Current medicinal chemistry最新文献

{"title":"Resilience Against Resistance: Exploring Cutting-edge Therapies for Methicillin-resistant Staphylococcus aureus (MRSA).","authors":"Ravinder Sharma, Vikas Gupta, Bharat Parashar, Viney Chawla, Pooja A Chawla","doi":"10.2174/0109298673316661241002060518","DOIUrl":"https://doi.org/10.2174/0109298673316661241002060518","url":null,"abstract":"<p><p>Methicillin-resistant Staphylococcus aureus [MRSA] stands as an enduring threat within healthcare landscapes, characterized by its ability to rapidly evolve and develop resistance to conventional antibiotics. This comprehensive review embarks on a journey through the historical landscape of MRSA, elucidating its initial emergence and subsequent evolution of resistance mechanisms over time. The narrative unfolds to underscore the profound impact of MRSA on patient outcomes and healthcare systems globally. Current trends in MRSA therapies come under meticulous scrutiny, spotlighting the limitations and challenges associated with existing treatment modalities. This analysis underscores the critical need for transformative and innovative therapeutic strategies to effectively combat the ever-growing spectre of drug resistance in MRSA from the exploration of novel antibiotics designed to overcome resistance mechanisms to the promising potential of phage therapy and immunotherapies. Amidst the exploration of innovative therapies, the review identifies and discusses emerging issues and challenges in MRSA management. Insights are provided into the intricate web of obstacles hindering the adoption and implementation of new therapeutic strategies. Furthermore, the socio-economic implications of MRSA and drug resistance are brought to the forefront, emphasizing the broader impact on public health and healthcare systems. In parallel, historical perspectives on MRSA research illuminate key milestones in scientific understanding and technological advancements. The evolution of research strategies and their impact on our ability to comprehend and combat MRSA is examined, providing context for the current state of the field. In conclusion, this review summarizes major findings and drawing implications for the future of MRSA treatment. Recommendations for further research and clinical practice are outlined, encapsulating a holistic overview of the resilient efforts against resistance in the ongoing battle against MRSA.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460082","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":"Citrullination Accompanies the Development of Carotid Atherosclerotic Plaques.","authors":"Anastasia Kanonykina, Elena Velikanova, Victoria Markova, Leo Bogdanov, Daria Shishkova, Amin Shabaev, Maxim Sinitsky, Anna Sinitskaya, Alyona Poddubnyak, Anastasia Lazebnaya, Alexander Stepanov, Arina Tyurina, Arseniy Lobov, Bozhana Zainullina, Arseniy Yuzhalin, Anton Kutikhin","doi":"10.2174/0109298673327175240929222308","DOIUrl":"https://doi.org/10.2174/0109298673327175240929222308","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Citrullination represents a post-translational modification primarily mediated by peptidylarginine deiminase (PADI) 2 and 4 and resulting in the conversion of positively charged peptidylarginine to neutrally charged peptidylcitrulline. Molecular consequences of citrullination include the generation of neoepitopes which provoke the production of autoantibodies implicated in the development of autoimmune diseases. As citrullination initiates, promotes, and is enhanced by aseptic inflammation which plays a pivotal role in atherosclerosis, we proposed that citrullination might accompany the development of atherosclerotic vascular disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate features and patterns of citrullination in atherosclerotic plaques.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We collected carotid atherosclerotic plaques (n = 14) and adjacent arterial segments (n = 14) which were pairwise excised during the carotid endarterectomy. The tissues were examined employing proteomic profiling (ultra-high performance liquid chromatography-tandem mass spectrometry analysis), haematoxylin and eosin staining, Western blotting and immunofluorescence staining for peptidylcitrulline, PADI2, and PADI4, and gene expression analysis. To better explore the mechanisms of citrullination in the neointima, we have also stained excised plaques for the extracellular vesicle markers (CD9 and CD81) and assessed co-localisation of PADI2 (a citrullination marker) with CD81 (an extracellular vesicle marker). In order to study the systemic response to citrullination in an atherosclerotic vascular disease setting, we measured the level of anti-citrullinated protein antibodies in the serum of patients with ischaemic stroke and healthy volunteers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Proteomic profiling found 213 plaque-specific and 111 intact arteria-specific proteins, as well as 46 proteins and 13 proteins which have been respectively upregulated or downregulated in plaques as compared with the adjacent intact segments. Among the top 20 upregulated proteins were atherogenic apolipoprotein B-100, iron-associated protein haptoglobin, and matrix metal-loproteinase-9, together indicating the advanced stage of plaque progression. In comparison with the intact arterial segments, plaques demonstrated protein signatures of innate immune response and oxidative stress, suggesting aseptic inflammation as a driver of atherosclerotic vascular disease. Both peptidylcitrulline and PADI2 have been abundant in the neointima but negligible in tunica media; further, the levels of peptidylcitrulline, PADI2, and PADI4 were elevated in plaque lysates in comparison with those from adjacent arterial segments (p = 0.025, 0.025, and 0.010, respectively). Notably, PADI2 and peptidylcitrulline were co-localised with the cells in the neointima and a considerable proportion of PADI2 was co-localised with CD81-positive extracellular vesicles (p = 0.003). Albeit citrullinated h","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460056","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":"Elucidating the Role of Autophagy-related Genes in Polycystic Ovary Syndrome: Implications for Diagnostic Models and Immune Response Regulation.","authors":"Nan Li, Kai Yu, Delun Huang, Hua Guo, Xuehong Zhu, Zhong Lin","doi":"10.2174/0109298673337033241010072529","DOIUrl":"https://doi.org/10.2174/0109298673337033241010072529","url":null,"abstract":"<p><strong>Background: </strong>Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder that negatively affects female reproductive capacity. Although the association between autophagy and PCOS is known, there are few detailed studies on the association between autophagy-related genes and PCOS.</p><p><strong>Methods: </strong>Publicly available gene expression datasets (GSE102293, GSE138518, GSE34526, GSE114419, GSE137684, GSE155489) were used in a comprehensive analysis to identify a role for autophagy in PCOS. Batch effects were mitigated using the sva package, followed by WGCNA (weighted gene correlation network analysis) and ss- GSEA (single sample gene set enrichment analysis) to identify autophagy-related genes. Recursive feature elimination (RFE) and LASSO COX methods were used to identify important hub genes, and their correlation with immune cell activity was assessed using ssGSEA and Pearson correlation analysis.</p><p><strong>Results: </strong>High autophagy scores were observed in PCOS samples, and the dark green gene module with the highest autophagy correlation was identified. The differential analysis identified a total of 169 up-regulated genes versus 2 down-regulated genes in the PCOS samples, which were intersected by taking the intersection with the deep green module genes and resulted in 121 key genes. Subsequently, 6 hub genes (MMP25, CSF3R, SLPI, MMP9, CLEC4E, and SIGLEC10) were further identified based on RFE and LASSO algorithms. Diagnostic efficacy based on ROC curves showed six autophagy- associated hub genes with AUC values as high as 0.959 and 0.896 in the training and validation sets, respectively. Finally, we observed that these hub genes are strongly associated with immune function, especially chronic inflammation and aberrant immune activation pathways.</p><p><strong>Conclusion: </strong>In this study, we identified autophagy genes closely related to PCOS and constructed a gene model with high diagnostic accuracy. These findings not only provided potential new biomarkers for the diagnosis of PCOS but also revealed the key role of autophagy in the pathogenesis of PCOS.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460069","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":"Integrative Analysis Reveals Differential Characteristics of DDR1 Mutant and Wild-type Gastric Cancers and Constructs their Prediction Models.","authors":"Yonggang Tian, Yunqian Xie, Guirong Yi, FuBing Yu, Feihu Bai, Jun Wang, Dekui Zhang","doi":"10.2174/0109298673319260241014054643","DOIUrl":"https://doi.org/10.2174/0109298673319260241014054643","url":null,"abstract":"<p><strong>Introduction: </strong>The molecular typing of gastric cancer by TCGA is significant for the precision treatment of gastric cancer. However, the molecular typing of gastric cancer by TCGA lacks the typing of the rare gene DDR1. Therefore, this study aimed to integrate the analysis to reveal the differential features of DDR1 mutant and wild-type gastric cancers and construct their prediction models.</p><p><strong>Methods: </strong>RNAseq data from 375 gastric cancer patients were downloaded from the TCGA database to comprehensively compare the differences between mutant DDR1 and wild-type DDR1 gastric cancers and construct a prognostic model for wild-type DDR1 gastric cancer.</p><p><strong>Results: </strong>First, the mutation rate of DDR1 in gastric cancer was 3.23%. Second, the upregulated genes of mutant DDR1 gastric cancer were different from those of wild-type DDR1 gastric cancer in terms of KEGG and GO enrichment. Next, both mutant DDR1 gastric cancers and wild-type DDR1 gastric cancers were associated with EPIC scores and tumour stemness in macrophages. In addition, mutant DDR1 gastric cancers were associated with the iron death-related genes RPL8, CS, and FANCD2 and the m6A-related gene RBM15, compared with wild-type DDR1 gastric cancers. Finally, the established LASSO regression model confirmed that the survival rate of the high-risk group of wild-- type DDR1 gastric cancer would be lower than that of the low-risk group.</p><p><strong>Conclusion: </strong>This study may provide a new molecular typing method for gastric cancer by comparing the differences between mutant DDR1 and wild-type DDR1 gastric cancer.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460075","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":"Thrombosis in Hypertension: Pathophysiology, Biomarkers, and the Effect of Antihypertensive Treatment.","authors":"Panagiotis Theofilis, Evangelos Oikonomou, Paschalis Karakasis, Kyriakos Dimitriadis, Marios Sagris, Athanasios Sakalidis, Emmanouil Mantzouranis, Panayotis K Vlachakis, Konstantinos Pamporis, Konstantinos Tsioufis, Dimitris Tousoulis","doi":"10.2174/0109298673324637240930140545","DOIUrl":"https://doi.org/10.2174/0109298673324637240930140545","url":null,"abstract":"<p><p>Hypertension, characterized by elevated blood pressure levels, remains a global health concern due to its association with cardiovascular complications, notably thrombosis. Thrombosis, the formation of blood clots within blood vessels, poses a significant risk for myocardial infarction, stroke, and limb ischemia, leading to adverse patient outcomes. Understanding the pathophysiological mechanisms underlying thrombosis in hypertension is crucial for developing effective preventive and therapeutic strategies. Hypertension induces structural and functional alterations in the vasculature, endothelium, and platelets, creating a prothrombotic milieu. Endothelial dysfunction, increased platelet activation, and alterations in coagulation factors contribute to the heightened thrombotic risk observed in hypertensive individuals. Biomarkers associated with thrombotic events, such as mean platelet volume, D-Dimer, and fibrinogen offer valuable insights into the pathogenesis of thrombosis and may serve as prognostic indicators for cardiovascular events in hypertensive populations. Investigating the impact of antihypertensive treatment on thrombotic risk is essential, as these medications exert pleiotropic effects on the vasculature and hemostatic system. By elucidating the intricate interplay between hypertension and thrombosis, this review aims to enhance our understanding of cardiovascular risk in hypertensive individuals and identify novel therapeutic targets for preventing thrombotic complications.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460090","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":"Molecular Docking in Drug Discovery: Techniques, Applications, and Advancements.","authors":"Cinthia Aguiar, Ihosvany Camps","doi":"10.2174/0109298673325827240926081845","DOIUrl":"https://doi.org/10.2174/0109298673325827240926081845","url":null,"abstract":"<p><p>The primary objective of this study is to conduct a comprehensive review of the significance of molecular docking in the field of drug discovery. This includes an examination of the various approaches and methods used in molecular docking, as well as an exploration of the techniques used for interpreting and validating docking results. To gather relevant data, a systematic search was conducted using Web of Science, PubMed, and Google Scholar. The search focused on articles related to molecular docking methodologies and their applications in drug discovery. Additionally, alternative techniques that can be used for more precise simulations of ligand-protein interactions were also considered. Molecular docking has proven to be an incredibly rich and valuable process in the field of drug discovery. Its flexibility allows for the incorporation of advanced computational techniques, thereby enhancing the reliability and efficiency of drug discovery processes. The results of the study highlights the significant strides made in the field of molecular docking, demonstrating its potential to revolutionize drug discovery. Molecular docking continues to evolve, with new advancements being made regularly. Despite the challenges faced, these advancements have significantly contributed to the enhancement of molecular docking, solidifying its position as a crucial tool in the field of drug discovery.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460078","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":"Parthenolide Inhibits Tumor Cell Growth and Metastasis in Melanoma A2058 Cells.","authors":"Zahra Dorostgou, Malihe Hoseyni, Afsaneh Bahrami, Rahele Zhiani, Mahnaz Mohtashami","doi":"10.2174/0109298673334309240924081449","DOIUrl":"https://doi.org/10.2174/0109298673334309240924081449","url":null,"abstract":"<p><strong>Background: </strong>Skin melanoma is a potentially lethal cancer and ranks as the 17th most common cancer worldwide. Overcoming resistance to advanced-stage melanoma is a significant challenge in its treatment. Parthenolide (PAR) is recognized as a potent anticancer small molecule, yet its potential in treating melanoma is poorly investigated.</p><p><strong>Objective: </strong>Our objective was to investigate the apoptotic and anti-metastatic properties of PAR against the A2058 melanoma cells in vitro.</p><p><strong>Methods: </strong>This study employed various assays, such as cytotoxicity, apoptosis, cell cycle analysis, reactive oxygen species (ROS) production, mRNA expressions, western blotting, gelatin zymography, and scratch assay. The synergy between PAR and dacarbazine, a chemotherapy drug for treating skin cancer, was also assessed.</p><p><strong>Results: </strong>Our study revealed that PAR significantly reduced the viability of A2058 cancer cells, demonstrating greater potency against cancer cells compared to normal L929 cells (IC50: 20 μM vs. 27 μM after 24h). PAR increased ROS production, elevated mRNA expression of pro-apoptotic Bax and NME1 genes, and decreased expression of the MITF gene. PAR induced apoptosis and cell cycle arrest in A2058 cells, as evidenced by the increased proportion of cells in the late apoptotic phase and sub-G1 cell cycle arrest. MMP-2 and MMP-9 mRNA and protein expressions, gelatinase activity, and the migration of A2058 cells were also decreased by PAR, suggesting its potential to suppress cancer cell invasion.</p><p><strong>Conclusion: </strong>These results, along with the synergic effect with dacarbazine, indicated that PAR may have the potential to be a therapeutic drug for melanoma by triggering apoptosis and suppressing invasion and migration.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460081","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":"Booming Artificial Intelligence in Oral Cancer Diagnosis: From Image Processing to Stage Classification.","authors":"Shankari Gopalakrishnan, Dhamodharan Prabhu, Subash C B Gopinath","doi":"10.2174/0109298673340864241004052149","DOIUrl":"https://doi.org/10.2174/0109298673340864241004052149","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460055","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":"Impact of Obesity, Menopause, and Depression in Women's Health: An Attempt to Decipher the Complex Relationship.","authors":"Pervej Alom Barbhuiya, Manash Pratim Pathak","doi":"10.2174/0109298673317600240930052201","DOIUrl":"https://doi.org/10.2174/0109298673317600240930052201","url":null,"abstract":"<p><strong>Background: </strong>Menopause symptoms may be distressing, especially when they appear at a time when women are expected to play significant responsibilities in society. Numerous biological systems are influenced by the hormonal changes that start during the menopausal transition. This review attempts to decipher the complex relationship between obesity, menopause, and depression, citing some recent longitudinal and cross-sectional studies. Additionally, this study provides a summary of the different phytoestrogens, their sources, and probable mechanisms of action in addition to available therapeutic alternatives.</p><p><strong>Methodology: </strong>For this review purpose, the authors have gone through a vast number of articles from various scientific databases like PubMed, Google Scholar, and Web of Science.</p><p><strong>Results: </strong>It is becoming clear that the physiological basis for these menopausal symptoms is complicated and connected to estrogen deficiency, but not alone. Other hormones like FSH, LH, progesterone, and inhibin B are the major ones that are both directly and indirectly responsible for most of the menopausal symptoms. Numerous longitudinal and cross-sectional studies have found a direct relationship between the incidence of menopause and depression as well as obesity. Phytoestrogens like stilbene, lignans, isoflavone, and coumestan have been reported to be the alternatives to synthetic estrogen with lesser side effects, as reported in various studies.</p><p><strong>Conclusion: </strong>The complex relationship between depression, menopause, and obesity presents a complex obstacle to women's health and overall well-being. There might be a lot of promising prospects for revolutionary advancements in women's health during the menopausal stage in the future. Promising drug development that targets not just one but also the three conditions -obesity, menopause, and depression - as well as more thorough research are needed to improve the healthcare system for women who suffer from these conditions.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460074","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":"Development and Validation of a Cholesterol-related Gene Signature for Prognostic Assessment in Head and Neck Squamous Cell Carcinoma.","authors":"Jiarong Zheng, Dalong Shu, Rongwei Xu, Yucheng Zheng, Pei Lin, Yunfan Lin, Xinyuan Zhao, Li Cui, Xin Liao, Bing Guo","doi":"10.2174/0109298673336147241010065340","DOIUrl":"https://doi.org/10.2174/0109298673336147241010065340","url":null,"abstract":"<p><strong>Aim: </strong>This study seeks to develop a prognostic risk signature for head and neck squamous cell carcinoma (HNSCC) based on cholesterol-related genes (CholRG), aiming to enhance prognostic accuracy in clinical practice.</p><p><strong>Background: </strong>HNSCC poses significant challenges due to its aggressive behavior and limited response to standard treatments, resulting in elevated morbidity and mortality rates.In order to improve prognostic prediction in HNSCC, our study is inspired by the realization that cholesterol metabolism plays a critical role in accelerating the progression of cancer. To this end, we are developing a unique risk signature using CholRG.</p><p><strong>Objective: </strong>The aim of this study was to create a CholRG-based risk signature to predict HNSCC prognosis, aiding in clinical decision-making accurately.</p><p><strong>Method: </strong>The TCGA HNSCC dataset, along with GSE41613 and GSE65858, was obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, respectively. A CholRG-based risk signature was then developed and validated across various independent HNSCC cohorts. Moreover, a nomogram model incorporating CholRG-based risk signature was established. Additionally, functional enrichment analysis was conducted, and the immune landscapes of the high- and low-risk groups were compared. Finally, in vitro experiments were performed using lipid-based transfection to deliver siRNAs targeting ACAT1 to SCC1 and SCC23 cell lines, further examining the effects of ACAT1 knockdown on these cells.</p><p><strong>Results: </strong>Utilizing RNA-seq, microarray, and clinical data from public databases, we constructed and validated a CholRG-based risk signature that includes key genes such as ACAT1, CYP19A1, CYP27A1, FAXDC2, INSIG2, PRKAA2, and SEC14L2, which can effectively predict the clinical outcome of HNSCC. Additionally, our findings were reinforced by a nomogram model that integrates the risk score with clinical variables for more clinically practical prognostic assessment. In addition, patients at high risk show hypoxia and increased oncogenic pathways such as mTORC1 signaling, as well as a suppressed immune microenvironment marked by a reduction in the infiltration of important immune cells. Notably, in vitro experiments showed that ACAT1 depletion significantly suppressed the proliferation, colony formation, and invasion capabilities of HNSCC cells, confirming ACAT1's role in promoting malignancy.</p><p><strong>Conclusion: </strong>Collectively, our study not only underscores the importance of cholesterol metabolism in HNSCC pathogenesis but also highlights the CholRG-based risk signature as a promising tool for enhancing prognostic accuracy and personalizing therapeutic strategies.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460068","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}