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1.
Chemistry ; : e202400548, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536390

RESUMO

In the face of the growing energy crisis and environmental challenges, substantial efforts are now directed toward sustainable clean energy as a replacement for traditional fossil fuels. CO2 photoreduction into value-added chemicals and fuels is widely recognized as a promising approach to mitigate current energy and environmental concerns. Photocatalysts comprising single atoms (SAs) supported on two-dimensional (2D) semiconducting materials (SAs-2DSemi) have emerged as a novel frontier due to the combined merits of SA catalysts and 2D materials. In this study, we review advancements in metal SAs confined on 2DSemi substrates, categorized into four groups: (1) metal oxide-based, (2) g-C3N4-based, (3) emerging, and (4) hybridized 2DSemi, for photocatalytic CO2 conversion over the past few years. With a particular focus on highlighting the distinct advantages of SAs-2DSemi, we delve into the synthesis of state-of-the-art catalysts, their catalytic performances, and mechanistic elucidation facilitated by experimental characterizations and theoretical calculations. Following this, we outline the challenges in this field and offer perspectives on harnessing the potential of SAs-2DSemi as promising photocatalysts. This comprehensive review aims to provide valuable insights for the future development of 2D photocatalytic materials involving SAs for CO2 reduction.

2.
J Syst Sci Complex ; : 1-16, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36258771

RESUMO

Panoramic radiographs can assist dentist to quickly evaluate patients' overall oral health status. The accurate detection and localization of tooth tissue on panoramic radiographs is the first step to identify pathology, and also plays a key role in an automatic diagnosis system. However, the evaluation of panoramic radiographs depends on the clinical experience and knowledge of dentist, while the interpretation of panoramic radiographs might lead misdiagnosis. Therefore, it is of great significance to use artificial intelligence to segment teeth on panoramic radiographs. In this study, SWin-Unet, the transformer-based Ushaped encoder-decoder architecture with skip-connections, is introduced to perform panoramic radiograph segmentation. To well evaluate the tooth segmentation performance of SWin-Unet, the PLAGH-BH dataset is introduced for the research purpose. The performance is evaluated by F1 score, mean intersection and Union (IoU) and Acc, Compared with U-Net, Link-Net and FPN baselines, SWin-Unet performs much better in PLAGH-BH tooth segmentation dataset. These results indicate that SWin-Unet is more feasible on panoramic radiograph segmentation, and is valuable for the potential clinical application.

3.
Small ; 18(45): e2204490, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36161702

RESUMO

The switch of CO2 hydrogenation selectivity from CH4 to CO over TiO2 supported Rh catalysts is accomplished via selective encapsulation of Rh nanoparticles while exposing Rh single atoms by high-temperature reduction (HTR) according to their different strong metal-support interaction (SMSI) occurrence conditions, which can be reversed by subsequent oxidation treatment.

4.
Bioengineered ; 13(6): 14259-14269, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35730406

RESUMO

Diabetes mellitus, metabolic disease, is characterized by chronic hyperglycemia. Patients with diabetes mellitus are susceptible to infection and therefore have a higher prevalence and progression rate of periodontal disease. We aimed to study the effect of insulin and kruppel like factor 10 (KLF10) on osteoblasts proliferation and differentiation, and expression of bone metabolism-related molecules and related signaling pathway molecules of AKT serine/threonine kinase 1 (AKT) and nuclear factor kappa B subunit 1 (NF-κB) through in vitro experiments, which can provide theoretical basis for the dental implant osseointegration in diabetic patients. The osteoblasts (hFOB 1.19 cells) were subdivided into KLF10 gene over expression group, KLF10 gene knockdown group, and KLF10 gene knockdown + insulin treatment group. CCK-8 and ELISA were, respectively, used for analysis of cell proliferation and differentiation. In vitro experiments were applied to detect the mRNA and protein expression of bone metabolism-related molecules, respectively. GSE178351 dataset and GSE156993 dataset were utilized to explore the expression of KLF10 in periodontitis. In osteoblasts, insulin treatment increased the expression of KLF10. Insulin and KLF10 could reduce the proliferation and differentiation of osteoblasts. Knockdown of KLF10 could increase the expression of bone metabolism-related molecules and activate AKT and NF-κB pathways, whereas insulin reversed this effect. KLF10 was up-regulated in both patients with periodontitis and type 2 diabetes mellitus with periodontitis. It is assumed that knockdown of KLF10 in insulin resistance may promote osteoblasts differentiation and dental implant osseointegration in diabetic patients.


Assuntos
Implantes Dentários , Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/metabolismo , Fatores de Transcrição de Resposta de Crescimento Precoce/genética , Fatores de Transcrição de Resposta de Crescimento Precoce/metabolismo , Humanos , Insulina , Fatores de Transcrição Kruppel-Like/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Osseointegração , Osteoblastos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
5.
Nat Commun ; 13(1): 2648, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35551203

RESUMO

Semi-hydrogenation of acetylene in excess ethylene is a key industrial process for ethylene purification. Supported Pd catalysts have attracted most attention due to their superior intrinsic activity but often suffer from low selectivity. Pd single-atom catalysts (SACs) are promising to significantly improve the selectivity, but the activity needs to be improved and the feasible preparation of Pd SACs remains a grand challenge. Here, we report a simple strategy to construct Pd1/TiO2 SACs by selectively encapsulating the co-existed small amount of Pd nanoclusters/nanoparticles based on their different strong metal-support interaction (SMSI) occurrence conditions. In addition, photo-thermo catalysis has been applied to this process where a much-improved catalytic activity was obtained. Detailed characterization combined with DFT calculation suggests that photo-induced electrons transferred from TiO2 to the adjacent Pd atoms facilitate the activation of acetylene. This work offers an opportunity to develop highly stable Pd SACs for efficient catalytic semi-hydrogenation process.

6.
Front Endocrinol (Lausanne) ; 12: 811776, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35002982

RESUMO

Background and Aim: A growing body of evidence suggests that preadmission metformin use could decrease the mortality of septic patients with diabetes mellitus (DM); however, the findings remain controversial. Therefore, this meta-analysis was conducted on available studies to confirm the relationship between preadmission metformin use and mortality in patients with sepsis and DM. Methods: A comprehensive search of the PubMed, Embase, and Cochrane Library databases was performed for studies published before August 8, 2021. Observational studies assessing the correlation between metformin use and mortality in patients with sepsis and DM were considered eligible studies. We used the Newcastle-Ottawa Scale (NOS) to assess the outcome quality of each included article. Furthermore, the odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed using the inverse variance method with random effects modeling. Results: Eleven articles including 8195 patients were analyzed in this meta-analysis. All the included articles were scored as low risk of bias. Our results showed that preadmission metformin use had a lower mortality rate (OR, 0.74; 95% CIs, 0.62-0.88, P < 0.01) in patients with sepsis and DM. Surprisingly, there was no statistically significant difference in the levels of serum creatinine (weighted mean difference (WMD), 0.36; 95% CIs, -0.03-0.75; P = 0.84) and lactic acid (WMD, -0.16; 95% CIs, -0.49-0.18; P = 0.07) between preadmission metformin use and non-metformin use. Conclusions: This study is the most comprehensive meta-analysis at present, which shows that preadmission metformin use may reduce mortality and not increase the levels of serum creatinine and lactic acid in adult patients with sepsis and DM. Therefore, these data suggest that the potential efficacy of metformin could be assessed in future clinical studies. Systematic Review Registration: https://inplasy.com/?s=INPLASY2021100113, identifier INPLASY2021100113.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Sepse/diagnóstico , Sepse/tratamento farmacológico , Diabetes Mellitus Tipo 2/mortalidade , Testes Diagnósticos de Rotina/tendências , Humanos , Mortalidade/tendências , Admissão do Paciente/tendências , Prognóstico , Sepse/mortalidade
7.
Chem Rev ; 120(21): 11986-12043, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33112599

RESUMO

Metal atoms dispersed on the oxide supports constitute a large category of single-atom catalysts. In this review, oxide supported single-atom catalysts are discussed about their synthetic procedures, characterizations, and reaction mechanism in thermocatalysis, such as water-gas shift reaction, selective oxidation/hydrogenation, and coupling reactions. Some typical oxide materials, including ferric oxide, cerium oxide, titanium dioxide, aluminum oxide, and so on, are intentionally mentioned for the unique roles as supports in anchoring metal atoms and taking part in the catalytic reactions. The interactions between metal atoms and oxide supports are summarized to give a picture on how to stabilize the atomic metal centers, and rationally tune the geometric structures and electronic states of single atoms. Furthermore, several directions in fabricating single-atom catalysts with improved performance are proposed on the basis of state-of-the-art understanding in metal-oxide interactions.

8.
Proc Natl Acad Sci U S A ; 117(38): 23626-23635, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32883883

RESUMO

Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Genetic disruption of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation. Binding motifs for RUNX and other hematopoietic transcription factors are enriched at sites occupied by CHD7, and decreased RUNX1 occupancy correlated with loss of CHD7 localization. CHD7 physically interacts with RUNX1 and suppresses RUNX1-induced expansion of HSPCs during development through modulation of RUNX1 activity. Consequently, the RUNX1:CHD7 axis provides proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults, representing a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Proteínas de Ligação a DNA , Hematopoese , Animais , Diferenciação Celular , Linhagem Celular , Subunidade alfa 2 de Fator de Ligação ao Core/química , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Células-Tronco Hematopoéticas , Humanos , Masculino , Camundongos , Baço/citologia , Peixe-Zebra
9.
Angew Chem Int Ed Engl ; 59(29): 11824-11829, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32302045

RESUMO

Strong metal-support interaction (SMSI) has gained great attention in the field of heterogeneous catalysis. However, whether single-atom catalysts can exhibit SMSI remains unknown. Here, we demonstrate that SMSI can occur on TiO2 -supported Pt single atoms but at a much higher reduction temperature than that for Pt nanoparticles (NPs). Pt single atoms involved in SMSI are not covered by the TiO2 support nor do they sink into its subsurface. The suppression of CO adsorption on Pt single atoms stems from coordination saturation (18-electron rule) rather than the physical coverage of Pt atoms by the support. Based on the new finding it is revealed that single atoms are the true active sites in the hydrogenation of 3-nitrostyrene, while Pt NPs barely contribute to the activity since the NP sites are selectively encapsulated. The findings in this work provide a new approach to study the active sites by tuning SMSI.

10.
J Prosthet Dent ; 124(4): 495-499, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31879082

RESUMO

This clinical report described a digital workflow for the design, manufacture, and clinical delivery of a polyetherketoneketone (PEKK) removable dental prosthesis with a speech bulb. The process combined intraoral scanning, digital milling for the PEKK framework, and 3D printing for the definitive cast.


Assuntos
Desenho Assistido por Computador , Implantes Dentários , Benzofenonas , Palato Mole , Polímeros , Impressão Tridimensional , Fala
11.
Genes (Basel) ; 10(5)2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-31035529

RESUMO

In order to study the assembly mechanism of phycocyanin in red algae, the apo-phycocyanin genes (pcB and pcA) were cloned from Gracilariopsis lemaneiformis. The full length of phycocyanin ß-subunit (pcB) contained 519 nucleotides encoding a protein of 172 amino acids, and the full length of phycocyanin α-subunit(pcA) contained 489 nucleotides encoding a protein of 162 amino acids. Expression vector pACYCDuet-pcB-pcA was constructed and transformed into E. coli BL21 with pET-ho-pcyA (containing ho and pcyA gene to synthesize phycocyanobilin). The recombinant strain showed fluorescence activity, indicating the expression of optically active phycocyanin in E. coli. To further investigate the possible binding sites between phycocyanobilin and apo-phycocyanin, Cys-82 and Cys-153 of the ß subunit and the Cys-84 of the α subunit were respectively mutated, and four mutants were obtained. All mutant strains had lower fluorescence intensity than the non-mutant strains, which indicated that these mutation sites could be the active binding sites between apo-phycocyanin and phycocyanobilin (PCB). This research provides a supplement for the comprehensive understanding of the assembly mechanism of optically active phycocyanin in red algae.


Assuntos
Ficobilinas/genética , Ficocianina/genética , Rodófitas/genética , Sequência de Aminoácidos/genética , Sítios de Ligação/genética , Clonagem Molecular , Escherichia coli , Mutação/genética
12.
Gene ; 697: 123-130, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-30794916

RESUMO

Haematococcus pluvialis is an economic microalga to produce astaxathin. To study the nitrogen metabolic process of H. pluvialis, the transcription level and enzyme content of nitrite reductase at different nitrate and phosphorus concentrations were studied. In this research, nitrite reductase gene (nir) was first cloned from H. pluvialis, which consists of 5592 nucleotides and includes 12 introns. The cDNA ORF is 1776 bp, encoding a 592 amino acid protein with two conserved domains. Phylogenetic analysis showed that the nir gene in H. pluvialis had the highest affinity with other freshwater green algae. Nitrogen and phosphorus play an important role in the growth of H. pluvialis. The single factor experiments of nitrogen on growth conditions showed that the group with 0.2 g/L NaNO3 had a relative high biomass. The single factor experiments of phosphorus on growth conditions showed that the group with 0.06 g/L K2HPO4 had a relative high biomass. The transcription level and enzymatic activity of nitrite reductase were detected at different nitrate and phosphorus concentrations. In the absence of nitrogen and phosphorus in the medium, nitrite reductase activity is the highest. This research provides theoretical guidance for optimization of culture medium for H. pluvialis and also provides an experimental basis for understanding of nitrogen metabolism pathway in H. pluvialis.


Assuntos
Clorofíceas/genética , Nitrito Redutases/genética , Clorófitas/genética , Nitritos/metabolismo , Nitrogênio/metabolismo , Fósforo/metabolismo , Filogenia
13.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(2): 144-149, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30782276

RESUMO

OBJECTIVE: To study the features of pathogens in children with lower respiratory tract infection. METHODS: A total of 108 children who were hospitalized due to lower respiratory tract infection and underwent fiber bronchoscopy between January 2017 and June 2018 were enrolled. Bronchoalveolar lavage fluid samples were collected. Multiple quantitative real-time PCR was performed to detect pathogens. RESULTS: Of the108 children, 85 (78.7%) were found to have pathogens, among whom 52 (48.1%) had single pathogen infection and 33 (30.6%) had multiple pathogen infections. Mycoplasma pneumoniae was detected in 38 children (35.2%), and was the most common pathogen. The children aged 36 - <72 months had the highest detection rate of Mycoplasma pneumoniae. Both Streptococcus pneumoniae and Haemophilus influenzae were detected in 29 children (26.9%) and Streptococcus pneumoniae was mainly detected in children aged <24 months. Each of Acinetobacter baumannii, Candida albicans and Klebsiella pneumoniae was detected in 3 children. Among the 31 children with bronchopneumonia, 9 were found to have Haemophilus influenza, with the highest detection rate of 29%. Among the 34 children with lobar pneumonia, 22 were found to have Mycoplasma pneumoniae, with the highest detection rate of 65%. Among the 22 children with bronchial foreign bodies and bronchopneumonia, 10 were found to have Streptococcus pneumoniae, with the highest detection rate of 45%. CONCLUSIONS: In children with lower respiratory tract infection, Mycoplasma pneumoniae is the most common pathogen, followed by Streptococcus pneumoniae and Haemophilus influenzae. There are differences in the detection rates of pathogens between children with different ages and different types of lower respiratory tract infection.


Assuntos
Infecções Respiratórias , Líquido da Lavagem Broncoalveolar , Criança , Pré-Escolar , Haemophilus influenzae , Humanos , Lactente , Mycoplasma pneumoniae , Streptococcus pneumoniae
14.
PLoS One ; 13(12): e0208853, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30533058

RESUMO

Aurantiochytrium limacinum has received attention because of its abundance of polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA). DHA is synthesized through the polyketide synthase (PKS) pathway in A. limacinum. The related enzymes of the PKS pathway are mainly expressed by three gene clusters, called pks1, pks2 and pks3. In this study, the full-length pks3 gene was obtained by polymerase chain reaction amplification and Genome Walking technology. Based on a domain analysis of the deduced amino acid sequence of the pks3 gene, 3-ketoacyl-ACP reductase (KR) and dehydratase (DH) enzyme domains were identified. Herein, A. limacinum OUC168 was engineered by gene knock-in of KR and DH using the 18S rDNA sequence as the homologous recombination site. Total fatty acid contents and the degree of unsaturation of total fatty acids increased after the kr or dh gene was knocked in. The cloning and functional study of the pks3 gene of A. limacinum establishes a foundation for revealing the DHA synthetic pathway. Gene knock-in of the enzyme domain associated with PKS synthesis has the potential to provide effective recombinant strains with higher DHA content for industrial applications.


Assuntos
Hidroliases/genética , Oxirredutases/genética , Estramenópilas/genética , Clonagem Molecular , Ácidos Docosa-Hexaenoicos/metabolismo
15.
Chem Sci ; 9(32): 6679-6684, 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-30310601

RESUMO

Supported platinum-group metal (PGM) catalysts are widely used in many important industrial processes. Metal-support interaction is of great importance in tailoring their catalytic performance. Here, we report the first example of oxidative strong metal-support interactions (OMSIs) between PGM and hydroxyapatite (HAP) which can be extended to PGM and ZnO. It occurred under high-temperature oxidation conditions accompanied by the encapsulation of PGM by HAP and electron transfer between PGM and HAP. With this OMSI, the aggregation and leaching of PGMs were significantly inhibited, resulting in an excellent catalytic stability and much improved reusability of supported Pt and Pd catalysts, respectively. This is the first time to find that PGMs can manifest OMSI which benefits the stabilization of PGM catalysts under oxidative reaction conditions. This new type of SMSI not only contributed to a deeper understanding of SMSI but also provided a new way to develop new stable PGM catalysts.

16.
Blood ; 112(3): 480-92, 2008 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-18390836

RESUMO

CBFbeta is the non-DNA binding subunit of the core binding factors (CBFs). Mice with reduced CBFbeta levels display profound, early defects in T-cell but not B-cell development. Here we show that CBFbeta is also required at very early stages of natural killer (NK)-cell development. We also demonstrate that T-cell development aborts during specification, as the expression of Gata3 and Tcf7, which encode key regulators of T lineage specification, is substantially reduced, as are functional thymic progenitors. Constitutively active Notch or IL-7 signaling cannot restore T-cell expansion or differentiation of CBFbeta insufficient cells, nor can overexpression of Runx1 or CBFbeta overcome a lack of Notch signaling. Therefore, the ability of the prethymic cell to respond appropriately to Notch is dependent on CBFbeta, and both signals converge to activate the T-cell developmental program.


Assuntos
Subunidade beta de Fator de Ligação ao Core/fisiologia , Células Matadoras Naturais/citologia , Linfopoese , Receptores Notch/fisiologia , Linfócitos T/citologia , Animais , Linhagem da Célula , Subunidade beta de Fator de Ligação ao Core/deficiência , Fator de Transcrição GATA3/deficiência , Fator 1-alfa Nuclear de Hepatócito , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Fator 1 de Transcrição de Linfócitos T/deficiência
17.
Blood ; 109(1): 11-21, 2007 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-16940420

RESUMO

The family of core-binding factors includes the DNA-binding subunits Runx1-3 and their common non-DNA-binding partner CBFbeta. We examined the collective role of core-binding factors in hematopoiesis with a hypomorphic Cbfb allelic series. Reducing CBFbeta levels by 3- or 6-fold caused abnormalities in bone development, megakaryocytes, granulocytes, and T cells. T-cell development was very sensitive to an incremental reduction of CBFbeta levels: mature thymocytes were decreased in number upon a 3-fold reduction in CBFbeta levels, and were virtually absent when CBFbeta levels were 6-fold lower. Partially penetrant consecutive differentiation blocks were found among early T-lineage progenitors within the CD4- CD8- double-negative 1 and downstream double-negative 2 thymocyte subsets. Our data define a critical CBFbeta threshold for normal T-cell development, and situate an essential role for core-binding factors during the earliest stages of T-cell development.


Assuntos
Desenvolvimento Ósseo/fisiologia , Subunidade beta de Fator de Ligação ao Core/fisiologia , Granulócitos/patologia , Hematopoese/fisiologia , Megacariócitos/patologia , Subpopulações de Linfócitos T/patologia , Alelos , Animais , Linhagem da Célula , Ensaio de Unidades Formadoras de Colônias , Subunidades alfa de Fatores de Ligação ao Core/fisiologia , Subunidade beta de Fator de Ligação ao Core/deficiência , Subunidade beta de Fator de Ligação ao Core/genética , Fígado/embriologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Quimera por Radiação , Baço/embriologia , Timo/embriologia
18.
Leuk Res ; 31(4): 497-506, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17056112

RESUMO

In vitro and in vivo, myeloid leukemic and preleukemic cells exhibit variable sensitivity to the antiproliferative and proapoptotic effects induced already at low concentrations of DNA methyltransferase (DNMT) inhibitors. The molecular mechanisms underlying this variable sensitivity of leukemic blasts to azanucleosides such as 5-azacytidine and 5-aza-2'-deoxycytidine (DAC) may involve modifier effects of specific fusion proteins such as AML1/ETO. The cyclin-dependent kinase inhibitor p15/INK4b is one potential target of DNA demethylating activity in AML and MDS where it is frequently silenced by hypermethylation. To study sensitivity to DAC in myeloid leukemia cells, we chose the myeloid cell lines Kasumi-1 (expressing AML1/ETO), KG-1 and KG-1a (both AML1/ETO-negative) all of which a highly methylated p15/INK4b gene. Treatment with DAC resulted in dose-dependent regional demethylation of p15/INK4b in Kasumi-1 and KG-1, but only to a modest degree in KG-1a cells. Demethylation was associated with induction of p15/INK4b protein expression. Growth-inhibitory and proapoptotic activity of DAC was significantly higher in Kasumi-1 than in KG-1a cells, and sensitization of cells to a cooperating effect of All-trans retinoic acid and of the histone deacetylase (HDAC) inhibitor Trichostatin A was observed. DAC-induced growth inhibition and apoptosis were enhanced when AML1/ETO was conditionally expressed in AML1/ETO-negative U-937 cells. In conclusion, hypomethylation and reactivation of p15/INK4b in myeloid cell lines are among the molecular events associated with DAC-induced growth arrest and apoptosis. Further studies of AML1/ETO as a modifier of the epigenotype and sensitivity of myeloid cells to inhibitors of DNMTs and HDACs appear warranted.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Inibidor de Quinase Dependente de Ciclina p15/genética , Metilação de DNA , Metilases de Modificação do DNA/antagonistas & inibidores , Leucemia Mieloide/genética , Proteínas de Fusão Oncogênica/metabolismo , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Decitabina , Inibidores Enzimáticos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases , Histonas/efeitos dos fármacos , Histonas/metabolismo , Humanos , Ácidos Hidroxâmicos/farmacologia , Proteínas de Fusão Oncogênica/genética , Proteína 1 Parceira de Translocação de RUNX1 , Transcrição Gênica , Células Tumorais Cultivadas
19.
Development ; 133(21): 4183-92, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17038514

RESUMO

The chorio-allantoic placenta forms through the fusion of the allantois (progenitor tissue of the umbilical cord), with the chorionic plate. The murine placenta contains high levels of hematopoietic stem cells, and is therefore a stem cell niche. However, it is not known whether the placenta is a site of hematopoietic cell emergence, or whether hematopoietic cells originate from other sites in the conceptus and then colonize the placenta. Here, we show that the allantois and chorion, isolated prior to the establishment of circulation, have the potential to give rise to myeloid and definitive erythroid cells following explant culture. We further show that the hematopoietic potential of the allantois and chorion does not require their union, indicating that it is an intrinsic property of these tissues. These results suggest that the placenta is not only a niche for, but also a source of, hematopoietic cells.


Assuntos
Alantoide , Córion , Células-Tronco Hematopoéticas/fisiologia , Placenta/citologia , Placentação , Alantoide/citologia , Alantoide/fisiologia , Animais , Antígenos Ly/genética , Antígenos Ly/metabolismo , Células Cultivadas , Córion/citologia , Córion/fisiologia , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Embrião de Mamíferos/anatomia & histologia , Embrião de Mamíferos/fisiologia , Feminino , Células-Tronco Hematopoéticas/citologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Placenta/fisiologia , Gravidez , Células Estromais/citologia , Células Estromais/fisiologia , Técnicas de Cultura de Tecidos
20.
Expert Opin Ther Targets ; 9(1): 45-61, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15757481

RESUMO

Cancer-associated disturbances of regulated DNA methylation include both global hypomethylation and gene-specific (often even cancer-specific) hypermethylation. Both coexist and have become the subject of intense investigation. In haematological neoplasias, distinct sets of genes, including the p15/INK4b cell cycle inhibitor (mostly in myeloid malignancies) as well as p16/INK4a (only very infrequently in myeloid neoplasia), have been well characterised as to incidence of hypermethylation, concurrent gene inactivation and their re-expression following treatment with DNA methylation inhibitors. Several genes frequently methylated in haematological neoplasias have been studied with respect to their prognostic value. With the advance of low-dose schedules of demethylating agents (explored particularly in the elderly patient population) the rationale for reverting the 'hyper-methylator phenotype' has also prompted in vivo studies of gene reactivation following this type of treatment. However, ubiquitous surrogate markers for the efficacy of this type of treatment need to be developed. These may include reactivated haemoglobin F (HbF), as demethylating agents can result in clinically meaningful induction of HbF in patients with haemoglobinopathies. Because 'cancer testis antigens', which provide powerful signals for T cell cytotoxic activity on solid tumour cells, are usually silenced in leukaemia but can be reactivated in vitro and in vivo, they provide a rationale for an immuno-modulatory effect of demethylating therapy.


Assuntos
Epigênese Genética/genética , Inativação Gênica/fisiologia , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Metilação de DNA , Epigênese Genética/fisiologia , Humanos
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