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1.
Int J Mol Sci ; 24(11)2023 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-37298067

RESUMEN

Klebsiella pneumoniae is a common human commensal and opportunistic pathogen. In recent years, the clinical isolation and resistance rates of K. pneumoniae have shown a yearly increase, leading to a special interest in mobile genetic elements. Prophages are a representative class of mobile genetic elements that can carry host-friendly genes, transfer horizontally between strains, and coevolve with the host's genome. In this study, we identified 15,946 prophages from the genomes of 1437 fully assembled K. pneumoniae deposited in the NCBI database, with 9755 prophages on chromosomes and 6191 prophages on plasmids. We found prophages to be notably diverse and widely disseminated in the K. pneumoniae genomes. The K. pneumoniae prophages encoded multiple putative virulence factors and antibiotic resistance genes. The comparison of strain types with prophage types suggests that the two may be related. The differences in GC content between the same type of prophages and the genomic region in which they were located indicates the alien properties of the prophages. The overall distribution of GC content suggests that prophages integrated on chromosomes and plasmids may have different evolutionary characteristics. These results suggest a high prevalence of prophages in the K. pneumoniae genome and highlight the effect of prophages on strain characterization.


Asunto(s)
Klebsiella pneumoniae , Profagos , Humanos , Profagos/genética , Klebsiella pneumoniae/genética , Plásmidos/genética , Genómica , Factores de Virulencia/genética , Antibacterianos , Genoma Bacteriano
2.
Int J Mol Sci ; 23(9)2022 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-35562911

RESUMEN

Vibrio cincinnatiensis is a poorly understood pathogenic Vibrio species, and the underlying mechanisms of its genetic diversity, genomic plasticity, evolutionary dynamics, and pathogenicity have not yet been comprehensively investigated. Here, a comparative genomic analysis of V. cincinnatiensis was constructed. The open pan-genome with a flexible gene repertoire exhibited genetic diversity. The genomic plasticity and stability were characterized by the determinations of diverse mobile genetic elements (MGEs) and barriers to horizontal gene transfer (HGT), respectively. Evolutionary divergences were exhibited by the difference in functional enrichment and selective pressure between the different components of the pan-genome. The evolution on the Chr I and Chr II core genomes was mainly driven by purifying selection. Predicted essential genes in V. cincinnatiensis were mainly found in the core gene families on Chr I and were subject to stronger evolutionary constraints. We identified diverse virulence-related elements, including the gene clusters involved in encoding flagella, secretion systems, several pili, and scattered virulence genes. Our results indicated the pathogenic potential of V. cincinnatiensis and highlighted that HGT events from other Vibrio species promoted pathogenicity. This pan-genome study provides comprehensive insights into this poorly understood species from the genomic perspective.


Asunto(s)
Genoma Bacteriano , Vibrio , Transferencia de Gen Horizontal , Variación Genética , Genómica/métodos , Filogenia , Vibrio/genética
4.
Genome ; 59(12): 1063-1075, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27696900

RESUMEN

Stenotrophomonas maltophilia is a global multidrug-resistant human opportunistic pathogen in clinical environments. Stenotrophomonas maltophilia is also ubiquitous in aqueous environments, soil, and plants. Various molecular typing methods have revealed that S. maltophilia exhibits high levels of phenotypic and genotypic diversity. However, information regarding the genomic diversity within S. maltophilia and the corresponding genetic mechanisms resulting in said diversity remain scarce. The genome sequences of 17 S. maltophilia strains were selected to investigate the mechanisms contributing to genetic diversity at the genome level. The core and large pan-genomes of the species were first estimated, resulting in a large, open pan-genome. A species phylogeny was also reconstructed based on 344 orthologous genes with one copy per genome, and the contribution of four evolutionary mechanisms to the species genome diversity was quantified: 15%-35% of the genes showed evidence for recombination, 0%-25% of the genes in one genome were likely gained, 0%-44% of the genes in some genomes were likely lost, and less than 0.3% of the genes in a genome were under positive selection pressures. We observed that, among the four main mechanisms, homologous recombination plays a key role in maintaining diversity in S. maltophilia. In this study, we provide an overview of evolution in S. maltophilia to provide a better understanding of its evolutionary dynamics and its relationship with genome diversity.


Asunto(s)
Flujo Génico , Recombinación Genética , Selección Genética , Stenotrophomonas maltophilia/genética , Proteínas Bacterianas/genética , Evolución Molecular , Variación Genética , Genoma Bacteriano , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Infecciones Oportunistas/microbiología , Filogenia , Stenotrophomonas maltophilia/clasificación
5.
BMC Genomics ; 15: 1110, 2014 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-25511561

RESUMEN

BACKGROUND: During the past two decades, avian influenza A H9N2 viruses have spread geographically and ecologically in China. Other than its current role in causing outbreaks in poultry and sporadic human infections by direct transmission, H9N2 virus could also serve as an progenitor for novel human avian influenza viruses including H5N1, H7N9 and H10N8. Hence, H9N2 virus is becoming a notable threat to public health. However, despite multiple lineages and genotypes that were detected by previous studies, the migration dynamics of the H9N2 virus in China is unclear. Increasing such knowledge would help us better prevent and control H9N2 as well as other future potentially threatening viruses from spreading across China. The objectives of this study were to determine the source, migration patterns, and the demography history of avian influenza A H9N2 virus that circulated in China. RESULTS: Using Bayesian phylogeography framework, we showed that the H9N2 virus in mainland China may have originated from the Hong Kong Special Administrative Region (SAR). Southern China, most likely the Guangdong province acts as the primary epicentre for multiple H9N2 strains spreading across the whole country, and eastern China, most likely the Jiangsu province, acts as an important secondary source to seed outbreaks. Our demography inference suggests that during the long-term migration process, H9N2 evolved into multiple diverse lineages and then experienced a selective sweep, which reduced its genetic diversity. Importantly, such a selective sweep may pose a greater threat to public health because novel strains confer higher fitness advantages than strains being replaced and could generate new viruses through reassortment. CONCLUSION: Our analyses indicate that migratory birds, poultry trade and transportation have all contributed to the spreading of the H9N2 virus in China. The ongoing migration and evolution of H9N2, which poses a constant threat to the human population, highlights the need for a more comprehensive surveillance of wild birds and for the enhancement of biosafety for China's poultry industry.


Asunto(s)
Geografía , Subtipo H9N2 del Virus de la Influenza A/aislamiento & purificación , Filogenia , Animales , Teorema de Bayes , China , Humanos , Subtipo H9N2 del Virus de la Influenza A/clasificación , Análisis Espacio-Temporal
6.
Theor Biol Med Model ; 10: 18, 2013 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-23497207

RESUMEN

BACKGROUND: Toll-like receptor 9 (TLR9) recognises unmethylated CpG DNA and activates a signalling cascade, leading to the production of inflammatory cytokines such as TNF-α, IL-1, IL-6 and IL-12 via the adaptor protein MyD88. However, the specific sequence and structural requirements of the CpG DNA for the recognition of and binding to TLR9 are unknown. Moreover, the 3D structures of TLR9 and the TLR9-ODN complex have not been determined. In this study, we propose a reliable model of the interaction of the TLR9 ECD with CpG ODN using bioinformatics tools. RESULTS: The three-dimensional structures of two TLR9 ECD-CpG ODN complexes were constructed using a homology modelling and docking strategy. Based on the models of these complexes, the TLR9 ECD-CpG ODN interaction patterns were calculated. The results showed that the interface between the human TLR9 and the CpG ODN molecule is geometrically complementary. The computed molecular interactions indicated that LRR11 is the main region of TLR9 that binds to CpG ODN and that five positively charged residues within LRR11 are involved in the binding of the TLR9 ECD to the CpG ODN. Observations in the close-up view of these interactions indicated that these five positively charged residues contribute differently to the binding region within the TLR9 ECD-CpG ODN complex. 337Arg and 338Lys reside in the binding sites of ODN, forming hydrogen bonds and direct contacts with the CpG ODN, whereas 347Lys, 348Arg, and 353His do not directly contact the CpG ODN. These results are in agreement with previously reported experimental data. CONCLUSION: In this study, we present two structural models for the human and mouse TLR9 ECD in a complex with CpG ODN. Some features predicted by this model are consistent with previously reported experimental data. This complex model may lead to a better understanding of the function of TLR9 and its interaction with CpG ODN and will improve our understanding of TLR9-ligand interaction in general.


Asunto(s)
Simulación por Computador , Oligodesoxirribonucleótidos/metabolismo , Receptor Toll-Like 9/metabolismo , Aminoácidos/metabolismo , ADN/metabolismo , Humanos , Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Proteínas Repetidas Ricas en Leucina , Modelos Moleculares , Oligodesoxirribonucleótidos/química , Unión Proteica , Estructura Terciaria de Proteína , Proteínas/química , Proteínas/metabolismo , Receptor Toll-Like 9/química
7.
JAMA Netw Open ; 6(6): e2318611, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37326991

RESUMEN

Importance: Posttraumatic stress disorder (PTSD) is common in people who have experienced trauma, especially those hospitalized for surgery. Dexmedetomidine may reduce or reverse the early consolidation and formation of conditioned fear memory and prevent the occurrence of postoperative PTSD. Objective: To evaluate the effects of intraoperative and postoperative low-dose intravenous pumping dexmedetomidine on PTSD among patients with trauma undergoing emergency surgery. Design, Setting, and Participants: This double-blind, randomized clinical trial was conducted from January 22 to October 20, 2022, with follow-up 1 month postoperatively, in patients with trauma undergoing emergency surgery at 4 hospital centers in Jiangsu Province, China. A total of 477 participants were screened. The observers were blinded to patient groupings, particularly for subjective measurements. Interventions: Dexmedetomidine or placebo (normal saline) was administered at a maintenance dose of 0.1 µg/kg hourly from the start of anesthesia until the end of surgery and at the same rate after surgery from 9 pm to 7 am on days 1 to 3. Main Outcomes and Measures: The primary outcome was the difference in the incidence of PTSD 1 month after surgery in the 2 groups. This outcome was assessed with the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (CAPS-5). The secondary outcomes were the pain score within 48 hours and 1 month postoperatively; incidence of postoperative delirium, nausea, and pruritus; subjective sleep quality; anxiety; and occurrence of adverse events. Results: A total of 310 patients (154 in the normal saline group and 156 in the dexmedetomidine group) were included in the modified intention-to-treat analysis (mean [SD] age, 40.2 [10.3] years; 179 men [57.7%]). The incidence of PTSD was significantly lower in the dexmedetomidine group than in the control group 1 month postoperatively (14.1% vs 24.0%; P = .03). The participants in the dexmedetomidine group had a significantly lower CAPS-5 score than those in the control group (17.3 [5.3] vs 18.9 [6.6]; mean difference, 1.65; 95% CI, 0.31-2.99; P = .02). After adjusting for potential confounders, the patients in the dexmedetomidine group were less likely to develop PTSD than those in the control group 1 month postoperatively (adjusted odds ratio, 0.51; 95% CI, 0.27-0.94; P = .03). Conclusions and Relevance: In this randomized clinical trial, the administration of intraoperative and postoperative dexmedetomidine reduced the incidence of PTSD among patients with trauma. The findings of this trial support the use of dexmedetomidine in emergency trauma surgery. Trial Registration: Chinese Clinical Trial Register Identifier: ChiCTR2200056162.


Asunto(s)
Dexmedetomidina , Delirio del Despertar , Trastornos por Estrés Postraumático , Masculino , Humanos , Adulto , Dexmedetomidina/uso terapéutico , Dexmedetomidina/efectos adversos , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/prevención & control , Solución Salina , Delirio del Despertar/inducido químicamente , Administración Intravenosa
8.
Int J Biol Macromol ; 253(Pt 8): 127597, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37884245

RESUMEN

Talaromyces (Penicillium) marneffei is an intracellular pathogenic fungus. Some strains of this fungus have been misidentified due to the similarity between Talaromyces and Penicillium. T. marneffei has mainly been found to afflict immunocompromised individuals, causing respiratory, skin, and systemic mycosis. Mp1p is a key virulence factor that can help T. marneffei evade clearance by the normally functioning immune system. Understanding how novel functions arise is an intriguing question in many fields of biology. Mp1p has two homologous domains (Mp1p-LBD1 and Mp1p-LBD2). Sequence similarity searches with Mp1p-LBD sequences revealed Mp1p homologs in many other pathogenic fungi. Integrated information on the taxonomic distribution, phylogenetic relationships, and sequence similarity of Mp1p domains revealed that the ancestor of Mp1p-LBDs was acquired through horizontal gene transfer (HGT). Additional evidence revealed that Mp1p homologs have undergone extensive gene duplications in T. marneffei. Mp1p might be a result of gene fusion following gene duplication. Furthermore, we propose a new method for identifying Talaromyces and identify 4 strains with misclassification errors. Our results characterize the evolutionary mechanism of T. marneffei evasion of host innate immune defense and clearly demonstrate the role of gene duplication and HGT in the evolution of host immune escape by T. marneffei.


Asunto(s)
Micosis , Talaromyces , Humanos , Talaromyces/genética , Filogenia , Micosis/genética , Micosis/microbiología , Inmunidad Innata/genética
9.
Theor Biol Med Model ; 9: 19, 2012 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-22672438

RESUMEN

BACKGROUND: Computational identification of transcription factor binding sites (TFBSs) is a rapid, cost-efficient way to locate unknown regulatory elements. With increased potential for high-throughput genome sequencing, the availability of accurate computational methods for TFBS prediction has never been as important as it currently is. To date, identifying TFBSs with high sensitivity and specificity is still an open challenge, necessitating the development of novel models for predicting transcription factor-binding regulatory DNA elements. RESULTS: Based on the information theory, we propose a model for transcription factor binding of regulatory DNA sites. Our model incorporates position interdependencies in effective ways. The model computes the information transferred (TI) between the transcription factor and the TFBS during the binding process and uses TI as the criterion to determine whether the sequence motif is a possible TFBS. Based on this model, we developed a computational method to identify TFBSs. By theoretically proving and testing our model using both real and artificial data, we found that our model provides highly accurate predictive results. CONCLUSIONS: In this study, we present a novel model for transcription factor binding regulatory DNA sites. The model can provide an increased ability to detect TFBSs.


Asunto(s)
ADN/genética , Modelos Genéticos , Secuencias Reguladoras de Ácidos Nucleicos/genética , Saccharomyces cerevisiae/genética , Factores de Transcripción/metabolismo , Secuencia de Bases , Sitios de Unión/genética , Bases de Datos Genéticas , Regiones Promotoras Genéticas/genética , Unión Proteica/genética
10.
Front Microbiol ; 13: 1045314, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36466664

RESUMEN

Incompatibility groups IncA and IncC plasmids are of great concern due to their ability to disseminate antibiotic resistance in bacteria via conjugative transfer. A deep understanding of their genomic structures and evolutionary characteristics is of great significance for improving our knowledge about its multidrug-resistance evolution and dissemination. However, current knowledge of their backbone structure, features of core functional modules and the characteristics of variable regions is based on a few plasmids, which highlights the need for a comprehensive systematic study. The present study thoroughly compared and analysed 678 IncA and IncC plasmid genomes. We found that their core functional genes were occasionally deficient and sometimes existed as multiple functional copies/multiple families, which resulted in much diversity. The phylogeny of 13 core functional genes corresponded well to the plasmid subtypes. The conjugative transfer system gained diverse complexity and exhibited many previously unnoticed types with multiple combinations. The insertion of mobile genetic elements (MGEs) in plasmids varied between types and was present in 4 insertion spots in different types of plasmids with certain types of transposons, integrons and insertion sequences. The impact of gene duplication, deletion, the insertion of MGEs, genome rearrangement and recombination resulted in the complex dynamic variable backbone of IncA and IncC plasmids. And IncA and IncC plasmids were more complex than their closest relative SXT/R391 integrative conjugative elements (ICEs), which included nearly all of the diversity of SXT/R391 in key systems. Our work demonstrated a global and systematic view of the IncA and IncC plasmids and provides many new insights into their genome evolution.

11.
Front Psychiatry ; 13: 853795, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35280171

RESUMEN

Objective: Posttraumatic stress disorder (PTSD) is a frequent and disabling consequence of traumatic events. A previous study found that early use of propofol was a potential risk factor for PTSD. This prospective study aimed to investigate the effect of propofol and sevoflurane on PTSD after emergency surgery in trauma patients. Methods: A total of 300 trauma patients undergoing emergency surgery were randomly divided into two groups and anesthetized with propofol and/or sevoflurane. Perioperative clinical data were collected. The incidence of PTSD was evaluated with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) in the two groups 1 month after the operation. The relevance of the injury time and CAPS-5 scores was assessed by Spearman correlation analysis. Logistic regression analysis was used to analyze the risk factors for PTSD. Results: The incidence of PTSD in the propofol group was higher than that in the sevoflurane group 1 month postoperatively (23.2 vs. 12.2%, P = 0.014). The injury time was negatively correlated with the CAPS-5 score in the propofol group (r = -0.226, P < 0.001). In the logistic regression analysis, the utilization of propofol was an independent risk factor for PTSD (P = 0.017). Conclusion: Early use of propofol general anesthesia in emergency surgery for trauma patients may increase the risk of PTSD. Clinical Trial Registration: www.chictr.org.cn, identifier: ChiCTR2100050202.

12.
Theor Biol Med Model ; 8: 47, 2011 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-22188601

RESUMEN

BACKGROUND: With the development of experimental techniques and bioinformatics, the quantity of data available from protein-protein interactions (PPIs) is increasing exponentially. Functional modules can be identified from protein interaction networks. It follows that the investigation of functional modules will generate a better understanding of cellular organization, processes, and functions. However, experimental PPI data are still limited, and no modularity analysis of PPIs in pathogens has been published to date. RESULTS: In this study, we predict and analyze the functional modules of E. coli O157:H7 systemically by integrating several bioinformatics methods. After evaluation, most of the predicted modules are found to be biologically significant and functionally homogeneous. Six pathogenicity-related modules were discovered and analyzed, including novel modules. These modules provided new information on the pathogenicity of O157:H7. The modularity of cellular function and cooperativity between modules are also discussed. Moreover, modularity analysis of O157:H7 can provide possible candidates for biological pathway extension and clues for discovering new pathways of cross-talk. CONCLUSIONS: This article provides the first modularity analysis of a pathogen and sheds new light on the study of pathogens and cellular processes. Our study also provides a strategy for applying modularity analysis to any sequenced organism.


Asunto(s)
Escherichia coli O157/citología , Escherichia coli O157/patogenicidad , Proteínas de Escherichia coli/metabolismo , Mapas de Interacción de Proteínas , Secuencia Conservada , Bases de Datos de Proteínas , Escherichia coli O157/metabolismo , Anotación de Secuencia Molecular , Complejos Multiproteicos/metabolismo , Homología de Secuencia de Aminoácido
13.
Front Genet ; 11: 506, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32528528

RESUMEN

Recombination and positive selection are two key factors that play a vital role in pathogenic microorganisms' population adaptation and diversification. The Burkholderia cepacia complex (Bcc) represents bacterial species with high similarity, which can cause severe infections among cases suffering from the chronic granulomatous disorder and cystic fibrosis (CF). At present, no genome-wide study has been carried out focusing on investigating the core genome of Bcc associated with the two evolutionary forces. The general characteristics of the core genome of Bcc species remain scarce as well. In this study, we explored the core orthologous genes of 116 Bcc strains using comparative genomic analysis and studied the two adaptive evolutionary forces: recombination and positive selection. We estimated 1005 orthogroups consisting entirely of single copy genes. These single copy orthologous genes in some Cluster of Orthologous Groups (COG) categories showed significant differences in the comparison of several evolutionary properties, and the encoding proteins were relatively simple and compact. Our findings showed that 5.8% of the core orthologous genes strongly supported recombination; in the meantime, 1.1% supported positive selection. We found that genes involved in protein synthesis as well as material transport and metabolism are favored by selection pressure. More importantly, homologous recombination contributed more genetic variation to a large number of genes and largely maintained the genetic cohesion in Bcc. This high level of recombination between Bcc species blurs their taxonomic boundaries, which leads Bcc species to be difficult or impossible to distinguish phenotypically and genotypically.

14.
Medicine (Baltimore) ; 99(17): e19896, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32332664

RESUMEN

BACKGROUND: Delirium is a common postoperative complication in older patients undergoing thoracic surgery and presages poor outcomes. Postoperative pain is an important factor in the progression of delirium. The purpose of this study was to test whether continuous thoracic paravertebral block (PVB), a more effective approach for analgesia, could decrease the incidence of delirium in elderly patients undergoing esophagectomy. METHODS: A total of 180 geriatric patients undergoing esophagectomy were randomly divided into 2 groups and treated with PVB or patient-controlled analgesia (PCA). Perioperative plasma CRP, IL-1ß, IL-6, and TNF-α levels were detected in all patients. Pain intensity was measured by a numerical rating scale. Delirium was assessed using the confusion assessment method. RESULTS: The incidence of postoperative delirium was significantly lower in the PVB group than in the PCA group. Patients in the PVB group had lower plasma CRP, IL-1ß, IL-6, and TNF-α levels and less pain when coughing after surgery. CONCLUSIONS: Ultrasound-guided continuous thoracic paravertebral block improved analgesia, reduced the inflammatory reaction and decreased the occurrence of delirium after surgery.


Asunto(s)
Delirio/prevención & control , Esofagectomía/normas , Bloqueo Nervioso/métodos , Ultrasonografía/normas , Anciano , Anciano de 80 o más Años , Analgesia Controlada por el Paciente/métodos , Analgesia Controlada por el Paciente/normas , Delirio/tratamiento farmacológico , Esofagectomía/métodos , Femenino , Geriatría/métodos , Humanos , Masculino , Persona de Mediana Edad , Bloqueo Nervioso/normas , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos , Ultrasonografía/métodos , Ultrasonografía/estadística & datos numéricos
15.
Front Genet ; 11: 644, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32714372

RESUMEN

Enhancers are cis-regulatory DNA elements that positively regulate the transcription of target genes in a tissue-specific manner, and dysregulation of target genes could lead to various diseases, such as cancer. Recent studies have shown that enhancers can regulate microRNAs (miRNAs) and participate in their biological synthesis. However, the network of enhancer-regulated miRNAs across multiple cancers is still unclear. Here, a total of 2,418 proximal enhancer-miRNA interactions and 1,280 distal enhancer-miRNA interactions were identified through the integration of genomic distance, co-expression, and 3D genome data in 31 cancers. The results showed that both proximal and distal interactions exhibited a significant cancer type-specific feature trend at the tissue level rather than at the single-cell level, and there was a noteworthy positive correlation between the expression of the miRNA and the number of enhancers regulating the same miRNA in most cancers. Furthermore, we found that there was a high correlation between the formation of enhancer-miRNA pairs and the expression of enhancer RNAs (eRNAs) whether in distal or proximal regulation. The characteristics analysis showed that miRes (enhancers that regulated miRNAs) and non-miRes presented significant differences in sequence conservation, guanine-cytosine (GC) content, and histone modification signatures. Notably, GC content, H3K4me1, and H3K36me3 were present differently between distal and proximal regulation, suggesting that they might participate in chromosome looping of enhancer-miRNA interactions. Finally, we introduced a case study, enhancer: chr1:1186391-1186507 ∼ miR-200a was highly relevant to the survival of thyroid cancer patients and a cis-eQTL SNP on the enhancer affected the expression of the TNFRSF18 gene as a tumor suppressor.

16.
Artículo en Inglés | MEDLINE | ID: mdl-32695760

RESUMEN

Enhancers can act as cis-regulatory elements to control transcriptional regulation by recruiting transcription factors (TFs) in a distance and orientation-independent manner. However, it is still unclear how p53 participates in the enhancer network as TF in hepatic carcinoma under the condition of DNA damage. A total of 14,286 active enhancers were identified through the integration of stable and unstable enhancer RNAs (eRNAs) captured by CAGE and GRO-seq, respectively. Furthermore, 218 p53-bound enhancers (Enhp53) were identified by analyzing p53 ChIP-seq in HepG2 cells after DNA damage. The results showed that the enhancer expression and histone markers of enhancers (H3K4me1, H3K4me2, H3K4me3, H3K9ac, and H3K27ac) revealed significantly higher level on Enhp53 than Enhno-p53 which suggested that p53 participated in regulating enhancer activity and chromatin structure. By analyzing 124 TFs ChIP-seq from ENCODE, 93 TFs were found significantly enriched on Enhp53 such as GATA4, YY1, and CTCF, indicating p53 may co-regulate enhancers with TFs participation. Moreover, significantly differentially expressed 438 miRNAs and 1,264 mRNAs were identified by analyzing small RNA-seq and RNA-seq, and 26 Enhp53-miRNAs and 145 Enhp53-mRNA interactions were identified by the integration of 3D genome data and genomic distance. The functional enrichment analysis showed that these miRNA targets and mRNAs were significantly involved in tumor biological processes and signaling pathways such as DNA replication, p53 signaling pathway, hepatitis B, focal adhesion, etc. The above results indicated that p53 participated in regulating enhancer network in hepatic carcinoma and Enhp53 exhibited significantly different characteristics with Enhno-p53.

17.
Exp Ther Med ; 15(3): 2404-2410, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29456645

RESUMEN

We aimed to investigate the indirect influence of exposure to nicotine during pregnancy on the learning and memory of adult offspring mice. Thirty pregnant C57 mice were randomly divided into either the control group (CON) or the nicotine group (NIC), with 15 mice each. The CON group was given access to drug-free water, and the NIC group was given 60 g/ml nicotine in drinking water. Sixteen adult mice were randomly selected from the 8 litters for Morris water maze test. The level of products of related factors in the hippocampus of mice in the NIC and the CON groups were compared using the 1H-MRS method. The escape latency time that the adult offspring mice in the NIC group took in the place navigation test was significantly longer than that of the CON group. In addition, the NIC group took longer time to arrive at the plate than the CON group (P<0.05). mRNA and protein levels of NR1 in the hippocampus of the NIC group was significantly higher than that in the CON group (P<0.05).α7nACh mRNA in the hippocampus of the NIC group was not significantly different from that of the CON group (P>0.05), while the expression levels of α7nACh protein in the hippocampus of the NIC group was significantly lower than that in the CON group (P<0.05). Detection of protein level of muscarinic receptors in the hippocampus of adult offspring mice in the NIC group showed that when compared to the CON group, the expression levels of M1, M3, M5 of the NIC group was not significantly different from that of the CON group (P>0.05). Therefore, exposure to nicotine during pregnancy can cause damage to the learning ability of adult offspring mice but do not significantly influence their working memory.

18.
Exp Ther Med ; 14(3): 2148-2152, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28962135

RESUMEN

The present study determined the effect of dexmedetomidine (Dex) combined with flurbiprofen axetil (FA) on analgesia, immune response, and preservation of cognitive function in patients subjected to general anesthesia. We recruited 100 patients with thyroid surgery and randomly divided them into four groups: Dex (D), FA (F), Dex combined with FA (DF), and saline control (C). The extubation and recovery times for Groups D and DF were significantly longer than for Groups F and C. After extubation, the heart rate and mean arterial pressure for Groups F, D, and DF were significantly lower than for Group C, and data for Group DF was significantly lower than for Group F. The visual analog scale and Riker sedation agitation scores were significantly lower in Group DF than for the other three groups. T- and B-lymphocytes were significantly higher in Group DF than in the other three groups. Compared with Groups F and C, the levels of TNF-α and IL-6 in Group DF were significantly reduced, while IL-2 markedly increased. The combined use of Dex and FA significantly improved pain after general anesthesia thyroid surgery, reduced restlessness and postoperative cognitive dysfunction, enhanced immune function, and promoted wound repair.

19.
Front Microbiol ; 8: 2611, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29312274

RESUMEN

The H9N2 virus has been demonstrated to donate its genes to other subtypes of influenza A virus, forming new reassortant virus which may infect human beings. Understanding the genetic characteristic and the global transmission patterns of the virus would guide the prevention and control of potentially emerging avian influenza A virus. In this paper, we hierarchically classified the evolution of the H9N2 virus into three main lineages based on the phylogenetic characteristics of the virus. Due to the distribution of sampling locations, we named the three lineages as Worldwide lineage, Asia-Africa lineage, and China lineage. Codon usage analysis and selective positive site analysis of the lineages further showed the lineage-specific evolution of the virus. We reconstructed the transmission routes of the virus in the three lineages through phylogeography analysis, by which several epicenters for migration of the virus were identified. The hierarchical classification of the lineages implied a possible original seeding process of the virus, starting from the Worldwide lineages to the Asian-Africa lineages and to the China lineages. In the process of H9N2 virus global transmission, the United States was the origin of the virus. China Mainland, Hong Kong SAR, Japan, and Korea were important transfer centers. Based on both the transmission route and the distribution of the hosts in each lineage, we concluded that the wild birds' migration has contributed much to the long-distance global spread of the virus, while poultry trade and people's lifestyle may have contributed to the relatively short-distance transmission in some areas of the Asia and Africa.

20.
Exp Ther Med ; 11(1): 65-68, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26889218

RESUMEN

The number of elderly patients undergoing femoral head replacement surgeries is on the increase. These patients often suffer from comorbidity such as cardiovascular and cerebrovascular complications, which limits the ability of medical teams to employ anesthesia. Thus, alternative methods are required. The aim of this study was to examine the advantage of laryngeal mask airway (LMA) in the absence of muscle relaxant in elderly patients undergoing femoral head replacement operations. Fifty patients (27 males and 23 females) undergoing femoral head replacements were selected for the study between March 2013 and May 2014. The mean value for the age in this group was 74.6±12.5 years. The patients were randomly distributed into two groups of 25. One group was designated as the treatment group and the second group as the control group. For the treatment group, LMA without muscle relaxant was used, and the control group received routine anesthesia. Variations in heart rate (HR), mean arterial pressure (MAP) and oxygen saturation (SPO2) in the two groups were monitored at different times. Clinical efficacy and muscle relaxation effects were also analyzed. For the treatment group, the HR, MAP and SPO2 measurements did not reveal any significant variation while these values in the control group demonstrated important dissimilarities. Time to recovery, time to extubation and incidence of throat pain in the treatment group were all markedly decreased as compared to those in control group. The operation time in the treatment group was not significantly different to that of control group. The satisfaction of the muscle relaxation effect in the treatment group was significantly higher than that in the control group while the incidence of adverse reactions was not considerably different. In conclusion, the use of LMA without using muscle relaxant in femoral head replacement surgeries performed on elderly patients showed to be effective and safe.

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