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1.
Nucleic Acids Res ; 51(5): 2195-2214, 2023 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-36794705

RESUMEN

NF-κB activates the primary inflammatory response pathway responsible for methicillin-resistant Staphylococcus aureus (MRSA)-induced lung inflammation and injury. Here, we report that the Forkhead box transcription factor FOXN3 ameliorates MRSA-induced pulmonary inflammatory injury by inactivating NF-κB signaling. FOXN3 competes with IκBα for binding to heterogeneous ribonucleoprotein-U (hnRNPU), thereby blocking ß-TrCP-mediated IκBα degradation and leading to NF-κB inactivation. FOXN3 is directly phosphorylated by p38 at S83 and S85 residues, which induces its dissociation from hnRNPU, thus promoting NF-κB activation. After dissociation, the phosphorylated FOXN3 becomes unstable and undergoes proteasomal degradation. Additionally, hnRNPU is essential for p38-mediated FOXN3 phosphorylation and subsequent phosphorylation-dependent degradation. Functionally, genetic ablation of FOXN3 phosphorylation results in strong resistance to MRSA-induced pulmonary inflammatory injury. Importantly, FOXN3 phosphorylation is clinically positively correlated with pulmonary inflammatory disorders. This study uncovers a previously unknown regulatory mechanism underpinning the indispensable role of FOXN3 phosphorylation in the inflammatory response to pulmonary infection.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Neumonía , Humanos , FN-kappa B/genética , FN-kappa B/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , Fosforilación , Proteínas I-kappa B , Staphylococcus aureus Resistente a Meticilina/metabolismo , Transducción de Señal , Neumonía/genética , Proteínas de Ciclo Celular/metabolismo , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo
2.
Mol Ther ; 31(5): 1365-1382, 2023 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-36733250

RESUMEN

Mesenchymal stem cells regulate remote intercellular signaling communication via their secreted extracellular vesicles. Here, we report that menstrual blood-derived stem cells alleviate acute lung inflammation and injury via their extracellular vesicle-transmitted miR-671-5p. Disruption of this abundantly expressed miR-671-5p dramatically reduced the ameliorative effect of extracellular vesicles released by menstrual blood-derived stem cells on lipopolysaccharide (LPS)-induced pulmonary inflammatory injury. Mechanistically, miR-671-5p directly targets the kinase AAK1 for post-transcriptional degradation. AAK1 is found to positively regulate the activation of nuclear factor κB (NF-κB) signaling by controlling the stability of the inhibitory protein IκBα. This study identifies a potential molecular basis of how extracellular vesicles derived from mesenchymal stem cells improve pulmonary inflammatory injury and highlights the functional importance of the miR-671-5p/AAK1 axis in the progression of pulmonary inflammatory diseases. More importantly, this study provides a promising cell-based approach for the treatment of pulmonary inflammatory disorders through an extracellular vesicle-dependent pathway.


Asunto(s)
Vesículas Extracelulares , Lesión Pulmonar , MicroARNs , Neumonía , Humanos , FN-kappa B/genética , FN-kappa B/metabolismo , Inflamación/genética , Inflamación/terapia , Inflamación/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Neumonía/genética , Neumonía/terapia , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Lipopolisacáridos/farmacología , Proteínas Serina-Treonina Quinasas
3.
Plant Phenomics ; 6: 0220, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39139386

RESUMEN

Precise disease detection is crucial in modern precision agriculture, especially in ensuring the health of tomato crops and enhancing agricultural productivity and product quality. Although most existing disease detection methods have helped growers identify tomato leaf diseases to some extent, these methods typically target fixed categories. When faced with new diseases, extensive and costly manual annotation is required to retrain the dataset. To overcome these limitations, this study proposes a multimodal model PDC-VLD based on the open-vocabulary object detection (OVD) technology within the VLDet framework, which can accurately identify new tomato leaf diseases without manual annotation by using only image-text pairs. First, we developed a progressive visual transformer-convolutional pyramid module (PVT-C) that effectively extracts tomato leaf disease features and optimizes anchor box positioning using the self-supervised learning algorithm DINO, suppressing interference from irrelevant backgrounds. Then, a context feature guided module (CFG) was adopted to address the low adaptability and recognition accuracy of the model in data-scarce environments. To validate the model's effectiveness, we constructed a tomato leaf disease image dataset containing 4 base classes and 2 new categories. Experimental results show that the PDC-VLD model achieved 61.2% on the main evaluation metric mAP novel 50 , and 56.4% on mAP novel 75 , 87.7% on mAP base 50 , 81.0% on mAP all 50 , and 45.5% on average recall, outperforming existing OVD models. Our research provides an innovative solution for efficiently and accurately detecting new diseases, substantially reducing the need for manual annotation, and offering critical technical support and practical reference for agricultural workers.

4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(1): 102-5, 2016 Feb.
Artículo en Zh | MEDLINE | ID: mdl-26913403

RESUMEN

OBJECTIVE: To explore the value of multiparameter flow cytometry in diagnosis of non-Hodgkin's lymphoma (NHL). METHODS: Twenty patients with NHL admitted in Traditional Chinese Medicine Hospital of Zhengzhou from January 2009 to August 2014 years were enrolled into this study, among them 13 cases received lymnode puncture, 2 cases were given bone marrow aspiration, 2 cases received peripheral blood examination, 3 cases suffered lymphnode biopsy. RESULTS: After FCM immune typing and cytological smear, 6 cases was confirmed to be B-SLL, 1 case was B-NHL, 1 case was FL, 5 cases was DLBCL, 2 cases was T-NHL, 3 cases was T-LBL, 1 case was NK/T-NHL, 1 case was PTun. CONCLUSION: Multiparameter flow cytometry is valuable for diagnosis of non-Hodgkin's of lymphoma.


Asunto(s)
Citometría de Flujo , Linfoma no Hodgkin/diagnóstico , Biopsia , Médula Ósea , Hospitalización , Humanos , Linfoma de Células B/diagnóstico , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células T/diagnóstico
5.
Onco Targets Ther ; 8: 1239-43, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26060409

RESUMEN

This study explored the value of detection of human epididymis secretory protein 4 (HE4) and carbohydrate antigen 125 (CA125) from serum in diagnosis of early endometrial cancer of different pathological subtypes and discussed the mechanism of HE4 and CA125 in diagnosis. In this study, enzyme-linked immunosorbent assay and chemiluminescent immunoassay were used to detect HE4 and CA125 from serum in endometrial cancer and control groups. Besides, the concentration of HE4 and CA125 was compared in these two groups, and the expression of CA125 and HE4 and clinicopathological characteristics in patients with endometrial cancer were also analyzed. Compared with the control group, the expression of HE4 was much higher in serum of patients with endometrial cancer, while there was no obvious change in the expression of CA125. The threshold detection value was acquired by receiver operating characteristic analysis method, that is, 141.5 pmol/L and 54.5 U/L, respectively. When comparing the concentration of HE4 in patients with endometrial cancer at the early stage (stage I) with healthy people, the difference therein had statistical significance, but there was no obvious difference in CA125. HE4 and CA125 in diagnosis of endometrial cancer in the stages I and II were found with no statistically significant difference. The difference of HE4 in the stages II and III had statistical significance while the difference of CA125 had no statistical significance. The specificity of both HE4 and CA125 was 95%, and the sensitivity of HE4 to uterine papillary serous carcinomas was higher than that to endometrioid adenocarcinoma. Thus, the serum HE4 is much better than CA125 in detecting the endometrial cancer at an early stage.

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