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1.
Chemistry ; 30(31): e202400548, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38536390

RESUMEN

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.
Proc Natl Acad Sci U S A ; 117(38): 23626-23635, 2020 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-32883883

RESUMEN

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.


Asunto(s)
Subunidad alfa 2 del Factor de Unión al Sitio Principal , Proteínas de Unión al ADN , Hematopoyesis , Animales , Diferenciación Celular , Línea Celular , Subunidad alfa 2 del Factor de Unión al Sitio Principal/química , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Femenino , Células Madre Hematopoyéticas , Humanos , Masculino , Ratones , Bazo/citología , Pez Cebra
3.
Small ; 18(45): e2204490, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36161702

RESUMEN

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.
Chem Rev ; 120(21): 11986-12043, 2020 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-33112599

RESUMEN

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.

5.
J Prosthet Dent ; 124(4): 495-499, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31879082

RESUMEN

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.


Asunto(s)
Diseño Asistido por Computadora , Implantes Dentales , Benzofenonas , Paladar Blando , Polímeros , Impresión Tridimensional , Habla
6.
Angew Chem Int Ed Engl ; 59(29): 11824-11829, 2020 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-32302045

RESUMEN

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.

7.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(2): 144-149, 2019 Feb.
Artículo en Zh | MEDLINE | ID: mdl-30782276

RESUMEN

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.


Asunto(s)
Infecciones del Sistema Respiratorio , Líquido del Lavado Bronquioalveolar , Niño , Preescolar , Haemophilus influenzae , Humanos , Lactante , Mycoplasma pneumoniae , Streptococcus pneumoniae
8.
Front Plant Sci ; 15: 1403713, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911981

RESUMEN

Introduction: Blackheart is one of the most common physiological diseases in potatoes during storage. In the initial stage, black spots only occur in tissues near the potato core and cannot be detected from an outward appearance. If not identified and removed in time, the disease will seriously undermine the quality and sale of theentire batch of potatoes. There is an urgent need to develop a method for early detection of blackheart in potatoes. Methods: This paper used visible-near infrared (Vis/NIR) spectroscopy to conduct online discriminant analysis on potatoes with varying degrees of blackheart and healthy potatoes to achieve real-time detection. An efficient and lightweight detection model was developed for detecting different degrees of blackheart in potatoes by introducing the depthwise convolution, pointwise convolution, and efficient channel attention modules into the ResNet model. Two discriminative models, the support vector machine (SVM) and the ResNet model were compared with the modified ResNet model. Results and discussion: The prediction accuracy for blackheart and healthy potatoes test sets reached 0.971 using the original spectrum combined with a modified ResNet model. Moreover, the modified ResNet model significantly reduced the number of parameters to 1434052, achieving a substantial 62.71% reduction in model complexity. Meanwhile, its performance was evidenced by a 4.18% improvement in accuracy. The Grad-CAM++ visualizations provided a qualitative assessment of the model's focus across different severity grades of blackheart condition, highlighting the importance of different wavelengths in the analysis. In these visualizations, the most significant features were predominantly found in the 650-750 nm range, with a notable peak near 700 nm. This peak was speculated to be associated with the vibrational activities of the C-H bond, specifically the fourth overtone of the C-H functional group, within the molecular structure of the potato components. This research demonstrated that the modified ResNet model combined with Vis/NIR could assist in the detection of different degrees of black in potatoes.

9.
Bioengineered ; 13(6): 14259-14269, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35730406

RESUMEN

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.


Asunto(s)
Implantes Dentales , Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/metabolismo , Factores de Transcripción de la Respuesta de Crecimiento Precoz/genética , Factores de Transcripción de la Respuesta de Crecimiento Precoz/metabolismo , Humanos , Insulina , Factores de Transcripción de Tipo Kruppel/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Oseointegración , Osteoblastos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo
10.
J Syst Sci Complex ; : 1-16, 2022 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-36258771

RESUMEN

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.

11.
Nat Commun ; 13(1): 2648, 2022 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-35551203

RESUMEN

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.

12.
Front Endocrinol (Lausanne) ; 12: 811776, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35002982

RESUMEN

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.


Asunto(s)
Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Sepsis/diagnóstico , Sepsis/tratamiento farmacológico , Diabetes Mellitus Tipo 2/mortalidad , Pruebas Diagnósticas de Rutina/tendencias , Humanos , Mortalidad/tendencias , Admisión del Paciente/tendencias , Pronóstico , Sepsis/mortalidad
13.
Blood ; 112(3): 480-92, 2008 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-18390836

RESUMEN

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.


Asunto(s)
Subunidad beta del Factor de Unión al Sitio Principal/fisiología , Células Asesinas Naturales/citología , Linfopoyesis , Receptores Notch/fisiología , Linfocitos T/citología , Animales , Linaje de la Célula , Subunidad beta del Factor de Unión al Sitio Principal/deficiencia , Factor de Transcripción GATA3/deficiencia , Factor Nuclear 1-alfa del Hepatocito , Ratones , Ratones Endogámicos C57BL , Transducción de Señal , Factor 1 de Transcripción de Linfocitos T/deficiencia
14.
Genes (Basel) ; 10(5)2019 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-31035529

RESUMEN

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.


Asunto(s)
Ficobilinas/genética , Ficocianina/genética , Rhodophyta/genética , Secuencia de Aminoácidos/genética , Sitios de Unión/genética , Clonación Molecular , Escherichia coli , Mutación/genética
15.
Gene ; 697: 123-130, 2019 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-30794916

RESUMEN

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.


Asunto(s)
Chlorophyceae/genética , Nitrito Reductasas/genética , Chlorophyta/genética , Nitritos/metabolismo , Nitrógeno/metabolismo , Fósforo/metabolismo , Filogenia
16.
Chem Sci ; 9(32): 6679-6684, 2018 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-30310601

RESUMEN

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.

17.
PLoS One ; 13(12): e0208853, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30533058

RESUMEN

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.


Asunto(s)
Hidroliasas/genética , Oxidorreductasas/genética , Estramenopilos/genética , Clonación Molecular , Ácidos Docosahexaenoicos/metabolismo
18.
Leuk Res ; 31(4): 497-506, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17056112

RESUMEN

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.


Asunto(s)
Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/genética , Metilación de ADN , Metilasas de Modificación del ADN/antagonistas & inhibidores , Leucemia Mieloide/genética , Proteínas de Fusión Oncogénica/metabolismo , Azacitidina/análogos & derivados , Azacitidina/farmacología , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Decitabina , Inhibidores Enzimáticos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Inhibidores de Histona Desacetilasas , Histonas/efectos de los fármacos , Histonas/metabolismo , Humanos , Ácidos Hidroxámicos/farmacología , Proteínas de Fusión Oncogénica/genética , Proteína 1 Compañera de Translocación de RUNX1 , Transcripción Genética , Células Tumorales Cultivadas
19.
Leuk Res ; 28(10): 1001-4, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15289009

RESUMEN

Telomere length and telomerase have an important role in normal and malignant hematopoiesis. Telomere erosion can lead to chromosome end fusion and thereby contribute to genomic instability during tumorigenesis. Thus, like complex chromosomal aberrations, telomere length may be a prognostic factor in hematopoietic malignancies. A paper by Sieglova et al. in this issue of Leukemia Research reports on the prognostic impact of telomere shortening in bone marrow (BM) and peripheral blood (PB) specimens of myelodysplastic syndrome (MDS) and MDS converted-AML patients (pts). Their results underline the importance to study telomere biology together with cytogenetics, genomic and proteomic profiling as prognostic factors, in order to improve risk-adapted therapy of MDS and AML pts.


Asunto(s)
Células Madre Hematopoyéticas/metabolismo , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Células Madre Neoplásicas/metabolismo , Telomerasa , Telómero , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/metabolismo , Telomerasa/genética , Telomerasa/metabolismo , Telómero/genética , Telómero/metabolismo
20.
Leuk Res ; 28(12): 1267-71, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15475067

RESUMEN

The demethylating agents 5-aza-2'-deoxycytidine (decitabine, DAC) and 5-azacytidine at low doses induce hematologic and cytogenetic remissions in a subset of patients with MDS. It is unclear whether the correction of neutropenia involves differentiation of abnormal granulocyte precursors, or emergence of normal granulopoiesis. A previous study in three MDS patients, analyzing a differentiating activity of GM-CSF, had shown heterogenous granulocyte responses. The objective of our study was to determine the ratio of clonal and nonclonal peripheral blood granulocytes in MDS patients treated with DAC using FISH analysis. In two patients with initial severe neutropenia, an informative cytogenetic marker, complete normalization of peripheral blood neutrophils and a bone marrow cytogenetic response following DAC, >90% of the cells contributing to neutrophil normalization lacked this clonal marker. In one of them, an early and transient increase in clonal neutrophils was compatible also with a modest differentiating effect upon the dysplastic granulocyte precursors, whereas in a third patient, resistant to re-treatment with DAC, no expansion of either granulocyte population occurred. In the responders, leukocyte nadirs following DAC appeared less pronounced after conversion to normal cytogenetics. In conclusion, restoration of nonclonal hematopoiesis may be the predominant effect of DAC both in early and late stages of treatment, at least in patients achieving a hematologic and cytogenetic response.


Asunto(s)
Azacitidina/análogos & derivados , Azacitidina/administración & dosificación , Síndromes Mielodisplásicos/tratamiento farmacológico , Neutrófilos/efectos de los fármacos , Anciano , Azacitidina/farmacología , Proliferación Celular/efectos de los fármacos , Células Clonales/patología , Decitabina , Femenino , Granulocitos/citología , Granulocitos/efectos de los fármacos , Humanos , Hibridación Fluorescente in Situ , Recuento de Leucocitos , Leucopoyesis/efectos de los fármacos , Masculino , Síndromes Mielodisplásicos/sangre , Neutropenia
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