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1.
Exp Ther Med ; 27(5): 237, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38628657

RESUMO

Long non-coding RNAs (lncRNAs) have been previously researched in ankylosing spondylitis (AS). Nevertheless, there are few studies of lncRNAs and mRNAs associated with the pathogenesis of AS. Differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) between AS and normal samples were assessed using the R limma package. DOSE packages and 'clusterProfiler' were exploited for gene enrichment analysis. The functional association of proteins and protein interactions was assessed using the STRING database. To investigate the important genes and subnetworks in the protein-protein interaction network, the MCODE plug-in in the Cytoscape software was utilized. The gene mRNA was examined via reverse transcription-quantitative PCR. In total, 152 DEmRNAs and 204 DElncRNAs were observed between normal and AS samples. A total of 68 candidate genes related to DElncRNA were identified. These candidate genes were enriched in 30 cellular component terms, 22 molecular functions, 83 biological processes, 9 Kyoto Encyclopedia of Genes and Genomes, and 36 disease ontology pathways. NONHSAG037054.2 was the most related lncRNA to genes, and GABPA was the most connected gene to lncRNA in AS. The NCBI/GenBank accession number of the lncRNA NONHSAG037054.2 was not found because it is not included in NCBI. The information of lncRNA NONHSAG037054.2 can be found at the website (http://www.noncode.org/show_gene.php?id=NONHSAG037054 and https://www.genecards.org/cgi-bin/carddisp.pl?gene=ACAP2-IT1). In total, 13 microRNAs (miRNAs) and 46 miRNAs associated with NONHSAG037054.2 and GABPA, respectively, were found. A total of 173 RNA-binding protein genes were associated with both NONHSAG037054.2 and GABPA. In addition, GABPA was downregulated in AS samples, suggesting it may have diagnostic value in AS. In conclusion, NONHSAG037054.2 and GABPA are associated with AS. GABPA was downregulated in AS, and it could serve as a novel diagnostic factor for AS.

2.
Gene ; 914: 148381, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38492610

RESUMO

Low back pain influences people of every age and is one of the major contributors to the global cost of illness. Intervertebral disc degeneration (IVDD) is a major contributor to low back pain, but its pathogenesis is unknown. Recently, ferroptosis has been shown to have a substantial role in modulating IVDD progression. However, the function of ferroptosis-related long non-coding RNAs (lncRNAs) has rarely been reported in IVDD. Consequently, the research was conducted to explore the ferroptosis-related lncRNA signature in the IVDD occurrence and development. We analyzed two datasets (GSE167199 and GSE167931) archived in the NCBI Gene Expression Omnibus (GEO) public database. We screened differentially expressed genes (DEGs) and differentially expressed lncRNAs (DELncs) in these datasets using the limma package. Ferroptosis-related genes (FRGs) were derived from the FerrDb V2 website and the intersection of DEGs and FRGs was considered as differentially expressed ferroptosis-related genes (DFGs). These genes were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Correlations between DFGs and DELncs were shown by Pearson test to determine differential expression of ferroptosis-related lncRNAs. The Pearson test showed that CPEB1-HTR2A-AS1 and ACSL3-DNAJC27-AS1 pairs had correlation coefficients over 0.9. Twenty ferroptosis-related lncRNAs were identified and validated in IVDD. Eight of these lncRNAs were upregulated in IVDD nucleus pulposus cells, including HTR2A-AS1, MIF-AS1, SLC8A1-AS1, LINC00942, DUXAP8, LINC00161, LUCAT1 and LINC01615. Twelve were downregulated in IVDD nucleus pulposus cells, including DNAJC27-AS1, H19, LINC01588, LINC02015, FLNC1, CARMN, PRKG1-AS1, APCDD1L-DT, LINC00839, LINC00536, LINC00710 and LINC01535. Eighteen of the 20 lncRNAs (excluding H19 and LUCAT1) were identified as ferroptosis-related lncRNAs for the first time and verified in IVDD. We have identified a ferroptosis-related lncRNA signature involved in IVDD and revealed a close relationship between CPEB1 and HTR2A-AS1, and between ACSL3 and DNAJC27-AS1. Our findings indicate that ferroptosis-related lncRNAs are a new target set for the early detection and therapy of IVDD.


Assuntos
Ferroptose , Degeneração do Disco Intervertebral , RNA Longo não Codificante , Ferroptose/genética , RNA Longo não Codificante/genética , Degeneração do Disco Intervertebral/genética , Humanos , Perfilação da Expressão Gênica/métodos , Coenzima A Ligases/genética , Ontologia Genética , Bases de Dados Genéticas , Redes Reguladoras de Genes
3.
Biomater Sci ; 12(5): 1239-1248, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38231128

RESUMO

The regeneration of tendon and bone junctions (TBJs), a fibrocartilage transition zone between tendons and bones, is a challenge due to the special triphasic structure. In our study, a silk fibroin (SF)-based triphasic scaffold consisting of aligned type I collagen (Col I), transforming growth factor ß (TGF-ß), and hydroxyapatite (HA) was fabricated to mimic the compositional gradient feature of the native tendon-bone architecture. Rat tendon-derived stem cells (rTDSCs) were loaded on the triphasic SF scaffold, and the high cell viability suggested that the scaffold presents good biocompatibility. Meanwhile, increased expressions of tenogenic-, chondrogenic-, and osteogenic-related genes in the TBJs were observed. The in vivo studies of the rTDSC-seeded scaffold in a rat TBJ rupture model showed tendon tissue regeneration with a clear transition zone within 8 weeks of implantation. These results indicated that the biomimetic triphasic SF scaffolds seeded with rTDSCs have great potential to be applied in TBJ regeneration.


Assuntos
Fibroínas , Ratos , Animais , Fibroínas/química , Alicerces Teciduais/química , Biomimética , Tendões , Células-Tronco , Engenharia Tecidual/métodos , Seda/química
4.
Bioact Mater ; 19: 487-498, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35600973

RESUMO

The regeneration of articular cartilage remains a great challenge due to the difficulty in effectively enhancing spontaneous healing. Recently, the combination of implanted stem cells, suitable biomaterials and bioactive molecules has attracted attention for tissue regeneration. In this study, a novel injectable nanocomposite was rationally designed as a sustained release platform for enhanced cartilage regeneration through integration of a chitosan-based hydrogel, articular cartilage stem cells (ACSCs) and mesoporous SiO2 nanoparticles loaded with anhydroicaritin (AHI). The biocompatible engineered nanocomposite acting as a novel 3D biomimetic extracellular matrix exhibited a remarkable sustained release effect due to the synergistic regulation of the organic hydrogel framework and mesopore channels of inorganic mSiO2 nanoparticles (mSiO2 NPs). Histological assessment and biomechanical tests showed that the nanocomposites exhibited superior performance in inducing ACSCs proliferation and differentiation in vitro and promoting extracellular matrix (ECM) production and cartilage regeneration in vivo. Such a novel multifunctional biocompatible platform was demonstrated to significantly enhance cartilage regeneration based on the sustained release of AHI, an efficient bioactive natural small molecule for ACSCs chondrogenesis, within the hybrid matrix of hydrogel and mSiO2 NPs. Hence, the injectable nanocomposite holds great promise for use as a 3D biomimetic extracellular matrix for tissue regeneration in clinical diagnostics.

5.
Front Biosci (Landmark Ed) ; 28(12): 343, 2023 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-38179754

RESUMO

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease that affects axial joints such as the spine. Early diagnosis is essential to improve treatment outcomes. The purpose of this study is to uncover underlying genetic diagnostic features of AS. METHODS: We downloaded gene expression data from the Gene Expression Omnibus (GEO) database for three studies of groups of healthy and AS samples. After preprocessing and normalizing the data, we employed linear models to identify significant differentially expressed genes (DEGs) and further integrated the differential genes to acquire reliable differential transcriptional markers. Gene functional enrichment analysis was conducted to obtain enriched pathways and regulatory gene interactions were extracted from pathways to further elucidate pathway networks. Seventy-three reliably differentially expressed genes (DEGs) were integrated by differential analysis. Utilizing the regulatory relationships of the 21 Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway genes that were enriched in the analysis, a regulatory network of 622 genes was constructed and its topological properties were further analyzed. RESULTS: Functional enrichment analysis found 73 DEGs that were strongly associated with immune pathways like Th17, Th1 and Th2 cell differentiation. Using KEGG combined with DEGs, six hub genes (KLRD1, HLA-DRB3, HLA-DRB5, IL2Rß, CD247, and CXCL10) were suggested from the network. Of these, the IL2Rß gene was significantly differentially expressed compared with the normal control. CONCLUSION: IL2Rß (Interleukin-2 receptor beta) is strongly associated with the onset and progression of autoimmune joint diseases, and may be used as a potential biomarker of AS. This study offers new characteristics that can help in the diagnosis and individualized therapy of AS.


Assuntos
Redes Reguladoras de Genes , Espondilite Anquilosante , Humanos , Perfilação da Expressão Gênica , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/genética , Biomarcadores , Análise de Sequência com Séries de Oligonucleotídeos , Biologia Computacional
6.
Org Lett ; 24(7): 1566-1570, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35157457

RESUMO

Herein, by applying visible-light photoredox catalysis, we have achieved the catalytic deaminative alkylation of diphenylphosphine and phenyl phosphine with benzylamine-derived Katritzky salts at room temperature. The use of Eosin Y as photoredox catalyst and visible light can largely promote the reaction. A series of unsymmetrical tertiary phosphines were successfully synthesized, including phosphines with three different substituents that are otherwise difficult to obtain.

7.
iScience ; 24(11): 103332, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34805792

RESUMO

Deliberately optimizing the d-band position of an active component via electronic and lattice strain tuning is an effective way to boost its catalytic performance. We herein demonstrate this concept by constructing core-shell Au@NiPd nanoparticles with NiPd alloy shells of only three atomic layers through combining an Au catalysis with the galvanic replacement reaction. The Au core with larger electronegativity modulates the Pd electronic configuration, while the Ni atoms alloyed in the ultrathin shells neutralize the lattice stretching in Pd shells exerted by Au cores, equipping the active Pd metal with a favorable d-band position for electrochemical oxygen reduction reaction in an alkaline medium, for which core-shell Au@NiPd nanoparticles with a Ni/Pd atomic ratio of 3/7 exhibit a half-wave potential of 0.92 V, specific activity of 3.7 mA cm-2, and mass activity of 0.65 A mg-1 at 0.9 V, much better than most of the recently reported Pd-even Pt-based electrocatalysts.

8.
Adv Sci (Weinh) ; 8(12): e2004586, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34165902

RESUMO

Bone diseases constitute a major issue for modern societies as a consequence of progressive aging. Advantages such as open mesoporous channel, high specific surface area, ease of surface modification, and multifunctional integration are the driving forces for the application of mesoporous nanoparticles (MNs) in bone disease diagnosis and treatment. To achieve better therapeutic effects, it is necessary to understand the properties of MNs and cargo delivery mechanisms, which are the foundation and key in the design of MNs. The main types and characteristics of MNs for bone regeneration, such as mesoporous silica (mSiO2 ), mesoporous hydroxyapatite (mHAP), mesoporous calcium phosphates (mCaPs) are introduced. Additionally, the relationship between the cargo release mechanisms and bone regeneration of MNs-based nanocarriers is elucidated in detail. Particularly, MNs-based smart cargo transport strategies such as sustained cargo release, stimuli-responsive (e.g., pH, photo, ultrasound, and multi-stimuli) controllable delivery, and specific bone-targeted therapy for bone disease diagnosis and treatment are analyzed and discussed in depth. Lastly, the conclusions and outlook about the design and development of MNs-based cargo delivery systems in diagnosis and treatment for bone tissue engineering are provided to inspire new ideas and attract researchers' attention from multidisciplinary areas spanning chemistry, materials science, and biomedicine.


Assuntos
Doenças Ósseas/diagnóstico , Doenças Ósseas/terapia , Sistemas de Liberação de Medicamentos/métodos , Engenharia Tecidual/métodos , Regeneração Óssea , Portadores de Fármacos/química , Humanos , Nanopartículas/química
9.
Angew Chem Int Ed Engl ; 60(22): 12298-12303, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-33606348

RESUMO

An unprecedented and general titanium-catalyzed boration of alkyl (pseudo)halides (alkyl-X, X=I, Br, Cl, OMs) with borane (HBpin, HBcat) is reported. The use of titanium catalyst can successfully suppress the undesired hydrodehalogenation products that prevail using other transition-metal catalysts. A series of synthetically useful alkyl boronate esters are readily obtained from various (primary, secondary, and tertiary) alkyl electrophiles, including unactivated alkyl chlorides, with tolerance of other reducing functional groups such as ester, alkene, and carbamate. Preliminary studies on the mechanism revealed a possible radical reaction pathway. Further extension of our strategy to aryl bromides is also demonstrated.

10.
J Mol Cell Biol ; 12(1): 55-70, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30986855

RESUMO

PIP5k1ß is crucial to the generation of phosphotidylinosotol (4, 5)P2. PIP5k1ß participates in numerous cellular activities, such as B cell and platelet activation, cell phagocytosis and endocytosis, cell apoptosis, and cytoskeletal organization. In the present work, we aimed to examine the function of PIP5k1ß in osteoclastogenesis and osteogenesis to provide promising strategies for osteoporosis prevention and treatment. We discovered that PIP5k1ß deletion in mice resulted in obvious bone loss and that PIP5k1ß was highly expressed during both osteoclast and osteoblast differentiation. Deletion of the gene was found to enhance the proliferation and migration of bone marrow-derived macrophage-like cells to promote osteoclast differentiation. PIP5k1ß-/- osteoclasts exhibited normal cytoskeleton architecture but stronger resorption activity. PIP5k1ß deficiency also promoted activation of mitogen-activated kinase and Akt signaling, enhanced TRAF6 and c-Fos expression, facilitated the expression and nuclear translocation of NFATC1, and upregulated Grb2 expression, thereby accelerating osteoclast differentiation and function. Finally, PIP5k1ß enhanced osteoblast differentiation by upregulating master gene expression through triggering smad1/5/8 signaling. Therefore, PIP5k1ß modulates bone homeostasis and remodeling.


Assuntos
Remodelação Óssea/genética , Diferenciação Celular/genética , Homeostase/genética , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteogênese/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Animais , Movimento Celular/genética , Células Cultivadas , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Knockout , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Transdução de Sinais/genética
11.
J Cell Physiol ; 235(4): 3292-3308, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31612476

RESUMO

Emerging evidence suggests that microRNA plays a pivotal role in cell proliferation. Our previous research has certified that miR-146a attenuates osteoarthritis through the regulation of cartilage homeostasis. However, little information about the function of miR-146a in bone marrow-derived mesenchymal stem cells (BMSCs) proliferation and the underlying mechanism was available. Therefore, this study aims at investigating the role of miR-146a on the proliferation of BMSCs and the possible mechanisms involved. The function of miR-146a on BMSCs proliferation was studied through overexpression and knockdown of miR-146a or the indicated long noncoding RNAs (lncRNAs) in BMSCs and then the proliferation rate of the BMSCs were detected by Cell Counting Kit-8 assay, colony formation assay. Besides, flow cytometry was used to test the cell cycle state of BMSCs modified by overexpression or knockdown of miR-146a or lncRNA EPB41L4A-AS1 (EPB41L4A Antisense RNA 1) and small nucleolar RNA host gene 7 (SNHG7). The expression level of marker genes involved in modulating cell proliferation was evaluated by quantitative polymerase chain reaction and western blot analysis. We discovered that the knockdown of miR-146a significantly promoted BMSCs proliferation. Moreover, miR-146a could bind to and inhibit endogenous expression of EPB41L4A-AS1 and SNHG7. Further study demonstrated that overexpression of EPB41L4A-AS1 and SNHG7 significantly enhanced proliferation of BMSCs. For the first time, we certified that miR-146a suppressed BMSCs proliferation, but EPB41L4A-AS1 and SNHG7 promoted BMSCs proliferation in the present study. Mechanistically, miR-146a significantly inhibited BMSCs proliferation partly through miR-146a/EPB41L4A-AS1 SNHG7/cell proliferation signaling pathway axis.


Assuntos
Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , Proteínas de Transporte da Membrana Mitocondrial/genética , RNA Longo não Codificante/genética , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Diferenciação Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Células-Tronco Mesenquimais/citologia , Transdução de Sinais/genética
12.
J Bone Miner Res ; 34(11): 2149-2161, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31356686

RESUMO

MicroRNAs play important roles in osteoporosis and show great potential for diagnosis and therapy of osteoporosis. Previous studies have demonstrated that miR-146a affects osteoblast (OB) and osteoclast (OC) formation. However, these findings have yet to be identified in vivo, and it is unclear whether miR-146a is related to postmenopausal osteoporosis. Here, we demonstrated that miR-146a knockout protects bone loss in mouse model of estrogen-deficient osteoporosis, and miR-146a inhibits OB and OC activities in vitro and in vivo. MiR-146a-/- mice displayed the same bone mass as the wild type (WT) but exhibited a stronger bone turnover than the WT did under normal conditions. Nevertheless, miR-146a-/- mice showed an increase in bone mass after undergoing ovariectomy (OVX) compared with those subjected to sham operation. OC activities were impaired in the miR-146a-/- mice exposed to estrogen deficiency, which was diametrically opposite to the enhanced bone resorption ability of WT. Macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) from a bone microenvironment affect this extraordinary phenomenon. Therefore, our results implicate that miR-146a plays a key role in estrogen deficiency-induced osteoporosis, and the inhibition of this molecule provides skeleton protection. © 2019 American Society for Bone and Mineral Research.


Assuntos
Microambiente Celular/genética , Deleção de Genes , Fator Estimulador de Colônias de Macrófagos/metabolismo , MicroRNAs/genética , Osteoporose , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Animais , Camundongos , Camundongos Knockout , MicroRNAs/metabolismo , Osteoporose/genética , Osteoporose/metabolismo , Osteoporose/patologia , Osteoprotegerina/genética , Ovariectomia , Ligante RANK/genética
13.
J Cell Biochem ; 119(8): 6986-6996, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29741283

RESUMO

Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) is essential for the human bone formation, and emerging evidence shows that long non-coding RNAs (lncRNAs) play important roles in hBMSC osteogenic differentiation. MALAT1 is often regarded as a tumor-related lncRNA, but its function in mesenchymal stem cell differentiation remains to be defined. In this study, we aimed to investigate whether MALAT1 regulates Osterix (Osx) expression by sponging miR-143 to promote hBMSC osteogenic differentiation. Firstly, we found that the expression of MALAT1 was much lower in hBMSCs from osteoporosis patients and miR-143 was contrarily higher. In addition, MALAT1 expression increased, and miR-143 decreased when hBMSCs were treated with osteogenic induction. Then, we used short hairpin RNAs to knockdown MALAT1, and the results showed that hBMSC osteogenic differentiation decreased significantly, indicating that MALAT1 is a positive regulator of osteogenic differentiation in hBMSCs. Furthermore, by luciferase assays, we found that MALAT1 could directly bind to miR-143 and negatively regulate its expression. Similarly, miR-143 could directly bind to the target site on the Osx 3'-UTR and then inhibit Osx expression. Knockdown of MALAT1 decreased Osx expression, and co-transfection of miR-143 inhibitor could rescue Osx mRNA expression. While Osx expression was increased in MALAT1-overexpressing hBMSCs, it was reversed by the miR-143 mimics. Moreover, Osx silencing decreased ALP, OCN, and OPN mRNA expression induced by the miR-143 inhibitor. Altogether, our findings suggest that MALAT1 acts to regulate Osx expression through targeting miR-143; thus, it is considered as a positive regulator in hBMSC osteogenic differentiation.


Assuntos
Células da Medula Óssea/metabolismo , Diferenciação Celular , Regulação da Expressão Gênica , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Osteogênese , RNA Longo não Codificante/metabolismo , Fator de Transcrição Sp7/biossíntese , Células da Medula Óssea/citologia , Humanos , Células-Tronco Mesenquimais/citologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Fator de Transcrição Sp7/genética
14.
Front Pharmacol ; 8: 572, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28970797

RESUMO

Small-interfering RNA (siRNA) provides a rapid solution for drug design and provides new methods to develop customizable medicines. Polyethyleneimine 25 kDa (PEI25kDa) is an effective transfection agent used in siRNA delivery. However, the lack of degradable linkage causes undesirable toxicity, hindering its clinical application. We designed a low-molecular-weight cross-linked polyethylenimine named PEI-Et (Mn:1220, Mw:2895) by using degradable ethylene biscarbamate linkage with lower cytotoxicity and higher knockdown efficiency than PEI25kDa in delivery Chordin siRNA to human bone mesenchymal stem cells (hBMSCs). Suppression of Chordin by using anti-Chordin siRNA delivered by PEI-Et improved bone regeneration in vitro and in vivo associated with the bone morphogenetic protein-2 (BMP-2) mediated smad1/5/8 signaling pathway. Results of this study suggest that Chordin siRNA can be potentially used to improve osteogenesis associated with the BMP-2-mediated Smad1/5/8 signaling pathway and biodegradable biscarbamate cross-linked low-molecular-weight polyethylenimine (PEI-Et) is a therapeutically feasible carrier material to deliver anti-Chordin siRNA to hBMSCs.

15.
Sci Rep ; 7(1): 11421, 2017 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-28900178

RESUMO

Alloying platinum (Pt) with suitable transition metals is effective way to enhance their catalytic performance for methanol oxidation reaction, and reduce their cost at mean time. Herein, we report our investigation on the synthesis of bimetallic platinum-cobalt (PtCo) alloy nanoparticles, their activation, as well as the catalytic evaluation for methanol oxidation reaction. The strategy starts with the synthesis of PtCo alloy nanoparticles in an organic medium, followed by loading on carbon substrates. We then remove the capping agent by refluxing the carbon-supported PtCo particles in acetic acid before electrochemical measurements. We emphasize the change in composition of the alloys during refluxing process, and the initial PtCo alloys with Pt/Co ratio of 1/2 turns into stable alloys with Pt/Co ratio of 3/1. The final Pt3Co particles have uniform distribution on carbon substrates, and exhibit activity with 2.4 and 1.5 times of that for commercial Pt/C and PtRu/C for methanol oxidation reaction.

16.
Bioorg Med Chem Lett ; 27(10): 2234-2237, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28041832

RESUMO

A series of novel thiouracil derivatives containing an acyl thiourea moiety (7a-7x) have been synthesized by structural modification of a lead SecA inhibitor, 2. All the compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus, and Bacillus subtilis. Compounds 7c, 7m, 7u, 7v exhibited promising activities against above bacteria. Such four compounds were further tested for their inhibitory activity against SecA ATPase, and the results showed that compounds 7c and 7u had higher inhibitory activities than that of compound 2. Molecular docking work suggests that compound 7u might bind at a pocket close to the ATPase ATP-binding domain.


Assuntos
Adenosina Trifosfatases/antagonistas & inibidores , Antibacterianos/síntese química , Proteínas de Bactérias/antagonistas & inibidores , Desenho de Fármacos , Inibidores Enzimáticos/síntese química , Canais de Translocação SEC/antagonistas & inibidores , Tiouracila/análogos & derivados , Adenosina Trifosfatases/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Bacillus amyloliquefaciens/efeitos dos fármacos , Bacillus subtilis/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Inibidores Enzimáticos/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Terciária de Proteína , Canais de Translocação SEC/metabolismo , Proteínas SecA , Staphylococcus aureus/efeitos dos fármacos , Tiouracila/síntese química , Tiouracila/farmacologia
17.
Eur J Med Chem ; 127: 159-165, 2017 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-28039774

RESUMO

A series of novel thiouracil derivatives containing a triazolo-thiadiazole moiety (7a-7l) have been synthesized by structural modifications on a lead SecA inhibitor, 2. All the compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus, and Bacillus subtilis. Compounds 7d and 7g were also tested for their inhibitory activities against SecA ATPase due to their promising antimicrobial activities. The inhibitory activity of compound 7d was found to be higher than that of 2. Molecular docking work suggests that compound 7d might bind at a pocket close to the ATPase ATP-binding domain.


Assuntos
Adenosina Trifosfatases/antagonistas & inibidores , Proteínas de Bactérias/antagonistas & inibidores , Desenho de Fármacos , Canais de Translocação SEC/antagonistas & inibidores , Tiadiazóis/química , Tiouracila/síntese química , Tiouracila/farmacologia , Triazóis/química , Adenosina Trifosfatases/química , Adenosina Trifosfatases/metabolismo , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/enzimologia , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Técnicas de Química Sintética , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Simulação de Acoplamento Molecular , Conformação Proteica , Canais de Translocação SEC/química , Canais de Translocação SEC/metabolismo , Proteínas SecA , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/enzimologia , Tiouracila/química , Tiouracila/metabolismo
18.
Talanta ; 161: 22-30, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27769400

RESUMO

A novel covalent organic framework, Schiff base network-1 (SNW-1), was synthesized and used as a solid-phase microextraction (SPME) fiber coating material. The SNW-1 coated SPME fiber was fabricated by a covalent chemical cross-linking between the SNW-1 nanocomposite and a silanol-functionalized stainless steel wire substrate. Scanning electron microscopy and nitrogen isothermal adsorption results indicate that the new fiber coating exhibited a porous, homogenous surface with the Brunauer-Emmett-Teller surface of 668m2g-1. The prepared fiber was explored for the SPME of phenols from honey samples prior to their determination by gas chromatography-mass spectrometry. The developed method had large enrichment factors (136-816), low limits of detection (0.06-0.2ngg-1), good linearity (0.1-100.0ngg-1) and repeatability (<9.7%) for phenols. The recoveries for spiked phenols (1.0ngg-1 and 10.0ngg-1) in Wolfberry, Robinia and Codonopsis honey samples were in the range of 84.2-107.2% with the relative standard deviations ranging from 3.8% to 12.7%. The developed method was suitable for the determination of phenols from honey samples.


Assuntos
Mel/análise , Nanocompostos/química , Fenóis/análise , Bases de Schiff/química , Contaminação de Alimentos/análise , Limite de Detecção , Fenóis/química , Microextração em Fase Sólida , Aço Inoxidável/química
19.
J Environ Sci (China) ; 29: 146-50, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25766023

RESUMO

A 1-dodecanethiol-based phase-transfer protocol is developed for the extraction of noble metal ions from aqueous solution to a hydrocarbon phase, which calls for first mixing the aqueous metal ion solution with an ethanolic solution of 1-dodecanethiol, and then extracting the coordination compounds formed between noble metal ions and 1-dodecanethiol into a non-polar organic solvent. A number of characterization techniques, including inductively coupled plasma atomic emission spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis demonstrate that this protocol could be applied to extract a wide variety of noble metal ions from water to dichloromethane with an efficiency of >96%, and has high selectivity for the separation of the noble metal ions from other transition metals. It is therefore an attractive alternative for the extraction of noble metals from water, soil, or waste printed circuit boards.


Assuntos
Extração Líquido-Líquido/métodos , Metais/química , Compostos de Sulfidrila/química , Poluentes Químicos da Água/química , Água/química
20.
Sci Rep ; 4: 6414, 2014 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-25231376

RESUMO

Noble metal nanoparticles with hollow interiors and customizable shell compositions have immense potential for catalysis. Herein, we present an unique structure transformation phenomenon for the fabrication of alloy Cu3Pt nanoframes with polyhedral morphology. This strategy starts with the preparation of polyhedral Cu-Pt nanoparticles with a core-shell construction upon the anisotropic growth of Pt on multiply twinned Cu seed particles, which are subsequently transformed into alloy Cu3Pt nanoframes due to the Kirkendall effect between the Cu core and Pt shell. The as-prepared alloy Cu3Pt nanoframes possess the rhombic dodecahedral morphology of their core-shell parents after the structural evolution. In particular, the resulting alloy Cu3Pt nanoframes are more effective for oxygen reduction reaction but ineffective for methanol oxidation reaction in comparison with their original Cu-Pt core-shell precursors.

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