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1.
Nature ; 572(7767): 56-61, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31316207

RESUMEN

The radiation-based sterile insect technique (SIT) has successfully suppressed field populations of several insect pest species, but its effect on mosquito vector control has been limited. The related incompatible insect technique (IIT)-which uses sterilization caused by the maternally inherited endosymbiotic bacteria Wolbachia-is a promising alternative, but can be undermined by accidental release of females infected with the same Wolbachia strain as the released males. Here we show that combining incompatible and sterile insect techniques (IIT-SIT) enables near elimination of field populations of the world's most invasive mosquito species, Aedes albopictus. Millions of factory-reared adult males with an artificial triple-Wolbachia infection were released, with prior pupal irradiation of the released mosquitoes to prevent unintentionally released triply infected females from successfully reproducing in the field. This successful field trial demonstrates the feasibility of area-wide application of combined IIT-SIT for mosquito vector control.


Asunto(s)
Aedes/microbiología , Aedes/fisiología , Control de Mosquitos/métodos , Mosquitos Vectores/microbiología , Mosquitos Vectores/fisiología , Wolbachia/patogenicidad , Aedes/crecimiento & desarrollo , Animales , China , Copulación , Estudios de Factibilidad , Femenino , Humanos , Mordeduras y Picaduras de Insectos/prevención & control , Larva/crecimiento & desarrollo , Larva/microbiología , Larva/fisiología , Masculino , Mosquitos Vectores/crecimiento & desarrollo , Control de Calidad , Reproducción
2.
J Org Chem ; 86(1): 762-769, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33395741

RESUMEN

We report a solvent-directed and regioselective carbon-carbon bond cleavage of aryl ketones by azido-1,3,5-triazines (ATs), which is typically completed within 10 min in DMSO at room temperature, without using transition metal catalysts. The cleavage is driven by the steric hindrance in the adducts of aryl ketones and ATs, which is substantiated by DFT calculation. Our recent results showed that ATs present high reactivity in solution and high stability in solid state. This "stability-reactivity paradox" has been explained in light of the molecular and crystal structures of ATs.

3.
Proc Natl Acad Sci U S A ; 114(1): 113-118, 2017 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-27940911

RESUMEN

Dengue, a viral infection transmitted between people by mosquitoes, is one of the most rapidly spreading diseases in the world. Here, we report the analyses covering 11 y (2005-2015) from the city of Guangzhou in southern China. Using the first 8 y of data to develop an ecologically based model for the dengue system, we reliably predict the following 3 y of dengue dynamics-years with exceptionally extensive dengue outbreaks. We demonstrate that climate conditions, through the effects of rainfall and temperature on mosquito abundance and dengue transmission rate, play key roles in explaining the temporal dynamics of dengue incidence in the human population. Our study thus contributes to a better understanding of dengue dynamics and provides a predictive tool for preventive dengue reduction strategies.


Asunto(s)
Aedes/virología , Cambio Climático , Dengue/epidemiología , Dengue/transmisión , Insectos Vectores/virología , Animales , China/epidemiología , Clima , Virus del Dengue/patogenicidad , Brotes de Enfermedades , Humanos , Modelos Teóricos , Lluvia , Temperatura
4.
J Org Chem ; 83(18): 10916-10921, 2018 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-30122034

RESUMEN

We report a crystalline compound 2-azido-4,6-dimethoxy-1,3,5-triazine (ADT) as an intrinsically safe, highly efficient, and shelf-stable diazo-transfer reagent. Because the decomposition of ADT is an endothermal process (Δ H = 30.3 kJ mol-1), ADT is intrinsically nonexplosive, as proved by thermal, friction, and impact tests. The diazo-transfer reaction based on ADT gives diazo compounds in excellent yields within several minutes at room temperature. ADT is very stable upon >1 year storage under air at room temperature.

6.
JMIR Form Res ; 8: e54638, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39230941

RESUMEN

BACKGROUND: Every hospital manager aims to build harmonious, mutually beneficial, and steady-state departments. Therefore, it is important to explore a hospital department development assessment model based on objective hospital data. OBJECTIVE: This study aims to use a novel machine learning algorithm to identify key evaluation indexes for hospital departments, offering insights for strategic planning and resource allocation in hospital management. METHODS: Data related to the development of a hospital department over the past 3 years were extracted from various hospital information systems. The resulting data set was mined using neural machine algorithms to assess the possible role of hospital departments in the development of a hospital. A questionnaire was used to consult senior experts familiar with the hospital to assess the actual work in each hospital department and the impact of each department's development on overall hospital discipline. We used the results from this questionnaire to verify the accuracy of the departmental risk scores calculated by the machine learning algorithm. RESULTS: Deep machine learning was performed and modeled on the hospital system training data set. The model successfully leveraged the hospital's training data set to learn, predict, and evaluate the working and development of hospital departments. A comparison of the questionnaire results with the risk ranking set from the departments machine learning algorithm using the cosine similarity algorithm and Pearson correlation analysis showed a good match. This indicates that the department development assessment model and risk score based on the objective data of hospital systems are relatively accurate and objective. CONCLUSIONS: This study demonstrated that our machine learning algorithm provides an accurate and objective assessment model for hospital department development. The strong alignment of the model's risk assessments with expert opinions, validated through statistical analysis, highlights its reliability and potential to guide strategic hospital management decisions.


Asunto(s)
Departamentos de Hospitales , Aprendizaje Automático , Humanos , Encuestas y Cuestionarios , Departamentos de Hospitales/organización & administración , Algoritmos , Derivación y Consulta
7.
Sci Rep ; 14(1): 9186, 2024 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649690

RESUMEN

Osteosarcoma (OS) is the most common malignant bone tumor with high pathological heterogeneity. Our study aimed to investigate disulfidptosis-related modification patterns in OS and their relationship with survival outcomes in patients with OS. We analyzed the single-cell-level expression profiles of disulfidptosis-related genes (DSRGs) in both OS microenvironment and OS subclusters, and HMGB1 was found to be crucial for intercellular regulation of OS disulfidptosis. Next, we explored the molecular clusters of OS based on DSRGs and related immune cell infiltration using transcriptome data. Subsequently, the hub genes of disulfidptosis in OS were screened by applying multiple machine models. In vitro and patient experiments validated our results. Three main disulfidptosis-related molecular clusters were defined in OS, and immune infiltration analysis suggested high immune heterogeneity between distinct clusters. The in vitro experiment confirmed decreased cell viability of OS after ACTB silencing and higher expression of ACTB in patients with lower immune scores. Our study systematically revealed the underlying relationship between disulfidptosis and OS at the single-cell level, identified disulfidptosis-related subtypes, and revealed the potential role of ACTB expression in OS disulfidptosis.


Asunto(s)
Neoplasias Óseas , Regulación Neoplásica de la Expresión Génica , Osteosarcoma , Análisis de la Célula Individual , Transcriptoma , Microambiente Tumoral , Humanos , Osteosarcoma/genética , Osteosarcoma/patología , Osteosarcoma/mortalidad , Osteosarcoma/metabolismo , Microambiente Tumoral/genética , Pronóstico , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/mortalidad , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Perfilación de la Expresión Génica , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Actinas/metabolismo , Actinas/genética
8.
Inorg Chem ; 52(18): 10258-63, 2013 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-24004251

RESUMEN

The rotation of meso-aryl groups in porphyrins depends on the degree of macrocyclic distortion and is also influenced by the surrounding temperature. Dynamic NMR methods and crystal structures of series of nonplanar metalloporphyrins reveal that macrocyclic distortion lowers the rotational barrier by weakening the nonbinding interactions of neighboring groups, while increased temperature allows the rotational barrier to be overcome more readily. Two empirical methods are developed to acquire the rotational barrier. This type of strained molecule can act as an adjustable molecular turnstile through adjusting the degree of macrocyclic distortion and changing the surrounding temperature.

9.
Front Genet ; 14: 1210722, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37953920

RESUMEN

Background: Rheumatoid arthritis (RA) is a disabling autoimmune disease that affects multiple joints. Accumulating evidence suggests that imbalances in liquid-liquid phase separation (LLPS) can lead to altered spatiotemporal coordination of biomolecular condensates, which play important roles in carcinogenesis and inflammatory diseases. However, the role of LLPS in the development and progression of RA remains unclear. Methods: We screened RA and normal samples from GSE12021, GSE55235, and GSE55457 transcriptome datasets and GSE129087 and GSE109449 single-cell sequencing datasets from Gene Expression Omnibus database to investigate the pathogenesis of LLPS-related hub genes at the transcriptome and single cell sequencing levels. Machine learning algorithms and weighted gene co-expression network analysis were applied to screen hub genes, and hub genes were validated using correlation studies. Results: Differential analysis showed that 36 LLPS-related genes were significantly differentially expressed in RA, further random forest and support vector machine identified four and six LLPS-related genes, respectively, and weighted gene co-expression network analysis identified 396 modular genes. Hybridization of the three sets revealed two hub genes, MYC and MAP1LC3B, with AUCs of 0.907 and 0.911, respectively. Further ROC analysis of the hub genes in the GSE55457 dataset showed that the AUCs of MYC and MAP1LC3B were 0.815 and 0.785, respectively. qRT-PCR showed that the expression of MYC and MAP1LC3B in RA synovial tissues was significantly lower than that in the normal control synovial tissues. Correlation analysis between hub genes and the immune microenvironment and single-cell sequencing analysis revealed that both MYC and MAP1LC3B were significantly correlated with the degree of infiltration of various innate and acquired immune cells. Conclusion: Our study reveals a possible mechanism for LLPS in RA pathogenesis and suggests that MYC and MAP1LC3B may be potential novel molecular markers for RA with immunological significance.

10.
Chemistry ; 18(25): 7675-9, 2012 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-22588783

RESUMEN

Ruffle- and dome-type porphyrins were developed as model systems to investigate the role of deformation mode and degree of distortion in heme. Their crystal structures revealed that as the degree of distortion increases, cavity size can be contracted in the ruffle mode and expanded in the dome mode, and the size of cavity can exceed the limit of free metal ions from the fourth period (see scheme).


Asunto(s)
Hemo/química , Hemoproteínas/química , Porfirinas/química , Cristalografía por Rayos X , Modelos Moleculares , Estructura Molecular
11.
Sci Rep ; 12(1): 1222, 2022 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-35075167

RESUMEN

The significance of N6-methyladenosine (m6A) RNA modifications in the progression of breast cancer (BC) has been recognised. However, their potential role and mechanism of action in the tumour microenvironment (TME) and immune response has not been demonstrated. Thus, the role of m6A regulators and their downstream target gene components in BC remain to be explored. In this study, we used a series of bioinformatics methods and experiments to conduct exploratory research on the possible role of m6A regulators in BC. First, two regulatory modes of immune activation and inactivation were determined by tumour classification. The TME, immune cell infiltration, and gene set variation analysis results confirmed the reliability of this pattern. The prognostic model of the m6A regulator was established by the least absolute shrinkage and selection operator and univariate and multivariate Cox analyses, with the two regulators most closely related to survival verified by real-time quantitative reverse transcription polymerase chain reaction. Next, the prognostic m6A regulator identified in the model was crossed with the differential copy number of variant genes in invasive BC (IBC), and it was determined that YTHDF1 was a hub regulator. Subsequently, single-cell analysis revealed the expression patterns of m6A regulators in different IBC cell populations and found that YTHDF1 had significantly higher expression in immune-related IBC cells. Therefore, we selected the intersection of the BC differential expression gene set and the differential expression gene set of a cell line with knocked-down YTHDF1 in literature to identify downstream target genes of YTHDF1, in which we found IFI6, EIR, and SPTBN1. A polymerase chain reaction was conducted to verify the results. Finally, we confirmed the role of YTHDF1 as a potential prognostic biomarker through pan-cancer analysis. Furthermore, our findings revealed that YTHDF1 can serve as a new molecular marker for BC immunotherapy.


Asunto(s)
Adenosina/análogos & derivados , Neoplasias de la Mama/metabolismo , Carcinoma/metabolismo , ARN/metabolismo , Microambiente Tumoral , Adenosina/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/mortalidad , Carcinoma/tratamiento farmacológico , Carcinoma/inmunología , Carcinoma/mortalidad , Estudios de Casos y Controles , Humanos , Linfocitos Infiltrantes de Tumor , Terapia Molecular Dirigida , Pronóstico , Proteínas de Unión al ARN/metabolismo
12.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 23(9): 539-42, 2011 Sep.
Artículo en Zh | MEDLINE | ID: mdl-21944175

RESUMEN

OBJECTIVE: To assess the effects of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) on hypoxic pulmonary hypertension(HPH) in patients with acute high altitude reaction(AHAR) and its change after return to lower altitude. METHODS: Ninety-six officers and soldier participating in rescue of Yushu megaseism on April 14th in 2010, leaving low altitude area (1 500 m) rapidly to high altitude area(3 700 m) to undertake strenuous physical work were enrolled for study. All of them were male, aged 18-35 years, and they were divided into three groups according to the symptomatic scores of AHAR: without AHAR(group B, n=25), mild to moderate AHAR (group C, n=47 ) and severe AHAR (group D, n=24). Mean pulmonary artery pressure (mPAP), levels in serum HIF-1α and VEGF were measured at high altitude area after a stay of 50 days, and also after their return to lower altitude area (1 500 m) for 12 hours and 15 days. Fifty healthy volunteers at low altitude area served as control (group A). RESULTS: Level of mPAP (mm Hg, 1 mm Hg=0.133 kPa), serum HIF-1α (pg/L) and VEGF (ng/L) in group B (24.23±1.56, 68.80±7.52 and 82.56±6.32) were significantly higher than those in group A (18.50±1.30, 50.95±3.33 and 65.78±4.03), respectively (all P<0.01). Moreover, the value of all the parameters increased with increase in severity of AHAR, the respective value in group C were 28.42±1.32, 88.10±9.20 and 104.82±10.36, and in group D were 34.70±2.94, 117.93±13.46 and 136.77±12.03, and there were significant differences in comparing two groups (all P<0.01). At high altitude area, AHAR total score was positively correlated with mPAP, serum HIF-1α and VEGF (r=0.672, 0.737 and 0.634, respectively, all P<0.01), mPAP was positively correlated with serum HIF-1α and VEGF (r=0.706, 0.638, both P<0.01). Compared with group A, level of mPAP (29.08±4.22), serum HIF-1α (91.16±20.58) and VEGF (107.11±10.32) were significantly increased in 96 officers and soldiers who stayed for 50 days at an altitude of 3 700 m (all P<0.01), and the values were significantly decreased after returning to lower altitude area for 12 hours(23.05±3.18, 70.99±8.22 and 78.65±6.47) and 15 days(18.96±1.75, 52.31±4.92 and 63.08±4.55). The values showed significant difference between 12 hours and 15 days stay at 1 500 m (all P<0.01). The values of the determined parameters 15 days after return to lower altitude area showed no difference compared with those of group A (all P>0.05). CONCLUSION: Strenuous physical work at high altitude area, AHAR becomes more serious, and it is accompanied by higher values of HIF-1α, VEGF and mPAP, indicating that HPH is closely associated with elevation of HIF-1α and VEGF. These changes are improved after returning to lower altitude area for 12 hours, and they recover to normal lever after 15 days.


Asunto(s)
Mal de Altura/metabolismo , Altitud , Hipertensión Pulmonar/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adolescente , Adulto , Estudios de Casos y Controles , Desastres , Terremotos , Humanos , Hipertensión Pulmonar/etiología , Hipoxia/complicaciones , Hipoxia/metabolismo , Masculino , Estudios Prospectivos , Adulto Joven
13.
Org Lett ; 21(18): 7204-7208, 2019 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-31318569

RESUMEN

A novel solvent-directed click reaction between active methylene compounds and azido-1,3,5-triazines has been developed. In aqueous solution, the regiospecific trisubstituted 1,2,3-triazole products are quickly synthesized in high yields under mild conditions and easy to separate without column chromatography. This click reaction is controlled by the protonation of a nitrogen anion intermediate, and the postulated mechanism is substantiated by DFT calculations.

14.
ACS Appl Mater Interfaces ; 8(39): 25725-25732, 2016 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-27632582

RESUMEN

An efficient method to deliver active proteins into cytosol is highly desirable to advance protein-based therapeutics. Arginine-rich cell-penetrating peptides (RPPs) have been intensively studied for intracellular protein delivery, and their applications require further improvement on delivery efficiency, serum stability, and cytotoxicity. Designing synthetic analogs of RPPs provides an alternative way to achieve efficient cytosolic protein delivery. Herein we report the design and synthesis of a dendritic small molecule TG6, which is composed of one rigid planar core and four flexible arms with one guanidinium on each arm. Protein structure and function are well preserved in the TG6-protein conjugates, which are readily internalized into cytosol. Our study demonstrates that TG6 is a serum-stable and low-toxic molecular transporter delivering both small cargoes and large active proteins efficiently into cytosol.


Asunto(s)
Citosol , Arginina , Péptidos de Penetración Celular , Sistemas de Liberación de Medicamentos , Guanidina , Proteínas de Transporte de Membrana
15.
Org Lett ; 15(3): 606-9, 2013 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-23323599

RESUMEN

It was demonstrated experimentally that nonplanar iron porphyrins can be induced to undergo a conversion in their electronic configuration to form a cross-hybrid transition by compressing the macrocyclic core size for the central metal ion. A series of monostrapped iron porphyrins were used as model systems, and their electronic properties were probed using electron spin resonance and differential spectral analyses. These results indicate that the formation of a cross-hybrid transition stage is related to the stability of the high-valence state and potent oxidizing ability of the central iron ion.


Asunto(s)
Hemo/química , Hierro/química , Modelos Moleculares , Cristalografía por Rayos X , Espectroscopía de Resonancia por Spin del Electrón , Estructura Molecular , Oxidación-Reducción
16.
Artículo en Zh | MEDLINE | ID: mdl-24386810

RESUMEN

OBJECTIVE: To assess the relationship of high altitude de-adaptation response (HADAR) with acute high altitude response (AHAR) and cardiac function. METHODS: Ninety-six military personnel of rapid entering into high altitude (3 700 to 4 800 m) with strong physical work were analyzed, all subjects were male, aged 18 - 35 years. According to the symptomatic scores of AHAR were divided into 3 groups: sever AHAR (group A, 24), mild to moderate AHAR (group B, 47) and non-AHAR (group C, 25) at high altitude. According to the symptomatic scores of HADAR were divided into 3 groups: severe HADAR (group E, 19), mild to moderate HADAR (group F, 40) and non-HADAR (group G, 37) after return to lower altitude (1 500 m). Mean pulmonary arterial pressure (mPAP), right ventricular internal dimension (RVID), outflow tract of right ventricle (RVOT), left ventricular internal dimension (LVID), left ventricular ejection fraction (LVEF), cardiac muscle work index (Tei index), creatine kinase isoenzymes-MB (CK-MB), lactic dehydrogenase isoenzyme-1 (LDH-1) were measured at high altitude stayed 50 days and after return to lower altitude 12 h, 15 d, and 30 d. Fifty healthy volunteers (group D) at 1 500 m altitude served as control. RESULTS: Level of mPAP, RVID, RVOT, RVID/LVID ratio, Tei index, CK-MB,and LDH-1 were higher, and LVEF was lower in group A than those in group B, C and D, there were significant differences between group B and C, C and D (all P < 0.01). AHAR scores were positively correlated with HADAR scores (r = 0.863, P < 0.01). Twelve hours after return to lower altitude, level of mPAP, RVID, RVOT, RVI/LVID ratio, Tei index, CK-MB, and LDH-1 were higher, and LVEF was lower in group E than those in group F, G and D, there were significant differences between group F and G, G and D (all P < 0.01). Fifteen days after return to lower altitude, level of mPAP, RVID, RVOT, RVID/LVID ratio were higher in group E than those in group F, G, and D, there were significant differences between group F and G, and D (P < 0.01 or P < 0.05), there were no significant differences between group G and D (all P > 0.05), LVEF, Tei index, CK-MB, LDH-1 showed no significant differences among groups (all P > 0.05). Thirty days after return to lower altitude, these parameters in group E, F, and G showed no significantly differences compared with those of group D (all P > 0.05). CONCLUSION: The severity of HADAR is associated with severity of AHAR and cardiac injury, the more serious of AHAR and cardiac injury at high altitude, the more serious of HADAR and cardiac injury after return to lower altitude, the more long of restore of right cardiac morphologic injury.


Asunto(s)
Adaptación Fisiológica , Mal de Altura/metabolismo , Mal de Altura/fisiopatología , Miocardio/enzimología , Adolescente , Adulto , Altitud , Estudios de Casos y Controles , Corazón/fisiopatología , Pruebas de Función Cardíaca , Humanos , Masculino , Adulto Joven
17.
Exp Ther Med ; 6(3): 747-752, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24137259

RESUMEN

The aim of this study was to assess the expression levels of induced sputum interleukin (IL)-8 and IL-10 levels in patients with acute exacerbated chronic obstructive pulmonary disease (AECOPD) complicated with chronic cor pulmonale (CCP) at high altitude, and to evaluate the intervention effects of an inhaled corticosteroid (ICS) and a ß2-adrenoceptor agonist in this disease. A total of 186 patients with AECOPD complicated with CCP were randomly divided into three groups, with 62 cases in each. With regard to the two treatment groups, group A was treated with salmeterol/fluticasone (50 µg/250 µg, respectively) by airway inhalation twice daily, while group B received budesonide (1 mg) as a spray inhalation, twice daily. The routine treatment group (group C) received only routine treatment. The levels of IL-8 and IL-10 in the induced sputum and the predicted percentage of forced expiratory volume in one second (FEV1%pred), partial pressure of oxygen in arterial blood (PaO2) and partial pressure of carbon dioxide in arterial blood (PaCO2) were examined on admission and at a stable stage two weeks following treatment. Forty healthy volunteers served as a control group (group D). Compared with group D values, the IL-8 induced sputum level and the PaCO2 were significantly increased, while the level of IL-10, FEV1%pred and the PaO2 were markedly decreased in the three COPD groups prior to treatment. Following treatment, the induced sputum IL-8 level and the PaCO2 were significantly decreased, while the induced sputum IL-10 level, FEV1%pred and the PaO2 were markedly increased in the three treatment groups compared with the values pre-therapy (all P<0.01). The post-treatment parameters were significantly different among the three groups (P<0.01). The results indicate that IL-8 and IL-10 are involved in the airway inflammation of AECOPD complicated by CCP. Treatment with an ICS was demonstrated to be a successful method of reducing the local expression of IL-8 and increasing the local expression of IL-10; however, ICS combined with a long-acting ß2-adrenoceptor agonist (LABA) was more effective than the sole administration of ICS in patients with AECOPD complicated by CCP at high altitude.

18.
PLoS One ; 7(2): e31097, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22363556

RESUMEN

High altitude acclimatization and adaptation mechanisms have been well clarified, however, high altitude de-adaptation mechanism remains unclear. In this study, we conducted a controlled study on cardiac functions in 96 healthy young male who rapidly entered the high altitude (3700 m) and returned to the plains (1500 m) after 50 days. Ninety eight healthy male who remained at low altitude were recruited as control group. The mean pulmonary arterial pressure (mPAP), left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), cardiac function index (Tei index) were tested. Levels of serum creatine kinase isoform MB (CK-MB), lactate dehydrogenase isoenzyme-1 (LDH-1), endothelin-1 (ET-1), nitrogen oxide (NO), serum hypoxia-inducible factor-1α (HIF-1α), 8-iso-prostaglandin F(2α) (8-iso PGF(2α)), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured at an altitude of 3700 m and 1500 m respectively. The results showed that after short-term exposure to high altitude mPAP and Tei index increased significantly, while LVEF and LVFS decreased significantly. These changes were positively correlated with altitude. On the 15(th) day after the subjects returned to low altitude, mPAP, LVEF and LVFS levels returned to the same level as those of the control subjects, but the Tei index in the returned subjects was still significantly higher than that in the control subjects (P<0.01). We also found that changes in Tei index was positively correlated with mPAP, ET-1, HIF-1α and 8-iso PGF(2α) levels, and negatively correlated with the level of NO, LVEF, LVFS, CK-MB and LDH-1. These findings suggest that cardiac function de-adapts when returning to the plains after short-term exposure to high altitude and the function recovery takes a relatively long time.


Asunto(s)
Aclimatación/fisiología , Altitud , Exposición a Riesgos Ambientales , Pruebas de Función Cardíaca , Adolescente , Adulto , Presión Sanguínea/fisiología , Creatina Quinasa/sangre , Citocinas/sangre , Diástole/fisiología , Dinoprost/análogos & derivados , Dinoprost/sangre , Radicales Libres/sangre , Geografía , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/sangre , Masculino , Malondialdehído/metabolismo , Miocardio/enzimología , Arteria Pulmonar/fisiología , Sístole/fisiología , Factores de Tiempo , Adulto Joven
19.
Vaccine ; 29(20): 3695-702, 2011 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-21419774

RESUMEN

Our previous work applied a combination of bioinformatics approaches and in vitro assays to identify the dengue-2 virus (DENV-2)-specific B- and T-cell epitopes. In this report, we first evaluated the antigenicity of both B- and T-cell epitopes reacting with different sera against DENV-2 by ELISA as well as the ability of T-cell epitope to activate CD4(+) T-cell producing IFN-γ using ELISPOT, which showed a specific reactivity between either B- or T-cell epitope and DENV-2 antisera, and a significant increase of IFN-γ producing cells in DENV-2 infected mice. Then, a multi-epitope peptide containing the above B-, T-cell epitopes of envelope domain III (EDIII) of DENV-2 and pan-DR epitope (PADRE) was bioinformatically designed and synthesized. The verification of its immunogenicity and protective effect was performed in in vitro and in vivo experiments. The results showed that a high level of antibody in mice elicited by the multi-epitope peptide was detected by ELISA and the anti-peptide sera binding to the vero cells infected with DEN-2 was observed with immunofluorescence test. More importantly, the peptide could induce lymphoproliferation in vitro and a predominant Th1 type of immune response was examined by flow cytometry. We also found that the virus replication in the mice vaccinated with the multi-epitope peptide was obviously less than that of the control groups. These results may provide some important information for the development of dengue vaccine.


Asunto(s)
Vacunas contra el Dengue/inmunología , Virus del Dengue/inmunología , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito T/inmunología , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Chlorocebus aethiops , Dengue/inmunología , Dengue/prevención & control , Femenino , Inmunidad Celular , Inmunidad Humoral , Inmunización , Inmunoglobulina G/análisis , Inmunoglobulina G/inmunología , Interferón gamma/sangre , Ratones , Ratones Endogámicos C57BL , Pruebas de Neutralización , ARN Viral/sangre , Vacunas de Subunidad/genética , Vacunas de Subunidad/inmunología , Células Vero
20.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 27(4): 457-60, 2011 Nov.
Artículo en Zh | MEDLINE | ID: mdl-22295525

RESUMEN

OBJECTIVE: To assess the effect of oxidative stress in development of acute high altitude response (AHAR) during the process of strong physical work at high altitude and its change after return to lower altitude. METHODS: Ninety-six officers and soldiers of rapid entering into high altitude (3 700 m) with strong physical work were analyzed, all subjects were male, aged 18-35 years. According to the symptomatic scores of AHAR were divided into 3 groups: severe AHAR (group A, n = 24), mild AHAR (group B, n = 47) and without AHAR (group C, n = 25). Levels in serum 8-iso prostaglandinF2alpha(8-iso-PGF2alpha), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured at higher altitude stayed 50 d and after return to lower altitude (1 500 m) 12 h and 15 d, and 50 healthy volunteers (group D) at 1 500 m altitude served as controll. RESULTS: Levels of serum 8-iso-PGF2alpha and MDA [(9.53 +/- 0.47) microg/L, (8.91 +/- 0.39) micromol/L] were significantly higher in group A than those in group B [(8.34 +/- 0.42) microg/L, (7.31 +/- 0.32) micromol/L] , group C [(7.02 +/- 0.48) microg/L, (6.41 +/- 0.23) micromol/L] and group D [(5.13 +/- 0.56) microg/L, (5.48 +/- 0.33) micromol/L], (all P < 0.01), and serum SOD [(52.08 +/- 3.44) micro/ml] was significantly lower in group A than that in group B [62.27 +/- 2.54) micro/ml], group C [(71.99 +/- 3.35) micro/ml] and group D [(80.78 +/- 3.44) micro/ ml] (all P < 0.01), there were significant differences between group B and C, C and D (all P < 0.01). At altitude 3 700 m 50 d, AHAR scores was positively correlated with serum 8-iso-PGF2alpha and MDA (all P < 0.01), negatively correlated with SOD (P < 0.01). Serum 8-iso-PGF2alpha and MDA were negatively correlated with SOD (all P < 0.01). Levels of serum 8-iso-PGF2alpha and MDA were significantly higher at altitude of 3 700 m 50 d than those at altitude of 1 500 m 12 h,15 d in group D (all P < 0.01), and serum SOD was significantly lower than that at 1 500 m 12 h,15 d in group D (all P < 0.01), there were significantly difference between at 1 500 m 12 h and 15 d (all P < 0.01), there were no difference between at 15 d in group D (all P > 0.05). CONCLUSION: The more serious of oxidative stress and oxidative/antioxidative imbalance, the more serious of AHAR, oxidative stress and oxidative/antioxidative imbalance may be involved in the development of AHAR. The changes were obviously improved after return to lower altitude 12 h, and recovered to normal after 15 d.


Asunto(s)
Mal de Altura/fisiopatología , Estrés Oxidativo/fisiología , Esfuerzo Físico/fisiología , Adolescente , Adulto , Altitud , Humanos , Masculino , Adulto Joven
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