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1.
New Phytol ; 241(4): 1732-1746, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38037458

RESUMO

Lysine acetylation is an evolutionarily conserved and widespread post-translational modification implicated in the regulation of multiple metabolic processes, but its function remains largely unknown in plant pathogenic fungi. A comprehensive analysis combined with proteomic, molecular and cellular approaches was presented to explore the roles of cytoplasmic acetylation in Fusarium oxsysporum f.sp. lycopersici (Fol). The divergent cytoplasmic deacetylase FolSir2 was biochemically characterized, which is contributing to fungal virulence. Based on this, a total of 1752 acetylated sites in 897 proteins were identified in Fol via LC-MS/MS analysis. Further analyses of the quantitative acetylome revealed that 115 proteins representing two major pathways, translational and ribosome biogenesis, were hyperacetylated in the ∆Folsir2 strain. We experimentally examined the regulatory roles of FolSir2 on K271 deacetylation of FolGsk3, a serine/tyrosine kinase implicated in a variety of cellular functions, which was found to be crucial for the activation of FolGsk3 and thus modulated Fol pathogenicity. Cytoplasmic deacetylation by FolSir2 homologues has a similar function in Botrytis cinerea and likely other fungal pathogens. These findings reveal a conserved mechanism of silent information regulator 2-mediated cytoplasmic deacetylation that is involved in plant-fungal pathogenicity, providing a candidate target for designing broad-spectrum fungicides to control plant diseases.


Assuntos
Fusarium , Proteômica , Cromatografia Líquida , Espectrometria de Massas em Tandem , Fungos , Processamento de Proteína Pós-Traducional , Doenças das Plantas/microbiologia
2.
Opt Express ; 32(4): 5760-5769, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439294

RESUMO

Heme is the prosthetic group for cytochrome that exists in nearly all living organisms and serves as a vital component of human red blood cells (RBCs). Tunable optical nonlinearity in suspensions of RBCs has been demonstrated previously, however, the nonlinear optical response of a pure heme (without membrane structure) solution has not been studied to our knowledge. In this work, we show optical nonlinearity in two common kinds of heme (i.e., hemin and hematin) solutions by a series of experiments and numerical simulations. We find that the mechanism of nonlinearity in heme solutions is distinct from that observed in the RBC suspensions where the nonlinearity can be easily tuned through optical power, concentration, and the solution properties. In particular, we observe an unusual phenomenon wherein the heme solution exhibits negative optical nonlinearity and render self-collimation of a focused beam at specific optical powers, enabling shape-preserving propagation of light to long distances. Our results may have potential applications in optical imaging and medical diagnosis through blood.


Assuntos
Eritrócitos , Heme , Humanos , Imagem Óptica
3.
Opt Lett ; 48(22): 5947-5950, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37966759

RESUMO

We demonstrate multiple flatbands and compact localized states (CLSs) in a photonic super-Kagome lattice (SKL) that exhibits coexistence of singular and nonsingular flatbands within its unique band structure. Specifically, we find that the upper two flatbands of an SKL are singular-characterized by singularities due to band touching with their neighboring dispersive bands at the Brillouin zone center. Conversely, the lower three degenerate flatbands are nonsingular and remain spectrally isolated from other dispersive bands. The existence of such two distinct types of flatbands is experimentally demonstrated by observing stable evolution of the CLSs with various geometrical shapes in a laser-written SKL. We also discuss the classification of the flatbands in momentum space, using band-touching singularities of the Bloch wave functions. Furthermore, we validate this classification in real space based on unit cell occupancy of the CLSs in a single SKL plaquette. These results may provide insights for the study of flatband transport, dynamics, and nontrivial topological phenomena in other relevant systems.

4.
Mol Plant Microbe Interact ; 33(10): 1242-1251, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32689887

RESUMO

Histone acetyltransferase plays a critical role in transcriptional regulation by increasing accessibility of target genes to transcriptional activators. Botrytis cinerea is an important necrotrophic fungal pathogen with worldwide distribution and a very wide host range, but little is known of how the fungus regulates the transition from saprophytic growth to infectious growth. Here, the function of BcSas2, a histone acetyltransferase of B. cinerea, was investigated. Deletion of the BcSAS2 gene resulted in significantly reduced acetylation levels of histone H4, particularly of H4K16ac. The deletion mutant ΔBcSas2.1 was not only less pathogenic but also more sensitive to oxidative stress than the wild-type strain. RNA-Seq analysis revealed that a total of 13 B. cinerea genes associated with pathogenicity were down-regulated in the ΔBcSas2.1 mutant. Independent knockouts of two of these genes, BcXYGA (xyloglucanase) and BcCAT (catalase), led to dramatically decreased virulence and hypersensitivity to oxidative stress, respectively. Chromatin immunoprecipitation followed by quantitative PCR confirmed that BcSas2 bound directly to the promoter regions of both these pathogenicity-related genes. These observations indicated that BcSas2 regulated the transcription of pathogenicity-related genes by controlling the acetylation level of H4K16, thereby affecting the virulence and oxidative sensitivity of B. cinerea.


Assuntos
Botrytis/fisiologia , Histonas , Estresse Oxidativo , Acetilação , Botrytis/genética , Botrytis/patogenicidade , Catalase/genética , Genes Fúngicos , Glicosídeo Hidrolases/genética , Histonas/genética , Doenças das Plantas/microbiologia , Virulência
5.
Anesthesiology ; 133(4): 905-918, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32930731

RESUMO

BACKGROUND: Alveolar epithelial cell apoptosis is implicated in the onset of ventilator-induced lung injury. Death-associated protein kinase 1 (DAPK1) is associated with cell apoptosis. The hypothesis was that DAPK1 participates in ventilator-induced lung injury through promoting alveolar epithelial cell apoptosis. METHODS: Apoptosis of mouse alveolar epithelial cell was induced by cyclic stretch. DAPK1 expression was altered (knockdown or overexpressed) in vitro by using a small interfering RNA or a plasmid, respectively. C57/BL6 male mice (n = 6) received high tidal volume ventilation to establish a lung injury model. Adeno-associated virus transfection of short hairpin RNA and DAPK1 inhibitor repressed DAPK1 expression and activation in lungs, respectively. The primary outcomes were alveolar epithelial cell apoptosis and lung injury. RESULTS: Compared with the control group, the 24-h cyclic stretch group showed significantly higher alveolar epithelial cell apoptotic percentage (45 ± 4% fold vs. 6 ± 1% fold; P < 0.0001) and relative DAPK1 expression, and this group also demonstrated a reduced apoptotic percentage after DAPK1 knockdown (27 ± 5% fold vs. 53 ± 8% fold; P < 0.0001). A promoted apoptotic percentage in DAPK1 overexpression was observed without stretching (49 ± 6% fold vs. 14 ± 3% fold; P < 0.0001). Alterations in B-cell lymphoma 2 and B-cell lymphoma 2-associated X are associated with DAPK1 expression. The mice subjected to high tidal volume had higher DAPK1 expression and alveolar epithelial cell apoptotic percentage in lungs compared with the low tidal volume group (43 ± 6% fold vs. 4 ± 2% fold; P < 0.0001). Inhibition of DAPK1 through adeno-associated virus infection or DAPK1 inhibitor treatment appeared to be protective against lung injury with reduced lung injury score, resolved pulmonary inflammation, and repressed alveolar epithelial cell apoptotic percentage (47 ± 4% fold and 48 ± 6% fold; 35 ± 5% fold and 34 ± 4% fold; P < 0.0001, respectively). CONCLUSIONS: DAPK1 promotes the onset of ventilator-induced lung injury by triggering alveolar epithelial cell apoptosis through intrinsic apoptosis pathway in mice.


Assuntos
Células Epiteliais Alveolares/metabolismo , Apoptose/fisiologia , Proteínas Quinases Associadas com Morte Celular/biossíntese , Lesão Pulmonar Induzida por Ventilação Mecânica/metabolismo , Células Epiteliais Alveolares/patologia , Animais , Células Cultivadas , Proteínas Quinases Associadas com Morte Celular/deficiência , Proteínas Quinases Associadas com Morte Celular/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Lesão Pulmonar Induzida por Ventilação Mecânica/patologia
6.
Molecules ; 25(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31906305

RESUMO

Lipid metabolism dysfunction and obesity are serious health issues to human beings. The current study investigated the effects of hyperbaric oxygen (HBO) against high fat diet (HFD)-induced lipid metabolism dysfunction and the roles of L-carnitine. C57/B6 mice were fed with HFD or normal chew diet, with or without HBO treatment. Histopathological methods were used to assess the adipose tissues, serum free fatty acid (FFA) levels were assessed with enzymatic methods, and the endogenous circulation and skeletal muscle L-carnitine levels were assessed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Additionally, western blotting was used to assess the expression levels of PPARα, CPT1b, pHSL/HSL, and UCP1. HFD treatment increased body/adipose tissue weight, serum FFA levels, circulation L-carnitines and decreased skeletal muscle L-carnitine levels, while HBO treatment alleviated such changes. Moreover, HFD treatment increased fatty acid deposition in adipose tissues and decreased the expression of HSL, while HBO treatment alleviated such changes. Additionally, HFD treatment decreased the expression levels of PPARα and increased those of CPT1b in skeletal muscle, while HBO treatment effectively reverted such changes as well. In brown adipose tissues, HFD increased the expression of UCP1 and the phosphorylation of HSL, which was abolished by HBO treatment as well. In summary, HBO treatment may alleviate HFD-induced fatty acid metabolism dysfunction in C57/B6 mice, which seems to be associated with circulation and skeletal muscle L-carnitine levels and PPARα expression.


Assuntos
Tecido Adiposo/metabolismo , Carnitina/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Tecido Adiposo/citologia , Animais , Carnitina/sangue , Carnitina/química , Carnitina O-Palmitoiltransferase/metabolismo , Cromatografia Líquida , Oxigenoterapia Hiperbárica , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/enzimologia , Músculo Esquelético/metabolismo , Obesidade/tratamento farmacológico , PPAR alfa/metabolismo , Fosforilação , Esterol Esterase/química , Esterol Esterase/metabolismo , Espectrometria de Massas em Tandem , Proteína Desacopladora 1/metabolismo
7.
Am J Physiol Lung Cell Mol Physiol ; 316(6): L1013-L1024, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30724098

RESUMO

Mechanical ventilation-induced pulmonary fibrosis plays an important role in the high mortality rate of acute respiratory distress syndrome (ARDS). Resolvin D1 (RvD1) displays potent proresolving activities. Epithelial-mesenchymal transition (EMT) has been proved to be an important pathological feature of lung fibrosis. This study aimed to investigate whether RvD1 can attenuate mechanical ventilation-induced lung fibrosis. Human lung epithelial (BEAS-2B) cells were pretreated with RvD1 for 30 min and exposed to acid for 10 min before being subjected to mechanical stretch for 48 h. C57BL/6 mice were subjected to intratracheal acid aspiration followed by mechanical ventilation 24 h later (peak inspiratory pressure 22 cmH2O, positive end-expiratory pressure 2 cmH2O, and respiratory rate 120 breaths/min for 2 h). RvD1 was injected into mice for 5 consecutive days after mechanical ventilation. Treatment with RvD1 significantly inhibited mechanical stretch-induced mesenchymal markers (vimentin and α-smooth muscle actin) and stimulated epithelial markers (E-cadherin). Tert-butyloxycarbonyl 2 (BOC-2), a lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2) antagonist, is known to inhibit ALX/FPR2 function. BOC-2 could reverse the beneficial effects of RvD1. The antifibrotic effect of RvD1 was associated with the suppression of Smad2/3 phosphorylation. This study demonstrated that mechanical stretch could induce EMT and pulmonary fibrosis and that treatment with RvD1 could attenuate mechanical ventilation-induced lung fibrosis, thus highlighting RvD1 as an effective therapeutic agent against pulmonary fibrosis associated with mechanical ventilation.


Assuntos
Ácidos Docosa-Hexaenoicos/uso terapêutico , Transição Epitelial-Mesenquimal/fisiologia , Fibrose Pulmonar/patologia , Respiração Artificial/efeitos adversos , Estresse Mecânico , Animais , Linhagem Celular , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/prevenção & controle , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/prevenção & controle
8.
Opt Express ; 27(19): 26331-26345, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31674517

RESUMO

Trajectory control of spatial solitons is an important subject in optical transmission field. Here we investigate the propagation dynamics of Laguerre-Gaussian soliton arrays in nonlinear media with a strong nonlocality and introduce two parameters, which we refer to as initial tangential velocity and displacement, to control the propagation path. The general analytical expression for the evolution of the soliton array is derived and the propagation properties, such as the intensity distribution, the propagation trajectory, the center distance, and the angular velocity are analyzed. It is found that the initial tangential velocity and displacement make the solitons sinusoidally oscillate in the x and y directions, and each constituent soliton undergoes elliptically or circularly spiral trajectory during propagation. A series of numerical examples is exhibited to graphically illustrate these typical propagation properties. Our results may provide a new perspective and stimulate further active investigations of multisoliton interaction and may be applied in optical communication and particle control.

9.
BMC Genomics ; 19(1): 209, 2018 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-29558883

RESUMO

BACKGROUND: Protein lysine malonylation, a newly discovered post-translational modification (PTM), plays an important role in diverse metabolic processes in both eukaryotes and prokaryotes. Common wheat is a major global cereal crop. However, the functions of lysine malonylation are relatively unknown in this crop. Here, a global analysis of lysine malonylation was performed in wheat. RESULTS: In total, 342 lysine malonylated sites were identified in 233 proteins. Bioinformatics analysis showed that the frequency of arginine (R) in position + 1 was highest, and a modification motif, KmaR, was identified. The malonylated proteins were located in multiple subcellular compartments, especially in the cytosol (45%) and chloroplast (30%). The identified proteins were found to be involved in diverse pathways, such as carbon metabolism, the Calvin cycle, and the biosynthesis of amino acids, suggesting an important role for lysine malonylation in these processes. Protein interaction network analysis revealed eight highly interconnected clusters of malonylated proteins, and 137 malonylated proteins were mapped to the protein network database. Moreover, five proteins were simultaneously modified by lysine malonylation, acetylation and succinylation, suggesting that these three PTMs may coordinately regulate the function of many proteins in common wheat. CONCLUSIONS: Our results suggest that lysine malonylation is involved in a variety of biological processes, especially carbon fixation in photosynthetic organisms. These data represent the first report of the lysine malonylome in common wheat and provide an important dataset for further exploring the physiological role of lysine malonylation in wheat and likely all plants.


Assuntos
Lisina/metabolismo , Malonatos/metabolismo , Proteínas de Plantas/metabolismo , Processamento de Proteína Pós-Traducional , Proteoma/análise , Triticum/metabolismo , Biologia Computacional , Proteômica/métodos
10.
Opt Express ; 26(15): 19182-19198, 2018 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-30114178

RESUMO

In this paper, we discuss the evolution of the Gaussian-shaped soliton clusters in strongly nonlocal nonlinear media, which is modeled by the nonlinear Schrödinger equation. The influences of three initial incident parameters (the initial transverse velocity, the initial position, the input power) on propagation dynamics of the soliton clusters are all discussed in detail. The results show that the intensity distribution, the trajectory, the center distance, and the angular velocity of the clusters can be controlled by adjusting the initial incident parameters. A series of analytical solutions on the propagation dynamics of the clusters are derived by borrowing ideas from classical physics. The results in this paper may have potential applications in the beam controlling and all-optical interconnection with the interacting characteristics of (2+1)-dimensional soliton clusters.

11.
Nucleic Acids Res ; 44(5): 1979-88, 2016 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-26847092

RESUMO

RNase II, a 3' to 5' processive exoribonuclease, is the major hydrolytic enzyme in Escherichia coli accounting for ∼90% of the total activity. Despite its importance, little is actually known about regulation of this enzyme. We show here that one residue, Lys501, is acetylated in RNase II. This modification, reversibly controlled by the acetyltransferase Pka, and the deacetylase CobB, affects binding of the substrate and thus decreases the catalytic activity of RNase II. As a consequence, the steady-state level of target RNAs of RNase II may be altered in the cells. We also find that under conditions of slowed growth, the acetylation level of RNase II is elevated and the activity of RNase II decreases, emphasizing the importance of this regulatory process. These findings indicate that acetylation can regulate the activity of a bacterial ribonuclease.


Assuntos
Proteínas de Escherichia coli/metabolismo , Escherichia coli/genética , Exorribonucleases/metabolismo , Regulação Bacteriana da Expressão Gênica , Lisina/metabolismo , Processamento de Proteína Pós-Traducional , Acetilação , Acetiltransferases/genética , Acetiltransferases/metabolismo , Domínio Catalítico , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Exorribonucleases/genética , Ligação Proteica , RNA Bacteriano/genética , RNA Bacteriano/metabolismo , Sirtuínas/genética , Sirtuínas/metabolismo
12.
BMC Genomics ; 18(1): 309, 2017 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-28427325

RESUMO

BACKGROUND: Protein lysine succinylation is an important post-translational modification and plays a critical regulatory role in almost every aspects of cell metabolism in both eukaryotes and prokaryotes. Common wheat is one of the major global cereal crops. However, to date, little is known about the functions of lysine succinylation in this plant. Here, we performed a global analysis of lysine succinylation in wheat and examined its overlap with lysine acetylation. RESULTS: In total, 330 lysine succinylated modification sites were identified in 173 proteins. Bioinformatics analysis showed that the modified proteins are distributed in multiple subcellular compartments and are involved in a wide variety of biological processes such as photosynthesis and the Calvin-Benson cycle, suggesting an important role for lysine succinylation in these processes. Five putative succinylation motifs were identified. A protein interaction network analysis revealed that diverse interactions are modulated by protein succinylation. Moreover, 21 succinyl-lysine sites were found to be acetylated at the same position, and 33 proteins were modified by both acetylation and succinylation, suggesting an extensive overlap between succinylation and acetylation in common wheat. Comparative analysis indicated that lysine succinylation is conserved between common wheat and Brachypodium distachyon. CONCLUSIONS: These results suggest that lysine succinylation is involved in diverse biological processes, especially in photosynthesis and carbon fixation. This systematic analysis represents the first global analysis of lysine succinylation in common wheat and provides an important resource for exploring the physiological role of lysine succinylation in this cereal crop and likely in all plants.


Assuntos
Lisina/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Processamento de Proteína Pós-Traducional , Proteômica , Ácido Succínico/metabolismo , Triticum/metabolismo , Acetilação , Ciclo do Carbono , Anotação de Sequência Molecular , Fotossíntese , Proteínas de Plantas/genética , Estrutura Secundária de Proteína , Transporte Proteico , Triticum/citologia , Triticum/genética
13.
Biochem Biophys Res Commun ; 472(1): 175-81, 2016 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-26915798

RESUMO

Inflammation plays a crucial role in acute ischemic stroke pathogenesis. Macrophage-derived Maresin 1 (MaR1) is a newly uncovered mediator with potent anti-inflammatory abilities. Here, we investigated the effect of MaR1 on acute inflammation and neuroprotection in a mouse brain ischemia reperfusion (I/R) model. Male C57 mice were subjected to 1-h middle cerebral artery occlusion (MCAO) and reperfusion. By the methods of 2,3,5-triphenyltetrazolium chloride, haematoxylin and eosin or Fluoro-Jade B staining, neurological deficits scoring, ELISA detection, immunofluorescence assay and western blot analysis, we found that intracerebroventricular injection of MaR1 significantly reduced the infarct volume and neurological defects, essentially protected the brain tissue and neurons from injury, alleviated pro-inflammatory reactions and NF-κB p65 activation and nuclear translocation. Taken together, our results suggest that MaR1 significantly protects against I/R injury probably by inhibiting pro-inflammatory reactions.


Assuntos
Anti-Inflamatórios/farmacologia , Isquemia Encefálica/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Anti-Inflamatórios/administração & dosagem , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Citocinas/metabolismo , Ácidos Docosa-Hexaenoicos/administração & dosagem , Regulação para Baixo/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Injeções Intraventriculares , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Degeneração Neural/patologia , Degeneração Neural/prevenção & controle , Neuroglia/efeitos dos fármacos , Neuroglia/patologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia
14.
Int J Syst Evol Microbiol ; 66(9): 3456-3462, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27263534

RESUMO

A Gram-stain-negative, aerobic, non-motile bacterial strain, 7Y-4T, was isolated from bark tissue of Populus × euramericana. The isolate was able to grow between 10 and 37 °C, with optimal growth occurring at 28-30 °C. Strain 7Y-4T was positive for oxidase and catalase activities, but did not reduce nitrite from nitrate. Positive reactions were observed for the activities of ß-galactosidase, urease and ß-glucosidase, but negative reactions for the activities of gelatinase and the production of indole, acetoin and H2S. Citrate was not utilized. The major fatty acids of strain 7Y-4T are iso-C15 : 0 (28.6 %), C16 : 1ω7c/C16 : 1ω6c (31.8 %) and iso-C17 : 0 3-OH (23.3 %).The major polar lipids of the novel isolate include phosphatidylethanolamine, three unknown phospholipids (PL1-3) and six unknown lipids (L1-6), and the predominant menaquinone is MK-7. The DNA G+C content is 41.7 mol%. Analysis of 16S rRNA gene sequences revealed that the novel isolate shared the greatest sequence similarity with Sphingobacterium hotanense XH4T (93.50 %). On the basis of phenotypic and genotypic characteristics, strain 7Y-4T represents a novel species of the genus Sphingobacterium, for which the name Sphingobacterium populi is proposed. The type strain is 7Y-4T (=CFCC 11742T=KCTC 42247T).


Assuntos
Filogenia , Populus/microbiologia , Sphingobacterium/classificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , Casca de Planta/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Sphingobacterium/genética , Sphingobacterium/isolamento & purificação , Vitamina K 2/análogos & derivados , Vitamina K 2/química
15.
J Neuroinflammation ; 11: 72, 2014 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-24708771

RESUMO

BACKGROUND: Microglia play key roles in innate immunity, homeostasis, and neurotropic support in the central nervous system. Similar to macrophages, microglia adopt two different activation phenotypes, the classical and alternative activation. Resolvin D1 (RvD1) is considered to display potent anti-inflammatory and pro-resolving actions in inflammatory models. In this present study, we investigate the effect of RvD1 on IL-4-induced alternative activation in murine BV-2 microglial cells. METHODS: BV-2 cells were incubated with RvD1 alone, IL-4 alone, or the combination of RvD1 and IL-4. Western blot and immunofluorescence were performed to detect protein levels of alternative activation markers arginase 1 (Arg1), chitinase 3-like 3 (Ym1). Moreover, we investigated the effects of RvD1 on IL-4-induced activation of signal transducer and activators of transcription 6 (STAT6) and peroxisome proliferator-activated receptor gamma (PPARγ). RESULTS: RvD1 promoted IL-4-induced microglia alternative activation by increasing the expression of Arg1 and Ym1. RvD1 also enhanced phosphorylation of STAT6, nuclear translocation of PPARγ and the DNA binding activity of STAT6 and PPARγ. These effects were reversed by butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (a formyl peptide receptor 2 antagonist). Further, the effects of RvD1 and IL-4 on Arg1 and Ym1 were blocked by the application of leflunomide (a STAT6 inhibitor) or GW9662 (a PPARγ antagonist). CONCLUSIONS: Our studies demonstrate that RvD1 promotes IL-4-induced alternative activation via STAT6 and PPARγ signaling pathways in microglia. These findings suggest that RvD1 may have therapeutic potential for neuroinflammatory diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Interleucina-4/farmacologia , Microglia/efeitos dos fármacos , Análise de Variância , Animais , Arginase/metabolismo , Linhagem Celular Transformada , Relação Dose-Resposta a Droga , Doxorrubicina/análogos & derivados , Doxorrubicina/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Isoxazóis/farmacologia , Leflunomida , Camundongos , PPAR gama/metabolismo , Fosforilação/efeitos dos fármacos , Fator de Transcrição STAT6/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
J Biol Chem ; 287(7): 4800-7, 2012 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-22194614

RESUMO

The Fanconi anemia complementation group A (FANCA) gene is one of 15 disease-causing genes and has been found to be mutated in ∼60% of Fanconi anemia patients. Using purified protein, we report that human FANCA has intrinsic affinity for nucleic acids. FANCA binds to both single-stranded (ssDNA) and double-stranded (dsDNA) DNAs; however, its affinity for ssDNA is significantly higher than for dsDNA in an electrophoretic mobility shift assay. FANCA also binds to RNA with an intriguingly higher affinity than its DNA counterpart. FANCA requires a certain length of nucleic acids for optimal binding. Using DNA and RNA ladders, we determined that the minimum number of nucleotides required for FANCA recognition is ∼30 for both DNA and RNA. By testing the affinity between FANCA and a variety of DNA structures, we found that a 5'-flap or 5'-tail on DNA facilitates its interaction with FANCA. A patient-derived FANCA truncation mutant (Q772X) has diminished affinity for both DNA and RNA. In contrast, the complementing C-terminal fragment of Q772X, C772-1455, retains the differentiated nucleic acid-binding activity (RNA > ssDNA > dsDNA), indicating that the nucleic acid-binding domain of FANCA is located primarily at its C terminus, where most disease-causing mutations are found.


Assuntos
DNA de Cadeia Simples/química , Proteínas de Ligação a DNA/química , Proteína do Grupo de Complementação A da Anemia de Fanconi/química , Proteínas de Ligação a RNA/química , RNA/química , Substituição de Aminoácidos , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Proteína do Grupo de Complementação A da Anemia de Fanconi/metabolismo , Humanos , Mutação de Sentido Incorreto , Mapeamento de Peptídeos , Ligação Proteica , Estrutura Terciária de Proteína , RNA/genética , RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
17.
Microbiol Spectr ; 11(4): e0108323, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37378525

RESUMO

Verticillium dahliae is a soilborne fungal pathogen that causes disease on many economically important crops. Based on the resistance or susceptibility of differential cultivars in tomato, isolates of V. dahliae are divided into three races. Avirulence (avr) genes within the genomes of the three races have also been identified. However, the functional role of the avr gene in race 3 isolates of V. dahliae has not been characterized. In this study, bioinformatics analysis showed that VdR3e, a cysteine-rich secreted protein encoded by the gene characterizing race 3 in V. dahliae, was likely obtained by horizontal gene transfer from the fungal genus Bipolaris. We demonstrate that VdR3e causes cell death by triggering multiple defense responses. In addition, VdR3e localized at the periphery of the plant cell and triggered immunity depending on its subcellular localization and the cell membrane receptor BAK1. Furthermore, VdR3e is a virulence factor and shows differential pathogenicity in race 3-resistant and -susceptible hosts. These results suggest that VdR3e is a virulence factor that can also interact with BAK1 as a pathogen-associated molecular pattern (PAMP) to trigger immune responses. IMPORTANCE Based on the gene-for-gene model, research on the function of avirulence genes and resistance genes has had an unparalleled impact on breeding for resistance in most crops against individual pathogens. The soilborne fungal pathogen, Verticillium dahliae, is a major pathogen on many economically important crops. Currently, avr genes of the three races in V. dahliae have been identified, but the function of avr gene representing race 3 has not been described. We investigated the characteristics of VdR3e-mediated immunity and demonstrated that VdR3e acts as a PAMP to activate a variety of plant defense responses and induce plant cell death. We also demonstrated that the role of VdR3e in pathogenicity was host dependent. This is the first study to describe the immune and virulence functions of the avr gene from race 3 in V. dahliae, and we provide support for the identification of genes mediating resistance against race 3.


Assuntos
Ascomicetos , Verticillium , Virulência/genética , Verticillium/genética , Imunidade Vegetal , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Doenças das Plantas/microbiologia
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(1): 141-145, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35123617

RESUMO

OBJECTIVE: To investigate the clinical characteristics and prognosis of multiple myeloma patients with myelofibrosis. METHODS: The clinical data of 263 patients with multiple myeloma (including 92 patients with myelofibrosis) treated in the department of hematology of our hospital from January 1, 2016 to June 31, 2020 were collected and retrospectively analyzed, the patients were divided into combined group and uncombined group. The MM stage, MM type, genetic characteristics and therapeutic effect of the patients in combined group and uncombined group were observed, and the relationship between the curative effect and the degree of myelofibrosis change of the patients in combined group was analyzed. RESULTS: There was no statistically difference in the MM staging and classification between multiple myeloma patients with or without myelofibrosis (P>0.05). The positive rate of FISH results of the patients in combined group was significantly higher than those in uncombined group, and was significantly correlated to 1q21 amplification, D13S319 deletion, and IgH breakage (P<0.05). After treatment, the effective rate of the patients in uncombined group was significantly higher than those in combined group, and the degree of fibrosis in the effective patients in combined group was significantly reduced. CONCLUSION: The survival rate of the patients with multiple myeloma complicated with myelofibrosis is shorter than that of the patients without myelofibrosis, and the overall prognosis is poor.


Assuntos
Mieloma Múltiplo , Mielofibrose Primária , Aberrações Cromossômicas , Humanos , Mieloma Múltiplo/complicações , Mielofibrose Primária/complicações , Prognóstico , Estudos Retrospectivos
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(1): 170-174, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35123622

RESUMO

OBJECTIVE: To compare the efficacy and safety of different chemotherapy regimens in elderly multiple myeloma (MM) patients with different Frailty scores. METHODS: The clinical data of elderly patients with MM were retrospectively analyzed, including age, treatment regimen, efficacy, adverse reactions, and the Frailty score included in the activity of daily living score, the instrumental activity of daily living scale and the Charlson comorbidity index. The patients were divided into fit group, mediate fit group and frail group according to the scoring standard. The treatment efficiency and adverse reaction rates of elderly MM with different physical conditions treated by different chemotherapy regimens were analyzed. RESULTS: Among the 70 patients, the effective rates of the patients in fit group, the mediate fit group, and the frail group were 79.5%, 81%, and 40%, and the effective rates of the fit patients in double and triple groups were 54.5% and 89.3%, 70% and 90.9% for mediate fit patients, 42.9% and 33.3% for frail patients, the triple regimen in fit patients showed obvious advantages, and the difference showed statistically significant (P<0.05), while the efficacy for mediate patients and frail patients showed no significant difference. During the induction of bortezomib, the incidence of adverse reactions for the patients in the triple group (78.6%) was higher than 67.9% in the double group, and the difference showed no statistically significant (P>0.05).There was no significant difference in the 1-year overall survival rate of the patients and with molecular genetic abnormalities among each groups. CONCLUSION: The therapeutic effect is related to the patient's physical condition. For patients with healthy physique, the triple regimen should be used first. For patients with weak physical constitution, the chemotherapy regimen with low drug toxicity should be selected for safety.


Assuntos
Fragilidade , Mieloma Múltiplo , Idoso , Bortezomib , Humanos , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(2): 481-486, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35395983

RESUMO

OBJECTIVE: To investigate the prognostic value of hemopoietic scoring system composed of hemoglobin (HB), platelet count (PLT) and mean corpuscular volume (MCV) in MM patients and its correlation with curative effect. METHODS: The clinical data of 172 newly diagnosed MM patients treated by bortezomib as the first-line regimen in our hospital from May 2014 to December 2019 were collected, three variables (HB≤100 g/L, PLT≤150×109/L, MCV≥96 fl) were introduced, each variable was distributed 1 score, the patients were divided into four groups (0, 1, 2 and 3 points in group 1, 2, 3 and 4, respectively), and the clinical characteristics and prognosis of the patients in the four groups were analyzed. The initial efficacy evaluation after 3-4 courses of treatment was carried out, and the curative effect of the patients in the different hematopoiesis score groups were compared. RESULTS: The median OS time of the patients in group 1, 2, 3 and 4 was 27.0, 22.5, 20.7 and 18.1 months, while the median PFS time were 23.0, 19.0, 18.0 and 14.0 months, respectively. The OS and PFS of the patients in low score group were significantly better than those in high score group (P=0.045, P=0.048). There was no significant difference in the curative effect of the patients treated by bortezomib after 3-4 courses (P>0.05). CONCLUSION: Hematopoiesis score can preliminarily predict the overall survival of newly diagnosed MM patients, but there is no significant difference between different scoring groups in the initial curative effect.


Assuntos
Mieloma Múltiplo , Bortezomib/uso terapêutico , Índices de Eritrócitos , Hemoglobinas/uso terapêutico , Humanos , Mieloma Múltiplo/diagnóstico , Prognóstico , Estudos Retrospectivos
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