RESUMO
Mesoporous silica nanoparticles (MSNPs) have been widely used for the delivery of different hydrophilic and hydrophobic drugs owing to their large surface area and ease of chemical alteration. On the other hand, triphenylphosphonium cation (TPP+) with high lipophilicity has a great mitochondrial homing property that stimulates the internalization of drugs into cells. Therefore, we designed a TPP-modified MSNP to enhance the algicidal activity of our new algicidal agent cyclohexyl-(3,4-dichlorobenzyl) amine (DP92). In this study, algicidal activity was evaluated by assessing the growth rate inhibition of two harmful algal blooms (HABs), Heterosigma akashiwo and Heterocapsa circularisquama, after treatment with DP92-loaded MSNP or TPP-MSNP and DP92 in DMSO (as control). For H. akashiwo, the IC50 values of TPP-MSNP and MSNP are 0.03 ± 0.01 and 0.16 ± 0.03 µM, respectively, whereas the value of the control is 0.27 ± 0.02 µM. For H. circularisquama, the IC50 values of TPP-MSNP and MSNP are 0.10 ± 0.02 and 0.29 ± 0.02 µM, respectively, whereas the value of the control is 1.90 ± 0.09 µM. Results have indicated that TPP-MSNP efficiently enhanced the algicidal activity of DP92, signifying the prospect of using DP92-loaded TPP-MSNP as an algicidal agent for the superior management of HABs.
Assuntos
Dinoflagellida , Nanopartículas , Aminas , Dimetil Sulfóxido , Proliferação Nociva de Algas , Nanopartículas/química , Dióxido de Silício/químicaRESUMO
Harmful algal blooms (HABs) are becoming a more serious ecological threat to marine environments; they not only produce toxins, resulting in the death of marine organisms, but they also adversely affect biodiversity, which is an indicator of the health of an ecosystem. Thus, to mitigate HABs, numerous studies have been conducted to develop an effective algicide, but few studies have elucidated the effect of algicides on marine environmental health. In this study, thiazolidinedione derivative 49 (TD49), which has been developed as an algicide for the dinoflagellate Heterocapsa circularisquama, was used, and we investigated changes in phytoplankton biomass (abundance, chlorophyll a, and carbon biomass) and biodiversity (diversity, evenness, and richness) following the application of TD49. To gain deeper understanding, a large-scale mesocosm (1300â¯L) experiment containing control and treatment with four different concentrations (0.2, 0.4, 0.6 and 1⯵M) was conducted for 10 days. Based on a previous study, TD49 shows algicidal activity against H. circularisquama depending on its concentration. The phytoplankton biomass in the TD49 treatments was generally lower than that in the control due to the algicidal effect of TD49 on H. circularisquama. The biodiversity indices (e.g., the Shannon-Weaver index) in the treatments were consistently higher than those in the control before depletion of nitrite + nitrate. Interestingly, the 0.6 µM TD49 treatment had higher biodiversity indices than the high-concentration treatment (1 µM), which appeared to show a better algicidal effect. These findings suggest that mitigation of H. circularisquama blooms with TD49 treatment may enhance phytoplankton biodiversity, but treatment with excessively high concentrations can lead to harmful effects. During the study period, regardless of the control and TD49 treatments, the total biomass of phytoplankton gradually decreased from the midpoint of the experiment to the end of the experiment. This was more likely caused by the depletion of nutrients than by the toxicity of TD49.
Assuntos
Herbicidas , Microbiota , Tiazolidinedionas , Biodiversidade , Biomassa , Clorofila A , Ecossistema , Proliferação Nociva de AlgasRESUMO
Osteoconductive, biocompatible, and resorbable organic/inorganic composites are most commonly used in fixation medical devices, such as suture anchors and interference screws, because of their unique physical and chemical properties. Generally, studies on biodegradable composites have focused on their mechanical properties based on the composition and the individual roles of organic and inorganic biomaterials. In this study, we prepared biodegradable organic/inorganic nanocomposite materials using the solvent mixing process and conventional molding. We used polylactic acid (PLA) as the matrix and nano-sized hydroxyapatite (nano-HAp) as the osteoconductive filler. The content of nano-HAp was varied in 0-30 wt% and its influence on the In-Vitro mechanical performance of PLA/HAp nanocomposites was evaluated. The In-Vitro mechanical properties of nanocomposites were evaluated using standardized tensile and flexural tests after different immersion times in simulated body fluid.
Assuntos
Durapatita , Nanocompostos , Poliésteres , Materiais Biocompatíveis , Teste de Materiais , PolímerosRESUMO
Organic/inorganic biocomposite materials for biodegradable fixation medical devices require osteoconductivity, biocompatibility, and adequate mechanical properties with biodegradation behavior. The objective of this study was to investigate the effect of Si ions substituted in ß-tricalcium phosphate (ß-TCP) on the mechanical properties of organic/inorganic biocomposites. Biodegradable composite materials were prepared with polylactic acid (PLA) as the matrix and nano Si-substituted ß-TCP as the osteoconductive filler by solvent mixing and conventional molding. The nanostructured Si-substituted ß-TCP powders were synthesized by co-precipitation, controlling the quantity of Si ions. The amount of nanostructured Si-substituted ß-TCP powders in composites was varied in the 0-40 wt% range and the material properties were compared with those of pure ß-TCP/PLA composites. The influence of Si ions on the mechanical properties of the composites was evaluated by tensile and flexural tests.
Assuntos
Fosfatos de Cálcio/química , Nanoestruturas , Poliésteres , Materiais Biocompatíveis , Teste de MateriaisRESUMO
A total of 38 hazardous constituents in mainstream cigarette smoke of low-yield cigarettes sold in Korea were selected and analyzed using established methods. Risk calculations were performed using risk algorithms employed in previous studies and Korean population-based exposure parameters. The median cumulative incremental lifetime cancer risk of male smokers could vary from 828â¯×â¯10-6 to 2510â¯×â¯10-6, and that of female smokers could range from 440â¯×â¯10-6 to 1300â¯×â¯10-6, depending on the smoking regimens. The median hazard index as the sum of hazard quotients of male smokers varied from 367 to 1,225, and that of female smokers varied from 289 to 970, depending on the smoking regimens. The sensitivity analysis for this risk assessment indicated that the constituent yields in mainstream cigarette smoke, average number of cigarettes smoked per day or year, and mouth-spill rate are the main risk factors. Statistical positive correlations between the average daily dose calculated by the exposure algorithm used in this study for individual smokers and biomarkers verified the reliability of this assessment. It could be concluded that inhalation of the constituents present in the mainstream of low-yield cigarettes has significant cancer and non-cancer health risks, although its effect on risk reduction is still unknown under the fixed machine-smoking conditions.
Assuntos
Exposição por Inalação/efeitos adversos , Neoplasias/induzido quimicamente , Nicotiana/efeitos adversos , Fumaça/efeitos adversos , Fumar/efeitos adversos , Produtos do Tabaco/efeitos adversos , Carcinógenos/toxicidade , Feminino , Humanos , Pulmão/metabolismo , Masculino , República da Coreia , Medição de Risco , Fumaça/análise , FumantesRESUMO
OBJECTIVE: To find an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that rapidly metabolises Prostaglandin E2 (PGE2) as a mediator of wound healing, we examined seven flavonoids for this role. RESULTS: 7,3',4'-Trimethoxyflavone (TMF) had the lowest IC50 value of 0.34 µM for 15-PGDH inhibition but >400 µM for cytotoxicity, indicating a high therapeutic index. TMF elevated PGE2 levels in a concentration-dependent manner in both A549 lung cancer and HaCaT cells. It also significantly increased mRNA expression of multidrug resistance-associated protein 4 (MRP4) and of prostaglandin transporter (PGT) slightly in HaCaT cells. In addition, TMF facilitated in vitro wound healing in a HaCaT scratch model, which was completely inhibited by adding both 15-PGDH and NAD+ as cofactor, confirming the involvement of PGE2 in its wound healing effect. CONCLUSION: TMF with a high therapeutic index can facilitate wound healing through PGE2 elevation by 15-PGDH inhibition.
Assuntos
Dinoprostona/metabolismo , Flavonas/farmacologia , Hidroxiprostaglandina Desidrogenases/antagonistas & inibidores , Cicatrização/efeitos dos fármacos , Células A549 , Linhagem Celular , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , NAD/metabolismo , Transportadores de Ânions Orgânicos/genéticaRESUMO
High-mobility group box 1 (HMGB1) enhances inflammatory reactions by potentiating the activity of pro-inflammatory mediators and suppressing the phagocytosis of apoptotic neutrophils. However, the effects of HMGB1 on phagocytosis induced by pro-resolving mediators, such as resolvins, have not been studied up until this point. In this study, we investigated the effects and underlying mechanism of HMGB1 on resolvin D1-induced phagocytosis of MDA-MB-231 cells, which were selected as a model system based on their phagocytic capability and ease of transfecting them with a plasmid or siRNA in several cancer cell lines. Then we confirmed effects of HMGB1 in THP-1 cells. Resolvin D1 (RvD1) enhanced phagocytosis in MDA-MB-231 and THP-1 cells. HMGB1 suppressed RvD1-induced phagocytosis in MDA-MB.231 and THP-1 cells. HMGB1 dose-dependently induced the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the inactivating enzyme in pro-resolving lipid mediators such as RvE1 and RvD1. Involvement of 15-PGDH in-HMGB-1-induced suppression of phagocytosis was examined using siRNA of 15-PGDH or 15-PGDH inhibitor, TD23. Surprisingly, the silencing of 15-PGDH increased phagocytotic activity of MDA-MB-231 cells. TD23 also enhanced phagocytosis of MDA-MB-231 and THP-1 cells. In conclusion, the release of HMGB1 during the inflammatory phase induces 15-PGDH expression, which suppresses the phagocytotic activity of macrophages. These processes might be involved in the mechanism that blocks the resolution of inflammation, thereby allowing acute inflammation to progress to chronic inflammation.
RESUMO
Administration of an efficient alginate lyase (AlgL) or AlgL mutant may be a promising therapeutic strategy for treatment of cystic fibrosis patients with Pseudomonas aeruginosa infections. Nevertheless, the catalytic activity of wild-type AlgL is not sufficiently high. It is highly desired to design and discover an AlgL mutant with significantly improved catalytic efficiency against alginate substrates. For the purpose of identifying an AlgL mutant with significantly improved catalytic activity, in this study, we first constructed and validated a structural model of AlgL interacting with substrate, providing a better understanding of the interactions between AlgL and its substrate. Based on the modeling insights, further enzyme redesign and experimental testing led to discovery of AlgL mutants, including the K197D/K321A mutant, with significantly improved catalytic activities against alginate and acetylated alginate in ciprofloxacin-resistant P. aeruginosa (CRPA) biofilms. Further anti-biofilm activity assays have confirmed that the K197D/K321A mutant with piperacillin/tazobactam is indeed effective in degrading the CRPA biofilms. Co-administration of the potent mutant AlgL and an antibiotic (such as a nebulizer) could be effective for therapeutic treatment of CRPA-infected patients with cystic fibrosis. Proteins 2016; 84:1875-1887. © 2016 Wiley Periodicals, Inc.
Assuntos
Alginatos/química , Proteínas de Bactérias/genética , Biofilmes/efeitos dos fármacos , Polissacarídeo-Liases/genética , Pseudomonas aeruginosa/efeitos dos fármacos , Acetilação , Alginatos/metabolismo , Sequência de Aminoácidos , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/farmacologia , Biocatálise , Biofilmes/crescimento & desenvolvimento , Ciprofloxacina/farmacologia , Clonagem Molecular , Farmacorresistência Bacteriana/efeitos dos fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Ácido Glucurônico/química , Ácido Glucurônico/metabolismo , Ácidos Hexurônicos/química , Ácidos Hexurônicos/metabolismo , Hidrólise , Cinética , Simulação de Dinâmica Molecular , Mutação , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/farmacologia , Piperacilina/farmacologia , Combinação Piperacilina e Tazobactam , Polissacarídeo-Liases/metabolismo , Polissacarídeo-Liases/farmacologia , Domínios Proteicos , Engenharia de Proteínas , Estrutura Secundária de Proteína , Pseudomonas aeruginosa/química , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Alinhamento de Sequência , Homologia Estrutural de ProteínaRESUMO
Harmful algal blooms (HABs) can lead to substantial socio-economic losses and extensive damage to aquatic ecosystems, drinking water sources and human health. Common algicidal techniques, including ozonation, ultrasonic treatment and dispersion of algae-killing chemicals, are unsatisfactory both economically and ecologically. This study therefore presents a novel alternative strategy for the efficient control of deleterious algae via the use of host-specific virus-like particles (VLPs) combined with chemically synthesized algicidal compounds. The capsid protein of HcRNAV34, a single-stranded RNA virus that infects the toxic dinoflagellate, Heterocapsa circularisquama, was expressed in and purified from Escherichia coli and then self-assembled into VLPsâ in vitro. Next, the algicidal compound, thiazolidinedione 49 (TD49), was encapsidated into HcRNAV34 VLPs for specific delivery to H. circularisquama. Consequently, HcRNAV34 VLPs demonstrated the same host selectivity as naturally occurring HcRNAV34 virions, while TD49-encapsidated VLPs showed a more potent target-specific algicidal effect than TD49 alone. These results indicate that target-specific VLPs for the delivery of cytotoxic compounds to nuisance algae might provide a safe, environmentally friendly approach for the management of HABs in aquatic ecosystems.
Assuntos
Dinoflagellida/efeitos dos fármacos , Dinoflagellida/virologia , Sistemas de Liberação de Medicamentos/métodos , Proliferação Nociva de Algas/efeitos dos fármacos , Vírus de RNA/fisiologia , Tiazolidinedionas/farmacologia , Sistemas de Liberação de Medicamentos/instrumentação , Ecossistema , Vírus de RNA/genéticaRESUMO
Recent studies have focused on prostaglandin E2 (PGE2) because PGE2 regulates vertebrate hematopoietic stem cell induction and engraftment. PGE2 acts through EP2 and EP4 receptors to mediate regeneration and hematopoietic stem cell (HSC) development via the Wnt signaling pathway. Previously we reported that inhibitors of 15-PGDH can control the intracellular levels of PGE2. Therefore, we developed new potent 15-PGDH inhibitor, 5-(3-bromo-4-phenethoxybenzylidene)thiazolidine-2,4-dione (TD191), with an IC50 of 4 nM and tested cell-based wound healing effects. This compound significantly increased the level of PGE2 (451 pg/mL) in A549 cells, which was about 7-fold higher than that of control. HaCaT cells exposed to TD191 showed significantly improved wound healing after 48 h in scratch wound healing test, whereas treatment of TD191 to the fibroblast Hs27 cells slightly decreased cell growth compared with control. SCL is a basic helix-loop-helix transcription factor that is an essential for HSC development. By qPCR, SCL expression in HaCaT cells was 2-fold enhanced after addition of TD191, while treatment of TD191 into fibroblast Hs27 cells was not significantly changed the expression levels of the gene. This data provides in vitro evidence that TD191 may have utility for the therapeutic management of wound healing without scar formation.
Assuntos
Compostos de Benzilideno/farmacologia , Tiazolidinas/farmacologia , Cicatrização/efeitos dos fármacos , Compostos de Benzilideno/síntese química , Compostos de Benzilideno/química , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Hidroxiprostaglandina Desidrogenases/antagonistas & inibidores , Hidroxiprostaglandina Desidrogenases/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade , Tiazolidinas/síntese química , Tiazolidinas/químicaRESUMO
We investigated the effects of the algicide thiazolidinedione derivative TD49 on microbial community in mesocosm experiments. The TD49 concentration exponentially decreased over time, with half-life of 3.5 h, following addition in the seawater (R2=0.98, P<0.001). Among microbial communities, heterotrophic bacteria and heterotrophic nanoflagellates (HNFs) grew well in all treatments following the addition of TD49. The abundance of HNFs lagged behind the increase in heterotrophic bacteria by 24 h in the 0.2 and 0.4 µM TD49 concentrations (R2=0.28, P<0.05), and by 48 h in the 0.6 and 1.0 µM TD49 concentrations (R2=0.30, P<0.05). This implies a strong concentration-dependent top-down effect of TD49 on microbial communities, with indications that the degradation of planktonic organisms, including the target alga, led to high heterotrophic bacteria concentrations, which in turn stimulated the population growth of predatory HNF. However, total ciliate numbers remained relatively low in the TD49 treatments relative to the control and blank groups, suggesting limited carbon flow from bacteria to these grazers even though the abundance of aloricate ciliates gradually increased toward the end of the experimental period, particularly at the high TD49 concentrations. TD49 appears to provide an environmentally safe approach to the control of harmful algal blooms (HABs) in aquatic ecosystems.
Assuntos
Anti-Infecciosos/toxicidade , Organismos Aquáticos/efeitos dos fármacos , Ecossistema , Monitoramento Ambiental , Tiazolidinedionas/toxicidade , Bactérias/crescimento & desenvolvimento , Carbono/metabolismo , Cilióforos , Meia-Vida , Proliferação Nociva de Algas , Herbicidas/metabolismo , Água do MarRESUMO
Esophageal tumors provide unique challenges and opportunities for developing and testing surveillance imaging technology for different tumor microenvironment components, including assessment of immune cell modulation, with the ultimate goal of promoting early detection and response evaluation. In this context, accessibility through the lumen using a minimally invasive approach provides a means for repetitive evaluation longitudinally by combining fluorescent endoscopic imaging technology with novel fluorescent nanoparticles that are phagocytized by immune cells in the microenvironment. The agent we developed for imaging is synthesized from Feraheme (ferumoxytol), a Food and Drug Administration-approved monocrystaline dextran-coated iron oxide nanoparticle, which we conjugated to a near-infrared fluorochrome, CyAL5.5. We demonstrate a high level of uptake of the fluorescent nanoparticles by myeloid-derived suppressor cells (MDSCs) in the esophagus and spleen of L2Cre;p120ctnflox/flox mice. These mice develop esophageal dysplasia leading to squamous cell carcinoma; we have previously demonstrated that dysplastic and neoplastic esophageal lesions in these mice have an immune cell infiltration that is dominated by MDSCs. In the L2Cre;p120ctnflox/flox mice, evaluation of the spleen reveals that nearly 80% of CD45+ leukocytes that phagocytized the nanoparticle were CD11b+Gr1+ MDSCs. After dexamethasone treatment, we observed concordant decreased fluorescent signal from esophageal lesions during fluorescent endoscopy and decreased CyAL5.5-fluorescent-positive immune cell infiltration in esophageal dysplastic lesions by fluorescence-activated cell sorting analysis. Our observations suggest that this translatable technology may be used for the early detection of dysplastic changes and the serial assessment of immunomodulatory therapy and to visualize changes in MDSCs in the esophageal tumor microenvironment.
Assuntos
Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/cirurgia , Óxido Ferroso-Férrico/química , Antígenos Comuns de Leucócito/imunologia , Animais , Antineoplásicos Hormonais/administração & dosagem , Carbocianinas/farmacocinética , Carcinoma de Células Escamosas/diagnóstico , Células Cultivadas , Dexametasona/administração & dosagem , Dimetil Sulfóxido/farmacologia , Endoscopia , Endoscopia Gastrointestinal , Neoplasias Esofágicas/diagnóstico , Óxido Ferroso-Férrico/farmacocinética , Corantes Fluorescentes/farmacocinética , Indóis/farmacocinética , Leucócitos , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Nanopartículas/química , Baço/imunologiaRESUMO
The objective of this study was to develop chromatographic methods for the determination of the modification degree and the characterization of poly(ethylene glycol)-modified polyamidoamine dendrimers (PEG-PAMAMs). The PEG-PAMAMs were prepared by reacting PAMAM generation 4 with monomethoxy PEG-nitrophenyl carbonate (mPEG-NPC). The modification degrees of PEG-PAMAMs were determined by quantifying 4-nitrophenol released from mPEG-NPC after PEGylation reaction using high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. The PEG-PAMAMs, which have poor UV absorbances, were characterized by HPLC with charged aerosol detection. This study demonstrates that the combination of these two detectors is a powerful tool for the preparation and characterization of PEG-PAMAMs.
Assuntos
Dendrímeros/química , Poliaminas/química , Polietilenoglicóis/análise , Cromatografia Líquida de Alta Pressão/métodos , Nitrofenóis/análiseRESUMO
Thiazolidinedione (TD) derivatives have been found to have an algicidal effect on harmful algal bloom microalgae. In this study, 75 TD derivatives were synthesized and analyzed for algicidal activity. Among these synthetic TDs, 18 TD derivatives showed specific algicidal activity on two strains belonging to the classes Raphidophyceae (Chattonella marina and Heterosigma akashiwo) and Dinophyceae (Cochlodinium polykrikoides). Two strains belonging to Bacillariophyceae (Navicula pelliculosa and Phaeodactylum EPV), one strain belonging to Dinophyceae (Amphidinium sp.), and a Eustigmatophycean microalga (Nannochloropsis oculata) showed less sensitivity to the TD derivatives than the other two phyla. The most reactive TD derivative, compound 2 (TD118), was selected and tested for morphological and physiological changes. TD118 effectively damaged the cell membrane of C. marina, H. akashiwo and C. polykrikoides. The O2 evolution and photosystem II efficiency (F(v)/F(m)) of C. marina, H. akashiwo and C. polykrikoides were also severely reduced by TD118 treatment. Amphidinium sp., N. pelliculosa, Phaeodactylum EPV and N. oculata showed less reduction of O2 evolution and the F(v)/F(m) by TD118. These results imply that the species-specific TD structure relationship may be due to structural and/or physiological differences among microalgal species.
Assuntos
Antifúngicos/farmacologia , Proliferação Nociva de Algas/efeitos dos fármacos , Tiazolidinedionas/farmacologia , Antifúngicos/química , Microalgas/classificação , Microalgas/efeitos dos fármacos , Relação Estrutura-Atividade , Tiazolidinedionas/químicaRESUMO
Hot deformation constitutive analysis and processing maps of ultrasonic melt treated (UST) A5052 alloy were carried out based on a hot torsion test in this study. The addition of the Al-Ti master alloy as a grain refiner with no UST produced a finer grain size than the UST and pure Ti sonotrode. The Al3Ti phase particles in the case of the Al-10Ti master alloy acted as a nucleus for grain refinement, while the Ti atoms dissolved in the melt from the sonotrode were considered to have less of a grain refinement effect, even under UST conditions, than the Al3Ti phase particles in the Al-Ti master alloy. The constitutive equations for each experimental condition by torsion test were derived. In the processing maps examined in this study, the flow instability region was not present under UST in the as-cast condition, but it existed under the no UST condition. The effects of UST examined in this study are considered as (i) the uniform distribution of Ti solutes from the sonotrode and (ii) the reduction of pores by the degassing effect. After the homogenization heat treatment, most instability regions disappeared because the microstructures became uniform following the decomposition of intermetallic compounds and distribution of solute elements.
RESUMO
Developing electroactive membranes for filtration has gained importance owing to their effectiveness in mitigating the long-lasting issue of fouling faced with traditional membranes. Here, we developed thin electroactive metallic films on to stainless steel mesh (SSM) using electrodeposition method and evaluated their performance for microalgae harvesting via electro filtration. The effect of electrodeposition parameters on membrane formulation and operating parameters for electro filtration, both in continuous and intermittent modes, were evaluated and optimum values were obtained using response surface methodology (RSM). The optimal combination of electrodeposition parameters is 1000 µA/cm2 and 5 min for deposition current density and time, respectively. Whereas the electric field strength of 20 V/mm with an application time of 1 min is suggested to be the optimal combination of electro filtration parameters for maximized flux recovery and corresponding experimental rejection efficiency of more than 90%. Overall, this research contributes to a better understanding of the parameters governing electro-filtration and offers insights for improving the performance of membrane-based microalgae harvesting systems.
Assuntos
Microalgas , Membranas Artificiais , Filtração , Eletricidade , MembranasRESUMO
Excessive scar formation is an aberrant form of wound healing and is an indication of an exaggerated function of fibroblasts and excess accumulation of extracellular matrix during wound healing. Much experimental data suggests that prostaglandin E2 (PGE2) plays a role in the prevention of excessive scarring. However, it has a very short half-live in blood, its oxidization to 15-ketoprostaglandins is catalyzed by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Previously, we reported that 15-PGDH inhibitors significantly increased PGE2 levels in A549 cells. In our continuing attempts to develop highly potent 15-PGDH inhibitors, we newly synthesized various thiazolidine-2,4-dione derivatives. Compound 27, 28, 29, and 30 demonstrated IC50 values of 0.048, 0.020, 0.038 and 0.048 µM, respectively. They also increased levels of PGE2 in A549 cells. Especially, compound 28 significantly increased level of PGE2 at 260 pg/mL, which was approximately fivefold higher than that of control. Scratch wounds were analyzed in confluent monolayers of HaCaT cells. Cells exposed to compound 28 showed significantly improved wound healing with respect to control.
Assuntos
Dinoprostona/metabolismo , Inibidores Enzimáticos/farmacologia , Hidroxiprostaglandina Desidrogenases/antagonistas & inibidores , Tiazolidinedionas/farmacologia , Cicatrização/efeitos dos fármacos , Linhagem Celular , Dinoprostona/química , Inibidores Enzimáticos/química , Humanos , Relação Estrutura-Atividade , Tiazolidinedionas/química , Cicatrização/fisiologiaRESUMO
We report on rapid thermal chemical vapor deposition growth of silicon nanowires (Si NWs) that contain a high density of gold nanoclusters (Au NCs) with a uniform coverage over the entire length of the nanowire sidewalls. The Au NC-coated Si NWs with an antibody-coated surface obtain the unique capability to capture breast cancer cells at twice the highest efficiency currently achievable (~88% at 40 min cell incubation time) from a nanostructured substrate. We also found that irradiation of breast cancer cells captured on Au NC-coated Si NWs with a near-infrared light resulted in a high mortality rate of these cancer cells, raising a fine prospect for simultaneous capture and plasmonic photothermal therapy for circulating tumor cells.
Assuntos
Ouro/química , Hipertermia Induzida/métodos , Nanoestruturas/química , Neoplasias Experimentais/terapia , Células Neoplásicas Circulantes/efeitos da radiação , Fototerapia/métodos , Silício/química , Linhagem Celular Tumoral , Ouro/efeitos da radiação , Humanos , Luz , Nanoestruturas/efeitos da radiação , Silício/efeitos da radiaçãoRESUMO
As of June 2022, 5 coronavirus disease 2019 (COVID-19) vaccine brands have been used in Korea's national immunization program. The Korea Disease Control and Prevention Agency has enhanced vaccine safety monitoring through a passive web-based reporting system and active text message-based monitoring. In this study, an enhanced safety monitoring system for COVID-19 vaccines is described and the frequencies and types of adverse events (AEs) associated with the 5 COVID-19 vaccine brands were analyzed. AE reports from the web-based COVID-19 Vaccination Management System and text message-based reports from recipients were analyzed. AEs were classified as nonserious or serious (e.g., death or anaphylaxis). The AE reporting rates were calculated based on the number of COVID-19 vaccine doses administered. A total of 125,107,883 doses were administered in Korea from February 26, 2021, to June 4, 2022. Among them, 471,068 AEs were reported, of which 96.1% were nonserious and 3.9% were serious. Among the 72,609 participants in the text message-based AE monitoring process, a higher AE rate of local and systemic reactions was reported for the 3rd versus 1st doses. A total of 874 cases of anaphylaxis (7.0 per 1,000,000 doses), 4 cases of thrombocytopenia syndrome (TTS), 511 cases of myocarditis (4.1 per 1,000,000 doses), and 210 cases of pericarditis (1.7 per 1,000,000 doses) were confirmed. Six fatalities were causally associated with COVID-19 vaccination (1 of TTS and 5 of myocarditis). Young adult age and female sex were related with a higher AE rate for COVID-19 vaccines. Most reported AEs were nonserious and of mild intensity.
RESUMO
The homology model of the wild type alginate lyase (AlyVI) marine bacterium Vibrio sp. protein, was built using the crystal structure of the Family 7 alginate lyase from Sphingomonas sp. A1. To rationalize the observed structure-affinity relationships of aliginate lyase alyVI with its (GGG) substrate, molecular docking, MD imulations and binding free energy calculations followed by site-directed mutagenesis and alyVI activity assays were carried out. Per-residue decomposition of the (GGG) binding energy revealed that the most important contributions were from polar and charged residues, such as Asn138, Arg143, Asn217, and Lys308, while van der Waals interactions were responsible for binding with the catalytic His200 and Tyr312 residues. The mutants H200A, K308A, Y312A, Y312F, and W165A were found to be inactive or almost inactive. However, the catalytic efficiency (k(cat)/K(m)) of the double mutant L224V/D226G increased by two-fold compared to the wild type enzyme. This first structural model with its substrate binding mode and the agreement with experimental results provide a suitable base for the future rational design of new mutated alyVI structures with improved catalytic activity.