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PURPOSE: The purpose of this study was to identify the factors influencing pediatric nurses' job stress, including their level of fatigue and partnerships with the parents of patients. This investigation aimed to findings of this study may lead to the development of strategies to reduce pediatric nurse's job stress. DESIGN AND METHODS: Participants were recruited from pediatric, pediatric intensive care, and neonatal intensive care units across seven general hospitals. Eligibility requires a minimum of 6 months of experience in pediatric nursing. The sample size was determined using the G*power program, considering various variables, including age, marital status, presence of children, and work-related characteristics, leading to a final sample size of 135, adjusted for a 10% dropout rate. Data collection was conducted through self-report questionnaires, and analysis involved frequency, percentage, mean, standard deviation, t-tests, ANOVA, and stepwise multiple regression, using SPSS Statistics 27.0. RESULTS: This study confirmed a significant correlation between pediatric nurses' fatigue and job stress, with higher levels of fatigue associated with increased job stress. Stepwise regression analysis showed that fatigue and age were significant predictors of job stress among pediatric nurses, explaining 23% of the variance. However, detailed analysis showed that younger nurses had lower job stress scores compared to older nurses. This result suggests that more experienced nurses may experience higher job stress due to increased responsibilities and emotional burdens. PRACTICE IMPLICATIONS: This study identified the need for effective strategies to manage fatigue and reduce job stress among pediatric nurses during the COVID-19 pandemic. Younger nurses, particularly those under 25 and between 26 and 30 years old, experience lower job stress compared to older nurses. Comprehensive support systems should be developed, including workload management, emotional support, and programs to enhance partnerships between nurses and parents. These strategies can improve job satisfaction and the quality of care provided to young patients. Additionally, they ensure a more resilient and effective healthcare workforce during pandemics and similar crises.
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COVID-19 , Fadiga , Enfermeiros Pediátricos , Estresse Ocupacional , Enfermagem Pediátrica , Humanos , Feminino , Masculino , COVID-19/epidemiologia , COVID-19/psicologia , Adulto , Enfermeiros Pediátricos/psicologia , Estresse Ocupacional/psicologia , Estresse Ocupacional/epidemiologia , Fadiga/psicologia , Fadiga/epidemiologia , Inquéritos e Questionários , Pais/psicologia , Pandemias , Relações Profissional-Família , SARS-CoV-2 , Recursos Humanos de Enfermagem Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricosRESUMO
PURPOSE: This study was conducted to develop a cultural competence scale for nurses regarding the lesbian, gay, bisexual, and transgender (LGBT) community and to test its validity and reliability. METHODS: The study adhered to the 8-step process outlined by DeVellis, with an initial set of 25 items derived through a literature review and individual interviews. Following an expert validity assessment, 24 items were validated. Subsequently, a preliminary survey was conducted among 23 nurses with experience caring for LGBT patients. Data were then collected from a final sample of 322 nurses using the 24 items. Item analysis, item-total score correlation, examination of construct and convergent validity, and reliability testing were performed. RESULTS: The item-level content validity index exceeded .80, and the explanatory power of the construct validity was 63.63%. The factor loadings varied between 0.57 and 0.80. The scale comprised five factors: cultural skills, with seven items; cultural awareness, with five items; cultural encounters, with three items; cultural pursuit, with three items; and cultural knowledge, with three items; totaling 21 items. Convergent validity demonstrated a high correlation, affirming the scale's validity. Internal consistency analysis yielded an overall reliability coefficient of 0.97, signifying very high reliability. Each item is scored from 1 to 6 (total score range, 21-126), with higher scores reflecting greater cultural competence in LGBT care. CONCLUSION: This scale facilitates the measurement of LGBT cultural competence among nurses. Therefore, its use should provide foundational data to support LGBT-focused nursing education programs.
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Competência Cultural , Enfermeiras e Enfermeiros , Psicometria , Minorias Sexuais e de Gênero , Humanos , Feminino , Masculino , Reprodutibilidade dos Testes , Inquéritos e Questionários , República da Coreia , Adulto , Enfermeiras e Enfermeiros/psicologia , Enfermeiras e Enfermeiros/estatística & dados numéricos , Psicometria/métodos , Pessoa de Meia-Idade , Pessoas Transgênero/psicologiaRESUMO
CD150, also termed signaling lymphocyte activation molecule family member 1, is a cell surface receptor expressed on T cells, B cells, dendritic cells (DCs) and some tumors. Stimulation of CD150 on immune cells induces cell proliferation and cytokine production. However, the function of CD150 in EpsteinBarr virus (EBV)infected B cells is still not fully understood. In the present study, CD150 expression on B cells increased rapidly following EBV infection, and various CD150 antibodies, measles viral proteins and recombinant CD150 proteins induced the secretion of multiple cytokines in both CD150+ EBVtransformed B cells and EBV+ lymphoma cells. Notably, the IL1α protein level showed the greatest increase among all cytokines measured. The culture supernatant containing these cytokines induced the rapid differentiation of monocytes to DCs after only 2 days in vitro, which was faster than the established DC maturation time. Furthermore, knockdown of CD150 expression led to a reduction in the secretion of multiple cytokines, and monocyte differentiation was partially inhibited by antiIL1α and antigranulocytemacrophage colonystimulating factor neutralizing antibodies. Collectively, the results of the present study suggest that CD150 activation triggers cytokine production in EBVtransformed B cells, and that measles virus coinfection might affect immune responses through the production of various cytokines in EBV+ lymphoma cells.
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Linfócitos B , Diferenciação Celular , Citocinas , Herpesvirus Humano 4 , Monócitos , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária , Humanos , Herpesvirus Humano 4/imunologia , Linfócitos B/metabolismo , Linfócitos B/imunologia , Linfócitos B/virologia , Citocinas/metabolismo , Monócitos/metabolismo , Monócitos/imunologia , Monócitos/virologia , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/metabolismo , Células Dendríticas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/virologia , Ativação Linfocitária/imunologiaRESUMO
Upon encountering allergens, CD4+ T cells differentiate into IL-4-producing Th2 cells in lymph nodes, which later transform into polyfunctional Th2 cells producing IL-5 and IL-13 in inflamed tissues. However, the precise mechanism underlying their polyfunctionality remains elusive. In this study, we elucidate the pivotal role of NRF2 in polyfunctional Th2 cells in murine models of allergic asthma and in human Th2 cells. We found that an increase in reactive oxygen species (ROS) in immune cells infiltrating the lungs is necessary for the development of eosinophilic asthma and polyfunctional Th2 cells in vivo. Deletion of the ROS sensor NRF2 specifically in T cells, but not in dendritic cells, significantly abolished eosinophilia and polyfunctional Th2 cells in the airway. Mechanistically, NRF2 intrinsic to T cells is essential for inducing optimal oxidative phosphorylation and glycolysis capacity, thereby driving Th2 cell polyfunctionality independently of IL-33, partially by inducing PPARγ. Treatment with an NRF2 inhibitor leads to a substantial decrease in polyfunctional Th2 cells and subsequent eosinophilia in mice and a reduction in the production of Th2 cytokines from peripheral blood mononuclear cells in asthmatic patients. These findings highlight the critical role of Nrf2 as a spatial and temporal metabolic hub that is essential for polyfunctional Th2 cells, suggesting potential therapeutic implications for allergic diseases.
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Asma , Fator 2 Relacionado a NF-E2 , Células Th2 , Animais , Feminino , Humanos , Camundongos , Asma/imunologia , Asma/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Eosinofilia/imunologia , Eosinofilia/metabolismo , Glicólise , Interleucina-33/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/metabolismo , Fosforilação Oxidativa , PPAR gama/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células Th2/imunologia , Células Th2/metabolismoRESUMO
Alcoholic liver disease (ALD) significantly affects immune cell function and leads to immunological dysregulation. This study explored the potential of granulocyte colony-stimulating factor (G-CSF) to mitigate the negative effects of alcohol on immune cells in a mouse model of ALD. To investigate the capacity of G-CSF, ALD was induced using a 17-day alcohol-enriched diet, followed by a single G-CSF dose prior to sampling. We focused on the dynamics of peripheral blood mononuclear cells using high-dimensional mass cytometry to detect subtle changes. Alcohol intake reduced the number of B cells, monocytes, dendritic cells, and NK cells while increasing the number of T cells. Notably, G-CSF treatment reversed the alcohol-induced increase in total CD4+ and CD8+ T cell populations. This effect was remarkable in naïve, effector CD4+ T cells and naïve CD8+ T cells. PhenoGraph and FlowSOM analysis further revealed the recovery effect of G-CSF on specific T cell subgroups, including central memory CD8+ T cells and double-negative T cells expressing Ly6chighCD44high, which are adversely affected by alcohol. These results enhance our understanding of the effect of ALD on immune function and suggest that G-CSF is a potential therapeutic agent, laying the foundation for future clinical research.
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Fator Estimulador de Colônias de Granulócitos , Hepatopatias Alcoólicas , Animais , Masculino , Camundongos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Modelos Animais de Doenças , Etanol/farmacologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Hepatopatias Alcoólicas/imunologia , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/patologia , Camundongos Endogâmicos C57BL , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologiaAssuntos
Varicela , Imunização Secundária , Humanos , Varicela/virologia , Evolução Fatal , Herpesvirus Humano 3/isolamento & purificação , Herpesvirus Humano 3/genética , Vacina contra Varicela/efeitos adversos , Vacina contra Varicela/administração & dosagem , Vacina contra Varicela/imunologia , Masculino , Imunocompetência , Feminino , Pré-EscolarRESUMO
Immunoregulatory mechanisms established in the lymphoid organs are vital for preventing autoimmunity. However, the presence of similar mechanisms in non-lymphoid tissues remains unclear. Through transcriptomic and lipidomic analyses, we find a negative association between psoriasis and fatty acid metabolism, as well as Th2 signature. Homeostatic expression of liver X receptor (LXR) and peroxisome proliferator-activated receptor gamma (PPARγ) is essential for maintaining fatty acid metabolism and for conferring resistance to psoriasis in mice. Perturbation of signal transducer and activator of transcription 6 (STAT6) diminishes the homeostatic levels of LXR and PPARγ. Furthermore, mice lacking STAT6, interleukin 4 receptor alpha (IL-4Rα), or IL-13, but not IL-4, exhibit increased susceptibility to psoriasis. Under steady state, innate lymphoid cells (ILCs) are the primary producers of IL-13. In human skin, inhibiting tonic type 2 immunity exacerbates psoriasis-like inflammation and IL-17A, while activating LXR or PPARγ inhibits them. Hence, we propose that tonic type 2 immunity, driven by IL-13-producing ILCs, represents a crucial tissue checkpoint that represses autoimmunity and maintains lipid homeostasis in the skin.
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Autoimunidade , Receptores X do Fígado , PPAR gama , Pele , Animais , Pele/imunologia , Pele/metabolismo , Pele/patologia , Humanos , Receptores X do Fígado/metabolismo , Camundongos , PPAR gama/metabolismo , Psoríase/imunologia , Psoríase/patologia , Psoríase/metabolismo , Camundongos Endogâmicos C57BL , Interleucina-13/metabolismo , Fator de Transcrição STAT6/metabolismo , Imunidade Inata , Masculino , Feminino , Linfócitos/imunologia , Linfócitos/metabolismoRESUMO
A recent study discovered a novel, complex developmental disability syndrome, most likely caused by maternal fentanyl use disorder. This Fetal Fentanyl Syndrome (FFS) is biochemically characterized by elevated 7-dehydrocholesterol (7-DHC) levels in neonates, raising the question if fentanyl inhibition of the dehydrocholesterol reductase 7 (DHCR7) enzyme is causal for the emergence of the pathophysiology and phenotypic features of FFS. To test this hypothesis, we undertook a series of experiments on Neuro2a cells, primary mouse neuronal and astrocytic cultures, and human dermal fibroblasts (HDFs) with DHCR7+/+ and DHCR7+/- genotype. Our results revealed that in vitro exposure to fentanyl disrupted sterol biosynthesis across all four in vitro models. The sterol biosynthesis disruption by fentanyl was complex, and encompassed the majority of post-lanosterol intermediates, including elevated 7-DHC and decreased desmosterol (DES) levels across all investigated models. The overall findings suggested that maternal fentanyl use in the context of an opioid use disorder leads to FFS in the developing fetus through a strong disruption of the whole post-lanosterol pathway that is more complex than a simple DHCR7 inhibition. In follow-up experiments we found that heterozygous DHCR7+/- HDFs were significantly more susceptible to the sterol biosynthesis inhibitory effects of fentanyl than wild-type DHCR7+/+ fibroblasts. These data suggest that DHCR7+/- heterozygosity of mother and/or developing child (and potentially other sterol biosynthesis genes), when combined with maternal fentanyl use disorder, might be a significant contributory factor to the emergence of FFS in the exposed offspring. In a broader context, we believe that evaluation of new and existing medications for their effects on sterol biosynthesis should be an essential consideration during drug safety determinations, especially in pregnancy.
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PURPOSE: Patients' perception of fall risk is a promising new indicator for fall prevention. Therefore, a fall risk perception questionnaire that can be used rapidly and repeatedly in acute care settings is required. This study aimed to develop a short version of the fall risk perception questionnaire (Short-FRPQ) for inpatients. METHODS: For the psychometric measurements, 246 inpatients were recruited from an acute care hospital. The construct (using confirmatory factor analysis and discriminant validity of each item), convergent, and known-group validities were tested to determine the validity of the Short-FRPQ. McDonald's omega coefficient was used to examine the internal consistency of reliability. RESULTS: In the confirmatory factor analysis, the fit indices of the Short-FRPQ, comprising 14 items and three factors, appeared to be satisfactory. The Short-FRPQ had a significantly positive correlation with the original scale, the Korean Falls Efficacy Scale-International, and the Morse Fall Scale. The risk of falls group, assessed using the Morse Fall Scale, had a higher score on the Short-FRPQ. McDonald's omega coefficient was .90. CONCLUSION: The Short-FRPQ presents good reliability and validity. As patient participation is essential in fall interventions, evaluating the fall risk perception of inpatients quickly and repeatedly using scales of acceptable validity and reliability is necessary.
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Acidentes por Quedas , Pacientes Internados , Percepção , Psicometria , Humanos , Acidentes por Quedas/prevenção & controle , Inquéritos e Questionários , Feminino , Masculino , Pacientes Internados/psicologia , Pessoa de Meia-Idade , Idoso , Adulto , Hospitais , Idoso de 80 Anos ou mais , Análise Fatorial , Medição de RiscoRESUMO
BACKGROUND: Gender sensitivity, which is the capacity to recognize and address issues of gender discrimination and inequality, is initiated with an awareness of gender differences. This is particularly crucial in nursing, where care is tailored to the holistic needs of individuals. Given the sensitive nature of nursing to gender variances, it is essential that the influences of nurses' own experiences and perceptions on their gender sensitivity are explored. This study is aimed at assessing the effects of childhood experiences of domestic violence and perceptions of sexism among healthcare providers on their gender sensitivity. Additionally, it seeks to provide empirical data to support the enhancement of gender-sensitive practices within nursing environments, thereby fostering a culture of gender equality, and helping to promote the practical application of gender equality within nursing organizations. METHODS: A cross-sectional survey was employed to gather data from 146 nurses aged 24 and above residing in Daegu. The general characteristics of these nurses, their childhood experiences of domestic violence, their perceptions of sexism, and their level of gender sensitivity were measured. The data were then subjected to a series of statistical analyses, including t-tests, one-way analysis of variance, Pearson's correlation coefficients, and hierarchical regression analysis, to identify the factors influencing gender sensitivity. RESULTS: It was revealed by the analysis that nurses' gender sensitivity was not significantly associated with their childhood experiences of domestic violence. However, a negative correlation was found between gender sensitivity and their perceptions of sexism (r = -0.46, p < 0.001). Additionally, age and perception of sexism were emerged as significant predictors of gender sensitivity, accounting for 42.7% of the variance in the regression model. CONCLUSION: This study identifies age and sexism perceptions as key predictors of gender sensitivity among nurses, accounting for 42.7% of the variance. It highlights the importance of recognizing generational cultural differences and implementing flexible practices in nursing organizations. Leaders should enhance cultural awareness and address sexism. Further research is needed on the role of societal and cultural norms in recognizing domestic violence. These findings emphasize the need for targeted interventions to improve gender sensitivity and support high-quality nursing care.
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Type 2 innate lymphoid cells (ILC2s) have emerged as key regulators of the immune response in renal inflammatory diseases such as lupus nephritis. However, the mechanisms underlying ILC2 adhesion and migration in the kidney remain poorly understood. Here, we revealed the critical role of integrin α4ß7 in mediating renal ILC2 adhesion and function. We found that integrin α4ß7 enables the retention of ILC2s in the kidney by binding to VCAM-1, E-cadherin, or fibronectin on structural cells. Moreover, integrin α4ß7 knockdown reduced the production of the reparative cytokine amphiregulin (Areg) by ILC2s. In lupus nephritis, TLR7/9 signaling within the kidney microenvironment downregulates integrin α4ß7 expression, leading to decreased Areg production and promoting the egress of ILC2s. Notably, IL-33 treatment upregulated integrin α4ß7 and Areg expression in ILC2s, thereby enhancing survival and reducing inflammation in lupus nephritis. Together, these findings highlight the potential of targeting ILC2 adhesion as a therapeutic strategy for autoimmune kidney diseases.
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Anfirregulina , Integrina alfa4 , Cadeias beta de Integrinas , Nefrite Lúpica , Linfócitos , Nefrite Lúpica/imunologia , Anfirregulina/imunologia , Linfócitos/imunologia , Integrina alfa4/genética , Integrina alfa4/imunologia , Humanos , Feminino , Animais , Camundongos , Modelos Animais de Doenças , Cadeias beta de Integrinas/genética , Cadeias beta de Integrinas/imunologia , Adesão Celular/imunologia , Movimento Celular/imunologia , Rim/efeitos dos fármacos , Rim/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Ligação Proteica/imunologia , Interleucina-33/farmacologia , Transdução de SinaisRESUMO
PURPOSE: Diabetes is a chronic metabolic disease that affects approximately 422 million people worldwide and leads to the death of 1.5 million people every year. The prevalence of diabetes among the population aged 30 or older in Korea has steadily increased since 2018, reaching 16.7% in 2020, with one in six adults having diabetes. This study was conducted to identify factors affecting weight management in overweight or obese patients with diabetes (OOPD) in Korea using data from the 2018-2022 National Health and Nutrition Examination Survey. Therefore, the goal of this study is to analyze weight perception and factors related to weight perception and to identify factors that influence weight loss efforts among OOPD in Korea. METHODS: Socioeconomic characteristics, disease morbidity, weight perception, and weight loss efforts were investigated in 950 participants. Data were analyzed using descriptive statistics, cross-tabulation, and logistic regression. RESULTS: Among the overweight or obese patients with diabetes, 24.4% perceived their weight to be normal, with a higher proportion among men (29.6%) than among women (14.6%). Weight loss efforts were 5.11 times (95% CI: 3.02-8.66) higher in people with overweight perceptions than in those with normal weight perceptions. Additionally, the rate was 1.54 times (95% CI: 1.06 2.25) higher in people with dyslipidemia than in those without dyslipidemia. CONCLUSION: These results suggest that weight management approaches for overweight or obese patients with diabetes should be designed individually based on weight perception and disease morbidity.
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Intracellular redox homeostasis in the airway epithelium is closely regulated through adaptive signaling and metabolic pathways. However, inhalational exposure to xenobiotic stressors such as secondary organic aerosols (SOA) can alter intracellular redox homeostasis. Isoprene hydroxy hydroperoxide (ISOPOOH), a ubiquitous volatile organic compound derived from the atmospheric photooxidation of biogenic isoprene, is a major contributor to SOA. We have previously demonstrated that exposure of human airway epithelial cells (HAEC) to ISOPOOH induces oxidative stress through multiple mechanisms including lipid peroxidation, glutathione oxidation, and alterations of glycolytic metabolism. Using dimedone-based reagents and copper catalyzed azo-alkynyl cycloaddition to tag intracellular protein thiol oxidation, we demonstrate that exposure of HAEC to micromolar levels of ISOPOOH induces reversible oxidation of cysteinyl thiols in multiple intracellular proteins, including GAPDH, that was accompanied by a dose-dependent loss of GAPDH enzymatic activity. These results demonstrate that ISOPOOH induces an oxidative modification of intracellular proteins that results in loss of GAPDH activity, which ultimately impacts the dynamic regulation of the intracellular redox homeostatic landscape in HAEC.
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Células Epiteliais , Oxirredução , Estresse Oxidativo , Compostos de Sulfidrila , Humanos , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Compostos de Sulfidrila/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Hemiterpenos/metabolismo , Peróxidos/metabolismoRESUMO
BACKGROUND: Compassion competence is a core nursing skill that is significant in understanding and alleviating the physical and mental distress of individuals. Self-leadership and nursing professional values are also reported as important factors in improving the clinical care practices of nurses and may have a positive effect on improving the compassion competence of nurses. However, there are few studies examining the relationship between these variables in community mental health nurses. AIM: This study investigated the mediating effect of professional values on the relationship between self-leadership and compassion competence of community mental health nurses. METHODS: A cross-sectional correlational study was conducted with 121 community mental health nurses from 30 mental health welfare centers in South Korea. Participants completed self-report scales on self-leadership, nursing professional values, and compassion competence. Baron and Kenny's regression method and the Sobel test revealed significant mediating effects of nursing professional values on the relationship between self-leadership and compassion competence. FINDINGS: Participants' mean compassion competence scores were 3.57 (SD = 0.45) on a 5-point scale. Compassion competence positively correlated with self-leadership (r = 0.67, P < .001) and nursing professional values (r = 0.60, P < .001). Nursing professional values played a partial mediating role in the relationship between self-leadership and compassion competence (Z = 3.23, P = .001). CONCLUSION: Compassion competence of community mental health nurses can be improved by promoting self-leadership and nursing professional values.
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Empatia , Liderança , Humanos , Estudos Transversais , Feminino , Masculino , Adulto , República da Coreia , Inquéritos e Questionários , Pessoa de Meia-Idade , Enfermagem Psiquiátrica , Competência Clínica/normas , Competência Clínica/estatística & dados numéricosRESUMO
BACKGROUND: Previous studies have suggested that platelets are associated with inflammation and steatosis and may play an important role in liver health. Therefore, we evaluated whether antiplatelet agents can improve metabolic disorder-related fatty liver disease (MASLD). METHODS: The mice used in the study were fed a high-fat-diet (HFD) and were stratified through liver biopsy at 18 weeks. A total of 22 mice with NAFLD activity scores (NAS) ≥ 4 were randomly divided into three groups (HFD-only, clopidogrel (CLO; 35 mg/kg/day), ticagrelor (TIC; 40 mg/kg/day) group). And then, they were fed a feed mixed with the respective drug for 15 weeks. Blood and tissue samples were collected and used in the study. RESULTS: The TIC group showed a significantly lower degree of NAS and steatosis than the HFD group (p = 0.0047), but no effect on the CLO group was observed. Hepatic lipogenesis markers' (SREBP1c, FAS, SCD1, and DGAT2) expression and endoplasmic reticulum (ER) stress markers (CHOP, Xbp1, and GRP78) only reduced significantly in the TIC treatment group. Inflammation genes (MCP1 and TNF-α) also decreased significantly in the TIC group, but not in the CLO group. Nile red staining intensity and hepatic lipogenesis markers were reduced significantly in HepG2 cells following TIC treatment. CONCLUSION: Ticagrelor attenuated NAS and hepatic steatosis in a MASLD mice model by attenuating lipogenesis and inflammation, but not in the CLO group.
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Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Clopidogrel/farmacologia , Clopidogrel/uso terapêutico , Ticagrelor/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , InflamaçãoRESUMO
Background Exercise is crucial for the well-being of people with Parkinson's disease (PD). Although there are challenges to exercising with PD, mobile apps are seen as potential solutions, though their impact is not yet fully understood. We developed a mobile app and a home-based exercise program specialised for people with PD and investigated the effect of the mobile exercise app for the people with PD. Methods Participants from the Movement Disorder Clinic were prompted to download and actively use our app for a duration of 2 weeks. Before commencing, we assessed their self-rated smartphone proficiency. Both at the start and after the 2-week period, we employed the International Physical Activity Questionnaire-Short Form and the PD Questionnaire-39 (PDQ-39) to evaluate their physical activity and overall quality of life (QoL). Exercise metrics were quantified in terms of metabolic equivalent minutes per week (MET-min/week). Furthermore, we gathered feedback on user satisfaction with the app at the end of the study. Results Out of 41 recruited patients, 25 completed the 2-week program and 16 dropped out. Median MET-min/week rose from 1386.0 to 3210.0 (P = 0.009), primarily in moderate activities (P = 0.049) and walking (P = 0.002). Median PDQ-39 scores showed improvement from 17.2 to 8.5 (P = 0.005) after the program. Conclusion The mobile app holds potential to enhance exercise and QoL for people with PD. For optimal benefits, future studies should focus on e-health literacy education, app quality enhancements, and a broader exercise program variety.
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Aplicativos Móveis , Doença de Parkinson , Humanos , Projetos Piloto , Qualidade de Vida , Doença de Parkinson/terapia , Exercício FísicoRESUMO
This study aimed to investigate the effects and mechanism of Lactobacillus gasseri BNR17, a probiotic strain isolated from human breast milk, on dexamethasone-induced muscle loss in mice and cultured myotubes. BALB/c mice were intraperitoneally injected with dexamethasone, and orally administered L. gasseri BNR17 for 21 days. L. gasseri BNR17 treatment ameliorated dexamethasone-induced decline in muscle function, as evidenced by an increase in forelimb grip strength, treadmill running time, and rotarod retention time in both female and male mice. In addition, L. gasseri BNR17 treatment significantly increased the mass of the gastrocnemius and quadriceps muscles. Dual-energy X-ray absorptiometry showed a significant increase in lean body mass and a decrease in fat mass in both whole body and hind limb after treatment with L. gasseri BNR17. It was found that L. gasseri BNR17 treatment downregulated serum myostatin level and the protein degradation pathway composed of muscle-specific ubiquitin E3 ligases, MuRF1 and MAFbx, and their transcription factor FoxO3. In contrast, L. gasseri BNR17 treatment upregulated serum insulin-like growth factor-1 level and Akt-mTOR-p70S6K signaling pathway involved in protein synthesis in muscle. As a result, L. gasseri BNR17 treatment significantly increased the levels of major muscular proteins such as myosin heavy chain and myoblast determination protein 1. Consistent with in vivo results, L. gasseri BNR17 culture supernatant significantly ameliorated dexamethasone-induced C2C12 myotube atrophy in vitro. In conclusion, L. gasseri BNR17 ameliorates muscle loss by downregulating the protein degradation pathway and upregulating the protein synthesis pathway.
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Dexametasona , Lactobacillus gasseri , Camundongos Endogâmicos BALB C , Fibras Musculares Esqueléticas , Proteínas Musculares , Músculo Esquelético , Atrofia Muscular , Probióticos , Ubiquitina-Proteína Ligases , Animais , Dexametasona/efeitos adversos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Camundongos , Feminino , Masculino , Proteínas Musculares/metabolismo , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/metabolismo , Atrofia Muscular/tratamento farmacológico , Lactobacillus gasseri/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Proteínas Ligases SKP Culina F-Box/metabolismo , Proteínas Ligases SKP Culina F-Box/genética , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genética , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
Recently identified human FOXP3lowCD45RA- inflammatory non-suppressive (INS) cells produce proinflammatory cytokines, exhibit reduced suppressiveness, and promote antitumor immunity unlike conventional regulatory T cells (Tregs). In spite of their implication in tumors, the mechanism for generation of FOXP3lowCD45RA- INS cells in vivo is unclear. We showed that the FOXP3lowCD45RA- cells in human tumors demonstrate attenuated expression of CRIF1, a vital mitochondrial regulator. Mice with CRIF1 deficiency in Tregs bore Foxp3lowINS-Tregs with mitochondrial dysfunction and metabolic reprograming. The enhanced glutaminolysis activated α-ketoglutarate-mTORC1 axis, which promoted proinflammatory cytokine expression by inducing EOMES and SATB1 expression. Moreover, chromatin openness of the regulatory regions of the Ifng and Il4 genes was increased, which facilitated EOMES/SATB1 binding. The increased α-ketoglutarate-derived 2-hydroxyglutarate down-regulated Foxp3 expression by methylating the Foxp3 gene regulatory regions. Furthermore, CRIF1 deficiency-induced Foxp3lowINS-Tregs suppressed tumor growth in an IFN-γ-dependent manner. Thus, CRIF1 deficiency-mediated mitochondrial dysfunction results in the induction of Foxp3lowINS-Tregs including FOXP3lowCD45RA- cells that promote antitumor immunity.
Assuntos
Proteínas de Ligação à Região de Interação com a Matriz , Doenças Mitocondriais , Neoplasias , Humanos , Camundongos , Animais , Linfócitos T Reguladores , Ácidos Cetoglutáricos/metabolismo , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Citocinas/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismoRESUMO
BACKGROUND/AIM: Nasopharyngeal carcinoma (NPC), a common cancer in Southern China, is associated with Epstein-Barr Virus (EBV) infection. Although many therapies for NPC have been established, the definite role of EBV in NPC remains unclear. Therefore, this work focuses on LMP2A, a latent EBV gene, and investigates whether LMP2A is related to peroxiredoxin 1 (PRDX1) in EBV-positive NPC. MATERIALS AND METHODS: The mRNA and protein expression levels of LMP2A, PRDX1, and beta-catenin were compared in patient samples. To identify molecular mechanisms, EBV-negative NP69 and EBV-positive C666-1 NPC cell lines were used. After making an agar cell block for cell slides, the intensity of LMP2A expression was observed visually. To measure the level of reactive oxygen species, both fluorescence microscope and flow cytometry were used. To investigate the intracellular signaling molecular mechanisms with and without the LMP2A gene, reverse transcription polymerase chain reaction and western blotting were used. RESULTS: Both patient samples and cells of nasopharyngeal carcinoma infected with EBV had increased expression of LMP2A compared with controls, and high ROS levels were identified. Cell viability assay showed that LMP2A promoted cell growth by regulating gene expression. Furthermore, LMP2A induced the expression of PRDX1 and beta-catenin. LMP2A also increased the expression of both cyclin B1 and cyclin D1. CONCLUSION: In NPC cells, PRDX1 and beta-catenin were regulated through LMP2A expression, which reduced cell growth through cell cycle-related gene expression. This study suggests that LMP2A could be a target molecule for inhibiting cancer progression in NPC cells infected with EBV.
Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4/genética , beta Catenina/metabolismo , Neoplasias Nasofaríngeas/patologiaRESUMO
The intricate role of innate type-2 cytokines in immune responses is increasingly acknowledged for its dual nature, encompassing both protective and pathogenic dimensions. Ranging from defense against parasitic infections to contributing to inflammatory diseases like asthma, fibrosis, and obesity, these cytokines intricately engage with various innate immune cells. This review meticulously explores the cellular origins of innate type-2 cytokines and their intricate interactions, shedding light on factors that amplify the innate type-2 response, including TSLP, IL-25, and IL-33. Recent advancements in therapeutic strategies, specifically the utilization of biologics targeting pivotal cytokines (IL-4, IL-5, and IL-13), are discussed, offering insights into both challenges and opportunities. Acknowledging the pivotal role of innate type-2 cytokines in orchestrating immune responses positions them as promising therapeutic targets. The evolving landscape of research and development in this field not only propels immunological knowledge forward but also holds the promise of more effective treatments in the future.