Combinatorial chemistry & high throughput screening最新文献

{"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}

{"title":"Evaluation of Carbamazepine and Gabapentin's Safety and Efficacy in Trigeminal Neuralgia Treatment: A Systematic Review and Meta-Analysis.","authors":"Yang Yan, Haitao Shang, Tao Han","doi":"10.2174/0113862073353707250204061916","DOIUrl":"https://doi.org/10.2174/0113862073353707250204061916","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to assess the safety and effectiveness of carbamazepine in treating trigeminal neuralgia in contrast to gabapentin. Hence, a systematic review and metaanalysis of randomised controlled trials had been carried out.</p><p><strong>Methods: </strong>The relevant studies were searched in PubMed and filtered according to the inclusion and exclusion criteria. Independently, two reviewers chose the studies, evaluated the quality of the investigations, and retrieved the data. RevMan was used for analysis when the data were collected and entered into the data extraction sheet. In addition to heterogeneity, the overall estimate measures were computed as mean differences with a 95% confidence interval for continuous data and relative risk for dichotomous data. To investigate the impact of outliers on the result, a sensitivity analysis was performed. A funnel plot was used to qualitatively evaluate the publishing bias. A total of 1,650 participants from 19 randomised controlled trials were evaluated.</p><p><strong>Results: </strong>The meta-analysis revealed that the group receiving gabapentin therapy had a similar overall effective rate to the group receiving carbamazepine therapy (OR = 1.94, 95% CI 1.46, 2.57, P = 0.32). Additionally, our meta-analysis revealed that the group receiving gabapentin therapy witnessed a significantly lower risk of adverse reactions than the group receiving carbamazepine therapy (OR= 0.29, 95% CI 0.22, 0.387, P<0.00001).</p><p><strong>Conclusion: </strong>In summary, the current trials comparing carbamazepine and gabapentin have had inadequate methodological quality. It is not possible to conclude that gabapentin is more effective than carbamazepine in terms of adverse effects based on the evidence that is currently available.</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":"143490963","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":"Rapid Screening and Effective Rabbit-Derived Fab Antibodies Production Based on Yeast Surface Display.","authors":"Weili Shen, Tingting Gong, Changli Shao","doi":"10.2174/0113862073352395250211052148","DOIUrl":"https://doi.org/10.2174/0113862073352395250211052148","url":null,"abstract":"<p><strong>Background: </strong>Antibodies have broad applications in various fields, such as biology and medicine. The screening and preparation of highly specific and sensitive antibodies are essential research areas. Several techniques for the preparation of mouse-derived antibodies have been developed, but limited studies on rabbit-derived antibodies with a broader antibody profile and easier humanization are reported.</p><p><strong>Objective: </strong>An improved yeast surface display technique was used for rapid screening of rabbitderived Fab antibodies.</p><p><strong>Method: </strong>After RNA extraction from peripheral rabbit blood, a cDNA library was obtained by reverse transcription. After recombinant vector construction, the expressed sequence in the form of Fab antibody structure was fused to the N-terminal end of Aga2p in the vector; a bidirectional promoter was inserted and successfully expressed in brewer's yeast EBY100. In addition, sequences, such as leucine zipper and inulinase signal peptide (INU), were inserted into the recombinant vector to improve the expression and stability of Fab antibody further.</p><p><strong>Results: </strong>A biotin-labeled salbutamol marker was synthesized, and two rabbit-derived salbutamol- Fab antibodies were screened in three weeks using fluorescence-activated cell sorting (FACS).</p><p><strong>Conclusion: </strong>After antigen-binding kinetic studies, the screened antibodies demonstrated good affinity and specificity.</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":"143491000","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":"Exploring the Blueprint of Life: The Innovation in Antibody and Protein Design.","authors":"Zhiwei Yang, Gerald H Lushington","doi":"10.2174/0113862073189534250217114015","DOIUrl":"https://doi.org/10.2174/0113862073189534250217114015","url":null,"abstract":"<p><p>The innovation in antibody and protein design highlights the transformation from empirical approaches to sophisticated strategies integrating computational methods and artificial intelligence (AI). Key principles, such as combinatorial, structure-based, consensus, and computational designs, have been pivotal in predicting structures from sequences (in silico design). Advances in tools, like AlphaFold and Rosetta suite, enable accurate structure prediction, facilitating the development of functional proteins and antibodies. However, challenges remain, including improving prediction accuracy, modeling flexible regions, understanding structural dynamics, and designing catalytic and binding sites. Despite these, the field promises groundbreaking advancements in biomedical sciences, enriching our understanding and serving human health and scientific discovery.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466942","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":"Investigation of LncRNA Expression Profiles and Analysis of Immune-Related lncRNA-miRNA-mRNA Networks in Neovascular Age-Related Macular Degeneration.","authors":"Liying Qin, Xiang Gao, Xiuhai Lu, Wencai Liu, Jingyi Tian, Gongqiang Yuan","doi":"10.2174/0113862073342212250102042734","DOIUrl":"https://doi.org/10.2174/0113862073342212250102042734","url":null,"abstract":"<p><strong>Introduction: </strong>Age-related Macular Degeneration (AMD) is a predominant cause of blindness in the elderly. The present study is the first to investigate the alteration of lncRNAs and mRNAs in neovascular AMD.</p><p><strong>Methods: </strong>Nine patients with neovascular AMD were included in the study. The control group comprised seven patients with epiretinal membranes. RNA sequencing was performed to obtain the differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs). Then, the DElncRNA-DEmRNA co-expression network, ceRNA network, and immune-related ceRNA subnetwork were constructed. Functional annotation of DEmRNAs between the two groups and DEmRNAs in networks was conducted. The immune cell distribution in neovascular AMD was also evaluated. Real-time qPCR (RT-qPCR) was used to validate the expression levels of key markers.</p><p><strong>Results: </strong>A total of 342 DEmRNAs and 157 DElncRNAs were obtained in neovascular AMD. Functional annotation indicated that these DEmRNAs significantly enriched immune systemrelated processes, such as positive regulation of B cell activation, immunoglobulin receptor binding, complement activation, and classical pathway. The DElncRNA-DEmRNA co-expression network, including 185 DElncRNA-DEmRNA co-expression pairs, and the ceRNA (DElncRNA-miRNA-DEmRNA) network, containing 45 lncRNA-miRNA pairs and 73 miRNAmRNA pairs, were constructed. The immune-related ceRNA subnetwork, including 2 lncRNAs, 5 miRNAs, and 3 mRNAs, was constructed. In addition, the distribution of immune cells was slightly different between the neovascular AMD group and the control group. RT-qPCR validation indicated the consistency between the RT-qPCR results and RNA sequencing results.</p><p><strong>Conclusion: </strong>In conclusion, STC1, S100A1, MEG3, MEG3-hsa-miR-608-S100A1, and MEG3- hsa-miR-130b-3p/hsa-miR-149-3p-STC1 may be related to the occurrence and development of neovascular AMD.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406187","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":"Therapeutic Potential of Desert Truffles in the Management of Eye Infections: Demystifying the Fact.","authors":"Md Abul Barkat","doi":"10.2174/0113862073356481250128045428","DOIUrl":"https://doi.org/10.2174/0113862073356481250128045428","url":null,"abstract":"<p><p>Truffle, an ascomycetous, hypogeous macrofungi, has long been recognized and valued for its therapeutic and dietary properties. Of late, a range of medicinal compounds, such as ergosterol, tuberoside anandamide, polysaccharides, and phenolics exhibiting anti-inflammatory, immunomodulatory, anticancer, antibacterial, and aphrodisiac properties have been identified in truffles. This review provides an update on contemporary truffle research with a focus on antimicrobial potentials and aims to draw the attention of researchers to exploit the therapeutic potential of truffles in the management of eye infections. The scholarly literature pertaining to the utilization of desert truffles in the management of ocular infections was systematically summarized and reviewed from multiple databases, including Scopus, Web of Science Core Collection, PubMed, and others. The essence of truffle is used as a remedy for trachoma and as an antiinflammatory agent for ocular problems. The most probable inhibitory constituents are the fungal lectins, polysaccharides, and laccases. Truffle lectins possess the ability to identify and remove bacterial exopolysaccharides. In addition, the fungal polysaccharides affect the bacterial defensive systems. Conversely, laccases facilitate the process of oxidizing phenols, resulting in the release of superoxide anion radicals and the production of hydrogen peroxide. The application of desert truffles in addressing ocular issues has been clinically observed to be satisfactory. The existing literature clearly indicates a pressing need for further investigation into the translation of the antimicrobial properties of crude truffle extract into truffle-based pharmaceutical formulations for clinical application.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390444","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 NR4A2 as a Potential Predictive Biomarker for Atherosclerosis.","authors":"Lebin Yuan, Ruru Bai, Xinhao Han, Jiajia Xiang","doi":"10.2174/0113862073357411250127080814","DOIUrl":"https://doi.org/10.2174/0113862073357411250127080814","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis, a leading cause of death globally, is characterized by the buildup of immune cells and lipids in medium to large-sized arteries. However, its precise mechanism remains unclear.</p><p><strong>Objective: </strong>The purpose of this study is to explore innovative and reliable biomarkers as a viable approach for the identification and management of atherosclerosis.</p><p><strong>Methods: </strong>The atherosclerosis-related datasets GSE100927 and GSE66360 were retrieved from the Gene Expression Omnibus (GEO) database. The Limma package in the R programming language was utilized, applying the criteria of |logFC| > 1 and P < 0.05. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the 127 identified DEGs using R. Machine learning techniques were then applied to these data to explore and pinpoint potential biomarkers. The diagnostic potential of these markers was assessed via Receiver Operating Characteristic (ROC) curve analysis. Finally, Western Blot, real-time quantitative PCR (qRT-PCR), and immunohistochemistry (IHC) were employed to confirm the key biomarkers.</p><p><strong>Results: </strong>Our research indicated that a total of 127 DEGs linked to atherosclerosis were successfully identified. Through the application of machine learning methods, eight critical genes were highlighted. Among these, Nuclear Receptor Subfamily 4 Group A Member-2 (NR4A2) emerged as the most promising marker for further investigation. CIBERSORT analysis revealed that NR4A2 expression levels were significantly correlated with multiple immune cell types, including B cells, plasma cells, and macrophages. Additional validation experiments confirmed that NR4A2 expression was indeed elevated in atherosclerotic plaques, supporting its potential as a biomarker for atherosclerosis.</p><p><strong>Conclusion: </strong>Our study identified NR4A2 as a potential immune-related biomarker for the diagnosis and treatment of atherosclerosis.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390402","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":"The Role of Jianpi Jiedu Recipe in Modulating the CRC Microenvironment.","authors":"Mengyao Li, Dongming Hua, Yuanyuan Feng, Zhiyan Wang, Xueqing Hu, Yan Wang","doi":"10.2174/0113862073339913241214051331","DOIUrl":"https://doi.org/10.2174/0113862073339913241214051331","url":null,"abstract":"<p><strong>Background: </strong>The anti-tumor effects of Traditional Chinese Medicine has been recognized in regulating the tumor microenvironment. Jianpi Jiedu Recipe (JPJDR) is clinically effective in enhancing the chemotherapy efficacy in Colorectal Cancer (CRC) treatment and significantly improved the quality of life of CRC patients. However, its therapeutic mechanism remains to be investigated.</p><p><strong>Material and methods: </strong>The active compounds of each herb in JPJDR were obtained from the HIT2.0 and HERB databases supported by evidence in literature. Single-cell RNA sequencing data of CRC were obtained from published studies (PMID: 32451460, 32103181, and 32561858). Pathway enrichment was analyzed using the reactome database, and gene correlation analysis was performed using the corrplot R software package. Gene expression regulated by JPJDR was verified by RT-qPCR.</p><p><strong>Results: </strong>Ye Pu Tao Teng, Ba Yue Zha, Huang Qi, Bai Zhu, Yi Yi Ren and Dang Shen contained 4,7, 18, 26,3 and 30 compounds, respectively, and they target to 38, 7, 262, 309, 50, 54 genes, respectively. JPJDR is involved in a range of immune-related biological processes, including cytokine signaling, cell proliferation, apoptosis and cellular senescence. JPJDR regulates various cell types in the CRC microenvironment, including malignant CRC cells, immune cells (including CD4+ T cell, CD8+ T cell, B cell, plasma cell, mast cell, and myeloid cell), and stromal cells (including fibroblast, pericyte, enteric glial cell, and endothelial cell). We confirmed that JPJDR significantly downregulated the expression of HMGB1 and MT2A in CRC.</p><p><strong>Conclusions: </strong>JPJDR regulates a range of cell types in the CRC microenvironment, including malignant CRC, immune cells and stromal cells. Downregulation of HMGB1 and MT2A might be the important mediators for JPJDR to modulate the CRC microenvironment.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390405","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}