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1.
Front Plant Sci ; 14: 1101766, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37077639

RESUMEN

Oiltea-camellia (C. oleifera) is a widely cultivated woody oil crop in Southern China and Southeast Asia. The genome of oiltea-camellia was very complex and not well explored. Recently, genomes of three oiltea-camellia species were sequenced and assembled, multi-omic studies of oiltea-camellia were carried out and provided a better understanding of this important woody oil crop. In this review, we summarized the recent assembly of the reference genomes of oiltea-camellia, genes related to economic traits (flowering, photosynthesis, yield and oil component), disease resistance (anthracnose) and environmental stress tolerances (drought, cold, heat and nutrient deficiency). We also discussed future directions of integrating multiple omics for evaluating genetic resources and mining key genes of important traits, and the application of new molecular breeding and gene editing technologies to accelerate the breeding process of oiltea-camellia.

2.
Viruses ; 14(11)2022 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-36366482

RESUMEN

Avian reoviruses (ARV) are a group of poultry pathogens that cause runting and stunting syndrome (RSS), a condition otherwise known as "frozen chicken", which are characterized by dramatically delayed growth in broilers. It has been known that p17, a nonstructural protein encoded by ARV, prohibits cellular proliferation by halting the cell cycle at the G2/M phase, the result of which is directly associated with the typical clinical sign of RSS. Nevertheless, the mechanism by which p17 modulates cell-cycle progression remains largely unknown. Here, we screened the interactome of ectopically expressed p17 through a yeast two-hybrid assay and identified Bub3, a cellular mitotic checkpoint protein, as a binding partner of p17. The infection of the Vero cells by ARV downregulated the Bub3 expression, while the knockdown of Bub3 alleviated the p17-modulated cell-cycle arrest during ARV infection. Remarkably, the suppression of Bub3 by RNAi in the Vero cells significantly reduced the viral mRNA and protein abundance, which eventually led to diminished virus replication. Altogether, our findings reveal that ARV p17 impedes host cell proliferation through a Bub3-dependent cell-cycle arrest, which eventually contributes to efficient virus replication. These results also unveil a hitherto unknown therapeutic target for RSS.


Asunto(s)
Orthoreovirus Aviar , Infecciones por Reoviridae , Chlorocebus aethiops , Animales , Células Vero , Pollos , Ciclo Celular , División Celular
3.
PLoS Pathog ; 18(7): e1010660, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35816513

RESUMEN

Coxiella burnetii is the etiological agent of the zoonotic disease Q fever, which is featured by its ability to replicate in acid vacuoles resembling the lysosomal network. One key virulence determinant of C. burnetii is the Dot/Icm system that transfers more than 150 effector proteins into host cells. These effectors function to construct the lysosome-like compartment permissive for bacterial replication, but the functions of most of these effectors remain elusive. In this study, we used an affinity tag purification mass spectrometry (AP-MS) approach to generate a C. burnetii-human protein-protein interaction (PPI) map involving 53 C. burnetii effectors and 3480 host proteins. This PPI map revealed that the C. burnetii effector CBU0425 (designated CirB) interacts with most subunits of the 20S core proteasome. We found that ectopically expressed CirB inhibits hydrolytic activity of the proteasome. In addition, overexpression of CirB in C. burnetii caused dramatic inhibition of proteasome activity in host cells, while knocking down CirB expression alleviated such inhibitory effects. Moreover, we showed that a region of CirB that spans residues 91-120 binds to the proteasome subunit PSMB5 (beta 5). Finally, PSMB5 knockdown promotes C. burnetii virulence, highlighting the importance of proteasome activity modulation during the course of C. burnetii infection.


Asunto(s)
Coxiella burnetii , Fiebre Q , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Interacciones Huésped-Patógeno , Humanos , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Mapas de Interacción de Proteínas , Fiebre Q/metabolismo , Vacuolas/metabolismo
4.
BMC Vet Res ; 18(1): 204, 2022 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-35624449

RESUMEN

BACKGROUND: Coxiella burnetii (Cb) is the causative agent of the zoonotic disease Q fever which is distributed worldwide. Molecular typing of Cb strains is essential to find out the infectious source and prevent Q fever outbreaks, but there has been a lack of typing data for Cb strains in China. The aim of this study was to investigate the genotypes of Cb strains in wild rats in Yunnan Province, China. RESULTS: Eighty-six wild rats (Rattus flavipectus) were collected in Yunnan Province and 8 of the 86 liver samples from the wild rats were positive in Cb-specific quantitative PCR (qPCR). The Cb strains from the 8 rats were then typed into 3 genotypes using 10-spacer multispacer sequence typing (MST), and 2 of the 3 genotypes were recognized as novel ones. Moreover, the Cb strains in the wild rats were all identified as genotype 1 using 6-loci multilocus variable number of tandem repeat analysis (MLVA). CONCLUSIONS: This is the first report of genotypic diversity of Cb strains from wild rats in China. Further studies are needed to explore the presence of more genotypes and to associate the genotypes circulating in the wildlife-livestock interaction with those causing human disease to further expand on the epidemiological aspects of the pathogen.


Asunto(s)
Coxiella burnetii , Fiebre Q , Enfermedades de los Roedores , Animales , China/epidemiología , Coxiella burnetii/genética , Genotipo , Tipificación Molecular/veterinaria , Fiebre Q/epidemiología , Fiebre Q/veterinaria , Ratas , Enfermedades de los Roedores/epidemiología
5.
Infect Immun ; 90(6): e0001622, 2022 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-35587202

RESUMEN

Coxiella burnetii, the causative agent of zoonotic Q fever, is characterized by replicating inside the lysosome-derived Coxiella-containing vacuole (CCV) in host cells. Some effector proteins secreted by C. burnetii have been reported to be involved in the manipulation of autophagy to facilitate the development of CCVs and bacterial replication. Here, we found that the Coxiella plasmid effector B (CpeB) localizes on vacuole membrane targeted by LC3 and LAMP1 and promotes LC3-II accumulation. Meanwhile, the C. burnetii strain lacking the QpH1 plasmid induced less LC3-II accumulation, which was accompanied by smaller CCVs and lower bacterial loads in THP-1 cells. Expression of CpeB in the strain lacking QpH1 led to restoration in LC3-II accumulation but had no effect on the smaller CCV phenotype. In the severe combined immune deficiency (SCID) mouse model, infections with the strain expressing CpeB led to significantly higher bacterial burdens in the spleen and liver than its parent strain devoid of QpH1. We also found that CpeB targets Rab11a to promote LC3-II accumulation. Intratracheally inoculated C. burnetii resulted in lower bacterial burdens and milder lung lesions in Rab11a conditional knockout (Rab11a-/- CKO) mice. Collectively, these results suggest that CpeB promotes C. burnetii virulence by inducing LC3-II accumulation via a pathway involving Rab11a.


Asunto(s)
Coxiella burnetii , Fiebre Q , Inmunodeficiencia Combinada Grave , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Modelos Animales de Enfermedad , Interacciones Huésped-Patógeno , Ratones , Ratones SCID , Plásmidos , Fiebre Q/microbiología , Inmunodeficiencia Combinada Grave/metabolismo , Vacuolas/microbiología , Virulencia
6.
PLoS Negl Trop Dis ; 15(7): e0009520, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34264939

RESUMEN

Q fever is a worldwide zoonosis caused by Coxiella burnetii (Cb). From January 2018 to November 2019, plasma samples from 2,382 patients with acute fever of unknown cause at a hospital in Zhuhai city of China were tested using metagenomic next-generation sequencing (mNGS). Of those tested, 138 patients (5.8%) were diagnosed with Q fever based on the presence of Cb genomic DNA detected by mNGS. Among these, 78 cases (56.5%) presented from Nov 2018 to Mar 2019, suggesting an outbreak of Q fever. 55 cases with detailed clinical information that occurred during the outbreak period were used for further analysis. The vast majority of plasma samples from those Cb-mNGS-positive patients were positive in a Cb-specific quantitative polymerase chain reaction (n = 38) and/or indirect immunofluorescence assay (n = 26). Mobile phone tracing data was used to define the area of infection during the outbreak. This suggested the probable infection source was Cb-infected goats and cattle at the only official authorized slaughterhouse in Zhuhai city. Phylogenic analysis based on genomic sequences indicated Cb strains identified in the patients, goat and cattle were formed a single branch, most closely related to the genomic group of Cb dominated by strains isolated from goats. Our study demonstrates Q fever was epidemic in 2018-2019 in Zhuhai city, and this is the first confirmed epidemic of Q fever in a contemporary city in China.


Asunto(s)
Coxiella burnetii/aislamiento & purificación , Fiebre Q/microbiología , Adulto , Animales , Bovinos , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/microbiología , Enfermedades de los Bovinos/transmisión , China/epidemiología , Coxiella burnetii/clasificación , Coxiella burnetii/genética , Brotes de Enfermedades , Femenino , Enfermedades de las Cabras/epidemiología , Enfermedades de las Cabras/microbiología , Enfermedades de las Cabras/transmisión , Cabras , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Metagenómica , Persona de Mediana Edad , Filogenia , Fiebre Q/diagnóstico , Fiebre Q/epidemiología , Fiebre Q/transmisión , Adulto Joven , Zoonosis/diagnóstico , Zoonosis/epidemiología , Zoonosis/microbiología , Zoonosis/transmisión
7.
Parasit Vectors ; 14(1): 287, 2021 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-34044867

RESUMEN

BACKGROUND: Hard ticks act as arthropod vectors in the transmission of human and animal pathogens and are widely distributed in northern China. The aim of this study is to screen the important tick-borne pathogens (TBPs) carried by hard ticks in Inner Mongolia using metagenomic next-generation sequencing (mNGS) and to estimate the risk of human infection imposed by tick bites. METHODS: The adult Dermacentor nuttalli (n = 203) and Ixodes persulcatus (n = 36) ticks feeding on cattle were collected. The pooled DNA samples prepared from these ticks were sequenced as the templates for mNGS to survey the presence of TBPs at the genus level. Individual tick DNA samples were detected by genus--specific or group-specific nested polymerase chain reaction (PCR) of these TBPs and combined with DNA sequencing assay to confirm the results of mNGS. RESULTS: R. raoultii (45.32%, 92/203), Candidatus R. tarasevichiae (5.42%, 11/203), Anaplasma sp. Mongolia (26.60%, 54/203), Coxiella-like endosymbiont (CLE) (53.69%, 109/203), and Babesia venatorum (7.88%, 16/203) were detected in D. nuttalli, while R. raoultii (30.56%, 11/36), Anaplasma sp. Mongolia (27.80%, 10/36), and CLE (27.80%, 10/36) were detected in I. persulcatus. The double- and triple-pathogen/endosymbiont co-infections were detected in 40.39% of D. nuttalli and 13.89% of I. persulcatus, respectively. The dual co-infection with R. raoultii and CLE (14.29%, 29/203) and triple co-infection with R. raoultii, Anaplasma sp. Mongolia, and CLE (13.79%, 28/203) were most frequent in D. nuttalli. CONCLUSIONS: This study provides insight into the microbial diversity of D. nuttalli and I. persulcatus in Inner Mongolia, China, reporting for the first time that Candidatus R. tarasevichiae had been found in D. nuttalli in China, and for the first time in the world that Anaplasma sp. Mongolia has been detected in I. persulcatus. This study proves that various vertically transmitted pathogens co-inhabit D. nuttalli and I. persulcatus, and indicates that cattle in Inner Mongolia are exposed to several TBPs.


Asunto(s)
Dermacentor/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Ixodes/genética , Metagenómica , Enfermedades por Picaduras de Garrapatas/diagnóstico , Anaplasma/genética , Anaplasma/aislamiento & purificación , Animales , Vectores Artrópodos/genética , Babesia/genética , Babesiosis/diagnóstico , Bovinos , Ixodes/clasificación , Ixodidae/genética , Mongolia , Reacción en Cadena de la Polimerasa , Rickettsia/genética , Infecciones por Rickettsia/diagnóstico , Infecciones por Rickettsia/veterinaria , Enfermedades por Picaduras de Garrapatas/parasitología
8.
Front Oncol ; 11: 680191, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33996610

RESUMEN

BACKGROUND: The association between driver genes and the incidence of thromboembolic events (TEs) in patients diagnosed with non-small-cell lung cancer (NSCLC) needs to be quantified to guide clinical management. METHODS: We interrogated PubMed, Embase, Web of Science and Cochrane library databases for terms related to venous thromboembolism (VTE) and arterial thromboembolism (ATE) in patients diagnosed with non-small-cell lung cancer harboring driver genes. This search was conducted for studies published between 1 January, 2000 and 31 December, 2020. A random-effects meta-analysis was performed to analyze the pooled incidence and odds ratios of VTE in patients with different driver genes. RESULTS: Of the 2,742 citations identified, a total of 25 studies that included 21,156 patients met eligibility criteria. The overall pooled incidence of VTE in patients with driver genes was 23% (95% CI 18-29). Patients with ROS1 rearrangements had the highest incidence of VTE (37%, 95%CI 23-52). ALK rearrangements were associated with increased VTE risks (OR=2.08,95% CI 1.69-2.55), with the second highest incidence of VTE (27%, 95%CI 20-35). Both groups of patients with EGFR and KRAS mutations did not show a significantly increased risk for VTE (OR=1.33, 95% CI 0.75-2.34; OR=1.31, 95% CI 0.40-4.28). CONCLUSIONS: ALK rearrangements were shown to be associated with increased VTE risks in patients diagnosed with non-small lung cancer, while there was no significant relation observed between VTE risks and EGFR or KRAS mutations in lung cancer patients.

9.
Front Plant Sci ; 12: 604251, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33613598

RESUMEN

The significance of the Chinese Loess Plateau (CLP) in maintaining biodiversity for northern China has rarely been shown, as previous phylogeographic studies are mostly woody species and they have revealed that Quaternary refugia are mainly located in mountain regions. We selected a drought-enduring endemic herb, Speranskia tuberculata (Euphorbiaceae), to determine its glacial refugia and postglacial demographic history. To this end, we sampled 423 individuals from 38 populations covering its entire geographic distribution. Three chloroplast DNA (cpDNA) fragments, two low-copy nuclear genes, and six nuclear microsatellites (nSSRs) were used and supplemented with ecological niche modeling (ENM) to infer the phylogeographic history of this species. Populations with private haplotypes and high haplotype diversity of cpDNA are mainly located in the CLP or scattered around northeastern China and the coastal region. Spatial expansion, detected using a neutrality test and mismatch distribution, may have resulted in a widely distributed ancestral cpDNA haplotype, especially outside of the CLP. For nuclear DNA, private haplotypes are also distributed mainly in the CLP. In nSSRs, STRUCTURE clustering identified two genetic clusters, which are distributed in the west (western cluster) and east (eastern cluster), respectively. Many populations belonged, with little to no admixture, to the western cluster while (hardly) pure populations of the eastern cluster were barely found. Genetic differentiation is significantly correlated with geographic distance, although genetic diversity is uniformly distributed. ENM suggests that the distribution of S. tuberculata has recently expanded northwards from the southern CLP, whereas it has experienced habitat loss in the south. Thus, S. tuberculata populations probably survived the last glacial maximum (LGM) in the southern CLP and experienced post-glacial expansion. Wind-dispersed pollen could bring the majority of genotypes to the front during spatial expansion, resulting in uniformly distributed genetic diversity. Based on evidence from molecular data and vegetation and climate changes since the LGM, we conclude that drought-enduring species, especially herbaceous species, are likely to have persisted in the CLP during the LGM and to have experienced expansion to other regions in northern China.

10.
Plant Divers ; 43(6): 462-471, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35024515

RESUMEN

The complex interactions of historical, geological and climatic events on plant evolution have been an important research focus for many years. However, the role of desert formation and expansion in shaping the genetic structures and demographic histories of plants occurring in arid areas has not been well explored. In the present study, we investigated the phylogeography of Arnebia szechenyi, a desert herb showing a near-circular distribution surrounding the Tengger Desert in Northwest China. We measured genetic diversity of populations using three maternally inherited chloroplast DNA (cpDNA) fragments and seven bi-paternally inherited nuclear DNA (nDNA) loci that were sequenced from individuals collected from 16 natural populations across its range and modelled current and historical potential habitats of the species. Our data indicated a considerably high level of genetic variation within A. szechenyi and noteworthy asymmetry in historical migration from the east to the west. Moreover, two nuclear genetic groups of populations were revealed, corresponding to the two geographic regions separated by the Tengger Desert. However, analysis of cpDNA data did not show significant geographic structure. The most plausible explanation for the discrepancy between our findings based on cpDNA and nDNA data is that A. szechenyi populations experienced long periods of geographic isolation followed by range expansion, which would have promoted generalized recombination of the nuclear genome. Our findings further highlight the important role that the Tengger Desert, together with the Helan Mountains, has played in the evolution of desert plants and the preservation of biodiversity in arid Northwest China.

11.
Artículo en Inglés | MEDLINE | ID: mdl-33014895

RESUMEN

Plague, which is caused by Yersinia pestis, is one of the most dangerous infectious diseases. No FDA-approved vaccine against plague is available for human use at present. To improve the immune safety of Y. pestis EV76 based live attenuated vaccine and to explore the feasibility of aerosolized intratracheal inoculation (i.t.) route for vaccine delivery, a plasminogen activator protease (pla) gene deletion mutant of the attenuated Y. pestis strain EV76-B-SHU was constructed, and its residual virulence and protective efficacy were evaluated in a mouse model via aerosolized intratracheal inoculation (i.t.) or via subcutaneous injection (s.c.). The residual virulence of EV76-B-SHUΔpla was significantly reduced compared to that of the parental strain EV76-B-SHU following i.t. and s.c. infection. The EV76-B-SHUΔpla induced higher levels of mucosal antibody sIgA in the bronchoalveolar lavage fluid of mice immunized by i.t. but not by s.c.. Moreover, after lethal challenge with Y. pestis biovar Microtus strain 201 (avirulent in humans), the protective efficacy and bacterial clearance ability of the EV76-B-SHUΔpla-i.t. group were comparable to those of the EV76-B-SHUΔpla-s.c. and EV76-B-SHU immunized groups. Thus, the EV76-B-SHUΔpla represents an excellent live-attenuated vaccine candidate against pneumonic plague and aerosolized i.t. represents a promising immunization route in mouse model.


Asunto(s)
Vacuna contra la Peste , Peste , Yersinia pestis , Animales , Modelos Animales de Enfermedad , Ratones , Peste/prevención & control , Vacunas Atenuadas
12.
BMC Microbiol ; 20(1): 251, 2020 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-32787788

RESUMEN

BACKGROUND: Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes a zoonotic disease commonly called Q fever globally. In this study, an up-converting phosphor technology-based lateral flow (UPT-LF) assay was established for the rapid and specific detection of phase I strains of C. burnetii. RESULTS: Specific monoclonal antibodies (10B5 and 10G7) against C. burnetii phase I strains were prepared and selected for use in the UPT-LF assay by the double-antibody-sandwich method. The detection sensitivity of the Coxiella-UPT-LF was 5 × 104 GE/ml for a purified C. burnetii phase I strain and 10 ng/ml for LPS of C. burnetii Nine Mile phase I (NMI). Good linearity was observed for C. burnetii phase I and NMI LPS quantification (R2 ≥ 0.989). The UPT-LF assay also exhibited a high specificity to C. burnetii, without false-positive results even at 108 GE/ml of non-specific bacteria, and good inclusivity for detecting different phase I strains of C. burnetii. Moreover, the performance of the Coxiella-UPT-LF assay was further confirmed using experimentally and naturally infected samples. CONCLUSIONS: Our results indicate that Coxiella-UPT-LF is a sensitive and reliable method for rapid screening of C. burnetii, suitable for on-site detection in the field.


Asunto(s)
Anticuerpos Monoclonales/análisis , Técnicas Biosensibles/métodos , Coxiella burnetii/aislamiento & purificación , Fiebre Q/diagnóstico , Animales , Anticuerpos Antibacterianos/análisis , Antígenos Bacterianos/inmunología , Coxiella burnetii/inmunología , Diagnóstico Precoz , Femenino , Humanos , Inmunización , Inmunoensayo , Masculino , Ratones , Pruebas en el Punto de Atención , Sensibilidad y Especificidad
14.
Immunotherapy ; 12(11): 771-776, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32611263

RESUMEN

Background: Angiosarcoma (AS) is a rare malignancy originating from lymphatic or vascular endothelial cells. Prognosis of the disease is usually dismal and there is no effective treatment. Immunotherapy has been proved to be effective for various cancer types. Programmed death-ligand 1 (PD-L1) expression is generally recognized as a biomarker for the prediction of response to anti-PD-(L)1 immunotherapies. Methods & results: Here, we discuss a single case by highlighting the treatment of the antiprogrammed cell death protein 1 drug pembrolizumab with high PD-L1 expression. CT scan demonstrated a confirmed size reduction of some lesions compared with original lesions, which indicates the possible clinical benefit. Conclusion: We speculate that early anti-PD-1 treatment may be a promising strategy for angiosarcoma patients with high PD-L1 expression.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Hemangiosarcoma/terapia , Inmunoterapia/métodos , Neoplasias Pulmonares/terapia , Anciano , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/genética , Biomarcadores de Tumor/antagonistas & inhibidores , Biomarcadores de Tumor/genética , Humanos , Masculino , Tórax/diagnóstico por imagen , Carga Tumoral , Regulación hacia Arriba
15.
PLoS One ; 14(12): e0225671, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31805090

RESUMEN

Q fever is a worldwide zoonosis caused by Coxiella burnetii. Human Q fever is typically acquired through inhalation of contaminated aerosols, resulting in an initial pulmonary infection. In this study, BALB/c mice were infected with C. burnetii via an intratracheal (IT) route using a non-invasive aerosol pulmonary delivery device to directly place the living C. burnetii organisms into the lungs of the mice. The bacterial loads, pathological lesions, and antibody and cellular responses were analyzed and compared with those of mice infected via an intraperitoneal (IP) route. Compared with mice infected via an IP route, mice infected via an IT route exhibited a higher bacterial load and more severe pathological lesions in the heart and lungs at days 3 and 7 post-infection (pi). The levels of interferon-γ and IL-12p70 in the serum of mice infected via the IT route were significantly higher than those of mice infected via the IP route at day 3 pi. In conclusion, this murine model of acute C. burnetii infection via IT inoculation closely resembles the natural route of C. burnetii infection than that of IP injection. Thus, this newly developed model will be useful for investigating the pathogenesis and immunity of C. burnetii aerosol infection, as well as for the evaluation of therapeutic drugs and preventive vaccines of Q fever.


Asunto(s)
Coxiella burnetii/inmunología , Fiebre Q/inmunología , Fiebre Q/patología , Aerosoles , Animales , Modelos Animales de Enfermedad , Femenino , Infusiones Parenterales , Interferón gamma/inmunología , Interleucina-12/inmunología , Pulmón/inmunología , Ratones , Ratones Endogámicos BALB C
17.
Vaccine ; 37(41): 6076-6084, 2019 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-31477436

RESUMEN

Human Q fever is recognized as a worldwide public health problem. It often occurs by inhalation of airborne aerosols contaminated with Coxiella burnetii, a gram-negative intracellular bacterium, mainly from domestic livestock. In this study, we analyzed the possibility to establish mucosal and systemic immunity against C. burnetii infection using a pulmonary delivery of chloroform-methanol residue of C. burnetii (CMR) vaccine. Mice were immunized by the intratracheal inoculation of CMR (IT-CMR) or the subcutaneous injection of CMR (SC-CMR), and the immunized mice were challenged with C. burnetii by the intratracheal route. The levels of IFN-γ, IL-12p70, IL-5, and IL-4 in the IT-CMR group in splenic T cells stimulated ex vivo were significantly higher than in the SC-CMR group. Significantly elevated sIgA to C. burnetii was detected in the bronchoalveolar lavage fluid of mice immunized by IT-CMR but not by SC-CMR, which might have contributed to the significant reduction in C. burnetii load and pathological lesions in the lungs of the mice after the challenge of C. burnetii. These results suggest that compared with SC-CMR in mice, IT-CMR was more efficient to elicit cellular and lung mucosal immune responses against aerosol infection of C. burnetii.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Vacunas Bacterianas/inmunología , Coxiella burnetii/inmunología , Inmunidad Mucosa/inmunología , Fiebre Q/prevención & control , Administración por Inhalación , Animales , Carga Bacteriana/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Cloroformo/química , Modelos Animales de Enfermedad , Femenino , Inmunoglobulina A/sangre , Interferón gamma/sangre , Subunidad p35 de la Interleucina-12/sangre , Interleucina-4/sangre , Interleucina-5/sangre , Metanol/química , Ratones , Ratones Endogámicos BALB C , Linfocitos T/inmunología , Vacunación
18.
Zhongguo Fei Ai Za Zhi ; 22(5): 312-318, 2019 May 20.
Artículo en Chino | MEDLINE | ID: mdl-31109441

RESUMEN

BACKGROUND: Advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma had a high overall incidence of brain metastasis during the full course, and local brain radiotherapy combined with systemic targeted therapy may be a better strategy. This study aimed to identify the prognostic factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients who received EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in combination with gamma knife radiosurgery. METHODS: Retrospective analysis of EGFR-mutant lung adenocarcinoma patients with brain metastases which developed at initial diagnosis or during EGFR-TKIs treatment period were performed. Intracranial progression free survival (PFS) was statistically analyzed between different subgroups to find out the prognostic factors including gender, age, smoking history, extracranial metastasis, EGFR mutation type, size and number of intracranial lesions, carcino-embryonic antigen (CEA) level, lung-molGPA score and so on. RESULTS: A total of 74 EGFR-mutant brain-metastatic lung adenocarcinoma patients were enrolled in this study, with median intracranial PFS of 14.7 months. One-year intracranial-progression-free rate was 58.5%, and two-year rate was 22.2%. Univariate survival analysis showed that patients with lower CEA level at initial diagnosis (<10 ng/L)(16.9 months vs 12.6 months, P=0.012) and smaller intracranial lesions (<2 cm)(15.4 months vs 10.8 months, P=0.021) and higher lung-molGPA score (>3)(15 months vs 12.6 months, P=0.041) were prone to have a superior intracranial PFS. Multivariate analysis showed that CEA≥10 ng/mL and intracranial lesion≥2 cm were the independent risk factors of intracranial PFS. CONCLUSIONS: EGFR-TKIs in combination with gamma knife radiosurgery was an efficient treatment option to control the cranial tumor lesion. CEA≥10 µg/L at initial diagnosis and intracranial lesion≥2 cm were the risk factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients receiving EGFR-TKIs in combination with gamma knife radiosurgery.


Asunto(s)
Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/terapia , Neoplasias Encefálicas/secundario , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Radiocirugia , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/radioterapia , Adulto , Anciano , Terapia Combinada , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos
19.
Vet Microbiol ; 228: 45-52, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30593379

RESUMEN

Fowl Adenoviruses (FAdVs) are widely-distributed pathogens across the globe. Fowl adenovirus serotype 4 (FAdV-4), the causative agent for chicken hydropericardium syndrome (HPS) with a high mortality in the infected flocks, has caused severe economic losses to the poultry industry of China in the past few years. Although vaccination against FAdV-4 has been implemented, the prevention and control of FAdV-4 infection is still not very successful. Here, we report that FAdV-4 markedly inhibits Leghorn male hepatoma (LMH) cell growth and this inhibition could be abolished by a small molecule SP600125, a JNK MAPK specific inhibitor. Furthermore, SP600125 considerably suppressed FAdV-4-induced phosphorylation of p38 and JNK MAPK. Importantly, SP600125 promoted type I interferon production associated with inhibition of FAdV-4 replication. Thus, FAdV-4 might employ the JNK MAPK pathway for the benefit of its replication, and SP600125 may have the potential of being used as an anti-virus drug for the control FAdV-4 infection.


Asunto(s)
Infecciones por Adenoviridae/veterinaria , Antracenos/farmacología , Aviadenovirus/efectos de los fármacos , Carcinoma Hepatocelular/veterinaria , Pollos/virología , Neoplasias Hepáticas/veterinaria , Enfermedades de las Aves de Corral/virología , Infecciones por Adenoviridae/virología , Animales , Aviadenovirus/inmunología , Aviadenovirus/fisiología , Carcinoma Hepatocelular/virología , Línea Celular Tumoral , Interferón Tipo I/metabolismo , Neoplasias Hepáticas/virología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Fosforilación/efectos de los fármacos , Serogrupo , Replicación Viral/efectos de los fármacos
20.
Virus Res ; 252: 29-40, 2018 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-29777734

RESUMEN

MicroRNAs (miRNAs), as post-transcriptional regulators, play important roles in the process of viral infection through inhibiting virus replication or modulating host immune response. However, the role of miRNAs in host response against infectious bursal disease virus (IBDV) infection is still unclear. In this study, we found that gga-miR-454 of the host was decreased in response to IBDV infection and that transfection of DF-1 cells with miR-454 inhibited IBDV replication via directly targeting the specific sequence of IBDV genomic segment B, while blockage of endogenous miR-454 by inhibitors enhanced virus replication. Furthermore, gga-miR-454 increased the expression of IFN-ß by targeting Suppressors of Cytokine Signaling 6 (SOCS6), enhancing the antiviral response of host cells. These findings highlight a crucial role of gga-miR-454 in host defense against IBDV infection.


Asunto(s)
Virus de la Enfermedad Infecciosa de la Bolsa/fisiología , MicroARNs/genética , Proteínas Supresoras de la Señalización de Citocinas/inmunología , Replicación Viral , Animales , Línea Celular , Pollos/inmunología , Pollos/virología , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno , Inmunidad Innata , Interferón beta/inmunología
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