Combinatorial chemistry & high throughput screening最新文献

{"title":"Computational Study for Preparation of Benzoimidazo[1,2-a]pyrimidines from Reaction of Benzaldehyde, Indanedione and 1H-benzo[d]imidazol-2- amine.","authors":"Yas Zibaei, Leila Zare Fekri, Mohammad Nikpassand","doi":"10.2174/0113862073362160250217093210","DOIUrl":"https://doi.org/10.2174/0113862073362160250217093210","url":null,"abstract":"<p><strong>Background: </strong>Benzoimidazo[1,2-a]pyrimidines are important compounds that have many useful effects in the body. They can help fight cancer, fungal infections, inflammation, and viruses. They can also help with various other health conditions. They can act as antineoplastic, antitubercular, parasitical activity, benzodiazepine receptor agonists, calcium channel blockers, potent P38 MAP kinase inhibitors, TIE-2 and/or VEGFR2 inhibitory activities, protein kinase inhibitors, and T cell activation. There are different methods to make the benzoimidazo[1,2- a]pyrimidines. Some of them dealth with the one-pot threecomponent condensation reactions of β- dicarbonyl compounds, aldehyde and 1H-benzo[d]imidazol-2-amine in the presence of catalyst. Although the synthesis of this group of compounds has been done before, and the products have been identified from the spectroscopic point of view, the kinetics and reaction mechanism have not been investigated. The strength of these calculations is that evaluation of the activation energy of various steps suggests possible mechanisms, probable mechanisms, and valuable synthetic intermediates.</p><p><strong>Methods: </strong>In this report, seven possible mechanisms for synthesizing the benzoimidazo[1,2- a]pyrimidines have been investigated using density functional theory (DFT) at the B3LYP/6- 311G** level of theory. Each synthetic route involves condensation of the benzaldehyde, indanedione and 1H-benzo[d]imidazol-2-amine molecules to yield the proposed product. The calculations showed that the suggested method has six steps; its initiation step includes the Knoevenagel reaction between indanedione and aldehyde, and the rate determining state is dehydration in the fifth step.</p><p><strong>Result: </strong>Six potential pathways for the reaction will occur. Then, we focused on the best pathway and studied it in detail. The ways that three chemicals-indanedione (R1), benzaldehyde (R2), and 1H-benzo[d]imidazol-2-amine (R3) react with each other were studied using ab-initio program by ChemBio3D, Gauss View, and Gaussian 09. The Density Functional Theory (DFT) using the B3LYP basis set was used to improve the arrangement of molecules involved in the three-part creation of a specific compound called 12-phenyl-5H-benzo[4,5]imidazo[1,2-a]indeno[1,2- d]pyrimidin-13(12H)-one (P).</p><p><strong>Conclusion: </strong>During the study of the six mechanisms, the proposed pathway 2 is the best mechanism for this reaction because its rate-determining step has the lowest activation energy value. This route consists of 6 steps, the fifth step of which is related to the conversion of IM4 to IM5 (relative ΔE: 109.80 Kj/mol), during which a dehydration reaction is performed, and this step occurs by passing through transition state TS5 (Total Energy (Hart./particles: -1194.747403).</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dry Powder Inhaler of Sustained-Release Microspheres Containing Glycyrrhizin: Factorial Design and Optimization.","authors":"Arpita Chakraborty, Riya Mahar, Nidhi Nainwal","doi":"10.2174/0113862073333147250127053403","DOIUrl":"https://doi.org/10.2174/0113862073333147250127053403","url":null,"abstract":"<p><strong>Background: </strong>Glycyrrhizin is a saponin glycoside of the liquorice plant. It is commonly used to treat respiratory problems. Inhalable glycyrrhizin formulation in asthma can be a good alternative for widely used inhaled corticosteroids that exhibit side effects upon long-term use.</p><p><strong>Aim: </strong>Asthma is a major and prevalent respiratory disease. However, the rate of drug development in this arena is quite slow, as indicated by merely four new drugs approved by the USFDA in the last 6 years for respiratory diseases.</p><p><strong>Objective: </strong>We herein propose to design and develop Glycyrrhizin-inhalable microspheres for the treatment of asthma.</p><p><strong>Method: </strong>A 32 full factorial design was applied to show the effect of the two independent variables (polycaprolactone, and polyvinyl alcohol concentration) on each of the selected dependent variables (drug loading and entrapment efficiency).</p><p><strong>Results: </strong>The optimized microspheres were spherical and 1-5 μm in size. The formulation showed a fine particle fraction of 78%, indicating that the powders were suitable for inhalation. The Drug loading and encapsulation efficiency of the optimized formulation were found to be 9.8% and 40.98%, respectively. The aerosolization study on the Anderson cascade impactor showed that deposition of particles of formulation blended with lactose was better than nonblended formulation and drug in the lungs.</p><p><strong>Conclusion: </strong>In comparison to the pure drug, optimized formulation prolonged drug residency in the lung for more than 12 hrs after inhalation. Inhalable microparticles of glycyrrhizin provide sustained and prolonged drug release in the lungs along with protection of drugs against pulmonary degradation.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agaricus blazei Murill Extract (FA-2-b-β) Induces Ferroptosis in Diffuse Large B-Cell Lymphoma via the Nrf2/Ho-1 Pathway.","authors":"Rong Li, Dan Huang, Along Wu, Yanqin Sun","doi":"10.2174/0113862073363731250218054917","DOIUrl":"https://doi.org/10.2174/0113862073363731250218054917","url":null,"abstract":"<p><strong>Introduction: </strong>Ferroptosis is a recently identified iron-dependent programmed cell death closely linked to the progression of diffuse large B-cell lymphoma (DLBCL). While studies have shown that FA-2-b-β extracted from Agaricus blazei Murill affects various malignancies, its specific role in modulating ferroptosis in DLBCL and the underlying mechanisms are not yet clear.</p><p><strong>Objectives: </strong>This study aims to elucidate the anticancer properties and mechanisms of FA-2-b-β in inducing ferroptosis in DLBCL cells.</p><p><strong>Methods: </strong>The cell counting kit 8 assay was carried out to evaluate the inhibition of cellular proliferation. Ferroptosis was evaluated using the ferrous colorimetric method, together with kits for measuring malondialdehyde (MDA), reduced glutathione (GSH), reactive oxygen species (ROS), western blotting, JC-1 assays, and transmission electron microscopy. Reverse transcriptionquantitative polymerase chain reaction and western blot were conducted to determine whether FA- 2-b-β affected nuclear factor erythroid 2- related factor 2 (Nrf2) and heme oxygenase 1 (HO-1).</p><p><strong>Results: </strong>FA-2-b-β induced ferroptosis in DLBCL cells by elevating the ROS and MDA levels, facilitating the accretion of Fe²⁺, diminishing GSH, upregulating the expression of PTGS2, and downregulating the expression of FTH1, SLC7A11, and GPX4. Furthermore, FA-2-b-β caused structural damage to mitochondria and diminished the mitochondrial membrane potential. The ferroptosis triggered by FA-2-b-β also led to the downregulation of Nrf2 and HO-1, thereby regulating the Nrf2/HO-1 pathway.</p><p><strong>Conclusion: </strong>FA-2-b-β suppressed DLBCL cell growth by inducing ferroptosis through the Nrf2/HO-1 pathway, making it an attractive potential therapeutic option.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing the Mechanism of Buzhong Yiqi Tang in Ameliorating Autoimmune Thyroiditis via the Toll-like Receptor Pathway.","authors":"Zhuo Zhao, Jiayun Li, Donglin Liu, Hao Gao, Zhe Jin, Zhimin Wang, Yiran Chen, Si Chen, Ziyu Liu, Xiao Yang","doi":"10.2174/0113862073357259250214111143","DOIUrl":"https://doi.org/10.2174/0113862073357259250214111143","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Autoimmune thyroiditis (AIT) is one of the most common autoimmune diseases and often causes hypothyroidism in patients. As a traditional formulation in my country, Buzhong Yiqi decoction (BZYQD) has significant effects in improving clinical symptoms of AIT and reducing autoantibody titers, but its specific mechanism of action needs to be further explored. The purpose of this study was to explore the effective targets and related mechanisms of Buzhong Yiqi decoction in AIT mice based on transcriptome sequencing technology.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Forty NOD.H-2h4 mice were selected and 0.05% NaI was drinking ad libitum for 8 weeks to establish AIT mice, and drug intervention was performed according to groups for 8 weeks. The groups were as follows: control group, Model Group, Buzhong Yiqi Decoction group (9.56 g·kg-1) and Positive control group (Se yeast tablets, 3.033×10-5 g·kg-1), of which Buzhong Yiqi Decoction was the clinical equivalent dose. Thyroid tissues of the Model Group, blank group and Buzhong Yiqi Decoction group were subjected to transcriptome sequencing to analyze the expression of differential genes, and enrichment analysis was carried out. Hematoxylin and eosin staining (HE staining) was used to detect the pathological changes in thyroid tissues, and enzymelinked immunosorbent assay (ELISA) was used to detect the content of serum thyroglobulin antibody (TGAb) to determine the intervention effect of Buzhong Yiqi Decoction; Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was performed based on the transcriptome sequencing results to detect the expression of TLR8, JUN, TICAM2, TIRAP, and IL-1β mRNA in thyroid tissue.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;According to the transcriptome results, compared with the blank group, there were 327 significantly up-regulated genes and 440 significantly down-regulated genes in the Model Group; compared with the Model Group, there were 502 significantly up-regulated genes and 380 significantly down-regulated genes in the Buzhong Yiqi Decoction group, mainly enriched in immune inflammation and other related pathways including Toll-like receptors. Animal experiments showed that compared with the control group, the model group had obvious lymphocyte infiltration in thyroid tissue under light microscope, a significant increase in inflammatory cells, a significant increase in TGAb content in serum, and a significant increase in TLR8, JUN, TICAM2, TIRAP, IL-1β mRNA expression was observed (P&lt;0.05 or P&lt;0.01). Compared with the Model Group, Buzhong Yiqi Decoction could significantly improve the inflammatory damage of thyroid tissue in AIT mice, reduce the content of TGAb in serum, and down-regulate the expression of TLR8, JUN, TICAM2, TIRAP, IL-1β mRNA (P&lt;0.05 or P&lt;0.01).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Buzhong Yiqi Decoction can effectively improve the inflammatory damage of AIT, and inhibiting the abnormal activation of the Toll-like re","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Targeting Neutrophil Extracellular Traps as a Promising Approach for Breast Cancer Treatment.","authors":"Jiale Mi, Jiani Guo, Kang Kang, Shiqi Wang, Mingde Huang","doi":"10.2174/0113862073376243250130060239","DOIUrl":"https://doi.org/10.2174/0113862073376243250130060239","url":null,"abstract":"<p><p>Neutrophils release neutrophil extracellular traps (NETs), a reticular structure mainly composed of antimicrobial peptides, DNA, and histones. Neutrophil elastase (NE), matrix metalloproteinase- 9, and histone G are the key components of NETs critically involved in breast cancer invasion and migration, which suggests an important role of NETs in tumorigenesis and metastasis. Studies have reported that NETs significantly promote breast cancer invasion, intravascular infiltration, and distant metastasis by inducing epithelial-mesenchymal transition (EMT), remodeling the extracellular matrix, and modulating the immune microenvironment. Meanwhile, NETs also function crucially in capturing circulating tumor cells, forming a pre-metastatic microenvironment, and awakening dormant cancer cells. Notably, NETs are also closely associated with chemotherapy and immunotherapy resistance in breast cancer. Therapeutic strategies targeting NETs, including DNase I, PAD4 inhibitors, elastase inhibitors, and histone C inhibitors, have been widely studied. These targeted therapies can effectively suppress the generation of NETs, improve drug efficacy, and delay tumor metastasis. This review aimed to systematically elucidate the mechanism of action of NETs in the progression and drug resistance of breast cancer and explore potential targeted therapeutic strategies against NETs. These strategies could effectively inhibit the generation of NETs, delay the progression of breast cancer, and improve therapeutic efficacy. An in-depth study of the mechanism of action of NETs and the clinical significance of their targeted interventions is expected to provide a new direction for breast cancer treatment.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling the Physico-Chemical Characteristics of Benzenes through the Application of Zagreb Rho Indices.","authors":"İdris Çiftçi","doi":"10.2174/0113862073367066250218103438","DOIUrl":"https://doi.org/10.2174/0113862073367066250218103438","url":null,"abstract":"<p><p>The exploration of Quantitative Structure-Property Relationship (QSPR) frameworks utilizes topological indices to clarify the chemical and physical attributes of molecular entities. In the current investigation, we initially identified the rho degree of a vertex in conjunction with the Zagreb rho indices associated with connected graphs, marking a notable progression within the field of (chemical) graph theory. We demonstrate that there are correlations exceeding 0.94 between the Zagreb rho indices and the physicochemical properties of benzenes, which encompass boiling point, pi-electron energy, molecular weight, polarization, molecular volume, and relative formula mass. Our results reveal that the correlation coefficients between the Zagreb rho indices and the established degree-based topological indices of benzenes exceed 0.93. Additionally, we performed structural sensitivity and abruptness analyses of these novel indices and compared them with alternative topological indices. The results and analyses provide evidence that Zagreb rho indices are pertinent to QSPR research initiatives.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"20D-Dynamic Representation of Protein Sequences Combined with K-means Clustering.","authors":"Dorota Bielińska-Wąż, Piotr Wąż, Agata Błaczkowska","doi":"10.2174/0113862073359729250220131623","DOIUrl":"https://doi.org/10.2174/0113862073359729250220131623","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this research is to demonstrate that alignment-free bioinformatics approaches are effective tools for analyzing the similarity and dissimilarity of protein sequences. All numerical parameters representing sequences are expressed analytically, ensuring precision, clarity, and efficient processing, even for large datasets and long sequences. Additionally, a novel approach for identifying previously unknown virus strains is introduced.</p><p><strong>Methods: </strong>A novel approach is proposed, integrating the unique features of our newly developed method, the 20D-Dynamic Representation of Protein Sequences, with the K-means clustering algorithm. The sequences are represented as clouds of material points in a 20-dimensional space (20D-dynamic graphs), with their spatial distribution being unique to each protein sequence. The numerical parameters, referred to as descriptors in molecular similarity theory, represent quantities characteristic of dynamic systems and serve as input data for the K-means clustering algorithm.</p><p><strong>Results: </strong>Examples of the application of the approach are presented, including projections of the 20D-dynamic graphs onto 3D spaces, which serve as a visual tool for comparing sequences. Additionally, cluster plots for the analyzed sequences are provided using the proposed method.</p><p><strong>Conclusion: </strong>It has been demonstrated that the 20D-Dynamic Representation of Protein Sequences, combined with the K-means clustering algorithm, successfully classifies subtypes of influenza A virus strains.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Mitochondrial-related Characteristic Biomarkers in Osteosarcoma using Bioinformatics and Machine Learning.","authors":"Jingyi Hou, Yu Zhang, Ning Yang, Bin Chen, Chengbing Chang, Haipeng Gu, Yanqi Liu, Naiqiang Zhu","doi":"10.2174/0113862073350964241203080017","DOIUrl":"https://doi.org/10.2174/0113862073350964241203080017","url":null,"abstract":"<p><strong>Background/aims: </strong>Osteosarcoma (OS), a malignant tumor originating in bone or cartilage, primarily affects children and adolescents. Notably, substantial alterations in mitochondrial energy metabolism have been observed in OS; however, the specific contribution of mitochondrial- related genes (MRGs) to OS pathogenesis and prognosis remains unclear. Herein, we identified novel diagnostic biomarkers associated with mitochondrial-related processes in OS via comprehensive bioinformatics analysis. </p Methods: OS mRNA expression profiles were retrieved from GSE16088 and GSE19276 databases. Mitochondrial-related differentially expressed genes (MitoDEGs) were identified by integrating differentially expressed analysis with mitochondrial-localized genes. A protein-protein interaction network was constructed, and machine learning algorithms (LASSO regression analysis and SVM-RFE) identified characteristic MitoDEGs. Subsequently, immune cell infiltration, microenvironment analysis, and single-cell RNA sequencing (scRNA-seq) analyzed differences in characteristic MitoDEGs, and RT-PCR was used for in vitro verification of characteristic MitoDEGs.</p><p><strong>Results: </strong>MitoDEGs in OS were significantly enriched in the pathways associated with mitochondrial function and immune regulation. Two MitoDEGs, UCP2 and PRDX4, were identified via LASSO and SVM-RFE. Correlation analysis demonstrated a close association between UCP2 and PRDX4 expression levels and immune cell infiltration, particularly in CD8+ T and native CD4+ T cells, as observed in both immune cell and scRNA-seq analyses. Furthermore, RTPCR confirmed the expression levels of UCP and PRDX4 at the cellular level, which was consistent with the bioinformatics results.</p><p><strong>Conclusion: </strong>This study identified UCP2 and PRDX4 as characteristic MitoDEGs and potential diagnostic biomarkers for OS using machine learning algorithms. These findings provide novel insights into the clinical applications of these biomarkers for OS diagnosis.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin Inhibits Ectopic Lesion Formation in Mice by Modulating the MAT2A/PRMT5 Pathway through PPARγ Activation.","authors":"Shun Zhang, Yuan-Yuan Zhang, Qiu-Xia Zeng, Li Wang, Kong-Xian Li, Qi Chen","doi":"10.2174/0113862073379671250219103011","DOIUrl":"https://doi.org/10.2174/0113862073379671250219103011","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to examine the impact of quercetin on a mouse model of endometriosis and elucidate its underlying mechanisms.</p><p><strong>Methods: </strong>An endometriosis model was established using C57BL/6 mice, which were divided into three groups: 1) sham group, 2) model group, and 3) model group treated with daily gavage administration of 100 mg/kg/d quercetin. After three weeks, mice were euthanized, and histopathological examination was performed using hematoxylin and eosin (HE) staining. The microstructure of the lesions was examined using electron microscopy, and the expression level of Sadenosylmethionine (SAM) was measured using enzyme-linked immunosorbent assay (ELISA). Additionally, the expressions of related proteins, such as the peroxisome proliferator-activated receptor-γ (PPARγ) and methionine adenosyl-transferase 2A (MAT2A), were analyzed via Western blotting. Immunohistochemistry was employed to evaluate the expressions of Ki67, vimentin, vascular endothelial growth factor (VEGF), and Caspase-1.</p><p><strong>Results: </strong>The endometriosis mice model was successfully established and characterized by ectopic lesions displaying transparent or red vesicular or nodular features with a visible vascular network on the surface. In the model group, endometrial epithelial hyperplasia exhibited columnar morphology, increased mesenchymal cell numbers, and regular cell morphology. Conversely, in the medication group, endometrial stromal cell numbers were sparse, cell morphology was irregular, and numerous vacuoles were observed in the endometrial tissue, indicative of apoptotic cell morphology changes. In comparison to the sham group, no statistically significant alterations were observed in the expression levels of SAM (P > 0.05). Conversely, the expression of PPARγ exhibited a notable decline. MAT2A, PRMT5, cyclin D1, and C-MYC expressions were increased, and vimentin, Ki67, VEGF, and caspase-1 expressions were strongly positive, with statistically significant differences (P < 0.05). In contrast, compared to the model group, the quercetin intervention group exhibited significantly reduced ectopic lesion weights, increased PPARγ expression, and significantly reduced protein expression levels of MAT2A, PRMT5, SAM, cyclin D1, and C-MYC. Furthermore, expressions of vimentin, Ki67, VEGF, and caspase-1 were weakly positive, with statistically significant differences (P < 0.05).</p><p><strong>Conclusion: </strong>Quercetin modulated the transcription of the MAT2A/PRMT5 gene by activating PPARγ activity, thereby influencing the ectopic implantation and growth of endometrial cells.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UPLC-Q-TOF-MS, Network Pharmacology and Molecular Docking to Reveal the Antidepressant Mechanism of the Different Components of Medicinal and Edible Lilies (Lilium sp. pl).","authors":"Zhaoyang Tan, Linghe Huang, Yanqiu Tian, Sai Jiang, Zhi Wang, Hongping Long, Qiaozhen Tong, Shunxiang Li, Lin Jiang","doi":"10.2174/0113862073368704250131085339","DOIUrl":"https://doi.org/10.2174/0113862073368704250131085339","url":null,"abstract":"<p><strong>Background and objectives: </strong>To explore the mechanism of action of the differential components of medicinal and edible lilies in treating depression by network pharmacology using UPLC-Q-TOF-MS technology.</p><p><strong>Methods: </strong>The chemical composition of medicinal and edible lilies was analyzed, screening for unique medicinal compounds. Searched for depression-related targets. Constructed PPI networks. Performed GO and KEGG analyses. Built a network of differential components, and conducted molecular docking. In addition, the contents of regaloside before and after lily processing were compared Results: Medicinal lilies and edible lilies have 17 main differences, including regaloside B and regaloside E. There are 179 targets for actives, 2690 for antidepressants, and 98 intersected. Core targets (7) led to 238 GO processes and 107 KEGG pathways. The molecular docking results showed that 17 components, including regaloside B, regaloside E, (25R)-3β,17α-Dihydroxy-5α- spirostan-6-one 3-O-α-L- rhamnopyranosyl-(1→2)-β- D-glucopyranoside (Named: Lilium lancifolium saponin), etc. could act on 7 potential targets such as EGFR, HSP90AA1, STAT3, TNF, etc. to exert antidepressant effects.</p><p><strong>Conclusion: </strong>This study employed a network pharmacology combined with a molecular docking approach to compare the active constituents of medicinal and edible lilies in antidepressants, and their pharmacological mechanisms, both theoretically and technically. The phytoconstituents were found to act mainly by inhibiting the inflammatory response in depression. Especially Lilium lancifolium saponin may have a close relationship with antidepressants. These results provide some justification for lilies in the treatment of depression.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}