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1.
Oncogene ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846573

RESUMO

PR domain zinc finger protein 4 (PRDM4) is a transcription factor that plays key roles in stem cell self-renewal and tumorigenesis. However, its biological role and exact mechanism in cervical cancer remain unknown. Here, both immunohistochemistry (IHC) and Western blot assays demonstrated that the expression of PRDM4 in cervical cancer tissues was much lower than that in the normal cervix. A xenograft assay showed that PRDM4 overexpression in the cervical cancer cell lines SiHa and HeLa dramatically inhibited cell proliferation and tumorigenic potential in vivo. Conversely, the silencing of PRDM4 promoted cervical cancer cell proliferation and tumorigenic potential. Mechanistically, PRDM4 induced cell cycle arrest at the transition from G0/G1 phase to S phase by upregulating p27 and p21 expression and downregulating Cyclin D1 and CDK4 expression. Furthermore, the PI3K/AKT signaling pathway was inactivated in PRDM4-overexpressing cells, which decreased the levels of p-AKT and upregulated the expression of PTEN, an inhibitor of the PI3K/AKT signaling pathway, at both the transcriptional and translational levels. Dual-luciferase reporter assays and qChIP assays confirmed that PRDM4 transactivated the expression of PTEN by binding to two specific regions in the PTEN promoter. Furthermore, PTEN silencing or a PTEN inhibitor rescued the cell defects induced by PRDM4 overexpression. Therefore, our data suggest that PRDM4 inhibits cell proliferation and tumorigenesis by downregulating the activity of the PI3K/AKT signaling pathway by directly transactivating PTEN expression in cervical cancer.

2.
Sci Rep ; 11(1): 721, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436924

RESUMO

Expression of stress response genes can be regulated by abscisic acid (ABA) dependent and ABA independent pathways. Osmotic stresses promote ABA accumulation, therefore inducing the expression of stress response genes via ABA signaling. Whereas cold and heat stresses induce the expression of stress response genes via ABA independent pathway. ABA induced transcription repressors (AITRs) are a family of novel transcription factors that play a role in ABA signaling, and Drought response gene (DRG) has previously been shown to play a role in regulating plant response to drought and freezing stresses. We report here the identification of DRG as a novel transcription factor and a regulator of ABA response in Arabidopsis. We found that the expression of DRG was induced by ABA treatment. Homologs searching identified AITR5 as the most closely related Arabidopsis protein to DRG, and homologs of DRG, including the AITR-like (AITRL) proteins in bryophytes and gymnosperms, are specifically presented in embryophytes. Therefore we renamed DRG as AITRL. Protoplast transfection assays show that AITRL functioned as a transcription repressor. In seed germination and seedling greening assays, the aitrl mutants showed an increased sensitivity to ABA. By using qRT-PCR, we show that ABA responses of some ABA signaling component genes including some PYR1-likes (PYLs), PROTEIN PHOSPHATASE 2Cs (PP2Cs) and SUCROSE NONFERMENTING 1 (SNF1)-RELATED PROTEIN KINASES 2s (SnRK2s) were reduced in the aitrl mutants. Taken together, our results suggest that AITRLs are a family of novel transcription repressors evolutionally conserved in embryophytes, and AITRL regulates ABA response in Arabidopsis by affecting ABA response of some ABA signaling component genes.

3.
Cell Death Dis ; 12(1): 105, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479226

RESUMO

Homeobox B4 (HOXB4), which belongs to the homeobox (HOX) family, possesses transcription factor activity and has a crucial role in stem cell self-renewal and tumorigenesis. However, its biological function and exact mechanism in cervical cancer remain unknown. Here, we found that HOXB4 was markedly downregulated in cervical cancer. We demonstrated that HOXB4 obviously suppressed cervical cancer cell proliferation and tumorigenic potential in nude mice. Additionally, HOXB4-induced cell cycle arrest at the transition from the G0/G1 phase to the S phase. Conversely, loss of HOXB4 promoted cervical cancer cell growth both in vitro and in vivo. Bioinformatics analyses and mechanistic studies revealed that HOXB4 inhibited the activity of the Wnt/ß-catenin signaling pathway by direct transcriptional repression of ß-catenin. Furthermore, ß-catenin re-expression rescued HOXB4-induced cervical cancer cell defects. Taken together, these findings suggested that HOXB4 directly transcriptional repressed ß-catenin and subsequently inactivated the Wnt/ß-catenin signaling pathway, leading to significant inhibition of cervical cancer cell growth and tumor formation.

4.
J Cell Mol Med ; 24(21): 12464-12475, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32954681

RESUMO

NF-YA is considered as a crucial regulator for the maintenance of cancer stem cell (CSC) and involved in various types of malignant tumours. However, the exact function and molecular mechanisms of NF-YA in the progression of cervical cancer remains poorly understood. Here, the expression of NF-YA detected by immunohistochemistry was gradually increased from normal cervical tissues, to the high-grade squamous intraepithelial lesions, and then to cervical cancer tissues. NF-YA promoted the cell proliferation and tumorigenic properties of cervical cancer cells as well as tumorsphere formation and chemoresistance in vitro. The luciferase reporter assay combined with mutagenesis analyses and Western blotting showed that NF-YA trans-activated the expression of SOX2 in cervical cancer. Furthermore, quantitative chromatin immunoprecipitation (qChIP) and electrophoretic mobility shift assay (EMSA) confirmed that NF-YA protein directly bound to the CCAAT box region located upstream of the SOX2 promoter. Together, our data demonstrated that NF-YA was highly expressed in cervical cancer and promoted the cell proliferation, tumorigenicity and CSC characteristic by trans-activating the expression of SOX2.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32867133

RESUMO

OBJECTIVE: The outbreak of infectious diseases has a negative influence on public health and the economy. The prediction of infectious diseases can effectively control large-scale outbreaks and reduce transmission of epidemics in rapid response to serious public health events. Therefore, experts and scholars are increasingly concerned with the prediction of infectious diseases. However, a knowledge mapping analysis of literature regarding the prediction of infectious diseases using rigorous bibliometric tools, which are supposed to offer further knowledge structure and distribution, has been conducted infrequently. Therefore, we implement a bibliometric analysis about the prediction of infectious diseases to objectively analyze the current status and research hotspots, in order to provide a reference for related researchers. METHODS: We viewed "infectious disease*" and "prediction" or "forecasting" as search theme in the core collection of Web of Science from inception to 1 May 2020. We used two effective bibliometric tools, i.e., CiteSpace (Drexel University, Philadelphia, PA, USA) and VOSviewer (Leiden University, Leiden, The Netherlands) to objectively analyze the data of the prediction of infectious disease domain based on related publications, which can be downloaded from the core collection of Web of Science. Then, the leading publications of the prediction of infectious diseases were identified to detect the historical progress based on collaboration analysis, co-citation analysis, and co-occurrence analysis. RESULTS: 1880 documents that met the inclusion criteria were extracted from Web of Science in this study. The number of documents exhibited a growing trend, which can be expressed an increasing number of experts and scholars paying attention to the field year by year. These publications were published in 427 different journals with 11 different document types, and the most frequently studied types were articles 1618 (83%). In addition, as the most productive country, the United States has provided a lot of scientific research achievements in the field of infectious diseases. CONCLUSION: Our study provides a systematic and objective view of the field, which can be useful for readers to evaluate the characteristics of publications involving the prediction of infectious diseases and for policymakers to take timely scientific responses.


Assuntos
Bibliometria , Doenças Transmissíveis , Surtos de Doenças , Publicações , Doenças Transmissíveis/epidemiologia , Eficiência , Previsões , Humanos , Países Baixos , Philadelphia
6.
Sci Rep ; 10(1): 13754, 2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32792555

RESUMO

Muscle oxygenation (MO) status is the dynamic balance between O2 utilization and O2 delivery. Low-impact high-intensity interval exercise MO responses in the exercise and recovery stage are still unclear. We compared the differences in MO and physiological parameters between high-intensity interval water-based exercise (WHIIE) and high-intensity interval land bike ergonomic exercise (LBEHIIE) in postmenopausal women. Eleven postmenopausal women completed WHIIE or LBEHIIE in counter-balanced order. Eight sets were performed and each exercise set included high intensity with 80% heart rate reserve (HRR) in 30 s and dynamic recovery with 50% HRR in 90 s. Muscle tissue oxygen saturation index (TSI), total hemoglobin (tHb), oxy-hemoglobin (O2Hb), and deoxy-hemoglobin (HHb) were recorded. Blood lactate, heart rate and rating of perceived exertion (RPE) were measured at pre and post-exercise. Under similar exercise intensity, RPE in WHIIE was lower than that in LBEHIIE. The heart rate in WHIIE was lower than that in LBEHIIE at 1 and 2 min post-exercise. During the dynamic recovery, TSI, tHb, and O2Hb in water were higher than on land. A negative correlation was found between the change in TSI and lactate concentration (r = - 0.664). WHIIE produced greater muscle oxygenation during dynamic recovery. Muscle TSI% was inversely related to blood lactate concentration during exercise in water.

7.
J Vet Diagn Invest ; 32(5): 695-699, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32667260

RESUMO

Atypical porcine pestivirus (APPV) had been detected in many countries. However, to date, a commercial detection kit is not available because of a lack of specific monoclonal antibodies (mAbs) to APPV. We generated 7 mAbs targeting the NS3 protein of APPV. Isotyping results indicated that all of these mAbs are IgG1 with a kappa light chain. We analyzed the epitopes recognized by mAbs 2B6, 6G11, 8D1, 8D3, and 8F12, which recognized the same linear epitope (GRIKSAYSDE); the 6H3 and 7E10 mAbs recognized 2 different conformational epitopes. Applications of these antibodies were verified by ELISA, western blot, indirect immunofluorescence assay, and flow cytometry. The antibodies were functionally workable for these immunoassays except for 8F12, which could not be used in flow cytometry.

8.
Nat Commun ; 11(1): 3665, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32694568

RESUMO

Groundwater (GW) overexploitation is a critical issue in North China with large GW level declines resulting in urban water scarcity, unsustainable agricultural production, and adverse ecological impacts. One approach to addressing GW depletion was to transport water from the humid south. However, impacts of water diversion on GW remained largely unknown. Here, we show impacts of the central South-to-North Water Diversion on GW storage recovery in Beijing within the context of climate variability and other policies. Water diverted to Beijing reduces cumulative GW depletion by ~3.6 km3, accounting for 40% of total GW storage recovery during 2006-2018. Increased precipitation contributes similar volumes to GW storage recovery of ~2.7 km3 (30%) along with policies on reduced irrigation (~2.8 km3, 30%). This recovery is projected to continue in the coming decade. Engineering approaches, such as water diversions, will increasingly be required to move towards sustainable water management.

9.
Cancer Med ; 9(14): 5200-5209, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32441484

RESUMO

BACKGROUND: Ovarian cancer (OC) is the deadliest gynecological cancer. The absence of biomarkers in early detection and chemotherapy resistance is a principal cause of treatment failure in OC. METHODS: In this study, next generation sequencing (NGS) was used to sequence the mRNA of 44 OC patients including 14 chemotherapy insensitive and 18 sensitive patients. Differentially expressed genes (DEGs) from OC patients (compared with healthy controls) and chemotherapy sensitive patients (compared with chemotherapy insensitive patients) were identified by edgeR v3.12.0 in R v3.2.2, which were enriched using Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG). The common DEGs in cancer occurring and chemotherapy sensitivity were further screened. Among them, genes participating in chemotherapy sensitivity associated pathways were regarded as chemotherapy sensitivity-related key genes. Quantitative real-time PCR (qPCR) and immunohistochemistry (IHC) were used to verify the expression of the key genes. RESULTS: We found 1588 DEGs between OC patients and healthy controls (HCs), which were mainly enriched in cell cycle pathway. Meanwhile, 249 DEGs were identified between chemotherapy sensitive and insensitive OC patients, which were mainly enriched in MAPK signaling pathway, ERBB signaling pathway, TNF signaling pathway, and IL-17 signaling pathway. Thirty-five DEGs were shared in chemotherapy sensitivity group and cancer occurring group. Among them, there are five genes (JUND, JUNB, MUC5B, NRG1, and NR4A1) participating in the above four chemotherapy sensitivity-related pathways. It is remarkable that JUND is in the upstream of MUC5B in IL-17 signaling pathway and their expressions were verified by qPCR and IHC. CONCLUSIONS: The expression levels of the key genes related to chemotherapy sensitivity might be used as biomarkers to predict the treatment outcome and as a target to improve prognosis.

10.
Nat Commun ; 11(1): 2627, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32457302

RESUMO

Detection and manipulation of spin current lie in the core of spintronics. Here we report an active control of a net spin Hall angle, θSHE(net), in Pt at an interface with a ferroelectric material PZT (PbZr0.2Ti0.8O3), using its ferroelectric polarization. The spin Hall angle in the ultra-thin Pt layer is measured using the inverse spin Hall effect with a pulsed tunneling current from a ferromagnetic La0.67Sr0.33MnO3 electrode. The effect of the ferroelectric polarization on θSHE(net) is enhanced when the thickness of the Pt layer is reduced. When the Pt layer is thinner than 6 nm, switching the ferroelectric polarization even changes the sign of θSHE(net). This is attributed to the reversed polarity of the spin Hall angle in the 1st-layer Pt at the PZT/Pt interface when the ferroelectric polarization is inverted, as supported by the first-principles calculations. These findings suggest a route for designing future energy efficient spin-orbitronic devices using ferroelectric control.

11.
Sci Total Environ ; 719: 137517, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32120112

RESUMO

Global climate change and decreases in available land are significant challenges that humans are currently facing. Alternative management approaches for sugarcane fields have great potential to help mitigate these problems in China. We hypothesized that soybean intercropping with reduced nitrogen input could increase crop productivity and reduce the carbon footprint (CF) of sugarcane fields in China. Therefore, a long-term field experiment from 2009 to 2017 in the Pearl River Delta of China was chosen to test this hypothesis. The results showed that the energy yields of sugarcane/soybean intercropping systems were 17.8%-39.4% higher than those of sugarcane monocropping systems. The energy yields of the same cropping systems using conventional and reduced N inputs (525 kg ha-1 and 300 kg ha-1) did not show a significant difference. Additionally, the CF values of the unit yield (CFY) for sugarcane/soybean intercropping were 3.2%-30.4% lower than those of the monocropping systems, showing the higher CF efficiency of the intercropping pattern, although the difference was not significant. The CF of the unit area (CFA) and the CFY of all the cropping patterns at the conventional N level were 19.5%-62.0% higher than that at the reduced N level, demonstrating that reducing the nitrogen input could significantly lower the CF of the sugarcane fields. In addition, the high N level cased negative effects in terms of increasing the crop productivity and reducing the CF of the soybean/sugarcane intercropping pattern. In conclusion, sugarcane/soybean intercropping with reduced N input improved crop productivity while lowering the CF of sugarcane fields in China. The sugarcane/soybean (1:2) intercropping with 300 kg N ha-1 system showed the best benefits in the Pearl River Delta of China. These advanced agricultural practices contributed to improved farmland use efficiency and clean production in an agricultural system.


Assuntos
Saccharum , Soja , Agricultura , Pegada de Carbono , China , Fertilizantes , Nitrogênio
12.
Proc Natl Acad Sci U S A ; 117(13): 7090-7094, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32179681

RESUMO

Electronic phase separation in complex oxides is the inhomogeneous spatial distribution of electronic phases, involving length scales much larger than those of structural defects or nonuniform distribution of chemical dopants. While experimental efforts focused on phase separation and established its correlation with nonlinear responses under external stimuli, it remains controversial whether phase separation requires quenched disorder for its realization. Early theory predicted that if perfectly "clean" samples could be grown, both phase separation and nonlinearities would be replaced by a bicritical-like phase diagram. Here, using a layer-by-layer superlattice growth technique we fabricate a fully chemically ordered "tricolor" manganite superlattice, and compare its properties with those of isovalent alloyed manganite films. Remarkably, the fully ordered manganite does not exhibit phase separation, while its presence is pronounced in the alloy. This suggests that chemical-doping-induced disorder is crucial to stabilize the potentially useful nonlinear responses of manganites, as theory predicted.

13.
Plant Signal Behav ; 15(4): 1744293, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-32213123

RESUMO

ABA regulates abiotic stress tolerance in plants via activating/repressing gene expression. However, the functions of many ABA response genes remained unknown. C/VIFs are proteinaceous inhibitors of the CWI and VI invertases. We report here the involvement of C/VIF1 in regulating ABA response and salt tolerance in Arabidopsis. We found that the expression level of C/VIF1 was increased in response to ABA treatment. By using CRISPR/Cas9 gene editing, we generated transgene-free c/vif1 mutants. We also generated C/VIF1 overexpression plants by expressing C/VIF1 under the control of the 35S promoter. We examined ABA response of the 35S:C/VIF1 transgenic plants and the c/vif1 mutants by using seed germination and seedling greening assays, and found that the 35S:C/VIF1 transgenic plants showed an enhanced sensitivity to ABA treatment in both assays. On the other hand, the c/vif1 mutants showed slight enhanced tolerance to ABA only at the early stage of germination. We also found that salt tolerance was reduced in the 35S:C/VIF1 transgenic plants in seed germination assays, but slightly increased in the c/vif1 mutants. Taken together, our results suggest that C/VIF1 is an ABA response gene, and C/VIF1 is involved in the regulation of ABA response and salt tolerance in Arabidopsis.

14.
Front Physiol ; 10: 1174, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572219

RESUMO

Objective: Ischemic stroke is a complex multifactorial disease caused by interactions among polygenetic, environmental, and lifestyle factors with limited effective treatments. Multi-herbal formulae have long been used for stroke through herbal compatibility in traditional Chinese medicine (TCM); however, there is still a lack of evidence due to their unimaginable complexity. Herbal pairs represent the simplest and basic features of multi-herbal formulae, which are of great significance in clarifying herbal compatibility. Here, we aim to investigate the neuroprotective effects of the herbal compatibility of Ginseng and Rhubarb on a cerebral ischemia/reperfusion (I/R) injury model of rats. Methods: Male adult SD rats were randomly divided into a sham group, a normal saline (NS) group, a Ginseng group, a Rhubarb group, and a Ginseng + Rhubarb (GR) group, a Carbenoxolone [CBX, gap junction (GJ) specific inhibitor] group, and a GR + CBX group. Each group was further assigned into four subgroups according to ischemic time (6 h, 1 day, 3 days, and 7 days). The cerebral I/R injury model was established according to the modified Zea Longa method. The Neurological Deficiency Score (NDS) was assessed by the Zea-Longa scale; the cerebral infarction area was detected by TTC (2,3,5-triphenyltetrazolium chloride) staining; and the expression of connexin-43 (Cx43) and aquaporin-4 (AQP4) were detected based on an immunofluorescence technique and quantitative real-time-PCR. Results: Compared to the I/R group, both the independent and combined use of Ginseng and Rhubarb can significantly improve NDS (P < 0.05), decrease the percentage of the cerebral infarction area around the infarction penumbra (P < 0.05) and down-regulate the expression of Cx43 and AQP4 after I/R injury (P < 0.05). The GR had more significant effects than that of Ginseng and Rhubarb (P < 0.05). Compared with the GR group, the GR + CBX group significantly improved in NDS (P < 0.05), and decreased the percentage of the cerebral infarction area (P < 0.05) and expression of Cx43 and AQP4 protein (P < 0.05). Conclusion: The herbal compatibility of Ginseng and Rhubarb synergistically exerts neuroprotective function during acute cerebral I/R injury, mainly through reducing the expression of Cx43 and AQP4.

15.
Chem Commun (Camb) ; 55(83): 12463-12466, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31576854

RESUMO

Herein, an ultrasensitive electrochemical biosensor is proposed for the quantification of the Flu A virus biomarker DNA (fDNA), and is based on loop-mediated isothermal amplification-generated hydrogen ions (LAMP-H+) which induce the formation of the dimer i-motif structure (DiMS) for signal transduction, coupled with exonuclease III (ExoIII)-assisted DNA walking for signal dual-amplification.


Assuntos
Técnicas Biossensoriais , DNA Viral/análise , Técnicas Eletroquímicas , Vírus da Influenza A/química , Técnicas de Amplificação de Ácido Nucleico , Prótons , Biomarcadores/análise , Dimerização , Íons/química
16.
PLoS One ; 14(9): e0218583, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31545795

RESUMO

The CRISPR/Cas9 genome editing technique has been widely used to generate transgene-free mutants in different plant species. Several different methods including fluorescence marker-assisted visual screen of transgene-free mutants and programmed self-elimination of CRISPR/Cas9 construct have been used to increase the efficiency of genome edited transgene-free mutant isolation, but the overall time length required to obtain transgene-free mutants has remained unchanged in these methods. We report here a method for fast generation and easy identification of transgene-free mutants in Arabidopsis. By generating and using a single FT expression cassette-containing CRISPR/Cas9 construct, we targeted two sites of the AITR1 gene. We obtained many early bolting plants in T1 generation, and found that about two thirds of these plants have detectable mutations. We then analyzed T2 generations of two representative lines of genome edited early bolting T1 plants, and identified plants without early bolting phenotype, i.e., transgene-free plants, for both lines. Further more, aitr1 homozygous mutants were successful obtained for both lines from these transgene-free plants. Taken together, these results suggest that the method described here enables fast generation, and at the mean time, easy identification of transgene-free mutants in plants.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Sistemas CRISPR-Cas , Edição de Genes , Mutação , Transgenes , Análise Mutacional de DNA , Expressão Gênica , Marcação de Genes , Loci Gênicos , Genótipo , Fenótipo , Plantas Geneticamente Modificadas
17.
Biomaterials ; 223: 119465, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31518842

RESUMO

Drug nanovehicles owning tumor microenvironment responsive and modulating capacities are highly demanding for effective tumor chemotherapy but still lack of exploration. Here, a kind of core-releasable satellite nanovehicles was rational constructed, which is composed of polydopamine (PDA) cores as photothermal agents and the carrier for small satellite nanoparticles (NPs) and drugs, G5Au NPs as the drug-loading satellites for deep tumor drug delivery and as catalase-like agents for relieving tumor hypoxia, doxorubicin (DOX) as the model chemotherapeutic drug loaded by both PDA and G5Au NPs, and polyethylene glycol (PEG) shells to improve biosafety. The developed drug-loaded nanovehicles (denoted as PDA-G5Au-PEG@DOX) can release G5Au satellites and DOX in stimuli-responsive manners. Thorough drug delivery in solid tumor can be realized via transporting DOX to the near-by area of and remote area from blood vessels by PDA and G5Au, respectively. Monitored by photoacoustic imaging and near-infrared fluorescence imaging, these PDA-G5Au-PEG@DOX NPs could accumulate in 4T1 tumor effectively. Under this guidance, significant tumor growth suppression could be achieved by the treatment of PDA-G5Au-PEG@DOX NPs plus laser without detectable side effects during the treatment period. The developed drug-loaded core-satellite nanovehicles with tumor microenvironment responsive/modulating capacities are of great potential in precise tumor treatments.


Assuntos
Antineoplásicos/uso terapêutico , Doxorrubicina/administração & dosagem , Nanomedicina/métodos , Neoplasias/tratamento farmacológico , Hipóxia Tumoral , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Hipertermia Induzida , Indóis/farmacologia , Ligantes , Camundongos , Nanopartículas/uso terapêutico , Transplante de Neoplasias , Oxigênio/metabolismo , Técnicas Fotoacústicas , Fototerapia , Polietilenoglicóis/química , Polímeros/farmacologia , Espectroscopia de Luz Próxima ao Infravermelho , Esferoides Celulares
18.
Oncogene ; 38(43): 6940-6957, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31409905

RESUMO

ZFP42 zinc finger protein (REX1), a pluripotency marker in mouse pluripotent stem cells, has been identified as a tumor suppressor in several human cancers. However, the function of REX1 in cervical cancer remains unknown. Both IHC and western blot assays demonstrated that the expression of REX1 protein in cervical cancer tissue was much higher than that in normal cervical tissue. A xenograft assay showed that REX1 overexpression in SiHa and HeLa cells facilitated distant metastasis but did not significantly affect tumor formation in vivo. In addition, in vitro cell migration and invasion capabilities were also promoted by REX1. Mechanistically, REX1 overexpression induced epithelial-to-mesenchymal transition (EMT) by upregulating VIMENTIN and downregulating E-CADHERIN. Furthermore, the JAK2/STAT3-signaling pathway was activated in REX1-overexpressing cells, which also exhibited increased levels of p-STAT3 and p-JAK2, as well as downregulated expression of SOCS1, which is an inhibitor of the JAK2/STAT3-signaling pathway, at both the transcriptional and translational levels. A dual-luciferase reporter assay and qChIP assays confirmed that REX1 trans-suppressed the expression of SOCS1 by binding to two specific regions of the SOCS1 promoter. Therefore, all our data suggest that REX1 overexpression could play a crucial role in the metastasis and invasion of cervical cancer by upregulating the activity of the JAK2/STAT3 pathway by trans-suppressing SOCS1 expression.


Assuntos
Transição Epitelial-Mesenquimal/genética , Fatores de Transcrição Kruppel-Like/genética , Metástase Neoplásica/genética , Transdução de Sinais/genética , Proteína 1 Supressora da Sinalização de Citocina/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Animais , Caderinas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células HeLa , Humanos , Janus Quinase 2/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica/patologia , Biossíntese de Proteínas/genética , Fator de Transcrição STAT3/genética , Transcrição Genética/genética , Regulação para Cima/genética , Vimentina/genética
19.
Nat Commun ; 10(1): 3877, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462635

RESUMO

Tailoring molecular spinterface between novel magnetic materials and organic semiconductors offers promise to achieve high spin injection efficiency. Yet it has been challenging to achieve simultaneously a high and nonvolatile control of magnetoresistance effect in organic spintronic devices. To date, the largest magnetoresistance (~300% at T = 10 K) has been reached in tris-(8-hydroxyquinoline) aluminum (Alq3)-based organic spin valves (OSVs) using La0.67Sr0.33MnO3 as a magnetic electrode. Here we demonstrate that one type of perovskite manganites, i.e., a (La2/3Pr1/3)5/8Ca3/8MnO3 thin film with pronounced electronic phase separation (EPS), can be used in Alq3-based OSVs to achieve a large magnetoresistance (MR) up to 440% at T = 10 K and a typical electrical Hanle effect as the Hallmark of the spin injection. The contactless magnetic field-controlled EPS enables us to achieve a nonvolatile tunable MR response persisting up to 120 K. Our study suggests a new route to design high performance multifunctional OSV devices using electronic phase separated manganites.

20.
PLoS One ; 14(7): e0215494, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365524

RESUMO

Roles for SOX2 have been extensively studied in several types of cancer, including colorectal cancer, glioblastoma and breast cancer, with particular emphasis placed on the roles of SOX2 in cancer stem cell. Our previous study identified SOX2 as a marker in cervical cancer stem cells driven by a full promoter element of SOX2 EGFP reporter. Here, dual-luciferase reporter and mutagenesis analyses were employed, identifying key cis-elements in the SOX2 promoter, including binding sites for SOX2, OCT4 and NF-YA factors in SOX2 promoter. Mutagenesis analysis provided additional evidence to show that one high affinity-binding domain CCAAT box was precisely recognized and bound by the transcription factor NF-YA. Furthermore, overexpression of NF-YA in primitive cervical cancer cells SiHa and C33A significantly activated the transcription and the protein expression of SOX2. Collectively, our data identified NF-YA box CCAAT as a key cis-element in the SOX2 promoter, suggesting that NF-YA is a potent cellular regulator in the maintenance of SOX2-positive cervical cancer stem cell by specific transcriptional activation of SOX2.


Assuntos
Fator de Ligação a CCAAT/metabolismo , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição SOXB1/genética , Ativação Transcricional , Neoplasias do Colo do Útero/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Regiões Promotoras Genéticas
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