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Understanding the evolution of antibiotic resistance is important for combating drug-resistant bacteria. In this work, we investigated the adaptive response of Pseudomonas aeruginosa to ciprofloxacin. Ciprofloxacin-susceptible P. aeruginosa ATCC 9027, CIP-E1 (P. aeruginosa ATCC 9027 exposed to ciprofloxacin for 14 days) and CIP-E2 (CIP-E1 cultured in antibiotic-free broth for 10 days) were compared. Phenotypic responses including cell morphology, antibiotic susceptibility, and production of pyoverdine, pyocyanin and rhamnolipid were assessed. Proteomic responses were evaluated using comparative iTRAQ labelling LC-MS/MS to identify differentially expressed proteins (DEPs). Expression of associated genes coding for notable DEPs and their related regulatory genes were checked using quantitative reverse transcriptase PCR. CIP-E1 displayed a heterogeneous morphology, featuring both filamentous cells and cells with reduced length and width. By contrast, although filaments were not present, CIP-E2 still exhibited size reduction. Considering the MIC values, ciprofloxacin-exposed strains developed resistance to fluoroquinolone antibiotics but maintained susceptibility to other antibiotic classes, except for carbapenems. Pyoverdine and pyocyanin production showed insignificant decreases, whereas there was a significant decrease in rhamnolipid production. A total of 1039 proteins were identified, of which approximately 25â% were DEPs. In general, there were more downregulated proteins than upregulated proteins. Noted changes included decreased OprD and PilP, and increased MexEF-OprN, MvaT and Vfr, as well as proteins of ribosome machinery and metabolism clusters. Gene expression analysis confirmed the proteomic data and indicated the downregulation of rpoB and rpoS. In summary, the response to CIP involved approximately a quarter of the proteome, primarily associated with ribosome machinery and metabolic processes. Potential targets for bacterial interference encompassed outer membrane proteins and global regulators, such as MvaT.
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Ciprofloxacina , Infecciones por Pseudomonas , Humanos , Ciprofloxacina/farmacología , Pseudomonas aeruginosa/genética , Cromatografía Liquida , Proteómica , Piocianina , Espectrometría de Masas en Tándem , Antibacterianos/farmacologíaRESUMEN
The adsorption ability of hydrogen, hydroxide, and oxygenic intermediates plays a crucial role in electrochemical water splitting. Electron-deficient metal-active sites can prompt electrocatalytic activity by improving the adsorption ability of intermediates. However, it remains a significant challenge to synthesize highly abundant and stable electron-deficient metal-active site electrocatalysts. Herein, we present a general approach to synthesizing a hollow ternary metal fluoride (FeCoNiF2) nanoflake array as an efficient and robust bifunctional electrocatalyst for the hydrogen evolution reaction (HER) and urea oxidation reaction (UOR). We find that the F anion withdraws electrons from the metal centers, inducing an electron-deficient metal center catalyst. The rationally designed hollow nanoflake array exhibits the overpotential of 30 mV for HER and 130 mV for UOR at a current density of 10 mA cm-2 and superior stability without decay events over 150 h at a large current density of up to 100 mA cm-2. Remarkably, the assembled urea electrolyzer using a bifunctional hollow FeCoNiF2 nanoflake array catalyst requires cell voltages of only 1.352 and 1.703 V to afford current densities of 10 and 100 mA cm-2, respectively, which are 116 mV less compared with that required for overall water splitting.
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Rhinovirus (RV) infections in asthmatic patients are often associated with asthma exacerbation, characterized by worsened airways hyperreactivity and increased immune cell infiltration to the airways. The C-X-C chemokines, CXCL3 and CXCL5, regulate neutrophil trafficking to the lung via CXCR2, and their expression in the asthmatic lung is associated with steroid-insensitive type 2 inflammatory signatures. Currently, the role of CXCL3 and CXCL5 in regulating neutrophilic and type 2 responses in viral-induced asthma exacerbation is unknown. Inhibition of CXCL3 or CXCL5 with silencing RNAs in a mouse model of RV-induced exacerbation of asthma attenuated the accumulation of CXCR2+ neutrophils, eosinophils, and innate lymphoid cells in the lung and decreased production of type 2 regulatory factors IL-25, IL-33, IL-5, IL-13, CCL11, and CCL24. Suppression of inflammation was associated with decreased airways hyperreactivity, mucus hypersecretion, and collagen deposition. Similar results were obtained by employing RC-3095, which has been shown to bind to CXCR2, or by depletion of neutrophils. Our data demonstrate that CXCL3 and CXCL5 may be critical in the perpetuation of RV-induced exacerbation of asthma through the recruitment of CXCR2-positive neutrophils and by promoting type 2 inflammation. Targeting the CXCL3/CXCL5/CXCR2 axis may provide a new therapeutic approach to attenuating RV-induced exacerbations of asthma.
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Asma/inmunología , Quimiocina CXCL5/inmunología , Quimiocinas CXC/inmunología , Quimiotaxis de Leucocito/inmunología , Neutrófilos/inmunología , Receptores de Interleucina-8B/inmunología , Rhinovirus/inmunología , Animales , Hiperreactividad Bronquial/inmunología , Eosinófilos/inmunología , Inmunidad Innata/inmunología , Inflamación/inmunología , Pulmón/inmunología , Linfocitos/inmunología , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
Kesterite Cu2ZnSnS4 (CZTS) thin films in which the Cu site was partially replaced with Ag were prepared by spray deposition on an Mo-coated glass substrate. Successful replacement of Cu components in the CZTS lattice with Ag up to an Ag/(Cu + Ag) ratio of 0.20 was achieved. Samples with relatively low contents of Ag (Ag/(Cu + Ag) ratios of 0.05 and 0.10) showed obvious grain growth compared to that of bare CZTS, whereas samples with higher Ag contents showed an appreciable decrease in grain sizes. Photoelectrochemical properties for water reduction (H2 production), which was examined after surface modifications with an In2S3/CdS double layer and Pt catalyst for H2 evolution, depended strongly on such morphological differences; a maximum conversion efficiency, i.e., half-cell solar to hydrogen efficiency, of 2.4% was achieved by the photocathode based on the film with an Ag/(Cu + Ag) ratio of 0.10. Minority carrier dynamics examined by photoluminescence measurements indicated that such an active sample of PEC H2 production had a relatively long carrier lifetime, suggesting that the suppression of carrier recombination at grain boundaries in the bulk of these kesterite films is one of the important factors for enhancing PEC functions.
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BACKGROUND AND OBJECTIVE: Influenza virus (FLU), rhinovirus (RV) and respiratory syncytial virus (RSV) are the most common acute respiratory infections worldwide. Infection can cause severe health outcomes, while therapeutic options are limited, primarily relieving symptoms without attenuating the development of lesions or impaired lung function. We therefore examined the inflammatory response to these infections with the intent to identify common components that are critical drivers of immunopathogenesis and thus represent potential therapeutic targets. METHODS: BALB/c mice were infected with FLU, RV or RSV, and lung function, airway inflammation and immunohistopathology were measured over a 10-day period. Anti-IL-17A mAb was administered to determine the impact of attenuating this cytokine's function on the development and severity of disease. RESULTS: All three viruses induced severe airway constriction and inflammation at 2 days post-infection (dpi). However, only FLU induced prolonged inflammation till 10 dpi. Increased IL-17A expression was correlated with the alterations in lung function and its persistence. Neutralization of IL-17A did not affect the viral replication but led to the resolution of airway hyperresponsiveness. Furthermore, anti-IL-17A treatment resulted in reduced infiltration of neutrophils (in RV- and FLU-infected mice at 2 dpi) and lymphocytes (in RSV-infected mice at 2 dpi and FLU-infected mice at 10 dpi), and attenuated the severity of immunopathology. CONCLUSION: IL-17A is a common pathogenic molecule regulating disease induced by three prevalent respiratory viruses. Targeting the IL-17A pathway may provide a unified approach to the treatment of these respiratory infections alleviating both inflammation-induced lesions and difficulties in breathing.
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Interleucina-17/inmunología , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Picornaviridae/inmunología , Infecciones por Virus Sincitial Respiratorio , Animales , Pulmón/fisiopatología , Ratones , Ratones Endogámicos BALB C , Orthomyxoviridae , Virus Sincitiales Respiratorios/inmunología , RhinovirusRESUMEN
Respiratory syncytial virus (RSV) infection induces asthma exacerbations, which leads to worsening of clinical symptoms and may result in a sustained decline in lung function. Exacerbations are the main cause of morbidity and mortality associated with asthma, and significantly contribute to asthma-associated healthcare costs. Although glucocorticoids are used to manage exacerbations, some patients respond to them poorly. The underlying mechanisms associated with steroid-resistant exacerbations remain largely unknown. We have previously established a mouse model of RSV-induced exacerbation of allergic airways disease, which mimics hallmark clinical features of asthma. In this study, we have identified key roles for macrophage IFN-γ and IL-27 in the regulation of RSV-induced exacerbation of allergic airways disease. Production of IFN-γ and IL-27 was steroid-resistant, and neutralization of IFN-γ or IL-27 significantly suppressed RSV-induced steroid-resistant airway hyperresponsiveness and airway inflammation. We have previously implicated activation of pulmonary macrophage by TNF-α and/or MCP-1 in the mechanisms of RSV-induced exacerbation. Stimulation of pulmonary macrophages with TNF-α and/or MCP-1 induced expression of both IFN-γ and IL-27. Our findings highlight critical roles for IFN-γ and IL-27, downstream of TNF-α and MCP-1, in the mechanism of RSV-induced exacerbation. Thus, targeting the pathways that these factors activate may be a potential therapeutic approach for virus-induced asthma exacerbations.
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Asma/inmunología , Interferón gamma/metabolismo , Interleucina-27/metabolismo , Macrófagos Alveolares/inmunología , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitiales Respiratorios/inmunología , Animales , Asma/complicaciones , Células Cultivadas , Quimiocina CCL2/inmunología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Humanos , Activación de Macrófagos , Macrófagos Alveolares/virología , Masculino , Ratones , Ratones Endogámicos BALB C , Infecciones por Virus Sincitial Respiratorio/complicaciones , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Viral respiratory infections trigger severe exacerbations of asthma, worsen disease symptoms, and impair lung function. To investigate the mechanisms underlying viral exacerbation, we established a mouse model of respiratory syncytial virus (RSV)-induced exacerbation after allergen sensitization and challenge. RSV infection of OVA-sensitized/challenged BALB/c mice resulted in significantly increased airway hyperresponsiveness (AHR) and macrophage and neutrophil lung infiltration. Exacerbation was accompanied by increased levels of inflammatory cytokines (including TNF-α, MCP-1, and keratinocyte-derived protein chemokine [KC]) compared with uninfected OVA-treated mice or OVA-treated mice exposed to UV-inactivated RSV. Dexamethasone treatment completely inhibited all features of allergic disease, including AHR and eosinophil infiltration, in uninfected OVA-sensitized/challenged mice. Conversely, dexamethasone treatment following RSV-induced exacerbation only partially suppressed AHR and failed to dampen macrophage and neutrophil infiltration or inflammatory cytokine production (TNF-α, MCP-1, and KC). This mimics clinical observations in patients with exacerbations, which is associated with increased neutrophils and often poorly responds to corticosteroid therapy. Interestingly, we also observed increased TNF-α levels in sputum samples from patients with neutrophilic asthma. Although RSV-induced exacerbation was resistant to steroid treatment, inhibition of TNF-α and MCP-1 function or depletion of macrophages suppressed features of disease, including AHR and macrophage and neutrophil infiltration. Our findings highlight critical roles for macrophages and inflammatory cytokines (including TNF-α and MCP-1) in viral-induced exacerbation of asthma and suggest examination of these pathways as novel therapeutic approaches for disease management.
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Pulmón/inmunología , Macrófagos/inmunología , Hipersensibilidad Respiratoria/inmunología , Infecciones por Virus Sincitial Respiratorio/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Alérgenos/inmunología , Animales , Asma/inmunología , Quimiocina CCL2/análisis , Quimiocina CCL2/metabolismo , Citocinas/biosíntesis , Citocinas/inmunología , Dexametasona/uso terapéutico , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Humanos , Inflamación , Pulmón/fisiopatología , Pulmón/virología , Ratones , Ratones Endogámicos BALB C , Neutrófilos/inmunología , Ovalbúmina/administración & dosificación , Ovalbúmina/inmunología , Hipersensibilidad Respiratoria/fisiopatología , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/fisiopatología , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/fisiología , Virus Sincitial Respiratorio Humano/efectos de la radiación , Saliva/inmunología , Factor de Necrosis Tumoral alfa/análisis , Rayos UltravioletaRESUMEN
Rice (Oryza sativa L.) is one of the major staple food crops of nearly two-third of the world's population. However, rice blast caused by fungus Pyricularia oryzae is generally considered the most serious disease of cultivated rice worldwide due to its extensive distribution and destructiveness under favourable climatic conditions. In this report, the combination between chitosan (CS) and silver (Ag), Ag@CS, was introduced for antifungal activity against Pyricularia oryzae extracted from blast-infected leaves. In detail, Ag@CS nanoparticles (NPs) were first synthesized and further mixed with Trihexad 700 WP (Tri), Ag@CS-Tri, against the fungus by agar diffusion method. The prepared Ag@CS-Tri NPs were characterized by Fourier transform infrared (FTIR), dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). In aqueous condition, Ag@CS-Tri NPs were successfully prepared and existed as spherical NPs with particle size of 17.26 ± 0.89 nm, which is an ideal size for their uptake into plant cells, indicating that the size of their parentally Ag@CS NPs is small enough to combine Tri, and their diameter is large enough to effectively penetrate the cellular membrane and kill fungi. More importantly, the antifungal property of Ag@CS-Tri NPs was significantly increased with inhibition zone around 25 nm compared with only around 12 nm of Ag@CS at the same concentration of Ag (2 ppm) and CS (4000 ppm). These results demonstrated that the synergistic effect of Tri and Ag@CS NPs can be a potential candidate with high antifungal activity for the use of antibiotics in agriculture.
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Antifúngicos/farmacología , Quitosano , Nanopartículas del Metal , Pyricularia grisea/efectos de los fármacos , Antifúngicos/química , Plata , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
BACKGROUND: Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. Steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including neutrophilic forms of disease. However, steroid-insensitive patients with eosinophil-enriched inflammation have also been described. The mechanisms that underpin infection-induced, severe steroid-insensitive asthma can be elucidated by using mouse models of disease. OBJECTIVE: We sought to develop representative mouse models of severe, steroid-insensitive asthma and to use them to identify pathogenic mechanisms and investigate new treatment approaches. METHODS: Novel mouse models of Chlamydia, Haemophilus influenzae, influenza, and respiratory syncytial virus respiratory tract infections and ovalbumin-induced, severe, steroid-insensitive allergic airway disease (SSIAAD) in BALB/c mice were developed and interrogated. RESULTS: Infection induced increases in the levels of microRNA (miRNA)-21 (miR-21) expression in the lung during SSIAAD, whereas expression of the miR-21 target phosphatase and tensin homolog was reduced. This was associated with an increase in levels of phosphorylated Akt, an indicator of phosphoinositide 3-kinase (PI3K) activity, and decreased nuclear histone deacetylase (HDAC)2 levels. Treatment with an miR-21-specific antagomir (Ant-21) increased phosphatase and tensin homolog levels. Treatment with Ant-21, or the pan-PI3K inhibitor LY294002, reduced PI3K activity and restored HDAC2 levels. This led to suppression of airway hyperresponsiveness and restored steroid sensitivity to allergic airway disease. These observations were replicated with SSIAAD associated with 4 different pathogens. CONCLUSION: We identify a previously unrecognized role for an miR-21/PI3K/HDAC2 axis in SSIAAD. Our data highlight miR-21 as a novel therapeutic target for the treatment of this form of asthma.
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Asma/genética , Chlamydia muridarum/inmunología , Haemophilus influenzae/inmunología , Histona Desacetilasa 2/metabolismo , Subtipo H1N1 del Virus de la Influenza A/inmunología , MicroARNs/metabolismo , Fosfohidrolasa PTEN/metabolismo , Neumonía/genética , Virus Sincitiales Respiratorios/inmunología , Infecciones del Sistema Respiratorio/genética , Animales , Antagomirs/genética , Asma/tratamiento farmacológico , Asma/inmunología , Dexametasona/uso terapéutico , Modelos Animales de Enfermedad , Resistencia a Medicamentos , Regulación de la Expresión Génica , Histona Desacetilasa 2/genética , Humanos , Ratones , Ratones Endogámicos BALB C , MicroARNs/genética , Fosfohidrolasa PTEN/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Neumonía/tratamiento farmacológico , Neumonía/inmunología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/inmunologíaRESUMEN
Platelet integrin αIIbß3 possesses a Leu/Pro polymorphism at residue 33 (Leu33/HPA-1a or Pro33/HPA-1b). The Pro33 isoform has been suggested to exhibit prothrombotic features. αIIbß3-expressing CHO (Chinese hamster ovary) cells on immobilized fibrinogen show activation of the MAP kinase family member ERK2, with an enhanced ERK2 activity in Pro33 cells compared to Leu33 cells. In our present work, we examined how the Leu/Pro polymorphism modulates the ERK2 activation stimulated by 2 differently triggered outside-in signalings. We either treated the CHO cells with Mn2+ or allowed them to adhere to fibrinogen. Moreover, we studied which signaling cascades are involved in ERK2 activation. In contrast to immobilized fibrinogen, Mn2+ did not significantly increase ERK2 activation. However, Mn2+ had a synergistic effect on ERK2 phosphorylation when combined with immobilized fibrinogen. Pro33 cells adherent to fibrinogen exhibited a significantly greater ERK2 activity than Leu33 cells in the presence of Mn2+, which peaked after 10 min of adhesion. Our data showed that Src family and rho kinases play a crucial role in the integrin αIIbß3-dependent outside-in signaling to ERK2.
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Sistema de Señalización de MAP Quinasas , Manganeso/farmacología , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/genética , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/genética , Quinasas Asociadas a rho/genética , Familia-src Quinasas/genética , Animales , Plaquetas/metabolismo , Células CHO , Cationes Bivalentes , Adhesión Celular/efectos de los fármacos , Cricetulus , Fibrinógeno/química , Fibrinógeno/metabolismo , Regulación de la Expresión Génica , Humanos , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Mutación , Fosforilación , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Quinasas Asociadas a rho/metabolismo , Familia-src Quinasas/metabolismoRESUMEN
The design of three-dimensional (3D) scaffolds should focus on creating highly porous, 3D structures with an interconnected pore network that supports cell growth. The scaffold's pore interconnectivity is directly linked to vascularization, cell seeding, guided cell migration, and transportation of nutrients and metabolic waste. In this study, different types of food flavors including monosodium glutamate, sugar, and sodium chloride were used as the porogens along with PCL/PVP blend polymer for solvent casting/particulate leaching method. The morphology, porosity, interconnectivity, chemical composition, water absorption, and mechanical properties of the fabricated scaffolds are carefully characterized. The scaffolds are biocompatible in bothin vitroandin vivoexperiments and do not trigger any inflammatory response while enhancing new bone formation and vascularization in rabbit calvaria critical-sized defects. The new bone merges and becomes denser along with the experiment timeline. The results indicate that the 3D PCL/PVP scaffolds, using monosodium glutamate as porogen, exhibited suitable biological performance and held promise for bone tissue engineering in oral and maxillofacial surgery.
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Materiales Biocompatibles , Glutamato de Sodio , Solventes , Ingeniería de Tejidos , Andamios del Tejido , Animales , Andamios del Tejido/química , Conejos , Ingeniería de Tejidos/métodos , Porosidad , Solventes/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Poliésteres/química , Ensayo de Materiales , Cráneo/efectos de los fármacos , Polivinilos/química , Regeneración Ósea/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacología , Huesos/metabolismoRESUMEN
Introduction: Vitamin D3 plays a vital role in bone health, with low levels of vitamin D3 being related to skeletal fragility, fractures, and metabolic disorders such as diabetes. Metformin is known as an antihyperglycemic agent for regulating blood sugar. A correlation between diabetes mellitus and osteoporosis is attracting considerable interest, and research to find the prevention and treatment is gradually being studied. In this study, we investigated the effect of metformin and vitamin D3 on osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells (AT-MSCs) under high d-glucose concentrations and optimized by combining vitamin D3 and metformin in the process. Methods: ROS production of AT-MSCs under high d-glucose conditions was measured by DCFH-DA assay. The differentiated AT-MSCs were analyzed by Alizarin Red S staining and optical density measurement. The investigation involved the examination of osteogenic master genes' expressions using quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques. Results: Interestingly, the results have shown that human AT-MSCs will exhibit high ROS accumulation and low osteogenic differentiation capabilities, indicated by low calcium deposition, as well as low expression of indicative genes such as ALP, Runx-2 under high d-glucose conditions. The combination of vitamin D3 and metformin remarkedly accelerated the osteogenic differentiation of AT-MSCs under high d-glucose concentrations more effectively than the administration of either agent. Conclusions: This study partially explains an aspect of an in vitro model for pre-clinical drug screening for osteoporosis-related diabetic pathological mechanisms, which can be applied for further research on the prevention or treatment of osteoporosis in diabetic patients.
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BACKGROUND: This study investigated post-traumatic stress disorder (PTSD), anxiety, depression and their related factors among coronavirus disease 2019 (COVID-19) patients during the fourth wave of the pandemic in Vietnam. METHODS: Vietnamese-fluent confirmed COVID-19 patients for at least 3 d were recruited in this online cross-sectional study to answer a three-part questionnaire including participants' sociodemographic characteristics, PTSD (Impact of Event Scale-Revised) and anxiety and depression (Hospital Anxiety and Depression Scale). Associated factors were determined using multivariable binary logistic regression models. RESULTS: Of 1544 responses, the majority were female (53.0%), ages 18-39 y (74.8%) and were isolated and treated at field hospitals (72.2%). Family or friends were the greatest sources of mental support (68.2%), followed by healthcare providers (51.1%). The overall prevalence rates of PTSD, anxiety and depression among COVID-19 patients were 22.9%, 11.2% and 17.4%, respectively. Risk factors included older age, higher education, getting infected from the public, knowing someone who died from COVID-19 and high perception of life threat. Meanwhile, mental assistance from family or friends, a greater number of supporters, living with someone not vulnerable and higher salaries were significantly protective factors. CONCLUSIONS: The psychological responses associated with some sociodemographic details. Family or friends should be the first line of mental interventions for COVID-19 patients.
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COVID-19 , Trastornos por Estrés Postraumático , Humanos , Femenino , Masculino , COVID-19/epidemiología , Trastornos por Estrés Postraumático/epidemiología , Depresión/epidemiología , Depresión/psicología , Pandemias , Estudios Transversales , Vietnam/epidemiología , SARS-CoV-2 , Ansiedad/epidemiología , Ansiedad/psicologíaRESUMEN
Dynamic hydrogel systems from N,O-carboxymethyl chitosan (NOCC) are investigated in the past years, which has facilitated their widespread use in many biomedical engineering applications. However, the influence of the polymer's oxidation levels on the hydrogel biological properties is not fully investigated. In this study, chitosan is converted into NOCC and introduced to react spontaneously with oxidized xanthan gum (OXG) to form several injectable hydrogels with controlled degradability. Different oxidation levels of xanthan gum, as well as NOCC/OXG volume ratios, are trialed. The infrared spectroscopy spectra verify chemical modification on OXG and successful crosslinking. With increasing oxidation levels, more dialdehyde groups are introduced into the OXG, resulting in changes in physical properties including gelation, swelling, and self-healing efficiency. Under different volume ratios, the hydrogel shows a stable structure and rigidity with higher mechanical properties, and a slower degradation rate. The shear-thinning and self-healing properties of the hydrogels are confirmed. In vitro assays with L929 cells show the biocompatibility of all formulations although the use of a high amount of OXG15 and OXG25 limited the cell proliferation capacity. Findings in this study suggested a suitable amount of OXG at different oxidation levels in NOCC hydrogel systems for tissue engineering applications.
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Quitosano , Quitosano/química , Hidrogeles/farmacología , Hidrogeles/química , PolímerosRESUMEN
Dual-drug delivery systems for anticancer therapy have recently attracted substantial attention due to their potency to overcome limitations of conventional anti-cancer drugs, tackle drug resistance problems, as well as improve the therapeutic efficacy. In this study, we introduced a novel nanogel based on folic acid-gelatin-pluronic P123 (FA-GP-P123) conjugate to simultaneously deliver quercetin (QU) and paclitaxel (PTX) to the targeted tumor. The results indicated that the drug loading capacity of FA-GP-P123 nanogels was significantly higher than that of P123 micelles. The kinetic release profiles of QU and PTX from the nanocarriers were governed by Fickian diffusion and swelling behavior, respectively. Notably, FA-GP-P123/QU/PTX dual-drug delivery system induced higher toxicity to MCF-7 and Hela cancer cells than either QU or PTX individual delivery system, and the non-targeted dug delivery system (GP-P123/QU/PTX), indicating the synergistic combination of dual drugs and FA positive targeting effect. Furthermore, FA-GP-P123 could effectively deliver QU and PTX to tumors in vivo after administration into MCF-7 tumor-bearing mice, which resulted in 94.20 ± 5.90 % of tumor volume reduced at day 14. Moreover, the side effects of the dual-drug delivery system were significantly reduced. Overall, we suggest FA-GP-P123 as potential nanocarrier for dual-drug delivery for targeted chemotherapy.
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Gelatina , Paclitaxel , Ratones , Animales , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Gelatina/farmacología , Quercetina/farmacología , Nanogeles , Línea Celular Tumoral , Resistencia a Antineoplásicos , Sistemas de Liberación de Medicamentos/métodos , Micelas , Ácido Fólico/farmacología , Portadores de Fármacos/farmacologíaRESUMEN
In this study, multilayered scaffolds composed of polycaprolactone (PCL)-gelatin/poly(lactic-co-glycolic acid) (PLGA)-gelatin/PLGA-chitosan artificial blood vessels were fabricated using a double-ejection electrospinning system. The mixed fibers from individual materials were observed by scanning electron microscopy. The effects of the cross-linking process on the microstructure, mechanical properties and biocompatibility of the fibers were examined. The tensile stress and liquid strength of the cross-linked artificial blood vessels were 2.3 MPa and 340 mmHg, respectively, and were significantly higher than for the non-cross-linked vessel (2.0 MPa and 120 mmHg). The biocompatibility of the cross-linked artificial blood vessel scaffold was examined using the MTT assay and by evaluating cell attachment and cell proliferation. The cross-linked PCL-gelatin/PLGA-gelatin/PLGA-chitosan artificial blood vessel scaffold displayed excellent flexibility, was able to withstand high pressures and promoted cell growth; thus, this novel material holds great promise for eventual use in artificial blood vessels.
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Continuously porous hydroxyapatite (HAp)/t-ZrO2 composites containing concentric laminated frames and microchanneled bodies were fabricated by an extrusion process. To investigate the mechanical properties of HAp/t-ZrO2 composites, the porous composites were sintered at different temperatures using a microwave furnace. The microstructure was designed to imitate that of natural bone, particularly small bone, with both cortical and spongy bone sections. Each microchannel was separated by alternating lamina of HAp, HAp-(t-ZrO2) and t-ZrO2. HAp and ZrO2 phases existed on the surface of the microchannel and the core zone to increase the biocompatibility and mechanical properties of the HAp-ZrO2 artificial bone. The sintering behavior was evaluated and the optimum sintering temperature was found to be 1400 °C, which produced a stable scaffold. The material characteristics, such as the microstructure, crystal structure and compressive strength, were evaluated in detail for different sintering temperatures. A detailed in vitro study was carried out using MTT assay, western blot analysis, gene expression by polymerase chain reaction and laser confocal image analysis of cell proliferation. The results confirmed that HAp-ZrO2 performs as an artificial bone, showing excellent cell growth, attachment and proliferation behavior using osteoblast-like MG63 cells.
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In this study, two distinct systems of biomaterials were fabricated and their potential use as a bilayer scaffold (BS) for skin bioengineering applications was assessed. The initial biomaterial was a polycaprolactone/poly(lacto-co-glycolic acid) (PCL/PLGA) membrane fabricated using the electrospinning method. The PCL/PLGA membrane M-12 (12% PCL/10% PLGA, 80:20) displayed strong mechanical properties (stress/strain values of 3.01 ± 0.23 MPa/225.39 ± 7.63%) and good biocompatibility as demonstrated by adhesion of keratinocyte cells on the surface and ability to support cell proliferation. The second biomaterial was a hydrogel composed of 2% chitosan and 15% gelatin (50:50) crosslinked with 5% glutaraldehyde. The CG-3.5 hydrogel (with 3.5% glutaraldehyde (v/v)) displayed a high porosity, ≥97%, good compressive strength (2.23 ± 0.25 MPa), ability to swell more than 500% of its dry weight and was able to support fibroblast cell proliferation. A BS was fabricated by underlaying the membrane and hydrogel casting method to combine these two materials. The physical properties and biocompatibility were preliminarily investigated and the properties of the two biomaterials were shown to be complementary when combined. The upper layer membrane provided mechanical support in the scaffold and reduced the degradation rate of the hydrogel layer. Cell viability was similar to that in the hydrogel layer which suggests that addition of the membrane layer did not affect the biocompatibility.
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Quitosano/química , Gelatina/química , Hidrogeles/química , Ácido Láctico/química , Poliésteres/química , Ácido Poliglicólico/química , Piel , Materiales Biocompatibles/química , Adhesión Celular , Proliferación Celular , Fibroblastos/citología , Fibroblastos/fisiología , Humanos , Microscopía Electrónica de Rastreo , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Estrés Mecánico , Factores de Tiempo , Ingeniería de Tejidos/métodosRESUMEN
Bone cement is used as a mortar for securing bone implants, as bone void fillers or as spacers in orthopaedic surgery. Antibiotic-loaded bone cements (ALBCs) have been used to prevent and treat prosthetic joint infections by providing a high antibiotic concentration around the implanted prosthesis. High antibiotic concentrations are, on the other hand, often associated with tissue toxicity. Controlling antibiotic release from ALBCS is key to achieving effective infection control and promoting prosthesis integration with the surrounding bone tissue. However, current ALBCs still need significant improvement in regulating antibiotic release. In this review, we first provide a brief introduction to prosthetic joint infections, and the background concepts of therapeutic efficacy and toxicity in antibiotics. We then review the current state of ALBCs and their release characteristics before focusing on the research and development in controlling the antibiotic release and osteo-conductivity/inductivity. We then conclude by a discussion on the need for better in vitro experiment designs such that the release results can be extrapolated to predict better the local antibiotic concentrations in vivo.
RESUMEN
AIM: This study measured the level of knowledge, attitudes and practices towards COVID-19 prevention and examined associated factors among patients at a national tertiary general hospital in Vietnam. METHODS: Adult patients admitted to University Medical Center during research period were recruited in a cross-sectional study, which employed a convenience sampling method with a 4-component questionnaire in order to examine the patients' consciousness towards COVID-19 spreading prevention based on four aspects: demographic characteristics (10 items), knowledge (14 items), attitudes (6 items), and practices (7 items). RESULTS: The study involved 2769 respondents (18-90 years) with the mean age of 38.05±13.91 years. About two thirds of the respondents obtained diploma degree or higher (63.4%) and shared their living space with others (64.4%). The majority of patients settled in urban area (74.9%). All participants stayed informed about COVID-19, with the most commonly used channels like television (75.2%), the Internet (72.2%) and phone (69.8%). The vast majority showed sufficient knowledge (93.7%) and positive attitudes (76.3%). Just over half of participants remained good practiced of COVID-19 prevention (57.7%). On average, the factors of younger age, higher educational level, frequency and department of admission, and the number of COVID-19 informative channels were significantly associated with sufficient knowledge, positive attitudes, and good practices regarding preventive action against COVID-19 spreading. The optimistic attitude and having more undergoing chronic diseases were associated with the likelihood of well-practiced COVID-19 preventive measures (OR 3.63, 95% CI 1.54-8.55, p=0.003 and OR 0.86, 95% CI 0.78-0.98, p=0.02, respectively). CONCLUSION: The results of this study demonstrated that the likelihood of good preventive practices in the fight against COVID-19 pandemic was influenced by attitudes and several sociodemographic factors. More drastic interventions for the prevention of COVID-19 should be widely furnished and equipped in hospitals, through various routes to maximize the efficiency and adherence to prevention practices.