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1.
Bioorg Chem ; 90: 103061, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31216505

RESUMEN

Ginsenoside M1 (M1) was considered to be the main antitumor component of ginsenoside metabolites in the body. In order to enhance its potency on antitumor effect, three novel M1 3'-ester derivatives (1c, 2c, 3c) were synthesized and evaluated. The yield of these derivatives was between 41% and 69%. Compared with M1, 2c and 3c can improve the efficacy of the inhibition on breast cancer MCF-7 and MDA-MB-231 cells, especially for MCF-7 (fold: 0.7-4.2, p < 0.0001). Further study suggested that 2c and 3c may cause cell autophagy and promote apoptosis in MCF-7 cells. The results indicated the 3'-ester modified M1 derivatives 2c and 3c possess higher abilities of inhibition growth towards triple-positive breast cancer and provided a new source for synthesis of potential anti-breast cancer drugs.


Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Apoptosis , Autofagia , Neoplasias de la Mama/patología , Ésteres/química , Ginsenósidos/química , Neoplasias de la Mama/tratamiento farmacológico , Proliferación Celular , Femenino , Humanos , Células MCF-7
2.
Glycoconj J ; 34(1): 51-59, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27726058

RESUMEN

Sialic acid modification is a kind of post-translational modification. To investigate the regulation effect of sialic acid on neural differentiation, we used CycloManN propanyl perac (CycloManN pro), a metabolic precursor of sialic acid, to treat PC12 cells. We noted that CycloManN pro indeed robustly promoted global sialylation detected by MAL II lectin blot in PC12 cells. Simultaneously, we interestingly found that the neurite outgrowth of PC12 cells was significantly promoted by the CycloManN pro treatment. The profile analysis of sialylated proteins showed that a protein band at 55KD was greatly enhanced especially in PC12L cells after CycloManN pro treatment. After enrichment with lectin MAL II, the proteins in this band were analyzed by mass spectrometry. The results showed that 23 proteins were in the band, but the score of vimentin was the highest among them. To investigate further the role of vimentin in the process of neurite differentiation, vimentin construct was transfected into PC12 cells. We interestingly observed that ectopic expression of vimentin significantly enhanced the neurite outgrowth induced by CycloManN pro. However, after three potential glycosylation sites (Ser-7, Thr-33, Ser-34:) of vimentin were mutated to alanine, overexpression of the mutated vimentin completely lost the enhancement activity for the neural differentiation even in the presence of CycloManN pro. Taken together, our study demonstrated that vimentin was important in the induction of neural differentiation by CycloManN pro.


Asunto(s)
Neuritas/metabolismo , Proyección Neuronal , Procesamiento Proteico-Postraduccional , Ácidos Siálicos/metabolismo , Vimentina/metabolismo , Animales , Lectinas/metabolismo , Mutación , Células PC12 , Ratas , Vimentina/genética
3.
Biomed Environ Sci ; 27(5): 388-90, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24827721

RESUMEN

This study aimed to determine the in vitro activity of quinupristin-alfopristin against Streptococcus sp. isolated in China. This agent is not yet available for clinical use, but it has been tested against a high proportion of resistant Staphylococcus aureus strains. A total of 156 streptococcal isolates, which were recovered from various geographic areas and diseases, were tested using the Etest (AB Biodisk, Solna, Sweden). Quinupristin-alfopristin showed excellent activity against all of the tested streptococci isolates. These results provide useful data for the clinical use of quinupristin-alfopristin in China.


Asunto(s)
Antibacterianos/farmacología , Streptococcus/efectos de los fármacos , Virginiamicina/farmacología , China , Pruebas de Sensibilidad Microbiana
4.
Biomed Environ Sci ; 26(11): 877-85, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24331532

RESUMEN

OBJECTIVE: To investigate molecular characterization of streptococcus pyogenes isolates involved in an outbreak of scarlet fever in China in 2011. METHODS: Seventy-four Streptococcal pyogenes involved in an outbreak of scarlet fever were isolated from pediatric patients in the areas with high incidence in China from May to August of 2011. Emm genotyping, pulsed-field gel electrophoresis (PFGE), superantigen (SAg) genes and antimicrobial susceptibility profiling were analyzed for these isolates. RESULTS: A total of 4 different emm types were identified. Emm12 was the most prevalent type which contained four predominating PFGE patterns corresponding to four different virulence and superantigen profiles. Emm12 (79.7%) and emm1 (14.9%) accounted for approximately 94% of all the isolates. The speA gene was all negative in emm12 isolates and positive in emm1 isolates. All strains were resistant to erythromycin, and 89.4% of them were resistant to erythromycin, tracycline, and clindamycin simultaneously. CONCLUSION: Several highly diversified clones with a high macrolide resistance rate comprise a predominant proportion of circulating strains, though no new emm type was found in this outbreak. The data provide a baseline for further surveillance of scarlet fever, which may contribute to the explanation of the outbreak and development of a GAS vaccine in China.


Asunto(s)
Brotes de Enfermedades , Escarlatina/epidemiología , Streptococcus pyogenes/genética , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Niño , China/epidemiología , Farmacorresistencia Bacteriana , Electroforesis en Gel de Campo Pulsado , Humanos , Incidencia , Epidemiología Molecular , Escarlatina/tratamiento farmacológico , Escarlatina/microbiología , Streptococcus pyogenes/efectos de los fármacos , Streptococcus pyogenes/aislamiento & purificación , Streptococcus pyogenes/patogenicidad , Virulencia
5.
Microbiol Spectr ; 11(3): e0274122, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-36995237

RESUMEN

The aim of this study was to investigate the transferability of acquired linezolid resistance genes and associated mobile genetic elements in an Enterococcus faecalis isolate QZ076, cocarrying optrA, cfr, cfr(D), and poxtA2 genes. MICs were determined by broth microdilution. Whole-genome sequencing (WGS) was performed using the Illumina and Nanopore platforms. The transfer of linezolid resistance genes was investigated by conjugation, using E. faecalis JH2-2 and clinical methicillin-resistant Staphylococcus aureus (MRSA) 109 as recipients. E. faecalis QZ076 harbors four plasmids, designated pQZ076-1 to pQZ076-4, with optrA located in the chromosomal DNA. The gene cfr was located on a novel pseudocompound transposon, designated Tn7515, integrated into the 65,961-bp pCF10-like pheromone-responsive conjugative plasmid pQZ076-1. Tn7515 generated 8-bp direct target duplications (5'-GATACGTA-3'). The genes cfr(D) and poxtA2 were colocated on the 16,397-bp mobilizable broad-host-range Inc18 plasmid pQZ076-4. The cfr-carrying plasmid pQZ076-1 could transfer from E. faecalis QZ076 to E. faecalis JH2-2, along with the cfr(D)- and poxtA2-cocarrying plasmid pQZ076-4, conferring the corresponding resistant phenotype to the recipient. Moreover, pQZ076-4 could also transfer to MRSA 109. To the best of our knowledge, this study presented the first report of four acquired linezolid resistance genes [optrA, cfr, cfr(D), and poxtA2] being simultaneously present in the same E. faecalis isolate. The location of the cfr gene on a pseudocompound transposon in a pheromone-responsive conjugative plasmid will accelerate its rapid dissemination. In addition, the cfr-carrying pheromone-responsive conjugative plasmid in E. faecalis was also able to mobilize the interspecies transfer of the cfr(D)- and poxtA2-cocarrying plasmid between enterococci and staphylococci. IMPORTANCE In this study, the simultaneous occurrence of four acquired oxazolidinone resistance genes [optrA, cfr, cfr(D), and poxtA2] was identified in an E. faecalis isolate of chicken origin. The association of the cfr gene with a novel pseudocompound transposon Tn7515 integrated into a pCF10-like pheromone-responsive conjugative plasmid will accelerate its dissemination. Moreover, the location of the resistance genes cfr(D) and poxtA2 on a mobilizable broad-host-range Inc18 family plasmid represents the basis for their intra- and interspecies dissemination with the aid of a conjugative plasmid and further accelerates the spreading of acquired oxazolidinone resistance genes, such as cfr, cfr(D), and poxtA2, among Gram-positive pathogens.


Asunto(s)
Infecciones por Bacterias Grampositivas , Staphylococcus aureus Resistente a Meticilina , Oxazolidinonas , Animales , Linezolid/farmacología , Antibacterianos/farmacología , Enterococcus faecalis/genética , Pollos , Farmacorresistencia Bacteriana/genética , Genes Bacterianos/genética , Plásmidos/genética , Pruebas de Sensibilidad Microbiana , Cromosomas , Infecciones por Bacterias Grampositivas/epidemiología
6.
Front Microbiol ; 12: 667415, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34149653

RESUMEN

lsa(E) is a pleuromutilin, lincosamide, and streptogramin A (PLSA phenotype) resistance gene that was first described in S. aureus and was thought to have been transferred from Enterococcus sp. This study aimed to elucidate the prevalence of the lsa(E) gene among E. faecium isolates at a tertiary teaching hospital and to evaluate the transferability of the lsa(E) gene from E. faecium to S. aureus in vitro. A total of 96 E. faecium strains isolated from one hospital in Beijing in 2013 were analysed for quinupristin-dalfopristin (QDA) resistance genes, and multilocus sequence typing (MLST) was performed. The transferability of QDA resistance between ten E. faecium strains and four S. aureus strains was determined by filter mating. Genome sequencing of the transconjugant was performed. A total of 46 E. faecium isolates (46/96, 47.92%) tested positive for lsa(E), while two isolates (2/96, 2.08%) tested positive for lsa(A). Thirty-six lsa(E)-positive strains (36/46, 78.3%) belonged to ST78. Among 40 mating tests, lsa(E) was successfully transferred through one conjugation at a frequency of 1.125 × 10-7 transconjugants per donor. The QDA resistance of the transconjugant N7435-R3645 was expressed at a higher level (MIC = 16 mg/L) than that of the parent S. aureus strain (MIC = 0.38 mg/L). Next-generation sequencing (NGS) analysis of the transconjugant N7435-R3645 showed that the complete sequence of the lsa(E)-carrying plasmid pN7435-R3645 had a size of 92,396 bp and a G + C content of 33% (accession no. MT022086). The genetic map of pN7435-R3645 had high nucleotide similarity and shared the main open reading frame (ORF) features with two plasmids: E. faecium pMG1 (AB206333.1) and E. faecium LS170308 (CP025078.1). The rep gene of pN7435-R3645 showed 100% identity with that of pMG1, although it did not belong to the rep1-19 family but instead a unique rep family. Multiple antibiotic resistance genes, including lsa(E), aadE and lnu(B), erm(B), ant6-Ia, and lnu(B), were present on the plasmid. In conclusion, an lsa(E)-carrying plasmid that can be transferred by conjugation from E. faecium to S. aureus in vitro was identified. This multidrug resistance (MDR) pMG1-like plasmid may act as a vector in the dissemination of antimicrobial resistance among species.

7.
Biomed Environ Sci ; 23(4): 251-8, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20934111

RESUMEN

OBJECTIVE: During 2003-2005, an outbreak of meningitis due to Neisseria meningitidis serogroup C occurred in China. With the aim to find strain clues result in the final epidemics, the ancestral strain 053442, a clinical isolate, and a carrier strain 053426 with different gene type were analyzed. METHODS: Clinical strain 053442 and carrier strain 053426 were cultured on GC agar plates under the same condition. Two-dimensional electrophoresis was performed using the pH 3-10 nonlinear IPG strips of 24 cm length, and all the protein spots were identified by matrix-assisted laser desorption/ionization time of flight spectrometry. RESULTS: 502 and 380 protein spots were identified in 053426 and 053442 respectively, relating to 266 and 202 different genes covering a wide range of cellular functions. The express volume and number of proteins involved in energy metabolism, protein synthesis and amino acid biosynthesis in 053426 were higher than in 053442. Virulence factor Opa, Opc and a series of proteins involved in pilus assembly and retraction were identified in 053442, which appear to be of primary importance in colonization and invasion of human cells. Compared to 053442, virulence protein species were less in 053426, with lower express volumes too. No Opa and Opc were detected in 053426. CONCLUSIONS: The different protein expression profiles of the clinical strain 053442 and carrier strain 053426 in the present study provide some clues of the different pathogenicity of the two strains, which may account for result in the final epidemics.


Asunto(s)
Proteínas Bacterianas/análisis , Técnicas de Tipificación Bacteriana , Brotes de Enfermedades , Meningitis Meningocócica/epidemiología , Meningitis Meningocócica/microbiología , Neisseria meningitidis Serogrupo C/aislamiento & purificación , Proteoma/análisis , China/epidemiología , Electroforesis en Gel Bidimensional , Humanos , Meningitis Meningocócica/líquido cefalorraquídeo , Neisseria meningitidis Serogrupo C/clasificación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
8.
Anal Chim Acta ; 1131: 1-8, 2020 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-32928469

RESUMEN

A simple but effective method for the detection of miRNAs was proposed by integrating exonuclease-III assisted target recycling amplification and repeated-fishing strategy. In the proposed method, exonuclease-III assisted target recycling amplification reaction is adopted to produce a large amount of DNA fragments with fluorescence group at its 5' end in the presence of the target miRNA, which are then repeatedly fished out from the reaction mixture by a gold foil modified with a capture probe and transferred into a so-called 'product tube'. The amount of the target miRNA can then be determined from the fluorescence measurement of the solution in the 'product tube'. Application to the detection of miRNA-155 in samples of KH-2 and BRSA-2B cells revealed that the proposed method could achieve sensitive and accurate quantification of the target miRNA with a limit of detection of 36 fM and recovery rates in the range from 96.2% to 105%. Its simplicity, sensitivity and resistance to possible fluorescence interferences in complex biological samples make the proposed method a potentially competitive alternative for miRNAs detection in complex biological samples.


Asunto(s)
Técnicas Biosensibles , MicroARNs , ADN , Exodesoxirribonucleasas , Oro , Límite de Detección , Técnicas de Amplificación de Ácido Nucleico
9.
J Clin Microbiol ; 47(3): 715-20, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19116348

RESUMEN

In this study, 68 group A streptococcus (GAS) isolates associated with two outbreaks of acute glomerulonephritis (AGN) in China were analyzed by emm typing. A total of 11 different emm types were identified. Analysis of emm type distribution suggested that AGN outbreaks in two counties were caused by emm60.1- and emm63.0-type GAS. These two types were further characterized by pulsed-field gel electrophoresis, multilocus sequence typing, sof sequence typing, and PCR-based identification of streptococcal pyrogenic exotoxin A, B, and C (speA, speB, and speC) genes. In antimicrobial susceptibility tests, all outbreak strains were resistant to erythromycin and tetracycline, and the rates of resistance of nonoutbreak strains to the two antibiotics were 63.6% and 90.9%. This study is also the first to report a nephritogenic M63 GAS strain.


Asunto(s)
Brotes de Enfermedades , Glomerulonefritis/epidemiología , Glomerulonefritis/microbiología , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/microbiología , Streptococcus pyogenes/clasificación , Streptococcus pyogenes/genética , Adolescente , Animales , Antibacterianos/farmacología , Antígenos Bacterianos/genética , Proteínas de la Membrana Bacteriana Externa/genética , Toxinas Bacterianas/genética , Técnicas de Tipificación Bacteriana , Proteínas Portadoras/genética , Niño , Preescolar , China/epidemiología , Análisis por Conglomerados , Dermatoglifia del ADN , ADN Bacteriano/química , ADN Bacteriano/genética , Electroforesis en Gel de Campo Pulsado , Genotipo , Humanos , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , Streptococcus pyogenes/aislamiento & purificación
10.
Zhonghua Yu Fang Yi Xue Za Zhi ; 43(2): 137-40, 2009 Feb.
Artículo en Zh | MEDLINE | ID: mdl-19534907

RESUMEN

OBJECTIVE: To analyze multilocus sequence typing (MLST) of methicillin-resistant Staphylococcus aureus (MRSA) strains in 2000 and 2005, and get a primary knowledge of MLST Characterization of MRSA. METHODS: Sequence analysis was conducted on seven allelic genes of 29 methicillin-resistant Staphylococcus aureus strains and 2 methicillin-sensitive Staphylococcus aureus (MSSA) strains and the allelic profiles were gained from internet database. RESULTS: All 12 MRSA strains in 2000 were sequence type (ST) 239 and 10 MRSA strains in 2005 were ST239, while 7 MRSA strains in 2005 were new types, ST5 (41.18%, 7/17). ST6 and ST630 were allelic profiles of 2 MSSA strains. ST239 was the most prevalent allelic profile (75.86%, 22/29), while ST5 was the second prevalent allelic profile (24.14%, 7/29) among all isolates. CONCLUSION: ST239 and ST5 are the most prevalent MRSA clones in this research. MRSA strains have different allelic profile from MSSA strains. MLST might provide an unambiguous method for assigning MRSA and MSSA isolates to known clones or assigning them as novel clones via the internet. Further studies need to be taken by increasing strains.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina/clasificación , Staphylococcus aureus Resistente a Meticilina/genética , Técnicas de Tipificación Bacteriana , Secuencia de Bases , ADN Bacteriano/genética , Genes Bacterianos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos
11.
Zhongguo Zhong Yao Za Zhi ; 33(11): 1284-6, 2008 Jun.
Artículo en Zh | MEDLINE | ID: mdl-18831208

RESUMEN

OBJECTIVE: To analyze the monosaccharide composition in the polysaccharides from Rhaponticum uniforum, determine the content of monosaccharide, and provide some references for further research. METHOD: The monosaccharide composition was determined by high performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Phenol-sulfuric acid method was used for the determination of the content of polysaccharide. RESULT: The monosaccharides composition in polysaccharides from R. uniforum are glucose, arabonose and fructose. Their molar ratios are 1 : 1.61 : 2.21. The content of polysaccharide is 95.78%, taking the mixture of monosaccharide compositions as reference substances. CONCLUSION: HPAEC-PAD can be used to analyze the monosaccharide composition in the polysaccharide with high precision, and the method of phenol-sulfuric acid is simple, convenient and reliable.


Asunto(s)
Leuzea/química , Monosacáridos/análisis , Polisacáridos/análisis , Calibración , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Monosacáridos/aislamiento & purificación , Polisacáridos/aislamiento & purificación , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
12.
J Inorg Biochem ; 101(10): 1404-9, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17640736

RESUMEN

The novel Pd(II) complex, [Pd(2)(micro-bzta)(4)].1.5DMSO (where bzta=benzothiazole-2-thiolate) has been synthesized and structurally characterized by element analysis, IR and single-crystal X-ray diffractometry. In the binuclear complex, two palladium(II) are bridged by four deprotonated benzothiazole-2-thialate in a head to tail disposition and the distance of the two Pd(II) is 2.747 A. Three-dimensional structure of the complex was constructed though S...S (3.339 A) weak interaction and pi...pi stack. The binding of the title complex with fish sperm DNA (FS-DNA) has been investigated by absorption and fluorescence spectra. The results indicate that the complex bind to FS-DNA in an intercalative mode and the intrinsic binding constant K of the title complex with FS-DNA is about 1.2 x 10(4)M(-1). Gel electrophoresis assay demonstrates the ability of the complex to cleave the pUC19 plasmid DNA.


Asunto(s)
Benzotiazoles/química , ADN/química , Paladio/química , Animales , Cristalografía por Rayos X , Electroforesis en Gel de Agar , Peces , Masculino , Modelos Moleculares , Estructura Molecular , Análisis Espectral
13.
World J Gastroenterol ; 13(27): 3742-6, 2007 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-17659737

RESUMEN

AIM: To investigate whether anti-H pylori antibodies have cross-reaction with antigens of erythrocyte membrane. METHODS: Blood samples were collected from 14 volunteers (8 positive and 6 negative for H pylori detected by (13)C-urea breath test) of the general population. Erythrocyte membrane proteins of the subjects were examined by Western blot using anti-H pylori serum. The proteins related to the positive bands were identified by mass spectrum analysis. RESULTS: Anti-H pylori antibodies had cross-reaction with the proteins of about 50 kDa of erythrocyte membranes in all samples independent of H pylori infection. One protein in the positive band was identified as Chain S, the crystal structure of the cytoplasmic domain of human erythrocyte Band-3 protein. CONCLUSION: Anti-H pylori antibodies cross-react with some antigens of human erythrocyte membrane, which may provide a clue for the relationship between H pylori infection and vascular disorders.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Membrana Eritrocítica/inmunología , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Proteínas de la Membrana/inmunología , Adulto , Proteína 1 de Intercambio de Anión de Eritrocito/inmunología , Reacciones Cruzadas , Membrana Eritrocítica/microbiología , Femenino , Infecciones por Helicobacter/sangre , Infecciones por Helicobacter/microbiología , Humanos , Masculino , Persona de Mediana Edad
14.
Huan Jing Ke Xue ; 38(9): 3610-3619, 2017 Sep 08.
Artículo en Zh | MEDLINE | ID: mdl-29965239

RESUMEN

The impacts of reactive nitrogen (Nr) on the environment significantly increase with population and rapid urbanization. In order to study gaseous Nr and Nr loads to waterbodies at the provincial scale, we established anthropogenic emission inventories in prefecture-level cities in Fujian Province and analyzed the changes in Nr emissions for the years 2000, 2005, and 2010. The total Nr emissions were calculated as 538.4, 587.0, and 620.0 Gg in those three years, respectively. The emissions of Nr increased in nine prefecture-level cities except in Zhangzhou. Among these nine cities, Putian is the fastest growing one. The largest emitters were Zhangzhou and Quanzhou, while Ningde and Xiamen were the smallest ones. Agricultural ecosystems and livestock were the main sources of Nr emissions, both of them accounting for more than 90% of total anthropogenic Nr emissions. Despite rapid growth, energy activities had a minor contribution to total Nr emissions. The per area Nr emissions of each prefecture-level city were highest in Xiamen in the southeast coastal area and lowest in Sanming located in the northwest inland region in 2010. However, the patterns of GDP, population, and emission intensities showed the opposite trends to per area Nr emissions, lowest in Xiamen and highest in Nanping. We further discussed the significance of Nr emissions reductions in different areas based on the analysis of the characteristics of Nr emission sources in prefecture-level cities. The results provide a scientific basis for reducing Nr emissions in Fujian Province and its prefecture-level cities.

15.
Artículo en Inglés | MEDLINE | ID: mdl-12050812

RESUMEN

The full length cDNA of human B lymphocyte stimulator (hBLyS) was amplified by using PCR method from cDNA library of human placenta. After purifying and sequencing, the DNA fragment of functional domain of hBLyS (hsDNA fragment)was amplified by using nested PCR method from the PCR product. The prokaryotic expression plasmid pET-30a( )/ hBLyS was constructed with recombinant DNA techniques after purifying and identifying the hsDNA fragment. Then the plasmid pET-30a( )/ hBLyS was transformed into lambdaDE3 cells and the recombination protein was found to be highly expressed the expression product was purified by affinity chromatography gel, Ni(2 )-IDA, made in our laboratory. The experimental results showed that the sequence of the PCR product was identical with the published hBLyS cDNA sequence and purity of the recombination protein we obtained was high. The activity of the purified recombination protein was very significant in the proliferation test of B lymphocytes.

16.
Int J Hematol ; 96(4): 428-37, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23054645

RESUMEN

Leukemias bearing rearrangements of chromosome 11q23 are of particular interest due to their unique clinical and biological characteristics. 11q23 abnormalities occur in up to 70 % of infant leukemias, and about 10 % of adult acute myelogenous leukemias (AML). Two major rearrangements of the MLL gene are found in MLL-related leukemia. The most common of these is balanced translocations in which the N-terminal portion of MLL is fused to the C-terminus of the translocation partner. To date, nearly 100 different chromosome bands have been described in rearrangements involving MLL, and more than 70 known fusion partners of MLL have been cloned and characterized at the molecular level. Another major aberration of the MLL gene creates a repeat within the N-terminal MLL resulting in an internal partial tandem duplication (PTD). As a consequence, an extra amino-terminus is added in-frame to full-length MLL, resulting in leukemogenic MLL-PTD. MLL-PTD occurs predominantly in myeloid dysplasia syndromes, secondary AML (s-AML), and de novo AML. The presence of an MLL rearrangement generally confers a poor prognosis. MLL fusions and MLL-PTD are transcriptional regulators that take control of targets normally controlled by MLL, with the clustered HOX homeobox genes as prominent examples. Several epigenetic regulators that modify DNA or histones have been implicated in MLL fusion driven leukemogenesis, including DNA methylation, histone acetylation, and histone methylation. Recently, the histone methyltransferase DOT1L, the bromodomain and extra-terminal (BET) family member BRD4, and the MLL-interacting protein Menin have emerged as important mediators of MLL fusion-mediated leukemic transformation. The clinical development of targeted inhibitors of these epigenetic regulators has heralded promise for the treatment of MLL fusion leukemia. Although the biological function and molecular mechanism for MLL-PTD remains largely unknown, based on the primary protein structure of MLL-PTD and the knowledge gained so far from MLL fusions, newly developed inhibitors of epigenetic regulators could potentially also prove effective in the treatment of MLL-PTD related leukemias.


Asunto(s)
Epigénesis Genética , Regulación Leucémica de la Expresión Génica , Leucemia/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , Animales , Ensayos Clínicos como Asunto , Hematopoyesis/genética , Humanos , Leucemia/tratamiento farmacológico , Leucemia/metabolismo , Terapia Molecular Dirigida , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo
17.
World J Gastroenterol ; 16(11): 1385-96, 2010 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-20238406

RESUMEN

AIM: To extend the knowledge of the dynamic interaction between Helicobacter pylori (H. pylori) and host mucosa. METHODS: A time-series cDNA microarray was performed in order to detect the temporal gene expression profiles of human gastric epithelial adenocarcinoma cells infected with H. pylori. Six time points were selected to observe the changes in the model. A differential expression profile at each time point was obtained by comparing the microarray signal value with that of 0 h. Real-time polymerase chain reaction was subsequently performed to evaluate the data quality. RESULTS: We found a diversity of gene expression patterns at different time points and identified a group of genes whose expression levels were significantly correlated with several important immune response and tumor related pathways. CONCLUSION: Early infection may trigger some important pathways and may impact the outcome of the infection.


Asunto(s)
Mucosa Gástrica , Perfilación de la Expresión Génica , Helicobacter pylori/patogenicidad , Línea Celular Tumoral , Análisis por Conglomerados , Mucosa Gástrica/microbiología , Mucosa Gástrica/fisiología , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiología , Factores de Tiempo
18.
Prog Neuropsychopharmacol Biol Psychiatry ; 34(6): 930-3, 2010 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-20420877

RESUMEN

Accumulating evidence showed that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. Recent studies have reported that the Val66Met polymorphism of the BDNF gene may be associated with susceptibility for schizophrenia and age of onset of this disease, with mix results. In the present study, the BDNF Val66Met gene polymorphism was examined in 387 inpatients (259 men and 128 women) meeting the DSM-IV criteria for schizophrenia and unrelated 365 healthy controls (255 men and 110 women). The schizophrenia symptomatology was assessed by the Positive and Negative Syndrome Scale (PANSS). Age of onset was defined as the age at which the psychotic symptoms first appeared. Our results showed that genotype frequency distributions and allelic frequencies did not differ between patients and controls. No interaction was found between sex and genotypes. Analysis of covariance (ANCOVA) showed a significance of the BDNF Val66Met genotypes on the age of onset (F=3.76, p<0.02), after adjusting sex, age and duration of illness. Furthermore, ANCOVA showed that the significance of the BDNFVal66Met genotypes on age of onset was increased comparing the Val66Met heterozygotes with the combination of Val66Val and Met66Met homozygotes (F=5.85, p<0.01). Our results suggest that the BDNF Val66Met polymorphism may not contribute directly to the susceptibility to schizophrenia, but to the onset of the disease. Furthermore, our results show the heterozygous effect of the BDNF Val66Met gene on the clinical variability of schizophrenia phenotype.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/genética , Esquizofrenia/genética , Adulto , Edad de Inicio , Análisis de Varianza , Pueblo Asiatico/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple
19.
Zhonghua Liu Xing Bing Xue Za Zhi ; 26(6): 444-7, 2005 Jun.
Artículo en Zh | MEDLINE | ID: mdl-16185462

RESUMEN

OBJECTIVE: To Investigate the differences of sorbitol fermentation related genes and optimize molecular analysis method for distinguishing an epidemic with nonepidemic strains of Vibrio cholerae. METHODS: Sequence analysis on four genes of sugar fermentation stimulation protein, periplasmic maltose-binding protein, periplasmic phosphate-binding protein and periplasmic amino acid-binding protein. RESULTS: In this study, the following data was noticed: for O1 serogroup El Tor biotype V. cholerae, twenty-four epidemic and eight nonepidemic strains were chosen; For O139 serogroup V. cholerae, five epidemic and four nonepidemic strains were chosen. With those genes of sugar fermentation stimulation protein, there were three point mutations. The 106th, 150th, 378th oligonucleotide in epidemic strains were A, A and T, comparing to the nonepidemic strains which were G, G and C. When comparing the protein sequences, epidemic strains had a Threonine at 36th amino acid, whereas nonepidemic strains had an Alanine. The results in O139 serogroup were consistent with those in O1 serogroup El Tor biotype strains. Another two point mutations were found in the genes of periplasmic maltose-binding protein. The 999th, 1003rd oligonucleotides in epidemic strains were A and C, while in nonepidemic which were G and T. For the gene of periplasmic amino acid-binding protein, two point mutations were noticed. The 504th and 690th oligonucleotides in epidemic strains were T and C, but were C and T in nonepidemic. However, no amino acid differences were found in periplasmic maltose-binding protein and periplasmic amino acid-binding protein. For periplasmic amino acid-binding protein gene, there was no difference on oligonucleotide between epidemic and nonepidemic strains. CONCLUSION: Results suggested that SNPs in these genes might serve as a useful tool to distinguish the epidemic strains from nonepidemic strains. The 36th amino acid mutation of sugar fermentation stimulation protein in epidemic and nonepidemic strains might change the activity of the protein which might be associated with sorbitol fermentation.


Asunto(s)
Proteínas Portadoras/genética , Proteínas de Unión Periplasmáticas/genética , Proteínas de Unión a Fosfato/genética , Vibrio cholerae/genética , Secuencia de Aminoácidos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Secuencia de Bases , Proteínas Portadoras/metabolismo , Fermentación , Proteínas de Unión a Maltosa , Datos de Secuencia Molecular , Proteínas de Unión Periplasmáticas/metabolismo , Proteínas de Unión a Fosfato/metabolismo , Mutación Puntual , Análisis de Secuencia de Proteína , Sorbitol , Vibrio cholerae/metabolismo
20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 24(6): 447-8, 2003 Jun.
Artículo en Zh | MEDLINE | ID: mdl-12848906

RESUMEN

OBJECTIVE: To investigate the antimicrobial activity of Pariet, Tekpron, Nexium, respectively, against Helicobacter pylori (H. pylori) in vitro. METHODS: Antimicrobial effects of these medicines were evaluated through detection of MICs for 3 H. pylori strains isolated from different countries. RESULTS: The MIC(99) contents were 2.25 mg/L, 42.5 mg/L and 360 mg/L, respectively, for the three medicines. The strains under testing exhibited the same susceptibility to each medicine. Nexium did not inhibit the bacteria under the concentration of 3.6 - 36 mg/L with more and bigger H. pylori colonies seen when compared with controls. CONCLUSIONS: The growth inhibitory activity appeared to be different among the three PPI medicines under investigation, with Rabeprazole the most potential agent of the three. Data suggested that the action of growth inhibition in vitro was resting on the characteristic of the given PPI as well as the supplements of the medicine.


Asunto(s)
Bencimidazoles/farmacología , Inhibidores Enzimáticos/farmacología , Esomeprazol/análogos & derivados , Esomeprazol/farmacología , Helicobacter pylori/efectos de los fármacos , Inhibidores de la Bomba de Protones , 2-Piridinilmetilsulfinilbencimidazoles , Lansoprazol , Pruebas de Sensibilidad Microbiana , Rabeprazol
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