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1.
J Appl Toxicol ; 44(3): 470-483, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37876240

RESUMO

Extensive, long-term exposure to cigarette smoke (CS) was recently suggested to be a risk factor for pulmonary hypertension, although further validation is required. The vascular effects of CS share similarities with the etiology of pulmonary hypertension, including vascular inflammation and remodeling. Thus, we examined the influence of CS exposure on the pathogenesis of monocrotaline (MCT)-induced pulmonary hypertension, hypothesizing that smoking might accelerate the development of primed pulmonary hypertension. CS was generated from 3R4F reference cigarettes, and rats were exposed to CS by inhalation at total particulate matter concentrations of 100-300 µg/L for 4 h/day, 7 days/week for 4 weeks. Following 1 week of initial exposure, rats received 60 mg/kg MCT and were sacrificed and analyzed after an additional 3 weeks of exposure. MCT induced hypertrophy in pulmonary arterioles and increased the Fulton index, a measure of right ventricular hypertrophy. Additional CS exposure exacerbated arteriolar hypertrophy but did not further elevate the Fulton index. No significant alterations were observed in levels of endothelin-1 and vascular endothelial growth factor, or in hematological and serum biochemical parameters. Short-term inhalation exposure to CS exacerbated arteriolar hypertrophy in the lung, although this effect did not directly aggravate the overworked heart under the current experimental conditions.


Assuntos
Fumar Cigarros , Hipertensão Pulmonar , Ratos , Animais , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/patologia , Monocrotalina/toxicidade , Monocrotalina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Exposição por Inalação/efeitos adversos , Ratos Sprague-Dawley , Hipertrofia , Artéria Pulmonar/patologia
2.
Drug Chem Toxicol ; 45(5): 2109-2115, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33906534

RESUMO

The self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG) is a novel small-interfering RNA (siRNA) nanoparticle that is used for treatment of pulmonary fibrosis. We investigated the potential genotoxicity of SAMiRNA-AREG based on the guidelines published by the Organization for Economic Cooperation and Development. In the bacterial reverse mutation assay (Ames test), SAMiRNA-AREG did not induce mutations in Salmonella typhimurium TA100, TA1535, TA98, and TA1537 and Escherichia coli WP2uvrA at concentrations of up to 3000 µg/plate with or without metabolic activation. The SAMiRNA-AREG (concentrations up to 500 µg/mL) did not induce chromosomal aberrations in cultured Chinese hamster lung cells with or without metabolic activation. In the in vivo mouse bone marrow micronucleus assay, the SAMiRNA-AREG (concentrations up to 300 mg/kg body weight) did not affect the proportions of polychromatic erythrocytes and total erythrocytes, nor did it increase the number of micronucleated polychromatic erythrocytes in ICR mice. Collectively, these results suggest that SAMiRNA-AREG is safe with regard to genotoxicity such as mutagenesis or clastogenesis under the present experimental conditions. These results might support the safety of SAMiRNA-AREG as a potential therapeutic agent for pharmaceutical development.


Assuntos
Micelas , Nanopartículas , Anfirregulina/genética , Animais , Aberrações Cromossômicas , Cricetinae , Cricetulus , Escherichia coli/genética , Camundongos , Camundongos Endogâmicos ICR , Testes para Micronúcleos , Testes de Mutagenicidade , Nanopartículas/toxicidade , RNA Interferente Pequeno/genética
3.
Int J Mol Sci ; 23(24)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36555376

RESUMO

Mitochondria are organelles that play a vital role in cellular survival by supplying ATP and metabolic substrates via oxidative phosphorylation and the Krebs cycle. Hence, mitochondrial dysfunction contributes to many human diseases, including metabolic syndromes, neurodegenerative diseases, cancer, and aging. Mitochondrial transfer between cells has been shown to occur naturally, and mitochondrial transplantation is beneficial for treating mitochondrial dysfunction. In this study, the migration of mitochondria was tracked in vitro and in vivo using mitochondria conjugated with green fluorescent protein (MTGFP). When MTGFP were used in a coculture model, they were selectively internalized into lung fibroblasts, and this selectivity depended on the mitochondrial functional states of the receiving fibroblasts. Compared with MTGFP injected intravenously into normal mice, MTGFP injected into bleomycin-induced idiopathic pulmonary fibrosis model mice localized more abundantly in the lung tissue, indicating that mitochondrial homing to injured tissue occurred. This study shows for the first time that exogenous mitochondria are preferentially trafficked to cells and tissues in which mitochondria are damaged, which has implications for the delivery of therapeutic agents to injured or diseased sites.


Assuntos
Fibrose Pulmonar Idiopática , Mitocôndrias , Camundongos , Humanos , Animais , Mitocôndrias/metabolismo , Pulmão/metabolismo , Fibrose Pulmonar Idiopática/metabolismo , Fibroblastos/metabolismo
4.
Int J Mol Sci ; 23(5)2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35269890

RESUMO

(1) Background: Progression of chronic obstructive pulmonary disease (COPD) leads to irreversible lung damage and inflammatory responses; however, biomarker discovery for monitoring of COPD progression remains challenging. (2) Methods: This study evaluated the metabolic mechanisms and potential biomarkers of COPD through the integrated analysis and receiver operating characteristic (ROC) analysis of metabolic changes in lung, plasma, and urine, and changes in morphological characteristics and pulmonary function in a model of PPE/LPS-induced COPD exacerbation. (3) Results: Metabolic changes in the lungs were evaluated as metabolic reprogramming to counteract the changes caused by the onset of COPD. In plasma, several combinations of phenylalanine, 3-methylhistidine, and polyunsaturated fatty acids have been proposed as potential biomarkers; the α-aminobutyric acid/histidine ratio has also been reported, which is a novel candidate biomarker for COPD. In urine, a combination of succinic acid, isocitric acid, and pyruvic acid has been proposed as a potential biomarker. (4) Conclusions: This study proposed potential biomarkers in plasma and urine that reflect altered lung metabolism in COPD, concurrently with the evaluation of the COPD exacerbation model induced by PPE plus LPS administration. Therefore, understanding these integrative mechanisms provides new insights into the diagnosis, treatment, and severity assessment of COPD.


Assuntos
Lipopolissacarídeos , Doença Pulmonar Obstrutiva Crônica , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Lipopolissacarídeos/metabolismo , Pulmão/metabolismo , Camundongos , Equipamento de Proteção Individual , Doença Pulmonar Obstrutiva Crônica/diagnóstico
5.
Comput Inform Nurs ; 40(7): 438-446, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34723872

RESUMO

When provided with opportunities to view the world from the patients' perspective, nursing students can experience the same practical occurrences and feelings that patients encounter, consequently becoming more aware of their discomfort and pain. This study aimed to evaluate the performance of the patient experience virtual reality blended learning program developed for nursing students. This study is significant in that it presents a program that enables nursing students to not only experience being perioperative patients themselves but also experience their conditions in places other than hospitals, which are generally used as training locations. The analytical results of this study indicated that nursing students who virtually experienced the conditions of perioperative patients through virtual reality blended learning showed increased levels of empathy, positive attitudes toward patient safety treatment, confidence in nursing care, and clinical skill performance. The developed program in this study blended various teaching methods with a virtual reality platform to help junior nursing students with practical and effective perioperative training increase their levels of empathy by simulating the experiences and perspectives of perioperative patients.


Assuntos
Bacharelado em Enfermagem , Estudantes de Enfermagem , Realidade Virtual , Competência Clínica , Bacharelado em Enfermagem/métodos , Humanos , Aprendizagem , Avaliação de Resultados da Assistência ao Paciente
6.
Int J Toxicol ; 40(5): 453-465, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34286615

RESUMO

The present study investigated the potential subchronic toxicity of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG) in mice. The test reagent was administered once-daily by intravenous injection for 4 weeks at 0, 100, 200, or 300 mg/kg/day doses. Additional recovery groups (vehicle control and high dose groups) were observed for a 2-week recovery period. During the test period, mortality, clinical signs, body weight, food consumption, ophthalmology, urinalysis, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. An increase in the percentages of basophil and large unstained cells was observed in the 200 and 300 mg/kg/day groups of both sexes. In addition, the absolute and relative weights of the spleen were higher in males given 300 mg/kg/day relative to the concurrent controls. However, these findings were considered of no toxicological significance because the changes were minimal, were not accompanied by other relevant results (eg, correlating microscopic changes), and were not observed at the end of the 2-week recovery period indicating recovery of the findings. Based on the results, SAMiRNA-AREG did not cause treatment-related adverse effects at dose levels of up to 300 mg/kg/day in mice after 4-week repeated intravenous doses. Under these conditions, the no-observed-adverse-effect level of the SAMiRNA-AREG was ≥300 mg/kg/day in both sexes and no target organs were identified.


Assuntos
Anfirregulina/administração & dosagem , Nanopartículas/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Anfirregulina/toxicidade , Animais , Feminino , Injeções Intravenosas , Masculino , Camundongos Endogâmicos ICR , Micelas , Nanopartículas/toxicidade , Nível de Efeito Adverso não Observado , RNA Interferente Pequeno/toxicidade , Testes de Toxicidade Subaguda
7.
J Clin Nurs ; 30(7-8): 961-974, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33434358

RESUMO

AIMS AND OBJECTIVES: To understand hospice palliative care nurses' (HPCNs) perceptions towards spiritual care and their competence to provide spiritual care. BACKGROUND: Previous research has shown that many nurses lack a clear understanding of the concept of spirituality and feel inadequately prepared to assess patients' spiritual needs. Studies on competence in spiritual care are mostly descriptive, and the evidence for improving it is limited. DESIGN: A mixed-methods research design was used. METHODS: Quantitative data were collected from 282 nurses in forty hospice palliative care (HPC) institutions in South Korea and analysed using descriptive statistics, independent t-test, one-way ANOVA with Bonferroni test and multiple regression. Qualitative data collection involved two stages: first, an open-ended question posed to 282 nurses, and second, focus group interviews conducted with six HPC experts. Both qualitative data sets were analysed separately using content analysis. This study followed the GRAMMS guidelines. RESULTS: Of the six dimensions of spiritual care competence (SCC), the mean scores were highest in 'attitude towards the patient's spirituality' and 'communication', whereas the 'assessment and implementation of spiritual care' and 'professionalisation and improving the quality of spiritual care' had the lowest mean scores. Through content analysis, 4 themes regarding the meaning of spiritual care, 3 themes regarding requirements for spiritual care and 2 themes regarding preparedness for spiritual care were revealed. They perceived the needs of the understanding of spiritual care based on the attributes of spirituality, the education in systematic assessments and implementation for spiritual care with standardised terminology, and the opportunity to reflect on nurses' own spirituality. CONCLUSIONS: Practical SCC training for HPCNs and the subsequent development of clinical practice guidelines are of vital importance. RELEVANCE TO CLINICAL PRACTICE: The results of this study provide a useful resource to develop educational programmes for strengthening the SCC of nurses and the entire HPC team.


Assuntos
Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Hospitais para Doentes Terminais , Espiritualidade , Humanos , Cuidados Paliativos , Percepção , República da Coreia
8.
J Nanobiotechnology ; 18(1): 17, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964393

RESUMO

This study aimed to develop a new colon-targeted drug delivery system via the preparation of ternary nanocomposite carriers based on organic polymer, aminoclay and lipid vesicles. Budesonide (Bud), an anti-inflammatory drug was chosen as a model drug and encapsulated into three different formulations: liposome (Bud-Lip), aminoclay-coated liposome (AC-Bud-Lip), and Eudragit® S100-aminoclay double coated liposome (EAC-Bud-Lip). The formation of the aminoclay-lipid vesicle nanocomposite was confirmed by energy dispersive X-ray spectrum, transmission electron microscopy, and Fourier-transform infrared spectroscopy. All formulations were produced with a high encapsulation efficiency in a narrow size distribution. Drug release from EAC-Bud-Lip was approximately 10% for 2-h incubation at pH 1.2, implying the minimal drug release in acidic gastric condition. At pH 7.4, EAC-Bud-Lip underwent significant size reduction and exhibited drug release profiles similar to that from AC-Bud-Lip, implying the pH-dependent removal of the outer coating layer. Compared to free Bud solution, EAC-Bud-Lip achieved a higher drug uptake in Caco-2 cells and exhibited a stronger inhibition of TNF-α and IL-6 secretion in LPS-stimulated Raw264.7 cells. Furthermore, a bio-distribution study in mice demonstrated that Eudragit® S100-aminoclay dual coating led to a higher colonic distribution with a longer residence time, which correlated well with the delayed systemic drug exposure in rats. Taken together, the present study suggests that the ternary nanocomposite carrier consisting of Eudragit® S100, aminoclay, and lipid vesicle might be useful as an effective colon-targeted drug delivery system.


Assuntos
Anti-Inflamatórios/química , Budesonida/química , Argila/química , Colo/metabolismo , Lipídeos/química , Lipossomos/química , Nanocompostos/química , Animais , Anti-Inflamatórios/farmacocinética , Budesonida/farmacocinética , Células CACO-2 , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Interleucina-6/metabolismo , Masculino , Camundongos , Ácidos Polimetacrílicos/química , Células RAW 264.7 , Ratos Sprague-Dawley , Solubilidade , Propriedades de Superfície , Distribuição Tecidual , Fator de Necrose Tumoral alfa/metabolismo
9.
J Toxicol Environ Health A ; 81(11): 384-396, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29590002

RESUMO

Cadmium (Cd) is a toxic metal present in tobacco smoke, air, food, and water. Inhalation is an important route of Cd exposure, and lungs are one of the main target organs for metal-induced toxicity. Cd inhalation is associated with an increased risk of pulmonary diseases. The present study aimed to assess the effects of repeated exposure to low-dose Cd in a mouse model of polyhexamethylene guanidine (PHMG)-induced lung fibrosis. Mice were grouped into the following groups: vehicle control (VC), PHMG, cadmium chloride (CdCl2), and PHMG + CdCl2. Animals in the PHMG group exhibited increased numbers of total cells and inflammatory cells in the bronchoalveolar lavage fluid (BALF) accompanied by inflammation and fibrosis in lung tissues. These parameters were exacerbated in mice in the PHMG + CdCl2 group. In contrast, mice in the CdCl2 group alone displayed only minimal inflammation in pulmonary tissue. Expression of inflammatory cytokines and fibrogenic mediators was significantly elevated in lungs of mice in the PHMG group compared with that VC. Further, expression of these cytokines and mediators was enhanced in pulmonary tissue in mice administered PHMG + CdCl2. Data demonstrate that repeated exposure to low-dose Cd may enhance the development of PHMG-induced pulmonary fibrosis.


Assuntos
Cloreto de Cádmio/toxicidade , Cádmio/toxicidade , Guanidinas/administração & dosagem , Pulmão/patologia , Fibrose Pulmonar/patologia , Administração por Inalação , Animais , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente
10.
Nanomedicine ; 14(2): 557-567, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29248675

RESUMO

This study aimed to design an effective formulation for enhancing the tumor-targeted delivery of sorafenib. Three sorafenib-loaded liposomal formulations including uncoated liposome (SF-Lip), hyaluronic acid-coated liposome (HA-SF-Lip), and PEGylated hyaluronic acid-coated liposome (PEG-HA-SF-Lip) were developed with narrow size distribution and high encapsulation efficiency. The cellular uptake and cytotoxicity of HA-SF-Lip and PEG-HA-SF-Lip were greater than those of SF-Lip in MDA-MB-231 cells overexpressing CD44, whereas there were no significant differences in MCF-7 cells with low CD44 expression, indicating the CD44-mediated cellular uptake of coated liposomes. In comparison with sorafenib solution, PEG-HA-SF-Lip increased the systemic exposure and plasma half-life in rats by 3-fold and 2-fold, respectively. Consistently, PEG-HA-SF-Lip was the most effective for tumor growth inhibition through CD44 targeting in the MDA-MB-231 tumor xenograft mouse model. Taken together, the present study suggests that PEG-HA-SF-Lip might be effective for the tumor-targeted delivery of sorafenib with enhanced systemic exposure and longer blood circulation.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Ácido Hialurônico/química , Lipossomos/química , Polietilenoglicóis/química , Sorafenibe/farmacologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Sobrevivência Celular , Feminino , Hemólise/efeitos dos fármacos , Humanos , Camundongos , Ratos , Ratos Sprague-Dawley , Sorafenibe/administração & dosagem , Sorafenibe/química , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Comput Inform Nurs ; 36(3): 147-153, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29120912

RESUMO

This study evaluated a system thinking-based simulation program for the care of patients with congestive heart failure. Participants were 67 undergraduate nursing students from a nursing college in Seoul, South Korea. The experimental group was given a 4-hour system-thinking program and a 2-hour simulation program, whereas the control group had a 4-hour case study and a 2-hour simulation program. There were significant improvements in critical thinking in both groups, but no significant group differences between educational methods (F = 3.26, P = .076). Problem-solving ability in the experimental group was significantly higher than in the control group (F = 5.04, P = .028). Clinical competency skills in the experimental group were higher than in the control group (t = 2.12, P = .038). A system thinking-based simulation program is a more effective learning method in terms of problem-solving ability and clinical competency skills compared to the existing simulation program. Further research using a longitudinal study is needed to test the long-term effect of the intervention and apply it to the nursing curriculum.


Assuntos
Competência Clínica , Insuficiência Cardíaca/terapia , Aprendizagem Baseada em Problemas/métodos , Treinamento por Simulação/métodos , Pensamento , Currículo , Avaliação Educacional , Humanos , Estudos Longitudinais , República da Coreia , Estudantes de Enfermagem
12.
Molecules ; 23(8)2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30087305

RESUMO

Nintedanib (NDN), a tyrosine kinase inhibitor, has been shown to have anti-tumor, anti-inflammatory, and anti-fibrotic effects in several reports. We investigated the protective effects of NDN against polyhexamethylene guanidine phosphate (PHMG)-induced lung fibrosis in mice. The following three experimental groups were evaluated: (1) vehicle control; (2) PHMG (1.1 mg/kg); and (3) PHMG & NDN (60 mg/kg). PHMG induced pulmonary inflammation and fibrosis by intratracheal instillation in mice. In contrast, NDN treatment effectively alleviated the PHMG induced lung injury, and attenuated the number of total cells and inflammatory cells in the bronchoalveolar lavage fluid, including the fibrotic histopathological changes, and also reduced the hydroxyproline content. NDN also significantly decreased the expression of inflammatory cytokines and fibrotic factors, and the activation of the NLRP3 inflammasome in lung tissues. These results suggest that NDN may mitigate the inflammatory response and development of pulmonary fibrosis in the lungs of mice treated with PHMG.


Assuntos
Indóis/uso terapêutico , Substâncias Protetoras/uso terapêutico , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Animais , Peso Corporal/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Citocinas/metabolismo , Guanidinas , Hidroxiprolina/metabolismo , Indóis/farmacologia , Inflamassomos/metabolismo , Mediadores da Inflamação/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Fibrose Pulmonar/patologia
13.
Comput Inform Nurs ; 35(3): 145-151, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27820714

RESUMO

Nursing care for patients with central nervous system problems requires advanced professional knowledge and care skills. Nursing students are more likely to have difficulty in dealing with adult patients who have severe neurological problems in clinical practice. This study investigated the effect on the metacognition, team efficacy, and learning attitude of nursing students after an integrated simulation and problem-based learning program. A real scenario of a patient with increased intracranial pressure was simulated for the students. The results showed that this method was effective in improving the metacognitive ability of the students. Furthermore, we used this comprehensive model of simulation with problem-based learning in order to assess the consequences of student satisfaction with the nursing major, interpersonal relationships, and importance of simulation-based education in relation to the effectiveness of the integrated simulation with problem-based learning. The results can be used to improve the design of clinical practicum and nursing education.


Assuntos
Metacognição , Doenças do Sistema Nervoso/diagnóstico , Simulação de Paciente , Aprendizagem Baseada em Problemas/métodos , Estudantes de Enfermagem/psicologia , Adulto , Atitude do Pessoal de Saúde , Competência Clínica , Bacharelado em Enfermagem , Feminino , Humanos , Relações Interpessoais , Masculino , Informática em Enfermagem , Estudantes de Enfermagem/estatística & dados numéricos , Adulto Jovem
14.
Healthcare (Basel) ; 12(19)2024 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-39408127

RESUMO

BACKGROUND/OBJECTIVES: In perioperative nursing practice, nursing students can engage in direct, in-person clinical experiences in perioperative environments; however, they face limitations due to infection and contamination risks. This study aimed to develop and evaluate educational content for perioperative clinical practice for nursing students using virtual reality (VR) and haptic technology. METHODS: The program, based on the Unity Engine, was created through programming and followed the system development lifecycle (SDLC) phases of analysis, design, implementation, and evaluation. This program allows nursing students to engage in perioperative practice using VR and haptic technology, overcoming previous environmental limitations and enhancing practical and immersive experiences through multi-sensory stimuli. RESULTS: Expert evaluations indicated that the developed content was deemed suitable for educational use. Additionally, a usability assessment with 29 nursing students revealed high levels of presence, usability, and satisfaction among the participants. CONCLUSIONS: This program can serve as a foundation for future research on VR-based perioperative nursing education.

15.
Genes Genomics ; 46(9): 1097-1106, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39115674

RESUMO

BACKGROUND: Granzymes are essential serine proteases in cytotoxic T cells and natural killer (NK) cells, with GZMK's expression being less understood. This study aims to uncover GZMK expression profiles across various immune cell types using single-cell RNA sequencing meta-analysis. OBJECTIVE: This study aims to uncover GZMK expression profiles across various immune cell types using single-cell RNA sequencing meta-analysis. METHODS: We conducted a meta-analysis using cellxgene, an interactive data exploration platform developed by the Chan Zuckerberg Initiative. We focused on mature T cells, NK cells, B cells, and NKT cells. We also checked transcription factor binding sites at the granzyme gene promoter regions using JASPAR. Comparative analysis was also done using mouse single-cell RNA sequencing data. RESULTS: GZMK was the most lowly expressed in NK cells and mature NKT cells in most tissues except for colon and lymph nodes. In mature T cells, GZMK is similarly or more highly expressed than other granzymes. HBCA data revealed weak expression of GZMK in NK cells but strong expression in effector memory CD8-positive, alpha-beta T cells. Combined data shows no significant difference in GZMK expression between cell types. Subtype analysis shows that GZMK expression was higher in CD16-negative, CD56-bright NK cells when compared to CD16-positive, CD56-dim NK cells. We also identified unique transcription factor binding sites for GZMK. While this pattern in mouse data with low Gzmk expression in NK cells and higher T cells was repeated. CONCLUSION: GZMK expression is distinctively regulated among immune cells and tissues, with unique promoter regions and transcription factor binding sites contributing to this differential expression. These insights into GZMK's role in immune function and regulation offer potential therapeutic targets.


Assuntos
Granzimas , Células Matadoras Naturais , Análise de Célula Única , Granzimas/genética , Granzimas/metabolismo , Animais , Análise de Célula Única/métodos , Camundongos , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/imunologia , Humanos , RNA-Seq/métodos , Linfócitos B/metabolismo , Linfócitos B/imunologia , Células T Matadoras Naturais/metabolismo , Células T Matadoras Naturais/imunologia , Regiões Promotoras Genéticas , Sítios de Ligação , Análise da Expressão Gênica de Célula Única
16.
Heliyon ; 10(3): e25045, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38317961

RESUMO

Inhalation of polyhexamethylene guanidine phosphate (PHMG) can cause pulmonary fibrosis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) are enzymes that produce reactive oxygen species, which may be involved in tissue damage in various lung diseases. To investigate whether the Nox2 isoform of Nox is involved in the progression of PHMG-induced lung damage, we studied the contribution of Nox2 in PHMG-induced lung injury in Nox2-deficient mice. We treated wild-type (WT) and Nox2 knockout mice with a single intratracheal instillation of 1.1 mg/kg PHMG and sacrificed them after 14 days. We analyzed lung histopathology and the number of total and differential cells in the bronchoalveolar lavage fluid. In addition, the expressions of cytokines, chemokines, and profibrogenic genes were analyzed in the lung tissues. Based on our results, Nox2-deficient mice showed less PHMG-induced pulmonary damage than WT mice, as indicated by parameters such as body weight, lung weight, total cell count, cytokine and chemokine levels, fibrogenic mediator expression, and histopathological findings. These findings suggest that Nox2 may have the potential to contribute to PHMG-induced lung injury and serves as an essential signaling molecule in the development of PHMG-induced pulmonary fibrosis by regulating the expression of profibrogenic genes.

17.
Food Chem Toxicol ; 183: 114201, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38013002

RESUMO

Exposure to particulate matter is currently recognized as a serious aggravating factor of respiratory diseases. In this study, we investigated the effects of particulate matter (PM) on the respiratory system in BALB/c mice and NCI-H292 cells. PM (0, 2.5, 5 and 20 mg/kg) was administered to mice by intra-tracheal instillation for 7 days. After a 7 day-repeated treatment of PM, we evaluated inflammatory cytokines/cell counts in bronchoalveolar lavage fluid (BALF) and conducted pulmonary histology and functional test. We also investigated the role of TXNIP/NF-κB and SIRT1-mediated p53 and TGF-ß/Smad3 pathways in PM-induced airway inflammation and pulmonary dysfunction. PM caused a significant increase in pro-inflammatory cytokines, inflammatory cell counts in bronchoalveolar lavage fluid. PM-mediated oxidative stress down-regulated thioredoxin-1 and up-regulated thioredoxin-interacting protein and activation of nuclear factor-kappa B in the lung tissue and PM-treated NCI-H292 cells. PM suppressed sirtuin1 protein levels and increased p53 acetylation in PM-exposed mice and PM-treated NCI-H292 cells. In addition, PM caused inflammatory cell infiltration and the thickening of alveolar walls by exacerbating the inflammatory response in the lung tissue. PM increased levels of transforming growth factor-ß, phosphorylation of Smad3 and activation of α-smooth muscle actin, and collagen type1A2 in PM-exposed mice and PM-treated NCI-H292 cells. In pulmonary function tests, PM exposure impaired pulmonary function resembling pulmonary fibrosis, characterized by increased resistance and elastance of the respiratory system, and resistance, elastance, and damping of lung tissues, whereas decreased compliance of the respiratory system, forced expired volume and forced vital capacity. Overall, PM-mediated oxidative stress caused airway inflammation and pulmonary dysfunction with pulmonary fibrosis via TXNIP pathway/NF-κB activation and modulation of the SIRT1-mediated TGF-ß/Smad3 pathways. The results of this study can provide fundamental data on the potential adverse effects and underlying mechanism of pulmonary fibrosis caused by PM exposure as a public health concern. Due to the potential toxicity of PM, people with respiratory disease must be careful with PM exposure.


Assuntos
Material Particulado , Fibrose Pulmonar , Doenças Respiratórias , Animais , Humanos , Camundongos , Proteínas de Transporte/metabolismo , Citocinas/metabolismo , Inflamação/metabolismo , Pulmão/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo , Material Particulado/toxicidade , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Doenças Respiratórias/induzido quimicamente , Sirtuína 1/genética , Sirtuína 1/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína Smad3/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-36900904

RESUMO

Several studies have examined the effect of virtual reality (VR) education. However, they are mostly systematic reviews or meta-analyses focusing on doctors and residents; they fail to consider VR medical education for a broader range of learners. We evaluated the effectiveness of VR education for health professionals and identified the essential features of education. Randomized controlled trials published from January 2000 to April 2020 were identified from PubMed, Embase, CINAHL, and the Cochrane Library (n = 299). The randomized studies' bias risk was evaluated using Cochrane's Risk of Bias tool. Meta- and subgroup-analyses were conducted using Review Manager 5.4.1. The overall effect was measured using Hedges' g and determined using Z-statistics (p < 0.05). Heterogeneity was assessed using X2 and I2 statistics. Among the identified records, 25 studies were selected through systematic review, and 18 studies were included in the meta-analysis. We identified a significant improvement in the VR group's skill and satisfaction levels, and that less immersive VR was more efficacious for knowledge outcomes than fully immersive VR. Maximizing the advantages of VR will increase learning opportunities and complement the limited clinical experience, thus improving medical services. A systematic and efficient VR medical education program will greatly enhance learners' core competencies.


Assuntos
Médicos , Realidade Virtual , Humanos , Pessoal de Saúde/educação , Aprendizagem , Competência Clínica
19.
Bull Environ Contam Toxicol ; 89(2): 234-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22673765

RESUMO

The purpose of this study was to examine the effects of veterinary antibiotics, including amoxicillin (AMX), chlortetracycline (CTC) and tylosin (TYL), on the biochemical mechanism of human embryonic kidney cells (HEK293). CTC and TYL inhibited HEK293 cell proliferation, in both time- and dose-dependent manners, and changed the cell morphology; whereas, AMX showed no cytotoxic effects. The cell cycle analysis of CTC and TYL revealed G1-arrest in HEK293 cells. Western blot analysis also showed that CTC and TYL affected the activation of DNA damage responsive proteins, as well as cell cycle regulatory proteins, such as p53, p21(Waf1/Cip1) and Rb protein, which are crucial in the G1-S transition. The activation of p21(Waf1/Cip1) was significantly up-regulated over time, but there was no change in the level of CDK2 expression. The results of this study suggest that veterinary antibiotics, even at low level concentrations on continuous exposure, can potentially risk the development of human cells.


Assuntos
Antibacterianos/efeitos adversos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Exposição Ambiental/análise , Amoxicilina/efeitos adversos , Western Blotting , Clortetraciclina/efeitos adversos , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Dano ao DNA/efeitos dos fármacos , Células HEK293 , Humanos , Proteína do Retinoblastoma/genética , Proteína do Retinoblastoma/metabolismo , Fatores de Risco , Tilosina/efeitos adversos , Regulação para Cima
20.
Artigo em Inglês | MEDLINE | ID: mdl-35564962

RESUMO

This study focused on the effects of aroma foot massage on sleep quality and constipation relief among older adult residents in nursing facilities. This research used a non-equivalent control group and a quasi-experimental design. The participants included 40 older adults aged ≥70 years residing in two nursing facilities in Seoul City. The aroma foot massage nursing intervention consisted of a preparation stage using jojoba carrier (aroma recipe) oil and lavender oil, an aroma foot massage stage, and a finishing stage. Sleep quality scores after the experiment increased by 3.72 at post-test (M = 38.44) compared to pre-test (M = 34.72), which confirmed that sleep quality improved significantly following intervention in the experimental group as compared to the control group (F = 14.45, p = 0.001). Furthermore, the frequency of defecation in the experimental group was significantly higher than that in the control group (Z = −3.93, p < 0.001). Similarly, the constipation assessment scores decreased at post-test significantly by 2.39 in the experimental group as compared to the control group (F = 17.87, p < 0.001). These results confirm that aroma foot massage is an effective nursing intervention for alleviating constipation symptoms and improving sleep quality. Therefore, we recommend that aroma foot massage be used as a complementary intervention in combination with drug-based treatment to improve sleep quality and relieve the constipation symptoms experienced by older adults living in nursing facilities.


Assuntos
Odorantes , Qualidade do Sono , Idoso , Constipação Intestinal/terapia , Humanos , Massagem , Instituições Residenciais
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