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1.
Int J Nanomedicine ; 14: 7475-7488, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571859

RESUMO

Background: Wear particle-induced inflammatory osteolysis and the consequent aseptic loosening constitute the leading reasons for prosthesis failure and revision surgery. Several studies have demonstrated that the macrophage polarization state and immune response play critical roles in periprosthetic osteolysis and tissue repair, but the immunomodulatory role of lithium chloride (LiCl), which has a protective effect on wear particle-induced osteolysis by suppressing osteoclasts and attenuating inflammatory responses, has never been investigated. Methods: In this work, the immunomodulatory capability of LiCl on titanium (Ti) nanoparticle-stimulated transformation of macrophage phenotypes and the subsequent effect on osteogenic differentiation were investigated. We first speculated that LiCl attenuated Ti nanoparticle-stimulated inflammation responses by driving macrophage polarization and generating an immune micro-environment to improve osteogenesis. Furthermore, a metal nanoparticle-stimulated murine air pouch inflammatory model was applied to confirm this protective effect in vivo. Results: The results revealed that metal nanoparticles significantly activate M1 phenotype (proinflammatory macrophage) expression and increase proinflammatory cytokines secretions in vitro and in vivo, whereas LiCl drives macrophages to the M2 phenotype (anti-inflammatory macrophage) and increases the release of anti-inflammatory and bone-related cytokines. This improved the osteogenic differentiation capability of rat bone marrow mesenchymal stem cells (rBMSCs). In addition, we also provided evidence that LiCl inhibits the phosphorylation of the p38 mitogen-activated protein kinase (p38) and extracellular signal-regulated kinase (ERK) pathways in wear particle-treated macrophages. Conclusion: LiCl has the immunomodulatory effects to alleviate Ti nanoparticle-mediated inflammatory reactions and enhance the osteogenic differentiation of rBMSCs by driving macrophage polarization. Thus, LiCl may be an effective therapeutic alternative for preventing and treating wear debris-induced inflammatory osteolysis.

2.
Int Immunopharmacol ; 76: 105865, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31476694

RESUMO

Wear particle-induced periprosthetic inflammatory osteolysis and resultant aseptic loosening are major causes of orthopedic implant failure, for which there are no effective treatments other than revision surgery. Crocin, a carotenoid compound derived from crocus flowers, has anti-inflammatory properties, but its immunomodulatory function and role in particle-induced osteolysis are not well characterized. Here we report the effect of crocin on titanium (Ti) particle-induced macrophage polarization and osteogenic differentiation. We found that crocin induced anti-inflammatory (M2) macrophage polarization and attenuated Ti particle-induced inflammation by promoting the expression of anti-inflammatory cytokines in vitro as well as in vivo in a mouse air-pouch model. Additionally, crocin pre-treated macrophages promoted osteogenic differentiation of co-cultured mouse bone mesenchymal stem cells (BMSCs). These effects were mediated via inhibition of p38 and c-Jun N-terminal kinase signaling. Our results indicate that crocin suppresses Ti particle-induced inflammation and enhances osteogenic differentiation of BMSCs by inducing M2 macrophage polarization, highlighting its therapeutic potential for preventing wear particle-induced osteolysis.

3.
Biosens Bioelectron ; 145: 111699, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31563802

RESUMO

Covalent organic frameworks (COFs), as an emerging class of porous crystalline polymers, are built by the combination of the light elements through the strong covalent bonds. In the past decade, COFs have been reported to show plenty of unique properties (such as ordered channels, large specific surface area, highly tunable porosity, optional building blocks, predictable and stable structure, and abundant functional groups), and have been widely applied in multiple fields. Recently, to further improve the potential performances of COFs and extend their applicability, a number of COFs with various functionalities have been successfully developed through the functionalization modification. In this review, we summarized the advanced design and construction of functionalized COFs, including COFs with post-synthetic modification, COFs-based composites (e.g. COFs-metal nanoparticles composites, COFs-metal oxide nanoparticles composites, COFs-MOFs composites, and COFs-enzyme composites), and molecularly imprinted COFs. Impressively, the applications of functionalized COFs to sensing also have been comprehensively summarized, including colorimetric sensing, fluorescent sensing, electrochemical sensing, and other sensing (such as quartz crystal microbalance (QCM) sensing, photoelectrochemical sensing, and humidity sensing). In the end, future opportunities and challenges in this promising field are tentatively proposed.

4.
Ann Clin Transl Neurol ; 6(9): 1825-1835, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31478596

RESUMO

OBJECTIVE: Dexmedetomidine (DEX) exhibits neuroprotective effects as a multifunctional neuroprotective agent in numerous neurological disorders. However, in traumatic brain injury (TBI), the molecular mechanisms of these neuroprotective effects remain unclear. The present study investigated whether DEX, which has been reported to exert protective effects against TBI, could attenuate neuroinflammatory-induced apoptosis and clarified the underlying mechanisms. METHODS: A weight-drop model was established, and DEX was intraperitoneally injected 30 min after inducing TBI in rats. The water content in the brain tissue was measured. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays were performed on histopathological tissue sections to evaluate neuronal apoptosis. Enzyme-linked immunosorbent assay and PCR were applied to detect the levels of the inflammatory factors, TNF-α, IL-1ß, IL-6, and NF-κB. RESULTS: TBI-challenged rats exhibited significant neuronal apoptosis, which was characterized via the wet-to-dry weight ratio, neurobehavioral functions, TUNEL assay results and the levels of cleaved caspase-3, Bax upregulation and Bcl-2, which were attenuated by DEX. Western blot, immunohistochemistry, and PCR results revealed that DEX promoted Nrf2 expression and upregulated expression of the Nrf2 downstream factors, HO-1 and NQO-1. Furthermore, DEX treatment markedly prevented the downregulation of inflammatory response factors, TNF-α, IL-1ß and NF-κB, and IL-6. INTERPRETATION: Administering DEX attenuated inflammation-induced brain injury in a TBI model, potentially via the Nrf2 signaling pathway.

5.
J Mater Chem B ; 7(36): 5541-5553, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31451811

RESUMO

Prevention of implant-associated infections and insufficient bone tissue integration is critical to exploit the immunomodulatory properties and antibacterial effects of implant materials, which have attracted considerable attention. Modulation of the functions of immune cells in different environments is crucial for managing infection and inferior bone integration via immunomodulation. In this work, sodium butyrate, a fermentation product of gut microbiota, was loaded onto 3D porous sulfonated polyetheretherketone (SP) to modulate the immune responses of cells in different environments. Evaluation of in vitro antibacterial effects showed that sodium butyrate-loaded SP exhibited superior antibacterial activity, especially in the samples containing high concentrations of sodium butyrate. Under bacterial stimulation, the phagocytic activity of macrophages increased with an increase in the sodium butyrate concentration via the production of reactive oxygen species (ROS), which favoured bactericidal activity in the implant-associated infection stage. For bacterial elimination, sodium butyrate-containing SP could polarize macrophages to the M2 phenotype and subsequently stimulate anti-inflammatory cytokine secretion, which is considered beneficial for bone regeneration in the tissue repair stage. In vitro osteogenesis was evaluated and the results demonstrated that treatment with sodium butyrate-containing SP increased the expression of osteogenic genes and proteins. An in vivo rat osteomyelitis model was used to evaluate the protective effect of the SP-loaded with sodium butyrate on bone destruction and osteolysis under infection conditions. To study osteogenesis in vivo, a rat femoral model without infection was used. The results indicated that the SP-B2 group exhibited superior anti-infection capacity and induced new bone formation around the implant in vivo. Treatment with sodium butyrate-containing porous SP modulated the macrophage response under different stimuli, thereby serving as a new approach for the design of smart implant materials with superior antibacterial and bone repair properties.

6.
Plant Sci ; 286: 28-36, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31300139

RESUMO

MYB family genes act as important regulators modulating the response to abiotic stress in plants. However, much less is known about MYB proteins in cotton. Here, we found that a cotton MYB gene, GhMYB73, was induced by NaCl and abscisic acid (ABA). Silencing GhMYB73 expression in cotton increased sensitivity to salt stress. The cotyledon greening rate of Arabidopsis thaliana over-expressing GhMYB73 under NaCl or mannitol treatment was significantly enhanced during the seedling germination stage. What's more, several osmotic stress-induced genes, such as AtNHX1, AtSOS3 and AtP5CS1, were more highly induced in the over-expression lines than in wild type under salt treatment, supporting the hypothesis that GhMYB73 contributes to salinity tolerance by improving osmotic stress resistance. Arabidopsis lines over-expressing GhMYB73 had superior germination and cotyledon greening under ABA treatment, and some abiotic stress-induced genes involved in ABA pathways (AtPYL8, AtABF3, AtRD29B and AtABI5), had increased transcription levels under salt-stress conditions in these lines. Furthermore, we found that GhMYB73 physically interacts with GhPYL8 and AtPYL8, suggesting that GhMYB73 regulates ABA signaling during salinity stress response. Taken together, over-expression of GhMYB73 significantly increases tolerance to salt and ABA stress, indicating that it can potentially be used in transgenic technology approaches to improve cotton salt tolerance.


Assuntos
Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Gossypium/fisiologia , Proteínas de Plantas/genética , Estresse Salino/genética , Fatores de Transcrição/genética , Arabidopsis/genética , Inativação Gênica , Genes myb , Gossypium/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Tolerância ao Sal/genética , Fatores de Transcrição/metabolismo
7.
BMC Plant Biol ; 19(1): 307, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31299897

RESUMO

BACKGROUND: DNA methylation is a crucial epigenetic modification, which is involved in many biological processes, including gene expression regulation, embryonic development, cell differentiation and genomic imprinting etc. And it also involves many key regulatory genes in eukaryotes. By tracing the evolutionary history of methylation-related genes, we can understand the origin and expansion time of these genes, which helps to understand the evolutionary history of plants, and we can also understand the changes of DNA methylation patterns in different species. However, most studies on the evolution of methylation-related genes failed to be carried out for the whole DNA methylation pathway. RESULTS: In this study, we conducted a comprehensive identification of 33 methylation-related genes in 77 species, and investigated gene origin and evolution throughout the plant kingdom. We found that the origin of genes responsible for methylation maintenance and demethylation evolved early, while most de novo methylation-related genes appeared late. The methylation-related genes were expanded by whole genome duplication and tandem replication, but were also accompanied by a large number of gene absence events in different species. The gene length and intron length varied a lot in different species, but exon structure and functional domains were relatively conserved. The phylogenetic relationships of methylation-related genes were traced to reveal the evolution history of DNA methylation in different species. The expression patterns of methylation-related genes have changed during the evolution of species, and the expression patterns of these genes in different species can be clustered into four categories. CONCLUSIONS: The study describes a global characterization of DNA methylation-related genes in the plant kingdom. The similarities and differences in origin time, gene structure and phylogenetic relationship of these genes lead us to understand the evolutionary conservation and dynamics of DNA methylation in plants.


Assuntos
Metilação de DNA , Epigênese Genética , Impressão Genômica , Plantas/genética , Evolução Molecular , Éxons/genética , Íntrons/genética , Filogenia
8.
J Biomed Nanotechnol ; 15(6): 1172-1184, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31072426

RESUMO

Magnesium is an attractive candidate for orthopedic implants due to its similar mechanical properties to human bone and biodegradability. However, the high corrosion rate of magnesium accompanying with high pH value and poor osteogenic activity hinder its further application. In this study, we employed micro arc oxidation (MAO) to improve corrosion resistance by introduce nanoporous coating on AZ91 magnesium. Meanwhile, we added lithium, an angiogenic and osteogenic element, to the coating (named as Li-MAO) by reaction in a lithium-containing electrolyte to simultaneously enhance angiogenic and osteogenic activity of AZ91. The favorable corrosion resistance of Li-MAO was verified by electrochemical and immersion test in vitro. Better biocompatibility was observed in Li-MAO samples by cell counting kit-8 (CCK-8) and live/dead assay. The in vitro results of immunofluorescence staining, Alizarin red staining and osteogenic-related genes expression indicated better osteogenic ability of Li-MAO group, which may result from the activation the Wnt/ß-catenin pathway. In vitro angiogenic tests also demonstrated better angiogenesis in Li-MAO group. A bone defect repair model was built to evaluate the in vivo osseointegration of samples. The outcomes of micro-computed tomography (Micro-CT) scanning, sequential fluorochrome labeling and Van Gieson staining suggested better in vivo bone repair ability of Li-MAO than other groups. Our promising results both in vitro and in vivo demonstrated that lithium-containing nanoporous coating can improve corrosion resistance, angiogenesis and osseointegration of magnesium alloy, which may forward the clinic application of Li-MAO magnesium.


Assuntos
Nanoporos , Ligas , Materiais Revestidos Biocompatíveis , Corrosão , Lítio , Magnésio , Osseointegração , Oxirredução , Microtomografia por Raio-X
9.
Plant Biotechnol J ; 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31116473

RESUMO

The base-editing technique using CRISPR/nCas9 (Cas9 nickase) or dCas9 (deactivated Cas9) fused with cytidine deaminase is a powerful tool to create point mutations. In this study, a novel G. hirsutum-Base Editor 3 (GhBE3) base-editing system has been developed to create single-base mutations in the allotetraploid genome of cotton (Gossypium hirsutum). A cytidine deaminase sequence (APOBEC) fused with nCas9 and uracil glycosylase inhibitor (UGI) was inserted into our CRISPR/Cas9 plasmid (pRGEB32-GhU6.7). Three target sites were chosen for two target genes, GhCLA and GhPEBP, to test the efficiency and accuracy of GhBE3. The editing efficiency ranged from 26.67 to 57.78% at the three target sites. Targeted deep sequencing revealed that the C→T substitution efficiency within an 'editing window', approximately six-nucleotide windows of -17 to -12 bp from the PAM sequence, was up to 18.63% of the total sequences. The 27 most likely off-target sites predicted by CRISPR-P and Cas-OFFinder tools were analysed by targeted deep sequencing, and it was found that rare C→T substitutions (average < 0.1%) were detected in the editing windows of these sites. Furthermore, whole-genome sequencing analyses on two GhCLA-edited and one wild-type plants with about 100× depth showed that no bona fide off-target mutations were detectable from 1500 predicted potential off-target sites across the genome. In addition, the edited bases were inherited to T1 progeny. These results demonstrate that GhBE3 has high specificity and accuracy for the generation of targeted point mutations in allotetraploid cotton.

10.
J Cell Biochem ; 120(9): 14899-14907, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31042302

RESUMO

Breviscapine (BVP) has been widely used in the treatment of several systemic diseases, including those of the cardiovascular and cerebrovascular systems. But, few studies have looked at the neuroprotective effects of BVP and its potential effect in treating traumatic brain injury (TBI). The present study investigated the neuroprotective effect of BVP following TBI and illuminated the underlying mechanism. The weight drop-induced closed diffuse traumatic brain injury method was used to induce TBI in rats. BVP was injected intraperitoneally 30 minutes after TBI. Neurologic scores were performed to measure behavioral outcomes. Nissl staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays were performed on histopathologic tissue sections to evaluate neuronal apoptosis. The nuclear factor erythroid 2-related factor 2 (Nrf2) and its related downstream proteins, including heme oxygenase-1 (HO-1) and quinine oxidoreductase-1 (NQO1) were detected with Western blots. BVP treatment alleviated or attenuated TBI-induced neuron cell apoptosis and improved neurobehavioral functions through the upregulated expression of Nrf2 and its related downstream proteins. This study, using the drug, BVP, we present new mechanisms responsible for neuronal apoptosis in TBI with possible involvement of the Nrf2 pathway.

11.
Biosens Bioelectron ; 137: 178-198, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31100598

RESUMO

The nanomaterials with enzyme-like catalytic activity, named as nanozymes, have aroused wide research interest owing to their striking merits. Metal-organic frameworks (MOFs) have showed great prospect in the construction of novel nanozymes. In this review, firstly, we summarize the most recent contributions in the design construction of the MOFs-based nanozymes. Then, we concentrate our attention on their applications in the fields of sensing and cancer therapies. According to the design strategies, we categorized MOFs-based nanozymes into four classes for review (i.e. pristine MOFs, MOFs with modification, MOFs-based nanocomposites, and MOF derivatives). Meanwhile, the emerging and fascinating 2D MOFs-based nanozymes were also reviewed. A variety of novel applications are also discussed, including nanozymes catalytic mediated signal amplification in sensing applications (e.g. colorimetric sensing, fluorescent sensing, chemiluminescent sensing, electrochemical sensing, and surface-enhanced Raman scattering (SERS)), and nanozymes catalytic mediated cancer therapy (i.e. cancer-starvation therapy, enhancing photodynamic therapy, and cancer-starvation and PDT synergistic therapy). At the end of the article, future opportunities and challenges in this promising research area are tentatively proposed.

13.
Biomaterials ; 208: 8-20, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30986611

RESUMO

Metal ions or nanoparticles are believed to be promising additives in developing antibacterial biomaterials, owing to possessing favorable bactericidal effects against antibiotic-resistant bacteria. However, the immunomodulatory antibacterial activity of metal ions has seldom been reported. Herein, a porous microstructure designed to trap methicillin-resistant Staphylococcus aureus (MRSA) is fabricated on polyetheretherketone biomaterial surface through sulfonation (SPEEK), following which copper (Cu) nanoparticles, which can kill the trapped MRSA, are immobilized on SPEEK surface using a customized magnetron sputtering technique. In vitro antibacterial and immunological experiments indicate that the Cu-incorporated SPEEK can exert a desirable bactericidal effect against MRSA through the combination of "trap killing" and "contact killing" actions; meanwhile, macrophages cultured on the Cu-incorporated SPEEK can be activated and polarized to a pro-inflammatory phenotype along with improved phagocytic ability on the MRSA. Further in vivo implant-associated infection models evidence the superior antibacterial activity of the Cu-incorporated SPEEK. These results demonstrate multimodal antibacterial actions of the Cu-incorporated SPEEK, which is capable of imposing direct antibacterial and indirect immunomodulatory antibacterial effects simultaneously, in order to prevent and cure MRSA infection. It is believed that this study may shed light on developing novel biomaterial implants that combine antibacterial and immunomodulatory functions.

14.
Plant J ; 99(3): 494-505, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31002209

RESUMO

Recombination breaks up ancestral linkage disequilibrium, creates combinations of alleles, affects the efficiency of natural selection, and plays a major role in crop domestication and improvement. However, there is little knowledge regarding the variation in the population-scaled recombination rate in cotton. We constructed recombination maps and characterized the difference in the genomic landscape of the population-scaled recombination rate between Gossypium hirsutum and G. arboreum and sub-genomes based on the 381 sequenced G. hirsutum and 215 G. arboreum accessions. Comparative genomics identified large structural variations and syntenic genes in the recombination regions, suggesting that recombination was related to structural variation and occurred preferentially in the distal chromosomal regions. Correlation analysis indicated that recombination was only slightly affected by geographical distribution and breeding period. A genome-wide association study (GWAS) was performed with 15 agronomic traits using 267 cotton accessions and identified 163 quantitative trait loci (QTL) and an important candidate gene (Ghir_COL2) for early maturity traits. Comparative analysis of recombination and a GWAS revealed that the QTL of fibre quality traits tended to be more common in high-recombination regions than were those of yield and early maturity traits. These results provide insights into the population-scaled recombination landscape, suggesting that recombination contributed to the domestication and improvement of cotton, which provides a useful reference for studying recombination in other species.

15.
J Biol Chem ; 294(17): 7057-7067, 2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-30862676

RESUMO

Cotton (Gossypium spp.) is one of the most important economic crops and exhibits yield-improving heterosis in specific hybrid combinations. The genic male-sterility system is the main strategy used for producing heterosis in cotton. To better understand the mechanisms of male sterility in cotton, we carried out two-dimensional electrophoresis (2-DE) and label-free quantitative proteomics analysis in the anthers of two near-isogenic lines, the male-sterile line 1355A and the male-fertile line 1355B. We identified 39 and 124 proteins that were significantly differentially expressed between these two lines in the anthers at the tetrad stage (stage 7) and uninucleate pollen stage (stage 8), respectively. Gene ontology-based analysis revealed that these differentially expressed proteins were mainly associated with pyruvate, carbohydrate, and fatty acid metabolism. Biochemical analysis revealed that in the anthers of line 1355A, glycolysis was activated, which was caused by a reduction in fructose, glucose, and other soluble sugars, and that accumulation of acetyl-CoA was increased along with a significant increase in C14:0 and C18:1 free fatty acids. However, the activities of pyruvate dehydrogenase and fatty acid biosynthesis were inhibited and fatty acid ß-oxidation was activated at the translational level in 1355A. We speculate that in the 1355A anther, high rates of glucose metabolism may promote fatty acid synthesis to enable anther growth. These results provide new insights into the molecular mechanism of genic male sterility in upland cotton.

16.
J Exp Bot ; 70(5): 1525-1538, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30715415

RESUMO

Abscission is a process that allows plants to shed tissues or organs via cell separation, and occurs throughout the life cycle. Removal of leaves through the use of chemical defoliants is very important for mechanical harvesting of cotton (Gossypium hirsutum). However, our knowledge of the molecular mechanisms of the defoliation response involved is limited. In this study, RNA-seq was conducted in order to profile the differentially expressed genes (DEGs) between cultivars X50 (sensitive to chemical defoliants) and X33 (relatively insensitive) at different time points after treatment with thidiazuron and ethephon (TE). A total of 2434 DEGs were identified between the two cultivars across the different time-points. Functional categories according to GO and KEGG analyses revealed that plant hormone signal transduction and zeatin biosynthesis were involved in the response to TE. Cytokinin oxidase/dehydrogenase (CKX) genes and ethylene-related genes were up-regulated following TE treatment, and were associated with increased level of ethylene, especially in cultivar X50. Down-regulation of GhCKX3 resulted in delayed defoliation and a reduced ethylene response. The results show that crosstalk between cytokinin and ethylene regulates cotton defoliation, and provide new insights into the molecular mechanisms underlying the mode of action of defoliants in cotton.

17.
Acta Biomater ; 86: 323-337, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30641289

RESUMO

To address periprosthetic joint infection (PJI), a formidable complication after joint arthroplasty, an implant with excellent osseointegration and effective antibacterial activity has being extensively pursued and developed. In this work, the mouse beta-defensin-14 (MBD-14) was immobilized on the polyetheretherketone (PEEK) surface with three-dimensional (3D) porous structure to improve its antibacterial activity and osseointegration. An in vitro antibacterial evaluation showed that the porous PEEK loaded with MBD-14 wages a durable and effective fight against both Staphylococcus aureus (gram-positive) and Pseudomonas aeruginosa (gram-negative). In addition to the superior antibacterial activity, we found that the enhanced proliferation and osteogenic differentiation of bone mesenchymal stem cells were verified through various in vitro analyses. To evaluate the in vivo bactericidal effect and osseointegration of the samples, the rat femoral models with infection and non-infection were established. The enhanced osseointegration of the MBD-14-loaded samples was found in both two in vivo models. And no bacteria survived on the surfaces of samples with a relatively high MBD-14 concentration. Above results indicate that the 3D porous PEEK coating loaded with MBD-14 simultaneously yields excellent osseointegration while exerting durable and broad-spectrum antibacterial activity. And it paves the way for PEEK to be applied clinically to address PJI. STATEMENT OF SIGNIFICANCE: (1). By using the physio-chemical technique including sulfonation and lyophilization etc., a three-dimensional porous network is developed on polyetheretherketone (PEEK) surface, in which mouse beta-defensin-14 (MBD-14, a broad-spectrum antimicrobial peptide) is then loaded. It endows PEEK with antibacterial activity and osseointegration. (2). Two in vivo animal models with infection and non-infection are used to prove the new bone formation around the samples. (3). Supplementary material also proves that MBD-14 promotes the osteogenic differentiation of BMSCs. However, its potential mechanism needs to be further studied in future. (4). The modified PEEK, including excellent osseointegration and a durable and broad-spectrum antibacterial activity, could be applied clinically to address PJI which is a hot potato for surgeons and patients undergoing total joint arthroplasty.

18.
Plant Mol Biol ; 99(4-5): 379-393, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30671725

RESUMO

KEY MESSAGE: A U-box E3 ubiquitin ligase GhPUB17 is inhibited by GhCyP3 with antifungal activity and acts as a negative regulator involved in cotton resistance to Verticillium dahliae. E3 ubiquitin ligases, the key component enzymes of the ubiquitin-proteasome system, which contains the most diverse structural and functional members involved in the determination of target specificity and the regulation of metabolism, have been well documented in previous studies. Here, we identify GhPUB17, a U-box E3 ligase in cotton that has ubiquitination activity and is involved in the cotton immune response to Verticillium dahliae. The expression level of GhPUB17 is downregulated in the ssn mutant with a constitutively activated immune response (Sun et al., Nat Commun 5:5372, 2014). Infection with V. dahliae or exogenous hormone treatment, including jasmonic acid and salicylic acid, significantly upregulated GhPUB17 in cotton roots, which suggested a possible role for this E3 ligase in the plant immune response to pathogens. Moreover, GhPUB17-knockdown cotton plants are more resistant to V. dahliae, whereas GhPUB17-overexpressing plants are more susceptible to the pathogen, which indicated that GhPUB17 is a negative regulator of cotton resistance to V. dahliae. A yeast two-hybrid (Y2H) assay identified GhCyP3 as a protein that interacts with GhPUB17, and this finding was confirmed by further protein interaction assays. The downregulation of GhCyP3 in cotton seedlings attenuated the plants' resistance to V. dahliae. In addition, GhCyP3 showed antifungal activity against V. dahliae, and the E3 ligase activity of GhPUB17 was repressed by GhCyP3 in vitro. These results suggest that GhPUB17 negatively regulates cotton immunity to V. dahliae and that the antifungal protein GhCyP3 likely interacts with and inhibits the ligase activity of GhPUB17 and plays an important role in the cotton-Verticillium interaction.


Assuntos
Antifúngicos/farmacologia , Família 3 do Citocromo P450/antagonistas & inibidores , Gossypium/metabolismo , Imunidade Vegetal/fisiologia , Ubiquitina-Proteína Ligases/efeitos dos fármacos , Verticillium/patogenicidade , Ciclopentanos , Ciclofilinas , Família 3 do Citocromo P450/genética , Resistência à Doença/genética , Resistência à Doença/imunologia , Regulação para Baixo , Regulação da Expressão Gênica de Plantas , Técnicas de Silenciamento de Genes , Inativação Gênica , Oxilipinas , Doenças das Plantas/imunologia , Imunidade Vegetal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/imunologia , Proteínas de Plantas/metabolismo , Raízes de Plantas , Proteínas Recombinantes , Ácido Salicílico , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
19.
Plant J ; 98(2): 329-345, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30604574

RESUMO

Primary metabolism plays an important role in plant growth and development, however the relationship between primary metabolism and the adaptive immune response is largely unknown. Here, we employed RNA interference (RNAi), virus-induced gene silencing (VIGS) technology, phytohormone profiling, genetic studies, and transcriptome and metabolome analysis to investigate the function of the tryptophan synthesis pathway in the resistance of cotton to V. dahliae. We found that knock-down of GbTSA1 (Tryptophan Synthase α) and GbTSB1 (tryptophan synthase ß) induced a spontaneous cell death phenotype in a salicylic acid (SA)-dependent manner and enhanced resistance to V. dahliae in cotton plants. Metabolome analysis showed that indole and indolic metabolites were highly accumulated in GbTSA1- or GbTSB1-silenced plants. Transcriptomic analysis showed that exogenous indole promotes the expression levels of genes involved in SA synthesis and the defense response. Similarly, indole application strongly enhanced cotton resistance to V. dahliae. These results suggested that metabolic intermediates in the Trp synthesis pathway may be a signal to activate SA synthesis. These results also provided a strategy to elicit plant defense responses by the application of indole.

20.
Nat Genet ; 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30510239

RESUMO

Allotetraploid cotton species (Gossypium hirsutum and Gossypium barbadense) have long been cultivated worldwide for natural renewable textile fibers. The draft genome sequences of both species are available but they are highly fragmented and incomplete1-4. Here we report reference-grade genome assemblies and annotations for G. hirsutum accession Texas Marker-1 (TM-1) and G. barbadense accession 3-79 by integrating single-molecule real-time sequencing, BioNano optical mapping and high-throughput chromosome conformation capture techniques. Compared with previous assembled draft genomes1,3, these genome sequences show considerable improvements in contiguity and completeness for regions with high content of repeats such as centromeres. Comparative genomics analyses identify extensive structural variations that probably occurred after polyploidization, highlighted by large paracentric/pericentric inversions in 14 chromosomes. We constructed an introgression line population to introduce favorable chromosome segments from G. barbadense to G. hirsutum, allowing us to identify 13 quantitative trait loci associated with superior fiber quality. These resources will accelerate evolutionary and functional genomic studies in cotton and inform future breeding programs for fiber improvement.

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