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1.
Plant Physiol ; 195(4): 2829-2842, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-38758114

RESUMEN

Lespedeza potaninii, a xerophytic subshrub belonging to the legume family, is native to the Tengger Desert and is highly adapted to drought. It has important ecological value due to its drought adaptability, but the underlying molecular mechanisms remain largely unknown. Here, we report a 1.24 Gb chromosome-scale assembly of the L. potaninii genome (contig N50 = 15.75 Mb). Our results indicate that L. potaninii underwent an allopolyploid event with 2 subgenomes, A and B, presenting asymmetric evolution and B subgenome dominance. We estimate that the 2 diploid progenitors of L. potaninii diverged around 3.6 million years ago (MYA) and merged around 1.0 MYA. We revealed that the expansion of hub genes associated with drought responses, such as the binding partner 1 of accelerated cell death 11 (ACD11) (BPA1), facilitated environmental adaptations of L. potaninii to desert habitats. We found a novel function of the BPA1 family in abiotic stress tolerance in addition to the known role in regulating the plant immune response, which could improve drought tolerance by positively regulating reactive oxygen species homeostasis in plants. We revealed that bZIP transcription factors could bind to the BPA1 promoter and activate its transcription. Our work fills the genomic data gap in the Lespedeza genus and the tribe Desmodieae, which should provide theoretical support both in the study of drought tolerance and in the molecular breeding of legume crops.


Asunto(s)
Adaptación Fisiológica , Sequías , Genoma de Planta , Adaptación Fisiológica/genética , Evolución Molecular , Fabaceae/genética , Fabaceae/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas , Filogenia
2.
Pharmacol Res ; 202: 107122, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38428703

RESUMEN

The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8+ T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8+ T cells contained a fraction of CD39hi cells that constituted about 6.6% of total CD8+ T cells in tumors. These CD39hi cells enriched for GC-infiltrating CD8+ T cells with features of exhaustion in transcriptional, phenotypic, metabolic and functional profiles. Additionally, GC-infiltrating CD39hiCD8+ T cells were also identified for tumor-reactive T cells, as these cells expanded in vitro were able to recognize autologous tumor organoids and induced more tumor cell apoptosis than those of expanded their CD39int and CD39-CD8+ counterparts. Furthermore, CD39 enzymatic activity controlled GC-infiltrating CD39hiCD8+ T cell effector function, and blockade of CD39 efficiently enhanced their production of cytokines IFN-γ and TNF-α. Finally, high percentages of GC-infiltrating CD39hiCD8+ T cells correlated with tumor progression and independently predicted patients' poor overall survival. These findings provide novel insights into the association of CD39 expression level on CD8+ T cells with their features and potential clinical implications in GC, and empowering those exhausted tumor-reactive CD39hiCD8+ T cells through CD39 inhibition to circumvent the suppressor program may be an attractive therapeutic strategy against GC.


Asunto(s)
Linfocitos T CD8-positivos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Citocinas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
3.
BMC Public Health ; 24(1): 1934, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39026285

RESUMEN

BACKGROUND: Many effective therapies for psoriasis are being applied in clinical practice in recent years, however, some patients still can't achieve satisfied effect even with biologics. Therefore, it is crucial to identify factors associated with the treatment efficacy among psoriasis patients. This study aims to explore factors influencing the treatment efficacy of psoriasis patients based on decision tree model and logistic regression. METHODS: We implemented an observational study and recruited 512 psoriasis patients in Shanghai Skin Diseases Hospital from 2021 to 2022. We used face-to-face questionnaire interview and physical examination to collect data. Influencing factors of treatment efficacy were analyzed by using logistic regression, and decision tree model based on the CART algorithm. The receiver operator curve (ROC) was plotted for model evaluation and the statistical significance was set at P < 0.05. RESULTS: The 512 patients were predominately males (72.1%), with a median age of 47.5 years. In this study, 245 patients achieved ≥ 75% improvement in psoriasis area and severity index (PASI) score in week 8 and was identified as treatment success (47.9%). Logistic regression analysis showed that patients with senior high school and above, without psoriasis family history, without tobacco smoking and alcohol drinking had higher percentage of treatment success in patients with psoriasis. The final decision tree model contained four layers with a total of seventeen nodes. Nine classification rules were extracted and five factors associated with treatment efficacy were screened, which indicated tobacco smoking was the most critical variable for treatment efficacy prediction. Model evaluation by ROC showed that the area under curve (AUC) was 0.79 (95%CI: 0.75 ~ 0.83) both for logistic regression model (0.80 sensitivity and 0.69 specificity) and decision tree model (0.77 sensitivity and 0.73 specificity). CONCLUSION: Psoriasis patients with higher education, without tobacco smoking, alcohol drinking and psoriasis family history had better treatment efficacy. Decision tree model had similar predicting effect with the logistic regression model, but with higher feasibility due to the nature of simple, intuitive, and easy to understand.


Asunto(s)
Árboles de Decisión , Psoriasis , Humanos , Psoriasis/terapia , Femenino , Masculino , Persona de Mediana Edad , China , Modelos Logísticos , Adulto , Resultado del Tratamiento , Encuestas y Cuestionarios , Índice de Severidad de la Enfermedad
4.
Plant Biotechnol J ; 20(3): 592-609, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34717292

RESUMEN

Melilotus species are used as green manure and rotation crops worldwide and contain abundant pharmacologically active coumarins. However, there is a paucity of information on its genome and coumarin production and function. Here, we reported a chromosome-scale assembly of Melilotus albus genome with 1.04 Gb in eight chromosomes, containing 71.42% repetitive elements. Long terminal repeat retrotransposon bursts coincided with declining of population sizes during the Quaternary glaciation. Resequencing of 94 accessions enabled insights into genetic diversity, population structure, and introgression. Melilotus officinalis had relatively larger genetic diversity than that of M. albus. The introgression existed between M. officinalis group and M. albus group, and gene flows was from M. albus to M. officinalis. Selection sweep analysis identified candidate genes associated with flower colour and coumarin biosynthesis. Combining genomics, BSA, transcriptomics, metabolomics, and biochemistry, we identified a ß-glucosidase (BGLU) gene cluster contributing to coumarin biosynthesis. MaBGLU1 function was verified by overexpression in M. albus, heterologous expression in Escherichia coli, and substrate feeding, revealing its role in scopoletin (coumarin derivative) production and showing that nonsynonymous variation drives BGLU enzyme activity divergence in Melilotus. Our work will accelerate the understanding of biologically active coumarins and their biosynthetic pathways, and contribute to genomics-enabled Melilotus breeding.


Asunto(s)
Cumarinas , Melilotus , Cumarinas/metabolismo , Melilotus/química , Melilotus/genética , Melilotus/metabolismo , Fitomejoramiento , Biología de Sistemas , Transcriptoma/genética
5.
Int J Mol Sci ; 23(13)2022 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-35806414

RESUMEN

The GRAS gene family is a plant-specific family of transcription factors, which play an important role in many metabolic pathways, such as plant growth and development and stress response. However, there is no report on the comprehensive study of the GRAS gene family of Melilotus albus. Here, we identified 55 MaGRAS genes, which were classified into 8 subfamilies by phylogenetic analysis, and unevenly distributed on 8 chromosomes. The structural analysis indicated that 87% of MaGRAS genes have no intron, which is highly conservative in different species. MaGRAS proteins of the same subfamily have similar protein motifs, which are the source of functional differences of different genomes. Transcriptome and qRT-PCR data were combined to determine the expression of 12 MaGRAS genes in 6 tissues, including flower, seed, leaf, stem, root and nodule, which indicated the possible roles in plant growth and development. Five and seven MaGRAS genes were upregulated under ABA, drought, and salt stress treatments in the roots and shoots, respectively, indicating that they play vital roles in the response to ABA and abiotic stresses in M. albus. Furthermore, in yeast heterologous expression, MaGRAS12, MaGRAS34 and MaGRAS33 can enhance the drought or salt tolerance of yeast cells. Taken together, these results provide basic information for understanding the underlying molecular mechanisms of GRAS proteins and valuable information for further studies on the growth, development and stress responses of GRAS proteins in M. albus.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Melilotus , Perfilación de la Expresión Génica , Genoma de Planta , Melilotus/genética , Familia de Multigenes , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Saccharomyces cerevisiae/metabolismo , Estrés Fisiológico/genética
6.
Int J Mol Sci ; 24(1)2022 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-36613571

RESUMEN

Melilotus albus is a high-quality forage, due to its high protein content, and aboveground biomass and salt tolerance. Rab (Ras-related protein in the brain) proteins are the largest GTPase family which play a key role in intracellular membrane transport, and many Rab genes have been identified in eukaryotes. The growth and distribution of M. albus are severely hampered by soil salinization. However, little is known about candidate genes for salt tolerance in M. albus. In this study, 27 Rab family genes were identified for the first time from M. albus, and divided into eight groups (Groups A-H). The number of introns in MaRabs ranged from one to seven, with most genes containing one intron. In addition, most MaRab proteins showed similarities in motif composition. Phylogenetic analysis and structural-domain comparison indicated that Rab family genes were highly conserved in M. albus. Members of the MaRab gene family were distributed across all eight chromosomes, with the largest distribution on chromosome 1. Prediction of the protein interaction network showed that 24 Rab proteins exhibited protein-protein interactions. Analysis of the promoter cis-acting elements showed that MaRab-gene family members are extensively involved in abiotic stress responses. RNA-seq data analysis of the MaRab-gene-expression patterns suggested that the Rab gene family possesses differentially expressed members in five organs and under salt stress, drought stress, and ABA (Abscisic Acid) treatment. Differentially expressed genes under drought stress, salt stress and ABA stress were validated by quantitative real-time PCR. Furthermore, heterologous expression in yeast was used to characterize the functions of MaRab1 and MaRab17, which were upregulated in reaction to salt stress. In summary, this study provided valuable information for further research into the molecular mechanism of the response of M. albus to saline stress, as well as the possibility of developing cultivars with high salt-resistance characteristics.


Asunto(s)
Melilotus , Tolerancia a la Sal , Tolerancia a la Sal/genética , Melilotus/genética , Filogenia , Proteínas de Plantas/metabolismo , Genoma de Planta , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas , Familia de Multigenes
7.
J Cell Mol Med ; 25(18): 8579-8587, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34378306

RESUMEN

As the direct contacting site for pathogens and allergens, the mucosal barrier plays a vital role in the lungs and intestines. Innate lymphoid cells (ILCs) are particularly resident in the mucosal barrier and participate in several pathophysiological processes, such as maintaining or disrupting barrier integrity, preventing various pathogenic invasions. In the pulmonary mucosae, ILCs sometimes aggravate inflammation and mucus hypersecretion but restore airway epithelial integrity and maintain lung tissue homeostasis at other times. In the intestinal mucosae, ILCs can increase epithelial permeability, leading to severe intestinal inflammation on the one hand, and assist mucosal barrier in resisting bacterial invasion on the other hand. In this review, we will illustrate the positive and negative roles of ILCs in mucosal barrier immunity.


Asunto(s)
Mucosa Intestinal/inmunología , Linfocitos/inmunología , Mucosa Respiratoria/inmunología , Animales , Humanos , Inmunidad Innata , Linfocitos/citología
8.
BMC Anesthesiol ; 21(1): 66, 2021 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-33653263

RESUMEN

BACKGROUND: Estimating the depth of anaesthesia (DoA) is critical in modern anaesthetic practice. Multiple DoA monitors based on electroencephalograms (EEGs) have been widely used for DoA monitoring; however, these monitors may be inaccurate under certain conditions. In this work, we hypothesize that heart rate variability (HRV)-derived features based on a deep neural network can distinguish different anaesthesia states, providing a secondary tool for DoA assessment. METHODS: A novel method of distinguishing different anaesthesia states was developed based on four HRV-derived features in the time and frequency domain combined with a deep neural network. Four features were extracted from an electrocardiogram, including the HRV high-frequency power, low-frequency power, high-to-low-frequency power ratio, and sample entropy. Next, these features were used as inputs for the deep neural network, which utilized the expert assessment of consciousness level as the reference output. Finally, the deep neural network was compared with the logistic regression, support vector machine, and decision tree models. The datasets of 23 anaesthesia patients were used to assess the proposed method. RESULTS: The accuracies of the four models, in distinguishing the anaesthesia states, were 86.2% (logistic regression), 87.5% (support vector machine), 87.2% (decision tree), and 90.1% (deep neural network). The accuracy of deep neural network was higher than those of the logistic regression (p < 0.05), support vector machine (p < 0.05), and decision tree (p < 0.05) approaches. Our method outperformed the logistic regression, support vector machine, and decision tree methods. CONCLUSIONS: The incorporation of four HRV-derived features in the time and frequency domain and a deep neural network could accurately distinguish between different anaesthesia states; however, this study is a pilot feasibility study. The proposed method-with other evaluation methods, such as EEG-is expected to assist anaesthesiologists in the accurate evaluation of the DoA.


Asunto(s)
Anestesia/estadística & datos numéricos , Electrocardiografía/métodos , Frecuencia Cardíaca/efectos de los fármacos , Redes Neurales de la Computación , Árboles de Decisión , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Máquina de Vectores de Soporte/estadística & datos numéricos
9.
Int J Mol Sci ; 22(19)2021 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-34639166

RESUMEN

Coumarins, natural products abundant in Melilotus albus, confer features in response to abiotic stresses, and are mainly present as glycoconjugates. UGTs (UDP-glycosyltransferases) are responsible for glycosylation modification of coumarins. However, information regarding the relationship between coumarin biosynthesis and stress-responsive UGTs remains limited. Here, a total of 189 MaUGT genes were identified from the M. albus genome, which were distributed differentially among its eight chromosomes. According to the phylogenetic relationship, MaUGTs can be classified into 13 major groups. Sixteen MaUGT genes were differentially expressed between genotypes of Ma46 (low coumarin content) and Ma49 (high coumarin content), suggesting that these genes are likely involved in coumarin biosynthesis. About 73.55% and 66.67% of the MaUGT genes were differentially expressed under ABA or abiotic stress in the shoots and roots, respectively. Furthermore, the functions of MaUGT68 and MaUGT186, which were upregulated under stress and potentially involved in coumarin glycosylation, were characterized by heterologous expression in yeast and Escherichia coli. These results extend our knowledge of the UGT gene family along with MaUGT gene functions, and provide valuable findings for future studies on developmental regulation and comprehensive data on UGT genes in M. albus.


Asunto(s)
Cumarinas/metabolismo , Genoma de Planta , Glucuronosiltransferasa/metabolismo , Melilotus/metabolismo , Proteínas de Plantas/metabolismo , Estrés Fisiológico , Uridina Difosfato/metabolismo , Cromosomas de las Plantas/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Estudio de Asociación del Genoma Completo , Glucuronosiltransferasa/genética , Glicosilación , Melilotus/genética , Melilotus/crecimiento & desarrollo , Filogenia , Proteínas de Plantas/genética , Transcriptoma
10.
J Cell Mol Med ; 24(5): 2761-2771, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31970850

RESUMEN

Lung immune responses to respiratory pathogens and allergens are initiated in early life which will further influence the later onset of asthma. The airway epithelia form the first mechanical physical barrier to allergic stimuli and environmental pollutants, which is also the key regulator in the initiation and development of lung immune response. However, the epithelial regulation mechanisms of early-life lung immune responses are far from clear. Our previous study found that integrin ß4 (ITGB4) is decreased in the airway epithelium of asthma patients with specific variant site. ITGB4 deficiency in adult mice aggravated the lung Th2 immune responses and enhanced airway hyper-responsiveness (AHR) with a house dust mite (HDM)-induced asthma model. However, the contribution of ITGB4 to the postnatal lung immune response is still obscure. Here, we further demonstrated that ITGB4 deficiency following birth mediates spontaneous lung inflammation with ILC2 activation and increased infiltration of eosinophils and lymphocytes. Moreover, ITGB4 deficiency regulated thymic stromal lymphopoietin (TSLP) production in airway epithelial cells through EGFR pathways. Neutralization of TSLP inhibited the spontaneous inflammation significantly in ITGB4-deficient mice. Furthermore, we also found that ITGB4 deficiency led to exaggerated lung allergic inflammation response to HDM stress. In all, these findings indicate that ITGB4 deficiency in early life causes spontaneous lung inflammation and induces exaggerated lung inflammation response to HDM aeroallergen.


Asunto(s)
Células Epiteliales/metabolismo , Hipersensibilidad/complicaciones , Hipersensibilidad/inmunología , Integrina beta4/metabolismo , Pulmón/patología , Neumonía/complicaciones , Animales , Animales Recién Nacidos , Hiperreactividad Bronquial/complicaciones , Citocinas/metabolismo , Células Epiteliales/patología , Receptores ErbB/metabolismo , Hipersensibilidad/parasitología , Hipersensibilidad/fisiopatología , Pulmón/parasitología , Linfocitos/inmunología , Ratones Transgénicos , Fosforilación , Pyroglyphidae/fisiología , Linfopoyetina del Estroma Tímico
11.
Clin Sci (Lond) ; 134(13): 1735-1749, 2020 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-32608482

RESUMEN

Airway epithelial cells (AECs) play a key role in asthma susceptibility and severity. Integrin ß4 (ITGB4) is a structural adhesion molecule that is down-regulated in the airway epithelium of asthma patients. Although a few studies hint toward the role of ITGB4 in asthmatic inflammation pathogenesis, their specific resultant effects remain unexplored. In the present study, we determined the role of ITGB4 of AECs in the regulation of Th2 response and identified the underpinning molecular mechanisms. We found that ITGB4 deficiency led to exaggerated lung inflammation and AHR with higher production of CCL17 in house dust mite (HDM)-treated mice. ITGB4 regulated CCL17 production in AECs through EGFR, ERK and NF-κB pathways. EFGR-antagonist treatment or the neutralization of CCL17 both inhibited exaggerated pathological marks in HDM-challenged ITGB4-deficient mice. Together, these results demonstrated the involvement of ITGB4 deficiency in the development of Th2 responses of allergic asthma by down-regulation of EGFR and CCL17 pathway in AECs.


Asunto(s)
Asma/inmunología , Quimiocina CCL17/inmunología , Células Epiteliales/inmunología , Integrina beta4/inmunología , Pulmón/inmunología , Animales , Asma/genética , Quimiocina CCL17/genética , Receptores ErbB/genética , Receptores ErbB/inmunología , Femenino , Humanos , Integrina beta4/genética , Masculino , Ratones , Ratones Noqueados , Células Th2/inmunología
12.
Molecules ; 23(4)2018 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-29614822

RESUMEN

Melilotus albus and Melilotus officinalis are widely used in forage production and herbal medicine due to the biological activity of their coumarins, which have many biological and pharmacological activities, including anti-HIV and anti-tumor effects. To comprehensively evaluate M. albus and M. officinalis coumarin content (Cou), morphological variation, and molecular phylogeny, we examined the Cou, five morphological traits and the molecular characterization based on the trnL-F spacer and internal transcribed spacer (ITS) regions of 93 accessions. Significant (p < 0.05) variation was observed in the Cou and all five morphological traits in both species. Analysis of population differentiation (Pst) of the phenotypic traits showed that powdery mildew resistance (PMR) had the greatest Pst, meaning that this trait demonstrated the largest genetic differentiation among the accessions. The Pst values of dry matter yield (DMY) and Cou were relatively high. Biplot analysis identified accessions with higher DMY and higher and lower Cou. Analysis of molecular sequence variation identified seven haplotypes of the trnL-F spacer and 13 haplotypes of the ITS region. Based on haplotype and sequence analyses, the genetic variation of M. officinalis was higher than that of M. albus. Additionally, ITS sequence analysis showed that the variation among accessions was larger than that among species across three geographical areas: Asia, Europe, and North America. Similarly, variation among accessions for both the trnL-F and ITS sequences were larger than the differences between the geographical areas. Our results indicate that there has been considerable gene flow between the two Melilotus species. Our characterization of Cou and the morphological and genetic variations of these two Melilotus species may provide useful insights into germplasm improvement to enhance DMY and Cou.


Asunto(s)
Cumarinas/metabolismo , Melilotus/clasificación , Melilotus/metabolismo , ADN de Cloroplastos/genética , Variación Genética/genética , Haplotipos/genética , Melilotus/genética , Filogenia , Análisis de Secuencia de ADN
13.
Biochem Biophys Res Commun ; 472(1): 75-82, 2016 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-26906624

RESUMEN

Drought and high salinity are two major abiotic factors that restrict alfalfa productivity. A dehydrin protein, CsLEA, from the desert grass Cleistogenes songorica was transformed into alfalfa (Medicago sativa L.) via Agrobacterium-mediated transformation using the bar gene as a selectable marker, and the drought and salt stress tolerances of the transgenic plants were assessed. Thirty-nine of 119 transformants were positive, as screened by Basta, and further molecularly authenticated using PCR and RT-PCR. Phenotype observations revealed that the transgenic plants grew better than the wild-type (WT) plants after 15d of drought stress and 10d of salt stress: the leaves of WT alfalfa turned yellow, whereas the transgenic alfalfa leaves only wilted; after rewatering, the transgenic plants returned to a normal state, though the WT plants could not be restored. Evaluation of physiologic and biochemical indices during drought and salt stresses showed a relatively lower Na(+) content in the leaves of the transgenic plants, which would reduce toxic ion effects. In addition, the transgenic plants were able to maintain a higher relative water content (RWC), higher shoot biomass, fewer photosystem changes, decreased membrane injury, and a lower level of osmotic stress injury. These results demonstrate that overexpression of the CsLEA gene can enhance the drought and salt tolerance of transgenic alfalfa; in addition, carrying the bar gene in the genome may increase herbicide resistance.


Asunto(s)
Sequías , Medicago sativa/genética , Medicago sativa/fisiología , Tolerancia a la Sal/genética , Aclimatación , Genes de Plantas , Medicago sativa/crecimiento & desarrollo , Fenotipo , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente , Proteínas Recombinantes/genética , Tolerancia a la Sal/fisiología , Estrés Fisiológico , Transformación Genética
14.
J Recept Signal Transduct Res ; 35(6): 523-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25264226

RESUMEN

It has been well documented that Momordica charantia polysaccharide (MCP) has multiple biological effects such as immune enhancement, anti-oxidation and anti-cancer. However, the potential protective effects of MCP on stroke damage and its relative mechanisms remain unclear. Our present study demonstrated that MCP could scavenge reactive oxygen species (ROS) in intra-cerebral hemorrhage damage, significantly attenuating the neuronal death induced by thrombin in primary hippocampal neurons. Furthermore, we found that MCP prevented the activation of the c-Jun N-terminal protein kinase (JNK3), c-Jun and caspase-3, which was caused by the intra-cerebral hemorrhage injury. Taken together, our study demonstrated that MCP had a neuroprotective effect in response to intra-cerebral hemorrhage and its mechanisms involved the inhibition of JNK3 signaling pathway.


Asunto(s)
Lesiones Encefálicas/tratamiento farmacológico , Hemorragia Cerebral/complicaciones , Proteína Quinasa 10 Activada por Mitógenos/metabolismo , Momordica charantia/química , Fármacos Neuroprotectores/farmacología , Fitoterapia , Polisacáridos/farmacología , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Lesiones Encefálicas/etiología , Lesiones Encefálicas/metabolismo , Radicales Libres/metabolismo , Immunoblotting , Técnicas para Inmunoenzimas , Inmunoprecipitación , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos
15.
Circ J ; 79(6): 1342-8, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25797071

RESUMEN

BACKGROUND: We investigated the acute vasodilator effects of i.v. fasudil, a specific Rho-kinase inhibitor, on pulmonary circulation in patients with congenital heart defects (CHD) and severe pulmonary arterial hypertension (PAH). METHODS AND RESULTS: Thirty-five patients (34.23±12.10 years old) with CHD and severe PAH were consecutively enrolled. All patients underwent heart catheterization. At baseline and 30 min after initiation of i.v. fasudil, the following hemodynamic parameters were measured and calculated: right atrial pressure, pulmonary and systemic artery pressure (PAP and SAP), pulmonary and systemic vascular resistance, pulmonary-to-systemic blood pressure ratio (Pp/Ps), pulmonary-to-systemic blood flow ratio (Qp/Qs), cardiac index (CI) and artery oxygen saturation (SaO2). After fasudil treatment, marked decrease in mean PAP (mPAP), pulmonary vascular resistance (PVR), total pulmonary resistance, pulmonary-to-systemic vascular resistance ratio (Rp/Rs) and mean Pp/Ps (mPp/Ps) was found, while Qp/Qs increased significantly without affecting CI and SAP. mPAP, PVR, Rp/Rs and Qp/Qs tended to be improved more significantly in the post-tricuspid shunt group compared with the pre-tricuspid shunt group. CONCLUSIONS: Fasudil was well tolerated in patients with CHD and severe PAH, and significantly reduced PAP and PVR without affecting CI, SAP or SaO2.


Asunto(s)
1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , Cardiopatías Congénitas/complicaciones , Hemodinámica/efectos de los fármacos , Hipertensión Pulmonar/tratamiento farmacológico , Terapia Molecular Dirigida , Inhibidores de Proteínas Quinasas/uso terapéutico , Vasodilatadores/uso terapéutico , Quinasas Asociadas a rho/antagonistas & inhibidores , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/uso terapéutico , Adolescente , Adulto , Cateterismo Cardíaco , Femenino , Humanos , Hipertensión Pulmonar/etiología , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/farmacología , Vasodilatadores/farmacología , Adulto Joven
16.
Liver Int ; 34(5): 748-58, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24134218

RESUMEN

BACKGROUND: Hyperammonaemia is a serious metabolic disorder commonly observed in patients with hepatic failure. However, it is unknown whether hyperammonaemia has a direct adverse effect on the hepatocytes and thereby serves as both a cause and effect of hepatic failure. AIMS: The purposes were to determine whether hepatic injury can be caused by hyperammonaemia, and if so, screen the key genes involved in hyperammonaemia. METHODS: Hyperammonaemic rats were established via intragastric administration of the ammonium chloride solution. The liver tissues were assessed via biochemistry, histology, immunohistochemistry and microarray analysis. Selected genes were confirmed by quantitative RT-PCR. RESULTS: Administration of the ammonium chloride caused the hyperammonaemia, accompanied with the changes of plasma markers indicating hepatic injury. A pathological assessment demonstrated increased apoptosis and higher level of cyclin D1 and cyclin A in hyperammonaemic rat liver. Microarray was performed on the liver samples and 198 differentially expressed genes were identified in hyperammonaemic rats and validated by quantitative RT-PCR. These genes were associated with many vital functional classes and belonged to different signal transduction pathways. CONCLUSIONS: This study demonstrates that hyperammonaemia can directly induce hepatic injury via the hepatocyte apoptosis. Gene expression profile may provide the possible explanations and mechanisms for the hepatic injury induced by hyperammonaemia.


Asunto(s)
Hiperamonemia/patología , Hígado/patología , Cloruro de Amonio , Animales , Apoptosis , Ciclina A/metabolismo , Ciclina D1/metabolismo , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Hiperamonemia/inducido químicamente , Hiperamonemia/metabolismo , Hígado/metabolismo , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Ratas Sprague-Dawley
17.
Ann Vasc Surg ; 28(5): 1306-11, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24560823

RESUMEN

BACKGROUND: This study aims to offer experimental data and indirect evidences for the application of percutaneous rotational atherectomy to treat patent ductus arteriosus (PDA). METHODS: Eleven dogs (6 male dogs and 5 female dogs; aged 14-20 months, with an average of 16.7±3.2 months; weight 20-25 kg, with an average of 22.7±2.5 kg) were enrolled in this study. The diameters of the left and right arteries ranged from 3.2 to 4.8 mm (average 3.9±0.6 mm) on percutaneous angiography. Percutaneous rotational atherectomy with proper rotablator (the size was 1-1.5 mm larger than the artery diameter) was performed in the arterial intima. After 4 weeks from percutaneous rotational atherectomy, arteriography was conducted to observe the changes in artery diameter. Then all dogs were sacrificed and the pathologic examination was conducted on the left and right axillary arteries. RESULTS: There were obvious changes with different degrees in 22 arteries, including 8 arteries with complete occlusion and 12 arteries with stenosis (≥2/3, 1/2, and 1/3 stenosis in 4, 4, and 4 arteries, respectively). The occlusion rate was 36.4% and the total effective rate was 90.9%. It was considered failure in other 2 arteries with <1/3 of stenosis. CONCLUSIONS: Percutaneous rotational atherectomy of arterial intima can promote the occlusion of arteries. This has provided a new choice for the treatment of PDA.


Asunto(s)
Arteriopatías Oclusivas/cirugía , Aterectomía/instrumentación , Arteria Axilar , Angiografía de Substracción Digital , Animales , Arteriopatías Oclusivas/diagnóstico por imagen , Modelos Animales de Enfermedad , Perros , Diseño de Equipo , Femenino , Estudios de Seguimiento , Masculino , Resultado del Tratamiento
18.
Front Med (Lausanne) ; 11: 1418917, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39144671

RESUMEN

Objective: Shared decision-making (SDM) is a collaborative process in which patients and healthcare providers jointly make a medical decision. This cross-sectional study aimed to identify the implementation status of shared decision-making among dermatologists engaging in medical esthetics in China and to identify factors associated with the good practice of SDM among them. Methods: From January to June 2023, a total of 1,287 dermatologists engaging in medical esthetics in China were recruited and completed the online interviews about their implementation of SDM based on the Shared Decision-Making Questionnaire for Doctors (SDM-Q-Doc). Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) to explore factors associated with the higher SDM score achievement among dermatologists with medical esthetic practice. Results: The median value of the total SDM score was 39, and 48% (621/1278) of dermatologists with medical esthetic practice achieved at least 40 out of 45 scores. Logistic regression indicated that dermatologists aged 40-49 or ≥ 50 years and those engaging in medical esthetic practice for ≥5 years were more likely to achieve at least 40 out of 45 scores compared to dermatologists aged <30 years with less than 5 years of medical esthetic practice. The ORs were 1.82 (95% CI: 1.13-3.12), 1.94 (95% CI: 1.13-3.61), and 1.76 (95% CI: 1.34-2.31), respectively. Conclusion: The SDM implementation level among Chinese dermatologists engaging in medical esthetics is high, especially for those who are older age and have more years of practice. Hence, it is highly recommended to promote and enhance SDM practice among younger dermatologists engaging in medical esthetics with less working experience.

19.
Plant Physiol Biochem ; 209: 108551, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38537382

RESUMEN

Water stress affects the metabolic regulation and delays the growth and development of alfalfa, causing a reduction in biomass. New alfalfa germplasm was created with improved drought tolerance in greenhouse conditions by introducing the key gene P5CDH1 from C. songorica, a xerophytic grass. However, the field adaptability and response mechanism of new drought-tolerant alfalfa germplasms under water stress are still unclear. In the present study, the yield and quality traits of transgenic CsP5CDH1 alfalfa lines under water stress and normal irrigation conditions were measured and analyzed for two years. The genetic variance components of the tested traits were calculated from the data fitted by the mixed linear model. The plant height of all lines showed significant genotypic variation (σ2g) (P < 0.05), and the stem diameter, stem number, and dry weight of all lines had a significant genotype × environment interaction (σ2ge) (P < 0.05). The heritability (H) of plant height, stem diameter, stem number, dry weight and leaf-to-stem ratio of alfalfa lines were 0.87, 0.52, 0.59, 0.52 and 0.50, respectively. There were significant genotype × environment interactions (σ2ge) (P < 0.05) for the quality traits of all lines. The heritabilities (H) of acid detergent fiber and neutral detergent fiber were 0.65 and 0.64, respectively. The results of transcriptional expression analysis with RNA-seq showed that the genes MsProDH1, MsProDH4, MsProDH5, MsP5CDH1, MsP5CS5, MsP5CS9, and MsP5CR1, which are involved in the proline metabolism pathway, played an important role in the drought tolerance of innovative alfalfa germplasm. Under water stress, with the regulation of key genes in the proline metabolism pathway, the proline content of all alfalfa lines increased to varying degrees. Among them, the proline content in the shoots and roots of transgenic line L6 was 7.29 times and 12.22 times that under normal irrigation conditions, respectively. The present study helped to clarify that the new germplasm of alfalfa transformed with the CsP5CDH gene synthesized a large amount of proline under water stress, and effectively slowed leaf water loss, thus improving the drought resistance of alfalfa.


Asunto(s)
Deshidratación , Sequías , Medicago sativa/metabolismo , Detergentes/metabolismo , Poaceae , Prolina/metabolismo
20.
Clin Cosmet Investig Dermatol ; 17: 1153-1164, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38800355

RESUMEN

Introduction: Shared decision making (SDM) is a collaborative process involving both healthcare providers and patients in making medical decisions, which gains increasing prominence in healthcare practice. But evidence on the level of SDM in medical practice and barriers as well as stimulus during the SDM implementation among aesthetic dermatologists is limited in China. Methods: From July to August 2023, 1938 dermatologists were recruited online in China. Data were collected through an electronic questionnaire covering: (1) demographic features; (2) SDM questionnaire physician version (SDM-Q-Doc); and (3) stimulus and barriers in SDM implementation. Logistic regression was applied to explore factors associated with SDM practice, barriers, and stimulus of SDM implementation, respectively. Results: The 1938 dermatologists included 1329 females (68.6%), with an average age of 35 years. The total SDM score ranged from 0 to 45, with a median value of 40 (IQR: 35-44), and the median stimulus score and barriers scores were 28 (IQR: 24-32) and 19 (IQR: 13-26), respectively. The prevalence of good SDM was 27.2%, logistic regression indicated that female dermatologists (odds ratio, OR=1.21, 95% confidence interval, CI: 0.96-1.51), and dermatologists with more years of aesthetic practice had a higher proportion of good SDM practice (OR was 1.44 for 5-9 years, 1.58 for 10-15 years and 1.77 for over 15 years). Moreover, female dermatologists and dermatologists with higher education level and serviced in private settings had lower barrier scores; female dermatologists and dermatologists with more years of aesthetic practice had higher stimulus scores. Conclusion: Chinese aesthetic dermatologists appear to implement SDM at an active level, with more stimulus and less barriers in SDM implementation. The integration of SDM into clinical practice among dermatologists is beneficial both for patients and dermatologists. Moreover, SDM practice should be strongly promoted and enhanced during medical aesthetics, especially among male dermatologists, dermatologists with less working experience, and those who work at public institutions.

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