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1.
Acta Otolaryngol ; : 1-4, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32068453

RESUMO

Background: It has been demonstrated that miRNAs play critical roles in the tumorigenesis and progression of various tumors.Objective: The purpose of this research was to determine the serum miR-632 levels in patients with laryngeal squamous cell carcinoma (LSCC) and to investigate its diagnostic and prognostic value.Materials and methods: We detected serum miR-632 levels in 162 LSCC patients and 42 healthy volunteers. The ROC curve was carried out to determine diagnostic accuracy.Results: We observed that serum miR-632 levels were upregulated in LSCC patients compared with healthy volunteers (p < .01). Subsequent results from ROC indicated that high sensitivity and specificity of serum miR-632 for diagnosing LSCC (area under the curve 0.8828). In addition, it was found that high expressions of serum miR-632 were significantly associated with advanced N stage (p = .020), histological grade (p = .001), and TNM stage (p = .014). Furthermore, patients with higher serum miR-632 expression had a shorter OS and DFS time than those with lower serum miR-632 levels.Conclusion: Our data revealed that serum miR-632 may be a potential noninvasive biomarker which may become a potential diagnostic and prognostic biomarker for LSCC patients.

2.
Crit Care ; 23(1): 300, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484582

RESUMO

RATIONALE: Our pilot study suggested that noninvasive ventilation (NIV) reduced the need for intubation compared with conventional administration of oxygen on patients with "early" stage of mild acute respiratory distress syndrome (ARDS, PaO2/FIO2 between 200 and 300). OBJECTIVES: To evaluate whether early NIV can reduce the need for invasive ventilation in patients with pneumonia-induced early mild ARDS. METHODS: Prospective, multicenter, randomized controlled trial (RCT) of NIV compared with conventional administration of oxygen through a Venturi mask. Primary outcome included the numbers of patients who met the intubation criteria. RESULTS: Two hundred subjects were randomized to NIV (n = 102) or control (n = 98) groups from 21 centers. Baseline characteristics were similar in the two groups. In the NIV group, PaO2/FIO2 became significantly higher than in the control group at 2 h after randomization and remained stable for the first 72 h. NIV did not decrease the proportion of patients requiring intubation than in the control group (11/102 vs. 9/98, 10.8% vs. 9.2%, p = 0.706). The ICU mortality was similar in the two groups (7/102 vs. 7/98, 4.9% vs. 3.1%, p = 0.721). Multivariate analysis showed minute ventilation greater than 11 L/min at 48 h was the independent risk factor for NIV failure (OR, 1.176 [95% CI, 1.005-1.379], p = 0.043). CONCLUSIONS: Treatment with NIV did not reduce the need for intubation among patients with pneumonia-induced early mild ARDS, despite the improved PaO2/FIO2 observed with NIV compared with standard oxygen therapy. High minute ventilation may predict NIV failure. TRIAL REGISTRATION: NCT01581229 . Registered 19 April 2012.

3.
Theor Appl Genet ; 132(10): 2815-2827, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31309244

RESUMO

KEY MESSAGE: An enhanced-grain number per spike locus from Agropyron cristatum 6PL was mapped onto 6PL (0.27-0.51) via deletion mapping, and its effect was further verified by evaluating a newly created translocation line. Agropyron cristatum (2n = 4x = 28, PPPP) is an important wild relative of common wheat and carries many desirable yield-related traits. The wheat-A. cristatum 6P disomic addition line 4844-12 exhibited high grain number per spike (GNS), high spikelet number per spike (SNS), and high kernel number per spikelet (KNS). In this study, five A. cristatum 6P deletion lines, five wheat-A. cristatum 6P translocation lines, and genetic populations of these lines were used to map the enhanced-GNS locus from A. cristatum chromosome 6P, which were genotyped via genomic in situ hybridization, fluorescence in situ hybridization, or molecular markers. According to the evaluation of the agronomic traits in four growing seasons (2014-2015, 2015-2016, 2016-2017, and 2017-2018), we found that the deletion lines and the translocation lines carrying the long arm of A. cristatum chromosome 6P (6PL) exhibited high GNS, SNS, and KNS, and the enhanced-GNS locus was ultimately mapped onto 6PL (0.27-0.51). To verify the localization results, we created a new translocation line WAT650a (T5BL•5BS-6PL) that carried 6PL (0.35-0.42); this line exhibited higher GNS and SNS than the recipient parent Fukuhokomugi (Fukuho). Collectively, the enhanced-GNS locus of A. cristatum 6PL can be important for improving yield traits in common wheat; the translocation lines with the enhanced-GNS locus can serve as novel and valuable germplasm resources for wheat breeding.


Assuntos
Agropyron/genética , Cromossomos de Plantas/genética , Grão Comestível/crescimento & desenvolvimento , Locos de Características Quantitativas , Deleção de Sequência , Translocação Genética , Triticum/genética , Agropyron/crescimento & desenvolvimento , Mapeamento Cromossômico , Grão Comestível/anatomia & histologia , Grão Comestível/genética , Marcadores Genéticos , Genótipo , Hibridização Genética , Triticum/crescimento & desenvolvimento
4.
Respirology ; 24(12): 1152-1155, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31157493

RESUMO

Non-invasive positive pressure ventilation (NPPV) is undoubtedly one of the most significant advancements in mechanical ventilation technology in the past 30 years. With accumulating evidence from clinical studies and support from clinical guidelines, NPPV is now widely used in hospitals and increasingly prescribed for home therapy in the Asia-Pacific region. However, in comparison with the developed Western countries, overall use of NPPV in the region is lagging behind. This study reviews this imbalance of NPPV use both in the acute and domiciliary settings in the Asia-Pacific region. Important issues related to NPPV use are also discussed along with speculation around potential strategies that could promote wider implementation of NPPV in the region. We hope this review will stimulate interest in the clinical application and potential research avenues for NPPV in the Asia-Pacific region, and promote education and staff training in the technique.

5.
mBio ; 10(3)2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088930

RESUMO

Helicobacter pylori colonizes about half of humans worldwide, and its presence in the gastric mucosa is associated with an increased risk of gastric adenocarcinoma, gastric lymphoma, and peptic ulcer disease. H. pylori strains carrying the cag pathogenicity island (cagPAI) are associated with increased risk of disease progression. The cagPAI encodes the Cag type IV secretion system (CagT4SS), which delivers the CagA oncoprotein and other effector molecules into human gastric epithelial cells. We visualized structures of native and mutant CagT4SS machines on the H. pylori cell envelope by cryoelectron tomography. Individual H. pylori cells contain multiple CagT4SS nanomachines, each composed of a wheel-shaped outer membrane complex (OMC) with 14-fold symmetry and an inner membrane complex (IMC) with 6-fold symmetry. CagX, CagY, and CagM are required for assembly of the OMC, whereas strains lacking Cag3 and CagT produce outer membrane complexes lacking peripheral components. The IMC, which has never been visualized in detail, is configured as six tiers in cross-section view and three concentric rings surrounding a central channel in end-on view. The IMC contains three T4SS ATPases: (i) VirB4-like CagE, arranged as a hexamer of dimers at the channel entrance; (ii) a hexamer of VirB11-like Cagα, docked at the base of the CagE hexamer; and (iii) VirD4-like Cagß and other unspecified Cag subunits, associated with the stacked CagE/Cagα complex and forming the outermost rings. The CagT4SS and recently solved Legionella pneumophila Dot/Icm system comprise new structural prototypes for the T4SS superfamily.IMPORTANCE Bacterial type IV secretion systems (T4SSs) have been phylogenetically grouped into two subfamilies. The T4ASSs, represented by the Agrobacterium tumefaciens VirB/VirD4T4SS, include "minimized" machines assembled from 12 VirB- and VirD4-like subunits and compositionally larger systems such as the Helicobacter pylori CagT4SS T4BSSs encompass systems closely related in subunit composition to the Legionella pneumophila Dot/IcmT4SS Here, we present structures of native and mutant H. pylori Cag machines determined by in situ cryoelectron tomography. We identify distinct outer and inner membrane complexes and, for the first time, visualize structural contributions of all three "signature" ATPases of T4SSs at the cytoplasmic entrance of the translocation channel. Despite their evolutionary divergence, the CagT4SS aligns structurally much more closely to the Dot/IcmT4SS than an available VirB/VirD4 subcomplex. Our findings highlight the diversity of T4SSs and suggest a structural classification scheme in which T4SSs are grouped as minimized VirB/VirD4-like or larger Cag-like and Dot/Icm-like systems.


Assuntos
Proteínas de Bactérias/genética , Helicobacter pylori/genética , Sistemas de Secreção Tipo IV/genética , Sistemas de Secreção Tipo IV/ultraestrutura , Antígenos de Bactérias/genética , Microscopia Crioeletrônica , Ilhas Genômicas , Humanos
6.
Front Plant Sci ; 9: 1484, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30364249

RESUMO

High-density genetic linkage maps are essential for precise mapping quantitative trait loci (QTL) in wheat (Triticum aestivum L.). In this study, a high-density genetic linkage map consisted of 6312 SNP and SSR markers was developed to identify QTL controlling kernel size and weight, based on a recombinant inbred line (RIL) population derived from the cross of Shixin828 and Kenong2007. Seventy-eight putative QTL for kernel length (KL), kernel width (KW), kernel diameter ratio (KDR), and thousand kernel weight (TKW) were detected over eight environments by inclusive composite interval mapping (ICIM). Of these, six stable QTL were identified in more than four environments, including two for KL (qKL-2D and qKL-6B.2), one for KW (qKW-2D.1), one for KDR (qKDR-2D.1) and two for TKW (qTKW-5A and qTKW-5B.2). Unconditional and multivariable conditional QTL mapping for TKW with respect to TKW component (TKWC) revealed that kernel dimensions played an important role in regulating the kernel weight. Seven QTL-rich genetic regions including seventeen QTL were found on chromosomes 1A (2), 2D, 3A, 4B and 5B (2) exhibiting pleiotropic effects. In particular, clusters on chromosomes 2D and 5B possessing significant QTL for kernel-related traits were highlighted. Markers tightly linked to these QTL or clusters will eventually facilitate further studies for fine mapping, candidate gene discovery and marker-assisted selection (MAS) in wheat breeding.

7.
iScience ; 6: 222-231, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-30240613

RESUMO

Pseudomonas species are a large class of gram-negative bacteria that exhibit significant biomedical, ecological, and industrial importance. Despite the extensive research and wide applications, genetic manipulation in Pseudomonas species, in particular in the major human pathogen Pseudomonas aeruginosa, remains a laborious endeavor. Here we report the development of a genome editing method pCasPA/pACRISPR by harnessing the CRISPR/Cas9 and the phage λ-Red recombination systems. The method allows for efficient and scarless genetic manipulation in P. aeruginosa. By engineering the fusion of the cytidine deaminase APOBEC1 and the Cas9 nickase, we further develop a base editing system pnCasPA-BEC, which enables highly efficient gene inactivation and point mutations in a variety of Pseudomonas species, such as P. aeruginosa, Pseudomonas putida, Pseudomonas fluorescens, and Pseudomonas syringae. Application of the two genome editing methods will dramatically accelerate a wide variety of investigations, such as bacterial physiology study, drug target exploration, and metabolic engineering.

8.
Theor Appl Genet ; 131(12): 2677-2698, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30255337

RESUMO

KEY MESSAGE: QTL for a wheat ideotype root system and its plasticity to nitrogen deficiency were characterized. Root system architecture-related traits (RRTs) and their plasticity to nitrogen availability are important for nitrogen acquisition and yield formation in wheat (Triticum aestivum L.). In this study, quantitative trait loci (QTL) analysis was conducted under different nitrogen conditions, using the seedlings of 188 recombinant inbred lines derived from a cross between Kenong 9204 and Jing 411. Fifty-three QTL for seven RRTs and fourteen QTL for the plasticity of these RRTs to nitrogen deficiency were detected. Thirty of these QTL were mapped in nine clusters on chromosomes 2B, 2D, 3A, 3D, 6B, 6D, 7A and 7B. Six of these nine clusters were also colocated with loci for nitrogen use efficiency (NUE)-related traits (NRTs). Among them, three QTL clusters (C2B, C6D and C7B) were highlighted, considering that they individually harbored three stable robust QTL (i.e., QMrl-2B.1, QdRs-6D and QMrl-7B). C2B and C7B stably contributed to the optimal root system, and C6D greatly affected the plasticity of RRTs in response to nitrogen deficiency. However, strong artificial selection was only observed for C7B in 574 derivatives of Kenong 9204. Covariance analysis identified QMrl-7B as the major contributor in C7B that affected the investigated NRTs in mature plants. Phenotypic analysis indicated that thousand kernel weight might represent a "concomitant" above-ground trait of the "hidden" RRTs controlled by C7B, which are used for breeding selection. Dissecting these QTL regions with potential breeding value will ultimately facilitate the selection of donor lines with both high yield and NUE in wheat breeding programs.


Assuntos
Nitrogênio/metabolismo , Raízes de Plantas/metabolismo , Locos de Características Quantitativas , Triticum/genética , Fenótipo , Melhoramento Vegetal , Raízes de Plantas/genética , Plântula/genética , Plântula/metabolismo , Triticum/metabolismo
9.
Appl Environ Microbiol ; 84(23)2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30217854

RESUMO

Klebsiella pneumoniae is a promising industrial microorganism as well as a major human pathogen. The recent emergence of carbapenem-resistant K. pneumoniae has posed a serious threat to public health worldwide, emphasizing a dire need for novel therapeutic means against drug-resistant K. pneumoniae Despite the critical importance of genetics in bioengineering, physiology studies, and therapeutic-means development, genome editing, in particular, the highly desirable scarless genetic manipulation in K. pneumoniae, is often time-consuming and laborious. Here, we report a two-plasmid system, pCasKP-pSGKP, used for precise and iterative genome editing in K. pneumoniae By harnessing the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 genome cleavage system and the lambda Red recombination system, pCasKP-pSGKP enabled highly efficient genome editing in K. pneumoniae using a short repair template. Moreover, we developed a cytidine base-editing system, pBECKP, for precise C→T conversion in both the chromosomal and plasmid-borne genes by engineering the fusion of the cytidine deaminase APOBEC1 and a Cas9 nickase. By using both the pCasKP-pSGKP and the pBECKP tools, the bla KPC-2 gene was confirmed to be the major factor that contributed to the carbapenem resistance of a hypermucoviscous carbapenem-resistant K. pneumoniae strain. The development of the two editing tools will significantly facilitate the genetic engineering of K. pneumoniae IMPORTANCE Genetics is a key means to study bacterial physiology. However, the highly desirable scarless genetic manipulation is often time-consuming and laborious for the major human pathogen K. pneumoniae We developed a CRISPR-Cas9-mediated genome-editing method and a cytidine base-editing system, enabling rapid, highly efficient, and iterative genome editing in both industrial and clinically isolated K. pneumoniae strains. We applied both tools in dissecting the drug resistance mechanism of a hypermucoviscous carbapenem-resistant K. pneumoniae strain, elucidating that the bla KPC-2 gene was the major factor that contributed to the carbapenem resistance of the hypermucoviscous carbapenem-resistant K. pneumoniae strain. Utilization of the two tools will dramatically accelerate a wide variety of investigations in diverse K. pneumoniae strains and relevant Enterobacteriaceae species, such as gene characterization, drug discovery, and metabolic engineering.


Assuntos
Sistemas CRISPR-Cas , Citidina Desaminase/metabolismo , Edição de Genes/métodos , Engenharia Genética/métodos , Genoma Bacteriano , Klebsiella pneumoniae/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas
10.
Exp Ther Med ; 15(6): 5344-5352, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29805549

RESUMO

Esophageal cancer is a malignant tumor with a relatively high invasiveness, metastatic potential and worldwide incidence among human cancers. The majority of patients with esophageal cancer are diagnosed in a late tumor stage due to a lack of advanced and sensitive protocols for the diagnosis of patients with early-stage esophageal cancer. In the current study, contrast-enhanced computerized tomography (CECT) combined with Chitosan-Fe3O4 nanoparticles targeting fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR; CECT-CNFV) were used to diagnose patients with suspected esophageal cancer. A Chitosan-Fe3O4-parceled bispecific antibody targeting FGFR and VEGFR was produced and its affinity to esophageal cancer cells was determined both in vitro and in vivo. A total of 320 patients with suspected esophageal cancer were voluntarily recruited to evaluate the efficacy of CECT-CNFV in the diagnosis of early-stage esophageal cancer. All participants were subjected to CT and CECT-CNFV to detect whether tumors were present in the esophageal area. A Chitosan-Fe3O4 nanoparticles contrast agent was orally administered at 20 min prior to CT and CECT-CNFV. The results demonstrated that CECT-CNFV improved diagnostic sensitivity and provided a novel protocol for the diagnosis of tumors in patients with suspected gastric cancer at an early-stage. Furthermore, the resolution ratio of images was enhanced by CECT-CNFV, which enabled the visualization of tiny tumor nodules in esophageal tissue. Clinical data demonstrated that CECT-CNFV diagnosed 200 patients with suspected early-stage esophageal cancer and 120 patients as tumor free. In addition, CECT-CNFV exhibited higher signal enhancement of tumor nodules than CT, suggesting a higher accuracy and accumulation of nanoparticle contrast agent within the tumor nodules of esophageal tissue. Notably, the survival rate of patients with esophageal cancer diagnosed at an early-stage by CECT-CNFV was higher than the mean five-year survival rate (P<0.01). In conclusion, CECT-CNFV enhanced the sensitivity and accuracy of CT in the diagnosis of early-stage esophageal cancer. Thus, CECT-CNFV may improve the accuracy of CT in the diagnosis of mural enhancement in patients with esophageal cancer.

11.
Respir Med ; 137: 48-54, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29605212

RESUMO

BACKGROUND: There are limited population based data on the prevalence of asthma in China. The China Asthma and Risk factors Epidemiologic (CARE) survey was designed to understand the prevalence and risk factors for asthma in mainland China. OBJECTIVES: The CARE survey aims to demonstrate the prevalence and risk factors of asthma in mainland China among adolescents (age >14 years) and adults. METHODS: The survey was performed between February 2010 and August 2012 in eight provinces/cities of seven areas in mainland China. The inhabitants (age, >14 years) recruited in this survey were through multi-stage cluster random sampling. Asthma diagnosis was based on medical history and lung function tests. Multivariable logistic regression was used to analyzed the risk factors for asthma. RESULTS: The study included 164 215 subjects (men, 79 692 [48.53%]; women, 84 523 [51.47%]). 2034 (1.24%) were asthmatic patients. Among all asthmatic patients, 521 (25.61%) were newly diagnosed. Univariable regression analysis showed that risk factors for asthma included smoking, first-degree relatives with asthma, allergic rhinitis, chronic bronchitis, COPD, pollinosis, allergic pneumonia, concomitant allergic diseases, BMI and raising pets. Multivariable logistic regression indicated that asthma risk factors included women, age stratification, smoking, first-degree relatives suffering from asthma or pollinosis, combined with allergic rhinitis, eczema or GERD. CONCLUSIONS: We speculated that the prevalence of asthma is increasing in mainland China among individuals aged >14 years in the past 10 years. A number of risk factors were identified. The risk factors of asthma would be further elucidated in our future work. CLINICAL IMPLICATIONS: Our CARE study highlights that asthma epidemic in mainland China should be paid more attention.


Assuntos
Asma/diagnóstico , Asma/epidemiologia , Bronquite Crônica/complicações , Hipersensibilidade/complicações , Prevalência , Rinite Alérgica/complicações , Adolescente , Adulto , Idoso , Asma/fisiopatologia , Bronquite Crônica/epidemiologia , China/epidemiologia , Feminino , Humanos , Hipersensibilidade/epidemiologia , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória/métodos , Rinite Alérgica/epidemiologia , Fatores de Risco , Fumar/efeitos adversos , Inquéritos e Questionários , Adulto Jovem
12.
Int J Mol Med ; 41(6): 3517-3526, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29532856

RESUMO

Mitochondrial dynamics have critical roles in aging, and their impairment represents a prominent risk factor for myocardial dysfunction. Mitochondrial deacetylase sirtuin (SIRT)3 contributes greatly to the prevention of redox stress and cell aging. The present study explored the role of SIRT3 on myocardium aging. Western blot analysis demonstrated that SIRT3 expression levels were significantly lower in the myocardia of aged mice compared with young mice. Immunoprecipitation and western blot assays indicated that the activity of mitochondrial manganese superoxide dismutase (MnSOD) and peroxisome proliferator­activated receptor Î³ coactivator (PGC)­1α was reduced in the aged heart. To further explore the association between SIRT3 and myocardial senescence, SIRT3 heart­specific knockout (SIRT3-/-) mice were used in the present study. The results revealed that obvious features of aging were present in the myocardium of SIRT3-/- mice, including mitochondrial protein dysfunction, enhanced oxidative stress, and energy metabolism dysfunction. SIRT3 deficiency impaired Parkin­mediated mitophagy by increasing p53­Parkin binding and blocking the mitochondrial translocation of Parkin in cardiomyocytes. Injection of autophagy agonist CCCP significantly increased the mitochondrial Parkin level in young wild­type hearts but not in aged hearts; the effect was less pronounced in SIRT3-/- hearts. These data suggest that CCCP­induced Parkin translocation was reduced in aged and SIRT3-/- hearts. CCCP­induced mitochondrial clearance, which could be rescued by autophagy antagonist bafilomycin­A1, was markedly weakened in aged and SIRT3-/- hearts vs. young hearts. SIRT3 deficiency exacerbated p53/Parkin­mediated mitophagy inhibition and disrupted mitochondrial homeostasis, suggesting that loss of SIRT3 may increase the susceptibility of aged hearts to cardiac dysfunction. Therapeutic activation of SIRT3 and improved mitochondrial function may ameliorate the symptoms of cardiac aging.


Assuntos
/fisiologia , Sirtuína 3/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Metabolismo Energético/fisiologia , Coração/fisiologia , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 3/deficiência , Sirtuína 3/genética , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/genética
13.
Proc Natl Acad Sci U S A ; 115(15): 3942-3947, 2018 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29581261

RESUMO

Metal acquisition is vital to pathogens for successful infection within hosts. Staphylopine (StP), a broad-spectrum metallophore biosynthesized by the major human pathogen, Staphylococcus aureus, plays a central role in transition-metal acquisition and bacterial virulence. The StP-like biosynthesis loci are present in various pathogens, and the proteins responsible for StP/metal transportation have been determined. However, the molecular mechanisms of how StP/metal complexes are recognized and transported remain unknown. We report multiple structures of the extracytoplasmic solute-binding protein CntA from the StP/metal transportation system in apo form and in complex with StP and three different metals. We elucidated a sophisticated metal-bound StP recognition mechanism and determined that StP/metal binding triggers a notable interdomain conformational change in CntA. Furthermore, CRISPR/Cas9-mediated single-base substitution mutations and biochemical analysis highlight the importance of StP/metal recognition for StP/metal acquisition. These discoveries provide critical insights into the study of novel metal-acquisition mechanisms in microbes.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Transporte/metabolismo , Cobalto/metabolismo , Imidazóis/metabolismo , Níquel/metabolismo , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/metabolismo , Zinco/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Transporte/química , Proteínas de Transporte/genética , Cobalto/química , Humanos , Níquel/química , Ligação Proteica , Domínios Proteicos , Infecções Estafilocócicas/metabolismo , Staphylococcus aureus/química , Staphylococcus aureus/genética , Zinco/química
14.
Int J Mol Sci ; 18(11)2017 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-29137188

RESUMO

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most destructive diseases of wheat (Triticum aestivum L.) worldwide. Agropyron cristatum (L.) Gaertn. (2n = 28, PPPP), one of the wild relatives of wheat, exhibits resistance to stripe rust. In this study, wheat-A. cristatum 6P disomic addition line 4844-12 also exhibited resistance to stripe rust. To identify the stripe rust resistance locus from A. cristatum 6P, ten translocation lines, five deletion lines and the BC2F2 and BC3F2 populations of two wheat-A. cristatum 6P whole-arm translocation lines were tested with a mixture of two races of Pst in two sites during 2015-2016 and 2016-2017, being genotyped with genomic in situ hybridization (GISH) and molecular markers. The result indicated that the locus conferring stripe rust resistance was located on the terminal 20% of 6P short arm's length. Twenty-nine 6P-specific sequence-tagged-site (STS) markers mapped on the resistance locus have been acquired, which will be helpful for the fine mapping of the stripe rust resistance locus. The stripe rust-resistant translocation lines were found to carry some favorable agronomic traits, which could facilitate their use in wheat improvement. Collectively, the stripe rust resistance locus from A. cristatum 6P could be a novel resistance source and the screened stripe rust-resistant materials will be valuable for wheat disease breeding.


Assuntos
Agropyron/genética , Basidiomycota/patogenicidade , Resistência à Doença/genética , Genes de Plantas , Triticum/genética , Agropyron/imunologia , Agropyron/microbiologia , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Triticum/imunologia , Triticum/microbiologia
15.
Cell Immunol ; 318: 29-34, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28669409

RESUMO

Basophils (BAs) are the least common granulocytes of all leukocytes, but they play an important role in orchestrating of chronic allergic inflammation. The Notch signaling pathway is a highly conserved pathway that influences cell lineage decisions and differentiation during various stages of development. However, the relationship between Notch signaling and BA remains to be elucidate. Here, we report that several Notch signaling molecules were found to be expressed in BAs. γ-secretase inhibitor (GSI) treatment increase BAs apoptosis, and suppress BAs proliferation. Furthermore, GSI reduced BAs in the S phase, with a concomitant accumulation in G1 and G2 phases. In addition, GSI also significantly down-regulated mRNA levels of cytokines IL-4, IL-6 and IL-13 induced by A23187, and this effect was dependent on MAPK pathway. Finally, IL-6 inhibition was specifically associated with ERK and IL-13 with JNK. Therefore, Notch signaling regulates BA biological function, at least partially via the modulation of MAPK.


Assuntos
Basófilos/imunologia , Hipersensibilidade/imunologia , Inflamação/imunologia , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Calcimicina/farmacologia , Ciclo Celular , Células Cultivadas , Doença Crônica , Citocinas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Mediadores da Inflamação/metabolismo , Camundongos , Oligopeptídeos/farmacologia , Receptores Notch/genética
16.
Angew Chem Int Ed Engl ; 56(31): 9116-9120, 2017 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-28561936

RESUMO

The biosynthesis of antibiotics in bacteria is usually believed to be an intracellular process, at the end of which the matured compounds are exported outside the cells. The biosynthesis of saframycin A (SFM-A), an antitumor antibiotic, requires a cryptic fatty acyl chain to guide the construction of a pentacyclic tetrahydroisoquinoline scaffold; however, the follow-up deacylation and deamination steps remain unknown. Herein we demonstrate that SfmE, a membrane-bound peptidase, hydrolyzes the fatty acyl chain to release the amino group; and SfmCy2, a secreted oxidoreductase covalently associated with FAD, subsequently performs an oxidative deamination extracellularly. These results not only fill in the missing steps of SFM-A biosynthesis, but also reveal that a FAD-binding oxidoreductase catalyzes an unexpected deamination reaction through an unconventional extracellular pathway in Streptmyces bacteria.


Assuntos
Antibióticos Antineoplásicos/biossíntese , Oxirredutases/metabolismo , Pró-Fármacos/metabolismo , Antibióticos Antineoplásicos/química , Biocatálise , Desaminação , Flavina-Adenina Dinucleotídeo/química , Isoquinolinas/química , Isoquinolinas/metabolismo , Pró-Fármacos/química , Streptomyces/metabolismo
17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 33(2): 159-163, 2017 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-28109142

RESUMO

Objective To study the expression levels of TNF-α and IL-1ß in the lung tissues of acute respiratory distress syndrome (ARDS) mice and their relationships with the severity of lung injury in the mice. Methods A mouse model of ARDS was induced by lipopolysaccharide (LPS). The morphological changes of lung tissue was observed by HE staining, and the lung injury score was calculated. Quantitative real-time PCR was employed to detect the mRNA expression levels of TNF-α and IL-1ß in lung tissues and ELISA was performed to test the protein levels of TNF-α and IL-1ß in bronchoalveolar lavage fluid (BALF). Results Compared with the control group, the alveolar and interstitial tissue structure of ARDS model mice was impaired and filled with inflammatory cells. The lung injury score of ARDS model mice reached the peak at the third day. The mRNA levels of TNF-α and IL-1ß in lung tissues of ARDS mice significantly increased, and respectively peaked at 30 minutes and 6 hours after LPS instillation. Simultaneously, the levels of TNF-α and IL-1ß in BALF of ARDS mice significantly increased, and the tendency was consistent with mRNA levels in lung tissues. Conclusion LPS-induced lung injury and the expression levels of TNF-α and IL-1ß in ARDS mice showed a similar "hump-like" increase over time. The high values of inflammatory mediators appeared before the peak of lung injury, which indicated that these inflammatory cytokines played an important role in the development of ARDS-caused inflammatory injury.


Assuntos
Interleucina-1beta/metabolismo , Pulmão/metabolismo , Síndrome do Desconforto Respiratório do Adulto/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Doença Aguda , Animais , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Lipopolissacarídeos , Pulmão/patologia , Camundongos , RNA Mensageiro/metabolismo , Síndrome do Desconforto Respiratório do Adulto/induzido quimicamente , Síndrome do Desconforto Respiratório do Adulto/patologia
18.
Cell Immunol ; 312: 35-41, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27889082

RESUMO

The newly discovered intracytosolic pattern recognition receptor nucleotide-binding oligomerization domain 2 (NOD2) has been studied as an important indicator of T helper 2 (Th2) inflammation, and its effect on regulatory T (Treg) cells is likely to modulate the immune response. In this study, we attempted to study the expression of NOD2 and its impact in human airway smooth muscle cells (HASMC). Quantitative real-time PCR (qRT-PCR) was used to measure the expression level of NOD2 in HASMC and comparisons were made between those from asthmatic and non-asthmatic donors; we found that NOD2 was significantly upregulated in asthma patient tissues and cell lines. In addition, overexpression of NOD2 apparently promotes cell proliferation and migration in HASMC. Gain-of-function in vitro experiments further showed that NOD2 overexpression significantly promotes pro-inflammatory cytokine release in HASMC. Subsequent experimental analysis indicated that thymic stromal lymphopoietin (TSLP) is involved in NOD2-mediated cellular effects in HASMC. Therefore, our results indicate that NOD2 is an asthma-related factor that can promote cell proliferation and inflammatory response by mediated expression of TSLP in HASMC. Taken together, our results indicate that NOD2 could serve as a potential diagnostic biomarker and therapeutic option for human asthma in the near future.


Assuntos
Asma/imunologia , Citocinas/metabolismo , Miócitos de Músculo Liso/imunologia , Proteína Adaptadora de Sinalização NOD2/metabolismo , Pneumonia/imunologia , Sistema Respiratório/patologia , Adolescente , Adulto , Idoso , Proliferação de Células , Células Cultivadas , Citocinas/genética , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteína Adaptadora de Sinalização NOD2/genética , Adulto Jovem
19.
Genome ; 59(10): 840-850, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27643577

RESUMO

Agropyron cristatum (2n = 4x = 28, PPPP) is a wild relative of common wheat and confers several desirable agronomic traits to wheat, such as high grain number per spike and enhanced resistance to certain diseases. Development of wheat - A. cristatum 6P translocation lines facilitates its utilization in wheat improvement. In this study, 26 wheat - A. cristatum 6P translocation lines were characterized by in situ hybridization (ISH) and 6P-specific sequence-tagged-site (STS) markers. These translocation lines carried different 6P chromosomal segments, which covered the whole 6P chromosome. FISH results showed that 15, 5, and 6 lines were translocated onto wheat A, B, and D genomes, respectively. Compared with the previous reports, a fine physical map of 6P chromosome was constructed, consisting of 31 chromosomal bins with 255 STS markers. Twelve translocation lines containing 6PS13∼14 chromosomal bins were highly resistant to leaf rust. Two lines showed high grain number per spike, and three lines displayed both enhanced grain number per spike and thousand-grain weight. Development of wheat - A. cristatum 6P translocation lines will not only provide novel wheat germplasm for wheat breeding but also be helpful to broaden the genetic basis of common wheat.


Assuntos
Cromossomos de Plantas , Característica Quantitativa Herdável , Translocação Genética , Triticum/genética , Agricultura , Produção Agrícola , Marcadores Genéticos , Hibridização in Situ Fluorescente , Repetições de Microssatélites , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Triticum/microbiologia
20.
Planta ; 244(3): 713-23, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27125388

RESUMO

MAIN CONCLUSION: A novel broad-spectrum powdery mildew resistance gene PmPB74 was identified in wheat- Agropyron cristatum introgression line Pubing 74. Development of wheat cultivars with broad-spectrum, durable resistance to powdery mildew has been restricted by lack of superior genetic resources. In this study, a wheat-A. cristatum introgression line Pubing 74, originally selected from a wide cross between the common wheat cultivar Fukuhokomugi (Fukuho) and Agropyron cristatum (L.) Gaertn (2n = 4x = 28; genome PPPP), displayed resistance to powdery mildew at both the seedling and adult stages. The putative alien chromosomal fragment in Pubing 74 was below the detection limit of genomic in situ hybridization (GISH), but evidence for other non-GISH-detectable introgressions was provided by the presence of three STS markers specific to A. cristatum. Genetic analysis indicated that Pubing 74 carried a single dominant gene for powdery mildew resistance, temporarily designated PmPB74. Molecular mapping showed that PmPB74 was located on wheat chromosome arm 5DS, and flanked by markers Xcfd81 and HRM02 at genetic distances of 2.5 and 1.7 cM, respectively. Compared with other lines with powdery mildew resistance gene(s) on wheat chromosome arm 5DS, Pubing 74 was resistant to all 28 Blumeria graminis f. sp tritici (Bgt) isolates from different wheat-producing regions of northern China. Allelism tests indicated that PmPB74 was not allelic to PmPB3558 or Pm2. Our work showed that PmPB74 is a novel gene with broad resistance to powdery mildew, and hence will be helpful in broadening the genetic basis of powdery mildew resistance in wheat.


Assuntos
Agropyron/genética , Ascomicetos/fisiologia , Resistência à Doença/genética , Interações Hospedeiro-Patógeno/genética , Triticum/genética , Mapeamento Cromossômico
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