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1.
Front Immunol ; 15: 1411392, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39351218

RESUMEN

Haploidentical hematopoietic cell transplantation (haplo-HCT) is associated with an increased risk of allograft rejection. Here, we employed a major histocompatibility complex (MHC)-mismatched allogeneic HCT (allo-HCT) murine model to better understand the role of Gal-1 in immune tolerance. Transplanted mice were classified into either rejected or engrafted based on donor chimerism levels. We noted significantly higher frequencies of CD4+ T cells, CD8+ T cells, natural killer cells, IFN-γ and TNF-α producing CD4+ T cells, and IFN-γ producing dendritic cells and macrophages in rejected mice. Conversely, we found significantly increased frequencies of regulatory T cells (Tregs), predominantly Helios+, IL-10-producing CD4+ T cells, type 1 regulatory (Tr1) cells, and the proportion of Tr1+Gal-1+ cells in engrafted mice. Further, Gal-1 specific blockade in Tregs reduced suppression of effector T cells in engrafted mice. Lastly, effector T cells from engrafted mice were more prone to undergo apoptosis. Collectively, we have shown that Gal-1 may favor HSC engraftment in an MHC-mismatched murine model. Our results demonstrate that Gal-1-expressing Tregs, especially at earlier time points post-transplant, are associated with inducing immune tolerance and stable mixed chimerism after HCT.


Asunto(s)
Galectina 1 , Trasplante de Células Madre Hematopoyéticas , Linfocitos T Reguladores , Animales , Ratones , Galectina 1/inmunología , Galectina 1/metabolismo , Linfocitos T Reguladores/inmunología , Ratones Endogámicos C57BL , Rechazo de Injerto/inmunología , Trasplante Homólogo , Complejo Mayor de Histocompatibilidad/inmunología , Supervivencia de Injerto/inmunología , Ratones Endogámicos BALB C , Tolerancia Inmunológica
2.
J Control Release ; 375: 601-613, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39278357

RESUMEN

Thermogenic brown adipose tissue (BAT) has emerged as an attractive target for combating obesity. However, pharmacological activation of energy expenditure by BAT and/or induction of browning of white adipose tissue (WAT) has been hampered by cardiovascular side effects. To address these concerns, we developed polylactide-co-glycolide acid (PLGA) microspheres loaded with mirabegron (MIR), a selective beta-3 adrenergic receptor (ADRB3) agonist, to achieve sustained local induction and activation of thermogenic adipocytes. MIR-loaded PLGA microspheres (MIR-MS) effectively activated brown adipocytes and enhanced the thermogenic program in white adipocytes. Moreover, treating isolated inguinal WAT (iWAT) with MIR-MS resulted in increased expression of browning markers and elevated lipolysis mainly via ADRB3. In mice, injection of MIR-MS over four weeks induced browning of iWAT at the injection site. Importantly, local MIR-MS injection successfully mitigated unwanted cardiovascular risks, including high systolic blood pressure (SBP) and heart rate, as compared to MIR-treated mice. Finally, injecting MIR-MS into human subcutaneous WAT led to a significant induction of lipolysis and an increase in the expression of thermogenic marker uncoupling protein 1 (UCP1). Taken together, our findings indicate that MIR-MS function as a local drug release system that induces browning of human and murine subcutaneous WAT while mitigating undesirable cardiovascular effects.

3.
RSC Adv ; 14(42): 30912-30923, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39346526

RESUMEN

Carbon nano-spheres (CNS) were synthesized via a hydrothermal method using d-glucose as a precursor, followed by pyrolysis in a nitrogen atmosphere. The resulting CNS were integrated into polysulfone (PSF) membranes to enhance their photothermal properties. Characterization using various techniques revealed improved thermal properties upon CNS inclusion, with a notable increase in membrane surface temperature and enhancement of contact angle (CA) and liquid entry pressure (LEP). Composite PSF membranes containing varying CNS concentrations (0.25-5%) exhibited optimal performance at 3% CNS concentration, demonstrating enhanced morphological conformation and photothermal attributes. Evaluation under tungsten bulbs light using a photothermal membrane distillation system showed significant improvement in membrane distillation flux, achieving a maximum water flux of 7.73 L m-2 h-1 and a salt rejection rate of 99.9%. These findings highlight the potential of hydrothermal CNS in enhancing photothermal properties and membrane performance for applications in desalination and wastewater treatment.

4.
CNS Neurosci Ther ; 30(9): e70025, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39228080

RESUMEN

AIMS: The study aimed to evaluate the potential benefits of luteolin treatment in Huntington's disease (HD), an inherited progressive neurodegenerative disorder. METHODS: HD N171-82Q transgenic and WT mice received luteolin or vehicle for treatment at 6 weeks of age. The mice's body weight changes and survival rates were monitored throughout the study, and a series of motor functional tests were conducted. Serum level of the marker NfL was also determined. Immunohistochemical staining and western blotting were utilized to assess the expression of huntingtin aggregates. RESULTS: Luteolin treatment enhanced survival and prevented weight loss in HD mice compared to the vehicle-treated HD group. Furthermore, the luteolin-treated HD mice exhibited enhanced motor coordination and balance and significantly reduced motor dysfunction. Also, luteolin decreased serum NfL levels in HD mice. Notably, the accumulation of huntingtin aggregates was significantly reduced in the brain's cortex, hippocampus, and striatum of luteolin-treated HD mice compared to the vehicle-treated HD group. CONCLUSION: Luteolin holds promise as a therapeutic agent for improving survival outcomes, managing motor dysfunction, and reducing huntingtin aggregates in HD. The findings are of significance as currently, there are no approved therapeutic interventions that reverse HD pathology or slow down its progression.


Asunto(s)
Modelos Animales de Enfermedad , Proteína Huntingtina , Enfermedad de Huntington , Luteolina , Ratones Transgénicos , Animales , Enfermedad de Huntington/tratamiento farmacológico , Enfermedad de Huntington/metabolismo , Luteolina/farmacología , Luteolina/uso terapéutico , Ratones , Proteína Huntingtina/genética , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Proteínas de Neurofilamentos/metabolismo , Masculino , Actividad Motora/efectos de los fármacos , Humanos
5.
Front Pharmacol ; 15: 1414790, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39246660

RESUMEN

Cancer prevention is currently envisioned as a molecular-based approach to prevent carcinogenesis in pre-cancerous stages, i.e., dysplasia and carcinoma in situ. Cancer is the second-leading cause of mortality worldwide, and a more than 61% increase is expected by 2040. A detailed exploration of cancer progression pathways, including the NF-kß signaling pathway, Wnt-B catenin signaling pathway, JAK-STAT pathway, TNF-α-mediated pathway, MAPK/mTOR pathway, and apoptotic and angiogenic pathways and effector molecules involved in cancer development, has been discussed in the manuscript. Critical evaluation of these effector molecules through molecular approaches using phytomolecules can intersect cancer formation and its metastasis. Manipulation of effector molecules like NF-kß, SOCS, ß-catenin, BAX, BAK, VEGF, STAT, Bcl2, p53, caspases, and CDKs has played an important role in inhibiting tumor growth and its spread. Plant-derived secondary metabolites obtained from natural sources have been extensively studied for their cancer-preventing potential in the last few decades. Eugenol, anethole, capsaicin, sanguinarine, EGCG, 6-gingerol, and resveratrol are some examples of such interesting lead molecules and are mentioned in the manuscript. This work is an attempt to put forward a comprehensive approach to understanding cancer progression pathways and their management using effector herbal molecules. The role of different plant metabolites and their chronic toxicity profiling in modulating cancer development pathways has also been highlighted.

6.
Surg Endosc ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39266760

RESUMEN

BACKGROUND: We previously showed worse outcomes among lower socioeconomic status (SES) groups following metabolic/bariatric surgery (MBS). In light of healthcare changes in response to COVID-19, this study aims to evaluate post-pandemic MBS outcomes and determine if prior socioeconomic disparities persisted in the post-COVID era. METHODS: A retrospective chart review of patients undergoing primary Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) between 2015 and 2022 was performed. Patients were stratified into pre- and post-COVID groups. Post-COVID cohort was further stratified into high (HT) and low (LT) tier status based on Distressed Communities Index, a geocoded composite measure of SES. Preoperative characteristics and postoperative outcomes were compared between pre- and post-COVID cohorts, as well as between post-COVID HT and LT groups. RESULTS: Of 709 patients, 82.9% were pre-COVID and 17.1% were post-COVID. Post-COVID cohort had greater rate of public insurance (46% vs. 37%, p < 0.001), longer wait time to surgery (mean 358 ± 609.8 days vs 241.9 ± 368.5 days, p = 0.045), and were more likely to undergo RYGB (69% vs. 56%, p = 0.010). Post-COVID patients also had lower risk of any complications on multivariable analysis (OR 0.599, 95% CI 0.372-0.963), had higher follow-up rates at post-discharge (95.8% vs 79.7%, p < 0.005), 6-month (93% vs. 82%, p < 0.001) and 12-month visits (75% vs. 63%, p = 0.005), and lost more weight at 12 months (67% excess weight loss (%EWL) vs. 58%EWL, p = 0.002). Among post-COVID HT and LT cohorts, previously seen disparities in complications were no longer seen. Finally, there were no differences in weight or follow-up rates between post-COVID HT and LT. CONCLUSIONS: Post-COVID changes to MBS care have resulted in improved short-term outcomes and reduced disparities for patients of lower SES. Further studies are needed to identify these positive factors to perpetuate practice patterns that optimize care for patients of all socioeconomic status.

7.
BMC Nurs ; 23(1): 676, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39322950

RESUMEN

BACKGROUND: Climate changes have led to health and environmental risks, so it has become essential to measure climate change literacy among the entire population, especially nursing students. The significant role of nursing students in raising public awareness and future healthcare roles emphasizes assessing the predictors of climate change literacy among nursing students. AIMS: This study seeks to identify the predictors of climate change literacy among nursing students in A Multi-Site Survey. DESIGN: A multi-site descriptive cross-sectional study adheres to the guidelines outlined in A Consensus-Based Checklist for Reporting Survey Studies collected for five months, from the 1st of July 2023 to November 2023. The study participants comprise 10,084 nursing students from all 27 governments in Egypt. The researcher used the Predictors of Nursing Students' Climate Change Literacy scale in this study. Data was collected, with 25 min average time to complete. Backward multiple linear regression was used to identify these predictors. RESULTS: In the current study, nursing students demonstrated a moderate understanding of climate science (mean score 14.38), communication and advocacy skills (mean score 14.41), and knowledge of adaptation and mitigation strategies (mean score 13.33). Climate health impacts (mean score 17.72) emerged as the domain with the highest level of knowledge. No significant differences in climate literacy were observed across diverse student backgrounds (all p-values were > 0.05). Perceived faculty knowledge of climate change positively correlated with all four domains of climate literacy and emerged as a significant predictor in multiple linear regression analyses (all p-values were < 0.001). IMPLICATION: While our findings highlight significant predictors of climate literacy, it is essential to recognize that these results identify associations rather than causal relationships. Based on these associations, it is recommended that nursing professionals be equipped with comprehensive knowledge of climate adaptation strategies to better advocate for and implement effective public health measures.

8.
BMC Nurs ; 23(1): 674, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39322958

RESUMEN

BACKGROUND: Organizational agility is the cornerstone of the complex dynamics for the success of healthcare organizations and the sustenance of nurses' career planning and professional development. AIM: Assess the organizational agility and the extent of nurses' career planning. It also sought to investigate the association between the two and the intermediating function that nurses` grit plays in this association. DESIGN: A cross-sectional descriptive design following STROBE guidelines was carried out. METHODS AND TOOLS: Data were collected from 300 nurses who made up the entire population sample that we used (a judgmental non-probability sampling technique) working across all in-patient care units at Itay El-Baroud General Hospital, in El Behaira governorate, using structured questionnaires as follows: the organizational agility questionnaire, the career planning scale, and the grit scale. The sociodemographic characteristics of the studied nurses were also collected. Statistical analyses were used to analyze the data, including ANOVA, Pearson correlation, and SEM, to determine whether career development may act as a mediator between organizational agility and the nurses' career planning. RESULTS: Rendering the findings of this study, more than half of nurses have a high perception regarding organizational agility and career planning. In contrast, the majority of them have a moderate perception regarding grit. In addition, there is a statistically high significant relationship between organizational agility and career planning. Also, there is a statistically high significant relationship between organizational agility and grit. There is a statistically high significant relationship between career planning and grit. CONCLUSION: The statistically substantial correlations among grit, career planning, and organizational agility demonstrate how interrelated they are. This implies that encouraging organizational flexibility and effective career planning techniques may have a good impact on nurses' resilience, which would ultimately result in a workforce of nurses who are more resilient and engaged. Additional investigation into the precise mechanisms behind these associations may yield important information for improving nurse wellbeing and retention. NURSING IMPLICATIONS: According to this study, putting organizational agility and career planning first can have a good impact on nurses' grit, which will make them more resilient and engaged workers. To encourage flexibility and growth among nurses, healthcare institutions should make training investments, provide clear career tracks, and support work-life balance. More investigation into the precise mechanisms underlying these connections may yield insightful information that improves nurse well-being and retention. The importance of organizational agility in creating a supportive work environment for nurses' career growth should be acknowledged by healthcare companies. This can lead to increased job satisfaction and lower turnover.

9.
BMC Nurs ; 23(1): 675, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39322967

RESUMEN

BACKGROUND: Since nurses are at the frontline of healthcare delivery, their actions and understanding of the environment have a big impact on how long healthcare systems can last. It is essential to comprehend the elements that impact nurses' sustainability consciousness to encourage ecologically conscious actions in the healthcare industry. AIM: This study aimed to explore the relationship between pro-social leader behaviors and nurses' sustainability consciousness and testify to the mediating role of organizational culture in this relationship. DESIGN: A cross-sectional descriptive correlational design by STROBE criteria was used. METHODS AND TOOLS: An approach to a judgmental non-probability sampling technique was employed to obtain data from 350 nurses in an Egyptian hospital. Three measurement surveys were employed: Organizational Culture Survey, Prosociality Scale, and, Sustainability Consciousness Questionnaire (SCQ-S). Relationships were shown using structural equation modeling and descriptive and inferential statistics. RESULTS: 53.4% of nurses have high perceptions of organizational culture, and the majority of nurses (85.7%) have high perceptions of prosocial leader behaviors. Furthermore, 60.9% of nurses have high perceptions of sustainability consciousness. Additionally, Prosocial leader behaviors positively correlated with organizational culture (r = 0.129) and nurses' sustainability consciousness (r = 0.274). The indirect effect of prosocial leader behaviors on nurses' sustainability consciousness through organizational culture is calculated by multiplying the coefficients of both direct effects (0.129 * 0.159 = 0.811). This means that for each unit increase in prosocial leader behaviors, we would expect a 0.811 unit increase in nurses' sustainability consciousness through the mediating effect of organizational culture. The model appears to match the data well based on the model fit parameters (CFI = 1.000, IFI = 1.000, RMSEA = 0.114). CONCLUSIONS: The study highlights the impact of pro-social leader behaviors on nurses' sustainability consciousness through the organizational culture as a mediating factor. NURSING IMPLICATIONS: Findings from this research can promote environmental stewardship and sustainable practices in the healthcare sector by illuminating the elements that can encourage and support a sustainability-oriented mindset among nurses. To promote a more sustainable future for the nursing profession, the findings can guide activities in nursing education, corporate culture transformation, and leadership development.

10.
Surg Obes Relat Dis ; 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39343661

RESUMEN

BACKGROUND: Severity stratification and longitudinal evaluation of metabolic conditions in response to Roux-en-Y gastric bypass (RYGB) are not standardized. Our Assessment of Obesity-related Metabolic Comorbidities (AOMC) scoring tool combines pharmacotherapy and biochemical data to objectively define type 2 diabetes (T2D), hypertension (HTN), and dyslipidemia (DYS) severity. We previously showed that AOMC more accurately describes disease severity than clinical history alone. OBJECTIVES: We aimed to show that AOMC more precisely and reproducibly measures metabolic disease response to RYGB and preoperative disease severity influences remission rates. SETTING: University hospital, United States. METHODS: AOMC scores for T2D, DYS, and HTN were calculated preoperatively and postoperatively (1-, 2-, and 5-years) for patients who underwent RYGB over 14 years. Generalized linear mixed-effect models were used to evaluate AOMC score trends and remission over time. RESULTS: Of 351 patients, 214, 188, and 303, presented with any T2D, DYS, or HTN respectively. One-year remission rates were: T2D 57.1%, DYS 59.7%, and HTN 29.3%. Over 5 years post-RYGB, remission rates declined for T2D (P < .05) and DYS (P < .05) but remained steady for HTN (P > .05). Remission was associated with preoperative disease severity: those with premetabolic disease had the highest remission rates (i.e., 1-year: pre-T2D 81.4%, pre-DYS 91.4%, pre-HTN 53.5%, all P < .05), while those with most severe scores preoperatively (untreated/uncontrolled) had the lowest remission rates. CONCLUSIONS: AOMC allows precise assessment of comorbidity severity and disease-specific postoperative quantification of comorbidity responses and remission rates. These findings can guide preoperative metabolic disease optimization and postoperative metabolic recovery expectations and standardize communication regarding comorbidity severity.

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