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1.
Anticancer Res ; 39(10): 5715-5720, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570472

RESUMO

BACKGROUND/AIM: The PRKCI gene encodes Protein kinase C iota. The overexpression of protein kinase C iota is associated with poor outcomes in patients with gastric and other cancers, but the role of the PRKCI gene in gastric cancer is not fully understood. Thus, we evaluated the clinical significance of PRKCI gene expression in gastric cancer. MATERIALS AND METHODS: PRKCI mRNA expression levels in cancerous tissues and adjacent normal mucosa from 398 patients with gastric cancer were measured. Relationships between PRKCI gene expression and clinicopathological characteristics and outcomes were examined. RESULTS: Overall survival was lower in patients with a high expression of PRKCI than in those with low expression (p=0.016). No other relationships were observed. A high PRKCI expression was found to be an independent prognostic factor (p=0.036, HR=1.44, 95%CI=1.02-2.02). CONCLUSION: PRKCI gene expression in cancerous tissue might be a useful prognostic factor in patients with gastric cancer after gastrectomy.


Assuntos
Expressão Gênica/genética , Isoenzimas/genética , Proteína Quinase C/genética , Neoplasias Gástricas/genética , Gastrectomia/métodos , Mucosa Gástrica/patologia , Humanos , Prognóstico , RNA Mensageiro/genética , Neoplasias Gástricas/patologia
2.
Medicine (Baltimore) ; 98(26): e16029, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261506

RESUMO

BACKGROUND: To study the occurrence and prognosis of acute respiratory distress syndrome (ARDS) using single nucleotide polymorphisms (SNPs) of TNF-α rs1800629, IL-6 rs1800796, and MyD88 rs7744 loci in the TLR4/NF-κB pathway. METHODS: Genotypes were analyzed for TNF-α rs1800629, IL-6 rs1800796, and MyD88 rs7744 loci. Plasma TNF-α and IL-6 levels and MyD88 mRNA expression in peripheral blood mononuclear cells (PBMCs) of 300 ARDS patients and 300 non-ARDS patients (control group) were examined. The patients were followed up for 60 days, and the prognosis outcome was recorded. RESULTS: The TNF-α rs1800629 locus A allele and the IL-6 rs1800796 locus G allele were found to be risk factors for ARDS (adjusted OR = 1.452, 95% CI: 1.211-1.689, P < .001 and adjusted OR = 1.205, 95% CI: 1.058-1.358, P = .005, respectively). The G allele at MyD88 rs7744 locus was a protective factor against ARDS (adjusted OR = 0.748, 95% CI: 0.631-0.876, P < .001). Compared with the other groups, homozygotes for TNF-α rs1800629, IL-6 rs1800796, and MyD88 rs7744 loci had higher expression levels, of which homozygotes for TNF-α rs1800629 and IL-6 rs1800796 loci had lower 60-day survival rates, while MyD88 rs7744 locus homozygotes had a higher 60-day survival rate. CONCLUSION: The effect of TNF-α rs1800629, IL-6 rs1800796, and MyD88 rs7744 SNPs on gene expression level is a likely cause of ARDS occurrence and poor prognosis.


Assuntos
NF-kappa B/genética , Polimorfismo de Nucleotídeo Único , Síndrome do Desconforto Respiratório do Adulto/genética , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Biomarcadores/sangue , Feminino , Expressão Gênica/genética , Humanos , Interleucina-6/sangue , Interleucina-6/genética , Masculino , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/sangue , Fator 88 de Diferenciação Mieloide/genética , NF-kappa B/sangue , Prognóstico , RNA Mensageiro/sangue , Síndrome do Desconforto Respiratório do Adulto/sangue , Síndrome do Desconforto Respiratório do Adulto/diagnóstico , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Transdução de Sinais , Análise de Sobrevida , Receptor 4 Toll-Like/sangue , Fator de Necrose Tumoral alfa/sangue
3.
BMC Plant Biol ; 19(1): 282, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31248374

RESUMO

BACKGROUND: Heavy metal toxicity has become a major threat to sustainable crop production worldwide. Thus, considerable interest has been placed on deciphering the mechanisms that allow plants to combat heavy metal stress. Strategies to deal with heavy metals are largely focused on detoxification, transport and/or sequestration. The P1B subfamily of the Heavy Metal-transporting P-type ATPases (HMAs) was shown to play a crucial role in the uptake and translocation of heavy metals in plants. Here, we report the locus-specific expression changes in the rice HMA genes together with several low-copy cellular genes and transposable elements upon the heavy metal treatment and monitored the transgenerational inheritance of the altered expression states. We reveal that plants cope with heavy metal stress by making heritable changes in gene expression and further determined gene-specific responses to heavy metal stress. RESULTS: We found most HMA genes were upregulated in response to heavy metal stress, and furthermore found evidence of transgenerational memory via changes in gene regulation even after the removal of heavy metals. To explore whether DNA methylation was also altered in response to the heavy metal stress, we selected a Tos17 retrotransposon for bisulfite sequencing and studied its methylation state across three generations. We found the DNA methylation state of Tos17 was altered in response to the heavy metal stress and showed transgenerational inheritance. CONCLUSIONS: Collectively, the present study elucidates heritable changes in gene expression and DNA methylation in rice upon exposure to heavy metal stress and discusses implications of this knowledge in breeding for heavy metal tolerant crops.


Assuntos
Adenosina Trifosfatases/genética , Epigênese Genética/genética , Expressão Gênica/genética , Metais Pesados/efeitos adversos , Oryza/genética , Proteínas de Plantas/genética , Poluentes do Solo/efeitos adversos , Adenosina Trifosfatases/metabolismo , Oryza/enzimologia , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Estresse Fisiológico
4.
Cancer Sci ; 110(8): 2629-2642, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31215104

RESUMO

Multigenerational adverse effects from the environment such as nutrition and chemicals are among important concerns in environmental health issues. Previously, we have found that arsenite exposure of only F0 females during their pregnancy increases hepatic tumors in the F2 males in C3H mice. In the current study, we investigated the association of DNA methylation with the hepatic tumor increase in the F2 males of the arsenite group. Reduced-representation bisulfite sequencing analysis newly identified that DNA methylation levels of regions around the transcriptional start sites of Tmem54 and Cd74 were decreased and the expression of these genes were significantly increased in the hepatic tumors of F2 males of the arsenite group. The associations between DNA methylation in these regions and gene expression changes were confirmed by treatment of murine hepatoma cell lines and hepatic stellate cell line with 5-aza-2'-deoxycytidine. Overexpression of Cd74 in Hepa1c1c7 cells increased Trib3 expression and suppressed the expression of tumor suppressor genes Id3 and Atoh8. Human database analysis using the Cancer Genome Atlas indicated that TMEM54, CD74, and TRIB3 were significantly increased and that ATOH8 was decreased in hepatocellular carcinoma. The data also showed that high expression of TMEM54 and TRIB3 and low expression of ATOH8 were associated with poor survival. These results suggested that an increase in Tmem54 and Cd74 expression via DNA methylation reduction was involved in the tumor increase in the F2 male offspring by gestational arsenite exposure of F0 females. This study also suggested that genes downstream of Cd74 were involved in tumorigenesis.


Assuntos
Arsenitos/efeitos adversos , Carcinoma Hepatocelular/genética , Metilação de DNA/genética , Neoplasias Hepáticas/genética , Animais , Antígenos de Diferenciação de Linfócitos B/genética , Antígenos de Neoplasias/genética , Carcinoma Hepatocelular/induzido quimicamente , Linhagem Celular Tumoral , Feminino , Expressão Gênica/genética , Antígenos de Histocompatibilidade Classe II/genética , Neoplasias Hepáticas/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C3H , Gravidez
5.
Nat Commun ; 10(1): 2489, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171815

RESUMO

Down syndrome (DS), trisomy of human chromosome 21 (Hsa21), results in a broad range of phenotypes. A recent study reported that DS cells show genome-wide transcriptional changes in which up- or down-regulated genes are clustered in gene expression dysregulation domains (GEDDs). GEDDs were also reported in fibroblasts derived from a DS mouse model duplicated for some Hsa21-orthologous genes, indicating cross-species conservation of this phenomenon. Here we investigate GEDDs using the Dp1Tyb mouse model of DS, which is duplicated for the entire Hsa21-orthologous region of mouse chromosome 16. Our statistical analysis shows that GEDDs are present both in DS cells and in Dp1Tyb mouse fibroblasts and hippocampus. However, we find that GEDDs do not depend on the DS genotype but occur whenever gene expression changes. We conclude that GEDDs are not a specific feature of DS but instead result from the clustering of co-regulated genes, a function of mammalian genome organisation.


Assuntos
Síndrome de Down/genética , Fibroblastos/metabolismo , Expressão Gênica/genética , Hipocampo/metabolismo , Animais , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Genoma , Genótipo , Camundongos , Família Multigênica , Fenótipo
6.
Anim Sci J ; 90(8): 1042-1049, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31237073

RESUMO

Glycogen synthase kinase beta (GSK3ß) plays an important role in skeletal muscle growth, regeneration, and repair. However, the mechanism of GSK3ß regulating MyHC2a expression is currently not clear. In this study, GSK3ß inhibition promoted skeletal muscle satellite cells (SMSCs) differentiation and increased expression of MyoD, MyoG, MyHC1, and MyHC2a genes. Then we cloned approximately 1.1 kb of goat MyHC2a gene promoter. The deletion fragment (-514/+55) of MyHC2a promoter exhibited the highest level of promoter activity, and a NFATc2 element in this region was responsible for MyHC2a promoter activity. Treatment of SB216713 significantly decreased the transcriptional activity of the fragment (-514/+55). Furthermore, GSK3ß inhibition had no effect on the luciferase activity of MyHC2a promoter after mutating the NFATc2-binding site. These results demonstrated that GSK3ß inhibition promoted SMSCs differentiation and regulated the MyHC2a gene expression through NFATc2 in goat-differentiated SMSCs.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/genética , Expressão Gênica/genética , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta/fisiologia , Músculo Esquelético/citologia , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Células Satélites de Músculo Esquelético/metabolismo , Animais , Diferenciação Celular/genética , Células Cultivadas , Feminino , Cabras , Luciferases/metabolismo , Fatores de Transcrição NFATC
7.
Microb Pathog ; 132: 335-342, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31100407

RESUMO

The aim of this study was to evaluate the effects of Bacillus subtilis and Bacillus atrophaeus on Galleria mellonella immunity challenged by Candida albicans. Firstly, we analyzed the susceptibility of G. mellonella to bacilli (vegetative and sporulating forms). It was found that both vegetative and sporulating forms were not pathogenic to G. mellonella at a concentration of 1 × 104 cells/larva. Next, larvae were pretreated with two species of Bacillus, in the vegetative and sporulating forms, and then challenged with C. albicans. In addition, the gene expression of antimicrobial peptides (AMPs) such as Gallerimycin, Gloverin, Cecropin-D and Galiomicin was investigated. Survival rates increased in the Bacillus treated larvae compared with control larvae inoculated with C. albicans only. Cells and spores of Bacillus spp. upregulated Gloverin, Galiomicin and Gallerimycin genes in relation to the control group (PBS + PBS). When these larvae were infected with C. albicans, the group pretreated with spores of B. atrophaeus and B. subtilis showed a greater increase in expression of Galiomycin (49.08-fold and 13.50-fold) and Gallerimycin (27.88-fold and 68.15-fold), respectively, compared to the group infected with C. albicans only (p = 0.0001). After that, we investigated the effects of B. subtilis and B. atrophaeus on immune system of G. mellonella evaluating the number of hemocytes, quantification of melanization, cocoon formation and colony forming units (CFU) count. Hemocyte count increased in response to stimulation by Bacillus, and a higher increase was achieved when larvae were inoculated with B. subtilis spores (p = 0.0011). In the melanization assay, all groups tested demonstrated lower production of melanin compared to that in the phosphate-buffered saline (PBS) group. In addition, full cocoon formation was observed in all groups analyzed, which corresponded to a healthier wax worm. Hemolymph culture revealed higher growth of B. atrophaeus and B. subtilis in the groups inoculated with spores. We concluded that spores and cells of B. atrophaeus and B. subtilis stimulated the immune system of G. mellonella larvae and protected them of C. albicans infection.


Assuntos
Bacillus/fisiologia , Candida albicans/patogenicidade , Interações entre Hospedeiro e Microrganismos/imunologia , Imunidade , Lepidópteros/imunologia , Alcaloides/genética , Alcaloides/metabolismo , Alcaloides/farmacologia , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bacillus subtilis/fisiologia , Contagem de Colônia Microbiana , Defensinas/genética , Defensinas/metabolismo , Defensinas/farmacologia , Modelos Animais de Doenças , Expressão Gênica/genética , Hemócitos/imunologia , Hemócitos/metabolismo , Hemolinfa , Interações entre Hospedeiro e Microrganismos/genética , Sistema Imunitário , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/farmacologia , Larva/imunologia , Larva/microbiologia , Lepidópteros/genética , Lepidópteros/microbiologia , Proteínas/genética , Proteínas/metabolismo , Proteínas/farmacologia , Quinolinas/metabolismo , Quinolinas/farmacologia , Esporos Bacterianos , Taxa de Sobrevida
8.
J Mol Histol ; 50(3): 239-251, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31049798

RESUMO

Reduced expression of endothelial nitric oxide synthase (eNOS) is a hallmark of endothelial dysfunction in diabetes, which predisposes diabetic patients to numerous cardiovascular complications including blunted angiogenesis. The Krüppel-like factor (KLF) five has been implicated as a central regulator of cardiovascular remodeling, but its role in endothelial cells (ECs) remains poorly understood. We show here that expression of endothelial KLF5 was significantly increased in the ECs from mouse diabetes mellitus type 2 (T2DM) model, when compared to non-diabetic or T1DM mouse. KLF5 up-regulation by insulin was dependent on activation of multiple pathways, including mammalian target of rapamycin, oxidative stress and Protein kinase C pathways. Hyperinsulinemia-induced KLF5 inhibited endothelial function and migration, and thereby compromised in vitro and in vivo angiogenesis. Mechanistically, KLF5 acted in concert with the MTA1 coregulator to negatively regulate NOS3 transcription, thereby leading to the diminished eNOS levels in ECs. Conversely, potentiation of cGMP content (the essential downstream effector of eNOS signaling) by pharmacological approaches successfully rescued the endothelial proliferation and in vitro tube formation, in the HUVECs overexpressing the exogenous KLF5. Collectively, the available data suggest that the augmentation of endothelial KLF5 expression by hyperinsulinemia may represent a novel mechanism for negatively regulating eNOS expression, and may thus help to explain for the T2DM-related endothelial dysfunction at the transcriptional level.


Assuntos
Hiperinsulinismo/genética , Fatores de Transcrição Kruppel-Like/genética , Neovascularização Patológica/genética , Óxido Nítrico Sintase Tipo III/genética , Animais , Movimento Celular/genética , Proliferação de Células/genética , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Expressão Gênica/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Hiperinsulinismo/patologia , Masculino , Camundongos , Estresse Oxidativo/genética , Proteína Quinase C/genética , Transdução de Sinais/genética
9.
BMC Bioinformatics ; 20(1): 229, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060502

RESUMO

BACKGROUND: A key challenge of identifying disease-associated genes is analyzing transcriptomic data in the context of regulatory networks that control cellular processes in order to capture multi-gene interactions and yield mechanistically interpretable results. One existing category of analysis techniques identifies groups of related genes using interaction networks, but these gene sets often comprise tens or hundreds of genes, making experimental follow-up challenging. A more recent category of methods identifies precise gene targets while incorporating systems-level information, but these techniques do not determine whether a gene is a driving source of changes in its network, an important characteristic when looking for potential drug targets. RESULTS: We introduce GeneSurrounder, an analysis method that integrates expression data and network information in a novel procedure to detect genes that are sources of dysregulation on the network. The key idea of our method is to score genes based on the evidence that they influence the dysregulation of their neighbors on the network in a manner that impacts cell function. Applying GeneSurrounder to real expression data, we show that our method is able to identify biologically relevant genes, integrate pathway and expression data, and yield more reproducible results across multiple studies of the same phenotype than competing methods. CONCLUSIONS: Together these findings suggest that GeneSurrounder provides a new avenue for identifying individual genes that can be targeted therapeutically. The key innovation of GeneSurrounder is the combination of pathway network information with gene expression data to determine the degree to which a gene is a source of dysregulation on the network. By prioritizing genes in this way, our method provides insights into disease mechanisms and suggests diagnostic and therapeutic targets. Our method can be used to help biologists select among tens or hundreds of genes for further validation. The implementation in R is available at github.com/sahildshah1/gene-surrounder.


Assuntos
Biologia Computacional/métodos , Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Algoritmos , Humanos
11.
Biomed Res Int ; 2019: 1321287, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016183

RESUMO

SERPINA1 is a member of serine protease inhibitors and is increasingly considered to be a regulator of innate immunity in human and animals. However, the expression and function of SERPINA1 gene in immune defense against viral infection remain unknown in ducks. The full-length du SERPINA1 cDNA sequence was obtained using reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). It contained 1457 nucleotide, including 47-bp 5' UTR, 135-bp 3' UTR, and 1275-bp open reading frame (ORF), and encodes a 424-amino acid protein. Then, the tissue expression profile of du SERPINA1 gene was determined. Real-time quantitative polymerase chain reaction (real-time qPCR) analysis revealed that du SERPINA1 mRNA is ubiquitous in various tissues, but higher expression levels were observed in lung and liver tissues. In addition, the expression pattern was investigated when the ducklings were challenged with duck hepatitis virus 1(DHV-1) and polyriboinosinic polyribocytidylic acid (poly I:C). After DHV-1 injection or poly I:C treatment, du SERPINA1 mRNA was up-regulated in the liver and kidney tissues. However, the peak time in two tissues was not consistent. In kidney, the expression lever of SERPINA1 increased immediately after the treatment while in liver tissue it kept steady until 12 h post-infection. Our results indicate that SERPINA1 has an active role in the antiviral response, and thus improve our understanding of the role of this protein.


Assuntos
Patos/genética , Expressão Gênica/genética , alfa 1-Antitripsina/genética , Regiões 3' não Traduzidas/genética , Regiões 5' não Traduzidas/genética , Sequência de Aminoácidos , Animais , Clonagem Molecular/métodos , DNA Complementar/genética , Vírus da Hepatite do Pato/genética , Rim/fisiologia , Fígado/fisiologia , Fases de Leitura Aberta/genética , Filogenia , RNA Mensageiro/genética , Alinhamento de Sequência , Análise de Sequência de DNA/métodos , Regulação para Cima/genética
12.
Biomed Res Int ; 2019: 1724898, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016185

RESUMO

With the rapid evolution of high-throughput technologies, time series/longitudinal high-throughput experiments have become possible and affordable. However, the development of statistical methods dealing with gene expression profiles across time points has not kept up with the explosion of such data. The feature selection process is of critical importance for longitudinal microarray data. In this study, we proposed aggregating a gene's expression values across time into a single value using the sign average method, thereby degrading a longitudinal feature selection process into a classic one. Regularized logistic regression models with pseudogenes (i.e., the sign average of genes across time as predictors) were then optimized by either the coordinate descent method or the threshold gradient descent regularization method. By applying the proposed methods to simulated data and a traumatic injury dataset, we have demonstrated that the proposed methods, especially for the combination of sign average and threshold gradient descent regularization, outperform other competitive algorithms. To conclude, the proposed methods are highly recommended for studies with the objective of carrying out feature selection for longitudinal gene expression data.


Assuntos
Expressão Gênica/genética , Transcriptoma/genética , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica/métodos , Humanos , Estudos Longitudinais
13.
Arch Virol ; 164(7): 1753-1760, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31025116

RESUMO

The expression of several structural proteins from a wide variety of viruses in heterologous cell culture systems results in the formation of virus-like particles (VLPs). These VLPs structurally resemble the wild-type virus particles and have been used to study viral assembly process and as antigens for diagnosis and/or vaccine development. Tomato blistering mosaic virus (ToBMV) is a tymovirus that has a 6.3-kb positive-sense ssRNA genome. We have employed the baculovirus expression vector system (BEVS) for the production of tymovirus-like particles (tVLPs) in insect cells. Two recombinant baculoviruses containing the ToBMV wild-type coat protein (CP) gene or a modified short amino-terminal deletion (Δ2-24CP) variant were constructed and used to infect insect cells. Both recombinant viruses were able to express ToBMV CP and Δ2-24CP from infected insect cells that self-assembled into tVLPs. Therefore, the N-terminal residues (2-24) of the native ToBMV CP were shown not to be essential for self-assembly of tVLPs. We also constructed a third recombinant baculovirus containing a small sequence coding for the major epitope of the chikungunya virus (CHIKV) envelope protein 2 (E2) replacing the native CP N-terminal 2-24 amino acids. This recombinant virus also produced tVLPs. In summary, ToBMV VLPs can be produced in a baculovirus/insect cell heterologous expression system, and the N-terminal residues 2-24 of the CP are not essential for this assembly, allowing its potential use as a protein carrier that facilitates antigen purification and might be used for diagnosis.


Assuntos
Baculoviridae/genética , Proteínas do Capsídeo/biossíntese , Tymovirus/crescimento & desenvolvimento , Tymovirus/genética , Proteínas do Envelope Viral/biossíntese , Montagem de Vírus/genética , Animais , Proteínas do Capsídeo/genética , Linhagem Celular , Vírus Chikungunya/genética , Expressão Gênica/genética , Lycopersicon esculentum/virologia , Mariposas/citologia , Proteínas do Envelope Viral/genética
14.
Chemosphere ; 226: 687-695, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30959453

RESUMO

Toxic effects of nanoparticles (NPs) on microorganisms have attracted substantial attention; however, there are few reports on whether NPs can affect the secondary metabolism of microbes. To investigate the toxic effects of Al2O3 NPs on cell growth and antibiotic secretion, Streptomyces coelicolor M145 was exposed to Al2O3 NPs with diameters of 30 and 80 nm and bulk Al2O3 at concentrations up to 1000 mg/L. The results indicated that differences in the toxicity of Al2O3 NPs were related to the particle size. In treatment with Al2O3 NPs, the maximum yields of undecylprodigiosin (RED) and actinorhodin (ACT) were 3.7- and 4.6-fold greater than that of the control, respectively, and the initial time of antibiotic production was much shorter. ROS quenching experiment by N-acetylcysteine (NAC) confirmed that ROS were responsible for the increased RED production. From 0 to 72 h, ROS had a significant impact on ACT production; however, after 72 h, the ROS content began to decrease until it disappeared. During ongoing exposure (0-144 h), ACT production continued to increase, indicating that in addition to ROS, nano effect of Al2O3 NPs also played roles in this process. Transcriptional analysis demonstrated that Al2O3 NPs could increase the expression levels of antibiotic biosynthetic genes and two-component systems (TCSs) and inhibit the expression levels of primary metabolic pathways. This study provides a new perspective for understanding the mechanisms of antibiotic production in nature and reveals important implications for exploring other uses of NPs in biomedical applications or regulation of antibiotics in nature.


Assuntos
Antibacterianos/metabolismo , Expressão Gênica/genética , Nanopartículas/química , Streptomyces coelicolor/química
15.
Immunity ; 50(5): 1202-1217.e7, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31027997

RESUMO

Stable changes in chromatin states and gene expression in cells of the immune system form the basis for memory of infections and other challenges. Here, we used naturally occurring cis-regulatory variation in wild-derived inbred mouse strains to explore the mechanisms underlying long-lasting versus transient gene regulation in CD8 T cells responding to acute viral infection. Stably responsive DNA elements were characterized by dramatic and congruent chromatin remodeling events affecting multiple neighboring sites and required distinct transcription factor (TF) binding motifs for their accessibility. Specifically, we found that cooperative recruitment of T-box and Runx family transcription factors to shared targets mediated stable chromatin remodeling upon T cell activation. Our observations provide insights into the molecular mechanisms driving virus-specific CD8 T cell responses and suggest a general mechanism for the formation of transcriptional and epigenetic memory applicable to other immune and non-immune cells.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Montagem e Desmontagem da Cromatina/genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Regulação da Expressão Gênica/genética , Coriomeningite Linfocítica/imunologia , Vírus da Coriomeningite Linfocítica/imunologia , Proteínas com Domínio T/genética , Animais , Linfócitos T CD8-Positivos/virologia , Linhagem Celular , Cromatina/genética , Epigênese Genética/genética , Feminino , Expressão Gênica/genética , Regulação da Expressão Gênica/imunologia , Variação Genética , Memória Imunológica/genética , Memória Imunológica/imunologia , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Coriomeningite Linfocítica/virologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transcrição Genética/genética
16.
Nat Rev Cancer ; 19(5): 255-269, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30962549

RESUMO

Recurrent chromosomal rearrangements leading to the generation of oncogenic fusion proteins are a common feature of many cancers. These aberrations are particularly prevalent in sarcomas and haematopoietic malignancies and frequently involve genes required for chromatin regulation and transcriptional control. In many cases, these fusion proteins are thought to be the primary driver of cancer development, altering chromatin dynamics to initiate oncogenic gene expression programmes. In recent years, mechanistic insights into the underlying molecular functions of a number of these oncogenic fusion proteins have been discovered. These insights have allowed the design of mechanistically anchored therapeutic approaches promising substantial treatment advances. In this Review, we discuss how our understanding of fusion protein function is informing therapeutic innovations and illuminating mechanisms of chromatin and transcriptional regulation in cancer and normal cells.


Assuntos
Cromatina/genética , Neoplasias/genética , Proteínas de Fusão Oncogênica/genética , Animais , Aberrações Cromossômicas , Expressão Gênica/genética , Humanos , Neoplasias/patologia , Transcrição Genética/genética
17.
Curr Protoc Neurosci ; 87(1): e66, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30883041

RESUMO

Advances in design and use of light-sensitive and light-emitting sensors have facilitated observation, measurement, and control of neuronal activities. Viruses are effective vectors for delivery of these valuable research tools to mammalian brains. Recombinant viruses are optimized to mediate regulatable, long-term, and cell-specific gene expression. Here, we describe production methods for three of the most commonly used types of recombinant viruses in neurobiology research: adeno-associated virus (AAV), retrovirus/lentivirus, and glycoprotein-deleted rabies virus. These viral constructs are frequently used for calcium imaging or to deliver neural tracers and optogenetic tools. Popular constructs are readily obtained commercially; however, customized virus production through commercial sources is time consuming and costly. This article aims to provide readers with detailed technical information for rapid production and validation of high-quality viral particles in a laboratory setting while highlighting advantages and limitations of each viral type. © 2019 by John Wiley & Sons, Inc.


Assuntos
Cálcio/metabolismo , Dependovirus/genética , Técnicas de Transferência de Genes , Neuroanatomia , Optogenética , Animais , Expressão Gênica/genética , Vetores Genéticos , Células HEK293 , Humanos , Lentivirus/genética , Optogenética/métodos
18.
Hum Cell ; 32(2): 193-201, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30868406

RESUMO

Bladder cancer (BC) is one of the most common tumors. Metabolic reprogramming is a feature of neoplasia and tumor growth. Understanding the metabolic alterations in bladder cancer may provide new directions for bladder cancer treatment. Sirtuin 1 (SIRT1) is a lysine deacetylase of multiple targets including metabolic regulators. In pancreatic cancer, the loss of SIRT1 is accompanied by a decreased expression of proteins in the glycolysis pathway, such as GLUT1, and cancer cell proliferation. Thus, we hypothesize that SIRT1 may interact with GLUT1 to modulate the proliferation and glycolysis phenotype in bladder cancer. In the present study, the expression of SIRT1 and GLUT1 was upregulated in BC tissues and cell lines and positively correlated in tissue samples. SIRT1 overexpression or GLUT1 overexpression alone was sufficient to promote cell proliferation and glucose uptake in BC cells. EX527, a specific inhibitor of SIRT1, exerted an opposing effect on bladder cancer proliferation and glucose uptake. The effect of EX527 could be partially reversed by GLUT1 overexpression. More importantly, SIRT1 overexpression significantly promoted the transcriptional activity and expression of GLUT1, indicating that SIRT1 increases the transcription activity and expression of GLUT1, therefore, promoting the cell proliferation and glycolysis in BC cells. Our study first reported that SIRT1/GLUT1 axis promotes bladder cancer progression via regulation of glucose uptake.


Assuntos
Expressão Gênica/genética , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Glucose/metabolismo , Sirtuína 1/genética , Sirtuína 1/fisiologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Glicólise/genética , Glicólise/fisiologia , Humanos , Regulação para Cima , Neoplasias da Bexiga Urinária/metabolismo
19.
DNA Cell Biol ; 38(5): 449-456, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30839233

RESUMO

Intracerebral hemorrhage (ICH) represents the most lethal form of stroke. We sought to identify potential genes that might contribute to progression of hypertension-induced spontaneous ICH (HIS-ICH). RNA-sequencing data set of cerebral vessel samples from HIS-ICH mice and normal mice was obtained from the Gene Expression Omnibus. Differential expression genes in HIS-ICH samples were obtained compared with normal samples followed by functional enrichment analysis. What is more, we explored the potential gene coexpression module (GCM) for HIS-ICH progression by using weighted gene coexpression network analysis. We further conducted protein-protein interaction network analysis for genes contained in GCM that was closely correlated with HIS-ICH to disclose their biological interactions. As a result, 554 genes were found to aberrantly express in HIS-ICH mice compared with normal mice, which were mainly associated with cancer-related pathways in addition to some well-known ICH-related pathways. A total of 28 GCMs were obtained, and darkturquoise module that contained 85 genes, which were closely associated with mitochondrion and hydrolase activity, was significantly correlated with HIS-ICH progression. Besides, we identified dense biological interactions among some genes in darkturquoise, such as Psma gene family and Hsp90a gene family. This study should shed new light on HIS-ICH progression and its treatment.


Assuntos
Hemorragia Cerebral/genética , Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Hipertensão/genética , Animais , Progressão da Doença , Perfilação da Expressão Gênica/métodos , Camundongos , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Análise de Sequência de RNA
20.
Am J Chin Med ; 47(2): 477-494, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30909731

RESUMO

Carnosine is an endogenous dipeptide found in the vertebrate skeletal muscles that is usually obtained through the diet. To investigate the mechanism by which carnosine regulates the migration and intravasation of human colorectal cancer (CRC) cells, we used cultured HCT-116 cells as an experimental model in this study. We examined HCT-116 cell migratory and intravasive abilities and expression of epithelial-mesenchymal transition (EMT)-associated molecules and matrix metalloproteinases (MMPs) after carnosine treatment. The results showed that both migration and invasion were inhibited in cells treated with carnosine. We found significant decreases in Twist-1 protein levels and increases in E-cadherin protein levels in HCT-116 cells after carnosine exposure. Although plasminogen activator (uPA) and MMP-9 mRNA and protein levels were decreased, TIMP-1 mRNA and protein levels were increased. Furthermore, the cytosolic levels of phosphorylated I κ B (p-I κ B) and NF- κ B DNA-binding activity were reduced after carnosine treatment. These results indicate that carnosine inhibits the migration and intravasation of human CRC cells. The regulatory mechanism may occur by suppressing NF- κ B activity and modulating MMP and EMT-related gene expression in HCT-116 cells.


Assuntos
Carnosina/farmacologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Caderinas/genética , Caderinas/metabolismo , Neoplasias Colorretais/irrigação sanguínea , Depressão Química , Células HCT116 , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Invasividade Neoplásica/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína 1 Relacionada a Twist/genética , Proteína 1 Relacionada a Twist/metabolismo
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