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1.
Artigo em Inglês | MEDLINE | ID: mdl-31669781

RESUMO

Interleukine-1ß (IL-1ß) is the first identified pro-inflammatory cytokine, which is cleaved by caspase-1 following the inflammasomes activation, playing critical roles in innate immunity. However, few studies have been performed to characterize the IL-1ß in lower vertebrates. Herein, we distinguished the Scophthalmus maximus IL-1ß (SmIL-1ß) from three IL-1ß like sequences and found that SmIL-1ß was cleaved by S. maximus caspase at a non-conserved Asp86, then targeted to the plasma membrane. Moreover, during the immersion infection of Edwardsiella piscicida, we found that E. piscicida were mainly colonized in gills at early time points and invaded to systemic sites after 5 days post infection, which was consistent with the dynamic up-regulated transcription of SmIL-1ß. Furthermore, knockdown of SmIL-1ß promotes the bacterial colonization in gills at early time points and result into systemic colonization, while overexpression of SmIL-1ß hampers the bacterial colonization in both spleen and kidney. Taken together, these data provide new insights into the molecular mechanisms of SmIL-1ß and reveal its role in limiting bacterial infection in vivo, which will support the idea for better understanding the evolutionary of IL-1ß functions in teleost.

2.
Br J Cancer ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31570753

RESUMO

BACKGROUND: The extracellular matrix (ECM) is essential for malignant tumour progression, as it is a physical barrier to various kinds of anticancer therapies. Matrix metalloproteinase (MMPs) can degrade almost all ECM components, and macrophages are an important source of MMPs. Studies using macrophages to treat tumours have shown that macrophages can enter tumour tissue to play a regulatory role. METHODS: We modified macrophages with a designed chimeric antigen receptor (CAR), which could be activated after recognition of the tumour antigen HER2 to trigger the internal signalling of CD147 and increase the expression of MMPs. RESULTS: Although CAR-147 macrophage treatment did not affect tumour cell growth in vitro compared with control treatment. However, we found that the infusion of CAR-147 macrophages significantly inhibited HER2-4T1 tumour growth in BALB/c mice. Further investigation showed that CAR-147 macrophages could reduce tumour collagen deposition and promote T-cell infiltration into tumours, which were consistent with expectations. Interestingly, the levels of the inflammatory cytokines TNF-α and IL-6, which are key factors in cytokine release syndrome, were significantly decreased in the peripheral blood in CAR-147 macrophage-transfused mice. CONCLUSION: Our data suggest that targeting the ECM by engineered macrophages would be an effective treatment strategy for solid tumours.

3.
FASEB J ; : fj201901259R, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31585506

RESUMO

The tick- and transfusion-transmitted human pathogen Babesia microti infects host erythrocytes to cause the pathologic symptoms associated with human babesiosis, an emerging disease with worldwide distribution and potentially fatal clinical outcome. Drugs currently recommended for the treatment of babesiosis are associated with a high failure rate and significant adverse events, highlighting the urgent need for more-effective and safer babesiosis therapies. Unlike other apicomplexan parasites, B. microti lacks a canonical lactate dehydrogenase (LDH) but instead expresses a unique enzyme, B. microti LDH (BmLDH), acquired through evolution by horizontal transfer from a mammalian host. Here, we report the crystal structures of BmLDH in apo state and ternary complex (enzyme-NADH-oxamate) solved at 2.79 and 1.89 Å. Analysis of these structures reveals that upon binding to the coenzyme and substrate, the active pocket of BmLDH undergoes a major conformational change from an opened and disordered to a closed and stabilized state. Biochemical assays using wild-type and mutant B. microti and human LDHs identified Arg99 as a critical residue for the catalytic activity of BmLDH but not its human counterpart. Interestingly, mutation of Arg99 to Ala had no impact on the overall structure and affinity of BmLDH to NADH but dramatically altered the closure of the enzyme's active pocket. Together, these structural and biochemical data highlight significant differences between B. microti and human LDH enzymes and suggest that BmLDH could be a suitable target for the development of selective antibabesial inhibitors.-Yu, L., Shen, Z., Liu, Q., Zhan, X., Luo, X., An, X., Sun, Y., Li, M., Wang, S., Nie, Z., Ao, Y., Zhao, Y., Peng, G., Ben Mamoun, C., He, L., Zhao, J. Crystal structures of Babesia microti lactate dehydrogenase BmLDH reveal a critical role for Arg99 in catalysis.

4.
Gigascience ; 8(10)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31634388

RESUMO

BACKGROUND: Achatina fulica, the giant African snail, is the largest terrestrial mollusk species. Owing to its voracious appetite, wide environmental adaptability, high growth rate, and reproductive capacity, it has become an invasive species across the world, mainly in Southeast Asia, Japan, the western Pacific islands, and China. This pest can damage agricultural crops and is an intermediate host of many parasites that can threaten human health. However, genomic information of A. fulica remains limited, hindering genetic and genomic studies for invasion control and management of the species. FINDINGS: Using a k-mer-based method, we estimated the A. fulica genome size to be 2.12 Gb, with a high repeat content up to 71%. Roughly 101.6 Gb genomic long-read data of A. fulica were generated from the Pacific Biosciences sequencing platform and assembled to produce a first A. fulica genome of 1.85 Gb with a contig N50 length of 726 kb. Using contact information from the Hi-C sequencing data, we successfully anchored 99.32% contig sequences into 31 chromosomes, leading to the final contig and scaffold N50 length of 721 kb and 59.6 Mb, respectively. The continuity, completeness, and accuracy were evaluated by genome comparison with other mollusk genomes, BUSCO assessment, and genomic read mapping. A total of 23,726 protein-coding genes were predicted from the assembled genome, among which 96.34% of the genes were functionally annotated. The phylogenetic analysis using whole-genome protein-coding genes revealed that A. fulica separated from a common ancestor with Biomphalaria glabrata ∼182 million years ago. CONCLUSION: To our knowledge, the A. fulica genome is the first terrestrial mollusk genome published to date. The chromosome sequence of A. fulica will provide the research community with a valuable resource for population genetics and environmental adaptation studies for the species, as well as investigations of the chromosome-level of evolution within mollusks.

5.
Mol Ecol Resour ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31599098

RESUMO

Microsatellites are widely distributed throughout nearly all genomes which have been extensively exploited as powerful genetic markers for diverse applications due to their high polymorphisms. Their length variations are involved in gene regulation and implicated in numerous genetic diseases even in cancers. Although much effort has been devoted in microsatellite database construction, the existing microsatellite databases still had some drawbacks, such as limited number of species, unfriendly export format, missing marker development, lack of compound microsatellites and absence of gene annotation, which seriously restricted researchers to perform downstream analysis. In order to overcome the above limitations, we developed PSMD (Pan-Species Microsatellite Database, http://big.cdu.edu.cn/psmd/) as a web-based database to facilitate researchers to easily identify microsatellites, exploit reliable molecular markers and compare microsatellite distribution pattern on genome-wide scale. In current release, PSMD comprises 678,106,741 perfect microsatellites and 43,848,943 compound microsatellites from 18,408 organisms, which covered almost all species with available genomic data. In addition to interactive browse interface, PSMD also offers a flexible filter function for users to quickly gain desired microsatellites from large data sets. PSMD allows users to export GFF3 formatted file and CSV formatted statistical file for downstream analysis. We also implemented an online tool for analysing occurrence of microsatellites with user-defined parameters. Furthermore, Primer3 was embedded to help users to design high-quality primers with customizable settings. To our knowledge, PSMD is the most extensive resource which is likely to be adopted by scientists engaged in biological, medical, environmental and agricultural research.

6.
J Med Food ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31657664

RESUMO

Anthocyanin-rich extracts have shown anti-inflammation activity in mouse colitis models. Cyanidin-3-glucoside (C3G) is one of the widespread anthocyanins in plants, and cyanidin (Cy) is the aglycone of C3G that can be generated in intestine under gut microorganism metabolism. To explore the anti-inflammatory activity of single anthocyanins compound and show the potential mechanism, the protective effects of C3G and its aglycone Cy on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in mice and lipopolysaccharide (LPS)-stimulated Caco-2 cellular monolayer inflammation were studied. The results showed that both C3G and Cy significantly improved the clinical symptoms and relieved the histological damage in TNBS-challenged mice. The activity of myeloperoxidase and the excretion of inflammatory cytokines tumor necrosis factor-α, interleukin-1ß, interleukin-6, and interferon-γ were also significantly inhibited at the administration dosage of 200 µmol/kg. In vitro studies showed that when LPS-stimulated Caco-2 cells were pretreated with C3G and Cy, the destruction of the intestinal epithelial barrier was ameliorated due to the improvement of the transepithelial electrical resistance and Lucifer yellow flux values, while there were no significant difference between C3G and Cy groups at the same dosage. Similarly, both C3G and Cy suppressed nitric oxide production and inflammatory cytokines secretion of LPS-induced Caco-2 cells. C3G and its aglycone Cy had similar anti-inflammatory activity in both colitis mice and Caco-2 cells. The results suggest that C3G and Cy may exert anti-inflammatory effects by protecting the intestinal barrier as well as by suppressing inflammatory cytokine secretion. Thus, C3G or Cy could be potential preventive agents or supplementary medicines for inflammatory bowel disease.

7.
J Agric Food Chem ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31618029

RESUMO

Time-domain nuclear magnetic resonance (NMR) is used for the characterization of wheat infested with Sitophilus zeamais. NMR parameters (T21, T22, P21, P22, and A21/22) were achieved by biexponential analysis combined with a discrete method. Sound wheat, S. zeamais, and S. zeamais/wheat binary mixture are all explored by this method to find the changes in the process of the number increase and growth stage. Based on different sets of NMR parameters, the classification and quantification of the stage and number are made by linear discriminant analysis and partial least squares regression with very high accuracy. The weight and moisture content information lack will make the misclassification rate increase but not by more than 7%. This NMR-based hidden-insect detection method, with fast and nondestructive advantages, was confirmed by X-ray and had a high potential to be equipped in the online analysis system.

8.
Nat Commun ; 10(1): 4067, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492885

RESUMO

ARID1A inactivation causes mitotic defects. Paradoxically, cancers with high ARID1A mutation rates typically lack copy number alterations (CNAs). Here, we show that ARID1A inactivation causes defects in telomere cohesion, which selectively eliminates gross chromosome aberrations during mitosis. ARID1A promotes the expression of cohesin subunit STAG1 that is specifically required for telomere cohesion. ARID1A inactivation causes telomere damage that can be rescued by STAG1 expression. Colony formation capability of single cells in G2/M, but not G1 phase, is significantly reduced by ARID1A inactivation. This correlates with an increase in apoptosis and a reduction in tumor growth. Compared with ARID1A wild-type tumors, ARID1A-mutated tumors display significantly less CNAs across multiple cancer types. Together, these results show that ARID1A inactivation is selective against gross chromosome aberrations through causing defects in telomere cohesion, which reconciles the long-standing paradox between the role of ARID1A in maintaining mitotic integrity and the lack of genomic instability in ARID1A-mutated cancers.

9.
J Cell Physiol ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31508820

RESUMO

Liver fibrosis (LF) is the result of a vicious cycle between inflammation-induced chronic hepatocyte injury and persistent activation of hepatic stellate cells (HSCs). Mesenchymal stem cell (MSC)-based therapy may represent a potential remedy for treatment of LF. However, the fate of transplanted MSCs in LF remains largely unknown. In the present study, the fate and antifibrotic effect of MSCs were explored in a LF model induced by CCl4 in mouse. Additionally, MSCs were stimulated in vitro with LF-associated factors, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and transforming growth factor-ß1 (TGF-ß1), to mimic the LF microenvironment. We unveiled that MSCs exhibited autophagy in response to the LF microenvironment through Becn1 upregulation both in vivo and in vitro. However, autophagy suppression induced by Becn1 knockdown in MSCs resulted in enhanced antifibrotic effects on LF. The improved antifibrotic potential of MSCs may be attributable to their inhibitory effects on T lymphocyte infiltration, HSCs proliferation, as well as production of TNF-α, IFN-γ, and TGF-ß1, which may be partially mediated by elevated paracrine secretion of PTGS2/PGE2 . Thus, autophagy manipulation in MSCs may be a novel strategy to promote their antifibrotic efficacy.

10.
J Med Chem ; 62(18): 8631-8641, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31498617

RESUMO

Mas-related G-protein-coupled receptor X1 (MRGPRX1) is a human sensory neuron-specific receptor and has been actively investigated as a therapeutic target for the treatment of pain. By use of two HTS screening hit compounds, 4-(4-(benzyloxy)-3-methoxybenzylamino)benzimidamide (5a) and 4-(2-(butylsulfonamido)-4-methylphenoxy)benzimidamide (11a), as molecular templates, a series of human MRGPRX1 agonists were synthesized and evaluated for their agonist activity using HEK293 cells stably transfected with human MrgprX1. Conversion of the benzamidine moiety into a 1-aminoisoquinoline moiety carried out in the later stage of structural optimization led to the discovery of a highly potent MRGPRX1 agonist, N-(2-(1-aminoisoquinolin-6-yloxy)-4-methylphenyl)-2-methoxybenzenesulfonamide (16), not only devoid of positively charged amidinium group but also with superior selectivity over opioid receptors. In mice, compound 16 displayed favorable distribution to the spinal cord, the presumed site of action for the MRGPRX1-mediated analgesic effects.

11.
Anal Chem ; 91(20): 13143-13151, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31507159

RESUMO

Human telomerase has been considered as a promising tumor marker for early cancer diagnosis and tumor progression monitoring. Current methods for detection of telomerase mainly rely on in vitro assays using cell lysate, which cannot provide information on telomerase activities in living systems. Only the few reported intracellular probes possess high telomerase selectivity but involve no signal amplification process, which potentially limits their use in application scenarios requiring high sensitivity. The development of an ultrasensitive intracellular telomerase probe is of high demand but challenging, because of the difficulty in designing a robust amplification process in living cells. Inspired by the mechanism of telomerase primer binding and extension, we introduce a cascade amplification reaction-based nanoprobe for intracellular telomerase detection by incorporating DNAzyme and catalytic hairpin assembly onto MnO2 nanosheets. The MnO2 nanosheets can deliver and release multicomponent signal amplification motifs with designed ratio at the same intracellular position, thereby enabling the cascade process in cells to occur. The released Mn2+ ions from degraded MnO2 nanosheets can activate DNAzyme as a metal cofactor and facilitate endosomal escape, because of the ion sponge effect. We used the nanoprobe to successfully monitor the dynamic change of telomerase activity in the HeLa cell, as well as in three other types of cells. This cascade amplification nanoprobe provides ultrasensitive detection of telomerase activity, indicating its use as a promising bioassay for early cancer diagnosis.

12.
J Biol Chem ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511326

RESUMO

Ikzf1 is a Krüppel-like zinc-finger transcription factor that plays indispensable roles in T and B cell development. Though the function of Ikzf1 has been extensively studied, the molecular mechanism underlying T lymphopoiesis remains incompletely defined during the embryonic stage. Here, we report that the genetic ablation of ikzf1 in mutant zebrafish resulted in abrogated embryonic T lymphopoiesis. This was ascribed to the impaired thymic migration, proliferation and differentiation of hematopoietic stem/progenitor cells (HSPCs). Ccr9a and Irf4a, two indispensable factors in T lymphopoiesis, were the direct targets of Ikzf1 and were absent in the ikzf1 mutants. Genetic deletion of either ccr9a or irf4a in the corresponding mutant embryos led to obvious T-cell development deficiency, which was mainly caused by the disrupted thymic migration of HSPCs. Restoration of ccr9a in ikzf1 mutants obviously promoted HSPC thymus-homing. However, the HSPCs then failed to differentiate into T cells. Additional replenishment of irf4a efficiently induced HSPC proliferation and T-cell differentiation. Our findings further demonstrate that ikzf1 regulates embryonic T lymphopoiesis via Ccr9 and Irf4, and provide new insight into the genetic network of T lymphocyte development.

13.
Phys Rev E ; 100(1-1): 012105, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31499858

RESUMO

We investigate the finite-power performance of quantum heat engines working in the linear response regime where the temperature gradient is small. The engine cycles with working substances of ideal harmonic systems consist of two heat transfer and two adiabatic processes, such as the Carnot cycle, Otto cycle, and Brayton cycle. By analyzing the optimal protocol under maximum power we derive the explicitly analytic expression for the irreversible entropy production, which becomes the low dissipation form in the long duration limit. Assuming the engine to be endoreversible, we derive the universal expression for the efficiency at maximum power, which agrees well with that obtained from the phenomenological heat transfer laws holding in the classical thermodynamics. Through appropriate identification of the thermodynamic fluxes and forces that a linear relation connects, we find that the quantum engines under consideration are tightly coupled, and the universality of efficiency at maximum power is confirmed at the linear order in the temperature gradient.

14.
J Phys Chem Lett ; 10(20): 6081-6087, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31539474

RESUMO

Rationally designing cheap and efficient electrocatalysts at the atomic level is highly desirable for the hydrogen evolution reaction (HER). Here, we demonstrate a metallic MoS2 electrocatalyst decorated with platinum single atoms. When combined with electron microscopy observations, our synchrotron X-ray characterizations and theoretical calculations clearly reveal that the doped Pt atoms bond to S atoms on the surface of MoS2. Notably, these Pt single atoms serve as critical active centers for the HER through capturing H+ from the solution. The optimized Pt-MoS2 catalysts achieve significantly enhanced HER performance due to the single-atom coordination effect. This finding is expected to facilitate further realization of hybridized catalysts through the monatomic riveting strategy.

15.
Microbiol Res ; 229: 126325, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31563838

RESUMO

Edwardsiella bacteria cause economic losses to a variety of commercially important fish globally. Human infections are rare and result in a gastroenteritis-like illness. Because these bacteria are evolutionarily related to other Enterobacteriaceae and the host cytoskeleton is a common target of enterics, we hypothesized that Edwardsiella may cause similar phenotypes. Here we use HeLa and Caco-2 infection models to show that microtubules are severed during the late infections. This microtubule alteration phenotype was not dependant on the type III or type VI secretion system (T3SS and T6SS) of the bacteria as ΔT3SS and ΔT6SS mutants of E. piscicida EIB202 and E. tarda ATCC15947 that lacks both also caused microtubule disassembly. Immunolocalization experiments showed the host katanin catalytic subunits A1 and A like 1 proteins at regions of microtubule severing, suggesting their involvement in the microtubule disassembly events. To identify bacterial components involved in this phenotype, we screened a 2,758 transposon library of E. piscicida EIB202 and found that 4 single mutations in the atpFHAGDC operon disrupted microtubule disassembly in HeLa cells. We then constructed three atp deletion mutants; they all could not disassemble host microtubules. This work provides the first clear evidence of host cytoskeletal alterations during Edwardsiella infections.

16.
Am J Crit Care ; 28(5): 370-376, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31474607

RESUMO

BACKGROUND: High-flow oxygen therapy has been widely adopted, but its use for weaning patients from mechanical ventilation has not been reported. OBJECTIVE: To evaluate whether high-flow oxygen therapy improves the efficiency of weaning patients from mechanical ventilation. METHODS: In a single-center, prospective study, patients receiving mechanical ventilation were randomly assigned to 1 of 3 groups (T-tube, pressure support ventilation, or high-flow oxygen) during 2-hour spontaneous breathing trials in a 14-day study. Participants were followed up until hospital discharge or death. RESULTS: Of 268 patients included, 90 were assigned to the T-tube group, 96 to the pressure support ventilation group, and 82 to the high-flow oxygen group. The first-day 2-hour spontaneous breathing trial passing rates were higher in the pressure support ventilation and high-flow oxygen groups than in the T-tube group (P < .05). The time needed to pass the spontaneous breathing trial was less in the pressure support ventilation and high-flow oxygen groups than in the T-tube group (P < .05). The reintubation rate was lower and the successful weaning rate on the first day was higher in the high-flow oxygen group than in the T-tube and pressure support ventilation groups (P < .05). During the 14-day study period, the weaning time was less in the high-flow oxygen group than in the T-tube and pressure support ventilation groups (P < .05). CONCLUSION: High-flow oxygen therapy can reduce the time needed to wean patients from mechanical ventilation by shortening the time needed to pass a spontaneous breathing trial and by decreasing the reintubation rate.

17.
Environ Pollut ; 255(Pt 2): 113226, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31546075

RESUMO

In this paper, Fe3O4@MIL-68 (Al), a magnetic aluminum-based metal organic framework, was synthesized by a simple method and used as a novel and effective adsorbent for the removal of minocycline (MC) from aqueous solutions. The material was thoroughly characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and N2 adsorption isotherms. The characterization results showed that the original structure of MIL-68(Al) was unchanged by the addition of Fe3O4 nanoparticles, and that the obtained material had a strong magnetic response which also promoted its adsorption. Batch adsorption experiments were conducted by the varying the adsorption time, temperature, initial MC concentration and pH. The maximum adsorption amount of MC onto Fe3O4@MIL-68 (Al) was 248.05 mg g-1 (t = 160 min, pH = 6, Co = 60 mg L-1), and the adsorption kinetics followed a pseudo-second-order model, and the adsorption isotherms conformed to the Freundlich equation. The adsorption mechanism of the magnetic metal organic framework materials were determined to involve complex interactions, including Al-N and Fe-N covalent bonds, hydrogen bonding, electrostatic adsorption, and π-π stacking. Combined the results indicate that Fe3O4@MIL-68 (Al) is an outstanding adsorbent for the removal of MC from water.

18.
Medicine (Baltimore) ; 98(34): e16922, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441876

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have displayed dysregulated expression in several types of cancer. Nevertheless, their function and underlying mechanisms in cervical cancer remains largely unknown. This study aimed to describe the regulatory mechanisms in cervical cancer. METHODS: We downloaded the circRNAs expression profiles from Gene Expression Omnibus database, and RNAs expression profiles from The Cancer Genome Atlas database. We established a circRNA-miRNA-mRNA and circRNA-miRNA-hubgene network. The interactions between proteins were analyzed using the STRING database and hubgenes were identified using MCODE plugin. Then, we conducted a circRNA-miRNA-hubgenes regulatory module. Functional and pathway enrichment analyses were conducted using R packages "Clusterprofile". RESULTS: Six circRNAs, 15 miRNAs, and 158 mRNAs were identified to construct the ceRNA network of cervical cancer. PPI (protein-protein interaction) network and module analysis identified 7 hubgenes. Then, a circRNA-miRNA-hubgene subnetwork was constructed based on the 1 DEcircRNAs, 3 DEmiRNAs, and 3 DEmRNAs. The KEGG pathway analysis indicated DEmRNAs are involved in progesterone-mediated oocyte maturation, cell cycle, and oocyte meiosis. CONCLUSION: These ceRNAs are critical in the pathogenesis of cervical and may serve as future therapeutic biomarkers.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , RNA/genética , Neoplasias do Colo do Útero/genética , Biomarcadores Tumorais/genética , Feminino , Humanos , Mapas de Interação de Proteínas , RNA/metabolismo
19.
Fish Shellfish Immunol ; 93: 871-878, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31400510

RESUMO

Edwardsiella piscicida is an important pathogen that infects a wide range of hosts, from fish to human. Its infection leads to extensive losses in a diverse array of commercially important fish, like Japanese flounder, turbot, and tilapia. During the infection, type III secretion system (T3SS) and type VI secretion system (T6SS) of E. piscicida play significant roles, but how T3SS and T6SS cooperatively contribute to its virulence is still unknown. In this study, we first examined the roles of T3SS and T6SS in different processes during E. piscicida infection of host cells, and revealed that T3SS of E. piscicida is responsible for promoting bacterial invasion, the following intracellular replication and inducing cell death in host cells, while T6SS restrains E. piscicida intracellular replication and cell death in J774A.1 cells, which suggested that T3SS and T6SS antagonistically concert E. piscicida infection. Furthermore, we found an significant decrease in transcription level of IL-1ß in zebrafish kidney infected with T3SS mutant and an drastically increase in transcription level of TNF- α infected with T6SS mutant when compared with the wild-type. Interestingly, both T3SS and T6SS mutants showed significant attenuated virulence in the zebrafish infection model when compared with the wild-type. Finally, considering the cooperative role of T3SS and T6SS, we generated a mutant strain WEDΔT6SS based on the existing live attenuated vaccine (LAV) WED which showed improved vaccine safety and comparable immune protection. Therefore, WEDΔT6SS could be used as an optimized LAV in the future. Taken together, this work suggested a bilateral role of T3SS and T6SS which respectively act as spear and shield during E. piscicida infection, together contribute to E. piscicida virulence.

20.
Int J Biol Macromol ; 140: 1269-1276, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31470054

RESUMO

This study investigates the physico-mechanical and structural properties of ß-glucan (BG)/pullulan (PUL) composite edible films successfully prepared with 0-0.3 g of BG. Results demonstrated that BG addition significantly increases the elongation at break (p < 0.05), tensile strength, and water dissolution time of the resulting films. The transparency of the 0.2PUL:0.1BG film and the oxygen barrier property of the 0.15PUL:0.15BG film decreased remarkably compared with those of the plain films (0.3PUL:0BG and 0PUL:0.3BG) and other composite films (p < 0.05). FTIR indicated hydrogen bonding interactions between PUL and BG molecules, and microstructural observations showed that aggregated BG is homogeneously dispersed in the PUL continuous matrix. Among the films tested, the thermal stability of the 0.15PUL:0.15BG film was the best. A PUL:BG mixing ratio of 0.15:0.15 is thus suggested to provide the best film properties. This research offers an alternative method to improve PUL-based edible films.

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