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1.
Phys Chem Chem Phys ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32227028

RESUMO

Monolayer (ML) MoS2 is one of the most extensively studied two-dimensional (2D) semiconductors. However, it suffers from low carrier mobility and pervasive Schottky contact with metal electrodes. 2D semiconductor Bi2O2S, a sulfur analogue of 2D Bi2O2Se, has been prepared recently. ML fully hydrogen-passivated Bi2O2S2 (Bi2O2S2H2) posseses a comparable band gap (1.92 eV) with ML MoS2 (1.8 eV), but probably has a better device performance than ML MoS2. Based on the density functional theory, the electron and hole mobilities of ML Bi2O2S2H2 at 300 K are calculated to be 16 447-26 699 and 264-968 cm2 V-1 s-1, respectively. Then we firstly characterize the contact properties of ML half hydrogen-passivated Bi2O2S2 (Bi2O2S2H) with four bulk metal electrodes (Ti, Sc, Pd, and Pt) based on ab initio quantum transport simulation. In the lateral direction, a p-type Schottky contact is found in Pd and Pt electrodes, and the corresponding hole Schottky barrier heights (SBHs) are 0.54 and 0.99 eV, respectively. Remarkably, a coveted n-type Ohmic contact appears in Sc and Ti electrodes. Finally, the current on-off ratio of the ML hydrogen-passivated Bi2O2S2 field effect transistor with a Ti electrode reaches 105. Hence, the good intrinsic properties, contact properties, and large switching ability put ML hydrogen-passivated Bi2O2S2 in the rank of potential channel candidates for post-silicon era field effect transistors.

2.
Anim Sci J ; 91(1): e13361, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32219958

RESUMO

This study aims to evaluate the anti-heat stress effect of Chinese herbal medicine (CHM) prescription, rumen-protected γ-aminobutyric acid (RP-GABA), and CHM plus RP-GABA co-medication on growth performance, apparent digestibility, and serum parameters in heat-stressed beef cattle. Forty beef cattle were randomly divided into four groups. Control group was supplied with basal diet, while CHM, γ-aminobutyric acid (GABA), and CHM + GABA groups were, respectively, supplied with CHM, RP-GABA, and CHM plus RP-GABA in basal diet. Our result indicated that CHM + GABA elevated apparent digestibility including crude protein, Ca, P, crude fat (CF) (p < .01), and neutral detergent fiber (NDF) (p < .05), but no difference was found with CF and NDF digestibility both in CHM and GABA group (p > .05). More importantly, average daily gain (ADG) was improved in CHM, GABA, and CHM + GABA groups, while average daily feed intake (ADFI) significantly increased only in CHM + GABA groups (p < .05). Meanwhile, CHM + GABA displayed notably more positive effect in serum hormones, immune globulin, ions contents, and blood inflammatory cytokines than other treatment groups and control group. These results demonstrated that both CHM and GABA are effective in alleviating heat stress response and the co-medication has a synergistic effect on anti-heat stress.

3.
Ecotoxicol Environ Saf ; 192: 110267, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32044604

RESUMO

Endosulfan is a persistent organic pollutant and can cause endothelial dysfunction, closely related to cardiovascular diseases. Endothelial cell migration plays a critical role in atherosclerosis and angiogenesis. This study was aimed to investigate the effect of environmentally relevant doses of endosulfan and underlying molecular mechanism on endothelial cell migration. Human umbilical vein endothelial cells (HUVECs) were treated with DMSO (control) or endosulfan (0.1, 1, 10 and 20 µM) in the presence or absence of inhibitors. Wound healing and Transwell assay were employed to explore the effect of endosulfan on endothelial cell migration. The expression of genes or proteins was assayed by real-time PCR or immunoblotting. The results showed that endosulfan at relative low concentration (0.1, 1, 10 and 20 µM) increased cell migration ability horizontally and vertically at 12 h after exposure. In line with this cellular effect, Protein-tyrosine Phosphatase 4A3 (PTP4A3) expression was significantly increased in endosulfan-exposed endothelial cells. Specific inhibitor of PTP4A3 significantly inhibited 20 µM endosulfan-induced cell migration, the expression and phosphorylation of Src and phosphorylation of focal adhesion kinase (FAK). Exposure to endosulfan resulted in activation of various signaling pathways including phosphoinositide 3-kinase (PI3K)/AKT, mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB), which were suppressed by PTP4A3 inhibitor or specific inhibitor for each signaling pathway. Exposure to endosulfan significantly reduced nitric oxide production and caused oxidative stress in HUVECs. These findings suggest that endosulfan promoted cell migration through PTP4A3-mediated various signaling pathways in endothelial cells.

4.
Inorg Chem ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32105460

RESUMO

Full visible emission achieved by a single-phased system is of great interest to researchers for the development of high-quality solid-state lighting devices. Herein, novel Eu2+ and Mn2+ co-doped (1 - x)ß-Ca3(PO4)2-xCa9La(PO4)7 solid solution phosphors are designed to realize single-phased white light emission. The effects of variational x on lattice structure, color-tunable emission, thermal stability, and energy-transfer efficiency from Eu2+ to Mn2+ are systematically investigated. Tunable color emissions are achieved by manipulating the redistributions of Eu2+ ions among the different cationic sites under the influence of generated empty site in the M(4) site. Meanwhile, the changes of critical distances among the Eu2+ and Mn2+ caused by the variational x results in the changes of energy-transfer efficiency from different Eu2+ luminescent centers to Mn2+ due to the existence of structural confinement effect. The calculated results indicate that Eu1-Mn and Eu2-Mn possess higher energy-transfer efficiencies than other Eu-Mn pairs. Under the combined influence of the two effects, single-phased full visible white emission covering from 400 to 700 nm has been realized via the adjustment of solid solution, which makes the fabricated white-light-emitting diode (WLED) possess high color-rendering index (86.9) and R9 (87.2) as well as low correlated color temperature (3947 K). The results show that the 0.2ß-Ca3(PO4)2-0.8Ca9La(PO4)7:0.01Eu2+, 0.20Mn2+ could act as a promising phosphor for single-phased WLEDs. This work will open up a new avenue for tuning the multiple activator sites and energy-transfer efficiencies simultaneously to realize single-phased full visible white emission.

5.
BMC Genomics ; 21(1): 37, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931707

RESUMO

BACKGROUND: Light is the main source of energy and, as such, is one of the most important environmental factors for plant growth, morphogenesis, and other physiological responses. MicroRNAs (miRNAs) are endogenous non-coding RNAs that contain 21-24 nucleotides (nt) and play important roles in plant growth and development as well as stress responses. However, the role of miRNAs in the light response is less studied. We used tomato seedlings that were cultured in red light then transferred to blue light for 2 min to identify miRNAs related to light response by high-throughput sequencing. RESULTS: A total of 108 known miRNAs and 141 predicted novel miRNAs were identified in leaf samples from tomato leaves treated with the different light qualities. Among them, 15 known and 5 predicted novel miRNAs were differentially expressed after blue light treatment compared with the control (red light treatment). KEGG enrichment analysis showed that significantly enriched pathways included zeatin biosynthesis (ko00908), homologous recombination (ko03440), and plant hormone signal transduction (ko04075). Zeatin biosynthesis and plant hormone signal transduction are related to plant hormones, indicating that plant hormones play important roles in the light response. CONCLUSION: Our results provide a theoretical basis for further understanding the role of miRNAs in the light response of plants.

6.
Environ Pollut ; 258: 113701, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31818619

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants and could produce oxidative toxicity to plants. Our previous study has shown that miR398 is involved in response to phenanthrene treatment by targeting CSD1 and CSD2. However, it is not clear which is essential for CSD1 and CSD2 and how miR398 changes. In this study, we performed discontinuous PAGE to separate superoxide dismutase (SOD) isozymes and found that two bands of the cytosolic Cu/Zn-SOD are induced by phenanthrene at day 5 and 7. Low expression of pri-miR398 and high expression of pre-miR398 indicate that the conversion process from pri-miR398 to pre-miR398 is impeded, which causes decrease in mature miR398. The relative expression of CSD1 is entirely up-regulated, further confirming the important role of CSD1 in response to phenanthrene exposure. Besides, the overexpression of WRKY implies its potential function in answering the call from phenanthrene stress. Therefore, it is concluded that the gene silencing of CSD1 recedes due to the biosynthesis inhibition of miR398, causing the increase of SOD activity in response to phenanthrene exposure in wheat roots. Our results are useful not only for better understanding miRNAs regulation in detoxication of reactive oxygen species, but also for alleviating the toxicity to crops caused by PAHs.

8.
Cancer Biol Med ; 16(2): 299-311, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31516750

RESUMO

Objective: Vasculogenic mimicry (VM) channels that are lined by tumor cells are a functional blood supply in malignant tumors. However, the role of VM-initiating cells remains poorly understood. Cancer stem-like cells (CSCs) are positively correlated with VM. In this study, triple-negative breast cancer (TNBC) enriched with CSCs was used to investigate the relationship between VM and CSCs. Methods: The expression of several CSC markers was detected by immunohistochemistry in 100 human breast cancer samples. The clinical significance of CSC markers and the relationship between VM, CSCs, breast cancer subtypes, and VM-associated proteins were analyzed. CD133+ and ALDH+ human and mouse TNBC cells were isolated by FACS to examine the ability of VM formation and the spatial relationship between VM and CSCs. Results: CSCs were associated with TNBC subtype and VM in human invasive breast cancer. CSCs in TNBC MDA-MB-231 cells formed more VM channels and expressed more molecules promoting VM than the non-TNBC MCF-7 cells in vitro. MDA-MB-231 cells that encircled VM channels on Matrigel expressed CD133. Moreover, CSCs were located near VM channels in the 3D reconstructed blood supply system in human TNBC grafts. The CD133+ and ALDH+ cells isolated from TA2 mouse breast cancer formed more VM channels in vivo. Conclusions: CSCs line VM channels directly. Additionally, CSCs provide more VM-related molecules to synergize VM formation. The signaling pathways that control CSC differentiation may also be potential treatment targets for TNBC.

9.
Int J Genomics ; 2019: 9140572, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485438

RESUMO

The long history of asexual reproduction of garlic using garlic cloves has resulted in virus accumulation and genetic depression. Propagation of garlic seedlings by tissue culture can both eliminate viruses and improve breeding efficiency. Aerial bulbs are the first-choice materials for breeding virus-free garlic seedlings under external conditions, but they show dormancy just like garlic bulbs. However, low temperatures can quickly break dormancy. In this research, we used a high-throughput sequencing method to sequence aerial bulbs during dormancy and after low-temperature-induced breaking of dormancy to screen out the key differentially expressed genes (DEGs) associated with low temperature and to provide a theoretical basis for exploring the molecular mechanism of low-temperature-induced breaking of aerial bulb dormancy. The high-throughput transcriptome sequencing results showed that 6,675 DEGs were upregulated and 36,596 DEGs were downregulated in the aerial bulbs given low-temperature treatment. Then, 19,507 DEGs were assigned KEGG annotations, among which most DEGs were annotated to the metabolism pathway (11,817 genes, accounting for 60.58%), followed by the genetic information processing pathway (4,521 genes, accounting for 23.18%). The DEGs were mostly concentrated in pathways such as protein processing in the endoplasmic reticulum, plant-pathogen interaction, plant hormone signal transduction, and ribosome biogenesis in eukaryotes, with significant enrichment. The key DEGs related to calcium signaling, hormonal signaling, and transcription factors were screened out, including CaM, CDPK, and CML in accessory pathways of calcium signaling; GA20ox, GAI1, and GA2ox in accessory pathways of hormonal signaling; and transcription factor genes such as MYB, AP2/ERF, bHLH, MADS, and bZIP. qRT-PCR verification results were consistent with the sequencing results, indicating that the transcriptome sequencing data were accurate and reliable. Our results provide a theoretical basis for breaking the dormancy of aerial bulbs with low-temperature treatment to produce virus-free seedlings and increase the output and quality of garlic.

10.
ACS Nano ; 13(8): 8854-8864, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31322335

RESUMO

The development of silicon-based anode materials is important for improving the energy density of current lithium ion batteries. However, there are still strong demands for these materials with better cycle stability and higher reversible capacity. Here, a kind of dual bond restricted MXene-Si-CNT composite anode materials with enhanced electrochemical performance is reported. These dual bonds have been clearly revealed by an X-ray photoelectron spectroscopy technique and also proven by theoretical calculations with spontaneous reaction energy values (-0.190 and -0.429 eV/atom for Ti-Si and C-Si bonds, respectively). The cycle stability of the composites, prepared by a facile ball-milling synthetic method, can obviously be improved because of the existence of these dual bonds and the multidimensional constructed architecture. The MXene-Si-CNT composite with 60 wt % silicon possesses the best overall performance, with ∼80% capacity retention after 200 cycles, and achieves 841 mAh g-1 at 2 A g-1. This approach demonstrates a promising strategy to exploit high-performance anode materials and lessens the immanent negative effect of silicon-based materials. Furthermore, it is significant to extend this method to other anode materials with serious volumetric change problems during the cycling process.

11.
J Proteomics ; 203: 103380, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31102757

RESUMO

Thermophiles are organisms that grow optimally at 50 °C-80 °C and studies on the survival mechanisms of thermophiles have drawn great attention. Bacillus manusensis S50-6 is the type strain of a new thermophilic species isolated from hydrothermal vent in Manus Basin. In this study, we examined the growth and global responses of S50-6 to high temperature on molecular level using multi-omics method (genomics, proteomics, and metabolomics). S50-6 grew optimally at 50 °C (Favorable, F) and poorly at 65 °C (Non-Favorable, NF); it formed spores at F but not at NF condition. At NF condition, S50-6 formed long filaments containing undivided cells. A total of 1621 proteins were identified at F and NF conditions, and 613 proteins were differentially expressed between F and NF. At NF condition, proteins of glycolysis, rRNA mature and modification, and DNA/protein repair were up-regulated, whereas proteins of sporulation and amino acid/nucleotide metabolism were down-regulated. Consistently, many metabolites associated with amino acid and nucleotide metabolic processes were down-regulated at NF condition. Our results revealed molecular strategies of deep-sea B. manusensis to survive at unfavorable high temperature and provided new insights into the thermotolerant mechanisms of thermophiles. SIGNIFICANCE: In this study, we systematically characterized the genomic, proteomic and metabolomic profiles of a thermophilic deep-sea Bacillus manusensis under different temperatures. Based on these analysis, we propose a model delineating the global responses of B. manusensis to unfavorable high temperature. Under unfavorable high temperature, glycolysis is a more important energy supply pathway; protein synthesis is subjected to more stringent regulation by increased tRNA modification; protein and DNA repair associated proteins are enhanced in production to promote heat survival. In contrast, energy-costing pathways, such as sporulation, are repressed, and basic metabolic pathways, such as amino acid and nucleotide metabolisms, are slowed down. Our results provide new insights into the thermotolerant mechanisms of thermophilic Bacillus.

12.
J Plant Physiol ; 237: 1-11, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30999072

RESUMO

Iron (Fe) is an essential micronutrient element for plant growth. The S-nitrosoglutathione reductase (GSNOR) gene's functions under Fe-deficiency conditions are not well understood. Here, GSNOR expression was induced by Fe deficiency in tomato (Solanum lycopersicum L.) leaves and roots, while its overexpression alleviated chlorosis under Fe-deficiency conditions. GSNOR overexpression positively regulated the Fe distribution from root to shoot, which might result from the transcriptional regulation of genes involved in Fe metabolism. Additionally, the overexpression of GSNOR maintained redox homeostasis and protected chloroplasts from Fe-deficiency-related damage, resulting in a greater photosynthetic capacity. As a nitric oxide regulator, GSNOR's overexpression decreased the excessive accumulation of nitric oxide and S-nitrosothiols during the Fe deficiency, and maintained the homeostases of reactive oxygen species and reactive nitrogen species. Moreover, GSNOR overexpression, probably at the level of genes and proteins, along with protein S-nitrosylation, promoted Fe uptake and regulated the shoot/root Fe ratio under Fe-deficiency conditions.


Assuntos
Aldeído Oxirredutases/genética , Regulação da Expressão Gênica de Plantas , Homeostase , Ferro/deficiência , Lycopersicon esculentum/genética , Proteínas de Plantas/genética , Aldeído Oxirredutases/metabolismo , Ferro/metabolismo , Lycopersicon esculentum/enzimologia , Lycopersicon esculentum/metabolismo , Oxirredução , Proteínas de Plantas/metabolismo
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(2): 311-317, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-30998131

RESUMO

OBJECTIVE: To screen and verify the differentially expressed genes related with aging of bone marrow mesenchymal stem cells (BM-MSCs) in acute myeloid leukemia (AML) patients by bioinformatics, so as to provide new molecular markers for the research and clinical treatment of AML. METHODS: The gene expression profiling chip related with BM-MSCs in AML patients in our hospital and the gene chip GSE84881 selected from NCBI database GEO were used for data analysis and exploration. The DAVID analysis software was used to perform gene ontology (GO) enrichment analysis and KEGG pathway enrichment analysis. Furthermore, the differentially expressed genes related with aging of BM-MSCs in AML patients were identified. Bone marrow samples were collected and MSCs were amplified in vitro, and RT-PCR was used to verify the differentially expressed genes, which should be further identified with senescence-associated ß-galactosidase staining and MTT cell proliferation assays. RESULTS: A total of 247 differentially expressed genes were screened out by bioinformatics methods, including genes of 132 up-regulated expression and 115 down-regulated expression. Six differentially expressed genes related with aging of BM-MSCs in AML patients were screened out, including the genes of up-regulated expression, COL3A1 (P<0.05), CRYAB (P<0.01), DCN (P<0.05), and the genes of down-regulated expression, including CCL2 (P<0.05), CTSC (P<0.01) and IL6 (P<0.05). These 6 differentially expressed genes were consistent with data from chip assays, and which was significantly correlated with aging of BM-MSCs in AML patients. Meanwhile, the positive rate of senescence-associated ß-galactosidase staining in BM-MSCs of AML patients was significantly different from that of healthy donors (P<0.01). MTT cell proliferation assay showed that BM-MSCs in AML patients had proliferative ability lower than the healthy donors' BM-MSCs. CONCLUSION: The data here suggest novel clues for the clinical research and treatment of BM-MSCs aging in AML patients.


Assuntos
Leucemia Mieloide Aguda , Células-Tronco Mesenquimais , Células da Medula Óssea , Proliferação de Células , Células Cultivadas , Biologia Computacional , Humanos
14.
J Craniofac Surg ; 30(4): 1303-1307, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30817520

RESUMO

To study the influence of distraction osteogenesis (DO) on the maxillary growth as first-stage treatment of palatal defect. The uniform palate defect experimental animal models (21 miniature pigs) were established surgically. Then animals were randomly divided into negative control group (A, n = 6), conventional surgery group (B, n = 6), and distraction osteogenesis group (C, n = 9) respectively. The group A underwent none treatment as control group, the group B were undergoing a conventional defect repair surgery, and the group C were undergoing a distraction osteogenesis treatment. Cone beam computed tomography examination was performed monthly to analyze the growth of maxilla for 6 months. One pig of group C was randomly sacrificed at 2, 4, and 8 weeks after the completion of DO and the tissue of distraction gap was stained with hematoxylin-eosin and Masson staining. At the end of 6th months, all pigs were sacrificed and tissues of the surgical area were stained as previous described. The palate defect was repaired by the distraction osteogenesis with the successful bone formation on the distraction gap. Group A and group C kept a similar growth rate, but that of group B was relatively slow. Distraction osteogenesis is efficient and successful for closing the defect of palate and there is no significant disturbance on the subsequent growth of the maxilla.


Assuntos
Fissura Palatina/cirurgia , Maxila/crescimento & desenvolvimento , Osteogênese por Distração/métodos , Animais , Masculino , Maxila/cirurgia , Osteogênese/fisiologia , Distribuição Aleatória , Suínos , Porco Miniatura
15.
Sensors (Basel) ; 19(6)2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30901928

RESUMO

In this paper, a novel direction-of-arrival (DOA) estimation for unknown (anonymous) emitter signal (ES) based on time reversal (TR) and coprime array (CA) is proposed. The resolution and accuracy of DOA estimation are enhanced from two aspects: one is from the view of array arrangement: the new distribution of CA is designed to reduce the holes, increase the degree of freedom (DOF) and apertures by rotating and translating only one subarray, which simplifies the operation. The other one is from the view of the algorithm: a neoteric DOA estimation algorithm with noise suppression based on TR, Capon and adaptive neuro-fuzzy inference system (ANFIS) is proposed for solving the wide sidelobe, multipath effect, low resolution and accuracy produced by conventional algorithms, in particular, those cannot work effectively under the existed hole condition. Furthermore, the resubmitting distorted noise and channel noise are suppressed effectively, which is not taken into considered in the conventional Capon algorithm. Simulation results including the resolution, accuracy, root mean square error (RMSE), Cramér-Rao lower bound (CRLB) and the compared analyses on uniform linear array (ULA), nested array (NA) and minimum redundancy array(MRA) demonstrate the performance advantages of the proposed DOA estimation algorithm even at very low signal-to-noise ratio (SNR) condition.

17.
Chem Commun (Camb) ; 55(15): 2138-2141, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30640325

RESUMO

By using a low-cost, ternary AlCl3/LiCl/KCl inorganic molten salt as the electrolyte, an aluminum ion battery is able to work stably below 100 °C. When intergrated with a graphite paper cathode, the battery exhibits close performance and similar electrochemical transformations to inorganic electrolyte-based batteries operating at ≥120 °C.

18.
Talanta ; 196: 442-448, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30683390

RESUMO

Fluorescent carbon quantum dots are emerging as a new class of fluorescent probes due to their unique optical properties. Herein, we presented a simple, one-pot and effective preparation strategy for copper-functionalized carbon quantum dots (Cu-CDs). The Cu-CDs demonstrated excitation-independent emissions, high fluorescent quantum yield (~ 24.4%) and excellent fluorescent stability. The fluorescence of Cu-CDs could be quenched efficiently in the presence of histidine (His) due to the coordination occurring between surface Cu and imidazole side chains of His. Thus, the Cu-CDs could be used as an efficient fluorescent probe for His detection. Under optimal conditions, the fluorescent signals of Cu-CDs decreased linearly with the concentrations of His over a range of 0.1-15 µM. The detection limit was 30 nM. The proposed method provided obvious advantages of rapid response, convenience, simplicity, high selectivity and sensitivity. Moreover, good results also have been obtained for His detection in real biological fluid samples.


Assuntos
Carbono/química , Cobre/química , Corantes Fluorescentes/química , Histidina/análise , Pontos Quânticos/química , Adulto , Histidina/química , Humanos , Micro-Ondas
19.
Mol Med Rep ; 19(1): 309-319, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30431097

RESUMO

Gastric cancer is one of the leading causes of cancer-associated mortality worldwide. Cytotoxin­associated gene A (CagA) has been reported to be associated with gastric diseases. Phosphatase and tensin homolog (PTEN) and tet methylcytosine dioxygenase 1 (Tet1) are important tumor­suppressor genes. The present study aimed to investigate the underlying functions of CagA in human gastric cancer, and to explore the associations between CagA, PTEN and Tet1 in gastric cancer. For that purpose, CagA overexpression and Tet1 interference recombinant lentiviral plasmids were constructed. Quantitative polymerase chain reaction (qPCR) was utilized to screen gene expression in HGC­27 human gastric cancer cells overexpressing CagA. qPCR and western blotting were used to detect gene and protein expression, respectively. In addition, the methylation status of PTEN was detected by methylation­specific PCR. The expression levels of PTEN, Tet1, apolipoprotein B mRNA editing enzyme catalytic subunit (APOBEC)3A, APOBEC3C and APOBEC3F were significantly decreased in the CagA overexpression group compared with in the negative control group in HGC­27 cells. Compared with in the negative control group, the mRNA and protein expression levels of PTEN were markedly decreased in cells with Tet1 interference. The decreased expression of PTEN was associated with increased methylation levels in the cells. In addition, the protein expression levels of PTEN were significantly decreased in HGC­27 cells when CagA was overexpressed. The expression levels of PTEN and Tet1 were also markedly decreased in CagA+ gastric cancer tissues compared with in non­cancerous tissues. The decreased expression of PTEN in CagA+ gastric cancer tissues was associated with increased methylation levels. In conclusion, overexpression of CagA significantly decreased the expression of PTEN, Tet1, APOBEC3A, APOBEC3C and APOBEC3F in human gastric cancer. In addition, CagA increased DNA methylation and decreased PTEN expression, which was reversed by Tet1 overexpression. The present study may facilitate future therapeutic approaches targeting human gastric cancer.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Oxigenases de Função Mista/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias Gástricas/genética , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Ilhas de CpG , Citotoxinas/metabolismo , Humanos , Oxigenases de Função Mista/genética , PTEN Fosfo-Hidrolase/genética , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Células Tumorais Cultivadas
20.
FASEB J ; 33(4): 4755-4764, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30592634

RESUMO

The role of proinflammatory cytokines secreted by the bone marrow mesenchymal stromal cells (BM-MSCs) in the progression of acute myeloid leukemia (AML) is poorly understood. We compared C-X-C motif chemokine ligand (CXCL)8 expression levels in the BM-MSCs of patients with AML and normal control subjects and detected significantly higher levels in the former. Furthermore, CXCL8 was up-regulated in cocultures of BM-MSCs and leukemic cell lines compared with either monoculture. CXCL8 expression was significantly higher in MSCs compared with mononuclear cells in patients with de novo AML. To elucidate the function of paracrine CXCL8 in AML, we blocked CXCL8 binding to the C-X-C motif chemokine receptor (CXCR)2 in the AML cells using SB225002. Inhibition of CXCL8/CXCR2 binding decreased proliferation in the AML cells by inducing cell cycle arrest at the G0/G1 phase and apoptosis via decreased AKT phosphorylation. Blocking the PI3K/AKT signaling pathway by a specific inhibitor induced similar apoptosis induction and lower proliferation, suggesting that the PI3K/AKT signaling pathway was also involved in CXCL8 action. Taken together, our findings demonstrate that BM-MSCs are the main source of CXCL8 in the AML bone marrow microenvironment and promote leukemogenesis via the PI3K/AKT signaling pathway, indicating a novel therapeutic target.-Cheng, J., Li, Y., Liu, S., Jiang, Y., Ma, J., Wan, L., Li, Q., Pang, T. CXCL8 derived from mesenchymal stromal cells supports survival and proliferation of acute myeloid leukemia cells through the PI3K/AKT pathway.


Assuntos
Proliferação de Células/fisiologia , Interleucina-8/metabolismo , Interleucina-8/farmacologia , Células-Tronco Mesenquimais/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adolescente , Adulto , Idoso , Apoptose/efeitos dos fármacos , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Imunofluorescência , Células HL-60 , Humanos , Leucemia Mieloide Aguda/metabolismo , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Adulto Jovem
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