Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
Add more filters











Database
Language
Publication year range
1.
Sci Rep ; 13(1): 12779, 2023 08 07.
Article in English | MEDLINE | ID: mdl-37550341

ABSTRACT

As one of the malignant tumors with high mortality, the initial symptoms of liver cancer are not obvious. In addition, the liver is the largest internal organ of the human body, and its structure and distribution are relatively complex. Therefore, in order to help doctors judge liver cancer more accurately, this paper proposes a variant model based on Unet network. Before segmentation, the image is preprocessed, and Pulse Coupled Neural Network (PCNN) algorithm is used to filter the image adaptively to make the image clearer. For the segmentation model, the SE module is used as the input of the residual network, and then its output is connected to the Unet model through bilinear interpolation to perform the down-sampling and up-sampling operations. The dataset is a combination of Hainan Provincial People's Hospital and some public datasets Lits. The results show that this method has better segmentation performance and accuracy than the original Unet method, and the dice coefficient, mIou and other evaluation indicators have increased by at least 2.1%, which is a method that can be applied to cancer segmentation.


Subject(s)
Liver Neoplasms , Humans , Liver Neoplasms/diagnostic imaging , Neural Networks, Computer , Algorithms , Heart Rate , Image Processing, Computer-Assisted
2.
Cells ; 12(14)2023 07 20.
Article in English | MEDLINE | ID: mdl-37508563

ABSTRACT

Tissue inhibitor of metalloproteinases-1 (TIMP-1), an important regulator of matrix metalloproteinases (MMPs), has recently been shown to interact with CD74, a receptor for macrophage migration inhibitory factor (MIF). However, the biological effects mediated by TIMP-1 through CD74 remain largely unexplored. Using sequence alignment and in silico protein-protein docking analysis, we demonstrated that TIMP-1 shares residues with both MIF and MIF-2, crucial for CD74 binding, but not for CXCR4. Subcellular colocalization, immunoprecipitation, and internalization experiments supported these findings, demonstrating that TIMP-1 interacts with surface-expressed CD74, resulting in its internalization in a dose-dependent manner, as well as with a soluble CD74 ectodomain fragment (sCD74). This prompted us to study the effects of the TIMP-1-CD74 axis on monocytes and vascular smooth muscle cells (VSCMs) to assess its impact on vascular inflammation. A phospho-kinase array revealed the activation of serine/threonine kinases by TIMP-1 in THP-1 pre-monocytes, in particular AKT. Similarly, TIMP-1 dose-dependently triggered the phosphorylation of AKT and ERK1/2 in primary human monocytes. Importantly, Transwell migration, 3D-based Chemotaxis, and flow adhesion assays demonstrated that TIMP-1 engagement of CD74 strongly promotes the recruitment response of primary human monocytes, while live cell imaging studies revealed a profound activating effect on VSMC proliferation. Finally, re-analysis of scRNA-seq data highlighted the expression patterns of TIMP-1 and CD74 in human atherosclerotic lesions, thus, together with our experimental data, indicating a role for the TIMP-1-CD74 axis in vascular inflammation and atherosclerosis.


Subject(s)
Atherosclerosis , Monocytes , Humans , Proto-Oncogene Proteins c-akt , Tissue Inhibitor of Metalloproteinase-1 , Muscle, Smooth, Vascular , Inflammation , Cell Proliferation
3.
J Healthc Eng ; 2021: 7733654, 2021.
Article in English | MEDLINE | ID: mdl-34745510

ABSTRACT

Objective: This study was aimed to explore the accuracy of multi-slice spiral computed tomography (CT) scan in preoperative staging diagnosis of bladder cancer based on hybrid iterative reconstruction algorithm, so as to provide a more reasonable supporting basis for guiding clinical work in the future. Methods: Retrospectively, 120 patients admitted to hospital from July 2019 to April 2021, who were confirmed to be with urothelial carcinoma of the bladder by pathological examination after surgical treatment, were selected. CT images before processing were set as the control group and those after processing were set as the observation group according to whether they were processed by the hybrid iterative algorithm. Postoperative pathological examination was utilized as the standard for analysis. The accuracy and consistency of the two methods were compared. Results: The accuracy of the results of each stage of the observation group (T1 stage: 91.09%, T2 stage: 89.66%, T3 stage: 88.89%, and T4 stage: 88.89%) and consistency (T1 stage: 0.66, T2 stage: 0.69, T3 stage: 0.71, and T4 stage: 0.82) were higher than those of the control group (accuracy: T1-57.01%, T2-48.28%, T3-44.44%, and T4-44.44%). The consistency was as follows: T1-0.32, T2-0.24, T3-0.37, and T4-0.43, and the comparison was statistically significant (P < 0.05). Conclusion: The adoption value of the image features based on the hybrid iterative reconstruction algorithm in the diagnosis of bladder cancer staging was higher than that of the conventional multi-slice spiral CT, indicating that the hybrid iterative reconstruction algorithm had a good adoption prospect in clinical examination.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Algorithms , Humans , Neoplasm Staging , Retrospective Studies , Tomography, Spiral Computed/methods , Tomography, X-Ray Computed , Urinary Bladder Neoplasms/diagnostic imaging
5.
Chem Biol Drug Des ; 92(3): 1647-1656, 2018 09.
Article in English | MEDLINE | ID: mdl-29745030

ABSTRACT

α-Glucosidase is known to catalyze the digestion of carbohydrates and release free glucose into the digestive tract. Protein tyrosine phosphatase 1B (PTP1B) is engaged in the dephosphorylation of the insulin receptor and regulation of insulin sensitivity. Therefore, dual antagonists by targeting both α-glucosidase and PTP1B may be potential candidates for type 2 diabetes therapy. In this work, three series of novel N-aryl-ω-(benzoazol-2-yl)-sulfanylalkanamides were synthesized and assayed for their α-glucosidase and PTP1B inhibitory activities, respectively. Compound 3l, exhibiting the most effective α-glucosidase inhibitory activity (IC50  = 10.96 µm (3l), IC50  = 51.32 µm (Acarbose), IC50  = 18.22 µm (Ursolic acid)) and potent PTP1B inhibitory activity (IC50  = 13.46 µm (3l), IC50  = 14.50 µm (Ursolic acid)), was identified as a novel dual inhibitor of α-glucosidase and PTP1B. Furthermore, 3l is a highly selective PTP1B inhibitor because no inhibition was showed by 3l at 100 µm against PTP-MEG2, TCPTP, SHP2, or SHP1. Subsequent kinetic analysis revealed 3l inhibited α-glucosidase in a reversible and mixed manner. Molecular docking study indicated that hydrogen bonds, van der Waals, charge interactions and Pi-cation interactions all contributed to affinity between 3l and α-glucosidase/PTP1B.


Subject(s)
Amides/chemistry , Enzyme Inhibitors/chemical synthesis , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , alpha-Glucosidases/chemistry , Amides/metabolism , Binding Sites , Catalytic Domain , Enzyme Assays , Enzyme Inhibitors/metabolism , Hydrogen Bonding , Inhibitory Concentration 50 , Kinetics , Molecular Docking Simulation , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , Structure-Activity Relationship , alpha-Glucosidases/metabolism
6.
J Mol Graph Model ; 54: 10-8, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25241128

ABSTRACT

The catalytic activity of the histone deacetylase (HDAC) is directly relevant to the pathogenesis of cancer, and HDAC inhibitors represented a promising strategy for cancer therapy. SAHA (suberoanilide hydroxamic acid), an effective HDAC inhibitor, is an anti-cancer agent against T-cell lymphoma. However, SAHA has adverse effects such as poor pharmacokinetic properties and severe toxicities in clinical use. In order to identify better HDAC inhibitors, a compound database was established by core hopping of SAHA, which was then docked into HDAC-8 (PDB ID: 1T69) active site to select a number of candidates with higher docking score and better interaction with catalytic zinc ion. Further ADMET prediction was done to give ten compounds. Molecular dynamics simulation of the representative compound 101 was performed to study the stability of HDAC8-inhibitor system. This work provided an approach to design novel high-efficiency HDAC inhibitors with better ADMET properties.


Subject(s)
Histone Deacetylase Inhibitors/chemistry , Hydroxamic Acids/chemistry , Humans , Lymphoma, T-Cell , Molecular Dynamics Simulation , Protein Structure, Secondary , Structure-Activity Relationship , Temperature
SELECTION OF CITATIONS
SEARCH DETAIL