Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Infect Immun ; : IAI0031521, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34543119

RESUMO

Mycobacterium tuberculosis is a chronic infectious disease pathogen. To date, tuberculosis is a major infectious disease that endangers human health. To better prevent and treat tuberculosis, it is important to study the pathogenesis of M. tb. Based on early-stage laboratory research results, in this study, we verified the upregulation of sod2 in Bacillus Calmette-Guérin (BCG) and H37Rv infection. By detecting BCG/H37Rv intracellular survival in sod2-silenced and sod2- overexpressing macrophages, sod2 was found to promote the intracellular survival of BCG/H37Rv. Then, miR-495 was determined to be downregulated by BCG/H37Rv. BCG/H37Rv can upregulate sod2 expression by miR-495 to promote the intracellular survival of BCG/H37Rv through a decline in ROS levels. This study provides a theoretical basis for developing new drug targets and treating tuberculosis.

2.
J Microbiol ; 59(9): 854-860, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34382147

RESUMO

Extraintestinal pathogenic Escherichia coli (ExPEC) is an important zoonotic pathogen that places severe burdens on public health and animal husbandry. There are many pathogenic factors in E. coli. The type VI secretion system (T6SS) is a nano-microbial weapon that can assemble quickly and inject toxic effectors into recipient cells when danger is encountered. T6SSs are encoded in the genomes of approximately 25% of sequenced Gram-negative bacteria. When these bacteria come into contact with eukaryotic cells or prokaryotic microbes, the T6SS assembles and secretes associated effectors. In the porcine ExPEC strain PCN033, we identified four classic rearrangement hotspot (Rhs) genes. We determined the functions of the four Rhs proteins through mutant construction and protein expression. Animal infection experiments showed that the Δrhs-1CT, Δrhs-2CT, Δrhs-3CT, and Δrhs-4CT caused a significant decrease in the multiplication ability of PCN033 in vivo. Cell infection experiments showed that the Rhs protein is involved in anti-phagocytosis activities and bacterial adhesion and invasion abilities. The results of this study demonstrated that rhs1, rhs3, and rh4 plays an important role in the interaction between PCN033 and host cell. Rhs2 has contribution to cell and mice infection. This study helps to elucidate the pathogenic mechanism governing PCN033 and may help to establish a foundation for further research seeking to identify potential T6SS effectors.


Assuntos
Infecções por Escherichia coli/veterinária , Proteínas de Escherichia coli/metabolismo , Doenças dos Suínos/microbiologia , Animais , Aderência Bacteriana , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/genética , Escherichia coli Extraintestinal Patogênica/genética , Escherichia coli Extraintestinal Patogênica/metabolismo , Feminino , Intestinos/microbiologia , Camundongos , Família Multigênica , Suínos
3.
Biochem Biophys Res Commun ; 575: 73-77, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34461438

RESUMO

The general characteristics of the effect of surfactants on the activity of lysozyme were demonstrated. The kinetics of bacterial cell lysis is consistent with the Michaelis-Menten equation and the presence of surfactants does not shift the pH-optimum of activity. Surfactants do not change the Km value but instead, affect the Vmax value. The experimental dependencies are well described by theoretical equations, which assume three surfactant binding sites on the lysozyme molecule. The dependencies of the activity of lysozyme on the surfactant concentration are either a step type (i.e., a higher plateau becomes a lower plateau), or a dependency with a maximum and continuation of the curve in the form of a plateau but with an increase in the surfactant concentration. It can be assumed that there is a mechanism for the regulation of lysozyme activity by an unknown natural factor that has a suitable hydrophobic radical capable of binding to the surface of lysozyme.

4.
Ecotoxicol Environ Saf ; 223: 112613, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34388656

RESUMO

Perfluorinated compounds (PFCs) are a type of ubiquitous contaminants spreading in the estuarine and coastal areas. Anadromous fish should deal with hypoosmotic challenge with PFCs stress during their migration from seawater to estuaries. However, few studies have been carried out to investigate the adverse impact of PFCs on fish osmoregulation and the underlying mechanism. In this study, Oryzias melastigma, an euryhaline fish model, were exposed to four representative PFC congeners including perfluorobutane sulfonate (PFBS), perfluorooctane sulfonates (PFOS), perfluorooctanoic acid (PFOA), and perfluorododecanoic acid (PFDoA) separately under both seawater and freshwater conditions. Histopathological changes in gills, ion homeostasis, Na+/K+-ATPase (NKA) activity, as well as the expression of related genes was detected upon exposure. Results showed that PFCs induced morphological changes in gills, disturbed the levels of major ions (Na+, Ca2+, Mg2+), and inhibited the NKA activity. Transcriptome analysis in fish gills during the acclimation to freshwater revealed that PFCs influenced the osmoregulation mainly by interfering with the endocrine system, signal transduction, as well as cellular community and motility. Validation with qRT-PCR confirmed that the mRNA expressions of osmoregulatory genes encoding hormones and receptors, as well as ion transmembrane transporters were disturbed by PFCs. Longer chain homolog (PFOS) showed a greater impact on osmoregulation than the shorter chain homolog (PFBS). Within the same carbon chain, sulfonic congener (PFOS) induced more serious injury to gills than carboxylic congener (PFOA). The interaction between PFCs and salinity varied in different adverse outcome. These results help to further understand the mechanism of how PFCs influence osmoregulation and elicit the need to assess the ecological risk of PFCs and other pollutants on anadromous migration.


Assuntos
Fluorcarbonetos , Oryzias , Aclimatação , Animais , Fluorcarbonetos/análise , Brânquias/metabolismo , Osmorregulação , Água do Mar
5.
J Biotechnol ; 339: 1-13, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34298024

RESUMO

Genetic manipulation of plant genes in prokaryotes has been widely used in molecular biology, but the function of a DNA sequence is far from being fully known. Here, we discovered that a plant protein-coding gene containing the CRAL_TRIO domain serves as a promoter in bacteria. We firstly characterized CitPITP1 from Citrus, which contains the CRAL_TRIO domain, and identified a 64-bp sequence (key64) that is critical for prokaryotic promoter activity. In vitro experiments indicated that the bacterial RNA polymerase subunit RpoD specifically binds to key64. We then expanded our research to fungi, plant and animal species to identify key64-like sequences. Five such prokaryotic promoters were isolated from Amborella, Rice, Arabidopsis and Citrus. Two conserved motifs were identified, and mutation analysis indicated that the nucleotides at positions 7, 29 and 30 are crucial for key64-like transcription activity. We detected full-length recombinant CitPITP1 from E. coli, and visualized a CitPITP1-GFP fusion protein in plant cells, supporting the idea that CitPITP1 encodes a protein. However, although exon 4 of CitPITP1 contained key64, it did not demonstrate promoter activity in plants. Our study describes a new basal promoter, provides evidence for neofunction of gene elements across different kingdoms, and provides new knowledge for the modular design of promoters.


Assuntos
Arabidopsis , Escherichia coli , Animais , Arabidopsis/genética , Bactérias/genética , Sequência de Bases , Éxons
6.
Int J Mol Sci ; 22(12)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198513

RESUMO

BACKGROUND: Pulmonary disease caused by Mycobacterium abscessus (M. abscessus) spreads around the world, and this disease is extremely difficult to treat due to intrinsic and acquired resistance of the pathogen to many approved antibiotics. M. abscessus is regarded as one of the most drug-resistant mycobacteria, with very limited therapeutic options. METHODS: Whole-cell growth inhibition assays was performed to screen and identify novel inhibitors. The IC50 of the target compounds were tested against THP-1 cells was determined to calculate the selectivity index, and then time-kill kinetics assay was performed against M. abscessus. Subsequently, the synergy of oritavancin with other antibiotics was evaluated by using checkerboard method. Finally, in vivo efficacy was determined in an immunosuppressive murine model simulating M. abscessus infection. RESULTS: We have identified oritavancin as a potential agent against M. abscessus. Oritavancin exhibited time-concentration dependent bactericidal activity against M. abscessus and it also displayed synergy with clarithromycin, tigecycline, cefoxitin, moxifloxacin, and meropenem in vitro. Additionally, oritavancin had bactericidal effect on intracellular M. abscessus. Oritavancin significantly reduced bacterial load in lung when it was used alone or in combination with cefoxitin and meropenem. CONCLUSIONS: Our in vitro and in vivo assay results indicated that oritavancin may be a viable treatment option against M. abscessus infection.


Assuntos
Antibacterianos/uso terapêutico , Lipoglicopeptídeos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus/fisiologia , Animais , Antibacterianos/farmacologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Imunossupressão , Espaço Intracelular/microbiologia , Lipoglicopeptídeos/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Células THP-1
7.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072443

RESUMO

As an important zoonotic pathogen, Streptococcus suis (S. suis) infection has been reported to be a causative agent for variety of diseases in humans and animals, especially Streptococcal toxic shock-like syndrome (STSLS), which is commonly seen in cases of severe S. suis infection. STSLS is often accompanied by excessive production of inflammatory cytokines, which is the main cause of death. This calls for development of new strategies to avert the damage caused by STSLS. In this study, we found for the first time that Baicalein, combined with ampicillin, effectively improved severe S. suis infection. Further experiments demonstrated that baicalein significantly inhibited the hemolytic activity of SLY by directly binding to SLY and destroying its secondary structure. Cell-based assays revealed that Baicalein did not exert toxic effects and conferred protection in S. suis-infected cells. Interestingly, compared with ampicillin alone, Baicalein combined with ampicillin resulted in a higher survival rate in mice severely infected with S. suis. At the same time, we found that baicalein can be combined with meropenem against MRSA. In conclusion, these results indicate that baicalein has a good application prospect.


Assuntos
Antibacterianos/farmacologia , Flavanonas/farmacologia , Infecções Estreptocócicas/microbiologia , Streptococcus suis/efeitos dos fármacos , Animais , Antibacterianos/química , Citocinas/biossíntese , Modelos Animais de Doenças , Farmacorresistência Bacteriana/efeitos dos fármacos , Quimioterapia Combinada , Flavanonas/química , Hemólise/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/metabolismo , Infecções Estreptocócicas/patologia , Relação Estrutura-Atividade
8.
Molecules ; 26(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33915741

RESUMO

As an important zoonotic pathogen, Streptococcus suis (S. suis) can cause a variety of diseases both in human and animals, especially Streptococcal toxic shock-like syndrome (STSLS), which commonly appears in severe S. suis infection. STSLS is often accompanied by excessive production of inflammatory cytokines, which is the main cause of host death. Therefore, it is urgent to find a new strategy to relieve the damage caused by STSLS. In this study, we found, for the first time, that apigenin, as a flavonoid compound, could combine with ampicillin to treat severe S. suis infection. Studies found that apigenin did not affect the growth of S. suis and the secretion of suilysin (SLY), but it could significantly inhibit the hemolytic activity of SLY by directly binding to SLY and destroying its secondary structure. In cell assays, apigenin was found to have no significant toxic effects on effective concentrations, and have a good protective effect on S. suis-infected cells. More importantly, compared with the survival rate of S. suis-infected mice treated with only ampicillin, the survival rate of apigenin combined with an ampicillin-treated group significantly increased to 80%. In conclusion, all results indicate that apigenin in combination with conventional antibiotics can be a potential strategy for treating severe S. suis infection.


Assuntos
Ampicilina/farmacologia , Antibacterianos/farmacologia , Apigenina/farmacologia , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Streptococcus suis/efeitos dos fármacos , Ampicilina/química , Ampicilina/uso terapêutico , Animais , Antibacterianos/química , Apigenina/química , Apigenina/uso terapêutico , Sítios de Ligação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Eritrócitos/efeitos dos fármacos , Proteínas Hemolisinas/antagonistas & inibidores , Proteínas Hemolisinas/química , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Ligação Proteica , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/metabolismo , Relação Estrutura-Atividade , Resultado do Tratamento
9.
Appl Environ Microbiol ; 87(10)2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33674433

RESUMO

Streptococcal toxic shock-like syndrome (STSLS) caused by the epidemic strain of Streptococcus suis leads to severe inflammation and high mortality. The life and health of humans and animals are also threatened by the increasingly severe antimicrobial resistance in Streptococcus suis There is an urgent need to discover novel strategies for the treatment of S. suis infection. Suilysin (SLY) is considered to be an important virulence factor in the pathogenesis of S. suis In this study, ellipticine hydrochloride (EH) was reported as a compound that antagonizes the hemolytic activity of SLY. In vitro, EH was found to effectively inhibit SLY-mediated hemolytic activity. Furthermore, EH had a strong affinity for SLY, thereby directly binding to SLY to interfere with the hemolytic activity. Meanwhile, it was worth noting that EH was also found to have a significant antibacterial activity. In vivo, compared with traditional ampicillin, EH not only significantly improved the survival rate of mice infected with S. suis 2 strain Sc19 but also relieved lung pathological damage. Furthermore, EH effectively decreased the levels of inflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor alpha [TNF-α]) and blood biochemistry enzymes (alanine transaminase [ALT], aspartate transaminase [AST], creatine kinase [CK]) in Sc19-infected mice. Additionally, EH markedly reduced the bacterial load of tissues in Sc19-infected mice. In conclusion, our findings suggest that EH can be a potential compound for treating S. suis infection in view of its antibacterial and antihemolysin activity.IMPORTANCE In recent years, the inappropriate use of antibiotics has unnecessarily caused the continuous emergence of resistant bacteria. The antimicrobial resistance of Streptococcus suis has also become an increasingly serious problem. Targeting virulence can reduce the selective pressure of bacteria on antibiotics, thereby alleviating the development of bacterial resistance to a certain extent. Meanwhile, the excessive inflammatory response caused by S. suis infection is considered the primary cause of acute death. Here, we found that ellipticine hydrochloride (EH) exhibited effective antibacterial and antihemolysin activities against S. suis in vitro In vivo, compared with ampicillin, EH had a significant protective effect on S. suis serotype 2 strain Sc19-infected mice. Our results indicated that EH, with dual antibacterial and antivirulence effects, will contribute to treating S. suis infections and alleviating the antimicrobial resistance of S. suis to a certain extent. More importantly, EH may develop into a promising drug for the prevention of acute death caused by excessive inflammation.


Assuntos
Antibacterianos/uso terapêutico , Proteínas de Bactérias/metabolismo , Elipticinas/uso terapêutico , Proteínas Hemolisinas/metabolismo , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus suis , Fatores de Virulência/metabolismo , Animais , Antibacterianos/farmacologia , Citocinas/sangue , Modelos Animais de Doenças , Elipticinas/farmacologia , Feminino , Hemólise/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Infecções Estreptocócicas/sangue , Streptococcus suis/efeitos dos fármacos , Streptococcus suis/crescimento & desenvolvimento , Streptococcus suis/metabolismo
10.
Rheumatol Int ; 41(5): 851-861, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33687528

RESUMO

Patients with rheumatic diseases are often more susceptible to different bacteria and viruses because of immune impairment, but it is not clear whether there is a higher risk of infection and a more serious course of disease for novel coronavirus (SARS-CoV-2). We performed this systematic review and meta analysis to assess the risk and clinical outcomes of COVID-19 in patients with rheumatic diseases compared with the general population. We searched PubMed, EMBASE, Scopus and Web of Science databases from January 1, 2020 to October 20, 2020 to determine epidemiological information related to patients with rheumatic diseases and COVID-19, including clear risk estimate or data that could be converted and extracted. We included 26 observational studies, totaling about 2000 patients with rheumatic diseases of whom were infected with COVID-19. Meta-analysis showed that the risk of COVID-19 infection in rheumatic patients was significantly higher than that in the general population (OR = 1.53, 95% CI 1.24-1.88, P = 0.000). In terms of hospitalization and severe clinical outcomes associated with COVID-19, we found that rheumatic patients showed similar results to the reference population (hospitalization OR = 1.36, 95% CI 0.81-2.29, P = 0.247; admitted to ICU OR = 1.94, 95% CI 0.88-4.27, P = 0.098; death OR = 1.29, 95% CI 0.84-1.97, P = 0.248). The presence of comorbidities, hypertension, lung diseases were significantly associated with the increased risk of COVID-19-related hospitalization in rheumatic patients and anti-TNF drugs were associated with lower hospitalization risk. Older age was related to severe COVID-19. Our meta-analysis indicated that rheumatic patients were at a higher risk of COVID-19 infection but might not lead to a more serious disease process.


Assuntos
COVID-19/mortalidade , Doenças Reumáticas/epidemiologia , Adulto , Idoso , Comorbidade , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Pandemias , Doenças Reumáticas/terapia , Medição de Risco , SARS-CoV-2 , Índice de Gravidade de Doença
11.
J Atheroscler Thromb ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33536397

RESUMO

AIM: Previously, we found that diabetes-related liver dysfunction is due to activation of the 5-HT2A receptor (5-HT2AR) and increased synthesis and degradation of 5-HT. Here, we investigated the role of 5-HT in the development of atherosclerosis. METHODS: The study was conducted using high-fat diet-fed male ApoE-/- mice, THP-1 cell-derived macrophages, and HUVECs. Protein expression and biochemical indexes were determined by Western blotting and quantitative analysis kit, respectively. The following staining methods were used: oil red O staining (showing atherosclerotic plaques and intracellular lipid droplets), immunohistochemistry (showing the expression of 5-HT2AR, 5-HT synthase, and CD68 in the aortic wall), and fluorescent probe staining (showing intracellular ROS). RESULTS: In addition to improving hepatic steatosis, insulin resistance, and dyslipidemia, co-treatment with a 5-HT synthesis inhibitor and a 5-HT2AR antagonist significantly suppressed the formation of atherosclerotic plaques and macrophage infiltration in the aorta of ApoE-/- mice in a synergistic manner. Macrophages and HUVECs exposed to oxLDL or palmitic acid in vitro showed that activated 5-HT2AR regulated TG synthesis and oxLDL uptake by activating PKCε, resulting in formation of lipid droplets and even foam cells; ROS production was due to the increase of both intracellular 5-HT synthesis and mitochondrial MAO-A-catalyzed 5-HT degradation, which leads to the activation of NF-κB and the release of the inflammatory cytokines TNF-α and IL-1ß from macrophages and HUVECs as well as MCP-1 release from HUVECs. CONCLUSION: Similar to hepatic steatosis, the pathogenesis of lipid-induced atherosclerosis is associated with activation of intracellular 5-HT2AR, 5-HT synthesis, and 5-HT degradation.

12.
Sci Total Environ ; 755(Pt 1): 142512, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33011596

RESUMO

Wet precipitation, as an important process of geochemical cycling and the most effective way of cleaning fine atmospheric particles (PM2.5), can introduce the toxic substances in the atmosphere into the water environment. The adverse effect of wet precipitation of PM2.5 on marine fish is still unclear. In this study, PM2.5 samples were collected from six locations along coastal areas of the south China sea for 30 days and used to simulate the impacts of multiday discontinuity wet precipitation of PM2.5 on marine medaka (Oryzias melastigma) in the case of 30 days discontinuity heavy rain (rainfall ≥ 7.6 mm/h and persist 1 h each day). Results showed that wet precipitation of PM2.5 significantly inhibited the body weight gain of fish. In accordance, the size and number of lipid droplets in liver of the exposed groups were lower than those in normal control (NC) group. The expressions of genes involving in lipid degradation including lipoprotein lipase gene (LPL) and carnitine palmitoyltransferase gene (CPT) were up-regulated after exposure. The composition, diversity and function of gut microbiome were affected by wet precipitation of PM2.5. PM2.5 from industrial areas that have higher concentrations of metal profiles show more obvious impacts than PM2.5 from agricultural leisure areas that possessed lower concentrations. All together, the results indicated that wet precipitation of PM2.5 can decrease the diversity of gut microbiome, affect the lipid metabolism, and finally suppress the growth of marine medaka. It confirmed the potential ecological risks of long-term rainfall in air pollution areas to the aquatic organisms.


Assuntos
Microbioma Gastrointestinal , Oryzias , Poluentes Químicos da Água , Animais , China , Material Particulado/toxicidade , Tiazóis , Poluentes Químicos da Água/toxicidade
13.
Arch Biochem Biophys ; 692: 108522, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32781051

RESUMO

About one quarter of people worldwide are infected with tuberculosis, and multi-drug resistant tuberculosis (MDR-TB) remains a health threat. It is known that two-Component Signal Transduction Systems (TCSs) of Mycobacterium tuberculosis are closely related to tuberculosis resistance, but the mechanism by which orphan response protein Rv3143 regulates strain sensitivity to drug is still unclear. This study found that Rv3143 overexpression resulted in approximately two-fold increase in Mycobacterium smegmatis antibiotic sensitivity. Transcriptome sequencing indicated that 198 potential genes were regulated by Rv3143, affecting the sensitivity of the strain to rifampicin (RIF). MSMEG_4740 promoter binding with Rv3143, was screened out by surface plasmon resonance (SPR). Rv1524, the homologous gene of MSMEG_4740, belonging to the glycosyltransferase (Gtf) family, was related to cell wall modification. By measuring ethidium bromide (EB) accumulation, we found when Rv3143 or MSMEG_4740, or Rv1524 was overexpressed, the cell wall permeability of Mycobacterium smegmatis was increased. In addition, a combination of Rv3143 and RIF was observed. Our findings provide a new strategy for treating drug-resistant tuberculosis by increasing the expression of Rv3143 to enhance the strain sensitivity to antibiotics.


Assuntos
Proteínas de Bactérias/metabolismo , Parede Celular/metabolismo , Farmacorresistência Bacteriana , Mycobacterium smegmatis/metabolismo , Proteínas de Bactérias/genética , Parede Celular/genética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Mycobacterium smegmatis/genética , Permeabilidade/efeitos dos fármacos , Rifampina/farmacologia , Transcriptoma/efeitos dos fármacos
14.
Rev Sci Instrum ; 91(7): 073908, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32752802

RESUMO

On the basis of the stress-strength model of the ball bearing with random parameters, the reliability sensitivity of the raceway strength is examined. The basic parameters are regarded as random variables subject to normal distribution. The Latin hypercube sampling method is adopted to obtain the samples, which are brought into the bearing model to obtain the corresponding maximum orthogonal shear stress. The explicit expression of shear stress was obtained by genetic algorithm-back propagation neural network fitting, and the limit-state equation is established in combination with the yield limit of bearing materials. First, this study analyzes the sensitivity of the maximum shear stress with respect to various parameters and obtains the effect of parameters on shear stress at various rotational speeds. Then, based on the stress-strength state equation, the strength reliability is obtained by using the improved first-order second-moment method, which is verified by Monte Carlo simulation. Finally, the reliability sensitivity with respect to the mean and standard variance of random variables is analyzed. This research can provide theoretical guidance for the design, production, and use of bearings.

15.
Microb Pathog ; 147: 104357, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32603765

RESUMO

The two-component system BaeSR is an extra-cytoplasmic stress response system in Escherichia coli, whose function is to be adapted to environmental stress. Recently, we have identified an active type VI secretion system in porcine extra-intestinal pathogenic Escherichia coli PCN033. DNA-protein interactions shows that BaeR directly binds to the promoter region of the T6SS and then induces its expression. Deletion of baeR/baeSR decreased zinc resistance of bacteria. Moreover, T6SS mutant Δhcp1/hcp2/hcp3 is more sensitive than wild type after exposure to external zinc, and complementation of hcp1 largely restored growth defect. Our study uncovers a new regulation mechanism of BaeSR system in response to metal stress. It reveals that BaeR-regulated T6SS is critical for bacteria survival under toxic zinc condition. In conclusion, T6SS contributes to zinc stress resistance in a BaeSR system-dependent manner.


Assuntos
Proteínas de Escherichia coli , Sistemas de Secreção Tipo VI , Animais , Proteínas de Bactérias/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Intestinos , Suínos , Sistemas de Secreção Tipo VI/genética , Sistemas de Secreção Tipo VI/metabolismo , Zinco
16.
Front Microbiol ; 11: 806, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32528422

RESUMO

Extraintestinal pathogenic Escherichia coli (ExPEC) strains are the cause of a majority of human extraintestinal infections globally, resulting in enormous direct economic and medical costs. The plasmid-mediated, colistin-resistant gene mcr-1 has broken through the ultimate defense line against MDR Gram-negative pathogens. There is an urgent need to discover the new compound intended for colistin-resistant E. coli. In this study, antibacterial targets of ellipticine hydrochloride (EH) were confirmed by localized surface plasmon resonance (LSPR) and decatenation assay. The LSPR analysis exhibited good binding between EH and E. coli topoisomerase IV. In this study, a synergistic effect is obvious in the combination of EH and colistin, to which eight of ten strains showed synergy, while two isolates (20%) showed no difference. The bacteria enumeration analysis of EH treatment group suggested that the decreased bacterial titer can be observed in various tissues of infected mice. EH treatment significantly decreased the levels of a variety of pro-inflammatory factors, such as TNF-α and IL-6. Moreover, other related lesions, such as inflammatory cell infiltration, alveolar interstitial congestion, and edema were observed to be relieved to different extents. This study reveals the anti-E. coli potential activities and molecular mechanism of EH and the therapeutical effectiveness of EH application to animals. It provides us with a new option for fighting against multidrug-resistant ExPEC infections in the future.

17.
Molecules ; 25(1)2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31861925

RESUMO

Background: Tuberculosis remains a global disease that poses a serious threat to human health, but there is lack of new and available anti-tuberculosis agents to prevent the emergence of drug-resistant strains. To address this problem natural products are still potential sources for the development of novel drugs. Methods: A whole-cell screening approach was utilized to obtain a natural compound enniatin A1 from a natural products library. The target compound's antibacterial activity against Mycobacterium tuberculosis (M. tuberculosis) was evaluated by using the resazurin reduction micro-plate assay (REMA) method. The cytotoxicity of the compound against Vero cells was measured to calculate the selectivity index. The intracellular inhibition activity of enniatin A1 was determined. We performed its time-kill kinetic assay against M. tuberculosis. We first tested its synergistic effect in combination with the first and second-line anti-tuberculosis drugs. Finally, we measured the membrane potential and intracellular ATP levels of M. tuberculosis after exposure to enniatin A1. Results: We identified enniatinA1 as a potential antibacterial agent against M. tuberculosis, against which it showed strong selectivity. Enniatin A1 exhibited a time-concentration-dependent bactericidal effect against M. tuberculosis, and it displayed synergy with rifamycin, amikacin, and ethambutol. After exposure to enniatinA1, the membrane potential and intracellular ATP levels of M. tuberculosis was significantly decreased. Conclusions: Enniatin A1 exhibits the positive potential anti-tuberculosis agent characteristics.


Assuntos
Trifosfato de Adenosina/metabolismo , Antituberculosos/farmacologia , Depsipeptídeos/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Mycobacterium tuberculosis/metabolismo , Tuberculose/tratamento farmacológico , Animais , Antituberculosos/agonistas , Chlorocebus aethiops , Depsipeptídeos/agonistas , Avaliação de Medicamentos , Sinergismo Farmacológico , Humanos , Células THP-1 , Células Vero
18.
Biosci Rep ; 39(2)2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30643010

RESUMO

Down-regulation of p16INK4a and miR-146b-5p contributes to tumorigenesis in osteosarcoma (OS). However, the correlation between p16INK4a and miR-146b-5p in OS proliferation remains largely unknown. In the present study, we demonstrated that miR-146b-5p expression was positively correlated with p16INK4a in OS, but inversely correlated with TNF receptor associated factor 6 (TRAF6) expression. Overexpression of miR-146b-5p dramatically suppressed OS cell proliferation. Mechanistically, we validated TRAF6 as a direct functional target of miR-146b-5p and found that miR-146b-5p overexpression significantly decreased the level of phosphorylated PI3k and Akt, which are the pivotal downstream effectors of TRAF6. Moreover, TRAF6 expression was positively correlated with Ki-67 but inversely correlated with miR-146b-5p expression. In OS cells, silencing of TRAF6 mimicked the anti-tumor effects of miR-146b-5p. p16INK4a is an important tumor suppressor gene frequently down-regulated in OS. We found that this inhibitory effect is associated with the suppression of the miR-146b-5p, and is mediated via up-regulating TRAF6 expression. Our findings identified p16INK4a and miR-146b-5p as tumor suppressors, and suggested p16INK4a, miR-146b-5p and TRAF6 as potential therapeutic candidates for malignant OS.


Assuntos
Neoplasias Ósseas/patologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/metabolismo , Osteossarcoma/patologia , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , MicroRNAs/genética , Osteossarcoma/genética , Osteossarcoma/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
19.
J Acoust Soc Am ; 142(1): 84, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28764435

RESUMO

In this paper, a broadband acoustic right-angle bend device in air is designed, fabricated and experimentally characterized. Perforated panels with various hole-sizes are used to construct the bend structure. Both the simulated and experimental results verify that the acoustic beam can be rotated effectively through the acoustic bend in a wide frequency range. This model may have potential applications in some areas such as sound absorption and acoustic detection in elbow pipes.

20.
Sci Rep ; 7(1): 2052, 2017 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-28515442

RESUMO

Pre-mRNA alternative splicing and alternative polyadenylation have been implicated to play important roles during eukaryotic gene expression. However, much remains unknown regarding the regulatory mechanisms and the interactions of these two processes in plants. Here we focus on an Arabidopsis gene OXT6 (Oxidative Tolerant-6) that has been demonstrated to encode two proteins through alternative splicing and alternative polyadenylation. Specifically, alternative polyadenylation at Intron-2 of OXT6 produces a transcript coding for AtCPSF30, an Arabidopsis ortholog of 30 kDa subunit of the Cleavage and Polyadenylation Specificity Factor. On the other hand, alternative splicing of Intron-2 generates a longer transcript encoding a protein named AtC30Y, a polypeptide including most part of AtCPSF30 and a YT521B domain. To investigate the expression outcome of OXT6 in plants, a set of mutations were constructed to alter the splicing and polyadenylation patterns of OXT6. Analysis of transgenic plants bearing these mutations by quantitative RT-PCR revealed a competition relationship between these two processes. Moreover, when both splice sites and poly(A) signals were mutated, polyadenylation became the preferred mode of OXT6 processing. These results demonstrate the interplay between alternative splicing and alternative polyadenylation, and it is their concerted actions that define a gene's expression outcome.


Assuntos
Processamento Alternativo , Proteínas de Arabidopsis/genética , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Íntrons , Mutação , Poli A/genética , Poliadenilação , Sítios de Splice de RNA
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...