational hotspots within the CEBPA gene, as well as hotspots of other co-occurring genetic mutations, between AML patients from Chinese and Caucasian populations. Some co-occurring mutations may be potential candidates for refining the prognoses of AML patients with CEBPAdm in the Chinese population.

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