Combinatorial chemistry & high throughput screening最新文献

{"title":"The Anti-PEDV Effects and Mechanisms of Forsythia Essential Oil Based on Network Pharmacology and Experimental Validation.","authors":"Ruiping Liang, Jianbo Guo, Kai Li, Xuan Wang, Xiaoxiao Ge, Jinhui Wang, Jing Sun, Chongbo Zhao, Huanxian Shi, Rongxia Qiao, Hongqing Zheng, Xiaofei Zhang","doi":"10.2174/0113862073358217250225052414","DOIUrl":"https://doi.org/10.2174/0113862073358217250225052414","url":null,"abstract":"<p><strong>Objective: </strong>Porcine epidemic diarrhea virus (PEDV), a member of the Coronaviridae, is responsible for acute diarrhea, vomiting, and dehydration, which can lead to high mortality in neonatal piglets. Previous research has indicated the antiviral potential of forsythia essential oil (FEO); however, its active components and mechanisms of action remain inadequately defined. This study aims to investigate the antiviral effects of FEO and elucidate its potential mechanisms for treating PEDV.</p><p><strong>Methods: </strong>The primary components of FEO were identified using gas chromatography-mass spectrometry (GC/MS) in conjunction with the National Institute of Standards and Technology Standard Spectrum (NIST) Database. Network pharmacology and weighting coefficients were employed to determine the key signaling pathways associated with PEDV-related diseases. Molecular docking simulations were conducted to explore the interactions between the active ingredients and their corresponding targets. The safety profile of FEO was assessed through cell viability assays utilizing the CCK8 method. Subsequently, immunofluorescence assays (IFA) and reverse transcription-quantitative polymerase chain reaction (RT-Q-PCR) were performed to provide evidence of the anti-PEDV effects. Additionally, the viral replication cycle was analyzed to identify the stages at which FEO exerts its antiviral effects. Finally, key targets were validated through RT-Q-PCR to further investigate the anti-PEDV mechanisms of FEO.</p><p><strong>Results: </strong>The IL-17 signaling pathway was identified as a critical pathway for the treatment of PEDV with FEO based on network pharmacology and weighting coefficient analyses. Furthermore, results from RT-Q-PCR and IFA demonstrated that FEO influenced the replication of PEDV during the attachment and internalization phases. Specifically, during the viral attachment phase, FEO significantly upregulated the expression of HSP90AA1 while downregulating MAPK14 expression, leading to a reduction in associated inflammatory factors. At the high dose of FEO, the expression of HSP90AA1 was higher than that of the model group by about 5-fold, and the expression of MAPK14 was lower than that of the model group by about 2-fold. Cell viability assay showed no significant cytotoxicity of FEO at 0.63 μL/mL, thus confirming its safety.</p><p><strong>Conclusion: </strong>The findings of this study suggest that FEO possesses potential antiviral properties against PEDV. Its novel mechanisms of action warrant further investigation, which may contribute to the development of effective therapeutic strategies for managing PEDV infections.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603857","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":"GLI3 is Inhibited by miR-143-3p and Attenuates Septic-induced Lung Injury and Inflammation by Targeting SFRP1.","authors":"Minqing Ma, Haixia Han, Xiaoya Luo, Jiakai Lin, Bin Sun","doi":"10.2174/0113862073354161250220121414","DOIUrl":"https://doi.org/10.2174/0113862073354161250220121414","url":null,"abstract":"<p><strong>Objectives: </strong>Transcription factors (TF) are the central regulatory hubs of signaling pathways in eukaryotic cells. Here, we explored the abnormal expression of TF in septic-induced lung injury by sequencing.</p><p><strong>Methods: </strong>The levels of target proteins were detected using Western Blot and Elisa. Cell function was evaluated using CCK8 and transwell assays. A double luciferase reporter assay was performed to detect interactions between target molecules.</p><p><strong>Results: </strong>We found that TF glioma-associated oncogene (GLI) family zinc finger 3 (GLI3) was abnormally low expressed in a lipopolysaccharide (LPS) induced acute lung injury (ALI) cell model. In an in vitro model, GLI3 overexpression promoted the proliferation and migration and inhibited apoptosis of lung epithelial cells in LPS-induced inflammatory environment. Importantly, GLI3 overexpression inhibited the secretion of inflammatory factors IL-1β, IL-6, and TNF-α. Additionally, miR-143-3p inhibited the expression of GLI3. MiR-143-3p inhibitor alleviated the cell damage caused by LPS, while knocking down GLI3 counteracted this effect, indicating that miR-143-3p downregulated GLI3 and inhibited its anti-inflammatory effect. Secreted frizzled related protein-1 (SFRP1) was upregulated in LPS-treated cells and SFRP1 promoter interacted with GLI3, suggesting that SFRP1 was a target of TF GLI3. Co-transfection with GLI3 knockdown and SFRP1 overexpression plasmids attenuated the secretion of inflammatory factors IL- 1β, IL-6, and TNF-α caused by GLI3 knockdown in LPS-treated cells, indicating that SFRP1 plays an anti-inflammatory role as a GLI3 target in the ALI cell model.</p><p><strong>Conclusions: </strong>miR-143-3p caused degradation of GLI3 mRNA and thus inhibited the transcription of SFRP1, leading to decreased proliferation and increased levels of inflammatory factors, providing new potential targets for the clinical diagnosis and treatment of ALI.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603849","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":"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}