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1.
ACS Appl Mater Interfaces ; 16(22): 28861-28873, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38785114

RESUMO

Next-generation advanced high-temperature sensors rely heavily on negative temperature coefficient thermosensitive ceramics with low cost, small volume, high sensitivity, and fast response. However, thus far, the enormous challenge of achieving ultrahigh stability and accuracy has become a critical bottleneck restricting the development of thermosensitive ceramics in high-temperature sensor applications. Here, we propose a high-entropy strategy to design a "cation valence self-equilibrium" system in CeNbO4+δ-based ceramics introducing redox couple compensation and ultrahigh density dislocations to solve the problem of temperature-dependent oxygen nonstoichiometry that restricts the performances of high-temperature thermosensitive ceramics. Ferroelastic domains are generated by enhancing the configurational entropy at both A and B sites, resulting in a dramatic increase of dislocation density to >1010 mm-2, which ultimately optimizes the thermosensitive performances. Extreme temperature measurement accuracy with R2 as high as 999.98‰ and RSS as low as 0.011 and high-temperature stability with ΔR/R0 as low as 0.23% after aging at 873 K for 1000 h are realized in high-entropy CeNbO4+δ-based ceramics, indicating a breakthrough in the comprehensive performances of thermosensitive ceramics. This work opens up an effective way to design thermosensitive materials with ultrahigh comprehensive performance to meet the requirements of advanced high-temperature sensors.

2.
Sensors (Basel) ; 24(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38732886

RESUMO

In this paper, a temperature measurement system with NTC (Negative Temperature Coefficient) thermistors was designed. An MCU (Micro Control Unit) primarily operates by converting the voltage value collected by an ADC (Analog-to-Digital Converter) into the resistance value. The temperature value is then calculated, and a DAC (Digital-to-Analog Converter) outputs a current of 4 to 20 mA that is linearly related to the temperature value. The nonlinear characteristics of NTC thermistors pose a challenging problem. The nonlinear characteristics of NTC thermistors were to a great extent solved by using a resistance ratio model. The high precision of the NTC thermistor is obtained by fitting it with the Hoge equation. The results of actual measurements suggest that each module works properly, and the temperature measurement accuracy of 0.067 °C in the range from -40 °C to 120 °C has been achieved. The uncertainty of the output current is analyzed and calculated with the uncertainty of 0.0014 mA. This type of system has broad potential applications in industry fields such as the petrochemical industry.

3.
ACS Appl Mater Interfaces ; 16(10): 12821-12832, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38416064

RESUMO

Next-generation high-temperature applications increasingly rely heavily on advanced thermistor materials with enhanced thermal stability and electrical performance. However, thus far, the great challenge of realizing high thermal stability and precision in a wide temperature range has become a key bottleneck restricting the high-temperature application. Here, we propose a high-entropy strategy to design novel high-temperature thermistor ceramics (La0.2Ce0.2Nd0.2Sm0.2Eu0.2)NbO4. Differences in atomic size, mass, and electronegativity in this high-entropy system cause high lattice distortion, substantial grain boundaries, and high dislocation density. These enhance the charge carrier transport and reduce the grain boundary resistance, thus synergistically broadening the temperature range. Our samples maintain high precision and thermal stability over a wide temperature range from room temperature to 1523 K (ΔT = 1250 K) with an aging value as low as 0.42% after 1000 h at 1173 K, showing breakthrough progress in high-temperature thermistor ceramics. This study establishes an effective approach to enhancing the performance of high-temperature thermistor materials through high-entropy strategies.

4.
Heliyon ; 9(11): e21185, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37964827

RESUMO

Background: Hearing loss is found in more than 5 % of cases worldwide. Hearing loss is divided into three types: Sensorineural hearing loss, Combined hearing loss and Conductive hearing loss. Among them, no less than 50 % of pediatric cases of sensorineural hearing loss are genetic. In Henan, China, there are no statistics on the allele frequency of deafness gene variants. Methods: We divided 2178 subjects enrolled at the Third Affiliated Hospital of Zhengzhou College from January 2019 to March 2021 into a hearing loss group and a normal control group. We performed array and pathogenicity classification for screening the 15 deafness gene variants, calculated and compared the allele frequency of the deafness gene variants, and then compared the hearing loss diagnosis rate between the hearing loss group and the normal control group. Results: We found that in the hearing loss group, the overall allele frequency of all detected variants was 16.6 %. Comparative analysis showed that the allele frequencies of GJB2 c.235delC variant, GJB3 c.538C > T variant and SLC26A4 c.919-2A > G variant were significantly higher than those of the East Asian population average in the gnomAD database. At the same time, our study confirmed that GJB3 c.538C > T variant may not be the disease-causing variant of hearing loss. Conclusions: These results support genetic counseling and rational prediction of risk for deafness.

5.
Front Chem ; 11: 1275274, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841206

RESUMO

The development of negative temperature coefficient (NTC) thermistor materials with a wide range of operating temperatures, high resistance (R), low thermal content (B) and good stability is significant for improving the overall performance of NTC thermistors. Traditional NTC thermistors materials are of the spinel, however, their practical applications are commonly limited to temperatures below approximately 200°C.In this study, it was found that a novel perovskite-structured solid solution (1-x)Bi0.2Sr0.5La0.3TiO3-xLaMnO3 (0.05 ≤ × ≤ 0.2) (BSLT-LM) showed good NTC performance from room temperature to high temperature (600°C) due to the stable structure at high temperatures. The ρ25, ρ100, ρ600 and B25/100, B25/600 constants of Bi0.2Sr0.5La0.3TiO3-0.1LaMnO3 NTC thermistors are approximately 1.76 × 108 Ω cm, 1.13 × 107 Ω cm, 9.89 × 102 Ω cm, 4063.91 K, 5472.34 K, respectively. The electrical conductivity of these solid solution refers to the electronic transition between Mn3+ and Mn4+, and oxygen vacancies. These results demonstrate the tremendous potential of perovskite-structured (1-x) Bi0.3Sr0.5La0.2TiO3-xLaMnO3 thermistor ceramics with NTC performance.

6.
Med Sci Monit ; 28: e935070, 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35818328

RESUMO

BACKGROUND Recently, the upregulation of LINC00963 expression has been reported in various cancer subtypes. LINC00963 expression can promote cancer cell invasion and metastasis. However, the clinical significance of LINC00963 in cervical and endocervical cancer (CESC) has remained relatively unexamined. MATERIAL AND METHODS We assessed the mRNA expression of LINC00963 in patients with CESC based on data acquired from The Cancer Genome Atlas (TCGA) to determine pathways involved in CESC pathogenesis with respect to LINC00963. We included 3 normal and 304 tumor samples in this study. RESULTS The scatter plot and paired plot showed differences in LINC00963 expression between normal and tumor samples (P<0.01). Overall survival (OS) analysis revealed that CESC patients with high expression of LINC00963 demonstrated worse prognosis than CESC patients with low expression of LINC00963 (P<0.01). Multivariate analysis with the Cox proportional hazards model indicated that the expression of LINC00963 (HR 0.297; 95% CI 0.115-0.776; P=0.012) and primary therapy outcome (HR 0.162; 95% CI 0.059-0.446; P=0.001) were independent prognostic factors for patients with CESC. GSEA results showed that reactome biological oxidations, inflammasomes, apoptosis, toll-like receptor signaling pathway, JAK/STAT signaling pathway, and NF-kappaB activation were differentially enriched in CESC samples with the high LINC00963 expression phenotype. CONCLUSIONS Our results confirmed the association of significantly high levels of LINC00963 expression in CESC with several observed clinical features. LINC00963 may be a potentially useful prognostic molecular biomarker associated with poor survival in patients with CESC.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Prognóstico , Transdução de Sinais/genética , Análise de Sobrevida , Regulação para Cima/genética , Neoplasias do Colo do Útero/genética
7.
Bioengineered ; 13(4): 8538-8547, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35331081

RESUMO

This study aimed to investigate the roles of the lysine (K)-specific demethylase 5C (KDM5C)-bone morphogenetic protein-7 (BMP-7) signaling pathway in the pathogenesis of severe preeclampsia (sPE). A total of 180 pregnant patients were enrolled in the study and classified into three groups: an early-onset sPE group (EOsPE) (n = 60), a late-onset sPE group (LOsPE) (n = 60), and a control group (normal pregnancy; n = 60). The messenger RNA (mRNA) and protein expression levels of bone morphogenetic protein receptor II (BMPRII), BMP-7, and KDM5C were detected in placenta samples from the two sPE groups, and their sites were evaluated using immunohistochemistry (IHC). The sPE groups showed an increased KDM5C mRNA expression, and the EOsPE group showed a decreased BMP-7 and BMPRII mRNA expression compared with the LOsPE group. However, contradictory results were discovered in terms of protein expression. Immunostaining of KDM5C, BMP-7, and BMPRII was observed in villous trophoblast and extravillous trophoblast cells. Compared with the control group, the staining intensity of KDM5C in the placental tissue trophoblast cell nucleus and vascular endothelial cells of the sPE groups was weaker, while that of BMP-7 and BMPRII was stronger, and the staining intensity was more subjective in the LOsPE group. Consistent findings were obtained by IHC and Western blot analysis. KDM5C nuclear-cytoplasmic translocation may regulate sPE through BMP-7 and its receptors. The KDM5C-BMP-7 signaling pathway may also lead to less invasion and increased apoptosis of the trophoblast cells, which is involved in the pathogenesis of sPE.


Assuntos
Proteína Morfogenética Óssea 7 , Receptores de Proteínas Morfogenéticas Ósseas Tipo II , Histona Desmetilases , Pré-Eclâmpsia , Proteína Morfogenética Óssea 7/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Células Endoteliais/metabolismo , Feminino , Histona Desmetilases/genética , Humanos , Incidência , Lisina , Placenta/metabolismo , Pré-Eclâmpsia/genética , Gravidez , RNA Mensageiro/genética
8.
Cancer Lett ; 468: 14-26, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31600529

RESUMO

Deregulation of SOX9 in esophageal cancer has been reported. However, the regulatory mechanisms underlying SOX9 during esophageal squamous cell carcinoma (ESCC) progression remain poorly understood. Here, we independently confirmed the increased SOX9 expression in two ESCC cohorts and its correlation with poor prognosis. We demonstrated that SOX9 was required for maintaining self-renewal, motility, and chemoresistance in vitro and that ectopic expression of SOX9 promoted tumorigenicity in vivo. Screening for potential SOX9-regulated miRNAs revealed that target genes of differentially expressed miRNAs were enriched in the PI3K/AKT signaling pathway and identified the downregulated miR-203a as a candidate. Mechanistically, SOX9 activation caused repression of miR-203a transcription by binding to miR-203a promoter, thus preventing the miR-203a-mediated inhibition of multiple PI3K/AKT/mTOR components, including PIK3CA, AKT2, and RPS6KB1. The association between SOX9 expression and PI3K/AKT/mTOR signaling was further validated in clinical samples. Moreover, rapamycin treatment attenuated the SOX9-mediated malignant phenotypes and potentiated cisplatin-mediated inhibition of tumor growth. Together, these findings uncover a novel activation of the PI3K/AKT pathway by the SOX9/miR-203a axis and define a subgroup of patients who may benefit from targeted therapy.


Assuntos
Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Fatores de Transcrição SOX9/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Estudos de Coortes , Progressão da Doença , Sinergismo Farmacológico , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Esofagectomia , Esôfago/patologia , Esôfago/cirurgia , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Transcrição Gênica , Ensaios Antitumorais Modelo de Xenoenxerto
9.
RSC Adv ; 9(44): 25488-25495, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-35530107

RESUMO

Mn1.1Co1.5Fe0.4O4 ceramics with tailored sintering temperature, microstructure, and NTCR characteristics were prepared using Bi2O3 sintering additive by a solid-state reaction route. Densification and morphological characterization indicate that bismuth trioxide can play a critical role in the sintering process. The results reveal that the sintering temperature can be decreased significantly from 1200 °C to 1050 °C by using the appropriate content of Bi2O3 additive. The resistivity decreases first and then increases with increasing Bi2O3 content. The obtained B 25/50 value and ρ 25 ranges were 3647-3697 K, and 800-1075 Ω cm, respectively. Oxygen sorption theory can be used to illustrate the optimal thermal stability (ΔR/R 0 = 0.10%). Complex impedance analysis further elucidates that grain boundaries make a dominant contribution to the total resistance. The mechanisms of grain boundary conduction and relaxation behavior are systematically analyzed. These findings open up a window for the further advancement of NTC ceramics at lower sintering temperature.

10.
J Matern Fetal Neonatal Med ; 32(2): 339-347, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29519182

RESUMO

PURPOSE: The aim of this study was to investigate the correlations and interactions between the polymorphisms of insulin resistance-related genes (ADIPOQ rs2241766), inflammation factors (TNF-α rs1800629, IL-6 rs1800795), obesity-related genes (GNB3 rs5443, ADRB rs1042714), and risk factors for gestational diabetes mellitus (GDM) such as diet structure in the development of GDM. MATERIALS AND METHODS: This research was conducted among women who visited the third-affiliate hospital of Zhengzhou University for pregnancy checkups from 1 June 2014 to 30 December 2014. Based on the results of a 75-g glucose tolerance test (OGTT), 140 pregnant women with GDM were randomly selected as a part of the GDM group and140 healthy, pregnant women as part of the control group. Relevant clinical and laboratory data for the child and the mother including her pregnancy outcomes and the delivery mode were collected for the epidemiological survey. RESULTS: The results showed that risk factors for GDM are advanced age, the hepatitis B virus, family history of diabetes, high body mass index before pregnancy, and weight gain of ≥10 kg before 24-week gestation. We found that diet structures were severely unbalanced. The polymorphisms rs2241766 and rs5443 were found to potentially be associated with GDM; moreover, a positive interaction was demonstrated between rs2241766 and age, and a negative interaction was demonstrated with weight gain of ≥10 kg before 24-week gestation. CONCLUSION: Our findings demonstrate that both environmental risk factors and genetic background contribute to the development of GDM.


Assuntos
Diabetes Gestacional/etiologia , Dieta , Interação Gene-Ambiente , Inflamação , Resistência à Insulina/fisiologia , Obesidade/genética , Adulto , Estudos de Casos e Controles , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/genética , Meio Ambiente , Feminino , Predisposição Genética para Doença , Humanos , Inflamação/complicações , Inflamação/epidemiologia , Inflamação/genética , Mediadores da Inflamação/metabolismo , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Obesidade/complicações , Obesidade/epidemiologia , Polimorfismo Genético , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/genética , Resultado da Gravidez/epidemiologia , Resultado da Gravidez/genética , Fatores de Risco
11.
Scand J Clin Lab Invest ; 78(3): 211-218, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29390883

RESUMO

Phenylketonuria (PKU, OMIM 261600) caused by phenylalanine hydroxylase (PAH) deficiency is an autosomal recessive disease that is characterized by abnormalities of phenylalanine metabolism. In this study, a total of 77 patients, originating from the central region of China and who were diagnosed with PAH deficiency at the third affiliated hospital of Zhengzhou University, were enrolled in this study. The 13 exons and 12 flanking introns of the PAH gene were analyzed by Sanger sequencing and next generation sequencing. The sequencing data were aligned to the hg19, PAHvdb and HGMD databases to characterize the genotypes of PKU patients, and genotype-phenotype correlations and BH4 responsiveness predictions were performed using BIOPKUdb. In total, 149 alleles were characterized among the 154 PKU alleles. These mutations were located in exons 2-13, and intron 12 of the PAH gene, with a relative frequency of ≥5%, for EX6-96A>G, p.R241C, p.R243Q, p.V399V and p.R53H. Additionally, a novel variant, p.D84G, was identified. The genotype correlated with clinical symptoms in 33.3-100% of the cases, depending on the disease severity, and BH4 responsiveness predictions show that only five patients with MHP-PKU and one patient with Mild-PKU were predicted to be BH4 responsive. In conclusion, we have characterized the mutational spectrum of PAH in the central region of China and have identified a novel mutation. The hotspot mutation information might be useful for screening, diagnosis and treatment of PKU.


Assuntos
Biopterinas/análogos & derivados , Genótipo , Mutação , Fenilalanina Hidroxilase/genética , Fenilcetonúrias/tratamento farmacológico , Fenilcetonúrias/genética , Alelos , Biopterinas/uso terapêutico , Criança , Pré-Escolar , China , Éxons , Feminino , Estudos de Associação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Recém-Nascido , Íntrons , Masculino , Fenilalanina Hidroxilase/deficiência , Fenilcetonúrias/diagnóstico , Fenilcetonúrias/enzimologia , Índice de Gravidade de Doença
12.
Epigenetics ; 12(8): 698-707, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28703658

RESUMO

Dysregulation of miR-203 by promoter methylation is associated with the development of various cancers. We aimed to explore the underlying link between promoter methylation and miR-203 expression in Kazakh esophageal squamous cell carcinoma (ESCC). MassARRAY® System spectrometry was used to quantitatively analyze the DNA methylation of 32 CpG sites within miR-203 in 99 Kazakh ESCC and 46 normal esophageal tissues (NETs) with similar population characteristics. We conducted real-time PCR to detect miR-203 expression levels and evaluated their association with methylation. Eleven CpG units within miR-203 promoter were frequently hypermethylated in ESCC compared with NETs (P < 0.05). The hypermethylation of several CpG units positively correlated with age, lower esophagus, constrictive type of ESCC, and moderately differentiated ESCC. Given the involvement of human papillomavirus (HPV) in etiology of ESCC was confirmed from our previous reports, herein we found that CpG units within miR-203 in HPV16-positive ESCC are more heavily methylated. Furthermore, miR-203 expression showed a nearly 4.5-fold decrease in ESCC than NETs (0.206 ± 0.336 vs. 0.908 ± 1.424, P < 0.001) and was significantly associated with lymph node metastasis (P = 0.012). The expression of miR-203 with 11 completely hypermethylated CpG units was approximately 6.5-fold lower than that with at least 1 unmethylated CpG unit (P < 0.001) and especially the CpG_15.16 and CpG_31.32 with higher methylation levels in ESCC tissues exhibited lower expression levels of miR-203, which indicated a reverse association between miR-203 methylation and expression. Hypermethylated miR-203 is a potential biomarker and targeted delivery of miR-203 could therefore serve as a preventive or therapeutic strategy for Kazakh ESCC.


Assuntos
Carcinoma de Células Escamosas/genética , Metilação de DNA , Neoplasias Esofágicas/genética , Inativação Gênica , MicroRNAs/genética , Idoso , Povo Asiático , Carcinoma de Células Escamosas/etnologia , Carcinoma de Células Escamosas/patologia , Ilhas de CpG , Neoplasias Esofágicas/etnologia , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Small ; 12(36): 5027-5033, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27294722

RESUMO

Mn-Co-Ni-O nanoceramic microspheres with high density, uniformity, and size tunability are successfully fabricated using in situ ink-jet printing and two step sintering (TSS) techniques. The microspheres, synthesized by an effective and facile reverse microemulsion method, consist of uncalcined Mn-Co-Ni-O nanocrystallines that show a well formed single tetragonal spinel phase and an average particle size distribution of ≈20 nm. The sintering behavior, microstructure, and electrical properties of the Mn-Co-Ni-O nanoceramic microspheres are systematically investigated and characterized. The results indicate that the sintered Mn-Co-Ni-O nanoceramic microspheres show high density and improved electrical properties. The highest R25 , B25/50 , Ea , and α25 values achieved at sintering temperature of 1150 °C are 4846.7 KΩ, 4320 K, 0.401 eV, and -5.24% K-1 , respectively for these Mn-Co-Ni-O nanoceramic microspheres. Furthermore, the formation mechanism of uncalcined Mn-Co-Ni-O nanocrystallines and an analysis of the TSS procedure of the nanoceramic microspheres are discussed.

14.
J Phys Chem Lett ; 6(13): 2622-8, 2015 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-26266744

RESUMO

We reported a facile single-solution fabrication method to grow large-scale CH3NH3PbBr3 hybrid perovskite single crystal at room temperature. The obtained single crystal in this experiment was 14 × 14 mm. The sample's in situ photophysics properties under dark and illumination, including the surface morphology, work function, surface current distribution, microcosmic I-V curves, as well as the polarization behavior, were in situ characterized by integrated utilization of a scanning probe microscopy, respectively. Piezoresponse force microscopy (PFM) phase angles indicated the existence of "polarization" in CH3NH3PbBr3 lattice. Interestingly, the "polarization effect" was enhanced by the plus light source. Moreover, a surface potential shift as large as 200 mV was observed under the condition of the illumination on and off. This research is proposed to provide an opportunity to take a fresh look at the architectural design and photovoltaic performance origin of the hybrid perovskite solar cells.

15.
Placenta ; 36(10): 1148-52, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26303759

RESUMO

INTRODUCTION: Placental dysfunction and increased inflammation are believed to underlie the pathogenesis of severe preeclampsia (PE). High-mobility group box 1 (HMGB1), a recently identified inflammatory cytokine, has been known to contribute to the development of inflammatory responses in PE. This study intends to elucidate the mechanisms of HMGB1-RAGE signaling pathway in the pathogenesis of PE. METHODS: The mRNA levels of relative gene of HMGB1 pathway, HMGB1, RAGE and NF-κB p65, were analyzed by real-time PCR in placentas collected from 61 normotensive pregnant women and 64 women with severe PE. Additionally, levels of HMGB1 and RAGE protein were detected in frozen placental specimens by western blot, and the locations of them were evaluated in the well-characterized tissue microarray by immunohistochemistry. ELISA was further used to detect HMGB1 level in maternal serum. RESULTS: Compared with matched control placentas, the mRNA levels of HMGB1, RAGE and NF-κB p65 were increased in severe preeclamptic placentas. In severe preeclamptic placentas, HMGB1 and RAGE immunoreactivity were increased in the cytoplasm of trophoblast cells. Western blot was employed to further confirm that RAGE protein level was elevated significantly in severe PE group. In addition, there was an increased level of HMGB1 in the maternal serum of severe PE group. DISCUSSION: HMGB1 nuclear-cytoplasmic translocation may induce the binding of HMGB1 to its receptors, consequently, intrigue NF-κB activity in severe PE. HMGB1-RAGE signaling pathway may be involved in the pathogenesis of PE.


Assuntos
Proteína HMGB1/sangue , Placenta/metabolismo , Pré-Eclâmpsia/sangue , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Fator de Transcrição RelA/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Gravidez , Transdução de Sinais
16.
Mol Cell Biochem ; 381(1-2): 31-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23660954

RESUMO

Preeclampsia complicates 5-10% of pregnancies and is a leading cause of maternal/fetal morbidity and mortality. Although the cause is unknown, the reduced migration/invasion of extravillous trophoblasts is generally regarded as a key feature of preeclampsia genesis. The present study examined the expression of activator protein-2α (AP-2α), tissue inhibitor of metalloproteinase 2 (TIMP-2), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and E-cadherin in severe preeclamptic placentas and normal placentas using real-time PCR and immunohistochemistry. The expression levels of AP-2α, TIMP-2, and E-cadherin were elevated, while MMP-2 and MMP-9 levels were decreased in severe preeclamptic placentas when compared with normal placentas. To explore the underlying molecular mechanisms, BeWo cells were transfected with an AP-2α-expression construct as well as a siRNA against AP-2α. The over-expression of AP-2α decreased the invasive abilities of BeWo cells. AP-2α induction was followed by the induction of TIMP-2 and E-cadherin and a significant reduction of MMP-2 and MMP-9. Whereas in AP-2α-silencing BeWo cells, we observed the decreased expression of TIMP-2 and E-cadherin and the increased expression of MMP-2 and MMP-9. We presume that AP-2α may suppress trophoblast invasion by repression of MMP-2 and MMP-9 and up-regulation of E-cadherin, thus leading to shallow placentation in severe preeclampsia.


Assuntos
Caderinas/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Fator de Transcrição AP-2/metabolismo , Regulação para Cima/genética , Adulto , Antígenos CD , Caderinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Neoplásicos/genética , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Invasividade Neoplásica , Placenta/metabolismo , Placenta/patologia , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Fator de Transcrição AP-2/genética , Transfecção
17.
J Matern Fetal Neonatal Med ; 26(16): 1581-5, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23581516

RESUMO

OBJECTIVE: Heat shock protein 70 (Hsp70), a highly conserved cellular stress protein, is produced in every organism from bacteria to man. The purpose of this study was to determine the difference in Hsp70 concentrations between term and preterm deliveries. METHODS: In total, 30 healthy term delivery and 99 preterm delivery (PD) women were recruited, including 46 women with preterm labor and intact membranes (PTL) with or without an intra-amniotic infection (IAI) and 53 women with a preterm premature rupture of membranes (PPROMs) with or without IAI. The Hsp70 levels in the maternal and the umbilical cord sera were tested by an enzyme-linked immunosorbent assay (ELISA); the expression levels of Hsp70 in the placentas were determined by immunoblotting and real-time PCR. RESULTS: In contrast to the expression levels in normal term controls, Hsp70 expression levels were upregulated in PD; similar changes in Hsp70 expression levels were detected in PD maternal and umbilical sera. Patients with IAI were associated with a higher Hsp70 concentration than those without IAI. CONCLUSION: These results suggest a probable contributing role of altered Hsp70 expression levels in the pathophysiology of PD.


Assuntos
Proteínas de Choque Térmico HSP70/metabolismo , Nascimento Prematuro/metabolismo , Nascimento a Termo/metabolismo , Adulto , Estudos de Casos e Controles , Corioamnionite/metabolismo , Feminino , Sangue Fetal/química , Sangue Fetal/metabolismo , Ruptura Prematura de Membranas Fetais/metabolismo , Proteínas de Choque Térmico HSP70/análise , Humanos , Recém-Nascido , Masculino , Mães , Trabalho de Parto Prematuro/metabolismo , Placenta/metabolismo , Gravidez/metabolismo , Complicações Infecciosas na Gravidez/metabolismo
18.
Arch Gynecol Obstet ; 288(4): 775-84, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23580009

RESUMO

OBJECTION: Preterm premature rupture of membranes (PPROM) is an obstetrics complication and is the leading cause of perinatal mortality and morbidity. PPROM results in critical care emergencies, and nearly all PPROM events are spontaneous and unpredictable. In addition, changes in the proteome in placental tissue during pregnancy that lead to PPROM are not clear. METHODS: We utilize a proteomics approach to study the molecular mechanisms behind human PPROM. A better understanding of proteome alteration could lead to the identification of better diagnostic/prognostic markers. Human placental tissue was collected in clearly differentiated cases of PPROM and in a healthy term control. Two-dimensional gel polyacrylamide electrophoresis coupled with mass spectrometry and bioinformatics analysis was utilized to identify proteins with altered expression. RESULTS: In this study, only the most important protein differences were selected for further analysis. Most of the identified proteins were structural/cytoskeletal components of the cell or involved in the regulation of energy metabolism and oxidative stress. CONCLUSIONS: As a result, this approach has led to the identification of several proteins involved in the underlying pathophysiological mechanisms that can further serve as novel diagnostic tools and targets for rational drug intervention.


Assuntos
Ruptura Prematura de Membranas Fetais/metabolismo , Placenta/metabolismo , Proteômica , Adulto , Biomarcadores/metabolismo , Western Blotting , Estudos de Casos e Controles , Eletroforese em Gel Bidimensional , Feminino , Humanos , Imuno-Histoquímica , Gravidez , Proteômica/métodos , Reação em Cadeia da Polimerase em Tempo Real , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
19.
J Mol Histol ; 43(6): 681-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22886241

RESUMO

Enhanced apoptosis of the cytotrophoblast in early pregnancy is associated with a high risk of preeclampsia. We and others have previously reported that the transcriptional factor, activator protein AP-2α, suppressed trophoblast migration and invasion. However, it is not clear whether AP-2α affects apoptosis in trophoblast cells and whether it regulates expression of apoptosis-related factors Bcl-2 and Bax. We analyzed the expression of AP-2α, Bcl-2 and Bax in placental tissues in severe preeclamptic pregnancies and normotensive pregnancies using immunohistochemistry and real time-PCR. Further, apoptosis was assessed by flow cytometric analysis in the human trophoblastic cell line, BeWo cells, in which AP-2α expression was transiently overexpressed or down-regulated by siRNA. There was significantly higher expression of AP-2α and Bax, but lower expression of Bcl-2 in severe preeclampsia placentas as compared to the control placentas. Overexpression of AP-2α in BeWo cells led to an increased rate of apoptosis, whereas apoptosis was decreased when AP-2α expression was reduced. Furthermore, overexpression of AP-2α increased Bax expression and decreased Bcl-2 expression, whereas down-regulation of AP-2α expression resulted in a decrease in Bax expression and an increase in Bcl-2 expression. AP-2α regulates expression of Bcl-2 and Bax and apoptosis in BeWo cells. These results suggest that AP-2α-mediated regulation of Bcl-2 and Bax regulation influences apoptosis which in turn leads to the pathogenesis of preeclampsia.


Assuntos
Apoptose/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição AP-2/metabolismo , Trofoblastos/citologia , Trofoblastos/metabolismo , Proteína X Associada a bcl-2/metabolismo , Apoptose/genética , Western Blotting , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Gravidez , Proteínas Proto-Oncogênicas c-bcl-2/genética , Reação em Cadeia da Polimerase em Tempo Real , Fator de Transcrição AP-2/genética , Proteína X Associada a bcl-2/genética
20.
Nanotechnology ; 22(33): 335301, 2011 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-21775806

RESUMO

We report a novel method to fabricate ordered arrays of gold-polymer composite nanorods with the orientation in the vertical direction using block copolymer (BCP) film. The salt precursor is selectively infiltrated within vertically aligned cylindrical domains of the BCP film by immersing the template in a simple aqueous solution of HAuCl(4). Scanning electron microscopy suggests that the salt might be uniformly positioned along the polymeric cylinders. A subsequent vacuum ultraviolet light irradiation simultaneously reduces the HAuCl(4) into spherical gold nanoparticles with mean diameter around 2 nm and removes the matrix of the BCP template to produce metal-polymer composite nanorods. While the solvent is methanol, the salt might be concentrated at the bottom of the BCP film. As a result, a periodic pattern of gold nanoparticles with average diameter around 11 nm is formed where the BCP film is completely etched away. The solvent can effectively tune the spatial distribution of the salt precursor along the polymeric cylinders, which is responsible for the different morphologies of the photochemically fabricated nanostructures.

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