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Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.
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Skeletal stem cells (SSC) have gained attentions as candidates for the treatment of osteoarthritis due to their osteochondrogenic capacity. However, the immunomodulatory properties of SSC, especially under delivery operations, have been largely ignored. In the study, we found that Pdpn+ and Grem1+ SSC subpopulations owned immunoregulatory potential, and the single-cell RNA sequencing (scRNA-seq) data suggested that the mechanical activation of microgel carriers on SSC induced the generation of Pdpn+Grem1+Ptgs2+ SSC subpopulation, which was potent at suppressing macrophage inflammation. The microgel carriers promoted the YAP nuclear translocation, and the activated YAP protein was necessary for the increased expression of Ptgs2 and PGE2 in microgels-delivered SSC, which further suppressed the expression of TNF-É, IL-1ß and promoted the expression of IL-10 in macrophages. SSC delivered with microgels yielded better preventive effects on articular lesions and macrophage activation in osteoarthritic rats than SSC without microgels. Chemically blocking the YAP and Ptgs2 in microgels-delivered SSC partially abolished the enhanced protection on articular tissues and suppression on osteoarthritic macrophages. Moreover, microgel carriers significantly prolonged SSC retention time in vivo without increasing SSC implanting into osteoarthritic joints. Together, our study demonstrated that microgel carriers enhanced SSC reprogramming towards immunomodulatory phenotype to regulate macrophage phenotype transformation for effectively osteoarthritic therapy by promoting YAP protein translocation into nucleus. The study not only complement and perfect the immunological mechanisms of SSC-based therapy at the single-cell level, but also provide new insight for microgel carriers in stem cell-based therapy.
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Osteosarcoma (OS) therapy faces many challenges, especially the poor survival rate once metastasis occurs. Therefore, it is crucial to explore new OS treatment strategies that can efficiently inhibit OS metastasis. Bioactive nanoparticles such as zinc oxide nanoparticles (ZnO NPs) can efficiently inhibit OS growth, however, the effect and mechanisms of them on tumor metastasis are still not clear. In this study, we firstly prepared well-dispersed ZnO NPs and proved that ZnO NPs can inhibit OS metastasis-related malignant behaviors including migration, invasion, and epithelial-mesenchymal transition (EMT). RNA-Seqs found that differentially expressed genes (DEGs) in ZnO NP-treated OS cells were enriched in wingless/integrated (Wnt) and hypoxia-inducible factor-1 (HIF-1) signaling pathway. We further proved that Zn2+ released from ZnO NPs induced downregulation of ß-catenin expression via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway. ZnO NPs combined with ICG-001, a ß-catenin inhibitor, showed a synergistic inhibitory effect on OS lung metastasis and a longer survival time. In addition, tissue microarray (TMA) of OS patients also detected much higher ß-catenin expression which indicated the role of ß-catenin in OS development. In summary, our current study not only proved that ZnO NPs can inhibit OS metastasis by degrading ß-catenin in HIF-1α/BNIP3/LC3B-mediated mitophagy pathway, but also provided a far-reaching potential of ZnO NPs in clinical OS treatment with metastasis.
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piRNAs play pivotal roles in maintaining genome stability, regulating gene expression, and modulating development and immunity. However, there are few piRNA-associated studies on honey-bees, and the regulatory role of piRNAs in the development of bee guts is largely unknown. Here, the differential expression pattern of piRNAs during the developmental process of the European honey-bee (Apis mellifera) larval guts was analyzed, followed by investigation of the regulatory network and the potential function of differentially expressed piRNAs (DEpiRNAs) in regulating gut development. A total of 843 piRNAs were identified in the larval guts of A. mellifera; among these, 764 piRNAs were shared by 4- (Am4 group), 5- (Am5 group), and 6-day-old (Am6 group) larval guts, while 11, 67, and one, respectively, were unique. The first base of piRNAs in each group had a cytosine (C) bias. Additionally, 61 up-regulated and 17 down-regulated piRNAs were identified in the "Am4 vs. Am5" comparison group, further targeting 9, 983 genes, which were involved in 50 GO terms and 142 pathways, while two up-regulated and five down-regulated piRNAs were detected in the "Am5 vs. Am6" comparison group, further targeting 1, 936 genes, which were engaged in 41 functional terms and 101 pathways. piR-ame-742536 and piR-ame-856650 in the "Am4 vs. Am5" comparison group as well as piR-ame-592661 and piR-ame-31653 in the "Am5 vs. Am6" comparison group were found to link to the highest number of targets. Further analysis indicated that targets of DEpiRNAs in these two comparison groups putatively regulate seven development-associated signaling pathways, seven immune-associated pathways, and three energy metabolism pathways. Moreover, the expression trends of five randomly selected DEpiRNAs were verified based on stem-loop RT-PCR and RT-qPCR. These results were suggestive of the overall alteration of piRNAs during the larval developmental process and demonstrated that DEpiRNAs potentially modulate development-, immune-, and energy metabolism-associated pathways by regulating the expression of corresponding genes via target binding, further affecting the development of A. mellifera larval guts. Our data offer a novel insight into the development of bee larval guts and lay a basis for clarifying the underlying mechanisms.
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Mel , Transcriptoma , Animais , Abelhas/genética , Citosina/metabolismo , Larva/genética , Larva/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transcriptoma/genéticaRESUMO
The daily life of people in the intelligent age is inseparable from electronic device, and a number of bacteria on touch screens are increasingly threatening the health of users. Herein, a photocatalytic TiO2/Ag thin film was synthesized on a glass by atomic layer deposition and subsequent in situ reduction. Ultraviolet-visible (UV-Vis) spectra showed that this film can harvest the simulated solar light more efficiently than that of pristine TiO2. The antibacterial tests in vitro showed that the antibacterial efficiency of the TiO2/Ag film against S. aureus and E. coli was 98.2% and 98.6%, under visible light irradiation for 5 min. The underlying mechanism was that the in-situ reduction of Ag on the surface of TiO2 reduced the bandgap of TiO2 from 3.44 to 2.61 eV due to the formation of Schottky heterojunction at the interface between TiO2 and Ag. Thus, TiO2/Ag can generate more reactive oxygen species for bacterial inactivation on the surface of electronic screens. More importantly, the TiO2/Ag film had great biocompatibility with/without light irradiation. The platform not only provides a more convenient choice for the traditional antibacterial mode but also has limitless possibilities for application in the field of billions of touch screens.
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Bacterial infection is an urgent public health problem. We design a novel photo-responsive hybrid material by growing small molecules of curcumin (Cur) in situ on a sea urchin-like Bi2S3 surface by a one-step hydrothermal reaction method, thus forming an organic-inorganic hybrid material with interfacial contact. The Bi2S3/Cur hybrid material has good antibacterial effect under 808 nm near-infrared (NIR) light irradiation. The antibacterial mechanism is that the electron redistribution at the interface of Bi2S3/Cur excited by 808 nm NIR light will cause a large number of electrons to gather on the side of Bi2S3, forming an internal electric field to drive the excited electrons from Bi2S3 to Cur, which accelerates the separation of photoexcited electron-hole pairs and enhances the production of reactive oxygen species (ROS). In conclusion, due to these synergistic effects of the photothermal properties of Bi2S3, the production of more ROS and the release of small molecules of Cur from traditional Chinese medicine in Bi2S3/Cur, the antibacterial efficacy against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) is 99.96% and 99.03%, respectively. In vivo experiments in animals show that Bi2S3/Cur can reduce the inflammatory response and promote wound healing. This paper presents a simple, rapid and safe strategy for the treatment of wound infections with near-infrared light.
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Curcumina , Animais , Curcumina/farmacologia , Staphylococcus aureus , Escherichia coli , Espécies Reativas de Oxigênio , Cicatrização , Antibacterianos/farmacologia , Ouriços-do-MarRESUMO
To date, few effective treatments have been licensed for nonalcoholic fatty liver disease (NAFLD), which a kind of chronic liver disease. Mammalian sterile 20-like kinase 1 (MST1) is reported to be involved in the development of NAFLD. Thus, we evaluated the suitability of a redox-unlockable polymeric nanoparticle Hep@PGEA vector to deliver MST1 or siMST1 (HCP/MST1 or HCP/siMST1) for NAFLD therapy. The Hep@PGEA vector can efficiently deliver the condensed functional nucleic acids MST1 or siMST1 into NAFLD-affected mouse liver to upregulate or downregulate MST1 expression. The HCP/MST1 complexes significantly improved liver insulin resistance sensitivity and reduced liver damage and lipid accumulation by the AMPK/SREBP-1c pathway without significant adverse events. Instead, HCP/siMST1 delivery exacerbates the NAFLD. The analysis of NAFLD patient samples further clarified the role of MST1 in the development of hepatic steatosis in patients with NAFLD. The MST1-based gene intervention is of considerable potential for clinical NAFLD therapy, and the Hep@PGEA vector provides a promising option for NAFLD gene therapy.
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Nanopartículas , Hepatopatia Gordurosa não Alcoólica , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Mamíferos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Oxirredução , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismoRESUMO
BACKGROUND: Repairing radiation-induced bone injuries remains a significant challenge in the clinic, and few effective medicines are currently available. Psoralen is a principal bioactive component of Cullen corylifolium (L.) Medik and has been reported to have antitumor, anti-inflammatory, and pro-osteogenesis activities. However, less information is available regarding the role of psoralen in the treatment of radiation-induced bone injury. In this study, we explored the modulatory effects of psoralen on skeletal stem cells and their protective effects on radiation-induced bone injuries. METHODS: The protective effects of psoralen on radiation-induced osteoporosis and irradiated bone defects were evaluated by microCT and pathological analysis. In addition, the cell proliferation, osteogenesis, and self-renewal of SSCs were explored. Further, the underlying mechanisms of the protective of psoralen were investigated by using RNA sequencing and functional gain and loss experiments in vitro and in vivo. Statistical significance was analyzed using Student's t test. The one-way ANOVA was used in multiple group data analysis. RESULTS: Here, we demonstrated that psoralen, a natural herbal extract, mitigated radiation-induced bone injury (irradiation-induced osteoporosis and irradiated bone defects) in mice partially by rescuing the stemness of irradiated skeletal stem cells. Mechanistically, psoralen restored the stemness of skeletal stem cells by alleviating the radiation-induced suppression of AKT/GSK-3ß and elevating NRF2 expression in skeletal stem cells. Furthermore, the expression of KEAP1 in skeletal stem cells did not significantly change in the presence of psoralen. Moreover, blockade of NRF2 in vivo partially abolished the promising effects of psoralen in a murine model of irradiation-induced osteoporosis and irradiated bone regeneration. CONCLUSIONS: In summary, our findings identified psoralen as a potential medicine to mitigate bone radiation injury. In addition, skeletal stem cells and AKT-GSK-3ß and NRF2 may thus represent therapeutic targets for treating radiation-induced bone injury.
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Osteoporose , Lesões por Radiação , Animais , Ficusina/farmacologia , Ficusina/uso terapêutico , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Osteoporose/etiologia , Osteoporose/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células-Tronco/metabolismo , Regulação para CimaRESUMO
Osteosarcoma, a malignant bone tumor that usually occurs in children and adolescents, has a high rate of death and disability, bringing great pains to society and families. Improving treatment approaches for osteosarcoma patients remains a constant and major goal for researchers and clinical groups due to the limited therapeutic efficiency and survival rate. MiRNAs have been reported to play a crucial role in osteosarcoma occurrence, progression, and metastasis, which provides a new insight for osteosarcoma therapy. In other words, the intervention of the involved miRNA may be a promising way for osteosarcoma. In this study, we developed ethanolamine (EA)-decorated poly(glycidyl methacrylate) (PGMA) polycations (termed as PGEAs) to deliver miR-223 for osteosarcoma inhibition. The introduced hydroxyl groups via EA modification in the PGEA vector can form a hydration shell, hinder protein adsorption, and help the PGEA-based delivery system escape from the in vivo clearance, which further benefits the accumulation of the delivery system in the tumor area. A series of in vitro anti-tumor assays illustrate that the PGEA-2 vector can efficiently deliver miR-223 into osteosarcoma cells for impressive anti-tumor effects via inhibiting malignant behavior of osteosarcoma cells, including proliferation, migration, and invasion. Osteosarcoma inhibition assays in vivo further confirmed the anti-tumor efficiency of PGEA-2/miR-223 complexes without inducing evident toxicity. This work will help develop miRNA for osteosarcoma therapy, and the proposed PGEA based delivery system also provides a promising and safe strategy for gene therapy of osteosarcoma.
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MicroRNAs , Osteossarcoma , Adolescente , Linhagem Celular Tumoral , Proliferação de Células , Criança , Terapia Genética , Humanos , MicroRNAs/genética , Osteossarcoma/genética , Osteossarcoma/terapia , PolieletrólitosRESUMO
Piwi-interacting RNAs (piRNAs), a class of small non-coding RNAs (ncRNAs), play pivotal roles in maintaining the genomic stability and modulating biological processes such as growth and development via the regulation of gene expression. However, the piRNAs in the Asian honeybee (Apis cerana) are still largely unknown at present. In this current work, on the basis of previously gained high-quality small RNA-seq datasets, piRNAs in the larval gut of Apis cerana cerana, the nominated species of A. cerana, were identified for the first time, followed by an in-depth investigation of the regulatory roles of differentially expressed piRNAs (DEpiRNAs) in the developmental process of the A. c. cerana. Here, a total of 621 piRNAs were identified in A. c. cerana larval guts, among which 499 piRNAs were shared by 4-(Ac4 group), 5-(Ac5 group), and 6-day-old (Ac6 group) larval guts, while the numbers of unique ones equaled 79, 37, and 11, respectively. The piRNAs in each group ranged from 24 nucleotides (nt) to 33 nt in length, and the first base of the piRNAs had a cytosine (C) bias. Additionally, five up-regulated and five down-regulated piRNAs were identified in the Ac4 vs. Ac5 comparison group, nine of which could target 9011 mRNAs; these targets were involved in 41 GO terms and 137 pathways. Comparatively, 22 up-regulated piRNAs were detected in the Ac5 vs. Ac6 comparison group, 21 of which could target 28,969 mRNAs; these targets were engaged in 46 functional terms and 164 pathways. The results suggested an overall alteration of the expression pattern of piRNAs during the developmental process of A. c. cerana larvae. The regulatory network analysis showed that piR-ace-748815 and piR-ace-512574 in the Ac4 vs. Ac5 comparison group as well as piR-ace-716466 and piR-ace-828146 in the Ac5 vs. Ac6 comparison group were linked to the highest number of targets. Further investigation indicated that targets of DEpiRNAs in the abovementioned two comparison groups could be annotated to several growth and development-associated pathways, such as the Jak/STAT, TGF-ß, and Wnt signaling pathways, indicating the involvement of DEpiRNAs in modulating larval gut development via these crucial pathways. Moreover, the expression trends of six randomly selected DEpiRNAs were verified using a combination of stem-loop RT-PCR and RT-qPCR. These results not only provide a novel insight into the development of the A. c. cerana larval gut, but also lay a foundation for uncovering the epigenetic mechanism underlying larval gut development.
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Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. There are still challenges for HCC treatments, especially high resistance of the cancer cells to chemotherapy and/or target therapy. In this study, a responsive charge-reversal vehicle consists of negatively charged heparin core and positively charged ethanolamine (EA)-modified poly(glycidyl methacrylate) (PGEA) shell (named Hep@PGEA) with self-accelerating release for condensed nucleic acids was proposed to deliver the pCas9 plasmid encoding clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) and the sgRNA targeting oncogene survivin to treat HCC. The Hep@PGEA/pCas9 system showed high anti-tumor efficiency via inducing apoptosis and inhibiting proliferation, migration and invasion capability of HCC cells. The Hep@PGEA/pCas9 system was further utilized to treat orthotopic HCC in mice via tail vein injection. The system exhibited an evident accumulation in the liver of mice and achieved obvious anti-tumor effects. The Hep@PGEA/pCas9 system also showed marked improvement of HCC therapy with sorafenib and provided promising combination HCC treatment potentials. Moreover, enrichment of the Hep@PGEA-based delivery system in liver highlights its possibilities for treatments of other liver diseases.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Sistemas CRISPR-Cas , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Edição de Genes , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Camundongos , OncogenesRESUMO
Mixtures of ionic liquids (ILs) and molecular solvents can overcome the drawbacks (high viscosity, high polarity, and high cost) of pure ILs and extend their practical use. The structural and interaction properties of ILs form the bases for understanding their properties. In this work, the structural properties of the mixtures of an IL, 1-(2'-hydroxylethyl)-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C2OHMIM][Tf2N]), with chloroform, a molecular solvent of weak polarity, in various concentrations were analysed using Fourier transform infrared spectroscopy and density functional theory calculations. Excess spectra were used to analyse the infrared spectra. The IL forms a stable ion cluster-CDCl3 complex with CDCl3 in the concentration range investigated. In the ion cluster-CDCl3 complex, the hydrogen atom of CDCl3 forms hydrogen-bonds with the fluorine atoms of the anion. In addition, the chlorine atom of CDCl3 forms a halogen-bond with the oxygen atom of the anion. All the hydrogen and halogen-bonds identified between the [C2OHMIM][Tf2N] ion cluster and CDCl3 exhibit low strength, closed shells, and electrostatically dominant interactions.
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Caffeic acid ester derivatives have been widely found in propolis extract and plants. In this work, the effect of ester groups with different aromatic and alkyl chains on the antioxidant activity of caffeic acid was performed on the double H+/e- process using DFT calculations. We found that 1) O3-H3â¯O4 intramolecular hydrogen-bonds exist in the catechol moiety of the investigated compounds, which have the same strength and are closed shell interactions, weak-strength and electrostatic in nature, making the 4-OH more favourable than 3-OH to trap free radicals. 2) In weak polarity phases, caffeic acid and its derivatives prefer to perform the double H+/e- processes via the dHAT mechanism. In the polar phases, the SdPLdET mechanism is more favoured. The first step of these mechanisms is more possible in 4-OH groups. 3) The ester group with different aromatic and alkyl chains would enhance the antioxidant capacities of caffeic acid.
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Alcanos/química , Antioxidantes/química , Ácidos Cafeicos/química , Ésteres/química , Hidrocarbonetos Aromáticos/química , Catecóis/química , Teoria da Densidade Funcional , Radicais Livres/química , Ligação de Hidrogênio , Modelos Moleculares , Solventes/química , Relação Estrutura-AtividadeRESUMO
A light-inspired hydroxyapatite (Hap)/nitrogen-doped carbon dots (NCDs) modified graphene oxide (GO) heterojunction film is developed, which shows a promoted separation of interfacial electrons and holes and an inhibited recombination efficiency via hole depletion. The metabolism of bacteria on this film is significantly inhibited under light irradiation, due to the enhanced photocatalytic and photothermal effects. In addition, the electron transfer from the plasmonic membrane to the GO/NCD/Hap film further inhibits the adenosine triphosphate process of bacteria, thus leading to the synergetic antibacterial efficacy. Meanwhile, the electron transfer between film and cell membrane induces the Ca2+ flow after irradiation, which can promote the migration and proliferation of cells and alkaline phosphatase enhancement, thus favoring the tissue reconstruction. An in vivo test discloses that the vascular injury repair is achieved through the Ca2+-activated PLCγ1/ERK pathway, identified by the enhanced CD31 expression. Moreover, the increased CD4+/CD8+ lymphocytes are ameliorative by activating the PI3K/P-AKT pathway. Consequently, the electron transfer boosts the synergic photodynamic and photothermal therapeutic effects for bacterial infection by Ca2+ flow for immunotherapy. This mild phototherapy approach with GO/NCDs/Hap, which can simultaneously repair injured vessels and relieve inflammation reactions, will increase the clinical application of noninvasive phototherapy in the near future.
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The reaction energetics of the multiple free radical scavenging mechanisms of ellagic acid and its derivatives were studied by DFT method. Ellagic acid and its derivatives that bear catechol or guaiacyl moieties can proceed multiple free radical scavenging processes. Intramolecular hydrogen-bonds were found in the most stable geometries of the investigated compounds and can influence the antioxidant activity of the related groups and hydrogen atom/proton loss sequence. The stronger hydrogen-bond, the weaker antioxidant activity of the hydrogen atom/proton-donating group. The preferred mechanisms vary among different phases. All of the investigated compounds prefer to trap free radicals by multiple HAT mechanisms in gas and benzene phases. The second HAT reaction preferably occurs in the same catechol or guaiacyl unit of the first HAT group with the formation of stable quinone or benzodioxole. The catechol and guaiacyl moieties not only retain high free radical scavenging ability of the parent compounds but even show increased potency for the second and fourth H+/eâ reactions. In water phase, ellagic acid and its derivatives would proceed consecutively PL reactions from the OH groups. The formed di/tri/tetra-anion would proceed one/four electron transfers following with single/double SPLET mechanism and electron donation reactions until forming the stable quinone or benzodioxole.
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Ácido Elágico , Hidrogênio , Antioxidantes , Transporte de Elétrons , Ácido Elágico/farmacologia , Sequestradores de Radicais Livres , Radicais Livres , PrótonsRESUMO
In order to improve antibacterial properties and cell biocompatibility of Ti-Cu alloy, an ultrasonic micro-arc oxidation (UMAO) has been applied to Ti-Cu alloy. The corrosion resistance, antibacterial activity and cell compatibility of Ti-Cu alloy before and after UMAO were studied in detail by means of electrochemical test, plate count method and CCK-8 test scanning electron microscopy (SEM) technology to evaluate the application possibilities of UMAO as a surface bio-modification method for Ti-Cu alloy. The surface microstructure characterisation showed that a typical porous coating with a pore diameter of 3-8 µm and a thickness of 5-15 µm was formed on the surface of the Ti-Cu alloy, which significantly improved the surface roughness and hydrophilicity. The plate count method demonstrated that UMAO coatings on Ti-Cu alloy showed strong antibacterial activity (≥99%) against Staphylococcus aureus (S. aureus) even after being immersed in a physiological saline for up to 20 days, indicating that UMAO-treated Ti-Cu alloy had very strong long-term antibacterial properties. It is believed that the strong long-term antimicrobial properties of Ti-Cu-UMAO samples were mainly due to the formation of Cu2O and CuO in UMAO coatings. The results of cell compatibility evaluation showed that UMAO treatment did not bring about cytotoxicity but improved the early adhesion of MC3T3 cell.
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Ligas/farmacologia , Antibacterianos/farmacologia , Materiais Biocompatíveis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Ligas/química , Animais , Antibacterianos/química , Materiais Biocompatíveis/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Oxirredução , Propriedades de Superfície , UltrassomRESUMO
Rooperol and its derivatives, derived from the Hypoxis rooperi plant, are polyphenolic and norlignan compounds with excellent antioxidant activities. The reaction enthalpies for the free-radical scavenging by rooperol and its six derivatives were studied using density functional theory. We found that the C-H groups played a significant role in the antioxidant activities in non-polar phases. In the gas and benzene phases, rooperol and its derivatives preferentially underwent the free-radical scavenging process via the 3âCH group by following the hydrogen atom transfer (HAT) mechanism. In polar phases, the sequential proton loss electron transfer (SPLET) was the most preferred mechanism, and the phenolic OâH groups played a significant role. Additionally, we found that when the hydrogen atom in the OH group was replaced by a glucose moiety, the antioxidant activity of the adjacent OH group was reduced. ROP, DHROP-I, DHROP-II, ROP-4â³-G and ROP-4'G have catechol moiety, they may proceed double step-wise mechanisms to trap free radicals. In the gas and benzene phases, the preferable mechanism is dHAT. In water phase, it is SPLHAT.
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Antioxidantes , Catecóis , Transporte de Elétrons , PrótonsRESUMO
Clinically, methicillin-resistant Staphylococcus aureus (MRSA) biofilm infection inevitably induces the failure of bone implants. Herein, a hydrophilic and viscous hydrogel of poly(vinyl alcohol) modified with chitosan, polydopamine, and NO release donor was formed on a red phosphorus nanofilm deposited on a titanium implant (Ti-RP/PCP/RSNO). Under the irradiation of near-infrared light (NIR), peroxynitrite (â¢ONOO-) was formed by the reaction between the released NO and superoxide (â¢O2-) produced by the RP nanofilm. Specifically, we revealed the antibacterial mechanism of the ONOO- against the MRSA biofilm. In addition, osteogenic differentiation was promoted and inflammatory polarization was regulated by the released NO without NIR irradiation through upregulating the expression of Opn and Ocn genes and TNF-α. The MRSA biofilm was synergistically eradicated by â¢ONOO-, hyperthermia, and â¢O2- under NIR irradiation as well as the immunoreaction of the M1 polarization. The in vivo results also confirmed the excellent osteogenesis and biofilm eradication by released NO from the RP/PCP/RSNO system under NIR irradiation, indicating the noninvasive tissue reconstruction of MRSA-infected tissues through phototherapy and immunotherapy.
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Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Biofilmes , Imunoterapia , Osteogênese , FototerapiaRESUMO
Bacterial infection is a serious public health issue because this may cause bacterial pneumonia and bacteria-infected sepsis. The conventional antibiotic therapy can cause bacterial resistance and other adverse effects. Herein, we designed a novel photoresponsive hybrid, in which MoS2 nanosheets were doped with copper ions (MoS2@Cu2+). This system can effectively kill bacteria under 660 nm visible light irradiation due to enhanced photocatalytic and photothermal performances. The underlying mechanism is that when doping copper ions in MoS2, the photogenerated electrons can be rapidly transferred from the conduction band of MoS2 to copper ions, consequently reducing the electron-hole recombination, thereby enhancing the yield of radical oxygen species (ROS). Besides the intrinsic photothermal performance of MoS2, the Cu2+ ion can absorb photons and transfer the photoenergy into heat due to the d-d transition of electrons, resulting in enhanced photothermal properties of MoS2@Cu2+ compared with pristine MoS2. Therefore, owing to the synergistic action of hyperthermia, ROS and released Cu2+, this system exhibited highly effective antibacterial efficacy when exposed to 660 nm light for 20 min, i.e., 99.64% against Staphylococcus aureus. The cytotoxicity test showed that the synthesized MoS2@Cu2+ had good biocompatibility. This system will be a potential platform for environmental disinfection, healing of bacteria-infected wounds and other rapid bacteria-killing fields.