RESUMO
As a mechanism compensating for obstructive coronary artery disease, coronary collateral circulation (CCC) has attracted cardiologists for a long time to explore its potential impact. In the present study, Chinese patients suffering from ≥95% coronary stenosis, as diagnosed by angiography, have been investigated for the correlation between CCC and lipoprotein(a) [Lp(a)] levels. A cohort of 654 patients was divided into four categories according to Rentrop grades 0, 1, 2, and 3. Lp(a) levels were divided into model 1, discretized with critical values of 33 and 66%, and model 2, discretized with a cutoff value of 30.0 mg/dL. Furthermore, we evaluated the correlation between CCC and serum Lp(a) levels. The four groups had significantly different Lp(a) levels (25.80±24.72, 18.99±17.83, 15.39±15.80, and 8.40±7.75 mg/dL; P<0.001). In model 1, concerning R0, the risk in the third Lp (a) tertile (OR=3.34, 95%CI=2.32-4.83) was greater than that in the first tertile. In model 2, concerning R0, the risk in Lp(a) >30.0 group (OR=6.77, 95%CI=4.44-10.4) was greater than that of Lp(a) <30.0 mg/dL. The worst condition of CCC can be predicted independently by Lp(a) levels. In addition to clinical usage, Lp(a) levels can also be utilized as biological markers.
Assuntos
Circulação Colateral/fisiologia , Doença da Artéria Coronariana/sangue , Circulação Coronária/fisiologia , Oclusão Coronária/sangue , Lipoproteína(a)/sangue , Biomarcadores/sangue , Estudos de Coortes , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
microRNA (miR)-142-3p is implicated in malignancy and has been identified as a biomarker for aggressive and recurrent lung adenocarcinomas. This study aimed to evaluate the inhibitory effect of miR-142-3p on apoptosis and inflammation induced by bleomycin in MLE-12 cells. MLE-12 cells were first transfected either with miR-142-3p mimic or miR-142-3p inhibitor and then the cells were exposed to 50 µg/mL of bleomycin. Thereafter, cell viability, apoptosis and the expression of pro-inflammatory cytokines were assessed using CCK-8, flow cytometry, RT-PCR and western blot analyses. Cox-2, PI3K, AKT and mTOR expressions were detected by western blotting after bleomycin was administered together with NS-398 (an inhibitor of Cox-2). As a result, cell viability was significantly decreased, as well as apoptosis and the expression of IL-1 and TNF-α were remarkably increased after 50 and 100 µg/mL of bleomycin administration. miR-142-3p overexpression alleviated bleomycin-induced apoptosis and overproduction of these two pro-inflammatory cytokines, while miR-142-3p suppression exhibited completely opposite results. Up-regulation of Cox-2 and inactivation of PI3K/AKT/mTOR were found in bleomycin-pretreated cells, while these abnormal regulations were partially abolished by miR-142-3p overexpression and NS-398. In conclusion, this study demonstrated that miR-142-3p overexpression protected bleomycin-induced injury in lung epithelial MLE-12 cells, possibly via regulating Cox-2 expression and PI3K/AKT/mTOR signaling pathway. These findings provide evidence that miR-142-3p may be a therapeutic strategy for idiopathic pulmonary fibrosis (IPF) treatment.
Assuntos
Apoptose/efeitos dos fármacos , Bleomicina/farmacologia , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo/efeitos dos fármacos , Pulmão/citologia , MicroRNAs/metabolismo , Linhagem Celular , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , TransfecçãoRESUMO
As a mechanism compensating for obstructive coronary artery disease, coronary collateral circulation (CCC) has attracted cardiologists for a long time to explore its potential impact. In the present study, Chinese patients suffering from ≥95% coronary stenosis, as diagnosed by angiography, have been investigated for the correlation between CCC and lipoprotein(a) [Lp(a)] levels. A cohort of 654 patients was divided into four categories according to Rentrop grades 0, 1, 2, and 3. Lp(a) levels were divided into model 1, discretized with critical values of 33 and 66%, and model 2, discretized with a cutoff value of 30.0 mg/dL. Furthermore, we evaluated the correlation between CCC and serum Lp(a) levels. The four groups had significantly different Lp(a) levels (25.80±24.72, 18.99±17.83, 15.39±15.80, and 8.40±7.75 mg/dL; P<0.001). In model 1, concerning R0, the risk in the third Lp (a) tertile (OR=3.34, 95%CI=2.32-4.83) was greater than that in the first tertile. In model 2, concerning R0, the risk in Lp(a) >30.0 group (OR=6.77, 95%CI=4.44-10.4) was greater than that of Lp(a) <30.0 mg/dL. The worst condition of CCC can be predicted independently by Lp(a) levels. In addition to clinical usage, Lp(a) levels can also be utilized as biological markers.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Circulação Colateral/fisiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Circulação Coronária/fisiologia , Oclusão Coronária/sangue , Lipoproteína(a)/sangue , Biomarcadores/sangue , Estudos de Coortes , Angiografia Coronária , Doença da Artéria Coronariana/fisiopatologia , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/fisiopatologia , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
microRNA (miR)-142-3p is implicated in malignancy and has been identified as a biomarker for aggressive and recurrent lung adenocarcinomas. This study aimed to evaluate the inhibitory effect of miR-142-3p on apoptosis and inflammation induced by bleomycin in MLE-12 cells. MLE-12 cells were first transfected either with miR-142-3p mimic or miR-142-3p inhibitor and then the cells were exposed to 50 μg/mL of bleomycin. Thereafter, cell viability, apoptosis and the expression of pro-inflammatory cytokines were assessed using CCK-8, flow cytometry, RT-PCR and western blot analyses. Cox-2, PI3K, AKT and mTOR expressions were detected by western blotting after bleomycin was administered together with NS-398 (an inhibitor of Cox-2). As a result, cell viability was significantly decreased, as well as apoptosis and the expression of IL-1 and TNF-α were remarkably increased after 50 and 100 μg/mL of bleomycin administration. miR-142-3p overexpression alleviated bleomycin-induced apoptosis and overproduction of these two pro-inflammatory cytokines, while miR-142-3p suppression exhibited completely opposite results. Up-regulation of Cox-2 and inactivation of PI3K/AKT/mTOR were found in bleomycin-pretreated cells, while these abnormal regulations were partially abolished by miR-142-3p overexpression and NS-398. In conclusion, this study demonstrated that miR-142-3p overexpression protected bleomycin-induced injury in lung epithelial MLE-12 cells, possibly via regulating Cox-2 expression and PI3K/AKT/mTOR signaling pathway. These findings provide evidence that miR-142-3p may be a therapeutic strategy for idiopathic pulmonary fibrosis (IPF) treatment.
Assuntos
Humanos , Bleomicina/farmacologia , Regulação para Baixo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , MicroRNAs/metabolismo , Ciclo-Oxigenase 2/metabolismo , Pulmão/citologia , Transfecção , Linhagem Celular , Pulmão/efeitos dos fármacos , Pulmão/metabolismoRESUMO
Neurokinin-1 receptor (NK1R) is a high affinity Substance P (SP) receptor and plays a key role in visceral hypersensitivity in irritable bowel syndrome (IBS). Early life stress is a significant risk factor in IBS. The aim of the present study was to investigate the influence of neonatal maternal separation on the expression and distribution of SP and its receptor along the brain-gut axis in a neonatal maternally separated rat model with visceral hypersensitivity. Male neonatal Sprague-Dawley rats, 2-21-day old, were randomly distributed into maternal separation groups of 3 h daily maternal separation (MS) or non-handling (NH). These rats underwent colorectal balloon distention (CRD) upon reaching adulthood. Immunofluorescence was used to examine the distal colon, lumbosacral spinal cord, and the brainstem to semi-quantitatively determine SP and NK1R expression before and after CRD. The following features were assessed: percentage SP-positive area in colonic muscle layer, the number of NK1R-positive myenteric plexus, SP-positive area and NK1-positivity score in the dorsal horn and the brainstem. Neither of these was altered in the MS and NH groups before or after CRD. These results suggest that the SP system might play little role in the development of visceral hyperalgesia in the neonatal maternal separation rat model.
Assuntos
Hiperalgesia/metabolismo , Síndrome do Intestino Irritável/metabolismo , Receptores da Neurocinina-1/metabolismo , Substância P/metabolismo , Animais , Colo/metabolismo , Síndrome do Intestino Irritável/patologia , Masculino , Privação Materna , Músculo Liso/metabolismo , Plexo Mientérico/metabolismo , Especificidade de Órgãos , Ratos Sprague-Dawley , Corno Dorsal da Medula Espinal/metabolismoRESUMO
The Bactrian camel is an important domesticated animal providing milk, meat, and other products in desert countries. In this study, 111 individuals representing 11 domestic Bactrian camel breeds from China, Mongolia, Russia, and one wild Bactrian camel group from Mongolia were selected for the preparation of mitochondrial DNA. The 1140-bp fragments of the cytochrome b gene (Cytb) were amplified by polymerase chain reaction and sequenced directly. Sequences of the 92 domestic and 19 wild Bactrian camel samples were analyzed with DNASTAR, and a phylogenic tree was constructed using MEGA. The analysis revealed sixteen haplotypes among the samples that were divided into two haplogroups: a domestic haplogroup (H1-H13, H15, and H16) and a wild haplogroup (H14). Haplotype diversity values were from 0.356 in the HosZogdort, to 0.889 in the Sunit Bactrian camel breed. The Sunit breed displayed the highest nucleotide diversity value (0.00115), and the HosZogdort breed had the lowest value (0.00031). All domestic Bactrian camels formed a single monophyletic lineage that is the sister group to wild Bactrian camels, a finding consistent with a single domestication event and independent maternal inheritance since domestication. In addition, the most common mitochondrial haplotypes (H1, H3, and H4) were shared between Chinese, Mongolian, and Russian domestic Bactrian camels, which indicated that there was no distinguishing geographic structure among the domestic breeds from these three regions. These findings provide important insights into patterns of relatedness among Bactrian camels from the Chinese, Mongolian, and Russian regions.
Assuntos
Camelus/genética , Citocromos b/genética , Animais , Animais Domésticos , Sequência de Bases , Cruzamento , China , DNA Mitocondrial/genética , Genes Mitocondriais , Variação Genética , Haplótipos , Mongólia , Filogenia , Federação Russa , Análise de Sequência de DNARESUMO
We examined the aberrant microRNA (miRNA) expression profile responsible for the changes in angiogenesis observed in endometriotic lesions. This study revealed characteristic miRNA expression profiles associated with endometriosis in endometrial tissue and endometriotic lesions from the same patient, and their correlation with the most important angiogenic and fibrinolytic factors. miRNA expression was quantified using a microRNA array and reverse-transcription microRNA polymerase chain reaction. Levels of vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor 2 (EGFR2), phosphatase and tensin homolog (PTEN), and C-X-C chemokine receptor type 4 (CXCR4) were quantified using enzyme-linked immunosorbent assay. The endometrial tissue showed significantly lower levels of miR-200b, miR-15a-5p, miR-19b-1-5p, miR-146a-5p, and miR-200c, and higher levels of miR-16-5p, miR-106b-5p, and miR-145-5p. VEGFA was significantly upregulated, whereas EGFR2, PTEN, and CXCR4 were markedly downregulated, in the endometriotic tissues compared to that in the normal endometrial tissues. In conclusion, differences in the miRNA levels could modulate the expression of VEGFA, EGFR2, PTEN, and CXCR4, and may play an important role in the pathogenesis of endometriosis. The higher angiogenic and proteolytic activities observed in the eutopic endometrium might facilitate the implantation of endometrial cells at ectopic sites.
Assuntos
Endometriose/genética , MicroRNAs/biossíntese , PTEN Fosfo-Hidrolase/biossíntese , Receptor ErbB-2/biossíntese , Receptores CXCR4/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese , Adulto , Endometriose/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , PTEN Fosfo-Hidrolase/genética , Receptor ErbB-2/genética , Receptores CXCR4/genética , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
The angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been reported to be associated with digestive system cancer; however, the results from previous studies have been conflicting. The present study aimed to investigate the association between the ACE I/D polymorphism and the risk of digestive system cancer using a meta-analysis of previously published studies. Databases were systematically searched to identify relevant studies published prior to December 2014. We estimated the pooled OR with its 95%CI to assess the association. The meta-analysis consisted of thirteen case-control studies that included 2557 patients and 4356 healthy controls. Meta-analysis results based on all the studies showed no significant association between the ACE I/D polymorphism and the risk of digestive system cancer (DD vs II: OR = 0.85, 95%CI = 0.59-1.24; DI vs II: OR = 0.94, 95%CI = 0.78-1.15; dominant model: OR = 0.96, 95%CI = 0.81- 1.15; recessive model: OR = 1.06, 95%CI = 0.76-1.48). Subgroup analyses by race and cancer type did not detect an association between the ACE I/D polymorphism and digestive system cancer risk. However, when the analyses were restricted to smaller studies (N < 500 patients), the summary OR of DI vs II was 0.80 (95%CI = 0.66-0.97). Our analyses detected a possibility of publication bias with a misestimate of the true association by smaller studies. Overall, meta-analysis results suggest the ACE I/D polymorphism might not be associated with susceptibility to digestive system cancer. Further large and well-designed studies are needed to confirm these conclusions.
Assuntos
Neoplasias do Sistema Digestório/genética , Peptidil Dipeptidase A/genética , Estudos de Casos e Controles , Neoplasias do Sistema Digestório/enzimologia , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Mutação INDEL , Polimorfismo Genético , Viés de Publicação , Fatores de RiscoRESUMO
Aseptic loosening associated with wear particle-induced inflammation is a major cause of joint implant failure. Recent studies have demonstrated the therapeutic effects of p38 mitogen-activated protein kinase (MAPK)-based therapies on chronic inflammatory diseases. The purpose of this study was to investigate whether SB203580, a p38 MAPK inhibitor, inhibits wear debris-induced inflammatory osteolysis in mice through downregulation of receptor activator of nuclear factor kß (RANK)/RANK ligand (RANKL). We used a murine osteolysis model to study the effect of SB203580 on RANKL/RANK signaling and titanium particle-induced osteolysis in vivo. Pouch membranes with intact bone implants were analyzed using histological analysis and transmission electron microscopy, and the levels of RANK and RANKL protein and mRNA were evaluated by immunohistological staining and real-time reverse transcriptase-polymerase chain reaction. SB203580 had less of an effect on RANK and RANKL expression under wear debris-induced conditions. The number of TRAP-positive cells was remarkably reduced in Ti-particle-induced pouch tissues. These effects were confirmed through the transmission electron microscopy results. These results suggest that p38 MAPK-based therapies are beneficial in preventing aseptic loosening associated with total joint replacement by modulating RANK-RANKL signaling.
Assuntos
Regulação para Baixo/efeitos dos fármacos , Inflamação/etiologia , Osteólise/etiologia , Próteses e Implantes/efeitos adversos , Inibidores de Proteínas Quinases/farmacologia , Ligante RANK/genética , Receptor Ativador de Fator Nuclear kappa-B/genética , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Fosfatase Ácida/metabolismo , Animais , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Bolsas Cólicas , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/patologia , Isoenzimas/metabolismo , Camundongos Endogâmicos BALB C , Osteólise/tratamento farmacológico , Osteólise/genética , Osteólise/patologia , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Ligante RANK/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Fosfatase Ácida Resistente a Tartarato , Titânio/efeitos adversos , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Essential genes are those genes that are needed by organisms at any time and under any conditions. It is very important for us to identify essential genes from bacterial genomes because of their vital role in synthetic biology and biomedical practices. In this paper, we developed a support vector machine (SVM)-based method to predict essential genes of bacterial genomes using only compositional features. These features are all derived from the primary sequences, i.e., nucleotide sequences and protein sequences. After training on the multiple samplings of the labeled (essential or not essential) features using a library for SVM, we obtained an average area under the ROC curve (AUC) of about 0.82 in a 5-fold cross-validation for Escherichia coli and about 0.74 for Mycoplasma pulmonis. We further evaluated the performance of the method proposed using the dataset consisting of 16 bacterial genomes, and an average AUC of 0.76 was achieved. Based on this training dataset, a model for essential gene prediction was established. Another two independent genomes, Shewanella oneidensis RW1 and Salmonella enterica serovar Typhimurium SL1344 were used to evalutate the model. Results showed that the AUC sores were 0.77 and 0.81, respectively. For the convenience of the vast majority of experimental scientists, a web server has been constructed, which is freely available at http://cefg.uestc.edu.cn:9999/egp.
Assuntos
Bactérias/genética , Proteínas de Bactérias/genética , Genes Essenciais , Bases de Dados Genéticas , Genoma Bacteriano , Dados de Sequência Molecular , Análise de Sequência , Máquina de Vetores de SuporteRESUMO
The herpes simplex virus 2 (HSV-2) is one of the most important sexually transmitted pathogens, and can facilitate the spread of human immunodeficiency virus. The currently available antiviral drugs have certain limitations. Nanosilver has received increasing attention recently with respect to its antibacterial and antiviral properties. The purpose of this study was to determine the inhibiting effect and mechanism of silver nanoparticles (Ag-NPs) on HSV-2. The cytotoxicity of Vero cells induced by different Ag-NP concentrations was investigated by using the methyl thiazolyl tetrazolium (MTT) assay. The inhibiting effect of Ag-NPs on HSV-2 at various times was also evaluated by using a plaque assay. The toxicity of 100 µg/mL Ag-NPs on Vero cells was very low. The mixture of Ag-NP suspension and HSV-2 prior to infecting cells could significantly inhibit the production of progeny viruses. Ag-NPs also inhibited the replication of HSV-2 for 24 h before infecting cells with HSV-2. Therefore, 100 µg/mL Ag-NPs could completely inhibit HSV-2 replication. Ag-NPs at nontoxic concentrations were capable of inhibiting HSV-2 replication when administered prior to viral infection or soon after initial virus exposure. This suggests that the mode of action of Ag-Nps occurs during the early phases of viral replication.
Assuntos
Antivirais/administração & dosagem , Herpesvirus Humano 2/efeitos dos fármacos , Nanopartículas Metálicas/administração & dosagem , Prata , Animais , Antivirais/química , Antivirais/toxicidade , Proliferação de Células/efeitos dos fármacos , Chlorocebus aethiops , Efeito Citopatogênico Viral/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Prata/química , Células Vero , Replicação Viral/efeitos dos fármacosRESUMO
We performed statistical analyses of five conserved features of genomic islands of bacteria. Analyses were made based on 104 known genomic islands, which were identified by comparative methods. Four of these features include sequence size, abnormal G+C content, flanking tRNA gene, and embedded mobility gene, which are frequently investigated. One relatively new feature, G+C homogeneity, was also investigated. Among the 104 known genomic islands, 88.5% were found to fall in the typical length of 10-200 kb and 80.8% had G+C deviations with absolute values larger than 2%. For the 88 genomic islands whose hosts have been sequenced and annotated, 52.3% of them were found to have flanking tRNA genes and 64.7% had embedded mobility genes. For the homogeneity feature, 85% had an h homogeneity index less than 0.1, indicating that their G+C content is relatively uniform. Taking all the five features into account, 87.5% of 88 genomic islands had three of them. Only one genomic island had only one conserved feature and none of the genomic islands had zero features. These statistical results should help to understand the general structure of known genomic islands. We found that larger genomic islands tend to have relatively small G+C deviations relative to absolute values. For example, the absolute G+C deviations of 9 genomic islands longer than 100,000 bp were all less than 5%. This is a novel but reasonable result given that larger genomic islands should have greater restrictions in their G+C contents, in order to maintain the stable G+C content of the recipient genome.
Assuntos
Sequência Conservada/genética , Genoma Bacteriano , Ilhas Genômicas , Bactérias/genética , Composição de Bases , RNA de Transferência/genéticaRESUMO
The aim of this study was to evaluate the effects of atorvastatin on left atrial (LA) function in paroxysmal atrial fibrillation patients. Fifty-eight paroxysmal atrial fibrillation patients were divided into two groups (treatment and control groups). The echocardiography parameters, including LA active emptying volume (LAAEV), LA active emptying fraction, LA maximum volume, LA total emptying volume, LA total emptying fraction, and LA ejection force (LAEF), were measured before treatment, and then 12 and 18 months after treatment. Compared to pre-treatment levels, the parameters reflecting LA pump function, such as LAAEV and LAEF, decreased significantly in treatment groups 12 months after treatment (P < 0.05). LAAEV and LAEF significantly increased 18 months after treatment (P < 0.05), and the indicators reflecting LA reservoir function, such as maximum volume, total emptying volume, and total emptying fraction increased significantly 18 months after treatment (P < 0.05). Compared with pre-treatment levels, LAAEV and LAEF decreased significantly 18 months after treatment in the control group (P < 0.05). These results demonstrated that long-term atorvastatin treatment could ameliorate the function of the atrium sinistrum.
Assuntos
Fibrilação Atrial/fisiopatologia , Função do Átrio Esquerdo/efeitos dos fármacos , Ácidos Heptanoicos/efeitos adversos , Pirróis/efeitos adversos , Adulto , Atorvastatina , Fibrilação Atrial/tratamento farmacológico , Ecocardiografia/efeitos dos fármacos , Feminino , Átrios do Coração/fisiopatologia , Ácidos Heptanoicos/administração & dosagem , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pirróis/administração & dosagemRESUMO
Horizontal gene transfer is an important mechanism for the evolution of microbial genomes, and many horizontal gene transfer events are facilitated by genomic islands (GIs). Until now, few reports have provided evidence for the co-evolution of horizontally transferred genes and their hosts. We obtained 17 groups of homologous GIs, all of which appear in 8 or more bacterial strains of the same species or genus. Using phylogenetic analyses, we found that the topological structure of a distance tree based on the proteins of each group of homologous GIs was consistent with that based on the complete proteomes of the hosts. This result clearly indicates that GIs and their bacterial hosts have co-evolved. In addition to presenting and providing evidence for a novel concept, i.e., the co-evolution of GIs and their bacterial hosts, we also describe a new and interesting detail for the phylogenetic analysis of horizontally transferred genes: consistent phylogenetic trees can be obtained by focusing on homologous GIs despite the commonly accepted theory that the phylogenies of horizontally transferred sequences and host organisms should be inconsistent.
Assuntos
Bactérias/genética , Evolução Molecular , Ilhas Genômicas/genética , Interações Hospedeiro-Patógeno/genética , Filogenia , Proteoma/genética , Staphylococcus aureus/genéticaRESUMO
We adopted the method of Zhang and Zhang (the Z-Island method) to identify genomic islands in seven human pathogens, analyzing their chromosomal DNA sequences. The Z-Island method is a theoretical method for predicting genomic islands in bacterial genomes; it consists of determination of the cumulative GC profile and computation of codon usage bias. Thirty-one genomic islands were found in seven pathogens using this method. Further analysis demonstrated that most have the known conserved features; this increases the probability that they are real genomic islands. Eleven genomic islands were found to code for products involved in causing disease (virulence factors) or in resistance to antibiotics (resistance factors). This finding could be useful for research on the pathogenicity of these bacteria and helpful in the treatment of the diseases that they cause. In a comparison of the distribution of mobility elements in genomic islands predicted by different methods, the Z-Island method gave lower false-positive rates. The Z-Island method was found to detect more known genomic islands than the two methods that we compared it with, SIGI-HMM and IslandPick. Furthermore, it maintained a better balance between specificity and sensitivity. The only inconvenience is that the steps for finding genomic islands by the Z-Island method are semi-automatic.
Assuntos
Bactérias , Infecções Bacterianas/genética , Cromossomos Bacterianos , Ilhas Genômicas , Análise de Sequência de DNA/métodos , Fatores de Virulência/genética , Bactérias/genética , Bactérias/patogenicidade , HumanosRESUMO
High mobility group box 1 (HMGB1) was discovered as a novel late-acting cytokine that contributes to acute lung injury (ALI). However, the contribution of HMGB1 to two-hit-induced ALI has not been investigated. To examine the participation of HMGB1 in the pathogenesis of ALI caused by the two-hit hypothesis, endotoxin was injected intratracheally in a hemorrhagic shock-primed ALI mouse model. Concentrations of HMGB1 in the lung of the shock group were markedly increased at 16 h (1.63 ± 0.05, compared to the control group: 1.02 ± 0.03; P < 0.05), with the highest concentration being observed at 24 h. In the sham/lipopolysaccharide group, lung HMGB1 concentrations were found to be markedly increased at 24 h (1.98 ± 0.08, compared to the control group: 1.07 ± 0.03; P < 0.05). Administration of lipopolysaccharide to the hemorrhagic shock group resulted in a notable HMGB1 increase by 4 h, with a further increase by 16 h. Intratracheal lipopolysaccharide injection after hemorrhagic shock resulted in the highest lung leak at 16 h (2.68 ± 0.08, compared to the control group: 1.05 ± 0.04; P < 0.05). Compared to the hemorrhagic shock/lipopolysaccharide mice, blockade of HMGB1 at the same time as lipopolysaccharide injection prevented significantly pulmonary tumor necrosis factor-alpha, interleukin-1beta and myeloperoxidase. Lung leak was also markedly reduced at 16 h; blockade of HMGB1 24 h after lipopolysaccharide injection failed to alter lung leak or myeloperoxidase at 48 h. Our observations suggest that HMGB1 plays a key role as a late mediator when lipopolysaccharide is injected after hemorrhagic shock-primed ALI and the kinetics of its release differs from that of one-hit ALI. The therapeutic window to suppress HMGB1 activity should not be delayed to 24 h after the disease onset.
Assuntos
Animais , Masculino , Camundongos , Lesão Pulmonar Aguda/metabolismo , Anticorpos/uso terapêutico , Proteína HMGB1/metabolismo , Mediadores da Inflamação/metabolismo , Choque Hemorrágico/metabolismo , Western Blotting , Ensaio de Imunoadsorção Enzimática , Endotoxinas/administração & dosagem , Endotoxinas/farmacologia , Proteína HMGB1/imunologia , Mediadores da Inflamação/imunologia , Camundongos Endogâmicos BALB CRESUMO
High mobility group box 1 (HMGB1) was discovered as a novel late-acting cytokine that contributes to acute lung injury (ALI). However, the contribution of HMGB1 to two-hit-induced ALI has not been investigated. To examine the participation of HMGB1 in the pathogenesis of ALI caused by the two-hit hypothesis, endotoxin was injected intratracheally in a hemorrhagic shock-primed ALI mouse model. Concentrations of HMGB1 in the lung of the shock group were markedly increased at 16 h (1.63 +/- 0.05, compared to the control group: 1.02 +/- 0.03; P < 0.05), with the highest concentration being observed at 24 h. In the sham/lipopolysaccharide group, lung HMGB1 concentrations were found to be markedly increased at 24 h (1.98 +/- 0.08, compared to the control group: 1.07 +/- 0.03; P < 0.05). Administration of lipopolysaccharide to the hemorrhagic shock group resulted in a notable HMGB1 increase by 4 h, with a further increase by 16 h. Intratracheal lipopolysaccharide injection after hemorrhagic shock resulted in the highest lung leak at 16 h (2.68 +/- 0.08, compared to the control group: 1.05 +/- 0.04; P < 0.05). Compared to the hemorrhagic shock/lipopolysaccharide mice, blockade of HMGB1 at the same time as lipopolysaccharide injection prevented significantly pulmonary tumor necrosis factor-alpha, interleukin-1beta and myeloperoxidase. Lung leak was also markedly reduced at 16 h; blockade of HMGB1 24 h after lipopolysaccharide injection failed to alter lung leak or myeloperoxidase at 48 h. Our observations suggest that HMGB1 plays a key role as a late mediator when lipopolysaccharide is injected after hemorrhagic shock-primed ALI and the kinetics of its release differs from that of one-hit ALI. The therapeutic window to suppress HMGB1 activity should not be delayed to 24 h after the disease onset.
Assuntos
Lesão Pulmonar Aguda/metabolismo , Anticorpos/uso terapêutico , Proteína HMGB1/metabolismo , Mediadores da Inflamação/metabolismo , Choque Hemorrágico/metabolismo , Animais , Western Blotting , Endotoxinas/administração & dosagem , Endotoxinas/farmacologia , Ensaio de Imunoadsorção Enzimática , Proteína HMGB1/imunologia , Mediadores da Inflamação/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Hepatocellular carcinoma (HCC) is one of the most common malignant tumours in the world, especially in Guangxi, China. The causes and mechanism of its tumourigenesis and development have not been completely clarified Some studies revealed that the hepatic local cellular immune function was one of the factors. In the present study, the local micro-environmental immune status was explored by investigating the number, distribution and function of CD3, CD57, CD20, CD68, and granzyme B (GrB) positive cells in 60 patients with HCC and 62 patients with liver cirrhosis (LC) and its relationship with the prognosis of the patients. The results showed that the number of T and B lymphocytes and natural killer (NK) cells in the liver of HCC patients was significantly higher than that in the LC and normal controls; while the number of macrophages (Mphi) was significantly lower The number of Mphi in the tissues decreased successively with the decrease of HCC differentiation; GrB-expressing cells in the liver predominantly consisted of CD57 positive cells. The number of NK cells, B lymphocytes and GrB-expressing cells in the cancerous tissues of stage I and II was significantly higher than that of stages III and IV. The number of T lymphocytes, NK cells, Mphi, and GrB-expressing lymphocytes in HCC cases without metastasis in 15 months was significantly higher than in the metastatic counterparts. The number of T and B lymphocytes, NK cells, and GrB-expressing cells decreased in patients with the progression of the HCC. These results suggest that the number of T and B lymphocytes, NK cells, Mphi and GrB-positive lymphocytes might be important markers in the estimation of hepatic local immune status and be useful factors for predicting the prognosis of HCC patients.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Carcinoma Hepatocelular/imunologia , Cirrose Hepática/imunologia , Nível de Saúde , Progressão da Doença , Cirrose Hepática/fisiopatologia , Células Matadoras Naturais , Estudos Retrospectivos , Linfócitos B , Linfócitos T , Biomarcadores , PrognósticoRESUMO
Hepatocellular carcinoma (HCC) is one of the most common malignant tumours in the world, especially in Guangxi, China. The causes and mechanism of its tumourigenesis and development have not been completely clarified Some studies revealed that the hepatic local cellular immune function was one of the factors. In the present study, the local micro-environmental immune status was explored by investigating the number, distribution and function of CD3, CD57, CD20, CD68, and granzyme B (GrB) positive cells in 60 patients with HCC and 62 patients with liver cirrhosis (LC) and its relationship with the prognosis of the patients. The results showed that the number of T and B lymphocytes and natural killer (NK) cells in the liver of HCC patients was significantly higher than that in the LC and normal controls; while the number of macrophages (Mphi) was significantly lower The number of Mphi in the tissues decreased successively with the decrease of HCC differentiation; GrB-expressing cells in the liver predominantly consisted of CD57 positive cells. The number of NK cells, B lymphocytes and GrB-expressing cells in the cancerous tissues of stage I and II was significantly higher than that of stages III and IV. The number of T lymphocytes, NK cells, Mphi, and GrB-expressing lymphocytes in HCC cases without metastasis in 15 months was significantly higher than in the metastatic counterparts. The number of T and B lymphocytes, NK cells, and GrB-expressing cells decreased in patients with the progression of the HCC. These results suggest that the number of T and B lymphocytes, NK cells, Mphi and GrB-positive lymphocytes might be important markers in the estimation of hepatic local immune status and be useful factors for predicting the prognosis of HCC patients.