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1.
Nat Biotechnol ; 42(3): 518-528, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37231262

RESUMO

The development of cancer neoantigen vaccines that prime the anti-tumor immune responses has been hindered in part by challenges in delivery of neoantigens to the tumor. Here, using the model antigen ovalbumin (OVA) in a melanoma model, we demonstrate a chimeric antigenic peptide influenza virus (CAP-Flu) system for delivery of antigenic peptides bound to influenza A virus (IAV) to the lung. We conjugated attenuated IAVs with the innate immunostimulatory agent CpG and, after intranasal administration to the mouse lung, observed increased immune cell infiltration to the tumor. OVA was then covalently displayed on IAV-CPG using click chemistry. Vaccination with this construct yielded robust antigen uptake by dendritic cells, a specific immune cell response and a significant increase in tumor-infiltrating lymphocytes compared to peptides alone. Lastly, we engineered the IAV to express anti-PD1-L1 nanobodies that further enhanced regression of lung metastases and prolonged mouse survival after rechallenge. Engineered IAVs can be equipped with any tumor neoantigen of interest to generate lung cancer vaccines.


Assuntos
Vacinas Anticâncer , Vírus da Influenza A , Neoplasias Pulmonares , Animais , Camundongos , Neoplasias Pulmonares/prevenção & controle , Vacinas Anticâncer/genética , Antígenos , Pulmão , Peptídeos , Vacinação , Antígenos de Neoplasias/genética
3.
Biochem Genet ; 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38071681

RESUMO

Ovarian cancer (OC) is a major gynecological malignancy with an annually increasing morbidity that poses a significant threat to the health of women worldwide. Most OC patients are diagnosed at an advanced stage. It is an urgent task to search for biomarkers for the diagnosis and treatment of OC. The lncRNA HCP5 (HCP5) was recently identified as an oncogene in several malignant tumors. However, the function of HCP5 in OC has rarely been reported. Herein, the levels of HCP5 and PTBP1 were found to be markedly increased in malignant OC tumor tissues and OC cell lines. In HCP5-silenced SKOV-3 and HEY cells, cell viability was markedly decreased, and the apoptosis rate was significantly increased, with more cells exhibiting G0/G1 arrest and increased expression of cleaved caspase-3 and cleaved caspase-9. Furthermore, the number of migrated cells, number of invaded cells, and migration distance were notably decreased by the knockdown of HCP5 in SKOV-3 cells and HEY cells. In the xenograft model established with SKOV-3 cells, the number of lung metastases, tumor growth, and Ki67 expression in tumor tissues were markedly decreased by the knockdown of HCP5, accompanied by an increased percentage of TUNEL-positive cells. HCP5 was found to be localized in the nucleus, and the interaction between HCP5 and PTBP1 was verified by RNA pull-down and RNA immunoprecipitation assays. Furthermore, in HCP5-overexpressing OC cells, the impacts of HCP5 on cell proliferation and apoptosis were significantly attenuated by the knockdown of PTBP1. Collectively, these results indicate that HCP5 facilitates the progression of OC by interacting with the PTBP1 protein.

4.
Sci Rep ; 13(1): 18435, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891374

RESUMO

Spermatogenesis is a complex process related to male infertility. Till now, the critical genes and specific mechanisms have not been elucidated clearly. Our objective was to determine the hub genes that play a crucial role in spermatogenesis by analyzing the differentially expressed genes (DEGs) present in non-obstructive azoospermia (NOA) compared to OA and normal samples using bioinformatics analysis. Four datasets, namely GSE45885, GSE45887, GSE9210 and GSE145467 were used. Functional enrichment analyses were performed on the DEGs. Hub genes were identified based on protein-protein interactions between DEGs. The expression of the hub genes was further examined in the testicular germ cell tumors from the TCGA by the GEPIA and validated by qRT-PCR in the testes of lipopolysaccharide-induced acute orchitis mice with impaired spermatogenesis. A total of 203 DEGs including 34 up-regulated and 169 down-regulated were identified. Functional enrichment analysis showed DEGs were mainly involved in microtubule motility, the process of cell growth and protein transport. PRM2, TEKT2, FSCN3, UBQLN3, SPATS1 and GTSF1L were identified and validated as hub genes for spermatogenesis. Three of them (PRM2, FSCN3 and TEKT2) were significantly down-regulated in the testicular germ cell tumors and their methylation levels were associated with the pathogenesis. In summary, the hub genes identified may be related to spermatogenesis and may act as potential therapeutic targets for NOA and testicular germ cell tumors.


Assuntos
Infertilidade Masculina , Neoplasias Embrionárias de Células Germinativas , Humanos , Masculino , Animais , Camundongos , Perfilação da Expressão Gênica , Espermatogênese/genética , Testículo/metabolismo , Infertilidade Masculina/patologia , Biologia Computacional , Neoplasias Embrionárias de Células Germinativas/patologia
5.
Mol Ther Nucleic Acids ; 31: 383-397, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36817723

RESUMO

Adeno-associated viruses (AAVs) are commonly used for in vivo gene therapy. Nevertheless, the wide tropism that characterizes these vectors limits specific targeting to a particular cell type or tissue. Here, we developed new chemically modified AAV vectors (Nε-AAVs) displaying a single site substitution on the capsid surface for post-production vector engineering through biorthogonal copper-free click chemistry. We were able to identify AAV vectors that would tolerate the unnatural amino acid substitution on the capsid without disrupting their packaging efficiency. We functionalized the Nε-AAVs through conjugation with DNA (AS1411) or RNA (E3) aptamers or with a folic acid moiety (FA). E3-, AS1411-, and FA-AAVs showed on average a 3- to 9-fold increase in transduction compared with their non-conjugated counterparts in different cancer cell lines. Using specific competitors, we established ligand-specific transduction. In vivo studies confirmed the selective uptake of FA-AAV and AS1411-AAV without off-target transduction in peripheral organs. Overall, the high versatility of these novel Nε-AAVs might pave the way to tailoring gene therapy vectors toward specific types of cells both for ex vivo and in vivo applications.

6.
Environ Sci Pollut Res Int ; 29(38): 57566-57578, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35353314

RESUMO

In this study, a method of preparing fertilizers with the fly ash from biomass power plants and the waste acid solution from flue gas desulfurization and denitrification was disclosed. In addition, the study also explored the effects of added fine particles, unburned biochar, and other commercial fertilizers on soil water retention and slow-release effect of fertilizers. The analysis was done by comparing the aggregation degrees of crystalline salt and the variations of the chemical bonds. The experimental results showed that the added fine particles could effectively increase the water absorption of fertilizers, which helped to improve soil water retention. Meanwhile, the fine particles could strengthen the special adsorption of basic compounds containing N, P, and other nutrients by biochar and enhance the slow-release effect of fertilizers. Although adding part commercial fertilizers weakened the water absorption of fertilizers slightly, it had only a relatively small effect on the aggregation of water-soluble crystalline salt on the surfaces of fine particles and biochar. Furthermore, the microwave was applied to promote the absorption of N by unburned biochar, during which only small amounts of volatile were released and lost. The experiments had confirmed that microwave irradiation could promote the agglomeration of biochar on crystalline salt effectively, thus enhancing the slow-release effect of crystalline salt in fertilizers. Finally, pot experiments demonstrated that the self-prepared fertilizer improved plant growth by its better water absorption and slow-release properties during the whole growth period, which had promising application potential as the slow-release fertilizer in the plant growth field.


Assuntos
Desnitrificação , Fertilizantes , Enxofre/química , Eliminação de Resíduos Líquidos , Ácidos/química , Biomassa , Carvão Vegetal/química , Fertilizantes/análise , Solo/química , Eliminação de Resíduos Líquidos/métodos , Água/análise
7.
Zool Res ; 42(1): 28-42, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33420763

RESUMO

Depression is a prevalent mental disorder that is associated with aging and contributes to increased mortality and morbidity. The overall prevalence of geriatric depression with clinically significant symptoms is currently on the rise. Recent studies have demonstrated that altered expressions of long non-coding RNAs (lncRNAs) in the brain affect neurodevelopment and manifest modulating functions during the depression. However, most lncRNAs have not yet been studied. Herein, we analyzed the transcriptome of dysregulated lncRNAs to reveal their expressions in a mouse model exhibiting depressive-like behaviors, as well as their corresponding response following antidepressant fluoxetine treatment. A chronic unpredictable mild stress (CUMS) mouse model was applied. A six-week fluoxetine intervention in CUMS-induced mice attenuated depressive-like behaviors. In addition, differential expression analysis of lncRNAs was performed following RNA-sequencing. A total of 282 lncRNAs (134 up-regulated and 148 down-regulated) were differentially expressed in CUMS-induced mice relative to non-stressed counterparts ( P<0.05). Moreover, 370 differentially expressed lncRNAs were identified in CUMS-induced mice after fluoxetine intervention. Gene Ontology (GO) analyses showed an association between significantly dysregulated lncRNAs and protein binding, oxygen binding, and transport activity, while the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these dysregulated lncRNAs might be involved in inflammatory response pathways. Fluoxetine effectively ameliorated the symptoms of depression in CUMS-induced mice by regulating the expression of lncRNAs in the hippocampus. The findings herein provide valuable insights into the potential mechanism underlying depression in elderly people.


Assuntos
Transtorno Depressivo/tratamento farmacológico , Fluoxetina/uso terapêutico , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Antidepressivos de Segunda Geração/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , RNA Longo não Codificante/genética , Estresse Psicológico
8.
J Exp Bot ; 72(7): 2584-2599, 2021 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-33483723

RESUMO

The photorespiratory pathway is highly compartmentalized. As such, metabolite shuttles between organelles are critical to ensure efficient photorespiratory carbon flux. Arabidopsis plastidic glycolate/glycerate translocator 1 (PLGG1) has been reported as a key chloroplastic glycolate/glycerate transporter. Two homologous genes, OsPLGG1a and OsPLGG1b, have been identified in the rice genome, although their distinct functions and relationships remain unknown. Herein, our analysis of exogenous expression in oocytes and yeast shows that both OsPLGG1a and OsPLGG1b have the ability to transport glycolate and glycerate. Furthermore, we demonstrate in planta that the perturbation of OsPLGG1a or OsPLGG1b expression leads to extensive accumulation of photorespiratory metabolites, especially glycolate and glycerate. Under ambient CO2 conditions, loss-of-function osplgg1a or osplgg1b mutant plants exhibited significant decreases in photosynthesis efficiency, starch accumulation, plant height, and crop productivity. These morphological defects were almost entirely recovered when the mutant plants were grown under elevated CO2 conditions. In contrast to osplgg1a, osplgg1b mutant alleles produced a mild photorespiratory phenotype and had reduced accumulation of photorespiratory metabolites. Subcellular localization analysis showed that OsPLGG1a and OsPLGG1b are located in the inner and outer membranes of the chloroplast envelope, respectively. In vitro and in vivo experiments revealed that OsPLGG1a and OsPLGG1b have a direct interaction. Our results indicate that both OsPLGG1a and OsPLGG1b are chloroplastic glycolate/glycerate transporters required for photorespiratory metabolism and plant growth, and that they may function as a singular complex.


Assuntos
Cloroplastos/metabolismo , Ácidos Glicéricos/metabolismo , Glicolatos/metabolismo , Oryza , Proteínas de Plantas/metabolismo , Dióxido de Carbono/metabolismo , Oryza/genética , Fotossíntese , Plastídeos/metabolismo , Isoformas de Proteínas/metabolismo
9.
Mol Plant ; 13(12): 1802-1815, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33075506

RESUMO

Several photorespiratory bypasses have been introduced into plants and shown to improve photosynthesis by increasing chloroplastic CO2 concentrations or optimizing energy balance. We recently reported that an engineered GOC bypass could increase photosynthesis and productivity in rice. However, the grain yield of GOC plants was unstable, fluctuating in different cultivation seasons because of varying seed setting rates. In this study, we designed a synthetic photorespiratory shortcut (the GCGT bypass) consisting of genes encoding Oryza sativa glycolate oxidase and Escherichia coli catalase, glyoxylate carboligase, and tartronic semialdehyde reductase. The GCGT bypass was guided by an optimized chloroplast transit peptide that targeted rice chloroplasts and redirected 75% of carbon from glycolate metabolism to the Calvin cycle, identical to the native photorespiration pathway. GCGT transgenic plants exhibited significantly increased biomass production and grain yield, which were mainly attributed to enhanced photosynthesis due to increased chloroplastic CO2 concentrations. Despite the increases in biomass production and grain yield, GCGT transgenic plants showed a reduced seed setting rate, a phenotype previously reported for the GOC plants. Integrative transcriptomic, physiological, and biochemical assays revealed that photosynthetic carbohydrates were not transported to grains in an efficient manner, thereby reducing the seed setting rate. Taken together, our results demonstrate that the GCGT photorespiratory shortcut confers higher yield by promoting photosynthesis in rice, mainly through increasing chloroplastic CO2 concentrations.


Assuntos
Biomassa , Luz , Oryza/crescimento & desenvolvimento , Oryza/efeitos da radiação , Fotossíntese/efeitos da radiação , Sementes/crescimento & desenvolvimento , Transporte Biológico/efeitos da radiação , Metabolismo dos Carboidratos/efeitos da radiação , Dióxido de Carbono/metabolismo , Respiração Celular/efeitos da radiação , Cloroplastos/metabolismo , Cloroplastos/efeitos da radiação , Cloroplastos/ultraestrutura , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Metaboloma/efeitos da radiação , Oryza/genética , Folhas de Planta/metabolismo , Folhas de Planta/efeitos da radiação , Folhas de Planta/ultraestrutura , Plantas Geneticamente Modificadas , Sementes/efeitos da radiação , Transcriptoma/genética
10.
BMC Microbiol ; 20(1): 183, 2020 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600253

RESUMO

BACKGROUND: The data on the prevalence of resistance to mupirocin (MUP), fusidic acid (FA) and retapamulin (RET) in methicillin-resistant Staphylococcus aureus (MRSA) from China are still limited. This study aimed to examine these three antibiotics resistance in 1206 MRSA clinical isolates from Eastern China. Phenotypic MUP, FA and RET resistance was determined by minimum inhibitory concentrations (MICs), and genotypic by PCR and DNA sequencing of the mupA/B, fusB-D, cfr, vgaA/Av/ALC/B/C/E, lsaA-C/E and salA and mutations in ileS, fusA/E, rplC, and 23S RNA V domain. The genetic characteristics of resistance isolates were conducted by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). RESULTS: Overall MRSA MUP, FA and RET resistance was low (5.1, 1.0 and 0.3%, respectively). MupA was the mechanism of high-level MUP resistance. All low-level MUP resistance isolates possessed an equivocal mutation N213D in IleS; of these, 2 reported an additional V588F mutation with an impact on the Rossman fold. FusA mutations, such as L461K, H457Q, H457Y and V90I were the primary FA mechanisms among high-level resistance isolates, most of which also contained fusC; however, all low-level resistance strains carried fusB. Except lsaE gene detected in one isolate, no other resistance mechanisms tested were found among RET-resistant isolates. Additionally, sixteen PFGE types (A-P) were observed, among which type B was the most common (49/76, 64.5%), followed by types E and G (4/76, 5.3% each) and types C and M (3/76, 3.9% each). All resistant strains were divided into 15 ST types by MLST. ST764 (24/76, 31.6%), ST630 (11/76, 14.5%), ST239 (9/76, 11.8%) and ST5 (7/76, 9.2%) were the major types. PFGE type B isolates with the aforementioned STs were mainly found in mupirocin resistant isolates. CONCLUSIONS: MUP, FA and RET exhibited highly activity against the MRSA isolates. Acquired genes and chromosome-borne genes mutations were responsible for MUP and FA resistance; however, the mechanism for some RET-resistant isolates remains to be further elucidated. Also, the surveillance to MUP in MRSA should be strengthened to prevent elevated resistance due to the expansion of clones.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Staphylococcus aureus Resistente à Meticilina/classificação , Infecções Estafilocócicas/epidemiologia , Técnicas de Tipagem Bacteriana , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , China/epidemiologia , DNA Bacteriano/genética , Diterpenos/farmacologia , Eletroforese em Gel de Campo Pulsado , Ácido Fusídico/farmacologia , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Mupirocina/farmacologia , Mutação , Prevalência , Análise de Sequência de DNA
11.
Front Microbiol ; 11: 265, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194524

RESUMO

Antibiotics have been described to modulate bacterial virulence gene expression. This study aimed to assess the changes caused by anti-Staphylococcus agents in the transcription of leucocidin ED (lukED) gene of Staphylococcus aureus strain Newman in vitro and in vivo and to determine whether the altered expression is agr dependent. The bacteria were exposed to subinhibitory concentrations [1/2, 1/4, or 1/8 minimal inhibitory concentration (MIC)] of 11 antibiotics, and the expression of lukE and agr-effector RNAIII was determined using qRT-PCR. In vivo experiments were performed to evaluate the impact exerted by six representative antibiotics on the transcription of both genes. Molecular analysis showed that in vitro lukE transcription was dramatically promoted in the Newman strain exposed to sub-MICs of vancomycin, trimethoprim-sulfamethoxazole, clindamycin, gentamicin, daptomycin, and ciprofloxacin and considerably reduced when stimulated by cefazolin, erythromycin, rifampicin, tigecycline, and linezolid. In the murine abscess model, tigecycline significantly decreased the transcription of lukE and the bacterial numbers, whereas vancomycin increased them; although cefazolin increased the lukE expression (contrary to the in vitro effect), it had a remarkable role in reducing bacterial load. The correspondence analysis shows that RNAIII expression varied under seven of 11 antibiotics in vitro, and six drugs in vivo were consistent with lukE transcripts. In conclusion, our data show that anti-Staphylococcus antibiotics exert modulatory effects on lukE expression in vitro and/or in vivo, and the changed expression caused by some drugs may be involved with agr activity, thus providing a guide to choose appropriate agents to avoid promoting bacterial virulence in lukED-positive S. aureus infections.

13.
Infect Drug Resist ; 12: 3557-3566, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814744

RESUMO

PURPOSE: Carbapenem-resistant Klebsiella pneumoniae (CRKP) have emerged worldwide and also being a major threat to children and neonate. In this study, we describe a nosocomial outbreak of NDM-5-producing Klebsiella pneumoniae in neonatal unit of a teaching hospital in China from September 2015 to September 2016. PATIENTS AND METHODS: We collected 12 carbapenem-resistant K. pneumoniae outbreak strains from 12 newborns and characterized these isolates for their antimicrobial susceptibility, clone relationships, and multi-locus sequence types using vitek-2 compact system, pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Resistant genes were detected by using PCR and sequencing. Plasmid conjugation experiment was carried out to determine the transferability of carbapenem resistance. PCR-based replicon typing (PBRT), S1 nuclease-PFGE, and southern blotting were conducted for plasmid profiling. RESULTS: All 12 K. pneumoniae isolates were resistant to carbapenems and carried bla NDM-5, bla TEM-1 and bla SHV-11. Furthermore, PFGE analysis showed that NDM-5-producing K. pneumoniae were clonally related and MLST assigned them to sequence type 337. Conjugative assays showed that plasmids harboring bla NDM-5 gene were self-transmissible. Plasmid analysis suggested that all bla NDM-5 gene located on a ~45 kb IncX3 type plasmid. CONCLUSION: To the best of our knowledge, this is the first report of a clone outbreak of bla NDM-5-carrying K. pneumoniae isolates from neonates. There is an urgent need for effective infection control measures to prevent bla NDM-5 variants from becoming epidemic in the neonates in the future.

14.
ACS Appl Mater Interfaces ; 11(33): 29934-29940, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31329412

RESUMO

Constructing advanced anode materials with suitable operational potential and high energy density toward metal ion batteries is of significance for next-generation batteries. Carbon-coated porous Sb2Te3 nanoplates with high density and suitable operational potential, prepared by a hydrothermal and carbonization technique, manifest good electrochemical performance, including excellent rate capability, high capacities, and outstanding cycling performance. This performance can be traced to its special structure, including porous Sb2Te3 and the shell of carbon, which can provide fast charge transfer paths and maintain the structural stability for the entire material. The proposed strategy here of embedding porous high-density anode material in two-dimensional carbon provides a new avenue for designing anode materials with excellent gravimetric and volumetric capacities toward superior energy storage.

15.
Front Microbiol ; 10: 1388, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275293

RESUMO

The toxic shock syndrome toxin-1 (TSST-1), encoded by tst gene, has been proposed to cause staphylococcal toxic shock syndrome (TSS) in a susceptible host, which highlights the need to evaluate the level of tst gene expression and molecular genetic characteristics of the tst-positive isolates. A total of 916 S. aureus isolates collected from seven hospitals in China were screened for the tst gene. The tst positive isolates were characterized by spa, SCCmec, PFGE, and agr typing. Representative strains were also subjected to MLST typing. qRT-PCR was used to quantify tst and major virulence regulator genes expression. We also sequenced the regions of promoter and open reading frame (ORF) of tst to investigate whether they correlate with the variation in tst expression. We found 208 (22.7%) of surveyed isolates including 198 (29.8%) of MRSA and 10 (4.0%) of MSSA isolates harbored the tst gene. The most common clone among tst positive MRSA isolates belonged to ST5 (CC5)-agr2-t002-SCCmecII. The amount of tst mRNA varied 8.4-folds among clinical S. aureus isolates. Sequencing the tst promoter revealed a base T deletion in tst high expressed isolates. As for major virulence regulators, srrA, sarT, RNAIII, and ccpA in four tst differentially expressed strains were detected to be highly expressed, respectively. Our study revealed high prevalence of ST5 (CC5)-agr2-t002-SCCmecII clone among tst positive MRSA in hospitals from China. The levels of tst expression among clinical S. aureus isolates varied, which may be associated with tst promoter and variations in specific virulence regulators.

16.
Nucleic Acids Res ; 47(19): e114, 2019 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-31361892

RESUMO

Application of viral vectors in gene delivery is attracting widespread attention but is hampered by the absence of control over transduction, which may lead to non-selective transduction with adverse side effects. To overcome some of these limitations, we proposed an unnatural amino acid aided caging-uncaging strategy for controlling the transduction capability of a viral vector. In this proof-of-principle study, we first expanded the genetic code of the lentiviral vector to incorporate an azido-containing unnatural amino acid (Nϵ-2-azidoethyloxycarbonyl-l-lysine, NAEK) site specifically within a lentiviral envelope protein. Screening of the resultant vectors indicated that NAEK incorporation at Y77 and Y116 was capable of inactivating viral transduction upon click conjugation with a photo-cleavable chemical molecule (T1). Exposure of the chimeric viral vector (Y77-T1) to UVA light subsequently removed the photo-caging group and restored the transduction capability of lentiviral vector both in vitro and in vivo. Our results indicate that the use of the photo-uncage activation procedure can reverse deactivated lentiviral vectors and thus enable regulation of viral transduction in a switchable manner. The methods presented here may be a general approach for generating various switchable vectors that respond to different stimulations and adapt to different viral vectors.


Assuntos
Vetores Genéticos/genética , Lentivirus/genética , Lisina/análogos & derivados , Transdução Genética , Azidas/efeitos da radiação , Linhagem Celular , Terapia Genética/métodos , Vetores Genéticos/efeitos da radiação , HIV-1/genética , Humanos , Lentivirus/efeitos da radiação , Lisina/genética , Lisina/efeitos da radiação , Raios Ultravioleta , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/efeitos da radiação
17.
Polymers (Basel) ; 11(5)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067730

RESUMO

Gambogenic acid (GNA) has been demonstrated with outstanding antitumor activity as a potential antitumor drug in recent years. However, the low solubility and deficient bioavailability of GNA seriously hinder its practical application in the clinic area. In this study, a novel amphiphilic block copolymer, poly (acrylic acid)-b-polycaprolactone (PAA-b-PCL) is prepared and assembled into pH-responsive polymeric micelles (PMs) as one mold of drug delivery system (DDS) with unique properties. Relevant investigation on PMs exhibits excellent carrying potential and pH-dependent release performance for GNA. The drug loading capacity (DLC) and drug loading efficiency (DLE) for GNA-loaded PMs can be achieved as high as 15.20 ± 0.07% and 83.67 ± 0.49%, respectively. The in vitro experiments indicate that the GNA releasing time, cytotoxicity, and cellular uptake are significantly enhanced. Especially, the peak concentration (Cmax) and area under the curve (AUC) are promoted sharply in the GNA-loaded PMs concentration-time curve. This study not only provides a novel way to widen the application of anticancer GNA in the future, but also extends the potential of stimuli-responsive copolymers to biomedical applications.

18.
J Antimicrob Chemother ; 74(1): 29-37, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30329062

RESUMO

Objectives: Development of resistance in Neisseria gonorrhoeae to ceftriaxone monotherapy or ceftriaxone plus azithromycin dual therapy is a global public health concern. The aim of this study was to analyse the trend in antimicrobial resistance in Hangzhou, China, over the period 2015-17. Methods: In total, 379 clinical isolates were collected from seven hospitals and antimicrobial susceptibility was determined using the agar dilution method. Isolates showing resistance to ceftriaxone, azithromycin or cefixime were analysed for the presence of resistance determinants. STs were determined with the N. gonorrhoeae multiantigen sequence typing (NG-MAST) method and phylogenetic analysis and strain clustering was determined using porB and tbpB sequences. Results: Ceftriaxone resistance, decreased susceptibility to ceftriaxone and azithromycin resistance were observed in 3%, 17% and 21% of the isolates, respectively. This resulted in 5% of the isolates showing both decreased susceptibility to ceftriaxone and azithromycin resistance. Importantly, resistance levels to ceftriaxone and azithromycin increased over the study period, resulting in 5% ceftriaxone resistance, 27% decreased susceptibility to ceftriaxone and 35% azithromycin resistance in 2017 and 11% of the isolates showing both decreased susceptibility to ceftriaxone and azithromycin resistance. Phylogenetic and cluster analysis showed the emergence and expansion in 2017 of a clonally related cluster containing strains with high abundance of decreased susceptibility to ceftriaxone and/or cefixime, which was related to the presence of the mosaic penA allele X. Co-resistance to azithromycin was also observed in this cluster. Conclusions: Our findings have major implications for the future reliability of ceftriaxone monotherapy and ceftriaxone plus azithromycin dual therapy in China.


Assuntos
Antibacterianos/farmacologia , Azitromicina/farmacologia , Ceftriaxona/farmacologia , Farmacorresistência Bacteriana , Gonorreia/epidemiologia , Gonorreia/microbiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Antígenos de Bactérias/genética , China/epidemiologia , Genes Bacterianos , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/isolamento & purificação , Filogenia , Prevalência
19.
J Clin Lab Anal ; 33(2): e22675, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30239047

RESUMO

BACKGROUND: Recently studies uncovered associations between polymorphisms of interleukin genes and the risk of asthma. However, the relationship between polymorphisms of interleukin-7 gene and the risk of children asthma has not been discovered yet. This study aims to investigate the relationship between single nucleotide polymorphisms (SNPs) on interleukin-7 gene and the risk of children asthma. METHODS: We genotyped eight SNPs of interleukin-7 gene in blood samples from 437 asthma patients and 489 healthy controls to analyze potential associations of these SNPs with the risk of asthma in children. RESULTS: A missense SNP rs766736182 (odds ratio (OR) = 2.185, 95% confidence interval (CI) = 1.561-2.252, P-value = 8.69468E-19) of the interleukin-7 gene is associated with the risk of children asthma. CONCLUSIONS: This study reveals that SNP rs766736182 of interleukin-7 is the risk factor for children asthma and implies potential role of immune system in the pathogenesis of children asthma.


Assuntos
Asma/epidemiologia , Asma/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Interleucina-7/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino
20.
Sci Rep ; 8(1): 7696, 2018 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-29769634

RESUMO

The amount of Panton-Valentine leukocidin (PVL) is diverse among Staphylococcus aureus isolates from different geographical regions, and its significance in some infections is disputed. However, data concerning this information in China are limited. Fifty-one lukSF-PV+ methicillin-resistant Staphylococcus aureus (MRSA) isolates gathered from varying infections were used for PVL production using enzyme-linked immunosorbent assay, and the quantity was analyzed in correlation with PVL isoform, genetic background of the isolate, and disease category. All isolates generated PVL with a range of 0.43-360.87 µg/mL, of which 56.9% isolates (29/51) generated 51-200 µg/mL of PVL; 11.8% (6/51) yielded PVL more than 200 µg/mL, and the rest (31.4%, 16/51) produced PVL of ≤50 µg/mL. The amount of PVL was not related to its variant and infection type, although isolates from skin and soft tissue infection had relatively high mean and median. Clonal complex (CC) 22 isolates might be the producer of relatively high concentrations of PVL; however, the difference among CCs was not analyzed due to a small number of CC isolates. The relevance of PVL production with the infection type, toxin isoform, and genetic characteristic of isolates may vary by clone type and also needs to be further evaluated using a large sample size and best concentration on in vivo environment.


Assuntos
Toxinas Bacterianas/biossíntese , Toxinas Bacterianas/genética , Exotoxinas/biossíntese , Exotoxinas/genética , Leucocidinas/biossíntese , Leucocidinas/genética , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Polimorfismo Genético , Infecções dos Tecidos Moles/epidemiologia , Infecções Estafilocócicas/complicações , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções dos Tecidos Moles/microbiologia , Infecções Estafilocócicas/microbiologia , Fatores de Virulência/genética , Adulto Jovem
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