Current medicinal chemistry最新文献

{"title":"Genetic Studies on Multiple Consanguineous Families Segregating Diverse Phenotypes of Microphthalmia Identified Novel and Recurrent Mutations.","authors":"Kashmala Samad, Fazeelat Samad, Abdulfatah M Alayoubi, Aisha Siddiqua, Mohammed Turki Hussain Alharthi, Hussam Baghdadi, Sumra Wajid Abbasi, Muzammil Ahmad Khan, Muhammad Latif","doi":"10.2174/0109298673365255250418092319","DOIUrl":"https://doi.org/10.2174/0109298673365255250418092319","url":null,"abstract":"<p><strong>Introduction: </strong>Anophthalmia/microphthalmia (A/M) and anterior segment dysgenesis (ASD) are severe ocular anomalies impacting eye morphology, occurring in 30 per 100,000 live births. Genetic research has identified over 30 genes linked to A/M anomalies, with their products mainly involved in eye organogenesis.</p><p><strong>Aims and objectives: </strong>This study examined two consanguineous A/M families to identify disease-associated pathogenic mutations and predict their functional impact.</p><p><strong>Methodology: </strong>Patients were clinically examined using A-scan and ophthalmic ultrasonography. Whole exome sequencing (WES) identified candidate pathogenic variants validated through Sanger sequencing. Computational analyses assessed the impact of these mutations on protein structure and function.</p><p><strong>Results: </strong>The clinical diagnosis of family A revealed microphthalmia with ASD, while family B presented with an A/M phenotype. Exome analysis of family A identified a novel missense variant, NM_012293:c.A3742G [p.(Arg1248Gly)], in the peroxidasin (PXDN) gene (ClinVar ID: VCV001333267.1). At the cellular level, PXDN is involved in establishing sulfilimine bonds in collagen IV, a component of the basement membrane, suggesting that ocular defects may result from impaired integrity of the basement membrane in the developing eye. In contrast, Family B exhibited a nonsense variant NM _012186:c.720C>A (p.- Cys240*) in the FOXE3 gene. This variant has been previously reported in other South Asian populations, suggesting a founder effect in subcontinent populations. Structural modeling and simulation analysis of mutant proteins revealed altered properties, thus corroborating the pathogenicity of the identified mutation.</p><p><strong>Conclusion: </strong>Our findings may contribute to the elucidation of genotype-phenotype correlations, potentially facilitating the molecular diagnosis of microphthalmia and ASD.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982254","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":"Spinosin Suppresses RANKL-induced Osteoclastogenesis and Alleviates LPS-induced Cranial Osteolysis: A Study Based on Network Pharmacology and Experimental Validation.","authors":"Qi Meng, Yang Su, Shankun Dong, Jianxun Ge, Lei Tian, Shui Sun","doi":"10.2174/0109298673371731250415115235","DOIUrl":"https://doi.org/10.2174/0109298673371731250415115235","url":null,"abstract":"<p><strong>Aim: </strong>Inflammatory osteolysis often characterizes many orthopedic diseases, with an important role played by the overactivity of osteoclasts. This research endeavoured to investigate the effects of spinosin, a potent ingredient in traditional Chinese medicine, on Lipopolysaccharide (LPS)-induced osteoclast activity and formation to alleviate osteolysis.</p><p><strong>Methods: </strong>Based on the molecular structure of spinosin, network pharmacology was used to predict its primary targets and mechanisms. LPS was used to stimulate pre-osteoclasts and to simulate an inflammatory environment. The effect of spinosin on osteoclast biology was subsequently examined via morphological study, qPCR, and western blot (WB). Moreover, LPS-induced cranial osteolysis mice were utilized, followed by micro- CT analysis, to reveal the curative effects in vivo.</p><p><strong>Results: </strong>Network pharmacology and molecular docking suggested that EGFR and Akt might be the key targets for the efficacy of spinosin in inflammatory osteolysis. The results of in vitro experiments demonstrated that spinosin significantly inhibited osteoclast function and activity in the inflammatory environment, and this effect might be achieved through regulating EGFR-Akt signaling. The results of animal experiments also showed spinosin-protected mice against LPS-induced bone loss.</p><p><strong>Conclusion: </strong>Spinosin can inhibit EGFR-mediated Akt phosphorylation, which in turn negatively affects downstream Nfatc1-mediated osteoclast-associated gene expression and subsequent osteoclast formation and functionality, mitigating the LPS-induced osteolysis. Our study proves that spinosin holds the promise of being an innovative drug to prevent inflammatory osteolysis.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983128","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":"Insights into the Antiparasitic Activity of Pyrazole-benzimidazole against Trypanosoma cruzi.","authors":"Vitoria Barbosa Paes, Leonardo da Silva Lara, Lorraine Martins Rocha Orlando, Guilherme Curty Lechuga, Thamyris Pérez de Souza, Byanca Silva Ferreira, Mariana de Oliveira Zago, Maurício Silva Dos Santos, Mirian Claudia de Souza Pereira","doi":"10.2174/0109298673342932241016032905","DOIUrl":"https://doi.org/10.2174/0109298673342932241016032905","url":null,"abstract":"<p><strong>Background: </strong>Chagas disease (CD), a life-threatening disease caused by Trypanosoma cruzi, remains a significant global public health concern. The limited efficacy of the available drugs (nifurtimox and benznidazole), their severe adverse events, and the unsatisfactory outcomes of clinical trials drive the search for new, effective, and safe drugs.</p><p><strong>Objective: </strong>This study describes the synthesis, structural characterization, and in vitro antiparasitic activity of novel pyrazole-benzimidazole derivatives against mammalian developmental stages of T. cruzi.</p><p><strong>Methods: </strong>Phenotypic screening was used to assess the effect of pyrazole-benzimidazole derivatives against T. cruzi. Three-dimensional cardiac spheroids were employed to evaluate the toxic effect and drug efficacy. Molecular docking and cysteine protease activity were also performed.</p><p><strong>Results: </strong>Pyrazole-benzimidazole derivatives showed activity against both trypomastigotes and intracellular amastigotes. Compounds 1i (IC50 = 6.6 μM) and 1j (IC50 = 9.4 μM) demonstrated the most potent activity with a high selectivity index (SI > 45) against intracellular amastigotes. Both compounds exhibited high efficacy on 3D cardiac spheroids, effectively reducing the parasite load by over 80%. Molecular docking analysis revealed that both compounds target the catalytic domain of cruzain through pi-stacking and hydrogen bonding interactions and inhibit T. cruzi cysteine protease. These derivatives also showed an additive effect in combination with the reference drug (Bz).</p><p><strong>Conclusion: </strong>Our findings emphasize the significance of pyrazole-benzimidazole hybrids in the search for new anti-T. cruzi agents.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990114","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":"Research Progress on the Effect of Exercise on Homocysteine.","authors":"Yanli Yu, Dong Wang","doi":"10.2174/0109298673354271250413015339","DOIUrl":"https://doi.org/10.2174/0109298673354271250413015339","url":null,"abstract":"<p><p>The effect of exercise on homocysteine (Hcy) levels is multifaceted and varies significantly across different populations. This review investigates how various exercise modalities-moderate to vigorous physical activity, acute intense exercise, aerobic exercise, and resistance training-affect Hcy concentrations, alongside the influence of demographic and health-related factors. Generally, moderate to vigorous physical activity is associated with lower Hcy levels, potentially reducing cardiovascular risk. In contrast, acute high-intensity exercises may temporarily increase Hcy levels due to immediate metabolic responses and oxidative stress. The effects of exercise on Hcy levels are influenced by age, sex, baseline health status, nutritional intake, fitness level, exercise type, and genetic factors. Aerobic exercise has been shown to improve cardiovascular and neuroprotective outcomes but may not significantly affect Hcy levels in the long term. Conversely, resistance training demonstrates varied effects, with some studies indicating significant reductions in Hcy levels, particularly in specific populations like overweight older adults, while others show negligible changes. Overall, while evidence supports the beneficial role of regular physical activity in modulating Hcy levels, the relationship is complex and affected by multiple factors. Further research is needed to clarify the underlying mechanisms and optimize exercise recommendations for different populations to control Hcy levels and associated health risks effectively.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062649","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 and Validation of BATF3 as a Promising Biomarker Gene for Peripheral T-cell Lymphoma.","authors":"Yidong Zhu, Jun Liu, Ting Zhang","doi":"10.2174/0109298673367678250414061434","DOIUrl":"https://doi.org/10.2174/0109298673367678250414061434","url":null,"abstract":"<p><strong>Background: </strong>Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of hematological malignancies. Treatment options are limited and often unsatisfactory, leading to a poor prognosis in most subtypes.</p><p><strong>Objective: </strong>his study aimed to identify potential biomarker genes for PTCL and to explore the underlying mechanisms by integrating machine learning, Mendelian Randomization (MR), and experimental validation.</p><p><strong>Methods: </strong>Microarray datasets (GSE6338, GSE14879, and GSE59307) were downloaded from the Gene Expression Omnibus database. Differential expression analysis was conducted to identify the Differentially Expressed Genes (DEGs) between patients with PTCL and controls. A machine learning algorithm was then used to further refine the selection of characteristic genes for PTCL. We integrated genome-wide association studies data with expression quantitative trait loci data to identify genes with potential causal relationships to PTCL. Functional analysis was performed to explore underlying mechanisms. Finally, the identified gene was validated in clinical samples from patients with PTCL and controls.</p><p><strong>Results: </strong>Based on 60 DEGs, the least absolute shrinkage and selection operator algorithm identified nine characteristic genes for PTCL. MR analysis revealed 203 genes with causal effects on PTCL, ultimately identifying one co-expressed gene: Basic Leucine Zipper ATF-like Transcription Factor 3 (BATF3). It demonstrated good predictive performance across various PTCL subtypes, with AUC values ranging from 0.7 to 1. Functional analysis suggested that BATF3 may play a role in PTCL through immune- related pathways. Experimental validation using clinical samples further suggested the potential of this biomarker gene in PTCL.</p><p><strong>Conclusion: </strong>By combining machine learning, MR, and experimental validation, we identified and validated BATF3 as a promising biomarker of PTCL. These findings provide insights into the molecular mechanisms underlying PTCL and may inform the development of effective treatment strategies for this disease.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972904","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":"Endothelial Function Biomarkers in Hypertension.","authors":"Panayotis K Vlachakis, Panagiotis Theofilis, Efstathios Manios, Anastasios Tentolouris, Maria Drakopoulou, Paschalis Karakasis, Aikaterini Vordoni, Eleni Korompoki, Evangelos Oikonomou, Costas Tioufis, Dimitrios Tousoulis","doi":"10.2174/0109298673349473250410132823","DOIUrl":"https://doi.org/10.2174/0109298673349473250410132823","url":null,"abstract":"<p><p>Hypertension (HTN) is a major cardiovascular risk factor, contributing to over 10.4 million deaths annually. HTN's pathophysiology involves complex mechanisms, including altered vascular resistance and hormonal regulation. Endothelial dysfunction, a hallmark of HTN, is characterized by reduced vasodilator production and increased vasoconstrictor and inflammatory cytokine generation, leading to elevated blood pressure (BP) and vascular damage. Early detection and intervention are crucial to prevent long-term complications. Identifying biomarkers of endothelial function in HTN can aid early disease detection and offer insights into underlying mechanisms. Blood sample-derived biomarkers include nitric oxide (NO), asymmetric dimethylarginine (ADMA), matrix metalloproteinases (MMPs), vascular cell adhesion molecule-1 (VCAM- 1), intercellular adhesion molecule-1 (ICAM-1), and endothelial microparticles. Imaging-based biomarkers such as flow-mediated dilation (FMD) and coronary flow reserve (CFR) are also significant. These biomarkers provide the means to identify inflammation, endothelial dysfunction, and vascular injury, enhancing disease pathogenesis understanding. Combined with accurate BP measurements, they contribute to early diagnosis and provide valuable insights that may inform treatment strategies. Baseline and sequential plasma biomarker measurements also indicate treatment efficacy. However, large-scale, prospective population studies are necessary to fully validate these biomarkers for clinical use.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987314","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":"Azole Homodimers as Promising Antifungal Agents: Synthesis, Biological Activity Evaluation and Molecular Modeling.","authors":"Sergey N. Lavrenov, Alexander Yu. Simonov, Alexey A. Panov, Svetlana E. Solovieva, Alexey B. Mantsyzov, Andrei V. Churakov, Alexey S. Trenin, Igor B. Levshin","doi":"10.2174/0109298673351661241219053546","DOIUrl":"10.2174/0109298673351661241219053546","url":null,"abstract":"<p><strong>Introduction: </strong>A new series of triazoles with antifungal activity have been synthesized in a one-step fashion by direct reaction of 2-(2,4-difluorophenyl)-2,3-epoxy-1-(1H-1,2,4-triazol-1-yl)propane with various diamines.</p><p><strong>Method: </strong>Obtained compounds were profiled for biological activity against pathogenic strains of fungi C. albicans and A. niger. Molecular modeling was used to predict binding modes.</p><p><strong>Result: </strong>The lead compound was 4 times more active against C. albicans than fluconazole and demonstrated a wider spectrum of activity, inhibiting the growth of A. niger.</p><p><strong>Conclusion: </strong>The results presented herein can contribute to the development of novel antifungal therapeutic agents.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996105","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 Pre-metastatic Niche-related Index Reveals the Immune Signature and Immunotherapy Response in Lung Adenocarcinoma.","authors":"Weichang Yang, Zhijian Wu, Shanshan Cai, Jiajia Xiang, Xiaoqun Ye","doi":"10.2174/0109298673354164250414003620","DOIUrl":"https://doi.org/10.2174/0109298673354164250414003620","url":null,"abstract":"<p><strong>Background: </strong>Metastasis is the leading cause of death in lung cancer patients. Pre-metastatic niche (PMN) plays an important role in pre-metastatic tumors. However, the development of clinical applications of PMN is still limited.</p><p><strong>Methods: </strong>Expression data for lung adenocarcinoma (LUAD) patients and PMN-related genes were downloaded from the UCSC Xena website and GeneCards database, respectively. Multiple combinations based on machine learning algorithms were used to screen signature genes and construct a PMN-associated index. Spearman analysis explored the correlation between the PMN-associated index and immune cell infiltration. In addition, we analyzed the clinical value of the PMN-associated index based on drug sensitivity analysis and TIDE scores.</p><p><strong>Results: </strong>The enrichment analyses suggested that PMN-related genes were mainly enriched in the PI3K-Akt and HIF-1 signaling pathways. We chose random survival forest, Lasso, and multivariate Cox regression analyses to construct the PMN-associated index based on the results of multiple machine learning algorithms. Six signature genes (SNAI2, CXCR4, TNFSF11, ENG, TIMP1, and PDGFB) were screened to construct the PMN-associated index. KM analysis suggested that the survival probability was greater in the low PMN-associated index group than in the high PMN-associated index group. In addition, we confirmed that LUAD patients with a low PMN-associated index were more likely to benefit from immunotherapy.</p><p><strong>Conclusion: </strong>We confirmed that the PMN-associated index is a valid predictor of prognosis, immune characteristics, and antitumor therapy efficacy in LUAD patients, which provides additional evidence for the potential clinical value of PMN development.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994325","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":"Melittin Inhibits Ovarian Cancer Cell Growth by Downregulating MMP9 Expression via the JAK2-STAT3 Signaling Pathway.","authors":"Hongyi Sun, Jie Ding, Yujia Jiang, Danying Zhang, Jin Yu, Shuai Sun, Jing Zhou, Chaoqin Yu","doi":"10.2174/0109298673355946250403071132","DOIUrl":"https://doi.org/10.2174/0109298673355946250403071132","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the target sites, core pathways, and mechanisms of action of melittin in treating ovarian cancer through network pharmacology, molecular docking, and experimental verification.</p><p><strong>Methods: </strong>Potential targets for melittin in ovarian cancer treatment were predicted using databases, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The binding of the drug to these targets was confirmed through molecular docking. The core targets and pathways were experimentally validated. A tumor-bearing nude mouse model was established, with the mice randomly divided into treatment and control groups. The treatment group received 5 mg/kg of melittin by intraperitoneal injection, whereas the control group received saline injections. Changes in mouse weight and tumor volume were monitored, and protein expression in mouse tumor tissues was assessed via immunohistochemistry and Western blotting at the end of the experiment.</p><p><strong>Results: </strong>Fifty-three common targets between melittin and ovarian cancer were identified in the SEA and GeneCards databases. The Protein-Protein Interaction (PPI) analysis highlighted core targets, including MMP9, STAT3, MMP2, STAT6, FURIN, and BRCA1. The GO enrichment results were related mainly to the metabolic processes of collagen degradation, extracellular matrix disassembly, external encapsulating structures, and phospholipase C-activated G-protein-coupled receptor signaling pathways. The KEGG pathway analysis revealed the enrichment of genes related to estrogen signaling, necroptotic apoptosis, the FoxO signaling pathway, microRNAs in cancer, the JAK-STAT signaling pathway, proteoglycans in cancer, and receptor-mediated carcinogenesis. Cell Counting Kit-8 (CCK8) assays, scratch wound healing tests, and Transwell invasion assays demonstrated that melittin significantly inhibited the proliferation, migration, and invasion of ovarian cancer cells. The Western blot results indicated that melittin downregulated the levels of p-JAK2, p-STAT3, and MMP9 in ovarian cancer cells. Molecular docking demonstrated that melittin bound stably to MMP9 and STAT3. The results of animal experiments indicated that melittin suppressed the growth of ovarian tumors in nude mice and significantly downregulated the expression of MMP9, p-JAK2, and p-STAT3 in tumor tissues (p<0.05).</p><p><strong>Conclusion: </strong>Melittin may inhibit the growth of ovarian cancer cells by downregulating MMP9 expression via the JAK2-STAT3 signaling pathway, thus exerting a therapeutic effect.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965278","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":"Comparative Glycoproteomic Analysis of Mouse 4T1 Breast Cancer Model.","authors":"Aik-Aun Tan, Yin-Ling Wong, Subash C B Gopinath, Lik Voon Kiew, Sreenivasan Sasidharan, Yeng Chen","doi":"10.2174/0109298673360978250329065548","DOIUrl":"https://doi.org/10.2174/0109298673360978250329065548","url":null,"abstract":"<p><strong>Background: </strong>Glycosylation is a post-translational modification process that plays a fundamental role in malignant transformation. Moreover, aberrant glycosylation is known to be associated with cancer progression. Thus, the characterization of cancer-specific protein glycosylation profiles might reveal important diagnostic and/or prognostic biomarkers for cancer.</p><p><strong>Objective: </strong>In the present study, we have analysed serum protein and glycoprotein profiles during breast cancer progression using a mouse model. Specifically, 4T1 tumour cells were injected into the mammary fat pad of BALB/c mice to induce tumours.</p><p><strong>Methods: </strong>Sera samples were subsequently collected weekly for four weeks and examined using two-dimensional electrophoresis (2D-E) coupled with lectin-based analysis, followed by mass spectrometry.</p><p><strong>Results: </strong>This glycoproteomic profiling identified eight differentially expressed proteins, of which alpha-1 protease inhibitor 2, contraption (CON), haptoglobin (HP), and kininogen-1 were significantly up-regulated during the first 4 weeks of tumour progression. Notably, aberrantly N-glycosylated prothrombin was also detected in sera samples from all mice over the 4 weeks post-tumour injection. Additionally, O-glycosylated alpha-2-macroglobulin, CON, and HP were detected in weeks 1 and 2, whereas O-glycosylated alpha-2-HS-glycoprotein and CON were detected on weeks 3 and 4 post-implantation.</p><p><strong>Conclusion: </strong>Our findings indicate that the combination of 2D-E with lectin-based chromatography represents an effective approach for identifying prognostic biomarkers for breast cancer.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986499","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}