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1.
Sci Total Environ ; 919: 170856, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38340836

RESUMEN

Inland alkaline wetlands play a crucial role in maintaining ecological functions. However, these wetlands are becoming more vulnerable to the effects of water level fluctuations caused by global climate change, especially concerning carbon (C) and nitrogen (N) cycling. Here, metagenomics sequencing was used to investigate microorganism diversity, C and N cycling gene abundance at three water level types (D (dry), MF (middle flooded), HF (high flooded)) along an inland alkaline wetland. Our findings reveal that water level was the most important factor in regulating the microbial communities. Distinct shifts in community composition were found along the water level increases, without fundamentally altering their composition. With the increase of water level, the relative abundance of pmoA decreased from 2.5 × 10-5 to 5.1 × 10-6. The C cycling processes shift from predominantly CO2-generated processes under low water levels to CO2 and CH4 co-generated processes under high water levels. The relative abundance of nosZ reached 4.9 × 10-5 in HF, while in D and MF, it is recorded at 4.5 × 10-5 and 3.4 × 10-5, respectively. Water levels accelerate N cycling and generating N2O intermediates. Furthermore, our study highlights the dynamic competition and cooperation between C and N cycling processes. This research provides a comprehensive biological understanding of the influence of varying water levels on soil C and N cycling processes in wetland.


Asunto(s)
Nitrógeno , Humedales , Carbono , Dióxido de Carbono/análisis , Suelo , Metano/análisis , Metano/química , Óxido Nitroso/análisis , Óxido Nitroso/química
2.
Evol Bioinform Online ; 19: 11769343231211071, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38020534

RESUMEN

Rooting and root development in Acer rubrum have important effects on overall growth. A. rubrum does not take root easily in natural conditions. In this study, the mechanisms of the miR396b-GRF1 module underlying rooting regulation in A. rubrum were studied. The subcellular localization and transcriptional activation of miR396b and its target gene growth regulating factor 1 (GRF1) were investigated. These experiments showed that GRF1 was localized in the nucleus and had transcriptional activation activity. Functional validation experiments in transgenic plants demonstrated that overexpression of Ar-miR396b inhibited adventitious root growth, whereas overexpression of ArGRF1 increased adventitious root growth. These results help clarify the molecular regulatory mechanisms underlying adventitious root growth in A. rubrum and provide some new insights into the rooting rate in this species.

3.
Environ Sci Pollut Res Int ; 30(48): 106378-106389, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37728677

RESUMEN

The increase in temperature caused by global climate change has promoted the salinization of wetlands. Inland saline-alkaline wetlands have an environment of over-humidity and shallow water and are hot spots for CH4 emissions. However, there are few reports on the effect of salinity on CH4 emissions in inland saline-alkaline wetlands. This study conducted simulation experiments of increased salinity to investigate the impact of salinity, habitat, and their interactions on CH4 emissions, as well as to examine the response of methanogenic archaea to salinity. Overall, salinity inhibited CH4 emissions. But there were different responses in the three habitat soils. Salinity decreased the relative abundance of methanogenic archaea and changed the community structure. In addition, salinity changed soil pH and dissolved organic carbon (DOC) and ammonium (NH4+) concentrations, which were significantly correlated with methanogenic archaea. Our study showed that salinity changed the soil physicochemical properties and characteristics of the methanogenic archaeal community, affecting CH4 emissions.


Asunto(s)
Archaea , Humedales , Metano , Salinidad , Ecosistema , Suelo/química , Dióxido de Carbono/análisis
4.
Genes (Basel) ; 14(6)2023 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-37372386

RESUMEN

Acer rubrum is difficult to root during cutting propagation. Auxin/indole-acetic acids (Aux/IAA) proteins, which are encoded by the early response genes of auxin, are transcriptional repressors that play important roles in auxin-mediated root growth and development. In this study, ArAux/IAA13 and ArAux/IAA16, which were significantly differentially expressed after 300 mg/L indole butyric acid treatment, were cloned. Heatmap analysis revealed that they might be associated with the process of adventitious root (AR) growth and development mediated by auxin. Subcellular localization analysis showed that they performed their function in the nucleus. Bimolecular fluorescence complementation assays revealed the interactions between them and two auxin response factor (ARF) proteins, ArARF10 and ArARF18, confirming their relevance to AR growth and development. Overexpression of transgenic plants confirmed that the overexpression of ArAux/IAA13 and ArAux/IAA16 inhibited AR development. These results help elucidate the mechanisms of auxin-mediated AR growth and development during the propagation of A. rubrum and provide a molecular basis for the rooting of cuttings.


Asunto(s)
Acer , Ácidos Indolacéticos/metabolismo , Indoles , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
5.
J Nurs Care Qual ; 38(4): E59-E65, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36917825

RESUMEN

BACKGROUND: Currently, there is no instrument available to assess intensive care unit (ICU) nurses' knowledge, attitudes, and practices (KAP) of central line-associated bloodstream infection (CLABSI) prevention practices. PURPOSE: To develop and validate a CLABSI questionnaire to measure ICU nurses' KAP (CLABSI-KAP-Q). METHODS: Data were collected from 255 nurses at 4 hospitals in Gansu Province, China. Questions on the CLABSI-KAP-Q were generated through a review of the literature, interviews with nurses, and multiple rounds of content validity evaluation by experts. The validity and reliability of the CLABSI-KAP-Q were assessed with exploratory factor analysis, confirmatory factor analysis, internal consistency, and correlation coefficients. RESULTS: The final version of the CLABSI-KAP-Q consisted of 32 items. The reliability was represented by a Cronbach α of 0.946, while the test-retest reliability was 0.945. The overall content validity was 0.95. CONCLUSIONS: The CLABSI-KAP-Q is shown to be valid and reliable and recommended for use in clinical practice.


Asunto(s)
Enfermeras y Enfermeros , Sepsis , Humanos , Reproducibilidad de los Resultados , Conocimientos, Actitudes y Práctica en Salud , Competencia Clínica , Unidades de Cuidados Intensivos , Encuestas y Cuestionarios , Psicometría
6.
Environ Sci Pollut Res Int ; 30(17): 50125-50133, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36790702

RESUMEN

Zhalong wetland is the largest inland saline wetland in Asia and susceptible to imbalance and frequent flooding during the freeze-thaw period. Changes in water level and temperature can alter the rate of greenhouse gas release from wetlands and have the potential to alter Earth's carbon budget. However, there are few reports on how water level, temperature, and their interactions affect greenhouse gas flux in inland saline wetland during the freeze-thaw period. This study revealed the characteristics of CO2 and CH4 fluxes in Zhalong saline wetlands at different water levels during the autumn freeze-thaw period and clarifies the response of CO2 and CH4 fluxes to water levels. The significance analysis of cumulative CO2 fluxes at different water levels showed that water levels did not have a significant effect on cumulative CO2 release fluxes from wetlands. Water levels, temperature, soil moisture content, soil nitrate, and ammonium nitrogen content and organic carbon content could explain 24.5-98.9% of CO2 and CH4 flux variation. There were significant differences in the average and cumulative CH4 fluxes at different water levels. The higher the water levels, the higher the CH4 fluxes. In short, water level had a significant effect on wetland methane fluxes, but not on carbon dioxide fluxes.


Asunto(s)
Gases de Efecto Invernadero , Humedales , Gases de Efecto Invernadero/análisis , Dióxido de Carbono/análisis , Óxido Nitroso/análisis , China , Metano/análisis , Suelo
7.
J Nurs Manag ; 30(7): 3022-3030, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35666670

RESUMEN

AIM: To assess the influence of professional identity on work engagement among nurses working in nursing homes in China. BACKGROUND: China is faced with an increasingly ageing population. There is a shortage of adequately trained nursing personnel and a high turnover rate among nurses. Work engagement is a key factor in improving nurses' performance and improving professional identity is critical to increase work productivity and satisfaction. METHODS: We conducted a cross-sectional survey of 272 nurses working in nursing homes. And the data were analysed by descriptive analyses, univariate analysis and Multiple regression analyses. RESULTS: The overall average work engagement score was 3.99 ± 1.04. Professional identity was the only factor that significantly influenced the 'vigour' and 'absorption' of nurses. Age, ethnicity and professional identity were significant predictors of 'dedication'. CONCLUSIONS: A positive professional identity can lead to a better work engagement among nurses working in nursing homes in China. IMPLICATIONS FOR NURSING MANAGEMENT: To enhance the work engagement of nurses working in nursing homes, nursing leaders should create a respectful and equal work environment, create a favourable image of the industry and the profession and strengthen training to improve the professional identity.


Asunto(s)
Enfermeras y Enfermeros , Personal de Enfermería en Hospital , Humanos , Compromiso Laboral , Satisfacción en el Trabajo , Estudios Transversales , Reorganización del Personal , Casas de Salud , Encuestas y Cuestionarios , Personal de Enfermería en Hospital/educación
8.
Front Public Health ; 10: 1001948, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36684961

RESUMEN

Objective: To investigate the epidemiology and influencing factors of social participation ability of rural older adults in China. Methods: From March to April 2021, 3450 older adults in poverty aged 60 and above registered in Jishishan County (J County) were selected by cluster sampling for a cross-sectional questionnaire survey and their social participation ability was assessed using the Ability Assessment of older adults (MZ/T039-2013). The results were statistically analyzed and an ordered multi-category logistic regression analysis was used to analyze the effect of influencing factors on the social participation ability of rural older adults. Results: 3,346 questionnaires were collected, with an effective recovery rate of 96.99%. Out of all the participants, 1,355 (40.5%) of the 3,346 cases had intact social participation ability, while 1,991 (59.5%) had different degrees of loss of social participation ability, of which 1,393 (41.14%) were mildly impaired, 419 (12.5%) were moderately impaired and 179 (5.3%) were severely impaired. Age, educational level, religious belief, living status, whether suffering from dementia and the occurrence of accidents in recent 30 days were influencing factors on the social participation ability (p < 0.05). Conclusion: The rate of impaired social participation ability among older adults was >50% and age, educational level, religious beliefs, living status, whether suffering from dementia, and the occurrence of accidents in recent 30 days (such as falls, choking, loss) were significant factors influencing the ability of social participation of rural older adults.


Asunto(s)
Demencia , Participación Social , Humanos , Anciano , Lactante , Estudios Transversales , Encuestas y Cuestionarios , China/epidemiología
9.
Phytother Res ; 35(10): 5720-5733, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34411362

RESUMEN

Tumor resistance is the main cause of treatment failure and is associated with many tumor factors. Jaridon 6, a new diterpene extracted from Rabdosia rubescens (Hemsl.) Hara, which has been previously extracted by our research team, has been tested having more obvious advantages in resistant tumor cells. However, its mechanism is unclear. In this study, we studied the effect and the specific mechanism of Jaridon 6 in resistant gastric cancer cells. Cytotoxicity test, colony test, western blotting, and nude test verified the anti-drug resistance ability of Jaridon 6 in the MGC803/PTX and MGC803/5-Fu cells. Jaridon 6 has shown obvious inhibitory effects in the sirtuin 1 (SIRT1) enzyme test. Transmission electron microscopy and immunofluorescence tests further proved the autophagic action of Jaridon 6. Jaridon 6 could inhibit the proliferation of the resistant gastric cancer cell in vivo and in vitro. Jaridon 6 inhibited SIRT1 enzyme and induced autophagy by inhibiting the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway. Thus, it may be considered for treating gastric cancer resistance by individual or combined administration, as an SIRT1 inhibitor and autophagy inducer.


Asunto(s)
Diterpenos de Tipo Kaurano , Isodon , Neoplasias Gástricas , Apoptosis , Autofagia , Línea Celular Tumoral , Proliferación Celular , Humanos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Sirtuina 1 , Neoplasias Gástricas/tratamiento farmacológico
10.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(4): 431-435, 2020 Aug 30.
Artículo en Chino | MEDLINE | ID: mdl-32895093

RESUMEN

Objective To investigate the differences in energy spectrum CT findings between anterior mediastinal lymphoma and thymic carcinoma. Methods Twenty-two cases of anterior mediastinal lymphoma and 28 cases of thymic carcinoma confirmed by biopsy in Tangshan People's Hospital were selected.The CT values and changes of iodine content and water content in lesion sites were measured by energy spectrum analysis software.The differences between anterior mediastinal lymphoma and thymic carcinoma were compared. Results The single-energy CT value of 40-80 keV in thymus carcinoma was higher than that in anterior mediastinal lymphoma(P=0.001,P=0.037,P=0.042,P=0.034,P=0.002;P=0.016,P=0.013,P=0.018,P=0.024,P=0.012).The difference in the single-energy CT value of 90-110 keV between anterior mediastinal lymphoma and thymic carcinoma showed no statistical significance(all P>0.05).The concentrations of water in the arterial and venous stages of thymic carcinoma were significantly lower than those in the anterior mediastinal lymphoma(P=0.030,P=0.037),whereas the iodine concentrations were significantly higher(P=0.026,P=0.000). Conclusion Anterior mediastinal lymphoma and thymic carcinoma have remarkably different 40-80 keV single energy CT value and iodine concentration in arterial and venous phases,which may be helpful for the differential diagnosis of these two malignancies.


Asunto(s)
Linfoma , Neoplasias del Mediastino , Timoma , Neoplasias del Timo , Humanos , Linfoma/diagnóstico por imagen , Neoplasias del Mediastino/diagnóstico por imagen , Timoma/diagnóstico por imagen , Neoplasias del Timo/diagnóstico por imagen , Tomografía Computarizada por Rayos X
11.
Medicine (Baltimore) ; 98(52): e18353, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31876709

RESUMEN

BACKGROUND: To determine the effectiveness of text message reminders (TMR) on medication adherence (MA) and to investigate the effects of TMR on clinical outcomes. METHODS: The PubMed, Cochrane library, EMbase, and China Biology Medicine databases were searched for randomized-controlled trials with TMR as the intervention for patients with coronary heart disease. Two reviewers independently extracted data and assessed the risk of bias. Meta-analysis was conducted using Stata 15.0 software. RESULTS: In total, 1678 patients in 6 trials were included. Compared with the control group, the MA was 2.85 times greater among the intervention group (RR [relative risk] 2.85; 95% confidence interval [CI] 1.07-7.58). TMR reduced systolic blood pressure (BP) (weighted mean difference) = -6.51; 95% CI -9.79 to -3.23), cholesterol (standard mean difference = -0.26; 95% CI -0.4 to -0.12) and increased the number of patients with BP <140/90 mm Hg (RR 1.39; 95% CI 1.26-1.54). CONCLUSION: TMR significantly promoted MA and reduced systolic BP, cholesterol level, and body mass index, but had no effect on mortality, diastolic BP, or lipoproteins. However, substantial heterogeneity existed in our analyses.


Asunto(s)
Enfermedad Coronaria/tratamiento farmacológico , Cumplimiento de la Medicación , Sistemas Recordatorios , Envío de Mensajes de Texto , Humanos
12.
Int J Infect Dis ; 87: 154-165, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31442627

RESUMEN

OBJECTIVES: It remains uncertain which catheter lock solution (CLS) to prevent catheter-related bloodstream infections (CRBSI) works best and is safest for patients. This study was performed to compare the efficacy of different CLSs for the prevention of CRBSI and ranked these CLSs for practical consideration. METHODS: The PubMed, Web of Science, Embase, and MEDLINE databases, earlier relevant meta-analyses, and the reference lists of included studies were searched. The primary outcome was CRBSI; secondary outcomes were catheter-related thrombosis and exit-site infections. A network meta-analysis was performed to estimate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 52 randomized controlled trials involving 9099 patients and evaluating 13 CLSs (single and combinations) were included. With regard to the quality of the evidence, the risk of bias was typically low or unclear (45 out of 52 trials, 86.5%). In the network meta-analysis, saline (OR 8.44, 95% CI 2.19-32.46), gentamicin+citrate (OR 2.92, 95% CI 1.32-6.42), ethanol (OR 5.33, 95% CI 1.22-23.32), and cloxacillin+heparin (OR 2.07, 95% CI 1.19-5.49) were associated with a greater effect on CRBSI than heparin. CONCLUSIONS: This network meta-analysis showed that minocycline-ethylenediaminetetraacetic acid (EDTA) seemed to be the most effective for the prevention of CRBSI and exit-site infection, and cefotaxime+heparin seemed to be the most effective for catheter-related thrombosis.


Asunto(s)
Antibacterianos/administración & dosificación , Bacteriemia/prevención & control , Infecciones Relacionadas con Catéteres/prevención & control , Humanos , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto
13.
BMJ Open ; 9(6): e030019, 2019 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-31256039

RESUMEN

INTRODUCTION: Catheter-related bloodstream infection (CRBSI) is a major complication after central venous catheter insertion, which is associated with significant morbidity, mortality and additional medical costs. Many lock solutions for CRBSI have been evaluated. However, using traditional pairwise meta-analyses to summarise the evidence does not allow the inclusion of data from treatments that have not been compared head to head, which could impact the precision of pooled estimates in a meta-analysis. Therefore, we evaluated the efficacy and safety of the different lock solutions for CRBSI through a network meta-analysis. METHODS AND ANALYSIS: The primary outcome of this network meta-analysis is the CRBSI. The secondary outcomes are exit-site infection and catheter-related thrombosis. We will search the PubMed, Embase, Web of Science and the Cochrane Library databases for recent relevant meta-analysis and their reference lists to include randomised controlled trials (RCTs) that compared lock solutions for CRBSI prevention. Two individuals will independently extract data from each included RCT according to a predesigned Excel spreadsheet and will assess the methodological quality using the Cochrane risk of bias tool. We will analyse the data using WinBUGS (V.1.4.3) and Stata (V.15.0). We will also estimate the pooled direct and indirect effects for all lock solutions using the network meta-analysis. ETHICS AND DISSEMINATION: As the present meta-analysis is performed based on previous published studies, no ethical approval and patient safety considerations are required. This study commenced on 18 January 2019, and its expected completion date is 1 December 2019. We will disseminate the results of our network meta-analysis through an international peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42019121089.


Asunto(s)
Infecciones Relacionadas con Catéteres/prevención & control , Catéteres Venosos Centrales/efectos adversos , Teorema de Bayes , Infecciones Relacionadas con Catéteres/etiología , Humanos , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto
14.
Medicine (Baltimore) ; 98(14): e14940, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30946317

RESUMEN

PURPOSE: The purpose of our study is to carry out a Bayesian network meta-analysis comparing the efficacy of different antimicrobial dressings for prevention of catheter-related blood infections (CRBSI) and rank these antimicrobial dressings for practical consideration. METHODS: We searched the PubMed, Cochrane library, Embase, earlier relevant meta-analysis and reference lists of included studies for randomized controlled trials (RCTs) that compared dressings for prevention of CRBSI. Two authors independently extracted data from each included RCT according to a predesigned Excel spreadsheet and assessed the methodological quality of included RCTs using the Cochrane risk of bias tool. Data was analyzed using the WinBUGS (V.1.4.3) and the Stata (V.15.0). RESULTS: Finally, 35 RCTs involving 8494 patients and evaluating 13 dressings were included. Network meta-analysis showed that transparent dressing may be the best way to prevent CRBSI. Suture and bordered polyurethane dressing might have the lowest risk of CRBSI rate per 1000 catheter-days, and sutureless securement device might lead to the lowest incidence of catheter failure. CONCLUSIONS: This network meta-analysis indicated that transparent dressings may be selected for the prevention of CRBSI in patients with central venous catheters, which is of importance in future research. Although evidence is scant, more attention should be paid to head-to-head comparisons of the most commonly used dressings in this field.


Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/prevención & control , Infecciones Relacionadas con Catéteres/prevención & control , Catéteres Venosos Centrales/microbiología , Adulto , Anciano , Bacteriemia/epidemiología , Vendajes/normas , Infecciones Relacionadas con Catéteres/tratamiento farmacológico , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/métodos , Catéteres Venosos Centrales/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Poliuretanos , Ensayos Clínicos Controlados Aleatorios como Asunto
15.
J Med Chem ; 62(5): 2772-2797, 2019 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-30803229

RESUMEN

The cullin-RING ubiquitin ligases (CRLs) are responsible for about 20% of cellular protein degradation and regulate diverse cellular processes, and the dysfunction of CRLs is implicated in human diseases. Targeting the CRLs has become an emerging strategy for the treatment of human diseases. Herein, we describe the discovery of a hit compound from our in-house library and further structure-based optimizations, which have enabled the identification of new triazolo[1,5- a]pyrimidine-based inhibitors targeting the DCN1-UBC12 interaction. Compound WS-383 blocks the DCN1-UBC12 interaction (IC50 = 11 nM) reversibly and shows selectivity over selected kinases. WS-383 exhibits cellular target engagement to DCN1 in MGC-803 cells. WS-383 inhibits Cul3/1 neddylation selectively over other cullins and also induces accumulation of p21, p27, and NRF2. Collectively, targeting the DCN1-UBC12 interaction would be a viable strategy for selective neddylation inhibition of Cul3/1 and may be of therapeutic potential for disease treatment in which Cul3/1 is dysregulated.


Asunto(s)
Péptidos y Proteínas de Señalización Intracelular/metabolismo , Pirimidinas/farmacología , Triazoles/farmacología , Enzimas Ubiquitina-Conjugadoras/metabolismo , Células Cultivadas , Humanos , Estructura Molecular , Unión Proteica , Pirimidinas/química , Triazoles/química
16.
J Pharm Pharmacol ; 69(2): 213-221, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28028809

RESUMEN

OBJECTIVES: To study the antitumour activity of a novel derivative of oridonin named geridonin in vitro and in vivo. METHODS: MTT and colony formation assay were used to test the cytotoxicity of geridonin; apoptosis, cell cycle arrest and the levels of reactive oxygen species were measured by flow cytometry; JC-1 staining assay was used to examine the mitochondrial membrane potential; the MGC 803 xenograft model was established to evaluate the antitumour effect of geridonin in vivo; H&E staining was performed for the histological analysis. KEY FINDINGS: In vitro, geridonin remarkably inhibited proliferation of gastrointestinal cancer cells including oesophageal, gastric, liver and colon cancers. On oesophageal, gastric cancer cells, geridonin displayed strong cytotoxicity than that of oridonin. In gastric cancer MGC 803 cells, geridonin triggered apoptosis through the mitochondrial pathway depending on caspase. In addition, geridonin sharply reduced the formation of cell colony, increased the intracellular levels of ROS and induced cell cycle arrest at G2/M phase. In vivo, geridonin delayed the growth of MGC 803 xenograft in athymic mice without obvious loss of bodyweight. CONCLUSIONS: The novel derivative of oridonin, geridonin, inhibited the growth of human gastric cancer cells MGC 803 both in vitro and in vivo mainly via triggering apoptosis depending on elevating intracellular level of ROS.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Diterpenos de Tipo Kaurano/farmacología , Especies Reactivas de Oxígeno/metabolismo , Animales , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Ensayo de Tumor de Célula Madre , Ensayos Antitumor por Modelo de Xenoinjerto
17.
J Control Release ; 233: 57-63, 2016 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-27164542

RESUMEN

Synthetic liposomes provide a biocompatible and biodegradable approach for delivering drugs and antigens. In addition, self-adjuvanting recombinant lipoproteins (rlipoproteins) can enhance Th1 anti-tumor immune responses via the TLR2 signaling pathway. To generate a liposomal rlipoprotein for a cancer immunotherapeutic vaccine, we assessed 3 types of synthetic liposomes for use with the rlipoproteins rlipoE7m and rlipoOVA. We determined that the cationic liposome DOTAP could stabilize anionic rlipoproteins and delay rlipoprotein release. Surprisingly, rlipoproteins and DOTAP could synergistically up-regulate CD83 expression in bone marrow-derived dendritic cells (BMDCs). Compared with other liposome formulations, the rlipoprotein/DOTAP formulation elicited higher cytotoxic T-lymphocyte (CTL) responses. To explore the mechanism of BMDC activation by rlipoprotein/DOTAP, we assessed the production of reactive oxygen species (ROS) and the TNF-α secretion of BMDCs. We observed that rlipoprotein/DOTAP induced ROS to the same extent as DOTAP did. In addition, TLR2 signaling was also required for the TNF-α secretion of rlipoprotein/DOTAP-treated BMDCs. Moreover, compared with rlipoOVA-treated BMDCs, rlipoOVA/DOTAP-treated BMDCs increased the levels of IFN-γ produced by OVA-specific T cells. We also observed that rlipoE7m/DOTAP treatment but not rlipoE7m treatment delayed tumor growth. These results indicate that the rlipoprotein/DOTAP formulation can synergistically activate BMDCs via ROS and the TLR2 signaling pathway. In summary, rlipoprotein/DOTAP is a novel and stable formulation for cancer immunotherapy.


Asunto(s)
Vacunas contra el Cáncer/administración & dosificación , Lipoproteínas/administración & dosificación , Neoplasias/terapia , Ovalbúmina/inmunología , Proteínas E7 de Papillomavirus/inmunología , Alérgenos/inmunología , Animales , Vacunas contra el Cáncer/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Células Dendríticas/inmunología , Ácidos Grasos Monoinsaturados/química , Lipoproteínas/inmunología , Lipoproteínas/uso terapéutico , Liposomas , Ratones Endogámicos C57BL , Neoplasias/inmunología , Neoplasias/patología , Compuestos de Amonio Cuaternario/química , Especies Reactivas de Oxígeno/metabolismo , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/uso terapéutico , Carga Tumoral/efectos de los fármacos
18.
Front Behav Neurosci ; 9: 262, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26483650

RESUMEN

Prospective memory (PM) refers to the ability to remember to perform intended actions in the future. Although PM deficits are a prominent impairment in schizophrenia, little is still known about the nature of PM in symptomatically remitted patients with schizophrenia. To address this issue, event-related brain potentials (ERPs) were recorded from 20 symptomatically remitted patients with schizophrenia and 20 healthy controls during an event-based PM paradigm. Behavioral results showed that symptomatically remitted patients with schizophrenia performed poorly on the PM task compared with healthy controls. On the neural level, the N300, a component of the ERPs related to PM cue detection, was reliable across these two groups, suggesting a degree of functional recovery of processes supporting cue detection in patients with symptomatically remitted schizophrenia. By contrast, the amplitude of the prospective positivity, a component of the ERPs related to PM intention retrieval, was significantly attenuated in symptomatically remitted schizophrenia patients relative to healthy controls. Furthermore, a significant positive correlation between the amplitude of the prospective positivity and accuracy on the PM task was found in those patients, indicating that patients' poor performance on this task may result from the failure to recover PM cue-induced intention from memory. These results provide evidence for the existence of altered PM processing in patients with symptomatically remitted schizophrenia, which is characterized by a selective deficit in retrospective component (intention retrieval) of PM. Therefore, these findings shed new light on the neurophysiological processes underlying PM in schizophrenia patients during clinical remission.

19.
J Immunol ; 192(9): 4233-41, 2014 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-24683188

RESUMEN

Cross-presentation is a key function of dendritic cells (DCs), which present exogenous Ags on MHC class I molecules to prime CTL responses. The effects of TLR triggering on the cross-presentation of exogenous Ags by DCs remain unclear. In this study, we used synthetic dipalmitoylated peptides and TLR2 agonist-conjugated peptides as models to elucidate the mechanisms of TLR2-mediated cross-presentation. We observed that the internalization of dipalmitoylated peptides by bone marrow-derived DCs was facilitated by TLR2 via clathrin-mediated endocytosis. The administration of these dipalmitoylated peptide-pulsed bone marrow-derived DCs eliminated established tumors through TLR2 signaling. We further demonstrated that the induction of Ag-specific CTL responses and tumor regression by dipalmitoylated peptides was TAP independent. In addition, presentation of dipalmitoylated peptides by MHC class I molecules was blocked in the presence of an endosomal acidification inhibitor (chloroquine) or a lysosomal degradation inhibitor (Z-FL-COCHO). The endocytosed dipalmitoylated peptide also passed rapidly from early endosome Ag-1-positive endosomes to RAS-related GTP-binding protein 7 (Rab7)-associated late endosomes compared with their nonlipidated counterparts. Furthermore, we found that dipalmitoylated peptide-upregulated Rab7 expression correlated with Ag presentation via the TLR2/MyD88 pathway. Both JNK and ERK signaling pathways are required for upregulation of Rab7. In summary, our data suggest that TLR2-mediated cross-presentation occurs through the upregulation of Rab7 and a TAP-independent pathway that prime CTL responses.


Asunto(s)
Reactividad Cruzada/inmunología , Citotoxicidad Inmunológica/inmunología , Células Dendríticas/inmunología , Transducción de Señal/inmunología , Receptor Toll-Like 2/inmunología , Animales , Western Blotting , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , Neoplasias Experimentales/inmunología , Linfocitos T Citotóxicos/inmunología , Proteínas de Unión al GTP rab/inmunología , Proteínas de Unión a GTP rab7
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