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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1540-1547, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607309

RESUMO

OBJECTIVE: To investigate the expression, mechanism and methylation level of miR-28-5p in multiple myeloma (MM), so as to provide the expirement basis for searching new targeted therapy. METHODS: RT-PCR was used to detect the expression levels of miR-28-5p and potential target CCND1 in CD138+ cells of the patients with MM and bone marrow mononuclear cells of patients with iron defficiency anemia(IDA) as control, Methylation-specific PCR(MSP) was used to detect methylation levels of CpG island in LPP/miR-28-5p promoter region and the correlation with other clinical indicators was analyzed. The 5-aza-2'-deoxycytidine (5-Aza-dC,DAC) was used to treat MM cell line U266; after drug treatment,MSP was used to analyze the methylation status of the CpG islands in LPP/miR-28-5p promoter; the qPCR was used to detect the expression levels of miR-28-5p,and the regulatory mechanism of miR-28-5p expression was explored furtherly. RESULTS: The methylation level of CpG island in LPP/miR-28-5p promoter region of MM patients was significantly higher than that of IDA patients. The relative expression level of miR-28-5p in MM patients was significantly lower than that of IDA patients. The relative expression level of miR-28-5p in newly diagnosed MM patients was higher than that in relapsed/progressive patients. The miR-28-5p target CCND1 was expressed at high levels in MM patients with LPP / miR-28-5p methylation, the expression level of miR-28-5p in MM patients correlated with ß2-MG concentration. 5-aza-dc could significantly inhibit the growth of U266 cell line, arrest the cell cycle in G1 phase, inhibit the biosynthesis of cellular RNA and protein and promote cell apoptosis. At the same time, up-regulation of miR-28-5p expression was found. CONCLUSION: The expression of miR-28-5p in MM patients is regulated by methylation of CpG islands in the promoter region of the genome.miR-28-5p may act as a tumor suppressor gene, and its low expression may be involved in the occurrence and development of MM, suggesting that miR-28-5p may become a new target for the treatment of MM.


Assuntos
MicroRNAs/genética , Mieloma Múltiplo , Linhagem Celular Tumoral , Ilhas de CpG , Metilação de DNA , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Humanos , Mieloma Múltiplo/genética
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1556-1560, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607311

RESUMO

OBJECTIVE: To investigate the effect of eukaryotic translation initiation factor 4E(eIF4E) on the autophagy of CD138+ plasma cells in multiple myeloma(MM). METHODS: Multiple myeloma CD138+ plasma cells were treated with eIF4E inhibitor 4EGI, the changes of autophagy-related factors LC3-II and Beclin1 were detected by fluorescent quantitative PCR and Western blot, the changes of cell proliferation inhibition were detected by MTT assay, and cell apoptosis was detected by flow cytometry. RESULTS: Quantitative fluorescence PCR showed that after treatment of myeloma cells with 4EGI, the expression levels of LC3-II and Beclin1 mRNA gradually increased with the enhancomer of 4EGI concentration and the prolongation of action time, and the differences were statistically significant (48 h: LC3-Ⅱ,r=0.942, Beclin1,r=0.952; 80 µg/ml: LC3-Ⅱ,r=0.966, Beclin1,r=0.998); Western blot showed that with the enhancement of 4EGI concentration, the expression of LC3-II and Beclin1 protein gradually increased(LC3-Ⅱ,r=0.923, Beclin1,r=0.977); CCK-8 showed that the inhibition rate of cells gradually increased (r=0.996); the apoptotic rate of 4EGI-treated groups (23.23±4.47, 7.59±1.67, 2.03±0.19) was significantly different from that of control group (0.03±0.04) (P<0.05). CONCLUSION: The inhibition of eIF4E can activate the autophagy of CD138+ plasma cells in multiple myeloma and induce the death of myeloma cells.


Assuntos
Autofagia , Mieloma Múltiplo , Proteína Beclina-1 , Linhagem Celular Tumoral , Fator de Iniciação 4E em Eucariotos , Humanos
3.
Acta Haematol ; : 1-10, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597158

RESUMO

BACKGROUND: The aim of this study was to detect the expression of long noncoding RNA small nucleolar RNA host gene 18 (SNHG18) andsemaphorin 5A (SEMA5A) genes in multiple myeloma (MM) patients and to explore the correlation of the expression of these genes with the clinical characteristics and prognosis of MM patients. METHODS: Forty-seven newly diagnosed MM, 18 complete remission MM, 13 refractory/relapse MM, and 22 iron deficiency anemia (serving as control) samples were extracted at the Department of Hematology, Second Affiliated Hospital of Xian Jiaotong University between January 2015 and December 2016. The clinical features of the MM patients are summarized. Real-time quantitative PCR was performed to analyze the relative expression levels of the SNHG18 and SEMA5Agenes. The clinical characteristics and overall survival (OS) of the MM patients were statistically analyzed while measuring different levels of SNHG18 and SEMA5Agene expression. At the same time, the correlation between the expression of SNHG18 and SEMA5A was also analyzed. RESULTS: The analysis confirmed that SNHG18 and its possible target gene SEMA5A were both highly expressed in newly diagnosed MM patients. After analyzing the clinical significance of SNHG18 and SEMA5A in MM patients, we found that the expression of SNHG18 and SEMA5A was related to the Durie-Salmon (DS), International Staging System (ISS), and Revised International Staging System (R-ISS) classification systems, and the Mayo Clinic Risk Stratification for Multiple Myeloma (mSMART; p < 0.05). Moreover, we observed a significant difference in OS between the SNHG18/SEMA5A high expression group and the low expression group. We found a positive correlation between SNHG18 and SEMA5A expression (r = 0.709, p < 0.01). Surprisingly, the expected median OS times of both the SNHG18 and SEMA5Ahigh expression groups were significantly decreased, which was in contrast to those of both the SNHG18 and SEMA5Alow expression groups and the single-gene high expression group (p < 0.05). CONCLUSION: High expression of both SNHG18 and SEMA5A is associated with poor prognosis in patients with MM.

4.
Ying Yong Sheng Tai Xue Bao ; 30(6): 1927-1935, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31257765

RESUMO

With the 14-year enclosed grassland and the grazed grassland as control, the impacts of anthropogenic shrublands (Caragana korshinskii) with the different planting years (3, 12, 22 a) and planting spaces (2, 8, 40 m) on soil organic carbon (SOC) contents were examined in the desert steppe of Eastern Ningxia, China. We further analyzed the spatial pattern and heterogeneity of SOC in 0-40 cm soil layer of the grassland area with introduced shrubs. The results showed that SOC in C. korshinskii shrublands had an increase trend with increased planting years and decreased spaces. The mean SOC with different planting years and spaces was 42.7% and 32.8% more than that in grazing land, respectively. There was no significant difference of SOC between shrublands and the 14-year enclosed grassland. The increase trend of SOC decreased by 27.0% in 22-year planting shrubland. The SOC content of 0-40 cm soil layer varied from 0.21 g·kg-1 to 26.04 g·kg-1 (with a mean of 3.75 g·kg-1), and the coefficient of SOC variation ranged from 90.9% to 114.7%. The SOC in 0-5 cm and 15-40 cm soil layers fitted the optimal theory formulation of Gaussian model, while that in 5-15 cm soil layer fitted a spherical model. The ranges (A0) of spatial autocorrelation in the 0-5 and 5-15 cm soil layers were smaller (3.11, 3.00 km) than that in 15-40 cm soil layer (10.10 km). The nugget/sill C0/(C0+C) of SOC in 0-5, 5-15 cm soil layer was 0.2% and 16.3%, indicating a strong spatial correlation, while that in 15-40 cm soil layer was 36.9%, with a moderate correlation. The shrub introdution could significantly accelerate the accumulation and fixation of SOC in top 40 cm soil layer in degraded desert steppe, but also intensified the spatial heterogeneity and SOC fragmentation. The SOC content in the anthropogenic shrublands had no significant difference from that in the enclosed desert steppe (14 years). The SOC spatial heterogeneity and the degree of fragmentation were weakened and decreased with the increasing soil layer depth.


Assuntos
Caragana/crescimento & desenvolvimento , Carbono/análise , Solo/química , China , Clima Desértico , Análise Espacial
5.
Chin Med J (Engl) ; 132(13): 1591-1598, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31205077

RESUMO

BACKGROUND: Natural anti-sense transcripts (NATs), which are transcribed from the complementary DNA strand of annotated genes, exert regulatory function of gene expression. Increasing studies recognized anti-sense transcription widespread throughout human cytomegalovirus (HCMV) genome, whereas the anti-sense transcription of RNA1.2 gene locus has never been investigated. In this study, the transcription of the RNA1.2 anti-sense strand was investigated in clinically isolated HCMV strain. METHODS: Strand-specific high-through RNA-sequencing (RNA-seq) was performed to find possible anti-sense transcripts (ASTs). For analyzing and visualization of RNA-seq data sets, Integrative Genomics Viewer software was applied. To confirm these possibilities, Northern blotting and rapid amplification of cDNA ends (RACE) were used. RESULTS: Transcription of the opposite strand of RNA1.2 gene locus was detected by RNA-sequencing using RNAs extracted from human embryonic lung fibroblasts infected with HCMV clinical isolate HAN. At least three HCMV NATs, named RNA1.2 AST 1, RNA1.2 AST2, and RNA1.2 AST3, were characterized by Northern blotting and RACE analyses. These RNA1.2 ASTs orientated from the complementary strand of RNA1.2 locus during the late phase of HCMV infection. The 5'- and 3'-termini of these transcripts were located within the opposite sequence of the predicted RNA1.2 gene. CONCLUSION: A cluster of novel NATs was transcribed from the opposite sequence of the HCMV RNA1.2 gene region.


Assuntos
Citomegalovirus/genética , RNA Antissenso/genética , Northern Blotting , Células Cultivadas , Genoma Viral/genética , Humanos , Software
6.
Blood Adv ; 3(5): 751-760, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30833275

RESUMO

The treatment of multiple myeloma (MM) with proteasome inhibitor (PI) bortezomib has significantly improved the survival of patients with MM. The 26S proteasome inhibitor targets the unfolded protein response (UPR) by inhibiting proteasome degradation of ubiquitinated paraprotein, subsequently leading to the lethal accumulation of paraprotein within the endoplasmic reticulum. According to secretory status of monoclonal immunoglobulin, newly diagnosed MM (NDMM) is divided into measurable and unmeasurable disease, which includes oligosecretory, nonsecretory, and nonproducer myeloma. The present study analyzed the clinical characteristics of 822 patients with NDMM who had either measurable or unmeasurable diseases and received bortezomib- or thalidomide-based therapies. Our results showed that the median progression-free survival (PFS) and overall survival (OS) of patients with MM was significantly longer in patients with measurable disease than those in oligosecretory, nonsecretory, and nonproducer MM (PFS: 27, 18, 19, and 2.0 months, respectively [P < .001]; OS: 51, 30, 22, and 2.0 months, respectively [P < .001]). Within the unmeasurable group, patients with nonproducer myeloma showed the shortest PFS and OS. Importantly, compared with thalidomide treatment, bortezomib significantly improved the PFS and OS of patients with MM with measurable disease (PFS: 25 and 33 months [P = .022], respectively; OS: 41 and 58 months [P < .001], respectively), but not those with unmeasurable disease (PFS: 18 and 16 months [P = .617], respectively; OS: 22 and 27 months [P = .743], respectively). Our results indicate that bortezomib-based therapy performed no better than thalidomide-based treatment in patients with unmeasurable MM. The results need to be confirmed in other patient cohorts, preferably in the context of a prospective trial.

7.
Biomed Environ Sci ; 31(8): 579-585, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30231962

RESUMO

OBJECTIVE: To investigate genetic and antibiotic resistance characteristics of Campylobacter jejuni (C. jejuni) isolated from Shenzhen. METHODS: Multilocs sequence typing and agar dilution methods were used to define the genotype and antibiotic resistance of C. jejuni, respectively. RESULTS: In total, 126 C. jejuni strains were isolated. The prevalence of C. jejuni was 5.3% in diarrheal patients. The prevalence in poultry meat (36.5%) was higher than that in cattle meat (1.1%). However, the prevalence in poultry cloacal swabs (27.0%) was lower than that in cattle stool (57.3%). Sixty-two sequence types were obtained, among which 27 of the STs and 10 alleles were previously unreported. The most frequently observed clonal complexes were ST 21 (11.9%), ST-22 (10.3%), and ST-403 (7.1%). ST-21, ST-45, ST-354, ST-403, and ST-443 complexes overlapped between isolates from patients and cattle, whereas ST-45 and ST-574 complexes overlapped between isolates from patients and poultry. All C. jejuni were resistant to at least one antibiotic. The highest resistance rate was toward ciprofloxacin (89.7%), followed by tetracycline (74.6%), and nalidixic acid (69.0%). CONCLUSION: This is the first report of the genotypes and antibiotic resistance of C. jejuni in Shenzhen. Overlapping clonal complexes were found between isolates from patients and cattle, and between patients and poultry.


Assuntos
Infecções por Campylobacter/microbiologia , Campylobacter jejuni/genética , Diarreia/microbiologia , Resistência Microbiana a Medicamentos/genética , Fezes/microbiologia , Adolescente , Adulto , Animais , Antibacterianos/farmacologia , Campylobacter jejuni/efeitos dos fármacos , Campylobacter jejuni/isolamento & purificação , Bovinos , Criança , Pré-Escolar , China , Genótipo , Humanos , Lactente , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Aves Domésticas , Adulto Jovem
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(4): 1022-1026, 2018 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30111401

RESUMO

OBJECTIVE: To investigate the proliferation- inhibitory and apoptosis inducing effect of ganglioside GM3 on human multiple myeloma cell line U266 cells and its possible mechanisms. METHODS: MTT assay and flow cytometry were used to observe the effects of GM3 ganglioside on proliferation and apoptosis of human myeloma cell line U266. Effects of different concentration of ganglioside GM3 on the mRNA expression level of BCL-2 and BAX were detected by Real-time PCR. RESULTS: MTT assay and Flow Cytometry showed that ganglioside GM3 could induce the apoptosis and inhibit the proliferation of multiple myeloma U266 cell line, and both the effects were enhanced with the increase of GM3 ganglioside concentration. Compared with the control group, the relative expression of BAX mRNA with the increase of GM3 concentration in experimental group was enhanced gradually(r=0.968), while the relative mRNA expression of anti-apoptotic gene BCL-2 was decreased gradually(r=-0.727). CONCLUSION: GM3 ganglioside can induce apoptosis and inhibit the proliferation of U266 cell line in a concentration dependent manner. The mechanism may be related with up- regulation of BAX expression and down-regulation of BCL-2.


Assuntos
Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Gangliosídeos , Humanos , Mieloma Múltiplo
9.
J Med Virol ; 90(3): 571-581, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29091300

RESUMO

The worldwide infection rate of herpesvirus is high, but the detailed prevalence in China, especially the central area, remains unclear. In the present study, the prevalence of herpes simplex virus (HSV), Epstein-Barr virus (EBV), and human cytomegalovirus (HCMV) was investigated in 303 healthy adults in Wuhan, a representative city in Central China. Viral-specific IgG and IgM titers were examined in the serum by chemiluminescent immunoassay, and the existence of viral genomic DNA in blood cells was determined by nested PCR. The overall IgG seroprevalences were 81.5%, 95.4%, and 93.7% for HSV, EBV, and HCMV, while the corresponding IgM seroprevalences were only 6.3%, 2.3%, and 0. The viral genomic DNA of HSV, EBV, and HCMV was identified in the blood samples of 5.9%, 14.2%, and 22.8% of the tested donors, respectively. Significantly, less HSV IgM-positive samples were found in the population over 20 years old than below 20 group; female displayed higher chances for HSV IgG and genome positivity; and occupations such as waiters and medical staffs were shown to be with higher risk for HCMV genome positivity. This study provided useful reference data for the HSV, EBV, and HCMV prevalence in central China, and suggested the potential importance of detecting viral genome to complement serum test data.


Assuntos
Anticorpos Antivirais/sangue , Citomegalovirus/isolamento & purificação , DNA Viral/sangue , Genoma Viral , Herpesvirus Humano 4/isolamento & purificação , Simplexvirus/isolamento & purificação , Adulto , China/epidemiologia , Infecções por Citomegalovirus/epidemiologia , Infecções por Vírus Epstein-Barr/epidemiologia , Feminino , Voluntários Saudáveis , Herpes Simples/epidemiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Reação em Cadeia da Polimerase , Prevalência , Estudos Soroepidemiológicos , Adulto Jovem
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(3): 813-817, 2017 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-28641641

RESUMO

OBJECTIVE: To investigate the expression of insulin-like growth factor binding protein 7 (IGFBP7 ) gene in multiple myeloma cell line U266, and study the effect of 5-aza-2'-deoxycytidine (5-aza-dc) on proliferation of U266 cells. METHODS: multiple myeloma cell line U266 was cultured in vitro. The bone marrow mononuclear cells from healthy persons(N-BMMNC) were collected and used as normal controls. The IGFBP7 mRNA expression of U266 cells and N-BMMNC were detected by real-time fluorescence quantitative PCR, the DNA methylation status of the IGFBP7 CpG island was measured by using methylation-specific PCR(MSP). The different concentrations of 5-aza-dc (5 µmol/L, 10 µmol/L, 20 µmol/L) were used to treat U266 cells for 48 hours, the RT-PCR and Western blot were used to detect the effect of IGFBP7 mRNA and protein expressions, the cell growth curve and Annexin V/PI were analyzed by flow cytometry. RESULTS: As compared with normal BMMNC, the lower expression of IGFBP7 gene was found in U266 cells, the obvious hypermethylation of the CpG island in the IGFBP7 promoter was observed. After treatment of U266 treating with different concentrations of 5-aza-dc, the IGFBP7 mRNA expression was up-regulated dose-dependently(P<0.05), the U266 cells grew slowly and apoptosis rates were enhanced dose-dependently. CONCLUSION: As the hypermethylalion of CpG island in IGFBP7 promoter is a frequent event in lower expression of IGFBP7 gene in U226 cells, the 5-aza-dc can up-regulate the expression of IGFBP7 , and can inhibit cell proliferation through induction of cell apoptosis and arrest of cell cycle.


Assuntos
Metilação de DNA , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Mieloma Múltiplo/genética , Linhagem Celular Tumoral , Proliferação de Células , Ilhas de CpG , Humanos , RNA Mensageiro/metabolismo
11.
Reprod Biol Endocrinol ; 15(1): 39, 2017 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-28545515

RESUMO

BACKGROUND: Previous studies examining associations between subclinical hypothyroidism (SCH) with in vitro fertilization (IVF) outcome indicate some benefits of levothyroxine (LT4) treatment. But IVF outcomes in treated SCH women whose serum Thyroid Stimulating Hormone (TSH) concentration did and did not exceed 2.5 mIU/L before the IVF cycle has not been studied thoroughly. METHODS: In this study, we performed a prospective cohort study with 270 treated subclinical hypothyroidism patients undergoing their first IVF retrieval cycle at a single cite. RESULTS: SCH in women receiving LT4 replacement with a basal TSH level between 0.2-2.5mIU/L displayed a similar rate of clinical pregnancy (47.4% vs 38.7%, P = .436), miscarriage (7.4% vs 16.7%, P = .379) and live birth (43.9% vs 32.3%, P = .288) compared to women with a basal TSH level between 2.5-4.2 mIU/L. CONCLUSION: Strictly controlled TSH (less than 2.5 mIU/L) before IVF may have no effect on the pregnancy rate in LT4 treated SCH women.


Assuntos
Fertilização In Vitro , Hipotireoidismo/tratamento farmacológico , Infertilidade Feminina/terapia , Resultado da Gravidez , Tiroxina/uso terapêutico , Adulto , Doenças Assintomáticas , Feminino , Fertilização In Vitro/estatística & dados numéricos , Terapia de Reposição Hormonal , Humanos , Hipotireoidismo/complicações , Hipotireoidismo/epidemiologia , Infertilidade Feminina/epidemiologia , Masculino , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Taxa de Gravidez , Testes de Função Tireóidea , Resultado do Tratamento
12.
Fish Shellfish Immunol ; 66: 345-353, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28476676

RESUMO

Streptococcus agalactiae (S. agalactiae) is an important fish pathogen, which has received more attention in the past decade due to the increasing economic losses in the tilapia industry worldwide. As existing effective vaccines of S. agalactiae in fish have obvious disadvantage, to select immunoprotective antigens and package materials would undoubtedly contribute to the development of novel oral vaccines. In the present study, surface immunogenic protein (sip) was selected from the S. agalactiae serovar I a genomes as immunogenic protein in DNA vaccine form with cationic chitosan and biodegradable and biocompatible PLGA. The pcSip plasmid in cationic-PLGA was successfully expressed in tissues of immunized tilapia and the immunogenicity was assessed in tilapia challenge model. A significant increase was observed in the cytokine levels of IL-1ß, TNF-α, CC1, CC2 in spleen and kidney tissues. Furthermore, immunized tilapia conferred different levels of protection against challenge with a lethal dose of highly virulent serovar I a S. agalactiae. Our results indicated that the pcSip plasmid in cationic-PLGA induced high level of antibodies and protection against S. agalactiae infection, could be effective oral DNA vaccine candidates.


Assuntos
Vacinas Bacterianas/imunologia , Doenças dos Peixes/prevenção & controle , Imunidade Inata , Imunogenicidade da Vacina , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae/imunologia , Tilápia , Animais , Quitosana/metabolismo , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Genes Bacterianos/imunologia , Ácido Láctico/química , Microesferas , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Distribuição Aleatória , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/prevenção & controle , Streptococcus agalactiae/genética , Distribuição Tecidual , Vacinas de DNA/imunologia
13.
Int J Mol Sci ; 17(3): 277, 2016 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-26927064

RESUMO

Streptococcus agalactiae is an important human and animal pathogen. To better understand the genetic features and evolution of S. agalactiae, multiple factors influencing synonymous codon usage patterns in S. agalactiae were analyzed in this study. A- and U-ending rich codons were used in S. agalactiae function genes through the overall codon usage analysis, indicating that Adenine (A)/Thymine (T) compositional constraints might contribute an important role to the synonymous codon usage pattern. The GC3% against the effective number of codon (ENC) value suggested that translational selection was the important factor for codon bias in the microorganism. Principal component analysis (PCA) showed that (i) mutational pressure was the most important factor in shaping codon usage of all open reading frames (ORFs) in the S. agalactiae genome; (ii) strand specific mutational bias was not capable of influencing the codon usage bias in the leading and lagging strands; and (iii) gene length was not the important factor in synonymous codon usage pattern in this organism. Additionally, the high correlation between tRNA adaptation index (tAI) value and codon adaptation index (CAI), frequency of optimal codons (Fop) value, reinforced the role of natural selection for efficient translation in S. agalactiae. Comparison of synonymous codon usage pattern between S. agalactiae and susceptible hosts (human and tilapia) showed that synonymous codon usage of S. agalactiae was independent of the synonymous codon usage of susceptible hosts. The study of codon usage in S. agalactiae may provide evidence about the molecular evolution of the bacterium and a greater understanding of evolutionary relationships between S. agalactiae and its hosts.


Assuntos
Códon/genética , Evolução Molecular , Seleção Genética , Streptococcus agalactiae/genética , Composição de Bases , Genoma Bacteriano , RNA de Transferência/genética
14.
J Med Virol ; 88(5): 859-70, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26426373

RESUMO

Human cytomegalovirus (HCMV) is the leading infectious cause of birth defects, and may lead to severe or lethal diseases in immunocompromised individuals. Several HCMV strains have been identified and widely applied in research, but no isolate from China has been characterized. In the present study, we isolated, characterized and sequenced the first Chinese HCMV clinical strain Han, and constructed the novel and functional HCMV infectious clone Han-BAC-2311. HCMV Han was isolated from the urine sample of a Chinese infant with multiple developmental disorders. It expresses HCMV specific proteins and contains a representative HCMV genome with minor differences compared to other strains. By homologous recombination using mini-F derived BAC vector pUS-F6, the infectious clone Han-BAC-2311 was constructed containing representative viral genes across the HCMV genome. The insertion site and orientation of BAC sequence were confirmed by restriction enzyme digestion and Southern blotting. The reconstituted recombinant virus HanBAC-2311 expresses typical viral proteins with the same pattern as that of wild-type Han, and also displayed a similar growth kinetics to wild-type Han. The identification of the first clinical HCMV strain in China and the construction of its infectious clone will greatly facilitate the pathogenesis studies and vaccine development in China.


Assuntos
Cromossomos Artificiais Bacterianos , Clonagem Molecular , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Grupo com Ancestrais do Continente Asiático , China , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/virologia , Feminino , Perfilação da Expressão Gênica , Humanos , Lactente , Recém-Nascido , Análise de Sequência de DNA , Urina/virologia , Proteínas Virais/biossíntese
15.
Mol Cell Biochem ; 406(1-2): 217-25, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25963667

RESUMO

It is well known that exercise training exhibits renal protective effects in animal models of hypertension and chronic renal failure. However, the mechanisms regulating these effects of exercise training remain unclear. This study aimed to investigate the role of mitochondrial function in exercise-induced attenuation of renal injury in spontaneously hypertensive rats (SHR). The adult male SHR and age-matched normotensive Wistar-Kyoto rats (WKY) were given moderate-intensity exercise for 12 weeks or treated with MitoQ10 for 8 weeks. In this work, exercise training in SHR reduced blood pressure, and effectively attenuated renal dysfunction, marked by reduced creatinine excretion, albuminuria, blood urea nitrogen, and glomerular sclerosis. Exercise training in SHR reduced MDA levels in plasma and kidneys and suppressed formation of 3-nitrotyrosine in kidneys. Exercise training suppressed mitochondrial ROS and [Formula: see text] formation, enhanced ATP formation, reduced mitochondrial swelling, and restored electron transport chain enzyme activity in kidneys of SHR. Furthermore, exercise training upregulated protein expression of uncoupling protein 2 and manganese superoxide dismutase in kidneys of SHR. In addition, treatment with mitochondria-targeted antioxidant MitoQ10 exhibited similar renal protective effects in SHR. In conclusion, chronic aerobic exercise training preserved mitochondrial function and abated oxidative stress in the kidneys of SHR, which may in part explain the protective effect of exercise on renal function and structure in hypertensive individuals.


Assuntos
Hipertensão/fisiopatologia , Rim/fisiopatologia , Mitocôndrias/metabolismo , Insuficiência Renal/terapia , Animais , Pressão Sanguínea , Terapia por Exercício , Hipertensão/terapia , Masculino , Malondialdeído/sangue , Estresse Oxidativo , Condicionamento Físico Animal , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Insuficiência Renal/fisiopatologia
16.
Eur J Pharmacol ; 741: 186-94, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25160740

RESUMO

The aim of present work was to investigate the underlying mechanism of vasculature-protecting effects of exercise training in aged rats. Experiment 1: aged rats were given moderate-intensity exercise for 12 weeks. Exercise training suppressed advanced glycation evidenced by reduced activity of aldose reductase, increased activity of glyoxalase 1, reduced levels of methylglyoxal and N(ε)-(carboxymethyl) lysine, and decreased expression of receptor for advanced glycation end products (RAGE) in aged aortas. Experiment 2: aged rats were given moderate-intensity exercise for 12 weeks or treated with FPS-ZM1, an inhibitor of RAGE. Exercise training attenuated aortic stiffening with age marked by reduced collagen levels, increased elastin levels and reduced pulse wave velocity (PWV), and prevented aging-related endothelial dysfunction marked by restored endothelium-mediated vascular relaxation of aortas in response to acetylcholine. Exercise training in aging aortas reduced formation of malondialdehyde, 3-nitrotyrosin and reactive oxygen species, increased GSH/GSSG ratio, suppressed activation of NFκB, and reduced levels of IL-6 and chemokine (C-C motif) ligand 2. Similar effects were demonstrated in aged rats treated with FPS-ZM1. Collectively, exercise suppressed advanced glycation in the aortas of aged rats, which, at least in part, explained the vasculature-protecting effects of exercise training in aged population.


Assuntos
Envelhecimento/metabolismo , Aorta Torácica/metabolismo , Benzamidas/farmacologia , Endotélio Vascular/metabolismo , Condicionamento Físico Animal/fisiologia , Receptores Imunológicos/metabolismo , Envelhecimento/efeitos dos fármacos , Animais , Aorta Torácica/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Masculino , Técnicas de Cultura de Órgãos , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos F344 , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/antagonistas & inibidores
17.
Cardiovasc Pathol ; 23(5): 298-305, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25087597

RESUMO

INTRODUCTION: It is well known that exercise alleviates aortic remodeling and preserves endothelial function in spontaneously hypertensive rats (SHRs). However, the underlying molecular mechanism remains unclear. This study aimed to investigate the role of renin-angiotensin system (RAS) components in exercise-induced attenuation of aortic remodeling and improvement of endothelial function in an animal model of human essential hypertension. METHODS: The 10-week-old male SHR and age-matched normotensive Wistar-Kyoto rats were given moderate-intensity exercise for 12weeks (four groups, n=80-86 in each group). RESULTS: In this work, exercise training reduced blood pressure and effectively attenuated aortic remodeling, marked by a reduction in aortic weight/length, wall thickness, and aortic levels of elastin and hydroxyproline, and improved endothelium-mediated vascular relaxations of aortas in response to acetylcholine. Exercise training in SHR reduced angiotensin II (AngII) levels and enhanced Ang-(1-7) levels in aortas. Exercise training in SHR suppressed aortic angiotensin-converting enzyme (ACE) and AngII type 1 receptor (AT1R) messenger RNA (mRNA) levels and protein expression and up-regulated ACE2, AngII type 2 receptor, and Mas mRNA levels and protein expression. In addition, exercise training in SHR increased levels of microRNA-27a (targeting ACE) and microRNA-155 (targeting AT1R) and decreased levels of microRNA-143 (targeting ACE2) in the aortas. CONCLUSION: Chronic aerobic exercise training improved RAS balance in the aortas, which may in part explain the protective effect of exercise on aortic function and structure. SUMMARY: Chronic aerobic exercise training improved RAS balance in the aortas, which may explain the protective effect of exercise on aortic function and structure, at least in part.


Assuntos
Aorta/metabolismo , Endotélio Vascular/metabolismo , Hipertensão/fisiopatologia , Condicionamento Físico Animal/fisiologia , Sistema Renina-Angiotensina/fisiologia , Remodelação Vascular/fisiologia , Animais , Aorta/patologia , Western Blotting , Hipertensão Essencial , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Reação em Cadeia da Polimerase em Tempo Real
18.
Exp Gerontol ; 56: 37-44, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24607516

RESUMO

Aging leads to large vessel arterial stiffening and endothelial dysfunction, which are important determinants of cardiovascular risk. The aim of present work was to assess the effects of chronic aerobic exercise training on aortic stiffening and endothelial dysfunction in aged rats and investigate the underlying mechanism about mitochondrial function. Chronic aerobic exercise training attenuated aortic stiffening with age marked by reduced collagen concentration, increased elastin concentration and reduced pulse wave velocity (PWV), and prevented aging-related endothelial dysfunction marked by improved endothelium-mediated vascular relaxation of aortas in response to acetylcholine. Chronic aerobic exercise training abated oxidative stress and nitrosative stress in aortas of aged rats. More importantly, we found that chronic aerobic exercise training in old rats preserved aortic mitochondrial function marked by reduced reactive oxygen species (ROS) formation and mitochondrial swelling, increased ATP formation and mitochondrial DNA content, and restored activities of complexes I and III and electron-coupling capacity between complexes I and III and between complexes II and III. In addition, it was found that chronic aerobic exercise training in old rats enhanced protein expression of uncoupling protein 2 (UCP-2), peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), manganese superoxide dismutase (Mn-SOD), aldehyde dehydrogenase 2 (ALDH-2), prohibitin (PHB) and AMP-activated kinase (AMPK) phosphorylation in aortas. In conclusion, chronic aerobic exercise training preserved mitochondrial function in aortas, which, at least in part, explained the aorta-protecting effects of exercise training in aging.


Assuntos
Envelhecimento/metabolismo , Aorta Torácica/metabolismo , Endotélio Vascular/metabolismo , Metabolismo Energético , Mitocôndrias/metabolismo , Esforço Físico , Doenças Vasculares/prevenção & controle , Rigidez Vascular , Trifosfato de Adenosina/metabolismo , Fatores Etários , Envelhecimento/patologia , Animais , Aorta Torácica/patologia , Aorta Torácica/fisiopatologia , DNA Mitocondrial/metabolismo , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Masculino , Mitocôndrias/patologia , Proteínas Mitocondriais/metabolismo , Dilatação Mitocondrial , Estresse Oxidativo , Fatores de Proteção , Ratos Endogâmicos F344 , Espécies Reativas de Oxigênio/metabolismo , Corrida , Fatores de Tempo , Doenças Vasculares/metabolismo , Doenças Vasculares/patologia , Doenças Vasculares/fisiopatologia , Remodelação Vascular , Vasodilatação
19.
Arch Virol ; 159(7): 1841-7, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24519460

RESUMO

In this study, we calculated the relative synonymous codon usage (RSCU) value and the effective number of codons (ENC) value to carry out principal component analysis (PCA) and correlation analysis of the codon usage pattern of the phosphoprotein gene (P gene) of spring viraemia of carp virus (SVCV). The synonymous codon usage pattern in P genes is geography-specific, based on PCA analysis. The high correlation between (G + C)1,2 % and (G + C)3 % suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage and base components in P genes. At least 40 out of 59 synonymous codons are similarly selected in all functional genes within five complete SVCV genomes, and the hosts based on the RSCU data. These results not only provide insight into variations in the codon usage pattern of SVCV but also may help in understanding the processes governing the evolution of SVCV.


Assuntos
Carpas , Códon , Doenças dos Peixes/virologia , Fosfoproteínas/metabolismo , Infecções por Rhabdoviridae/veterinária , Rhabdoviridae/metabolismo , Adaptação Fisiológica/genética , Animais , Regulação Viral da Expressão Gênica/fisiologia , Fosfoproteínas/genética , Filogenia , Rhabdoviridae/genética , Infecções por Rhabdoviridae/virologia , Proteínas Virais/genética , Proteínas Virais/metabolismo
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 21(6): 1496-500, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24370036

RESUMO

The objective of this study was to investigate the effect of the new generation of tyrosine kinase inhibitor flumatinib mesylate on C-MYC, HIF-1α and VEGF in multiple myeloma (MM) cell line U266. Different concentrations (1, 5, 10 µmol/L) of flumatinib mesylate were used to act on U266 cell line for 8, 16 and 24 h, and the expression of C-MYC, and HIF-1α genes was detected by real-time fluorescence-quantitative PCR, the expression of C-MYC, HIF-1α and VEGF was measured by Western blot. The results showed that the gene expression of C-MYC and HIF-1 genes decreased gradually with the increasing of flumatinib mesylate concentration (P < 0.05). At the same concentration of flumatinib mesylate, the expression of C-MYC and HIF-1α gene decreased gradually with prolonging of treatment time with the flumatinib mesylate (P < 0.05). When the flumatinib mesylate acted the U266 cell line for 16 h, the expression of C-MYC, HIF-1α and VEGF decreased gradually with the increasing of flumatinib mesylate concentration (P < 0.05). It is concluded that the flumatinib mesylate can reduce the expression of C-MYC, HIF-1 α and VEGF in U266 cell line in a time- and dose-dependent manners, so flumatinib mesylate may become a new drug for MM therapy.


Assuntos
Aminopiridinas/farmacologia , Benzamidas/farmacologia , Genes myc , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Linhagem Celular Tumoral , Regulação Leucêmica da Expressão Gênica , Humanos
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