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1.
Heliyon ; 10(9): e30069, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38699037

RESUMEN

In this study, we developed a scale to evaluate emotion management and its benefits for young athletes in China, and to analyze the impact of emotion management on their training efficiency. Following an extensive literature review, we used AMOS structural equation model software to develop a scale for evaluating the effects and benefits of emotion management on young athletes' training efficiency. Results showed that young athletes' emotion management training and its benefits can be divided into five dimensions: benefit evaluation, emotional cognition, emotion influence, emotion control, and emotion regulation. The internal consistency reliability of the formal scale was 0.895, and the internal consistency reliability of each subscale was between 0.734 and 0.901. The split-half reliability was 0.769, and the split-half reliability of each subscale was between 0.623 and 0.864. The KMO value was 0.904, P = 0.00 (p < 0.05), and the cumulative interpretation rate was 61.782 % of the total variance. The lowest factor load of a scale item was 0.436, and the highest factor load was 0.846. The common degree of all items was between 0.402 and 0.762, indicating that the scale has good validity. A SEM model verified that the scale has good construct validity. Significant correlational differences were observed among the levels. The results of the SEM structural equation model analysis showed that the model's NC = 2.660 (1 < NC < 3 indicates that the model has a simple fit), PGFI = 0.722, PNFI = 0.699, IFI = 0.851, PRA = 0.927, RMR = 0.006, and RMSEA = 0.07, thus, these indexes reached the standard of excellent model fitting. The strongest correlation was found between emotional cognition and benefit evaluation (R = 0.690), and the weakest correlation was found between emotion influence and benefit evaluation (R = 0.079). These findings provide a basis for measuring the effect of emotion management on training efficiency in the training process of young athletes and offer a theoretical reference for their emotional development while in training.

2.
World J Clin Cases ; 12(14): 2438-2444, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38765756

RESUMEN

BACKGROUND: Autoimmune pancreatitis (AIP) is a rare form of autoimmune-mediated pancreatitis, which is easily misdiagnosed as pancreatic cancer and thus treated surgically. We studied the diagnosis and treatment of a patient with type 1 AIP recently admitted to our hospital, and reviewed the literature to provide a reference for clinical diagnosis of AIP. CASE SUMMARY: The chief complaint was yellowing of the body, eyes and urine for 21 d. The patient's clinical presentation was obstructive jaundice and imaging suggested pancreatic swelling. It was difficult to distinguish between inflammation and tumor. Serum immunoglobulin G4 (IgG4) was markedly elevated. IgG4 is an important serological marker for type 1 AIP. The patient was diagnosed with AIP, IgG4-related cholangitis, acute cholecystitis and hepatic impairment. After applying hormonal therapy, the patient's symptoms improved significantly. At the same time, imaging suggested that pancreatic swelling subsided, and liver function and other biochemical indicators decreased. The treatment was effective. CONCLUSION: In patients with pancreatic swelling, the possibility of AIP should be considered.

3.
Cell ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38772371

RESUMEN

Peripheral sensory neurons widely innervate various tissues to continuously monitor and respond to environmental stimuli. Whether peripheral sensory neurons innervate the spleen and modulate splenic immune response remains poorly defined. Here, we demonstrate that nociceptive sensory nerve fibers extensively innervate the spleen along blood vessels and reach B cell zones. The spleen-innervating nociceptors predominantly originate from left T8-T13 dorsal root ganglia (DRGs), promoting the splenic germinal center (GC) response and humoral immunity. Nociceptors can be activated by antigen-induced accumulation of splenic prostaglandin E2 (PGE2) and then release calcitonin gene-related peptide (CGRP), which further promotes the splenic GC response at the early stage. Mechanistically, CGRP directly acts on B cells through its receptor CALCRL-RAMP1 via the cyclic AMP (cAMP) signaling pathway. Activating nociceptors by ingesting capsaicin enhances the splenic GC response and anti-influenza immunity. Collectively, our study establishes a specific DRG-spleen sensory neural connection that promotes humoral immunity, suggesting a promising approach for improving host defense by targeting the nociceptive nervous system.

4.
Heliyon ; 10(6): e28237, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38532996

RESUMEN

Acute myeloid leukemia (AML) represents as a prevalent and formidable hematological malignancy, characterized by notably low 5-year survival rates. Ferroptosis has been found to be correlated with cancer initiation, therapeutic response, and clinical outcome. Nevertheless, the involvement of Ferroptosis-related genes (FRGs) in AML remains ambiguous. Five independent AML cohorts totaling 1,470 (GSE37642, GSE12417, GSE10358, Beat-AML, and TCGA-AML) patients with clinical information were used to systematically investigated the influence of these FRGs expression on outcome and tumor microenvironment. The integration of these datasets led to the subdivision into training and validation sets. Nineteen FRGs were identified as correlated with the overall survival (OS) of AML patients, primarily enriched in ferroptosis, fatty acid metabolism, and leukemia-related signaling pathways. The prognostic signature, consisting of 11 FRGs, was formulated using LASSO-Cox stepwise regression analysis. Patients with high-risk scores exhibited reduced survival compared to those in the low-risk group. The receiver operating characteristic (ROC) analysis underscored the signature's robust predictive accuracy. The high predictive efficacy was confirmed by both internal and external validation datasets. Leukemia and signaling related to immune regulation were mainly enriched pathways of the differentially expressed genes by comparing high- and low-risk groups. The immune composition deconvolution might indicate an immunosuppressive niche in the high-risk patients. The pRRophetic algorithm exploration unveiled chemical drugs with potentially sensitivity among patients in both groups. Collectively, our study developed a ferroptosis-derived prognostic signature that provides the OS prediction and identifies the immune microenvironment for AML patients on large-scale AML cohorts.

5.
Heliyon ; 9(9): e19701, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37810038

RESUMEN

Objective: The objective of this research was to assess the level and determinants of medical personnel's knowledge, attitudes, and practices regarding the management of sexual health in breast cancer survivors residing in western China. Background: Sexual well-being is a crucial aspect of one's overall satisfaction with life. Once female sexual dysfunction (FSD) occurs, it will affect patients' satisfaction and life quality seriously. In all healthcare settings, the management of sexual health relies heavily on the vital contribution of medical personnel. Nevertheless, the sexual requirements of individuals with breast cancer are still partially unmet. Design: A web-based questionnaire was used to conduct a multi-centered, cross-sectional study involving medical staff from 26 hospitals in nine cities of Guizhou Province, China. Methods: Data was gathered from healthcare professionals using a validated tool, the knowledge, attitudes, practices assessment scale for managing the sexual health of breast cancer patients in medical staff. This tool was used to evaluate the knowledge, attitudes, and practices of medical staff regarding sexual health management. Results: In this study, a grand total of 3181 healthcare professionals took part. The overall KAP scores, including knowledge, attitudes, and practices, were 47.15 ± 11.91, 72.55 ± 12.56, and 58.61 ± 11.45, respectively. Three variables exhibited a strong and favorable correlation. The study identified significant concerns regarding the limited understanding of medical personnel regarding effective strategies for enhancing sexual health function in breast cancer patients, as well as their diminished confidence in addressing FSD. The scores of knowledge, attitudes, and practices related to sexual health management were significantly influenced by whether or not training was received. Conclusions: The study results emphasize the importance of adopting a holistic approach to enhance the understanding, perspectives, and behaviors of healthcare professionals regarding the management of sexual health. In addition to enhancing the standard of care for individuals with breast cancer.

6.
Front Cell Dev Biol ; 11: 1207642, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37691822

RESUMEN

Acute myeloid leukemia (AML) is one of the most aggressive hematological malignancies with a low 5-year survival rate and high rate of relapse. Developing more efficient therapies is an urgent need for AML treatment. Accumulating evidence showed that ferroptosis, an iron-dependent form of programmed cell death, is closely correlated with cancer initiation and clinical outcome through reshaping the tumor microenvironment. However, understanding of AML heterogeneity based on extensive profiling of ferroptosis signatures remains to be investigated yet. Herein, five independent AML transcriptomic datasets (TCGA-AML, GSE37642, GSE12417, GSE10358, and GSE106291) were obtained from the GEO and TCGA databases. Then, we identified two ferroptosis-related molecular subtypes (C1 and C2) with distinct prognosis and tumor immune microenvironment (TIME) by consensus clustering. Patients in the C1 subtype were associated with favorable clinical outcomes and increased cytotoxic immune cell infiltration, including CD8+/central memory T cells, natural killer (NK) cells, and non-regulatory CD4+ T cells while showing decreased suppressive immune subsets such as M2 macrophages, neutrophils, and monocytes. Functional enrichment analysis of differentially expressed genes (DEGs) implied that cell activation involved in immune response, leukocyte cell-cell adhesion and migration, and cytokine production were the main biological processes. Phagosome, antigen processing and presentation, cytokine-cytokine receptor interaction, B-cell receptor, and chemokine were identified as the major pathways. To seize the distinct landscape in C1 vs. C2 subtypes, a 5-gene prognostic signature (LSP1, IL1R2, MPO, CRIP1, and SLC24A3) was developed using LASSO Cox stepwise regression analysis and further validated in independent AML cohorts. Patients were divided into high- and low-risk groups, and decreased survival rates were observed in high- vs. low-risk groups. The TIME between high- and low-risk groups has a similar scenery in C1 vs. C2 subtypes. Single-cell-level analysis verified that LSP1 and CRIP1 were upregulated in AML and exhausted CD8+ T cells. Dual targeting of these two markers might present a promising immunotherapeutic for AML. In addition, potential effective chemical drugs for AML were predicted. Thus, we concluded that molecular subtyping using ferroptosis signatures could characterize the TIME and provide implications for monitoring clinical outcomes and predicting novel therapies.

7.
Life Sci Alliance ; 6(11)2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37657935

RESUMEN

Wnt/ß-catenin signaling plays a crucial role in cancer development, primarily activated by ß-catenin forming a transcription complex with LEF/TCF in the nucleus and initiating the transcription of Wnt target genes. Here, we report that LEF1, a member of the LEF/TCF family, can form intrinsically disordered region (IDR)-dependent condensates with ß-catenin both in vivo and in vitro, which is required for ß-catenin-dependent transcription. Notably, LEF1 with disrupted IDR lost its promoting activity on tumor proliferation and metastasis, which can be restored by substituting with FUS IDR. Our findings provide new insight into the essential role of liquid-liquid phase separation in Wnt/ß-catenin signaling and present a potential new target for cancer therapy.


Asunto(s)
Núcleo Celular , beta Catenina , beta Catenina/genética , Activación Transcripcional/genética , Vía de Señalización Wnt/genética
9.
Rev. bras. med. esporte ; 29: e2022_0010, 2023. tab
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1423374

RESUMEN

ABSTRACT Objectives: This study aimed to examine the relationship between vertical jumping at forces of specific time phase and sprint performance in teenage sprinters. Methods: Fifteen male teenage sprinters (age: 14±2 years, height: 168±2 cm, weight: 61±1 kg) participated in the study. The subjects performed the following bilateral/unilateral jumps on a force platform: a) squat jump (SJ), b) unilateral SJ (USJ), c) 40cm drop jump (DJ), and d) 20cm unilateral DJ (UDJ). The 60m sprint test was administered on the second day. Brower split timers were positioned to record subjects' 5m, 10m, 50m and 60m split times. The variables for inclusion were vertical jump height, maximum force, and force output at 120ms in all jumps and sprint time measures. Results: The results of the Pearson Product Moment Correlation analysis showed that SJ120ms was correlated to 5m and USJ120ms was correlated to 10m. UDJ120ms showed a stronger correlation with 50m than DJ120ms. Although significant correlations using maximum force and height were observed, there were inconsistent results between bilateral and unilateral jumps. Conclusion: Our results highlighted that jumps that have similar form with certain force outputs at specific event timing could more precisely predict sprint performance in teenage sprinters. USJ120ms and UDJ120ms could better predict the acceleration (10m) and high-speed phase (50m) in sprint performance, respectively. Moreover, coaches and practitioners should be cautious when using only jump height or maximum force to predict sprint performance, since the results could be inaccurate when specific movement variables are not thoughtfully considered. Level of evidence III.


RESUMEN Objetivos: Este estudio tuvo como objetivo examinar la relación entre el salto vertical y la fuerza en tiempo específico y el desempeño del sprint en velocistas adolescentes. Métodos: Participaron en el estudio quince adolescentes varones velocistas (edades: 14 ± 2 años, estatura: 168 ± 2 cm, peso: 61 ± 1 kg). Los individuos realizaron los siguientes saltos bilaterales y unilaterales en una plataforma de fuerza: a) squat jump (SJ), b) SJ unilateral (USJ), c) drop jump (DJ) de 40 cm e d) DJ unilateral (UDJ) de 20 cm. La prueba de sprint de 60 m se realizó el segundo día. Los cronómetros en el entrenamiento fraccionado se ajustaron para registrar tiempos de 5 m, 10 m, 50 m y 60 m. Las variables que se incluyeron fueron la altura del salto vertical, la fuerza máxima y la salida de fuerza a 120 m en todos los saltos y mediciones del tiempo del sprint. Resultados: Los resultados del análisis de correlación producto-tiempo de Pearson revelaron que el SJ de 120 m estaba correlacionado con 5 m y el USJ de 120 m estaba correlacionado con 10 m. El UDJ de 120 m tuvo una mayor correlación con el DJ de 50 m que con el de 120 m. Aunque se observaron correlaciones significativas con la fuerza y la altura máximas, algunos resultados fueron inconsistentes entre los saltos bilaterales y unilaterales. Conclusiones: Nuestros resultados pusieron de manifiesto que los saltos con una forma similar a determinadas salidas de fuerza en un tiempo específico del evento pueden predecir con mayor precisión el desempeño en el sprint en adolescentes velocistas. El USJ de 120 m y el UDJ de 120 m pueden predecir mejor, respectivamente, la aceleración (10 m) y la fase de alta velocidad (50 m) en el desempeño del sprint. Además, los entrenadores y practicantes deben ser cautelosos a la hora de utilizar únicamente la altura del salto o la fuerza máxima para predecir el desempeño en el sprint, ya que los resultados pueden ser inexactos cuando no se tienen en cuenta con precisión las variables específicas del movimiento. Nivel de evidencia III.


RESUMO Objetivos: Este estudo teve como objetivo examinar a relação entre o salto vertical e a força em tempo específico e o desempenho de sprint em velocistas adolescentes. Métodos: Quinze adolescentes velocistas do sexo masculino (idade: 14 ± 2 anos, estatura: 168 ± 2 cm, peso: 61 ± 1 kg) participaram do estudo. Os indivíduos realizaram os seguintes saltos bilaterais e unilaterais em uma plataforma de força: a) squat jump (SJ), b) SJ unilateral (USJ), c) drop jump (DJ) de 40 cm e d) DJ unilateral (UDJ) de 20cm. O teste de sprint de 60 m foi realizado no segundo dia. Os cronômetros rastreadores para treinos fracionados foram posicionados para registrar os tempos fracionados de 5 m, 10 m, 50 m e 60 m. As variáveis para inclusão foram altura do salto vertical, força máxima e saída de força a 120 m em todos os saltos e medidas de tempo do sprint. Resultados: Os resultados da análise da correlação produto-tempo de Pearson mostraram que o SJ de 120 m foi correlacionado com 5 m e USJ de 120 m foi correlacionado com 10 m. O UDJ de 120 m teve correlação mais forte com DJ de 50 m do que de 120 m. Embora tenham sido observadas correlações significativas com força e altura máximas, alguns resultados foram inconsistentes entre os saltos bilaterais e unilaterais. Conclusões: Nossos resultados destacaram que os saltos com forma semelhante a certas saídas de força no tempo específico do evento podem prever com mais precisão o desempenho no sprint em adolescentes velocistas. O USJ de 120 m e o UDJ de 120 m podem prever melhor, respectivamente, a aceleração (10 m) e a fase de alta velocidade (50 m) no desempenho no sprint. Além disso, treinadores e praticantes devem ser cautelosos ao usar apenas a altura do salto ou a força máxima para prever o desempenho no sprint, uma vez que os resultados podem ser imprecisos quando variáveis específicas do movimento não forem consideradas com precisão. Nível de evidência III.

10.
Front Genet ; 13: 914646, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35873484

RESUMEN

Head and neck squamous cell carcinoma (HNSCC) represents one of the most malignant and heterogeneous tumors, and the patients have low 5-year survival. Traditional Chinese medicine (TCM) has been demonstrated as an effective complementary and/or alternative therapy for advanced malignancies including HNSCC. It has been noted that several herbs that are used for preparing Yinchen Wuling San (YWLS) have anti-tumor activities, whereas their mechanisms of action remain elusive. In this study, network pharmacology and molecular docking studies were employed to explore the underlying mechanisms of action of YWLS against HNSCC. The 58 active ingredients from six herbs used for YWLS and their 506 potential targets were screened from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and SwissTargetPrediction database. A total of 2,173 targets associated with HNSCC were mainly identified from the DisGeNET and GeneCards databases. An active components-targets-disease network was constructed in the Cytoscape. Top 20 hub targets, such as AKT1, EGFR, TNF, ESR1, SRC, HSP90AA1, MAPK3, ERBB2, and CCND1, were identified by a degree in the protein-protein interaction (PPI) network. Gene functional enrichment analysis showed that PI3K-AKT, MAPK, Ras, TNF, and EGFR were the main signaling pathways of YWLS in treating HNSCC. There were 48 intersected targets such as EGFR, AKT1, and TNF that were associated with patients' outcomes by the univariate Cox analysis, and most of them had increased expression in the tumor as compared to normal tissues. The area under curves of receiver operating characteristic indicated their diagnostic potential. Inhibition of these survival-related targets and/or combination with EGFR or AKT inhibitors were promising therapeutic options in HNSCC. The partial active components of YWLS exhibited good binding with the hub targets, and ADME analysis further evaluated the drug-likeness of the active components. These compounds and targets identified in this study might provide novel treatment strategies for HNSCC patients, and the subsequent work is essential to verify the underlying mechanisms of YWLS against HNSCC.

11.
Expert Rev Respir Med ; 16(9): 1023-1033, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35730466

RESUMEN

BACKGROUND: Predicting omalizumab treatment response has been a challenge and significant aspect for selecting suitable severe allergic asthma patients for omalizumab use. OBJECTIVE: To determine which domains of pretreatment baseline characteristics predict omalizumab treatment response among asthmatic patients. METHODS: Electronic bases were searched for eligible studies that reported potential biomarkers that could predict omalizumab responsiveness and efficacy. Patients who accepted omalizumab treatment were stratified into responders and non-responders. WMD, OR, and their 95%CI were used to access the differences between those omalizumab receivers. Sensitivity analysis and subgroup analysis were conducted for potential heterogeneity. RESULTS: A total of 41 studies evaluating efficacy predictors of omalizumab were included in this meta-analysis. The pooled results showed that omalizumab responders had significantly younger age in the adult subgroup, higher pretreatment total serum IgE level, percent predicted FEV1 and FeNO than that non-responder. We further confirmed that higher blood eosinophil counts and total serum IgE levels are useful markers for selecting asthma patients who may benefit more from omalizumab. CONCLUSIONS: Pre-treatment blood eosinophil counts and total serum IgE level can be a useful efficacy predictor in selecting allergic asthma patients for omalizumab treatment.


Asunto(s)
Antiasmáticos , Asma , Adulto , Humanos , Omalizumab/efectos adversos , Antiasmáticos/uso terapéutico , Inmunoglobulina E , Resultado del Tratamiento , Asma/diagnóstico , Asma/tratamiento farmacológico , Biomarcadores
12.
Comput Intell Neurosci ; 2022: 3497942, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35392036

RESUMEN

This paper provides an in-depth analysis and study of the decomposition of sports biology of athletics events through multimedia image acquisition techniques. The proposed design uses SOPC hardware-software collaboration technology, which makes full use of the parallelism of hardware as well as the flexibility of software to essentially improve the speed of image processing and greatly improve the efficiency of image processing. The high speed and parallelism of hardware are used to realize the image acquisition part with high timing requirements and the preprocessing algorithm with a large number of operations and strong repetition, in addition to the difficulties of many initialization configuration parameters of each peripheral. Additionally, the need for frequent adjustment of peripheral working parameters is solved by making full use of the scalability and flexibility of software, and the control signals output by software can coordinate the work of each hardware module to ensure that each module of the system cooperates. It is also possible to coordinate the work of each hardware module through the control signal output from the software to ensure that each module of the system cooperates and operates in an orderly and efficient manner and provides the possibility of realizing a higher level of the image processing algorithm. The system includes four main factors: swinging action, supporting action, vacating action, and speed rhythm. Based on this system, 14 key kinematic indicators were selected to reflect the technical status of the youth walkers. The landing angle decreased with the increase of speed, and the landing technique was insufficient; it had better control of the large and small arm angle, and their stride width was open, while the other four athletes showed increased tension in the hip joint and upper limb with the increase of walking speed, as well as the wrong action of forward and internal rotation of the large and small arms.


Asunto(s)
Multimedia , Deportes , Adolescente , Algoritmos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Programas Informáticos
13.
Med Sci Monit ; 28: e934057, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-35031594

RESUMEN

BACKGROUND Psoas muscle density (PMD) as a nutritional indicator is a tool to evaluate sarcopenia, which is commonly diagnosed in patients with liver cirrhosis. However, there are limited data on its role in patients who have received a transjugular intrahepatic portosystemic shunt (TIPS). We aimed to determine the utility of PMD in predicting mortality of patients with TIPS implantation and to compare the clinical value of PMD, Child-Pugh score, model for end-stage liver disease (MELD) score, and MELD paired with serum sodium measurement (MELD-Na) score in predicting post-TIPS survival in 1 year. MATERIAL AND METHODS This retrospective study included 273 patients who met the criteria for study inclusion. All participants underwent computed tomography (CT) scans, Child-Pugh score evaluation, MELD-Na scoring, and MELD scoring. Post-TIPS survival time was estimated using the Kaplan-Meier survival curve. The prognostic values of scoring models such as the Child-Pugh score, MELD, MELD-Na, and PMD were evaluated using receiver operating characteristic curves. RESULTS During the 1-year follow-up period, 31 of 273 (11.36%) post-TIPS patients died. Multivariate analysis identified PMD as an independent protective factor. PMD showed a good ability to predict the occurrence of an endpoint within 1 year after TIPS. The area under the receiver operating characteristic curves for PMD, Child-Pugh score, MELD score, and MELD-Na for predicting mortality were, respectively, 0.72 (95% confidence interval [CI]: 0.663-0.773), 0.59 (95% CI: 0.531-0.651), 0.60 (95% CI: 0.535-0.655), and 0.58 (95% CI: 0.487-0.608). CONCLUSIONS PMD has appreciable clinical value for predicting the mortality of patients with TIPS implantation. In addition, PMD is superior to established scoring systems for identifying high-risk patients with a poor prognosis.


Asunto(s)
Cirrosis Hepática/mortalidad , Derivación Portosistémica Intrahepática Transyugular/mortalidad , Músculos Psoas/diagnóstico por imagen , Sarcopenia/diagnóstico por imagen , Sarcopenia/mortalidad , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Hígado/cirugía , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sarcopenia/etiología , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Tomografía Computarizada por Rayos X/métodos
14.
Biosci Rep ; 41(7)2021 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-34212178

RESUMEN

Aberrant RNA alternative splicing (AS) variants play critical roles in tumorigenesis and prognosis in human cancers. Here, we conducted a comprehensive profiling of aberrant AS events in acute myeloid leukemia (AML). RNA AS profile, including seven AS types, and the percent spliced in (PSI) value for each patient were generated by SpliceSeq using RNA-seq data from TCGA. Univariate followed by multivariate Cox regression analysis were used to identify survival-related AS events and develop the AS signatures. A nomogram was developed, and its predictive efficacy was assessed. About 27,892 AS events and 3,178 events were associated with overall survival (OS) after strict filtering. Parent genes of survival-associated AS events were mainly enriched in leukemia-associated processes including chromatin modification, autophagy, and T-cell receptor signaling pathway. The 10 AS signature based on seven types of AS events showed better efficacy in predicting OS of patients than those built on a single AS event type. The area under curve (AUC) value of the 10 AS signature for 3-year OS was 0.91. Gene set enrichment analysis (GSEA) confirmed that these survival-related AS events contribute to AML progression. Moreover, the nomogram showed good predictive performance for patient's prognosis. Finally, the correlation network of AS variants with splicing factor genes found potential important regulatory genes in AML. The present study presented a systematic analysis of survival-related AS events and developed AS signatures for predicting the patient's survival. Further studies are needed to validate the signatures in independent AML cohorts and might provide a promising perspective for developing therapeutic targets.


Asunto(s)
Empalme Alternativo , Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica , Leucemia Mieloide Aguda/genética , Transcriptoma , Bases de Datos Genéticas , Progresión de la Enfermedad , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Nomogramas , Valor Predictivo de las Pruebas , RNA-Seq , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo
15.
Front Immunol ; 12: 695865, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34135913

RESUMEN

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies that has an unfavorable outcome and a high rate of relapse. Autophagy plays a vital role in the development of and therapeutic responses to leukemia. This study identifies a potential autophagy-related signature to monitor the prognoses of patients of AML. Transcriptomic profiles of AML patients (GSE37642) with the relevant clinical information were downloaded from Gene Expression Omnibus (GEO) as the training set while TCGA-AML and GSE12417 were used as validation cohorts. Univariate regression analyses and multivariate stepwise Cox regression analysis were respectively applied to identify the autophagy-related signature. The univariate Cox regression analysis identified 32 autophagy-related genes (ARGs) that were significantly associated with the overall survival (OS) of the patients, and were mainly rich in signaling pathways for autophagy, p53, AMPK, and TNF. A prognostic signature that comprised eight ARGs (BAG3, CALCOCO2, CAMKK2, CANX, DAPK1, P4HB, TSC2, and ULK1) and had good predictive capacity was established by LASSO-Cox stepwise regression analysis. High-risk patients were found to have significantly shorter OS than patients in low-risk group. The signature can be used as an independent prognostic predictor after adjusting for clinicopathological parameters, and was validated on two external AML sets. Differentially expressed genes analyzed in two groups were involved in inflammatory and immune signaling pathways. An analysis of tumor-infiltrating immune cells confirmed that high-risk patients had a strong immunosuppressive microenvironment. Potential druggable OS-related ARGs were then investigated through protein-drug interactions. This study provides a systematic analysis of ARGs and develops an OS-related prognostic predictor for AML patients. Further work is needed to verify its clinical utility and identify the underlying molecular mechanisms in AML.


Asunto(s)
Proteínas Relacionadas con la Autofagia/genética , Autofagia/genética , Técnicas de Apoyo para la Decisión , Perfilación de la Expresión Génica , Leucemia Mieloide Aguda/genética , Nomogramas , Transcriptoma , Microambiente Tumoral/inmunología , Proteínas Relacionadas con la Autofagia/metabolismo , Bases de Datos Genéticas , Humanos , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/terapia , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo
16.
Front Public Health ; 9: 637529, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33816422

RESUMEN

This systematic review and meta-analysis aimed to evaluate the association between serum vitamin D concentration and the risk of urinary tract infection (UTI) in children. Human studies reported the serum vitamin D level in children with UTI and healthy controls were collected from PubMed, Scopus, Embase, and Cochrane databases. The strictly standardized mean difference (SSMD) and 95% confidence interval (CI) were calculated to evaluate the relationship between serum vitamin D levels and risk of UTI. The results of analysis showed that serum vitamin D levels in children with UTI were significantly lower than healthy control children (SSMD: 0.891, 95% CI: 0.707-1.075, p < 0.000; SSMD: 0.797, 95% CI: 0.500-1.094, p < 0.000, respectively). It can be concluded that there is a significant negative relationship between serum vitamin D level and risk of UTI in children.


Asunto(s)
Infecciones Urinarias , Niño , Bases de Datos Factuales , Humanos , Infecciones Urinarias/epidemiología , Vitamina D
17.
Nat Commun ; 12(1): 1275, 2021 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-33627666

RESUMEN

Synthetic lethality is emerging as an important cancer therapeutic paradigm, while the comprehensive selective treatment opportunities for various tumors have not yet been explored. We develop the Synthetic Lethality Knowledge Graph (SLKG), presenting the tumor therapy landscape of synthetic lethality (SL) and synthetic dosage lethality (SDL). SLKG integrates the large-scale entity of different tumors, drugs and drug targets by exploring a comprehensive set of SL and SDL pairs. The overall therapy landscape is prioritized to identify the best repurposable drug candidates and drug combinations with literature supports, in vitro pharmacologic evidence or clinical trial records. Finally, cladribine, an FDA-approved multiple sclerosis treatment drug, is selected and identified as a repurposable drug for treating melanoma with CDKN2A mutation by in vitro validation, serving as a demonstrating SLKG utility example for novel tumor therapy discovery. Collectively, SLKG forms the computational basis to uncover cancer-specific susceptibilities and therapy strategies based on the principle of synthetic lethality.


Asunto(s)
Mutaciones Letales Sintéticas/genética , Línea Celular Tumoral , Cladribina/uso terapéutico , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Humanos , Melanoma/tratamiento farmacológico , Melanoma/genética , Modelos Teóricos , Mutación/genética
18.
Gene ; 764: 145105, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-32882333

RESUMEN

Sarcoma (SARC) represents a group of highly histological and molecular heterogeneous rare malignant tumors with poor prognosis. There are few proposed classifiers for predicting patient's outcome. The Cancer Proteome Atlas (TPCA) and The Cancer Genome Atlas (TCGA) databases provide multi-omics datasets that enable a comprehensive investigation for this disease. The proteomic expression profile of SARC patients along with the clinical information was downloaded. 55 proteins were found to be associated with overall survival (OS) of patients using univariate Cox regression analysis. We developed a prognostic risk signature that comprises seven proteins (AMPKALPHA, CHK1, S6, ARID1A, RBM15, ACETYLATUBULINLYS40, and MSH6) with robust predictive performance using multivariate Cox stepwise regression analysis. Additionally, the signature could be an independent prognostic predictor after adjusting for clinicopathological parameters. Patients in high-risk group also have worse progression free intervals (PFI) than that of patients in low-risk group, but not for disease free intervals (DFI). The signature was validated using transcriptomic profile of SARC patients from TCGA. Potential mechanisms between high- and low-risk groups were identified using differentially expressed genes (DEGs) analysis. These DEGs were primarily enriched in RAS and MPAK signaling pathways. The signature protein molecules are candidate biomarkers for SARC, and the analysis of computational biology in tumor infiltrating lymphocytes and immune checkpoint molecules revealed distinctly immune landscapes of high- and low-risk patients. Together, we constructed a prognostic signature for predicting outcomes for SARC integrating proteomic and transcriptomic profiles, this might have value in guiding clinical practice.


Asunto(s)
Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica/inmunología , Pruebas Genéticas/métodos , Sarcoma/mortalidad , Microambiente Tumoral/inmunología , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/genética , Antígeno B7-H1/inmunología , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/genética , Antígeno CTLA-4/inmunología , Conjuntos de Datos como Asunto , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/inmunología , Supervivencia sin Progresión , Mapeo de Interacción de Proteínas , Proteómica , Curva ROC , Sarcoma/tratamiento farmacológico , Sarcoma/genética , Sarcoma/inmunología , Transcriptoma/genética , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/genética
20.
Front Genet ; 11: 978, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33005178

RESUMEN

Lung squamous cell carcinoma (LSCC) is the most common subtype of non-small cell lung cancer. Immunotherapy has become an effective treatment in recent years, while patients showed different responses to the current treatment. It is vital to identify the potential immunogenomic signatures to predict patient' prognosis. The expression profiles of LSCC patients with the clinical information were downloaded from TCGA database. Differentially expressed immune-related genes (IRGs) were extracted using edgeR algorithm, and functional enrichment analysis showed that these IRGs were primarily enriched in inflammatory- and immune-related processes. "Cytokine-cytokine receptor interaction" and "PI3K-AKT signaling pathway" were the most enriched KEGG pathways. 27 differentially expressed IRGs were significantly correlated with the overall survival (OS) of patients using univariate Cox regression analysis. A prognostic risk signature that comprises seven IRGs (GCCR, FGF8, CLEC4M, PTH, SLC10A2, NPPC, and FGF4) was developed with effective predictive performance by multivariable Cox stepwise regression analysis. Most importantly, the signature could be an independent prognostic predictor after adjusting for clinicopathological parameters, and also validated in two independent LSCC cohorts (GSE4573 and GSE17710). Potential molecular mechanisms and tumor immune landscape of these IRGs were investigated through computational biology. Analysis of tumor infiltrating lymphocytes and immune checkpoint molecules revealed distinct immune landscape in high- and low-risk group. The study was the first time to construct IRG-based immune signature in the recognition of disease progression and prognosis of LSCC patients.

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