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1.
BMC Public Health ; 24(1): 1413, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802838

RESUMEN

OBJECTIVE: To explore the factors affecting delayed medical decision-making in older patients with acute ischemic stroke (AIS) using logistic regression analysis and the Light Gradient Boosting Machine (LightGBM) algorithm, and compare the two predictive models. METHODS: A cross-sectional study was conducted among 309 older patients aged ≥ 60 who underwent AIS. Demographic characteristics, stroke onset characteristics, previous stroke knowledge level, health literacy, and social network were recorded. These data were separately inputted into logistic regression analysis and the LightGBM algorithm to build the predictive models for delay in medical decision-making among older patients with AIS. Five parameters of Accuracy, Recall, F1 Score, AUC and Precision were compared between the two models. RESULTS: The medical decision-making delay rate in older patients with AIS was 74.76%. The factors affecting medical decision-making delay, identified through logistic regression and LightGBM algorithm, were as follows: stroke severity, stroke recognition, previous stroke knowledge, health literacy, social network (common factors), mode of onset (logistic regression model only), and reaction from others (LightGBM algorithm only). The LightGBM model demonstrated the more superior performance, achieving the higher AUC of 0.909. CONCLUSIONS: This study used advanced LightGBM algorithm to enable early identification of delay in medical decision-making groups in the older patients with AIS. The identified influencing factors can provide critical insights for the development of early prevention and intervention strategies to reduce delay in medical decisions-making among older patients with AIS and promote patients' health. The LightGBM algorithm is the optimal model for predicting the delay in medical decision-making among older patients with AIS.


Asunto(s)
Algoritmos , Toma de Decisiones Clínicas , Accidente Cerebrovascular Isquémico , Humanos , Anciano , Femenino , Masculino , Estudios Transversales , Modelos Logísticos , Accidente Cerebrovascular Isquémico/terapia , Persona de Mediana Edad , Anciano de 80 o más Años , Alfabetización en Salud/estadística & datos numéricos
2.
Carbohydr Polym ; 335: 122110, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38616084

RESUMEN

A neutral heteropolysaccharide (PNANb) was isolated with alkali (0.1 M NaOH) from mycelia of Phellinus nigricans, and the structure, immunostimulating activity and some of the underlying molecular mechanisms of action of PNANb were explored in the current study. PNANb (14.95 kDa) predominantly consisted of Gal, Glc, and Man with minor Fuc. GC-MS and NMR analyses indicated that the backbone of PNANb was mainly composed of 6-α-Galp, 2,6-α-Galp with minor 3,6-ß-Glcp, which was substituted with complex side chains at C-2 of 2,6-α-Galp and C-3 of 3,6-ß-Glcp. Notably, PNANb (50 or 100 mg/kg) possessed immunoprotective effects in cyclophosphamide (Cy)-induced immunosuppressed C57BL/6 mice, which was supported by evidence including the enhancement of spleen and thymus indices, levels of serum immunoglobulins (IgG, IgM) and cytokines (IFN-γ, IL-2, IL-4, IL-10), and macrophage activity. However, the immunostimulation effects of PNANb were decreased when macrophages were depleted, underscoring the essential role of macrophages in the beneficial effects of PNANb in Cy-induced immunosuppressed mice. Further investigations in vitro indicated that PNANb activated macrophages through MAPK/NF-κB signaling pathways mediated by Toll-like receptor 4. Therefore, PNANb can serve as a prospective immunopotentiator in immunosuppression.


Asunto(s)
Adyuvantes Inmunológicos , Álcalis , Phellinus , Humanos , Masculino , Animales , Ratones , Ratones Endogámicos C57BL , Adyuvantes Inmunológicos/farmacología , Estudios Prospectivos , Ciclofosfamida/farmacología , Macrófagos
3.
J Clin Nurs ; 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38476038

RESUMEN

AIM: To investigate the factors that facilitate or hinder nurses in providing patient education. DESIGN: A mixed-method systematic review. DATA SOURCES: Six databases (Cochrane Library, PubMed, EMBASE, Web of Science, MEDLINE and ERIC) were systematically searched for relevant publications. METHODS: The study was conducted following the JBI for mixed-method systematic reviews, and the reporting followed the PRISMA guideline. Two researchers independently performed literature screening, literature evaluation, data extraction and synthesis. PROSPERO registration number: CRD42023427451. RESULTS: Twenty-six eligible articles were included, including 15 quantitative articles, 10 qualitative articles and 2 mixed-methods articles. The resultant synthesis of key findings led to the identification of these barriers and facilitators, categorised into five distinct levels: nurse-related factors, organisational factors, patient-related factors, the nurse-patient relationship and interdisciplinary collaboration. CONCLUSIONS: The findings highlight the factors that facilitate or hinder nurses in providing patient education, suggesting that multifaceted interventions can enhance the practice of patient education in nursing and support the development of appropriate patient education guidelines or public policies. RELEVANCE TO CLINICAL PRACTICE: This review delineates the facilitators and barriers influencing nurses' provision of patient education, offering an initial framework for nursing managers to craft interventions aimed at enhancing the quality of patient education provided by nurses, consequently elevating the overall quality of nursing.

4.
BMC Nurs ; 23(1): 64, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38267964

RESUMEN

BACKGROUND: Nursing interns often experience lots of challenges during their clinical nursing internships, which can adversely affect career decisions and result in a squandering of nursing education resources. Patient safety attitudes, professional identity and climate of caring may affect nursing interns' clinical experience. However, more evidence is requested to validate these relationships for nursing educators to develop effective education programs and facilitate interns' successful transition. METHODS: This was a cross-sectional study, which used a convenience sampling method to recruit 387 nursing interns during December 2022 to April 2023 in university affiliated hospital in Hunan province, China. Data were collected using standardized scales. Spearman correlation and multiple regression analysis were employed to examine the relationship between transition shock, patient safety attitudes, professional identity, and climate of caring. RESULTS: Nursing interns experienced transition shock at a moderate level and the highest levels of transition shock in response to overwhelming practicum workloads, with the second being related to the conflict between theory and practice. Transition shock was negatively correlated with patient safety attitudes, professional identity and climate of caring among nursing interns. CONCLUSIONS: Nursing managers and educators need to value the transition shock experienced by nursing interns. Our study suggests that developing a strong sense of professional identity and a positive attitude toward patient safety can be effective in reducing the level of transition shock among nursing interns. In addition, a caring climate within the nursing unit can significantly enhance the overall experience of nursing interns. This can be achieved by enhancing the support of clinical mentors, providing patient safety-focused education, and facilitating team communication among nurses.

5.
Sci Rep ; 14(1): 1600, 2024 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-38238472

RESUMEN

Acute lung injury (ALI) remains a high mortality rate with dramatic lung inflammation and alveolar epithelial cell death. Although fatty acid ß-oxidation (FAO) impairment has been implicated in the pathogenesis of ALI, whether Carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme for FAO, plays roles in lipopolysaccharide (LPS)-induced ALI remains unclear. Accordingly, we focused on exploring the effect of CPT1A in the context of ALI and the underlying mechanisms. We found that overexpression of CPT1A (AAV-CPT1A) effectively alleviated lung injury by reduction of lung wet-to-dry ratio, inflammatory cell infiltration, and protein levels in the BALF of ALI mice. Meanwhile, AAV-CPT1A significantly lessened histopathological changes and several cytokines' secretions. In contrast, blocking CPT1A with etomoxir augmented inflammatory responses and lung injury in ALI mice. Furthermore, we found that overexpression of CPT1A with lentivirus reduced the apoptosis rates of alveolar epithelial cells and the expression of apoptosis-related proteins induced by LPS in MLE12 cells, while etomoxir increased the apoptosis of MLE12 cells. Overexpression of CPT1A prevented the drop in bioenergetics, palmitate oxidation, and ATP levels. In conclusion, the results rendered CPT1A worthy of further development into a pharmaceutical drug for the treatment of ALI.


Asunto(s)
Lesión Pulmonar Aguda , Compuestos Epoxi , Lipopolisacáridos , Animales , Ratones , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/genética , Carnitina O-Palmitoiltransferasa/genética , Carnitina O-Palmitoiltransferasa/metabolismo , Lipopolisacáridos/metabolismo , Pulmón/patología
6.
J Ethnopharmacol ; 323: 117589, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38104875

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Shou Tai Wan (STW), a traditional Chinese medicine formula, has been historically used for the treatment of recurrent spontaneous abortion (RSA). Despite its long-standing usage, the exact mechanism underlying the therapeutic effects of STW remains unclear in the existing literature. AIMS OF THIS STUDY: To explore the Pharmacological Mechanism of STW on RSA. METHODS: A network pharmacological methodology was utilized to predict the active compounds and potential targets of STW, collect the RSA targets and other human proteins of STW, and analyze the STW related networks. The animal experiments were also performed to validate the effect of STW on RSA. RESULTS: The results of network analysis showed that STW may regulate PI3K/AKT, MAPK, FoxO signaling pathways and so on. Animal experiment established the RSA model with CBA/J × DBA/2 mice. It was found that STW can reduce the embryo absorption rate of RSA group (p < 0.05) and balance the expression of Th 1/Th2 type cytokines compared with the model group. After 14 days of administration, the decidual and placental tissues were taken and the CD4+ T cells were isolated, and the phosphorylation level of signaling pathway was detected by Springbio720 antibody microarray. This experiment found that STW can significantly up-regulate the phosphorylation levels of STAT3 and STAT6 proteins in the STAT signaling pathway, and down-regulating the phosphorylation level of STAT1 protein. STW also significantly up-regulated the phosphorylation levels of Raf1, A-Raf, Ask1, Mek1, Mek2, JKK1, ERK1, ERK2, c-fos, c-Jun and CREB proteins in the MAPK signaling pathway, and down-regulate the phosphorylation levels of MEK6 and IKKb proteins. Compared with the RSA group, the STW group increased the expression levels of ERK1/2 mRNA and proteins and p-ERK1/2 proteins, and there was a statistical difference (p < 0.05). This is consistent with the chip results. CONCLUSION: STW may achieve therapeutic effects by interfering with the signaling pathways, biological processes and targets discovered in this study. It provides a new perspective for revealing the immunological mechanism of STW in the treatment of RSA, and also provides a theoretical basis for the clinical use of STW in the treatment of RSA.


Asunto(s)
Aborto Habitual , Fosfatidilinositol 3-Quinasas , Ratones , Animales , Embarazo , Femenino , Humanos , Placenta , Ratones Endogámicos DBA , Ratones Endogámicos CBA , Aborto Habitual/tratamiento farmacológico
8.
Artículo en Inglés | MEDLINE | ID: mdl-37353313

RESUMEN

BACKGROUND AND OBJECTIVE: An in-depth understanding of what constitutes a good death among patients with cancer is vital to providing patient-centred palliative care. This review aimed to synthesise evidence on the perceptions of a good death among patients with cancer. METHODS: This systematic review involved a synthesis of qualitative data. A three-step process suggested by the Joanna Briggs Institute was used to synthesise the data. RESULTS: A total of 1432 records were identified, and five articles met the inclusion criteria. Seven synthesised findings emerged: (1) being aware of cancer, (2) pain and symptom management, (3) dying well, (4) being remembered after death, (5) individual perspectives of a good death, (6) individual behaviours leading to a good death, and (7) culture and religions. A structural framework was developed to elicit two layers that could be regarded as determinants of a good death. One layer suggested how multiple external issues impact a good death, whereas the other layer involves patients' internal attributes that shape their experiences of a good death. The elements in the two layers were inter-related to exert a crossover effect on good death in specific cultural and religious contexts. CONCLUSION: A good death is a process initiated from the time of awareness of cancer and extends beyond demise. Holistic approaches encompassing the management of physical and psychological distress along with psychosocial behavioural interventions to enhance patients' positive perspectives and behaviours are recommended to improve their quality of life and death.

9.
Carbohydr Polym ; 316: 120998, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37321719

RESUMEN

A neutral polysaccharide (POPAN) from Portulaca oleracea L. was isolated with alkali and purified to obtain. HPLC analysis suggested POPAN (40.9 kDa) was mainly composed of Ara and Gal with traces of Glc and Man. GC-MS and 1D/2D NMR analysis confirmed POPAN was an arabinogalactan possessing a backbone mainly composing of (1 â†’ 3)-α-l-Araf-linked arabinan and (1 â†’ 4)-ß-d-Galp-linked galactan, which was different from structure characterization of typical arabinogalactan reported previously. Importantly, we conjugated POPAN to BSA (POPAN-BSA), and detected the potential and mechanism of POPAN as an adjuvant in POPAN-BSA. The results indicated, in contrast to BSA, POPAN-BSA induced the robust and persistent humoral response in addition to the cellular response with Th2-biased immunity response in mice. Further investigations of mechanism revealed effects of POPAN-BSA were a result of POPAN as the adjuvant to: 1) significantly activate DCs in vitro or in vivo including the upgraded expressions of costimulators, MHCs and cytokines; 2) greatly facilitated the capture of BSA. Overall, present studies demonstrated POPAN can be a potential adjuvant as an immunopotentiator and an antigen delivery vehicle in its conjugate to recombinant protein vaccines.


Asunto(s)
Portulaca , Vacunas , Animales , Ratones , Adyuvantes Inmunológicos/farmacología , Portulaca/química , Álcalis , Polisacáridos/química , Galactanos/química
10.
Nurs Open ; 10(8): 5627-5637, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37170700

RESUMEN

AIM: The study aimed to translate and adapt the traditional Chinese Food Allergy Quality of Life-Parental Burden Questionnaire (TC-FAQL-PB) into simplified Chinese language and determine the validity and reliability of the translated version. DESIGN: A methodologic study design involving instrument translation and psychometric evaluation was used for the present study. METHODS: The simplified Chinese FAQL-PB (SC-FAQL-PB) was developed following Guillemin's guidelines for cross-cultural adaptation. A convenience sample of 230 participants was recruited. The psychometric properties were examined using internal consistency, test-retest reliability, item discrimination, content validity and construct validity. RESULTS: The values of I-CVI ranged from 0.83 to 1.00. The CFA model revealed that the study supported the two-factor model. The questionnaire had good internal consistency with a Cronbach's alpha coefficient of 0.946. The item-total correlation values ranged from 0.707 to 0.866. Test-retest reliability showed that the intraclass correlation coefficient was 0.926 (95% CI, 0.830-0.968).


Asunto(s)
Comparación Transcultural , Hipersensibilidad a los Alimentos , Humanos , Reproducibilidad de los Resultados , Calidad de Vida , Encuestas y Cuestionarios , China , Lenguaje , Hipersensibilidad a los Alimentos/diagnóstico
11.
Nurse Educ Pract ; 69: 103644, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37058995

RESUMEN

AIM: This theory-guided scoping review aims to provide an overview of existing literature about academic-practice partnerships in evidence-based nursing education. BACKGROUND: Academic-practice partnership is an approach to improve evidence-based nursing education, to promote evidence-based nursing practice which could reduce the nursing care discrepancy, improve the nursing care quality and patient safety, reduce healthcare costs and promote nursing professional development. However, the related research is limited and there is a lack of systematic review of related literature. DESIGN: A scoping review guided by the theories of the Practice-Academic Partnership Logic Model and the JBI Model of Evidence-Based Healthcare. METHODS: The researchers will use JBI guidelines for scoping reviews and related theories to guide this theory-guided scoping review. The researchers will systematically search Cochrane Library, PubMed, Web of Science, CINAHL, EMBASE, SCOPUS and Educational Resource Information Centre (ERIC) using major search concepts including academic-practice partnership, evidence-based nursing practice and education. Two reviewers will be responsible for independent literature screening and data extraction. Discrepancies would be solved by a third reviewer. EXPECTED RESULTS: This scoping review will identify related research gaps to provide implications for researchers and identify specific information to provide implications for developing interventions of academic-practice partnerships in evidence-based nursing education. REGISTRATION NUMBER: This scoping review had been registered on Open Science Framework (https://osf.io/83rfj).


Asunto(s)
Bachillerato en Enfermería , Atención de Enfermería , Estudiantes de Enfermería , Humanos , Enfermería Basada en la Evidencia
12.
Asia Pac J Oncol Nurs ; 10(1): 100168, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36578350

RESUMEN

Objective: This study aimed to examine the fidelity of intervention delivery and identify precursory factors contributing to the successful delivery and beneficial effects of family-oriented dignity therapy. Methods: This was a process evaluation with quantitative and qualitative methods alongside a randomized controlled trial from March to May 2019. Nonparametric statistics were used to analyze how participants' demographics (n â€‹= â€‹45 dyads) and process variables influenced the intervention effects. Fourteen patients, 11 family caregivers, and 11 nurses were interviewed to explore their perception of the intervention. Conventional content analysis was adopted to analyze the qualitative data. Results: The fidelity was achieved with minor deviations from the protocol. Higher educational level and higher income were significantly correlated with lower levels of existential distress (H â€‹= â€‹12.20, P â€‹= â€‹0.030) and higher spiritual well-being (H â€‹= â€‹-16.310, P â€‹= â€‹0.031), respectively. Higher levels of interest were significantly correlated with lower levels of existential distress (H â€‹= â€‹10.396, P â€‹= â€‹0.035) and peace of mind distress (H â€‹= â€‹-16.778, P â€‹= â€‹0.006) and higher levels of life meaning (H â€‹= â€‹-12.808, P â€‹= â€‹0.047). Patients who had higher response levels to the question were significantly correlated with lower levels of symptom distress (H â€‹= â€‹-13.879, P â€‹= â€‹0.035). Four major categories were identified from the interview data: (1) benefits of the intervention, (2) risks of the intervention, (3) factors that enhance successful dignity-conserving care, and (4) difficulties and barriers to the delivery of dignity-conserving care. Conclusions: Fidelity and precursory factors that enhance the beneficial effects of family-oriented dignity therapy were identified. Reinforcement strategies, such as using supplementary video, audio, and reading materials; developing a flexible approach to expressing feelings; and exploring lessons and achievements from various perspectives, are recommended for future research to enhance intervention effects. Trial registration: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1900020806).

13.
Nutr Diabetes ; 12(1): 49, 2022 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-36494332

RESUMEN

INTRODUCTION: Oxidative stress is linked to the development of gestational diabetes mellitus (GDM). Maternal antioxidant vitamins in early pregnancy may play a role in GDM occurrence. We aimed to investigate the associations of vitamins A and E in early pregnancy with the risk of GDM and to explore whether these antioxidant vitamins can be biomarkers for the early prediction of GDM. METHODS: We carried out a prospective cohort study conducted in Beijing and enrolled pregnant women (n = 667) with vitamins A and E measurements at 9 weeks (IQR 8-10) of gestation and having one-step GDM screened with a 75-g oral glucose tolerance test between 24 and 28 weeks of gestation. RESULTS: The vitamin A levels in early pregnancy were significantly higher in women with GDM than in those without GDM (p < 0.0001) and positively correlated with fasting blood glucose. In multivariate models, vitamin A levels were significantly associated with GDM (OR, 1.46; 95% CI: 1.14-1.88; p = 0.0032) per SD. A significant trend of risk effect on GDM risk across quartiles of vitamin A was observed (ptrend = 0.016). No significant association of serum vitamin E with GDM was observed overall. However, a noted trend of protective effect on GDM risk across quartiles of vitamin E/cholesterol ratio was observed (ptrend = 0.043). In ROC analysis, the multivariate model consisting of vitamin A and other risk factors showed the best predictive performance (AUC: 0.760; 95% CI: 0.705-0.815; p < 0.001). CONCLUSIONS: Higher levels of vitamin A in early pregnancy were significantly associated with an increased risk of GDM. Vitamin A has the potential to be a biomarker indicating pathogenesis of GDM.


Asunto(s)
Diabetes Gestacional , Femenino , Embarazo , Humanos , Estudios Prospectivos , Antioxidantes , Vitamina A , Glucemia/análisis , Vitaminas , Biomarcadores , Vitamina E
14.
Int J Biol Macromol ; 177: 422-429, 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33631260

RESUMEN

We isolated and purified a pectin from Portulaca oleracea L. (P. oleracea), and analysed its structure by high-performance size exclusion chromatography (HPSEC), high-performance liquid chromatography (HPLC), gas chromatograph-mass spectrometer (GC-MS), fourier transform infrared spectroscopy (FT-IR), and 1H, 13C nuclear magnetic resonance spectroscopy (NMR). The data indicated that this pectin (designated as POPW-HG) was a linear non-esterified homogalacturonan, which is unique in plants; its molecular weight was around 41.2 kDa. Meanwhile, POPW-HG as an adjuvant was evaluated in the mice immunized with OVA subcutaneously. OVA-specific antibody titres from the sera of immunized mice were tested by ELISA. It showed that POPW-HG significantly enhanced OVA-specific antibody titres (IgG, IgG1, and IgG2b) (p < 0.05) in a dose-dependent manner in the OVA-immunized mice, preliminarily indicating POPW-HG could increase an antibody response, Th1 and Th2 immune response. In addition, the ratio of IgG1/IgG2b suggested POPW-HG induced a Th2-biased response in the OVA-immunized mice. The results demonstrated POPW-HG could be a potential adjuvant candidate in vaccines.


Asunto(s)
Adyuvantes Inmunológicos , Inmunización , Ovalbúmina/farmacología , Pectinas , Portulaca/química , Adyuvantes Inmunológicos/química , Adyuvantes Inmunológicos/aislamiento & purificación , Adyuvantes Inmunológicos/farmacología , Animales , Ratones , Pectinas/química , Pectinas/aislamiento & purificación , Pectinas/farmacología
15.
Int J Biol Macromol ; 173: 327-340, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33482211

RESUMEN

We reported previously a recombinant protein (rP-HSP90C) containing epitope C from heat shock protein 90 of Candida albicans mediates protective immune responses against systemic candidiasis. However, it exhibits weak immunogenicity. Therefore, we evaluated the potential and mechanisms of thermosensitive chitosan hydrogel (CH-HG) as an adjuvant in rP-HSP90C vaccine. CH-HG synthesized by ionic cross-linking showed buffering capacity and control-released rP-HSP90C in vitro. In comparison to naked rP-HSP90C, CH-HG-loaded rP-HSP90C (CH-HG/rP-HSP90C) not only evoked a long-lasting rP-HSP90C-specific IgG, but also enhanced Th1, Th2, Th17 responses and the ratio of Th1/Th2 in vivo; Meanwhile, CH-HG/rP-HSP90C provoked a stronger CTL response than rP-HSP90C. Notably, CH-HG increased the protective immune responses against systemic candidiasis in rP-HSP90C-immunized mice since CH-HG/rP-HSP90C enhanced the survival rate of infected mice, and diminished the CFUs in kidneys compared to rP-HSP90C, which were similar to that of QuilA. Further in vitro investigation displayed CH-HG upgraded the expressions of costimulators, MHCs and cytokines in BMDCs compared to rP-HSP90C;CH-HG also promoted cellular uptake, endosomal escape and "cross-presentation" of rP-HSP90C. In addition, it recruited immune cells at the injection site. Our study demonstrated that CH-HG can be an efficient adjuvant in fungal vaccines.


Asunto(s)
Candida albicans/inmunología , Candidiasis/prevención & control , Quitosano/química , Epítopos/administración & dosificación , Proteínas HSP90 de Choque Térmico/química , Animales , Anticuerpos Antifúngicos/sangre , Candidiasis/inmunología , Epítopos/química , Epítopos/inmunología , Proteínas Fúngicas/química , Proteínas Fúngicas/inmunología , Proteínas HSP90 de Choque Térmico/inmunología , Hidrogeles , Inmunización , Masculino , Ratones , Células RAW 264.7 , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/química , Proteínas Recombinantes/inmunología
16.
PLoS Biol ; 17(10): e3000461, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31600191

RESUMEN

Dendritic spine development is crucial for the establishment of excitatory synaptic connectivity and functional neural circuits. Alterations in spine morphology and density have been associated with multiple neurological disorders. Autism candidate gene disconnected-interacting protein homolog 2 A (DIP2A) is known to be involved in acetylated coenzyme A (Ac-CoA) synthesis and is primarily expressed in the brain regions with abundant pyramidal neurons. However, the role of DIP2A in the brain remains largely unknown. In this study, we found that deletion of Dip2a in mice induced defects in spine morphogenesis along with thin postsynaptic density (PSD), and reduced synaptic transmission of pyramidal neurons. We further identified that DIP2A interacted with cortactin, an activity-dependent spine remodeling protein. The binding activity of DIP2A-PXXP motifs (P, proline; X, any residue) with the cortactin-Src homology 3 (SH3) domain was critical for maintaining the level of acetylated cortactin. Furthermore, Dip2a knockout (KO) mice exhibited autism-like behaviors, including excessive repetitive behaviors and defects in social novelty. Importantly, acetylation mimetic cortactin restored the impaired synaptic transmission and ameliorated repetitive behaviors in these mice. Altogether, our findings establish an initial link between DIP2A gene variations in autism spectrum disorder (ASD) and highlight the contribution of synaptic protein acetylation to synaptic processing.


Asunto(s)
Acetilcoenzima A/genética , Trastorno del Espectro Autista/genética , Cortactina/genética , Espinas Dendríticas/metabolismo , Morfogénesis/genética , Proteínas Nucleares/genética , Procesamiento Proteico-Postraduccional , Acetilcoenzima A/deficiencia , Acetilación , Secuencias de Aminoácidos , Animales , Animales Recién Nacidos , Trastorno del Espectro Autista/metabolismo , Trastorno del Espectro Autista/fisiopatología , Sitios de Unión , Cortactina/metabolismo , Espinas Dendríticas/ultraestructura , Modelos Animales de Enfermedad , Embrión de Mamíferos , Regulación del Desarrollo de la Expresión Génica , Prueba de Complementación Genética , Ratones , Ratones Noqueados , Proteínas Nucleares/deficiencia , Densidad Postsináptica/metabolismo , Densidad Postsináptica/ultraestructura , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Células Piramidales/metabolismo , Células Piramidales/ultraestructura , Transmisión Sináptica
17.
Iran J Pharm Res ; 18(2): 803-811, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31531063

RESUMEN

The objective of this study is to investigate the anti-tumor effect of Ginkgo biloba exocarp extracts (GBEE) on B16 melanoma bearing mice and its related molecular mechanisms. The B16-F10 melanoma solid tumor model was established in C57BL/6J mice. The tumor-bearing mice were treated with GBEE (50, 100, 200 mg/kg), taking cis-Dichlorodiamineplatinum (Ⅱ) (DDP, 3 mg/kg) as positive control and normal saline (NS) as model control. After 17 days of administration, the transplanted tumors was stripped and weighed, and the inhibition rate was calculated. Quantitative Reverse Transcription Polymerase chain reaction (qRT-PCR), Western Blot and immunohistochemistry were applied to detect mRNA and protein levels of related factors in B16 transplanted tumor tissues. The results indicated that GBEE (50, 100, 200 mg/kg) inhibited the growth of B16 transplanted solid tumor in C57BL/6J mice. Meanwhile, it inhibited the expression of CD34 and reduced microvessel density (MVD) in a dose-dependent manner. Moreover, GBEE dose-dependently down-regulated the mRNA and protein levels of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor 2 (VEGFR2). The phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) proteins were not changed obviously, but the protein levels of p-PI3K and p-Akt were down-regulated. Overall, the inhibitory effect of GBEE on the growth of B16 melanoma transplant tumor in mice is related to inhibiting angiogenesis, and the mechanism involves the regulation of PI3K/Akt/ HIF-lα/VEGF signaling pathway.

18.
Int J Biol Macromol ; 140: 895-906, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31442508

RESUMEN

Polysaccharides from Physalis alkekengi L. have been proven to possess many biological activities. In our previous study, a homogeneous polysaccharide (PPSB) was extracted and purified from the fruits of Physalis alkekengi L., and the structure characterization was analyzed. The present study aimed to investigate the effects of PPSB on RAW264.7 macrophage cells activation and the underlying molecular mechanism. PPSB could activate RAW264.7 cells by not only enhancing the pinocytic and phagocytic activity, but also promoting the production of NO, ROS, TNF-α, and IL-6 in RAW264.7 cells. Meanwhile, PPSB up-regulated the expression of major histocompatibility complex (MHC-I/II) and costimulatory molecules such as CD40, CD80 and CD86. Mechanism studies showed that PPSB induced the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) pathways. Moreover, the production of NO, TNF-α and IL-6 induced by PPSB in RAW264.7 cells were suppressed by specific MAPKs and NF-κB inhibitors. Further experiments with blocking antibodies demonstrated that the releases of NO, TNF-α and IL-6 and the activation of MAPKs and NF-κB induced by PPSB were decreased after TLR2 and TLR4 were blocked. Our date illustrated that PPSB was capable of activating the RAW264.7 cells via MAPKs and NF-κB signaling mediated by TLR2 and TLR4.


Asunto(s)
Frutas/química , Macrófagos/efectos de los fármacos , Macrófagos/fisiología , Physalis/química , Polisacáridos/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Citocinas/metabolismo , Activación de Macrófagos/efectos de los fármacos , Activación de Macrófagos/inmunología , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Fagocitosis , Polisacáridos/química , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/metabolismo
19.
J Nephrol ; 32(2): 265-272, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30588573

RESUMEN

BACKGROUND: The relationship between oral activated charcoal (OAC) and hyperphosphatemia and vascular calcification is not completely clear. We observed and recorded the effects of OAC on hyperphosphatemia and vascular calcification in stage 3-4 chronic kidney disease (CKD). METHODS: In a randomized controlled study, we included 97 patients with stage 3-4 CKD. In the first phase of the experiment, the patients were randomly divided into the OAC group and placebo group. The endpoint of this phase was the development of hyperphosphatemia. The patients with hyperphosphatemia were selected into the second phase of the study. These patients underwent coronary artery multidetector computed tomography (MDCT) and were randomly divided into three groups: the OAC group, the calcium carbonate (CC) group and the lanthanum carbonate (LC) group. RESULTS: The first and second phases of the experiment were followed for 12 months. In the first phase of the experiment, there was a statistically significant difference in the proportion of patients with hyperphosphatemia between the OAC and placebo groups (28.57% vs. 79.17%, X2 = 24.958, P = 0.000). In the second phase, the differences in coronary calcification score (CACS) between the OAC group, the CC group and the LC group were statistically significant (525.5 ± 104.2 vs 688.1 ± 183.7 vs 431.4 ± 122.5, P < 0.01). CONCLUSION: Oral activated charcoal effectively delays the onset of hyperphosphatemia in patients with chronic kidney disease. OAC appears to delay the development of vascular calcifications in stage 3-4 CKD patients.


Asunto(s)
Carbonato de Calcio/administración & dosificación , Carbón Orgánico/administración & dosificación , Quelantes/administración & dosificación , Hiperfosfatemia/prevención & control , Lantano/administración & dosificación , Fosfatos/sangre , Insuficiencia Renal Crónica/tratamiento farmacológico , Calcificación Vascular/prevención & control , Administración Oral , Adulto , Anciano , Biomarcadores/sangre , Carbonato de Calcio/efectos adversos , Carbón Orgánico/efectos adversos , Quelantes/efectos adversos , Femenino , Humanos , Hiperfosfatemia/sangre , Hiperfosfatemia/diagnóstico , Hiperfosfatemia/etiología , Lantano/efectos adversos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Factores de Tiempo , Resultado del Tratamiento , Calcificación Vascular/sangre , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/etiología
20.
Cell Mol Neurobiol ; 37(5): 831-841, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27568302

RESUMEN

Isocitrate dehydrogenase 1 (IDH1), one member of the IDH family can convert isocitrate to α-ketoglutarate (α-KG) via oxidative decarboxylation. IDH1 and IDH2 mutations have been identified in multiple tumor types and the mutations confer neomorphic activity in the mutant protein, resulting in the conversion of α-KG to the oncometabolite, D-2-hydroxyglutarate (2-HG). The subsequent accumulation of 2-HG results in epigenetic dysregulation via inhibition of α-KG-dependent histone and DNA demethylase. And the glutamate levels are reduced in IDH mutant cells compared to wild-type. We have known that diffuse gliomas contain a high frequency of mutations in the IDH1 gene. However, the expression of IDH1 and its roles in Intracranial hemorrhage (ICH) remain largely unknown. We observed increased expression of IDH1 in neurons after intracerebral hemorrhage. Up-regulation of IDH1 was found to be accompanied by the increased expression of active caspase-3 and pro-apoptotic Bcl-2-associated X protein and decreased expression of anti-apoptotic protein B cell lymphoma-2 in vivo and vitro studies. So we hypothesized that IDH1 was involved in the regulation of neuronal apoptosis. The present research for the first time detected the expression and variation of IDH1 surrounding the hematoma, and all data proved the involvement of IDH1 in neuronal apoptosis following ICH.


Asunto(s)
Envejecimiento/patología , Apoptosis , Encéfalo/patología , Hemorragia Cerebral/enzimología , Hemorragia Cerebral/patología , Isocitrato Deshidrogenasa/metabolismo , Neuronas/enzimología , Neuronas/patología , Animales , Conducta Animal , Biomarcadores/metabolismo , Western Blotting , Modelos Animales de Enfermedad , Masculino , Células PC12 , Ratas , Ratas Sprague-Dawley
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