RESUMO
Recombinant proteins hold significant importance in numerous disciplines. As the demand for expressing and purifying these proteins grows, the scientific community is in dire need of a simple yet versatile methodology that can efficiently purify these proteins. Aptamers as synthetic nucleic acid-based ligands with high affinity have shown promise in this regard, as they can capture targets through molecular recognition. In this study, novel aptamer-functionalized polydopamine-coated magnetic graphene oxide nanocomposites were facilely prepared, achieving an impressive average aptamer coverage density (45 nmol/mg). These nanocomposites exhibited a uniform structure and robust magnetic responsiveness. The findings indicated that they possess several advantages, such as rapid adsorption, substantial capacity (171.4 mg/g), and excellent reusability. Notably, due to the inherent properties of nucleic acids, the immobilized aptamer-magnetic beads can be utilized repeatedly with high purification efficiency. Finally, the nanocomposites were further employed to purify His-tagged proteins from actual samples. Remarkably, they were able to selectively and efficiently isolate His-tagged retinoid X receptor alpha protein from complex Escherichia coli lysate. The purified His-tagged retinoid X receptor alpha protein was analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. This confirmed the efficacy of developed nanocomposites, reinforcing their vast potential for purification of His-tagged recombinant proteins.
Assuntos
Aptâmeros de Nucleotídeos , Grafite , Indóis , Nanocompostos , Polímeros , Grafite/química , Polímeros/química , Polímeros/síntese química , Indóis/química , Aptâmeros de Nucleotídeos/química , Nanocompostos/química , Histidina/química , Escherichia coli , Tamanho da Partícula , Adsorção , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/químicaRESUMO
BACKGROUND: Effective treatments for the alveolar bone defect remain a major concern in dental therapy. The objectives of this study were to develop a fibrin and konjac glucomannan (KGM) composite hydrogel as scaffolds for the osteogenesis of nasal mucosa-derived ectodermal mesenchymal stem cells (EMSCs) for the regeneration of alveolar bone defect, and to investigate the osteogenesis-accelerating effects of black phosphorus nanoparticles (BPNs) embedded in the hydrogels. METHODS: Primary EMSCs were isolated from rat nasal mucosa and used for the alveolar bone recovery. Fibrin and KGM were prepared in different ratios for osteomimetic hydrogel scaffolds, and the optimal ratio was determined by mechanical properties and biocompatibility analysis. Then, the optimal hydrogels were integrated with BPNs to obtain BPNs/fibrin-KGM hydrogels, and the effects on osteogenic EMSCs in vitro were evaluated. To explore the osteogenesis-enhancing effects of hydrogels in vivo, the BPNs/fibrin-KGM scaffolds combined with EMSCs were implanted to a rat model of alveolar bone defect. Micro-computed tomography (CT), histological examination, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were conducted to evaluate the bone morphology and expression of osteogenesis-related genes of the bone regeneration. RESULTS: The addition of KGM improved the mechanical properties and biodegradation characteristics of the fibrin hydrogels. In vitro, the BPNs-containing compound hydrogel was proved to be biocompatible and capable of enhancing the osteogenesis of EMSCs by upregulating the mineralization and the activity of alkaline phosphatase. In vivo, the micro-CT analysis and histological evaluation demonstrated that rats implanted EMSCs-BPNs/fibrin-KGM hydrogels exhibited the best bone reconstruction. And compared to the model group, the expression of osteogenesis genes including osteopontin (Opn, p < 0.0001), osteocalcin (Ocn, p < 0.0001), type collagen (Col , p < 0.0001), bone morphogenetic protein-2 (Bmp2, p < 0.0001), Smad1 (p = 0.0006), and runt-related transcription factor 2 (Runx2, p < 0.0001) were all significantly upregulated. CONCLUSIONS: EMSCs/BPNs-containing fibrin-KGM hydrogels accelerated the recovery of the alveolar bone defect in rats by effectively up-regulating the expression of osteogenesis-related genes, promoting the formation and mineralisation of bone matrix.
Assuntos
Regeneração Óssea , Fibrina , Hidrogéis , Mananas , Células-Tronco Mesenquimais , Osteogênese , Fósforo , Ratos Sprague-Dawley , Alicerces Teciduais , Animais , Regeneração Óssea/efeitos dos fármacos , Ratos , Mananas/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Microtomografia por Raio-X , Nanopartículas , Mucosa Nasal , Processo Alveolar , Masculino , Proteína Morfogenética Óssea 2 , Subunidade alfa 1 de Fator de Ligação ao Core , OsteocalcinaRESUMO
Adhesives are applied extensively in daily life and industries, and people have developed numerous commercial polymeric adhesives. However, in most cases, these adhesives work on dry surfaces in air and form permanent bonds with the substrates, limiting the applications of adhesives. Inspired by the innate adhesive functions of some animals, such as geckos, spiders, mussels, and clingfish, scientists have developed various adhesive compositions and structures to meet various conditions. Here, we show a versatile subnanometer nanowire (SNW) adhesive with high strength and great reversibility, which could be prepared at a large scale through a facile room-temperature reaction. The SNW adhesive contacts the substrates at multiple sites due to the ultrahigh flexibility, and meanwhile, the multilevel interactions among the SNWs endow them with strong cohesion, so they exhibit good adhesive performance. This adhesive is applicable to various substrates, such as metals, polymers, and glass, and not only possesses good stability at room temperature in air but also is suitable for underwater environments and ultralow temperatures. Moreover, this adhesive could be easily recycled and removed from the substrates without any residue and damage. The SNW adhesive not only inspires the design of hierarchical adhesive structures with new contact modes but also has potential for practical applications.
Assuntos
Bivalves , Nanofios , Aranhas , Adesivos/química , Animais , Humanos , Polímeros/químicaRESUMO
PURPOSE: Lipid nanoparticles (LNPs) are widely utilized as means to deliver mRNA molecules. However, metric connections between biodistribution and pharmacokinetics (PK) of the nanoparticle carrier and transgene expression dynamics remain largely unknown. METHODS: LNPs containing mRNAs encoding the firefly luciferase gene were prepared with varying sizes. Biodistributions of injected LNPs in mice were measured by fluorescence bioimaging or liquid chromatography with tandem mass spectrometry. In addition, luciferase expression levels were determined by bioluminescence imaging and enzyme activity assays. RESULTS: Some intramuscularly injected LNPs were found circulating in the system, resulting in accumulation in the liver and spleen, especially when the LNP sizes were relatively small. Bigger LNPs were more likely to remain at the injection site. Transgene expression in the liver was found most prominent compared with other organs and tissues. CONCLUSIONS: Biomolecules such as mRNAs encapsulated in locally injected LNPs can reach other organs and tissues via systemic circulation. Gene expression levels are affected by the LNP biodistribution and pharmacokinetics (PK), which are further influenced by the particle size and injection route. As transfection efficiency varies in different organs, the LNP exposure and mRNA expression are not linearly correlated.
Assuntos
Nanopartículas , Animais , Expressão Gênica , Lipossomos , Camundongos , Nanopartículas/química , Tamanho da Partícula , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Distribuição TecidualRESUMO
OBJECTIVE: To investigate the disparity in dental caries between native and migrant children in Shanghai, China. METHODS: Between 2013 and 2015, a random cluster sample of native and migrant children aged 5, 9, 12 and 15 years was collected from each district in Shanghai. Oral examination was performed following the World Health Organization (WHO) method, and findings were reported as decayed-missing-filled teeth of primary dentition (dmft) and permanent dentition (DMFT). RESULTS: A total of 10 150 children were examined, and 33.6% of them were migrants. Migrant children had a higher prevalence of deciduous caries than native children (the 5-year-old age group, 67.8% vs 63.0%, P = 0.024; the 9-year-old age group, 75.9% vs 66.1%, P < 0.001), and higher dmft values were found in migrant children. But with respect to permanent teeth, no statistical differences were found between the two groups in caries prevalence or DMFT. After controlling for potential confounders by logistic regression, migrant children showed a higher risk of deciduous caries (odds ratio 1.42, 95% confidence interval 1.25-1.61, P < 0.001) but not of permanent caries. Migrant children exhibited relatively lower deciduous Restorative Care Index (RCI). However, 9- and 15-year-old migrant children had a higher permanent RCI than their native counterparts. CONCLUSIONS: Dental caries prevalence in migrant children was higher in the deciduous teeth but not in the permanent teeth compared to that in their native counterparts. School-based dental public health services may contribute to reducing the disparity in dental health status between migrant and native children.
Assuntos
Cárie Dentária , Migrantes , Adolescente , Criança , Pré-Escolar , China , Estudos Transversais , Índice CPO , Humanos , PrevalênciaRESUMO
BACKGROUND: During fresh fruit consumption, sensory texture is one factor that affects the organoleptic qualities. Chemical components of plant cell walls, including pectin, cellulose, hemicellulose and lignin, play central roles in determining the textural qualities. To explore the genes and regulatory pathways involved in fresh citrus' perceived sensory texture, we performed mRNA-seq analyses of the segment membranes of two citrus cultivars, Shiranui and Kiyomi, with different organoleptic textures. RESULTS: Segment membranes were sampled at two developmental stages of citrus fruit, the beginning and end of the expansion period. More than 3000 differentially expressed genes were identified. The gene ontology analysis revealed that more categories were significantly enriched in 'Shiranui' than in 'Kiyomi' at both developmental stages. In total, 108 significantly enriched pathways were obtained, with most belonging to metabolism. A detailed transcriptomic analysis revealed potential critical genes involved in the metabolism of cell wall structures, for example, GAUT4 in pectin synthesis, CESA1, 3 and 6, and SUS4 in cellulose synthesis, CSLC5, XXT1 and XXT2 in hemicellulose synthesis, and CSE in lignin synthesis. Low levels, or no expression, of genes involved in cellulose and hemicellulose, such as CESA4, CESA7, CESA8, IRX9 and IRX14, confirmed that secondary cell walls were negligible or absent in citrus segment membranes. A chemical component analysis of the segment membranes from mature fruit revealed that the pectin, cellulose and lignin contents, and the segment membrane's weight (% of segment) were greater in 'Kiyomi'. CONCLUSION: Organoleptic quality of citrus is easily overlooked. It is mainly determined by sensory texture perceived in citrus segment membrane properties. We performed mRNA-seq analyses of citrus segment membranes to explore the genes and regulatory pathways involved in fresh citrus' perceived sensory texture. Transcriptomic data showed high repeatability between two independent biological replicates. The expression levels of genes involved in cell wall structure metabolism, including pectin, cellulose, hemicellulose and lignin, were investigated. Meanwhile, chemical component contents of the segment membranes from mature fruit were analyzed. This study provided detailed transcriptional regulatory profiles of different organoleptic citrus qualities and integrated insights into the mechanisms affecting citrus' sensory texture.
Assuntos
Parede Celular/metabolismo , Citrus/citologia , Citrus/metabolismo , Frutas/metabolismo , Perfilação da Expressão Gênica , Paladar , Lignina/metabolismo , Membranas/citologia , Pectinas/metabolismo , Polissacarídeos/metabolismoRESUMO
BACKGROUND/AIMS: Excessive fluoride intake can induce cytotoxicity, DNA damage and cell-cycle changes in many tissues and organs, including the kidney. However, the underlying molecular mechanisms of fluoride-induced renal cell-cycle changes are not well understood at present. In this study, we used a mouse model to investigate how sodium fluoride (NaF) induces cell-cycle changes in renal cells. METHODS: Two hundred forty ICR mice were randomly assigned to four equal groups for intragastric administration of NaF (0, 12, 24 and 48 mg/kg body weight/day) for 42 days. Kidneys were taken to measure changes of the cell-cycle at 21 and 42 days of the experiment, using flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot methods. RESULTS: NaF, at more than 12 mg/kg body weight, induced G2/M phase cell-cycle arrest in the renal cells, which was supported by the finding of significantly increased percentages of renal cells in the G2/M phase. We found also that G2/M phase cell-cycle arrest was accompanied by up-regulation of p-ATM, p-Chk2, p-p53, p-Cdc25C, p-CDK1, p21, and Gadd45a protein expression levels; up-regulation of ATM, Chk2, p53, p21, and Gadd45a mRNA expression levels; down-regulation of CyclinB1, mdm2, PCNA protein expression levels; and down-regulation of CyclinB1, CDK1, Cdc25C, mdm2, and PCNA mRNA expression levels. CONCLUSION: In this mouse model, NaF, at more than 12 mg/ kg, induced G2/M phase cell-cycle arrest by activating the ATM-Chk2-p53/Cdc25C signaling pathway, which inhibits the proliferation of renal cells and development of the kidney. Activation of the ATM-Chk2-p53/Cdc25C signaling pathway is the mechanism of NaF-induced renal G2/M phase cell-cycle arrest in this model.
Assuntos
Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Rim/efeitos dos fármacos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fluoreto de Sódio/efeitos adversos , Animais , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Quinase do Ponto de Checagem 2/metabolismo , Feminino , Rim/citologia , Rim/metabolismo , Rim/patologia , Camundongos , Camundongos Endogâmicos ICR , Proteína Supressora de Tumor p53/metabolismo , Fosfatases cdc25/metabolismoRESUMO
PURPOSE: To identify mutations in COL2A1 and COL11A1 genes and to examine the genotype-phenotype correlation in a cohort of Chinese patients with Stickler syndrome. METHODS: A total of 16 Chinese probands with Stickler syndrome were recruited, including nine with a family history of an autosomal dominant pattern and seven sporadic cases. All patients underwent full ocular and systemic examinations. Sanger sequencing was used to analyze all coding and adjacent regions of the COL2A1 and COL11A1 genes. Multiplex ligation-dependent probe amplification was performed to detect the gross indels of COL2A1 and COL11A1. Bioinformatics analysis was performed to evaluate the pathogenicity of the variants. RESULTS: Five mutations in COL2A1 were identified in six of 16 probands, including three novel (c.85C>T, c.3356delG, c.3401delG) mutations and two known mutations (c.1693C>T, c.2710C>T). Of the five mutations, three were truncated mutations, and the other two were missense mutations. Putative pathogenic mutations of the COL11A1 gene were absent in this cohort of patients. Gross indels were not found in COL2A1 or COL11A1 in any of the probands. High myopia was the most frequent initial ocular phenotype of Stickler syndrome. In this study, 12 Chinese probands lacked obvious systemic phenotypes. CONCLUSIONS: In this study, three novel and two known mutations in the COL2A1 gene were identified in six of 16 Chinese patients with Stickler syndrome. This is the first study in a cohort of Chinese patients with Stickler syndrome, and the results expand the mutation spectrum of the COL2A1 gene. Analysis of the genotype-phenotype correlation showed that the early onset of high myopia with vitreous abnormalities may serve as a key indicator of Stickler syndrome, while the existence of mandibular protrusion in pediatric patients may be an efficient indicator for the absence of mutations in COL2A1 and COL11A1.
Assuntos
Artrite/genética , Povo Asiático/genética , Colágeno Tipo II/genética , Colágeno Tipo XI/genética , Doenças do Tecido Conjuntivo/genética , Perda Auditiva Neurossensorial/genética , Mutação , Descolamento Retiniano/genética , Adolescente , Adulto , Artrite/diagnóstico , Criança , Pré-Escolar , China/epidemiologia , Doenças do Tecido Conjuntivo/diagnóstico , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Perda Auditiva Neurossensorial/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Miopia/diagnóstico , Miopia/genética , Linhagem , Descolamento Retiniano/diagnósticoRESUMO
Toxic cyanobacterial blooms have occurred in various water bodies during recent decades and made serious health hazards to plants, animals and humans. Iron is an important micronutrient for algal growth and recently, the concentration of which has increased remarkably in freshwaters. In this paper, the cyanobacterium Microcystis aeruginosa FACHB-905 was cultivated under non-iron (0µM), iron-limited (10µM) and iron-replete (100µM) conditions to investigate the effects of iron on growth, antioxidant enzyme activity, EPS and microcystin production. The results showed that algal cell density and chlorophyll-a content were maximal at the highest iron concentration. Antioxidant enzymes activity increased notably under all three conditions in the early stage of experiment, of which the SOD activity recovered soon from oxidative stress in 10µM group. The productions of some protein-like substances and humic acid-like substances of bound EPS were inhibited in iron-containing groups in the early stage of experiment while promoted after the adaptation period of Microcystis aeruginosa. Iron addition is a factor affecting the formation of cyanobacterial blooms through its impact on the content of LB-EPS and the composition of TB-EPS. The intracellular MC-LR concentration and the productivity potential of MC-LR were the lowest in 0µM group and highest in 10µM group. No obvious extracellular release of MC-LR was observed during the cultivation time. Therefore, iron addition can promote the physiological activities of M. aeruginosa, but a greater harm could be brought into environment under iron-limited (10µM) condition than under iron-replete (100µM) condition.
Assuntos
Antioxidantes/metabolismo , Ferro/farmacologia , Microcistinas/biossíntese , Microcystis , Polímeros/análise , Clorofila/metabolismo , Clorofila A , Água Doce , Substâncias Húmicas/análise , Ferro/metabolismo , Microcystis/efeitos dos fármacos , Microcystis/enzimologia , Microcystis/crescimento & desenvolvimento , Oxirredução , Polímeros/metabolismo , Oligoelementos/metabolismoRESUMO
Noble metal nanocrystals have been extensively utilized as promising catalysts for chemical transformations and energy conversion. One of their significant applications lies in electrode materials in fuel cells (FCs) due to their superior electrocatalytic performance towards the reactions both on anode and cathode. Nowadays, tremendous efforts have been devoted to improve the catalytic performance and minimize the usage of precious metals. Constructing multicomponent noble metal nanocrystals with complex structures provides the opportunity to reach this goal due to their highly tunable compositions and morphologies, leading to the modification of the related electrochemical properties. In this review, we first highlight the recent advances in the controllable synthesis of noble metal alloy complex nanostructures including nanoframes/nanocages, branched structures, concave/convex structures, core-shell structures and ultrathin structures. Then the effects of the well-defined nanocrystals on the modified and improved electrochemical properties are outlined. Finally, we make a conclusion with the points on the challenges and perspectives of the controllable synthesis of noble metal alloy complex nanostructures and their electrocatalytic performance.
Assuntos
Ligas , Nanopartículas Metálicas , Metais Pesados , Catálise , Eletroquímica , NanotecnologiaRESUMO
Using bone regeneration scaffolds to repair craniomaxillofacial bone defects is a promising strategy. However, most bone regeneration scaffolds still exist some issues such as a lack of barrier structure, inability to precisely match bone defects, and necessity to incorporate biological components to enhance efficacy. Herein, inspired by a periosteum-bone complex, a class of multifunctional hierarchical porous poly(lactic-co-glycolic acid)/baicalein scaffolds is facilely prepared by the union of personalized negative mold technique and phase separation strategy and demonstrated to precisely fit intricate bone defect cavity. The dense up-surface of the scaffold can prevent soft tissue cell penetration, while the loose bottom-surface can promote protein adsorption, cell adhesion, and cell infiltration. The interior macropores of the scaffold and the loaded baicalein can synergistically promote cell differentiation, angiogenesis, and osteogenesis. These findings can open an appealing avenue for the development of personalized multifunctional hierarchical materials for bone repair.
Assuntos
Regeneração Óssea , Periósteo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Engenharia Tecidual , Alicerces Teciduais , Alicerces Teciduais/química , Regeneração Óssea/fisiologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Porosidade , Engenharia Tecidual/métodos , Osteogênese/fisiologia , Diferenciação Celular , Humanos , Modelos Animais de Doenças , Materiais Biocompatíveis/química , CamundongosRESUMO
Plastic debris has recently been proposed as a novel habitat for bacterial colonization, which can raise perturbations in bacterial ecology after burial in riverine sediments. However, community coalescence, as a prevalent process involving the interrelationships of multiple communities and their surrounding environments, has been rarely discussed to reveal the impact of the plastisphere on sedimentary bacterial community. This study analyzed the bacterial community in plastic debris and sediment along the Nujiang River, elucidating the role of the plastisphere in mediating community coalescence in sediments. Our results demonstrated that the plastisphere and sedimentary bacterial communities exhibited distinct biogeography along the river (r = 0.694, p < 0.01). Based on overlapped taxa and SourceTracker, the extent of coalescence between adjacent communities was in following orders: plastic-plastic (0.589) > plastic-sediment (0.561) > sediment-sediment (0.496), indicating the plastisphere promoted bacterial community coalescence along the river. Flow velocity and geographic distance were the major factors driving the plastisphere changes, suggesting that the plastisphere were vulnerable to dispersal. The null model and the neutral model provided additional support for the higher immigration ability of the plastisphere to overcome dispersal limitation, highlighting the potential importance of the plastisphere in community coalescence. Network analysis indicated the critical role of keystone species (Proteobacteria, Bacteroidetes, and Gemmatimonadetes) in mediating the coalescence between sedimentary bacterial community and the plastisphere. In summary, the plastisphere could mediate the coalescence of bacterial communities by overcoming dispersal limitation, which provides new perspectives on the plastisphere altering bacterial ecology in riverine sediments.
Assuntos
Bactérias , Sedimentos Geológicos , Plásticos , Rios , Rios/microbiologia , Rios/química , Sedimentos Geológicos/microbiologia , Sedimentos Geológicos/química , Bactérias/classificação , China , Microbiota , Monitoramento Ambiental , Resíduos/análise , Poluentes Químicos da Água/análiseRESUMO
Uniform Pt-Cu alloy nanocrystals in the shape of dendrite, yolk-cage, and box structures are prepared via a facile wet-chemical reduction route in which glycine is demonstrated to alter the reduction kinetics of metal cations, critical to the morphology of the obtained product. These alloy nanocrystals exhibit superior specific activity and stability in the electro-oxidation of methanol.
Assuntos
Ligas/química , Glicina/química , Nanopartículas/química , Paládio/química , Platina/química , Eletroquímica/métodos , CinéticaRESUMO
Introduction: The oral cavity and the gut tract are interconnected, and both contain abundant natural microbiota. Gut microbiota may interact with oral flora and participate in the development of periodontitis. However, the specific role of certain gut microbiota taxa for periodontitis has not been investigated. Mendelian Randomization is an ideal method to explore causal relationships avoiding reverse causality and potential confounding factors. Thus, we conducted a two-sample Mendelian Randomization study to comprehensively reveal the potential genetic causal effect of gut microbiota on periodontitis. Methods: SNPs strongly associated with 196 gut microbiota taxa (18,340 individuals) were selected as instrument variables, and periodontitis (17,353 periodontitis cases and 28,210 controls) was used as the outcome. The causal effect was analyzed via random effect inverse variance-weighted, weighted median, and MR-Egger. The sensitivity analyses were conducted using Cochran's Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests. Results: Nine gut microbiota taxa (Prevotella 7, Lachnospiraceae UCG-008, Enterobacteriales, Pasteurellales, Enterobacteriaceae, Pasteurellaceae, Bacteroidales S24.7 group, Alistipes, and Eisenbergiella) are predicted to play a causal role in enhancing the risk of periodontitis (p< 0.05). Besides, two gut microbiota taxa (Butyricicoccus and Ruminiclostridium 6) have potentially inhibitive causal effects on the risk of periodontitis (p< 0.05). No significant estimation of heterogeneity or pleiotropy is detected. Conclusion: Our study demonstrates the genetic causal effect of 196 gut microbiota taxa on periodontitis and provides guidance for the clinical intervention of periodontitis.
Assuntos
Microbioma Gastrointestinal , Microbiota , Periodontite , Humanos , Microbioma Gastrointestinal/genética , Análise da Randomização Mendeliana , Periodontite/genética , Microbiota/genética , Bacteroidetes , ClostridialesRESUMO
Wound infection by multidrug-resistant bacteria seriously threatens human life. Chronic wounds, with necrosis, persistent inflammation, and covered by hypoxic tissue, seriously hinder anti-infection treatments. Herein, we have developed a multifunctional hydrogel dressing with antibacterial activity in the hypoxia environment to promote wound healing. The hydrogel comprises Cypate-conjugated antimicrobial peptides (AMP-Cypates), liposome-encapsulated perfluorodecalin, and recombinant type III collagen. AMP-Cypates exhibited outstanding antibacterial activity, jointly achieved through antimicrobial peptide (AMP) activity, photothermal therapy (PTT), and photodynamic therapy (PDT). The perfluorodecalin liposomes act as the oxygen carrier to mitigate wound hypoxia condition and enhance the efficacy of PDT. The recombinant type III collagen in the hydrogel further promoted the healing of the wounds together with the eradication of bacterial infection. Taken together, the hydrogel dressing provides a platform for integrating multiple antimicrobial mechanisms for the rapid removal of bacterial infection and the healing of chronic wounds.
Assuntos
Anti-Infecciosos , Colágeno Tipo III , Humanos , Hidrogéis/farmacologia , Colágeno , Antibacterianos/farmacologia , Bandagens , Hipóxia , LipossomosRESUMO
Human enterovirus A71 (EV-A71) is the major causative agent of hand, foot, and mouth disease (HFMD), which may lead to neurological sequelae and even death. Although EV-A71 seriously threatens public health, there remains no efficient drug for the treatment of EV-A71 infection. We previously demonstrated that ROCK1 is a novel host dependency factor for EV-A71 replication and can serve as a target for the development of anti-EV-A71 therapeutics. In this study, we identified a subset of inhibitors with potential anti-EV-A71 activity by virtual screening using ROCK1 as a target. Among the hits, Dasabuvir, an HCV polymerase inhibitor, was found to have the best antiviral activity which is consistent with the ranking scores in Autodock Vina and iGEMDOCK. We found that Dasabuvir efficiently suppressed EV-A71 replication in a dose-dependent manner. Moreover, Dasabuvir not only efficiently suppressed the replication of EV-A71 in RD cells, but also in multiple cell lines, including HEK-293T, Caco-2, HT-29, HepG2, and Huh7. Besides, Dasabuvir alleviated the release of proinflammatory cytokines caused by EV-A71 infection. Notably, Dasabuvir also exhibited antiviral activity of CVA10, indicating it may have broad-spectrum antiviral activity against species Enteroviruses A. Hence, our results further confirm that ROCK1 can be a potential drug target and suggest Dasabuvir could be a clinical candidate for the treatment of EV-A71 infection.
Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Doença de Mão, Pé e Boca , Humanos , Células CACO-2 , Infecções por Enterovirus/tratamento farmacológico , Antivirais/farmacologia , Quinases Associadas a rhoRESUMO
OBJECTIVE: To develop a drug delivery system triptolide-polyethylenimine-cyclodextrin and to evaluate its anticancer activity in vitro. METHODS: Triptolide was conjugated to polyethylenimine-cyclodextrin by N, N'-carbonyldiimidazole to form triptolide-polyethylenimine-cyclodextrin. (1)H-NMR, FT-IR and XRD were used to confirm its structure. The anticancer effect of the polymer was assessed by MTT assay, erasion trace test and hematoxylin-eosin staining. The potential to condense siRNA and to delivery siRNA into cytoplasm was demonstrated by gel retardation assay, zeta-potential determination and fluorescence staining. RESULTS: Triptolide was successfully conjugated to polyethylenimine-cyclodextrin and the conjugation rate of triptolide was 10% (w/w). siRNA was effectively condensed by the polymer at the N/P ratio of 5, and its particle size was 300 ±15 nm and zeta potential was 8 ±2.5 mV. MTT assay, erasion trace test and hematoxylin-eosin staining revealed that triptolide-polyethylenimine-cyclodextrin had anticancer effect and low cytotoxicity to normal cells. The polymer was able to deliver siRNA to the cytoplasm effectively as demonstrated by fluorescence staining. CONCLUSION: Triptolide-polyethylenimine-cyclodextrin is able to inhibit the growth and migration of cancer cells in vitro and to carry siRNA into cells effectively. It is potential to be used as a novel prodrug for co-delivery of gene and drug in cancer treatment.
Assuntos
Antineoplásicos/administração & dosagem , Ciclodextrinas , Diterpenos/administração & dosagem , Portadores de Fármacos , Fenantrenos/administração & dosagem , Polietilenoimina , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Diterpenos/farmacologia , Compostos de Epóxi/administração & dosagem , Compostos de Epóxi/farmacologia , Humanos , Nanopartículas , Fenantrenos/farmacologia , PolímerosRESUMO
OBJECTIVE: To study the characteristics of cationic polymers polyethylenimine-ß-cyclodextrin (PEI-CyD), polyethylenimine-poly-(3-hydroxypropyl)-aspartamide (PEI-PHPA), N,N-Dimethyldipropylenetriamine-Bis(3-aminopropyl)amine-aspartamide (PEE-PHPA) in vitro and in vivo. METHODS: PEI-PHPA, PEI-CyD and PEE-PHPA were synthesized and the chemistry structure of PEI-PHPA, PEI-CyD and PEE-PHPA was confirmed by (1)H-NMR. The particle size and zeta potential of these polymers were measured, and capacity of plasmid DNA condensation was tested. The inhibition of COS-7, A549, HEK293 and C6 cells was measured by MTT assay. The transfection efficiency was determined in HEK293 cell lines. The toxicity, tissue distribution and transfection efficiency of cationic polymers were tested in vivo. RESULTS: When the N/P of polymers/DNA at 30, the particle sizes were close 250 nm and the zeta-potential were near 35 mv. They were able to condense DNA at N/P ratio < 5. The MTT assay showed that the IC(50) of PEE-PHPA was 21.5, 20.2, 7.30 and 37.1 µg/ml, and that of PEI25kD was 15.8, 18.3, 11.4 and 36.7 µg/ml in C6, COS-7, A549 and HEK293cell lines, respectively. The cell viability of PEI-CyD and PEI-PHPA in above cell lines was over 60%. They had high transfection efficiency in HEK293 cell lines. The LD(50) of PEI25Kd, PEI-CyD, PEI-PHPA and PEE-PHPA in vivo was 19.50, 100.4, 521.2 and 630.0, respectively by intraperitoneal (ip) injection. The contractions of these polymers were higher in kidney than in other organs and tissues.PEE-PHPA had slight effect on kidney and liver function. CONCLUSION: PEE and PEI25kD have higher transfection efficiency and higher toxicity; while PC and PHPA-PEI have lower toxicity and higher transfection efficiency to be used as non-viral gene vector.
Assuntos
Vetores Genéticos , Polietilenoimina , Transfecção , Cátions , Linhagem Celular Tumoral , Humanos , Polímeros , beta-CiclodextrinasRESUMO
PURPOSE: To investigate the relationship between dental implant mucosa (DIM) and dental implant papilla (DIP) levels and peri-implant soft tissue stability. METHODS: A total of 86 patients with tooth implant in Qingdao Haici Hospital from January 2015 to January 2019 were enrolled, the patients were followed up from initial treatment till December 2020. Various indexes were recorded at the implantation moment(T0), 4 weeks(T1), 2 years(T2) after implantation and end of follow up (T3), including marginal bone loss levels (MBLs), mid-buccal mucosal levels (MBMLs), modified sulcus bleeding index(mSBI), modified bleeding index(mBI) and implant stability quotient (ISQ). Then the correlation of those indexes was analyzed. SPSS 23.0 software package was used to analyze the data. RESULTS: The follow-up period was 1.0-5.2 years, with an average of (4.79±0.34) years; two cases were lost to follow up, and finally 84 cases (95 implants) were included. Compared with indexes at T0, mSBI, mPLI, mBI, the level of distal bone adjacent to the tooth contact point, and the middle bone level adjacent to the tooth contact point at T1, T2, and T3 decreased significantly(Pï¼0.05), and DIP height increased significantly; PD, MBLs and MBMLs at T0, T1, T2, and T3 showed no significant difference(Pï¼0.05). The level of distal bone adjacent to the tooth contact point, and the middle bone level adjacent to the tooth contact point had an impact on DIP(Pï¼0.05). There were 49 cases with papillae gain in height and 46 cases with papilla that lost height. ISQ of gain height group and loss height group was relatively high at T0(Pï¼0.05). Compared with T2, there was a decrease in ISQ in both groups at T1(Pï¼0.05). ISQ of gain height group was significantly higher than that of loss height group at T1 and T2 (Pï¼0.05). CONCLUSIONS: There is a dependent correction between dental implant mucosa and dental implant papilla levels, and the stability of peri-implant soft tissues depends on keratinized tissue height and DIP height.
Assuntos
Implantes Dentários para Um Único Dente , Implantes Dentários , Implantação Dentária Endóssea/efeitos adversos , Implantes Dentários/efeitos adversos , Prótese Dentária Fixada por Implante , Humanos , MucosaRESUMO
AgI quantum dot (QD)-based room-temperature fast ionic conductors are prepared via an aqueous route. New phase behavior and good performance are found in this material. This is a prototype of quantum dot-ionics.