Current medicinal chemistry最新文献

{"title":"Comparison of the Safety and Efficacy of Ciprofol Versus Propofol for Induction and Maintenance of General Anesthesia in Patients Under-going Thoracoscopic Surgery: A Prospective Randomized Controlled Trial.","authors":"Ying Wang, Baoling Zhao, Yiming Lin, Can Zhang, Huidan Zhou, Kangjie Xie","doi":"10.2174/0109298673352340250623105441","DOIUrl":"https://doi.org/10.2174/0109298673352340250623105441","url":null,"abstract":"<p><strong>Objective: </strong>Ciprofol is a novel sedative-anesthetic that functions similarly to propofol. This study aimed to evaluate the efficacy and safety of ciprofol for the induction and maintenance of general anesthesia in patients undergoing thoracoscopic surgery.</p><p><strong>Methods: </strong>A total of 120 patients undergoing thoracoscopic surgery for pulmonary nodules under general anesthesia were randomly assigned to the ciprofol group or the propofol group. Patients in the ciprofol group received an initial dose of 0.4 mg.kg-1 of ciprofol for anesthesia induction, followed by an infusion rate ranging from 0.4 mg.kg-1.h-1 to 2.4 mg.kg-1.h-1 for maintenance. In the propofol group, patients were administered an initial dose of 2.0 mg.kg-1 of propofol for induction, with a maintenance infusion rate ranging from 4.0 mg.kg-1.h-1 to 12 mg.kg-1.h-1. The primary outcome measured was the success rate of sedation. Secondary outcomes included the time to successful induction of anesthesia, changes in hemodynamics and bispectral index (BIS) within 10 minutes after the initial administration of the study medication, time to respiratory recovery and full alertness, and the incidence of adverse events.</p><p><strong>Results: </strong>The sedation success rate was 100% in both groups. In this study, statistical analyses revealed no significant differences in the time to eyelash reflex disappearance (p=0.599), induction success time (p=0.431), the moment when the BIS value first fell below 60 (p=0.538), the time to respiratory recovery (p=0.505), or the interval until full wakefulness (p=0.837). Notably, within the first 10 minutes following the initial administration of the study medication, the reduction in blood pressure was significantly more pronounced in the propofol group (p<0.05). Additionally, the mean BIS value was significantly higher in the propofol group (p<0.01). The required dosage of sedative medication was significantly lower in the ciprofol group (p<0.001). Compared to the propofol group, the ciprofol group exhibited a significant reduction in the incidence of adverse events during intubation (p=0.01), a marked decrease in injection pain (p=0.001), and a significant decrease in the incidence of intraoperative hypotension (p<0.05).</p><p><strong>Conclusion: </strong>Ciprofol exhibits comparable efficacy and safety profiles for both the induction and maintenance of general anesthesia in patients undergoing thoracoscopic surgery. Furthermore, it has been associated with a reduced dosage requirement, significantly lower mean BIS values, and a notable decrease in the incidence of injection pain and intraoperative hypotension.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583340","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":"Core Neuroinflammatory Pathways Contributing to Delayed Encephalopathy After Acute Carbon Monoxide Poisoning Revealed by Multi-omics and Single Nucleus RNA-Seq.","authors":"Jinlan Li, Jun Li, Junming Fu, Chuying Huang, Wenqi Lv, Chunlong Zhang, Tianjie Tian, Qunhui Liu, Shijun Yang, Yong Tan, Guogen Sun, Ying Xiang, Guoquan Huang, Ning Wang","doi":"10.2174/0109298673407372250623101809","DOIUrl":"https://doi.org/10.2174/0109298673407372250623101809","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The pathogenesis of Delayed Encephalopathy After Acute Carbon Monoxide Poisoning (DEACMP) remains mysterious, and specific predictive markers are lacking. This study aimed to elucidate the molecular underpinnings and identify predictive biomarkers of DEACMP through multi-omics and single-nucleusRNA sequencing (snRNA-seq).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Clinical data and blood samples were collected from 105 participants. Untargeted metabolomics sequencing was employed to profile serum metabolites across these participants. Additionally, individuals from the Healthy Controls (HCs), Acute Carbon Monoxide Poisoning patients (ACOP), Non-Delayed Encephalopathy After ACOP (DEACMP-N), and DEACMP groups (n=3 each) were randomly selected for transcriptome sequencing to identify potential predictive targets and pivotal signaling pathways associated with DEACMP. Furthermore, Severe DEACMP and Control rat models were established. Three rats from the Control, DEACMP, and DEACMP + Dexamethasone + Selenomethionine groups were selected for snRNA-seq. Immunofluorescence multiplexing and qRT-PCR (quantitative Reverse Transcription Polymerase Chain Reaction) were then performed to validate the identified predictive targets.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Analysis of clinical data from 105 participants highlights the pivotal role of inflammation in influencing the prognosis of carbon monoxide poisoning. Metabolomics analysis identified 19 metabolites that significantly differed between the DEACMP-N and DEACMP groups. Transcriptomics analysis of 12 participants indicated that DEACMP is primarily associated with six signaling pathways, including lysosome and tuberculosis. Considering that microglia are central nervous system immune effectors, the snRNA-seq analysis revealed altered gene expression and signaling pathways in microglia during DEACMP, with KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis highlighting neutrophil extracellular trap formation, lysosome, and tuberculosis as the predominant pathways. Differential gene analysis from transcriptome and snRNA-seq identified 28 genes differentially expressed in DEACMP. The STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) database, immune multiplexing, and qRT-PCR confirmed the pivotal role of the Ifngr1/Stat1/Ctss axis in DEACMP.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;This research identifies the Ifngr1/Stat1/Ctss axis as a key inflammatory mechanism in the pathogenesis of DEACMP, thereby clarifying previous uncertainties regarding the sequelae of carbon monoxide poisoning. The intersection of lysosomal and tuberculosis pathways, as revealed through metabolomic, transcriptomic, and single-nucleus RNA sequencing analyses-especially within microglia- offers novel mechanistic insights that could inform therapeutic interventions. While the integration of multiple omics methodologies enhances the robustness of these findings, their biological relevance to the pa","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583341","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":"Recent Advances in the Application of Mitochondria-targeted Fluorescent Probes.","authors":"Merve Inel, Ayşe Yildirim, Bahadir Ozturk, Mustafa Yilmaz","doi":"10.2174/0109298673368188250613112621","DOIUrl":"https://doi.org/10.2174/0109298673368188250613112621","url":null,"abstract":"<p><p>Mitochondria, the complex powerhouses of eukaryotic cells, lie at the core of energy production, metabolism, and signaling. Mitochondrial dysfunctions underlie a wide range of human diseases, and there is a need for simple and effective tools to target and study these organelles. This review focuses on the applications of mitochondria-targeted cationic probes. It provides an up-to-date review of recent publications investigating the effects of these cationic probes, which are designed to manipulate mitochondrial function and detect dysfunction in different cell lines. In addition, it analyzes the effects of mitochondria-targeted fluorescence cationic probes in vivo and in vitro studies, and their effects in probe studies.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575017","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":"Bridging Innovation: Exploring the Versatility of Value-added Biosurfactants Across Diverse Applications.","authors":"Sachin S Mali, Sudarshan Singh, Riya R Patil, Prajakta R Patil","doi":"10.2174/0109298673376660250612103900","DOIUrl":"https://doi.org/10.2174/0109298673376660250612103900","url":null,"abstract":"<p><p>Biosurfactants, derived from microorganisms and waste-biomass, are ecofriendly biomolecules with surfactant properties. Their biodegradability, low toxicity, and diverse applications across industries make them valuable for multifaceted applications including environmental, food, pharmaceutical, and cosmetic sectors. Biosurfactants offer a sustainable alternative to synthetic surfactants, with potential applications in environmental remediation, food processing, pharmaceuticals, and cosmetics. By integrating circular bioeconomy principles, reducing production costs, and exploring personalized applications, biosurfactants are poised to revolutionize industries, promoting sustainability and environmental health. Thus, continued innovation and interdisciplinary collaboration may further drive the development and utilization of biosurfactants, contributing to a cleaner, greener future. This review delves into the advancements in biosurfactant synthesis, their broad applications, and emerging research focusing on optimizing production processes through waste-biomass-valorisation and biotechnological innovations. The review article also addresses challenges in production cost and scalability. Future perspectives emphasize sustainable production strategies to enhance industrial viability.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552560","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":"Network Pharmacology and Validation Experiments Reveal Cryptotanshinone Inhibits Acute Myeloid Leukemia Progression by Activating Endoplasmic Reticulum Stress.","authors":"Jie Wei, Xiang You Yao, Yan Huang, Guan-Ye Nai, Rong-Rong Liu","doi":"10.2174/0109298673348269250611042934","DOIUrl":"https://doi.org/10.2174/0109298673348269250611042934","url":null,"abstract":"<p><strong>Introduction: </strong>Acute myeloid leukemia (AML) is the most common adult hematologic malignancy, with relapse and drug resistance posing major challenges despite treatment advances. Cryptotanshinone (CTS), a diterpenoid compound derived from Salvia miltiorrhiza, exhibits anticancer activity in various tumors. However, its role and mechanisms in AML remain unclear. This study aims to investigate the inhibitory effects of CTS on AML cells and its potential mechanisms.</p><p><strong>Methods: </strong>Network pharmacology was employed to identify potential AML-related targets of CTS, and a disease-drug-target interaction network was constructed. The effects of CTS on KG-1 cells were assessed using CCK-8 proliferation assays, cell cycle analysis and apoptosis detection. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to analyze the regulatory effects of CTS on the endoplasmic reticulum stress (ERS) signaling pathway. The role of the Hippo-YAP signaling pathway in CTS-induced AML inhibition was further explored.</p><p><strong>Results: </strong>Network pharmacology analysis identified key AML-related targets of CTS, enriched in multiple cancer-related signaling pathways. Experimental results showed that CTS inhibited KG-1 cell proliferation in a dose-dependent manner, induced S-phase arrest, and promoted apoptosis. Furthermore, CTS treatment significantly upregulated ERS- related key proteins. While YAP overexpression attenuated CTS-induced ERS activation and reduced apoptosis levels.</p><p><strong>Conclusion: </strong>This study indicates that CTS inhibits AML cell proliferation and induces apoptosis while activating the ERS signaling pathway. However, aberrant activation of the Hippo-YAP pathway weakens this effect. These findings provide novel theoretical insights into potential therapeutic strategies for AML.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552573","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":"Synthesis and Biological Assessment of 3',4',5'-Trimethoxychalcone Derivatives against A549 and Molecular Insight Through Molecular Docking and Dynamics Studies.","authors":"Ade Danova, Piyanuch Wonganan, Panupong Mahalapbutr, Yusuf Eka Maulana, Elvira Hermawati, Didin Mujahidin, Warinthorn Chavasiri","doi":"10.2174/0109298673351746250528165523","DOIUrl":"https://doi.org/10.2174/0109298673351746250528165523","url":null,"abstract":"<p><strong>Background: </strong>In our previous work, 3',4',5'-Trimethoxychalcone with 3,4-disubstituent (OCH3, OH) on the B ring exhibited high inhibitory activity against A549. Thus, this study aims to further study by replacing functional groups on the B ring with alkyl and halogen groups supported by molecular docking and dynamics studies targeting EGFR-TK to investigate the binding interaction and its stability.</p><p><strong>Methods: </strong>3',4',5'-Trimethoxychalcone derivatives were prepared from 3',4',5'- trimethoxyacetophenone and substituted benzaldehyde using Claisen-Schmidt condensation under base condition. The pure products were characterized by 1H, 13C NMR spectroscopy, and mass spectrometry. Cytotoxic activity was performed using the MTT assay method. Moreover, molecular docking and dynamics simulation were conducted using the YASARA package (v21.6.17) targeting EGFR-TK (PDB ID: 1M17).</p><p><strong>Results: </strong>New compound (2) and sixteen known compounds (1, 3-17) were obtained. Compounds 6 and 7 were two of the best active compounds with IC50 values of 0.43 and 5.47 μM. Molecular docking revealed that compounds 6, 7, and 14 exhibited similar binding interactions, including hydrogen bonding, van der Waals (vdW) forces, π-π stacking, and π-anions. Additionally, molecular dynamics analysis demonstrated that the complexation between the inhibitors (6, 7, 14, and erlotinib) and EGFR-TK was highly stable.</p><p><strong>Conclusion: </strong>The potential of 3',4',5'-trimethoxychalcone derivatives as anticancer agents for targeting A549 cancer cell lines warrants further investigation.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552575","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 Current and Potential Role of Pediatric Clinical Pharmacologists in Italy: A Review with Evidence Synthesis and Literature Analysis.","authors":"Anna Parzianello, Marina Steyde, Giuliana Decorti, Davide Grisafi, Gabriele Stocco","doi":"10.2174/0109298673291434250612050205","DOIUrl":"https://doi.org/10.2174/0109298673291434250612050205","url":null,"abstract":"<p><strong>Background: </strong>Considering infants and young children, it is well established that their physiological and developmental peculiarities should not be confused with those of other patient categories, such as adults or vulnerable patients. Indeed, their anatomic- functional characteristics specifically influence the drug pharmacokinetic/pharmacodynamic profile. Therefore, the availability of specialists devoted to pediatric pharmacology within multidisciplinary teams is highly desirable to improve the care of these patients.</p><p><strong>Objective: </strong>This work aims to describe the role of pediatric clinical pharmacologists in the context of pediatric clinical care in Italy, using a qualitative method based on the type of articles published.</p><p><strong>Methods: </strong>A literature review was conducted according to the PRISMA guidelines, considering articles published on the PubMed database between January 2017 and March 2022 and using specific MeSH terms. The papers were attributed to two blind assessors and then processed for discussion. To support article screening, focusing on the words contained in article titles, the R package evidence synthesis tool revtools was used.</p><p><strong>Results: </strong>The search identified a total of 1544 articles, of which 93 were selected. The articles analyzed mainly concern therapeutic drug monitoring and pharmacovigilance with adverse drug reactions.</p><p><strong>Conclusion: </strong>An insight into multidisciplinary work to prevent, diagnose, and treat pediatric diseases and to monitor treatments is provided in this study. However, this concept needs to be strengthened in the long term.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552576","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":"A Gene Signature Developed Based on Reactive Oxygen Species to Predict the Metabolism, Immunity, Mutational Status, and Prognostic Survival for Glioblastoma.","authors":"Liqian Xie, Huasong Gao, Shukun Hu","doi":"10.2174/0109298673311171240611050715","DOIUrl":"https://doi.org/10.2174/0109298673311171240611050715","url":null,"abstract":"<p><strong>Aim: </strong>To explore the mechanism of regulatory genes related to reactive oxygen species (ROS) in glioblastoma (GBM).</p><p><strong>Background: </strong>GBM is a brain malignancy with a poor prognosis. ROS plays a critical role in cellular metabolism, signaling, and senescence, and abnormalities in ROS are closely associated with cancer initiation and development. However, the role of ROSregulated genes in GBM remained unknown.</p><p><strong>Objective: </strong>To explore the role of ROS-regulated genes in GBM and to build a ROS-related prognostic model.</p><p><strong>Methods: </strong>RNA sequencing and clinical data from GBM patients were collected from public databases. The enrichment scores of ROS-correlated pathway gene sets obtained from The Molecular Signatures Database (MSiDB) were calculated using single sample gene set enrichment analysis (ssGSEA). Subsequently, key ROS-correlated gene modules were sectioned by weighted gene co-expression network analysis (WGCNA). Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were performed to screen ROS-related genes, which were used to develop a risk model. In addition, the correlation between patients in high-risk and low-risk groups and clinicopathological features, metabolism-related pathways, and pathways related to tumor progression was analyzed. Finally, the difference in immune cell infiltration between patients in the two risk groups was calculated using CIBERSORT.</p><p><strong>Results: </strong>We found that ROS-related genes could predict the prognosis of patients suffering from GBM and that abnormal activation of the ROS pathway increased the metabolism of sugars, fats, and amino acids. WGCNA identified gene modules closely associated with ROS. A prognostic risk model was created using three key genes (OSMR, SLC6A6, and UPP1). Immune infiltration analysis showed that high-risk Patients had higher levels of macrophage infiltration, and a high-RiskScore was positively correlated with multiple metabolism processes, programmed death, and epithelial-mesenchymal transition (EMT) pathway activity.</p><p><strong>Conclusion: </strong>The ROS-associated risk model could accurately predict tumor immunity and progression for GBM patients, acting as an effective predictor of GBM prognosis. The present discovery provided a novel understanding of the diagnosis and treatment of GBM patients.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552559","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":"Structural Model of the Oncostatin M (OSM)-OSMRβ-gp130 Ternary Complex Reveals Pathways of Allosteric Communication in OSM Signaling.","authors":"Qingqing Du, Ding Luo, Yan Qian, Weiwei Xue","doi":"10.2174/0109298673362742250508113436","DOIUrl":"https://doi.org/10.2174/0109298673362742250508113436","url":null,"abstract":"<p><strong>Introduction: </strong>Human oncostatin M (OSM) is a pleiotropic cytokine that regulates inflammatory and immune responses by binding to the heterodimer receptor complex OSM receptor beta (OSMRβ) and glycoprotein 130 (gp130). The distinct signaling pathways triggered by OSM are involved in multiple chronic inflammatory conditions, such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and cancers, making the OSM-bound receptor complex a significant therapeutic target. Currently, no 3D structure of human OSM recognition complex is available, and thus, the molecular mechanisms underlying OSM signaling remain poorly understood.</p><p><strong>Methods: </strong>In this study, for the first time, we proposed a full-length structural model of the human OSM-OSMRβ-gp130, generated using AlphaFold2 protein structure prediction and all-atom molecular dynamics (MD) simulation (~ 1.12 million atoms with explicit solvent), enabling investigation of the geometric and dynamic profiles of OSM- OSMRβ-gp130 structure at atomic-level.</p><p><strong>Results: </strong>Analysis of the simulation trajectory demonstrated that the structural rearrangements of the heterodimer receptors (i.e., OSMRβ and gp130) initiated by OSM binding mediated the signal transduction from the extracellular to the intracellular domains. In the representative conformation identified through clustering analysis, two main allosteric pathways contributed were found to mediate signal transduction from the allosteric region of OSM to the active sites of OSMRβ and gp130. Finally, two druggable binding sites located on OSM and gp130 were detected by dynamically monitoring pocket flexibility throughout the simulation. A comprehensive analysis of the OSM-OSMRβ-gp130 model was carried out with respect to OSM signaling.</p><p><strong>Conclusion: </strong>The findings of this study not only enhance the mechanistic understanding of OSM binding to the heteromeric OSMRβ/gp130 but also identify druggable binding sites for structure-based design of small molecules to inhibit the intracellular signal transduction.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552574","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 MFSD9: From Expression Patterns to Therapeutic Implications in LUAD.","authors":"Qian Wang, Meijuan Zhang, Yan Xiang, Dongbing Li, Meiling Zhang","doi":"10.2174/0109298673365714250617092105","DOIUrl":"https://doi.org/10.2174/0109298673365714250617092105","url":null,"abstract":"<p><strong>Introduction: </strong>This study explores the role of Major Facilitator Superfamily Domain-containing Protein 9 (MFSD9) in lung adenocarcinoma (LUAD) using bioinformatics and experimental validation, aiming to identify its potential as a biomarker and therapeutic target.</p><p><strong>Methods: </strong>Comprehensive analysis of MFSD9 expression across cancers, particularly LUAD, was carried out using The Cancer Genome Atlas (TCGA) dataset. Correlations between MFSD9 expression and clinical outcomes, immune infiltration, immune checkpoint genes, tumor mutational burden (TMB), microsatellite instability (MSI), mRNA expression-stemness index (mRNAsi), and drug sensitivity were examined. Validation was performed using the Human Protein Atlas (HPA), Gene Expression Omnibus (GEO) databases, and qRT-PCR in LUAD cell lines.</p><p><strong>Results: </strong>MFSD9 was significantly overexpressed in LUAD, correlating with reduced overall survival (OS) and progression-free survival (PFS) (p = 0.044 and p = 0.026, respectively). It was found to be an independent prognosis factor (p = 0.046). MFSD9 expression was associated with immune cell infiltration, immune checkpoint genes, TMB, MSI, and mRNAsi, and inversely correlated with sensitivity to certain drugs, including zygosporin A and lovastatin.</p><p><strong>Discussion: </strong>MFSD9 shows promise as a prognostic biomarker and therapeutic target in LUAD. Its role in immune modulation and tumor progression highlights its potential for immunotherapy. However, further experimental validation is needed to address study limitations.</p><p><strong>Conclusion: </strong>MFSD9 is a potential biomarker and therapeutic target in LUAD, with significant implications for prognosis and treatment response. Future studies should focus on functional validation and clinical application.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552561","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}