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1.
Nanomaterials (Basel) ; 12(15)2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35957059

RESUMO

Magnetic chitosan hydrogel has aroused immense attention in recent years due to their biomedical significance and magnetic responsiveness. Here, A new electrodeposition method is reported for the fabrication of a novel CuNi-based magnetic chitosan freestanding film (MCFF) in an acidic chitosan plating bath containing SDS-modified CuNi NPs. Contrary to chitosan's anodic and cathodic deposition, which typically involves electrochemical oxidation, the synthetic process is triggered by coordination of chitosan with Cu and Ni ions in situ generated by the controlled surface dissolution of the suspended NPs with the acidic plating bath. The NPs provide not only the ions required for chitosan growth but also become entrapped during electrodeposition, thereby endowing the composite with magnetic properties. The obtained MCFF offers a wide range of features, including good mechanical strength, magnetic properties, homogeneity, and morphological transparency. Besides the fundamental interest of the synthesis itself, sufficient mechanical strength ensures that the hydrogel can be used by either peeling it off of the electrode or by directly building a complex hydrogel electrode. Its fast and easy magnetic steering, separation and recovery, large surface area, lack of secondary pollution, and strong chelating capability could lead to it finding applications as an electrochemical detector or adsorbent.

2.
Adv Mater ; 34(38): e2205677, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35924314

RESUMO

The lithium (Li)-metal anode offers a promising solution for high-energy-density lithium-metal batteries (LMBs). However, the significant volume expansion of the Li metal during charging results in poor cycling stability as a result of the dendritic deposition and broken solid electrolyte interphase. Herein, a facile one-step roll-to-roll fabrication of a zero-volume-expansion Li-metal-composite anode (zeroVE-Li) is proposed to realize high-energy-density LMBs with outstanding electrochemical and mechanical stability. The zeroVE-Li possesses a sandwich-like trilayer structure, which consists of an upper electron-insulating layer and a bottom lithiophilic layer that synergistically guides the Li deposition from the bottom up, and a middle porous layer that eliminates volume expansion. This sandwich structure eliminates dendrite formation, prevents volume change during cycling, and provides outstanding flexibility to the Li-metal anode even at a practical areal capacity over 3.0 mAh cm-2 . Pairing zeroVE-Li with a commercial NMC811 or LCO cathode, flexible LMBs that offer a record-breaking figure of merit (FOM, 45.6), large whole-cell energy density (375 Wh L-1 , based on the volume of the anode, separator, cathode, and package), high-capacity retention (> 99.8% per cycle), and remarkable mechanical robustness under practical conditions are demonstrated.

3.
Chemosphere ; 303(Pt 3): 135189, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35660392

RESUMO

Understanding the pollution characteristics and assessing the ecological risk of toxic metals in mine soil are crucial to controlling and managing risks in abandoned mine areas. In this study, the profile soil pollution characteristics and modified ecological risk of As, Cd, Hg, Pb, Sb, and Tl for both the different mining functional areas and the downstream impacted areas at a large-scale abandoned arsenic-containing mine were studied. Results showed that both the profile soils at the mining functional areas and the surface layer in downstream sites are heavily polluted by As, Cd, Hg, Sb, and Tl. As, Hg, Sb, and Tl mainly accumulated on soils with a depth of 0-1.5 m. In contrast, these metals in the mining site were gradually increased with soil depth above the bedrock strata. Cd and Pb were mainly concentrated at depth of 2.5-3.5 m in the smelting with by-product processing site. The speciation of metals in the profile soils mainly occurred in residual fraction. However, high levels of potential mobile As and Sb were found in mining soils and smelting surface soils, as well as Tl in deep soils at mining functional sites and top soils at downstream sites, with their mean contents in these areas arrived to 2950 mg kg-1, 9.64 mg kg-1, and 0.98 mg kg-1, respectively. In addition, the modified ecological risk assessment (NIRIm) values revealed a substantial ecological risk of As, Cd, Hg, and Sb in both the entire profile soils at the mining, smelting sites and topsoil (0-1.5 m) at the adjacent downstream site. In summary, the pollution characteristics and potential ecological risk of toxic metals in profile soils from the different functional sites at arsenic-containing mine were significantly different and suitable control strategies for available toxic elements should be adopted in the different functional sites of mine.


Assuntos
Arsênio , Mercúrio , Metais Pesados , Poluentes do Solo , Cádmio , China , Monitoramento Ambiental/métodos , Poluição Ambiental , Chumbo , Mercúrio/análise , Metais Pesados/análise , Mineração , Medição de Risco , Solo , Poluentes do Solo/análise
4.
Materials (Basel) ; 15(4)2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35207953

RESUMO

Novel porous magnetic soft materials (pMSMs) based on a poly (vinyl alcohol) (PVA) porous matrix filled with CuNi nanoparticles (NPs) of around 70 nm were synthesized. Initially, magnetic CuNi NPs were fabricated by the reduction of Ni and Cu ions with hydrazine hydrate in ethylene glycol medium in the absence of other capping agents. The pMSMs are subsequently fabricated by mixing CuNi NPs and PVA through freezing-drying process. The as-obtained pMSMs can respond to a magnetic field, i.e., the compressive modulus increase under a magnetic field of 0.23 T. The experimental results indicate that CuNi NPs can easily move to form chain-like structures under the application of a magnetic field. A combination of direct observation and finite element modeling has shown that under the influence of a magnetic field, chain-like aggregates of CuNi NPs lead to self-reinforcement of the pMSMs and, thus, to the increased compressive modulus. From a technological point of view, these materials with good magnetic responsiveness and moderate mechanical strength have potential applications in artificial muscle, soft actuators and drug release, to name a few.

5.
Materials (Basel) ; 14(20)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34683814

RESUMO

The objective of this study was to investigate the composite behavior of rectangular concrete-filled cold-formed steel (CFS) tubular stub columns under axial compression. A fine finite 3D solid element model of rectangular concrete-filled cold-formed steel tubular stub column was established by ABAQUS, which utilized a constitutive model of cold-formed steel considering the cold-forming effect and a triaxial plastic-damage constitutive model of the infilled concrete. Good agreement was achieved and the average discrepancy between the experimental and FE results was less than 5%. Based on the verified models, a further parametric analysis was carried out to reveal the influence of various factors on the strength and behavior of the concrete-filled rectangular cold-formed steel tubular stub columns. The factors included constitutive models adopted for cold-formed steel, length over width ratio of the rectangular section, wall-thickness and width, and concrete strength and yield strength of the cold-formed steel. A total of 144 FE models were analyzed. The stress nephogram was reasonably simplified in accordance with the limit state and a theoretical formula considering confinement coefficient was proposed to estimate the ultimate bearing capacity of concrete-filled rectangular cold-formed steel tubular stub columns using the superposition method. The calculated results showed satisfactory agreement with both the experimental and FE results, which proved the validity and accuracy of the formula proposed in this paper. In the proposed formula, the confinement coefficient of square concrete-filled cold-formed steel tubular stub columns is larger than that of hot-rolled steel counterparts but smaller than that of the stainless steel counterparts.

6.
J Healthc Eng ; 2021: 8241193, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659696

RESUMO

The study aimed to investigate the dynamic changes of percutaneous partial oxygen pressure during the development and evolution of a hypertrophic scar. Twenty cases of hypertrophic scar patients at different stages were selected. A percutaneous oxygen monitor was used to measure oxygen partial pressure in the scar and normal skin tissue at 14, 30, 60, and 90 days after surgery. The changes of oxygen partial pressure, tissue structure, HIF-1α, and VEGF expression in the scar tissue were observed, and the correlation was analyzed. In the scar maturation process, with the prolongation of time, the partial oxygen pressure in the tissue increased gradually. The expression intensity of HIF-1α and VEGF decreased gradually, HIF-1α was positively correlated with VEGF (r = 0.98, P < 0.01), there was a negative correlation between oxygen partial pressure and HIF-1 α expression (r = -0.92, P < 0.01), and it was negatively correlated with VEGF (r = -0.88, P < 0.01). TcPO2 measurement can be used to assess scar maturity; HIF-1 α and VEGF may play an essential role in regulating partial oxygen pressure in the scar tissue.


Assuntos
Cicatriz , Oxigênio , Cicatriz/patologia , Humanos , Hiperplasia , Pressão Parcial , Fator A de Crescimento do Endotélio Vascular/fisiologia
8.
Appl Microbiol Biotechnol ; 105(12): 5123-5134, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34125278

RESUMO

Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tuberculosis) is a fatal infectious disease to human health, and the drug tolerance and immune evasion of M. tuberculosis were reported to be related to its biofilm formation; however, the difficulty of M. tuberculosis biofilm culture and its unknown global mechanism impede its further research. Here, we developed a modified in vitro M. tuberculosis biofilm model with shorter culture time. Then we used Illumina RNA-seq technology to determine the global gene expression profile of M. tuberculosis H37Rv biofilms. Over 437 genes are expressed at significantly different levels in biofilm cells than in planktonic cells; among them, 153 were downregulated and 284 were upregulated. Go enrichment analysis and KEGG pathway analysis showed that genes involved in biosynthesis and metabolism of sulfur metabolism, steroid degradation, atrazine degradation, mammalian cell entry protein complex, etc. are involved in M. tuberculosis biofilm cells. Especially, ATP-binding cassette (ABC) transporters Rv1217c and Rv1218c were significantly upregulated in biofilm, whereas efflux pump inhibitors (EPIs) piperine and 1-(1-naphthylmethyl)-piperazine (NMP) inhibited biofilm formation and the expression of the Rv1217c and Rv1218c genes in a concentration-dependent manner, respectively, indicating Rv1217c and Rv1218c are potential target genes of M. tuberculosis biofilm. This study is the first RNA-Seq-based transcriptome profiling of M. tuberculosis biofilms and provides insights into a potential strategy for M. tuberculosis biofilm inhibition. KEY POINTS: • Characterize M. tuberculosis transcriptomes in biofilm cells by RNA-seq. • Inhibit the expression of Rv1217c and Rv1218c repressed biofilm formation.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Biofilmes , Perfilação da Expressão Gênica , Estudos de Associação Genética , Humanos , Mycobacterium tuberculosis/genética , Transcriptoma
9.
Org Biomol Chem ; 19(21): 4701-4705, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-33988213

RESUMO

A practical one-pot protocol has been developed to synthesize diarylacetylenes from arylaldehydes by treatment with 1-(arylmethyl)benzotriazoles and LiN(SiMe3)2. The reaction proceeded through imine formation, Mannich-type addition and double elimination to deliver products in up to 99% yields with broad substrate scope. In addition, gram-scale synthesis of 1-bromo-4-(phenylethynyl)benzene has been demonstrated.

10.
Oncol Lett ; 21(2): 84, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33363621

RESUMO

Accumulating evidence has indicated that corosolic acid exerts anti-diabetic, anti-obesity, anti-inflammatory, anti-hyperlipidemic and anti-viral effects. More importantly, corosolic acid has recently attracted much attention due to its anticancer properties and innocuous effects on normal cells. Furthermore, the increasing proportion of obese and/or diabetic populations has led to an epidemic of non-alcoholic fatty liver disease (NAFLD), which frequently progresses to hepatocellular carcinoma (HCC). Evidence has indicated that NAFLD is closely associated with the development of HCC and comprises a high risk factor. The present review summarizes the anticancer effects of corosolic acid in vitro and in vivo, and its related molecular mechanisms. It also describes the inhibitory effects of corosolic acid on the progression of NAFLD and its associated molecular mechanisms, providing guidance for future research on corosolic acid in NAFLD-related HCC prevention and treatment. To the best of our knowledge, a review of corosolic acid as an anticancer agent has not yet been reported. Due to its multitargeted activity in cancer cells, corosolic acid exerts anticancer effects when administered alone, and acts synergistically when administered with chemotherapeutic drugs, even in drug-resistant cells. In addition, as a novel tool to treat metabolic syndromes, corosolic acid uses the same mechanism in its action against cancer as that used in the progression of NAFLD-related HCC. Therefore, corosolic acid has been suggested as an agent for the prevention and treatment of NAFLD-related HCC.

11.
Mol Cell Probes ; 52: 101583, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32360740

RESUMO

Previous studies have demonstrated that insulin-like growth factor-I (IGF-1) and reactive oxygen species (ROS) are involved in the development and progression of various cancers. However, their regulatory mechanism remains unknown. In this study, we treated cancer cells (HeLa, HepG2 and SW1116 cells) and normal cells (NCM-460) with IGF-1 at different concentrations and for different times and found that cancer cells produced large amounts of cytoplasmic ROS in cancer cells but not in normal cells. Further mechanistic analysis demonstrated that IGF-1 activated NFκB and NLRP3 inflammatory signalling in HeLa cells; systematic analysis indicated that IGF-1 activates NFκB and NLRP3, and the activation was cytosolic ROS- and NADPH oxidase 2 (NOX2)-dependent. Additionally, through coimmunoprecipitation experiments, we found that the IRS-1/COX2/mPGES-1/MAPKs/RAC2/NOX2 pathway nexus was involved in IGF-1-induced NFκB and NLRP3 production. Finally, we validated the regulatory mechanisms through IRS-1, mPGES-1 or NOX2 inhibition using their respective selective inhibitors or shRNA knockdown. Taken together, this is the first report on the mechanism by which IGF-1 activates NFκB and NLRP3 inflammatory signalling via ROS. These findings pave the way for an in-depth study of the role of IGF-1 and ROS in inflammation associated with the development and progression of cancer.


Assuntos
Inflamação/patologia , Fator de Crescimento Insulin-Like I/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Humanos , Proteínas Substratos do Receptor de Insulina/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Prostaglandina-E Sintases/metabolismo , Proteínas rac de Ligação ao GTP/metabolismo
12.
Vet Comp Oncol ; 18(4): 689-698, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32270590

RESUMO

The levels of insulin-like growth factor-l (IGF-1) and reactive oxygen species (ROS) are abnormally elevated in various tumour tissues, and IGF-1 has been reported to be associated with the development and progression of inflammation in cancers. In this study, we found that IGF-1 activated nuclear factor-κB (NF-κB) and NLRP3 inflammatory signalling via IRS-1/mPGES-1/NOX2-regulated ROS. Additionally, in the B16-F10 tumour-bearing mouse model, the number of tumours, tumour growth, invasion of tissues and expression of proinflammatory factors in peripheral blood were significantly decreased by treatment with an inhibitor combination compared with those of the IGF-1 group. Taken together, targeting IRS-1/mPGES-1/NOX2 to inhibit inflammation related to NF-κB and NLRP3 is a potential strategy for controlling the development and progression of cancer.


Assuntos
Fator de Crescimento Insulin-Like I/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neoplasias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Linhagem Celular , Progressão da Doença , Humanos , Camundongos
13.
Pol J Microbiol ; 68(4): 477-491, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31880892

RESUMO

This study explored a potential treatment against methicillin-resistant Staphylococcus aureus (MRSA) infections that combines thioridazine (TZ), an efflux pump inhibitor, and miconazole (MCZ), an autolysis inducer, with the anti-microbial drug cloxacillin (CXN). In vitro, the combination treatment of TZ and MCZ significantly reduced 4096-fold (Σ (FIC) = 0.1 - 1.25) the MIC value of CXN against S. aureus. In vivo, the combination therapy significantly relieved breast redness and swelling in mice infected with either clinical or standard strains of S. aureus. Meanwhile, the number of bacteria isolated from the MRSA135-infected mice decreased significantly (p = 0.0427 < 0.05) after the combination therapy when compared to monotherapy. Moreover, the number of bacteria isolated from the mice infected with a reference S. aureus strain also decreased significantly (p = 0.0191 < 0.05) after the combination therapy when compared to monotherapy. The pathological changes were more significant in the CXN-treated group when compared to mice treated with a combination of three drugs. In addition, we found that combination therapy reduced the release of the bacteria-stimulated cytokines such as IL-6, IFN-γ, and TNF-α. Cytokine assays in serum revealed that CXN alone induced IL-6, IFN-γ, and TNF-α in the mouse groups infected with ATCC 29213 or MRSA135, and the combination of these three drugs significantly reduced IL-6, IFN-γ, and TNF-α concentrations. Also, the levels of TNF-α and IFN-γ in mice treated with a combination of three drugs were significantly lower than in the CXN-treated group. Given the synergistic antibacterial activity of CXN, we concluded that the combination of CXN with TZ, and MCZ could be developed as a novel therapeutic strategy against S. aureus.This study explored a potential treatment against methicillin-resistant Staphylococcus aureus (MRSA) infections that combines thioridazine (TZ), an efflux pump inhibitor, and miconazole (MCZ), an autolysis inducer, with the anti-microbial drug cloxacillin (CXN). In vitro, the combination treatment of TZ and MCZ significantly reduced 4096-fold (Σ (FIC) = 0.1 ­ 1.25) the MIC value of CXN against S. aureus. In vivo, the combination therapy significantly relieved breast redness and swelling in mice infected with either clinical or standard strains of S. aureus. Meanwhile, the number of bacteria isolated from the MRSA135-infected mice decreased significantly (p = 0.0427 < 0.05) after the combination therapy when compared to monotherapy. Moreover, the number of bacteria isolated from the mice infected with a reference S. aureus strain also decreased significantly (p = 0.0191 < 0.05) after the combination therapy when compared to monotherapy. The pathological changes were more significant in the CXN-treated group when compared to mice treated with a combination of three drugs. In addition, we found that combination therapy reduced the release of the bacteria-stimulated cytokines such as IL-6, IFN-γ, and TNF-α. Cytokine assays in serum revealed that CXN alone induced IL-6, IFN-γ, and TNF-α in the mouse groups infected with ATCC 29213 or MRSA135, and the combination of these three drugs significantly reduced IL-6, IFN-γ, and TNF-α concentrations. Also, the levels of TNF-α and IFN-γ in mice treated with a combination of three drugs were significantly lower than in the CXN-treated group. Given the synergistic antibacterial activity of CXN, we concluded that the combination of CXN with TZ, and MCZ could be developed as a novel therapeutic strategy against S. aureus.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Farmacorresistência Bacteriana , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , beta-Lactamas/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Bacteriólise/efeitos dos fármacos , Cloxacilina/farmacologia , Quimioterapia Combinada , Humanos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Miconazol/farmacologia , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/citologia , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Tioridazina/farmacologia
14.
FASEB J ; 33(11): 12515-12527, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31461386

RESUMO

Diabetes mellitus (DM) affects bone metabolism and leads to osteoporosis; however, its pathogenetic mechanisms remain unknown. We found that high glucose (HG) conditions induced the production of reactive oxygen species (ROS) and the expression of proteins related to MAPKs [phosphorylated (p)-ERK, p-JNK, and p-p38], NF-κB (NF-κB, p-IκB, and IKK), and NACHT-LRR-PYD domains-containing protein 3 (NALP3) (NLRP3) [apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), caspase-1, IL-18, IL-1ß, and NLRP3] in osteoclasts (OCs) in vitro. Further analysis showed that in HG-induced OCs, ROS is an upstream signal for MAPKs, NF-κB, and the NLRP3 inflammasome. Moreover, MAPKs mediated the activation of NF-κB and NLRP3, whereas NF-κB up-regulated the NLRP3 inflammasome response. Interestingly, HG inducement enhanced the bone resorption of OCs but inhibited their efferocytosis, whereas insulin and lipoxin A4 (4) treatment reversed this phenomenon. In streptozotocin-induced diabetic rats in vivo, the numbers and the bone-resorption capacity of OCs as well as the serum levels of TRACP-5b were significantly increased, and the expression of MAPK-, NF-κB-, and NLRP3 inflammasome-related proteins in the proximal tibia were also significantly elevated; however, treatment with insulin and LXA4 reversed this elevation. Together, these results demonstrated that the activation of ROS/MAPKs/NF-κB/NLRP3 and the inhibition of efferocytosis in OCs are the main causes of osteoporosis in DM.-An, Y., Zhang, H., Wang, C., Jiao, F., Xu, H., Wang, X., Luan, W., Ma, F., Ni, L., Tang, X., Liu, M., Guo, W., Yu, L. Activation of ROS/MAPKs/NF-κB/NLRP3 and inhibition of efferocytosis in osteoclast-mediated diabetic osteoporosis.


Assuntos
Complicações do Diabetes/metabolismo , Diabetes Mellitus Experimental/metabolismo , Sistema de Sinalização das MAP Quinases , Osteoclastos/metabolismo , Osteoporose/metabolismo , Animais , Complicações do Diabetes/genética , Complicações do Diabetes/patologia , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Masculino , NF-kappa B/genética , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Osteoclastos/patologia , Osteoporose/genética , Osteoporose/patologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
15.
Artigo em Inglês | MEDLINE | ID: mdl-31380296

RESUMO

α-Hemolysin (Hla) is a significant virulence factor in Staphylococcus aureus (S. aureus)-caused infectious diseases such as pneumonia. Thus, to prevent the production of Hla when treating S. aureus infection, it is necessary to choose an antibiotic with good antibacterial activity and effect. In our study, we observed that Fosfomycin (FOM) at a sub-inhibitory concentration inhibited expression of Hla. Molecular dynamics demonstrated that FOM bound to the binding sites LYS 154 and ASP 108 of Hla, potentially inhibiting Hla. Furthermore, we verified that staphylococcal membrane-derived vesicles (SMVs) contain Hla and that FOM treatment significantly reduced the production of SMVs and Hla. Based on our pharmacological inhibition analysis, ERK and p38 activated NLRP3 inflammasomes. Moreover, FOM inhibited expression of MAPKs and NLRP3 inflammasome-related proteins in S. aureus as well as SMV-infected human macrophages (MΦ) and alveolar epithelial cells. In vivo, SMVs isolated from S. aureus DU1090 (an isogenic Hla deletion mutant) or the strain itself caused weaker inflammation than that of its parent strain 8325-4. FOM also significantly reduced the phosphorylation levels of ERK and P38 and expression of NLRP3 inflammasome-related proteins. In addition, FOM decreased MPO activity, pulmonary vascular permeability and edema formation in the lungs of mice with S. aureus-caused pneumonia. Taken together, these data indicate that FOM exerts protective effects against S. aureus infection in vitro and in vivo by inhibiting Hla in SMVs and blocking ERK/P38-mediated NLRP3 inflammasome activation by Hla.


Assuntos
Antibacterianos/farmacologia , Toxinas Bacterianas/antagonistas & inibidores , Fosfomicina/farmacologia , Proteínas Hemolisinas/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Pneumonia Estafilocócica/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Fatores de Virulência/antagonistas & inibidores , Animais , Antibacterianos/química , Toxinas Bacterianas/química , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Sítios de Ligação , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Vesículas Extracelulares , Fosfomicina/química , Regulação da Expressão Gênica , Proteínas Hemolisinas/química , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Interações Hospedeiro-Patógeno/genética , Humanos , Inflamassomos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pneumonia Estafilocócica/microbiologia , Pneumonia Estafilocócica/patologia , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Staphylococcus aureus/genética , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/patogenicidade , Células THP-1 , Fatores de Virulência/química , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
16.
J Pharm Pharmacol ; 71(9): 1429-1439, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31259423

RESUMO

OBJECTIVE: To explore the effect of cordycepin on reducing lipid droplets in adipocytes. METHODS: Rats were fed a 60% high-fat diet to construct a hyperlipidaemia animal model and then treated with cordycepin at different concentrations for 8 weeks. Adipocytes were extracted, and BODIPY staining was used to detect the size of the lipid droplets. The adipocyte membrane proteins ASC-1, PAT2 and P2RX5 were assessed to determine the transformation of white adipocytes to beige and brown adipocytes. In an in vitro study, 3T3-L1 cells were cultured, and Western blotting was used to determine the expression of the lipid droplet-related genes Fsp27, perilipin 3, perilipin 2, PPAR-γ, Rab5, Rab7, Rab11, perilipin 1, ATGL and CGI-58. RESULTS: We found that cordycepin could promote the transformation of white adipocytes into beige and brown adipocytes. Cordycepin also downregulated the lipid droplet-associated genes Fsp27, perilipin 3, perilipin 2, Rab5, Rab11 and perilipin 1. Moreover, cordycepin reduced the expression of protein CGI-58, which inhibits lipid droplet degradation. In addition, cordycepin significantly increased the expression of ATGL, suggesting that cordycepin might stimulate lipolysis by upregulating the expression of ATGL instead of CGI-58 and by downregulating the expression of perilipin 1. CONCLUSIONS: Cordycepin could blockade lipid droplet formation and promote lipid droplet degradation.


Assuntos
Adipócitos Bege/efeitos dos fármacos , Adipócitos Bege/metabolismo , Desoxiadenosinas/farmacologia , Gotículas Lipídicas/metabolismo , Lipólise/efeitos dos fármacos , Células 3T3-L1 , Animais , Peso Corporal/efeitos dos fármacos , Gotículas Lipídicas/efeitos dos fármacos , Lipídeos/sangue , Masculino , Camundongos , Perilipina-1/metabolismo , Perilipina-2/metabolismo , Perilipina-3/metabolismo , Proteínas , Ratos Sprague-Dawley , Proteínas rab5 de Ligação ao GTP
17.
Electrophoresis ; 40(20): 2736-2746, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31141184

RESUMO

Tuberculosis is highly persistent and displays phenotypic resistance to high concentrations of antimicrobials. Recent reports exhibited that Mycobacterium tuberculosis biofilm was implicated to its pathogenicity and drug resistance. In this study, there were 47 kinds of differential proteins in the biofilm of M. tuberculosis H37Rv cells compared with the planktonic bacteria, and 37 proteins were nonredundant and identified by proteomics approach, such as 2DE and LC-MS/MS. Moreover, six kinds of proteins were identified as HspX, which were conservative and highly expressed in biofilm. Note that 47 differential proteins were divided into seven categories, such as cell wall and cell processes, conserved hypotheticals, intermediary metabolism and respiration, and so on by TUBERCULIST. The Gene Ontology classification results showed that the largest protein group involved in metabolism, binding proteins, and catalytic function accounts for 30% and 57% of all identified proteins, respectively. Moreover, the protein interaction network analyzed by STRING showed that the minority proteins such as RpoA, SucC, Cbs, Tuf, DnaK, and GroeL in the interaction network have high network connectivity. These results implied that the proteins involved in metabolic process and catalytic function and the minority proteins mentioned above may play an important role in M. tuberculosis biofilm formation. To our knowledge, this is the first report about differential proteins between biofilm and planktonic M. tuberculosis, which provided the potential antigens for vaccines and target proteins for anti-mycobacterial drugs.


Assuntos
Proteínas de Bactérias/análise , Biofilmes , Mycobacterium tuberculosis , Proteoma/análise , Proteômica/métodos , Proteínas de Bactérias/metabolismo , Mycobacterium tuberculosis/química , Mycobacterium tuberculosis/citologia , Mycobacterium tuberculosis/metabolismo , Mycobacterium tuberculosis/fisiologia , Mapas de Interação de Proteínas/fisiologia , Proteoma/metabolismo
18.
Front Cell Neurosci ; 13: 199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31133815

RESUMO

Previous studies have demonstrated that T cells and microglia could fight against cerebral Listeria monocytogenes (Listeria); however, their synergistic anti-Listeria mechanisms remain unknown. Following Listeria infection in a culture system, we found that microglia, but not nerve cells, could release extracellular traps (ETs) which originated from microglial vesicles. Specific inhibitor analysis showed that extracellular DNA (eDNA), matrix metallopeptidases (MMP9 and MMP12), citrullinated histone H3, and peptidyl arginine deiminase 2 were the major components of microglial ETs (MiETs) and were also the components of vesicles. Systematic analysis indicated that Listeria-induced MiETs were cytosolic reactive oxygen species (ROS)- and NADPH oxidase (NOX)-dependent and involved ERK. MiETs were exhibited in Listeria-infected mouse brain and might protected against Listeria infection via bacterial killing in a mouse meningitis model, and MiETs existed in cerebrospinal fluid (CSF) from Listeria meningitis patients in vivo and in vitro. Additionally, interferon-γ could induce MiET formation in Listeria-infected microglia in vitro that was mediated by NOX, and there was a positive relationship between the elevated level of IFN-γ and eDNA and nucleosomes in the brain homogenates and CSF of Listeria meningitis model mice and in the CSF before treatment in clinical Listeria meningitis patients. Together, this is the first report of MiET formation, these findings pave the way for deeper exploration of the innate immune response to pathogens in CNS.

19.
Inflammation ; 42(4): 1463-1473, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31011928

RESUMO

Twelve polyketones were isolated from the fermentation broth of Penicillium sp., including six new compounds (supplementary material). Penicillium sp. is widely used in clinic as a highly effective and low toxic antibiotic. Among these compounds, (3R, 7R)-7-acetoxyl-9-oxo-de-O-methyllasiodiplodin named PS-2 showed significant anti-inflammatory activity. So, the anti-inflammatory mechanism of PS-2 was investigated by using lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. The results showed that PS-2 can significantly inhibit the overproduction of nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-6 (IL-6), whereas it showed no inhibition on the release of pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α). Cell-free colorimetric method demonstrated that PS-2 could obviously inhibit the enzymatic activity of cyclooxygenase-2 (COX-2). Western blot results indicated that PS-2 could significantly inhibit high expression of iNOS and COX-2 proteins. Further investigations on the anti-inflammatory mechanism showed that PS-2 could suppress the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), but did not exhibit obvious inhibition on the phosphorylation of c-JunN-terminal kinase (JNK) and phosphorylated 38 (p38). In addition, PS-2 inhibited the degradation of inhibitor of kappa-B alpha (IκB-α) and translocation to nucleus of nuclear factor kappa-B (NF-κB) p65 in RAW 264.7 macrophages. These results suggested that PS-2 might be an effective intervention against inflammatory diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/prevenção & controle , Macrolídeos/farmacologia , Macrófagos/patologia , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Penicillium/metabolismo , Animais , Mediadores da Inflamação , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Camundongos , Fosforilação/efeitos dos fármacos , Células RAW 264.7
20.
Int J Med Microbiol ; 309(1): 73-83, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30563740

RESUMO

Tuberculosis is a highly infectious disease and of high incidence in low-income countries that is caused by Mycobacterium tuberculosis (M. tuberculosis). M. tuberculosis can form biofilms in vitro and in vivo, and the cells in the biofilm can survive at high concentrations of antibiotics. CwlM is a peptidoglycan hydrolase (amidase) and can hydrolyze bacterial cell walls, and the effects of CwlM on autolysis and biofilms is worthy of in-depth study. In this study, we successfully constructed an in vitro biofilm model of M. tuberculosis and Mycobacterium smegmatis (M. smegmatis). Reverse transcription followed by real-time quantitative PCR (qPCR) revealed that the expression of cwlM in M. tuberculosis and M. smegmatis was significantly up-regulated during the middle stage of biofilm formation. Treatment with recombinant CwlM enhanced the autolytic ability of M. tuberculosis and M. smegmatis and reduced the formation of their biofilms. As M. smegmatis is a model bacterium of M. tuberculosis, we built the M. smegmatis cwlM-deletion strain MSΔ6935, whose autolytic ability, biofilm production, and eDNA and eRNA content were determined to be lower than those of its parental strain. In conclusion, the cwlM gene plays a key regulatory role in biofilm formation in M. tuberculosis and M. smegmatis. This study provided a theoretical basis for using peptidoglycan hydrolase as a target for the inhibition of biofilms.


Assuntos
Bacteriólise/genética , Biofilmes/crescimento & desenvolvimento , Mycobacterium smegmatis/genética , Mycobacterium tuberculosis/genética , N-Acetil-Muramil-L-Alanina Amidase/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sequência de Bases , Parede Celular/metabolismo , Humanos , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium smegmatis/enzimologia , Mycobacterium tuberculosis/enzimologia , N-Acetil-Muramil-L-Alanina Amidase/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Deleção de Sequência , Tuberculose/microbiologia
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