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Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) is important for the expression of genes associated with oxidative stress. The levels of NRF2 are controlled by Kelch-like ECH-associated protein 1 (KEAP1)-dependent degradation. Although oxidative stress is known to suppress KEAP1 activity to stabilize the levels of NRF2, the mechanism for this control is unclear. Here, we identify that KEAP1 is modified by SUMO1 at the lysine residue position 39 (K39). Arginine replacement of this lysine (K39R) in KEAP1 did not affect its stability, subcellular localization, or dimerization but promoted the formation of the Cullin 3 ubiquitin ligase and increased NRF2 ubiquitination. This was accompanied by decreased NRF2 expression. Gene reporter assays showed that the transcription of antioxidant response elements was heightened in KEAP1-WT cells compared to cells expressing the KEAP1-K39R SUMO1 substrate mutant. Consistent with this, chromatin immunoprecipitation assays revealed higher NRF2 binding to the promoter regions of antioxidant genes in cells expressing the KEAP1-WT compared to the KEAP1-K39R mutant protein in H1299 lung cancer cell. The significance of this suppression of KEAP1 activity by its SUMOylation was tested in a subcutaneous tumor model of H1299 lung cancer cell lines that differentially expressed the WT and K39R KEAP1 constructs. This model showed that mutating the SUMOylation site on KEAP1 altered the production of reactive oxygen species and suppressed tumor growth. Taken together, our study recognizes that NRF2-dependent redox control is regulated by the SUMOylation of KEAP1. These findings identify a potential new therapeutic option to counteract oxidative stress.
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The methyltransferase like 3 (METTL3) is a key component of the large N6-adenosine-methyltransferase complex in mammalian responsible for N6-methyladenosine (m6A) modification in diverse RNAs including mRNA, tRNA, rRNA, small nuclear RNA, microRNA precursor and long non-coding RNA. However, the characteristics of METTL3 in activation and post-translational modification (PTM) is seldom understood. Here we find that METTL3 is modified by SUMO1 mainly at lysine residues K177, K211, K212 and K215, which can be reduced by an SUMO1-specific protease SENP1. SUMOylation of METTL3 does not alter its stability, localization and interaction with METTL14 and WTAP, but significantly represses its m6A methytransferase activity resulting in the decrease of m6A levels in mRNAs. Consistently with this, the abundance of m6A in mRNAs is increased with re-expression of the mutant METTL3-4KR compared to that of wild-type METTL3 in human non-small cell lung carcinoma (NSCLC) cell line H1299-shMETTL3, in which endogenous METTL3 was knockdown. The alternation of m6A in mRNAs and subsequently change of gene expression profiles, which are mediated by SUMOylation of METTL3, may directly influence the soft-agar colony formation and xenografted tumor growth of H1299 cells. Our results uncover an important mechanism for SUMOylation of METTL3 regulating its m6A RNA methyltransferase activity.
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Adenosina/análogos & derivados , Metiltransferases/metabolismo , Adenosina/genética , Adenosina/metabolismo , Animais , Proteínas de Ciclo Celular , Células HeLa , Humanos , Lisina/metabolismo , Metiltransferases/genética , Camundongos Nus , Proteínas Nucleares/metabolismo , Estabilidade Proteica , Fatores de Processamento de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sumoilação , Transcriptoma , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Electromagnetic waves have caused great harm to military safety, high-frequency electronic components, and precision instruments, and so forth, which urgently requires the development of lightweight, high-efficiency, broadband electromagnetic waves (EMW) absorbing materials for protection. As the basic fibrous materials, carbon fibers (CFs) and SiC fibers (SiCf) have been widely applied in EMW absorption due to their intrinsic characteristics of low density, high mechanical properties, high conductivity, and dielectric loss mechanism. Nevertheless, it has remained a great challenge to develop lightweight EMW-absorbing fibrous materials with strong absorption capability and broad frequency range. In this review, the fundamental electromagnetic attenuation mechanisms are firstly introduced. Furthermore, the preparation, structure, morphology, and absorbing performance of CFs and SiCf-based EMW absorbing composites are summarized. In addition, prospective research opportunities are highlighted toward the development of fibrous absorbing materials with the excellent absorption performance.
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Nowadays, chronic diseases are the primary threat to public health and are getting younger. By taking the advantages of continuousness, convenience, and real-time response, wearable strain sensors have been given great attention to diagnose chronic diseases via analyzing the patient's health state. However, most physiological signals, such as limb tremor of Parkinson's disease, microexpression, and slight joint movement, are tiny and difficult to be detected. Therefore, the development of strain sensors characterized with ultrahigh sensitivity in a small strain range (ε < 10%) is urgent. Inspired by nacre's hierarchical structure, we have fabricated nacre-mimetic nanocomposites with "brick-and-mortar" architecture by employing polyacrylamide (PAM) and Ti3C2Tx MXene nanosheets through a layer-by-layer (LBL) spin-coating technique. The resultant nanocomposite-based strain sensor exhibits ultrahigh sensitivity in a small strain range (GF = 296.8, ε < 10%), attributed to the bioinspired hierarchical structure and hydrogen bond-enhanced interfacial interactions. In addition, a high reliability, broad working sensing range (453%), short response time (183 ms), skin-like tensile stress (7.2 MPa), and excellent durability (2000 cycles) are also achieved. Due to the ultrahigh sensitivity within a small strain, the reported strain sensor can accurately diagnose and distinguish Parkinson's disease symptoms, including thumb pill-rolling tremor, masked face (microexpression), intermittent shaking of the head, and limb cogwheel motion. This work provides new insights to design strain sensors with high sensitivity for monitoring tiny signals and for disease diagnosis.
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Nácar , Doença de Parkinson , Dispositivos Eletrônicos Vestíveis , Humanos , Doença de Parkinson/diagnóstico , Reprodutibilidade dos Testes , Doença CrônicaRESUMO
Inflammasome activity is important for the immune response and is instrumental in numerous clinical conditions. Here we identify a mechanism that modulates the central Caspase-1 and NLR (Nod-like receptor) adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD). We show that the function of ASC in assembling the inflammasome is controlled by its modification with SUMO (small ubiquitin-like modifier) and identify that the nuclear ZBTB16 (zinc-finger and BTB domain-containing protein 16) promotes this SUMOylation. The physiological significance of this activity is demonstrated through the reduction of acute inflammatory pathogenesis caused by a constitutive hyperactive inflammasome by ablating ZBTB16 in a mouse model of Muckle-Wells syndrome. Together our findings identify an further mechanism by which ZBTB16-dependent control of ASC SUMOylation assembles the inflammasome to promote this pro-inflammatory response.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Camundongos , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Caspase 1/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ligação Proteica , SumoilaçãoRESUMO
The leaf area index (LAI) is a very important parameter affecting land-atmosphere exchanges in land-surface processes; LAI is one of the basic feature parameters of canopy structure, and one of the most important biophysical parameters for modeling ecosystem processes such as carbon and water fluxes. Remote sensing provides the only feasible option for mapping LAI continuously over landscapes, but existing methodologies have significant limitations. To detect LAI accurately and quickly is one of tasks in the ecological and agricultural crop yield estimation study, etc. Emerging hyperspectral remote sensing sensor and techniques can complement existing ground-based measurement of LAI. Spatially explicit measurements of LAI extracted from hyperspectral remotely sensed data are component necessary for simulation of ecological variables and processes. This paper firstly summarized LAI retrieval method based on different level hyperspectral remote sensing platform (i. e., airborne, satelliteborne and ground-based); and secondly different kinds of retrieval model were summed up both at home and abroad in recent years by using hyperspectral remote sensing data; and finally the direction of future development of LAI remote sensing inversion was analyzed.
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Ecossistema , Modelos Teóricos , Folhas de Planta/química , Tecnologia de Sensoriamento Remoto/métodos , Análise Espectral/métodos , AlgoritmosRESUMO
The clinical severity of Staphylococcus aureus (S. aureus) respiratory infection correlates with antibacterial gene signature. S. aureus infection induces the expression of an antibacterial gene, as well as a central stress response gene, thus activating transcription factor 3 (ATF3). ATF3-deficient mice have attenuated protection against lethal S. aureus pneumonia and have a higher bacterial load. We tested the hypothesis that ATF3-related protection is based on the increased function of macrophages. Primary marrow-derived macrophages (BMDM) were used in vitro to determine the mechanism through which ATF3 alters the bacterial-killing ability. The expression of ATF3 correlated with the expression of antibacterial genes. Mechanistic studies showed that ATF3 upregulated antibacterial genes, while ATF3-deficient cells and lung tissues had a reduced level of antibacterial genes, which was accompanied by changes in the antibacterial process. We identified multiple ATF3 regulatory elements in the antibacterial gene promoters by chromatin immunoprecipitation analysis. In addition, Wild type (WT) mice had higher F4/80 macrophage migration in the lungs compared to ATF3-null mice, which may correlate with actin filament severing through ATF3-targeted actin-modifying protein gelsolin (GSN) for the macrophage cellular motility. Furthermore, ATF3 positively regulated inflammatory cytokines IL-6 and IL-12p40 might be able to contribute to the infection resolution. These data demonstrate a mechanism utilized by S. aureus to induce ATF3 to regulate antibacterial genes for antimicrobial processes within the cell, and to specifically regulate the actin cytoskeleton of F4/80 macrophages for their migration.
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Fator 3 Ativador da Transcrição , Staphylococcus aureus , Fator 3 Ativador da Transcrição/genética , Fator 3 Ativador da Transcrição/metabolismo , Animais , Antibacterianos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Macrófagos , Camundongos , Camundongos Knockout , Staphylococcus aureus/metabolismoRESUMO
Inflammatory bowel disease (IBD) has been reported to be associated with NLRP3 inflammasome activation. Therefore inhibiting inflammasome activation could be a new approach to treat IBD. Inflammasome inhibitors NLRP3-IN-2, JC124, and 3,4-methylenedioxy-ß-nitrostyrene (MNS) were previously reported to exert anti-inflammatory effects in various disease models but not in the dextran sulfate sodium (DSS)-induced colitis model. Here, we showed that MNS was more efficient in inhibiting the secretion of interleukin-1ß (IL-1ß) by blocking oligomerization of apoptosis-associated speck-like protein (ASC) than NLRP3-IN-2 and JC124. To investigate the protective effects of MNS on enteritis, we administered intragastric MNS to DSS-induced colitis mice. The results demonstrated that MNS attenuated DSS-induced body weight loss, colon length shortening, and pathological damage. In addition, MNS inhibited the infiltration of macrophages and inflammatory cells and reduced IL-1ß and IL-12p40 pro-inflammatory cytokines but had no significant effect on tumor necrosis factor α (TNF-α) and IL-6. Furthermore, we also found that the differentiation of IL-17A+interferon-γ (IFN-γ)+CD4+ T cell was decreased in the colon after MNS treatment, which might be mediated by IL-1ß, etc. cytokine release. Taken together, MNS alleviated DSS-induced intestinal inflammation by inhibiting NLRP3 inflammasome activation, which may function as an effective therapeutic for IBD.
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Braille recognition is of great significance for the visually impaired and blind people to achieve convenient communication and learning. A self-powered Braille recognition sensing system with long-term survivability and phonic function could provide those people with greatly enhanced access to information and thus improve their living quality. Herein, we develop a skin-like self-powered Braille recognition sensor with self-healing, temperature-resistant and stretchable properties, which is further connected with the designed audio system to realize real-time conversion from mechanical stimulus to electrical signals and then to audio signals. The sensor is fabricated using dynamic interaction-based self-healing materials, which constitute an imine bond-based cross-linked polymer for the triboelectric layer and a hydrogen bond-based organohydrogel for the electrode layer. Moreover, the conductive organohydrogel-based electrode is provided with stretchable, anti-freezing, and non-drying properties. Consequently, minimized impact on the output performance of the sensor is found under mechanical impact, harsh environments and large deformation, enabling a long lifespan, high durability, and good stability. The self-powered sensor can be applied in a Braille recognition system, in which the Braille characters can be further decoded and read out. This work shows a reliable and flexible device with promising prospects in information technology.
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Pessoas com Deficiência Visual , Eletrodos , Humanos , Iminas , Polímeros , TemperaturaRESUMO
Accumulating evidence suggests that tumor-infiltrating immune cells (TICs) in the tumor microenvironment (TME) serve as promising therapeutic targets. CXCL8 (IL-8) may also be a potential therapeutic target in cancer. CXCL8 is a potent chemotactic factor for neutrophils, myeloid-derived suppressor cells (MDSCs) and monocytes, which are considered immunosuppressive components in cancer-bearing hosts. Here, we identified the TME-related gene CXCL8 in a high-ImmuneScore population that contributed to better survival in colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) database. An integrated gene profile and functional analysis of TIC proportions revealed that the dendritic cell (DC) activation markers CD80, CD83, and CD86 were positively correlated with CXCL8 expression, suggesting that CXCL8 may be functional as antitumor immune response status in the TME. The gene signature was further validated in independent GSE14333 and GSE38832 cohorts from the Gene Expression Omnibus (GEO). To test the differential contributions of immune and tumor components to progression, three CRC cell lines, CT26, MC38 and HCT116, were used. In vitro results suggested no significant growth or survival changes following treatment with an inhibitor of the CXCL8 receptor (CXCR1/2) such as reparixin or danirixin. In vivo treatment with danirixin (antagonists of CXCR2) promoted tumor progression in animal models established with CT26 cells. CXCR2 antagonism may function via an immune component, with CXCR2 antagonist treatment in mice resulting in reduced activated DCs and correlating with decreased Interferon gamma (IFN-γ) or Granzyme B expressed CD8+ T cells. Furthermore, CXCL8 induced DC migration in transwell migration assays. Taken together, our data suggested that targeting the CXCL8-CXCR2 axis might impede DC activation or recruitment, and this axis could be considered a favorable factor rather than a target for critical antitumor effects on CRC.
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Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Células Dendríticas/patologia , Interleucina-8/metabolismo , Receptores de Interleucina-8B/metabolismo , Animais , Biomarcadores Tumorais/genética , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Células Dendríticas/metabolismo , Humanos , Interferon gama/metabolismo , Interleucina-8/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Receptores de Interleucina-8B/genética , Microambiente TumoralRESUMO
The tumor microenvironment (TME) comprises distinct cell types, including stromal types such as fibroblast cells and macrophage cells, which have recently become a critical factor in tumor development and progression. Here, we identified the TME-related gene, plexin domain containing 2 (PLXDC2), in a high-stromal-score population. And we revealed that this gene was related to poor survival and advanced (tumor-node-metastasis) stage in gastric cancer (GC) patients from The Cancer Genome Atlas database. An integrated gene profile and functional analysis of the proportions of tumor-infiltrating immune cells revealed that the expression of the M2 macrophages cell marker CD163 was positively correlated with PLXDC2 expression. In addition, the M2 macrophages gene signature and high PLXDC2 expression were associated with the inflammatory signaling pathway and the epithelial-to-mesenchymal transition (EMT)-related gene signature. Single-cell study of GC identified PLXDC2 was enriched specifically in fibroblasts and monocytes/macrophages populations, which supported its important role in the stroma. Furthermore, according to a tissue microarray immunohistochemistry analysis, the expression of PLXDC2 elevated in human GC stromal specimens compared to tumor tissue specimens. Moreover, PLXDC2 overexpression in the stromal compartment was associated with CD163-positive regulatory M2 macrophages, and its functions were related to the pathogenesis of GC. Multiplexed immunohistochemistry verified PLXDC2's correlation with EMT markers. Our data suggested that PLXDC2 was expressed in stromal cells and that its crosstalk with tumor-associated macrophages could contribute to cancer biology by inducing the EMT process.
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Recently, flexible electronics have been paid great attention due to their unique characteristics, such as high stretchability, arbitrary bending, and recoverable deformation. As a core component, flexible conductive materials with skin-like properties are desirable and valuable for the development of flexible electronics. However, the integration of skin-like mechanical properties, inherent self-healing ability, ultrahigh sensitivity, and electrical conductivity into one material is difficult to be realized. Here, this study reports a kind of conductive film (PAM-dc-fGO) fabricated by cross-linking intrinsic self-repair polyazomethine (PAM) and ethylenediamine-functionalized graphene oxide (fGO) through dynamic covalent bonds (imine bonds, -CHâN-). The as-prepared conductive films exhibit skin-like mechanical properties with a stretchability of 212-275% and elastic moduli of 0.76-4.23 MPa. In addition, the healing efficiency in mechanical properties of the 24 h healed specimen can restore up to 99%, and the healing efficiency in terms of electrical conductivity still maintains above 95% after five breaking/healing cycles, indicating an excellent capability of self-repair. Due to the ultrahigh sensing sensitivity with the gauge factor (GF) of 641, the PAM-dc-fGO film-based strain sensor can precisely detect the weak signals from the human body. Moreover, the remote monitoring of human motions with a long distance of about 100 cm has been successfully conducted by a PAM-dc-fGO proximity sensor. This work provides a new path for the development of multifunctional soft materials, and the sensors show great potential in health diagnoses and security protection applications.
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Condutividade Elétrica , Movimento/fisiologia , Dispositivos Eletrônicos Vestíveis , Módulo de Elasticidade , Etilenodiaminas/química , Grafite/química , Humanos , Hidrogéis/química , Fenômenos Fisiológicos da Pele , Transistores EletrônicosRESUMO
Long-term live cell tracking is desirable and necessary to understand the dynamics and complexity of biological interactions in stem cells and cancer cells. Conventional live cells fluorescence trackers are generally non-degradable and are showing increased toxicity concerns during the long-term application. Previously we developed biodegradable fluorescent poly(citrate)-based hybrid elastomers for bone regeneration applications. Here, we fabricated the photoluminescent poly(citrate-siloxane) nanoparticles (PCSNPs) through an oil/water emulsion method and demonstrated their long-term live stem cells/cancer cells imaging applications. PCSNPs showed a uniform size distribution (mean diameter 120â¯nm) and highly stable dispersability (above 30â¯days) in various physiological medium, as well as excellent fluorescent properties and photostability. PCSNPs possess excellent cellular biocompatibility, which could be efficiently internalized by cells and selectively image the cell lysosome with a high photostability. Compared with commercial Cell Tracker™ Green and Cell Tracker™ Red, the adipose-derived mesenchymal stem cells or human hepatoma cells were stably labeled by PCSNPs for over 14â¯days as they grew and developed (7 passages). Additionally, PCSNPs efficiently tracked cells up to 7â¯days in vivo through a non-invasively way compared with 1â¯day of commercial tracker. This study demonstrates an important strategy to design biodegradable multifunctional delivery platforms for biomedical applications such as long-term bioimaging.
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Rastreamento de Células/métodos , Elastômeros , Medições Luminescentes/métodos , Teste de Materiais , Células-Tronco Mesenquimais/citologia , Siloxanas , Elastômeros/química , Elastômeros/farmacologia , Células Hep G2 , Humanos , Células-Tronco Mesenquimais/metabolismo , Nanopartículas/química , Siloxanas/química , Siloxanas/farmacologiaRESUMO
Artificial muscle-like biomaterials have gained tremendous interests owing to their broad applications in regenerative medicine, wearable devices, bioelectronics and artificial intelligence. Unfortunately, key challenges are still existed for current materials, including biomimetic viscoelasticity, biocompatibility and biodegradation, multifunctionality. Herein, for the first time, we develop highly elastomeric, conductive and biodegradable poly (citric acid-octanediol-polyethylene glycol)(PCE)-graphene (PCEG) nanocomposites, and demonstrate their applications in myogenic differentiation and guiding skeletal muscle tissue regeneration. In PCEG nanocomposites, PCE provides the biomimetic elastomeric behavior, and the addition of reduced graphene oxide (RGO) endows the enhanced mechanical strength and conductivity. The highly elastomeric behavior, significantly enhanced modulus (400%-800%), strength (200%-300%) of PCEG nanocomposites with controlled biodegradability and electrochemical conductivity were achieved. The myoblasts proliferation and myogenic differentiation were significantly improved by PCEG nanocomposite. Significantly high in vivo biocompatibility of PCEG nanocomposites was observed when implanted in the subcutaneous tissue for 4 weeks in rats. PCEG nanocomposites could significantly enhance the muscle fibers and blood vessels formation in vivo in a skeletal muscle lesion model of rat. This study may provide a novel strategy to develop multifunctional elastomeric nanocomposites with high biocompatibility for potential soft tissue regeneration and stretchable bioelectronic devices.
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Biomimética , Diferenciação Celular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Nanocompostos/química , Polímeros/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citratos/química , Elastômeros , Condutividade Elétrica , Grafite/química , Masculino , Teste de Materiais , Camundongos , Desenvolvimento Muscular/efeitos dos fármacos , Músculo Esquelético/citologia , Polímeros/administração & dosagem , Polímeros/química , Ratos , Ratos Sprague-Dawley , Medicina Regenerativa , Engenharia TecidualRESUMO
Native human tissues possess incomparable biological performance due to their strong and viscoelastic mechanical properties, and biocompatible compositions. Herein, by a thermal polymerization and solvent hybridization method, we develop biomimetic polycitrate-gelatin hybrid polymers (PC-GT) with strong mechanical properties and tailored elastomeric behavior for tissue regeneration applications. The incorporation of gelatin significantly enhanced the mechanical properties and cellular biocompatibility of PC. PC-GT hybrids demonstrated the 135 times (from 7.5 to 1015MPa) and 11 times (from 4 to 46MPa) improvement for the elastomeric modulus and tensile strength respectively as compared with PC elastomers, while showing controlled stretchable and elastomeric behavior. In addition, PC-GT hybrids significantly improved the fibroblasts (L929) attachment and proliferation, suggesting their high biocompatibility. This study may provide a novel strategy to design biocompatible hybrid polymers with strong and elastomeric behavior for tissue regeneration and stretchable electronic devices applications.
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Elastômeros , Fibroblastos/metabolismo , Gelatina , Animais , Linhagem Celular , Ácido Cítrico/química , Ácido Cítrico/farmacologia , Elastômeros/química , Elastômeros/farmacologia , Gelatina/química , Gelatina/farmacologia , Teste de Materiais , CamundongosRESUMO
Biodegradable elastomeric biomaterials have attracted much attention in tissue engineering due to their biomimetic viscoelastic behavior and biocompatibility. However, the low mechanical stability at hydrated state, fast biodegradation in vivo, and poor osteogenic activity greatly limited bioelastomers applications in bone tissue regeneration. Herein, we develop a series of poly(octanediol citrate)-polyhedral oligomeric silsesquioxanes (POC-POSS) hybrids with highly tunable elastomeric behavior (hydrated state) and biodegradation and osteoblasts biocompatibility through a facile one-pot thermal polymerization strategy. POC-POSS hybrids show significantly improved stiffness and ductility in either dry or hydrated conditions, as well as good antibiodegradation ability (20-50% weight loss in 3 months). POC-POSS hybrids exhibit significantly enhanced osteogenic differentiation through upregulating alkaline phosphatase (ALP) activity, calcium deposition, and expression of osteogenic markers (ALPL, BGLAP, and Runx2). The high mechanical stability at hydrated state and enhanced osteogenic activity make POC-POSS hybrid elastomers promising as scaffolds and nanoscale vehicles for bone tissue regeneration and drug delivery. This study may also provide a new strategy (controlling the stiffness under hydrated condition) to design advanced hybrid biomaterials with high mechanical properties under physiological condition for tissue regeneration applications.
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Materiais Biocompatíveis/química , Plásticos Biodegradáveis/química , Regeneração Óssea , Osteogênese/efeitos dos fármacos , Engenharia Tecidual , Materiais Biocompatíveis/uso terapêutico , Plásticos Biodegradáveis/uso terapêutico , Osso e Ossos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Ácido Cítrico/química , Elastômeros/química , Elastômeros/uso terapêutico , Humanos , Fenômenos Mecânicos , Osteoblastos/efeitos dos fármacos , Resistência à Tração , Alicerces TeciduaisRESUMO
Biodegradable polymer biomaterials with intrinsical photoluminescent properties have attracted much interest, due to their potential advantages for tissue regeneration and noninvasive bioimaging. However, few of current biodegradable polymers possess tunable intrinsically fluorescent properties, such as high photostability, fluorescent lifetime, and quantum field, and strong mechanical properties for meeting the requirements of biomedical applications. Here, by a facile one-step thermal polymerization, elastomeric poly(silicone-citrate) (PSC) hybrid polymers are developed with controlled biodegradability and mechanical properties, tunable inherent fluorescent emission (up to 600 nm), high photostability (beyond 180 min for UV and six months for natural light), fluorescent lifetime (near 10 ns) and quantum yield (16%-35%), high cellular biocompatibility, and minimal inflammatory response in vivo, which provide advantages over conventional fluorescent dyes, quantum dots, and current fluorescent polymers. The promising applications of PSC hybrids for cell and implants imaging in vitro and in vivo are successfully demonstrated. The development of elastomeric PSC polymer may provide a new strategy in synthesizing new inorganic-organic hybrid photo-luminescent materials for tissue regeneration and bioimaging applications.
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Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Citratos/química , Polímeros/química , Regeneração/efeitos dos fármacos , Silício/química , Animais , Células Cultivadas , Citratos/administração & dosagem , Diagnóstico por Imagem/métodos , Elasticidade/efeitos dos fármacos , Elastômeros , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/química , Camundongos , Polímeros/administração & dosagem , Pontos Quânticos/administração & dosagem , Pontos Quânticos/química , Silício/administração & dosagemRESUMO
Ketogulonicigenium vulgare has been widely used in vitamin C two-step fermentation, which converts l-sorbose to 2-keto-l-gluonic acid. Here, the complete genome of K. vulgare SKV, which performs better fermentation production than K. vulgare Hbe602, is deciphered to understand the key differences in metabolism between K. vulgare strains SKV and Hbe602.
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Prostate cancer (PCa) is the second leading cause of cancer-related deaths in north American men, and most its related deaths are due to advanced and metastatic PCa. However, the molecular mechanisms underlying PCa progression are still unclear. Here we use a pair of prostate cell lines P69/M12, which have the same genetic background and the highly metastatic cell line M12 is a subline derived from P69, to identify the pathogenesis of PCa. We find that a key miRNA--miR186 is significantly reduced in M12 compared to that in P69. Further, we validate that miR186 is also downregulated in human PCa specimens, most significantly in the metastatic patient specimens. The low miR186 expression is correlated with poor patient survival. Through knockdown or overexpression of miR186 in PCa cell lines, we discover that miR186 strongly inhibits cell motility, invasive, soft-agar colony formation, 3D culture growth and vasculogenic mimicry (VM) formation capacity, as well as the epithelial-to-mesenchymal transition (EMT) process by downregulation of its target Twist1. Moreover, the inverse relationship between the expression levels of miR186 and Twist1 is confirmed in vivo tumor metastasis experiment and clinical specimens. Taken together, our findings demonstrate an important role of miR186/Twist1 axis in the regulation of PCa progression, suggesting a potential application of miR186/Twist1 in PCa treatment.
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MicroRNAs/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias da Próstata/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Regulação para Baixo , Humanos , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/biossíntese , MicroRNAs/genética , Proteínas Nucleares/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Transdução de Sinais , Proteína 1 Relacionada a Twist/genéticaRESUMO
Biodegradable poly(glycerol sebacate) (PGS) elastomers have received much attention as promising materials for potential applications in soft tissue repair and regeneration, due to their biomimetic viscoelastic properties. However, the low strength and the absence of bioactivity have limited their potential applications in hard (bone, tooth, tendon and ligament) tissue regeneration. Here, we introduced the molecular-level silica bioactive glass into the matrix of polymer elastomers to prepare bioactive hybrid elastomers (PGSSC) for bone tissue regeneration applications. We have shown here that our PGSSC provide some advantages over conventional bioactive materials and elastomers due to their controlled biomineralization (apatite-forming bioactivity), tunable elastic properties and biodegradation, and enhanced osteoblast proliferation. The tensile strength and the initial modulus of PGSSC hybrid elastomers ranged from 1 to 5 MPa and 2 to 32 MPa respectively by controlling silica phase contents, which are several times higher than pure PGS elastomers. PGSSC elastomers also showed enhanced hydrophilicity with contact angle ranging from 75 to 25 degree. The biological apatite was formed on the surfaces of PGSSC when soaked in simulated body fluid (SBF) for 1 day. The osteoblast (MC3T3) demonstrated significantly enhanced proliferation on PGSSC compared with PGS. The development of bioactive PGSSC hybrid elastomers may offer a new choice for bone tissue repair and regeneration.