Current medicinal chemistry最新文献

{"title":"CCNJL as a Prognostic Biomarker and Therapeutic Target in Cholangiocarcinoma.","authors":"Dongbing Li, Guizhen Lyu","doi":"10.2174/0109298673423479251024063207","DOIUrl":"https://doi.org/10.2174/0109298673423479251024063207","url":null,"abstract":"<p><strong>Introduction: </strong>Cholangiocarcinoma (CHOL) is a highly aggressive and lethal malignancy whose global incidence is increasing. This increase has been attributed to various factors, including an aging population and changes in environmental exposure. Therefore, the identification of reliable biomarkers for prognosis and treatment is crucial because of its poor survival rates and limited therapeutic options. This research examines the expression patterns and clinical relevance of Cyclin J Like (CCNJL) in CHOL, evaluating its potential as a candidate prognostic marker and immunotherapy target.</p><p><strong>Methods: </strong>We analyzed CCNJL expression in CHOL tissues compared with normal tissues using data from The Cancer Genome Atlas (TCGA) and the GSE31370 dataset. We performed differential expression analysis, Kaplan-Meier survival analysis, Cox regression analysis, and Gene Set Enrichment Analysis (GSEA) to elucidate relationships among CCNJL expression, clinical outcomes, immune infiltration, and drug sensitivity. CCNJL expression levels were validated in CHOL cell lines by quantitative real-time PCR (qRT-PCR).</p><p><strong>Results: </strong>CCNJL expression is significantly higher in CHOL tissues than in controls (mean ± SD: 1.714 ± 0.201 vs 0.165 ± 0.027; p < 0.001; AUC = 0.946). High CCNJL expression independently predicts worse overall survival (HR = 2.84, 95% CI = 1.01-7.95, p = 0.047) and disease-specific survival (HR = 3.40, 95% CI = 1.09-10.55, p = 0.035). GSEA linked high CCNJL expression to cytokine-cytokine receptor interaction, chemokine signaling, CAMs, and antigen processing. High CCNJL expression correlated inversely with CD8+ T-cell infiltration (p < 0.001) and with reduced sensitivity to elesclomol, tanespimycin, and selumetinib (all p < 0.05). qRT-PCR confirmed significant CCNJL up-regulation in CHOL cell lines.</p><p><strong>Discussion: </strong>CCNJL emerges as a novel, independent prognostic biomarker and a candidate immunotherapy target in CHOL. Its association with immune evasion and drug resistance suggests that therapeutic targeting of CCNJL could enhance antitumor immunity and restore drug sensitivity. Limitations include a modest sample size and a lack of functional validation; prospective multicenter studies and mechanistic investigations are warranted.</p><p><strong>Conclusion: </strong>CCNJL has the potential to act as a valuable prognostic indicator and immunotherapy target in CHOL. Its expression pattern and associations with clinical outcomes, immune characteristics, and drug sensitivity highlight its potential for improving diagnostic and therapeutic approaches. Future research should focus on elucidating the underlying mechanisms and validating these findings in larger cohorts.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834923","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":"Unveiling the Anti-cancer Potential of Vulpinic Acid: A Selective Therapeutic Agent Against Oral Squamous Cell Carcinoma.","authors":"Dilara Nur Şengüm, Ayşe Hale Alkan, Fatma Zeynep Bozkurt, Pelin Mutlu, Demet Cansaran-Duman","doi":"10.2174/0109298673440776260127212434","DOIUrl":"https://doi.org/10.2174/0109298673440776260127212434","url":null,"abstract":"<p><strong>Introduction: </strong>Lip and oral cavity cancers are among the most common types of cancer worldwide and remain a major health problem due to poor prognosis and treatment- related side effects. Therefore, identifying new naturally derived compounds with selective cytotoxic effects on oral cancer cells is essential. Vulpinic acid, a lichenderived secondary metabolite, has shown antioxidant and anticancer activities in various cancer types. However, its effects on oral cancer cells have not yet been clarified. This study aims to investigate the cytotoxic and apoptotic effects of vulpinic acid on oral cancer cells and to explore its possible molecular mechanisms.</p><p><strong>Methods: </strong>The cytotoxic effect of vulpinic acid on OSC-19 oral cancer and MRC-5 normal fibroblast cells was assessed using xCELLigence analysis. The impact of vulpinic acid on cell cycle progression, apoptotic mechanisms, colony formation, wound healing, and molecular-level effects was analyzed using flow cytometry, mitochondrial membrane potential assay, and qRT-PCR. The effect of vulpinic acid on BIRC5 protein levels was further confirmed by western blot analysis.</p><p><strong>Results: </strong>The results showed that the IC50 value of vulpinic acid was 59 μM in OSC-19 cells and 114 μM in MRC-5 cells, demonstrating its selective cytotoxic effect on oral cancer cells. Vulpinic acid treatment suppressed colony formation by 55.5% and reduced cell migration by 71.2-fold at 96 h. Cell cycle analysis revealed that vulpinic acid induced G1 phase arrest, while apoptosis analysis showed a decrease in mitochondrial membrane potential. qRT-PCR analysis revealed an upregulation of pro-apoptotic genes (BID, CASP4, CASP7, BAK1, BCL2L2) and downregulation of the anti-apoptotic gene survivin (BIRC5). According to western blot analysis, BIRC5 protein expression decreased 2.39-fold following vulpinic acid treatment.</p><p><strong>Discussion: </strong>These findings indicate that vulpinic acid has the potential to be considered as an anti-cancer agent.</p><p><strong>Conclusion: </strong>Further in vivo and clinical studies are required to validate its therapeutic efficacy and safety profile.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834724","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":"Innovative Applications of Cutting-Edge Nanomaterials in Diabetic Wound Healing.","authors":"Jie Wang, Min Zhu, Yuanzhi Tong, Yuejun Yang","doi":"10.2174/0109298673441167260102055715","DOIUrl":"https://doi.org/10.2174/0109298673441167260102055715","url":null,"abstract":"<p><p>Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia. Diabetic wound healing faces severe challenges, such as low treatment efficiency and susceptibility to infection due to its complex pathological microenvironment. Conventional treatments like antimicrobial dressings and debridement are limited by issues such as low drug bioavailability and poor tissue penetration. In recent years, nanomaterials have demonstrated significant potential in diabetic wound management by leveraging their unique physicochemical properties and multifunctional integration capabilities. They enable precise intervention in the wound microenvironment through targeted delivery, controlled release, and synergistic multi-mechanistic actions involving antibacterial, antioxidant, immunomodulatory, and pro-angiogenic aspects. This review systematically summarizes innovative applications of various cutting-edge nanomaterials in diabetic wound repair, including metal nanomaterials (e.g., Ag, Au), metal-organic frameworks (MOFs), polymeric nanomaterials (e.g., chitosan), ceramic nanomaterials, carbon- based nanomaterials (e.g., graphene, carbon quantum dots), lipid nanoparticles (LNPs), and exosomes. For instance, silver-loaded Prussian blue-chitosan nanocomposite (Ag@Chi-PB NPs) under near-infrared (NIR) laser activation achieved eradication rates of 65% and 60% against Methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) biofilms, respectively. Trisulfide lipid nanoparticles (TS LNPs) loaded with Interleukin-4 (IL4)-mRNA in diabetic mouse models reduced reactive oxygen species levels by 7-fold and increased M2 macrophage proportion to 53%. Moreover, a graphene-based composite hydrogel achieved nearly 99.7% wound closure within 14 days, demonstrating excellent conductivity and promoting re-epithelialization. This review focuses on the latest mechanistic insights and application advances of nanomaterials in chronic diabetic wound therapy, aiming to provide systematic and forward- looking academic references for researchers and clinicians and to promote their clinical translation.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835004","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":"Efficacy of SGLT2i and GLP-1RA in Acute Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials.","authors":"Huilei Zhao, Fuwei Liu, Jiayu Zhang, Yang Liu, Ziqi Tan, Jing Zhang, Peng Yu, Deju Zhang, Xinyu Liu, Taoli Fu, Jingyi Huang, Xiao Liu","doi":"10.2174/0109298673349221251203101854","DOIUrl":"https://doi.org/10.2174/0109298673349221251203101854","url":null,"abstract":"<p><strong>Introduction: </strong>The efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in acute myocardial infarction (AMI) remains uncertain. We aimed to investigate the effectiveness of SGLT2i and GLP-1RA in patients with AMI.</p><p><strong>Methods: </strong>We conducted a comprehensive search on PubMed, the Cochrane Library, Embase, and ClinicalTrials.gov databases to identify relevant randomized controlled trials (RCTs) up to January 2025. The primary outcomes included all-cause mortality and left ventricular ejection fraction (LVEF).</p><p><strong>Results: </strong>Six RCTs assessed SGLT2i (SGLT2i: n=5,660; placebo: n=5,651) and five assessed GLP-1RA (GLP-1RA: n=300; placebo: n=333). Compared with placebo, SGLT2i improved LVEF (mean difference = 1.58, p = 0.01, high certainty) and reduced heart failure hospitalization (HHF) (odds ratio = 0.78, p = 0.023, moderate certainty) in AMI patients. No significant benefit was observed in all-cause mortality with SGLT2i, and no significant benefits of GLP-1RA were observed in all-cause mortality, cardiac death, myocardial infarction relapse, infarct size, LVEF, left ventricular end-diastolic volume, or left ventricular end-systolic volume. TSA indicated potential false positives for the LVEF and HHF findings with SGLT2i.</p><p><strong>Discussion: </strong>Several limitations of the included studies include a small number of studies, heterogeneity in experimental design, and reliance on alternative endpoints.</p><p><strong>Conclusion: </strong>SGLT2i improved LVEF and reduced HHF in patients with AMI but did not significantly improve all-cause mortality. GLP-1RA did not significantly improve LVEF or major clinical endpoints. Further large-scale RCTs are needed to verify these results and provide more robust evidence.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834907","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 Anticancer Potential of Launaea mucronata: Biological Assessment, Molecular Docking, and Molecular Dynamics Simulations.","authors":"Ahmed A Al-Karmalawy, Aya Yaseen Mahmood Alabdali, Yasser A El-Amier, Arwa Omar Al Khatib, Radwan Alnajjar, Mohamed M Khalifa, Faten Farouk, Ahmed A Saadeldin, Salem Salman Almujri, Abdullah Yahya Abdullah Alzahrani, Rehab F Taher","doi":"10.2174/0109298673402314251104071536","DOIUrl":"https://doi.org/10.2174/0109298673402314251104071536","url":null,"abstract":"<p><strong>Background: </strong>Launaea mucronata has garnered the interest of chemists, particularly in the field of oncology. While not traditionally used for cancer treatment, studies have shown that its methanolic extract exhibits cytotoxic effects against human cancer cell lines.</p><p><strong>Methods: </strong>Herein, thirty-three metabolites were spotted in the aqueous extract of Launaea mucronata via UPLC-MS/MS, primarily flavonoids, hydroxycinnamic acid derivatives, and carboxylic acid derivatives. The extract's antiproliferative activity was tested on HCT-116 (colon), MCF7 (breast), and HePG2 (liver) cancer cells, showing notable potency. A molecular docking study assessed the extract's bioactive compounds for their binding to human DNA-Topo II enzyme complexes. Molecular dynamics simulations (200 ns) were performed on the top-scoring complexes (dicaffeoyl-succinoylquinic acid 7, tricaffeoyl quinic acid 10, feruloyl-O-p-coumaroyl- O-caffeoylshikimic acid 12, and kaempferol-rutinoside 23) using Schrödinger's Desmond package. Binding stability was further validated by MM-GBSA energy calculations via Schrödinger's thermal_mmgbsa.py script.</p><p><strong>Results: </strong>The IC50 values were 5.35 ± 0.09 μg/mL in the HePG2 cell line versus 48.99 ± 21.51 μg/mL for doxorubicin. Similarly, for the MCF7 cells, the recorded IC50 of the extract was found to be 5.60 ± 1.15 μg/mL versus 4.97 ± 0.35 μg/mL for doxorubicin.</p><p><strong>Discussion: </strong>A total of 33 metabolites of Launaea mucronata identified via UPLC-MS/MS were identified as promising anticancer candidates against both HePG2 and MCF7 cell lines. Additionally, their mechanisms of action involve DNA intercalation and inhibition of topoisomerase II (Topo II) through molecular docking, molecular dynamics, and MM-GBSA calculations.</p><p><strong>Conclusion: </strong>These findings highlight Launaea mucronata's promising anticancer potential, supported by both experimental and computational evidence.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834909","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":"Apatinib and Adebrelimab Exhibit Synergistic Antitumor effects in Small Cell Lung Cancer: An In Vitro Study.","authors":"Yiping Zhu, Xiangwei Cheng, Linfeng Wu, Yifan Wang, Laiquan Huang","doi":"10.2174/0109298673478917260414214002","DOIUrl":"https://doi.org/10.2174/0109298673478917260414214002","url":null,"abstract":"<p><strong>Background: </strong>Small cell lung cancer (SCLC) is a highly aggressive malignancy. This study investigated whether Apatinib (Apa) combined with Adebrelimab (Ade) exerted synergistic effects against SCLC.</p><p><strong>Methods: </strong>Half-maximal inhibitory concentration (IC50) value of Apa and Ade, administered alone or in combination, was determined in H446 and H1436 cells using cell counting kit-8 (CCK-8) assays. Synergistic effects were quantified by calculating fractional inhibitory concentration (FIC) indices. Cell proliferation, migration, and invasion were assessed by CCK-8, wound healing, and Transwell assays, respectively. After co-culture with CD8+ T cells, PD-L1 expression and CD8+ IFN-γ+ T cell proportion were measured by flow cytometry. TGF-β secretion and LDH release were detected using ELISA and LDH assay, respectively; the protein level of VEGFR2 and STAT3 was analyzed by western blot.</p><p><strong>Results: </strong>Apa alone exhibited IC50 values of 20.03 μM (H446) and 35.50 μM (H1436), while Ade alone exhibited 5.789 μM and 6.959 μM, respectively. The sum FIC values were 0.681 for H446 cells and 0.973 for H1436 cells. Compared with either monotherapy, combined treatment more effectively reduced cell viability, migration, and invasion. In co-culture experiments, the combination further suppressed PD-L1 expression and TGF-β secretion, increased CD8+ IFN-γ+ T cells and LDH release, and downregulated VEGFR2, p-STAT3, and PD-L1 protein levels.</p><p><strong>Discussion: </strong>This study demonstrated that the combination of Apa and Ade exerted synergistic anti-tumor effects against SCLC in vitro. Further investigation, including animal studies and clinical trials, is warranted to evaluate the efficacy and long-term safety of this combination therapy.</p><p><strong>Conclusion: </strong>In summary, the combination of Apa and Ade represented a promising innovative therapeutic strategy for SCLC.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834891","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":"Global Research Progress of Sepsis and Mitochondria: Bibliometrics and Visualized Analysis.","authors":"Luorui Shang, Yuju Cai, Shuhan Wang, Jinxiao Li, Fangyuan Zhou, Mengqi Zhang, Yuqing Wang, Jianghua Huang, Shenglan Yang","doi":"10.2174/0109298673433066260127165730","DOIUrl":"https://doi.org/10.2174/0109298673433066260127165730","url":null,"abstract":"<p><strong>Objective: </strong>Many studies have demonstrated a significant association between mitochondria and sepsis. As research on mitochondria continues to deepen, substantial advancements have been achieved in elucidating the connection between mitochondria and sepsis. Nevertheless, there has been no systematic bibliometric analysis or visualization of the related publications in this field. This study aims to visually present the knowledge system and research focus between mitochondria and sepsis through the method of bibliometrics.</p><p><strong>Methods: </strong>An extensive review of existing literature was conducted using the Web of Science Core Collection (WoSCC) database to identify publications investigating the relationship between mitochondria and sepsis. Subsequent bibliometric analysis was conducted using R software (version 4.4.0) with the Bibliometrix package (version 4.2.3), complemented by visualization and network analysis through VOSviewer (version 1.6.20) and CiteSpace (version 6.1.6).</p><p><strong>Results: </strong>From 1997 to 2025, the Web of Science Core Collection retrieved a total of 1993 relevant publications. The number of publications related to mitochondria and sepsis has continued to increase throughout this period. China, along with the United States and the United Kingdom, plays a central role in advancing research in this field. Leading institutions contributing to this area include the University of Pennsylvania, Harvard University, and the University of London. SINGER M and ZHANG Y are the top authors in this research field. The keyword analysis reveals that the high-frequency terms include sepsis, mitochondrial dysfunction, oxidative stress, and inflammation. We summarized the pathogenesis of sepsis related to mitochondria, as well as the existing and potential therapeutic drugs for sepsis that are associated with these mechanisms.</p><p><strong>Discussion: </strong>As the comprehensive bibliometric analysis in this field, our study visually presents key research trends and hotspots linking mitochondria to sepsis, emphasizing the significance of mitochondrial dysfunction and other factors in the pathogenesis of sepsis, offering a valuable framework for future scientific and clinical advancements.</p><p><strong>Conclusion: </strong>The field of mitochondrial research in sepsis has experienced steady growth over the past two decades, with substantial contributions from China, the United States, and the United Kingdom. Emerging evidence suggests that future investigations are likely to center on key pathological mechanisms such as mitochondrial dysfunction and oxidative stress.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834902","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":"Phytochemical Exploration and Anti-asthmatic Activity of Crude Methanol Extract and Derived Fractions of Sonchus asper (L.) Hill.","authors":"Khalil Ahmad, Abdullah, Munasib Khan, Shakil Ahmad","doi":"10.2174/0109298673440977260202210913","DOIUrl":"https://doi.org/10.2174/0109298673440977260202210913","url":null,"abstract":"<p><strong>Introduction: </strong>Asthma is a chronic inflammatory airway disease with limited curative therapies. Sonchus asper, traditionally used in Pakistan for asthma, was investigated for its phytochemical profile and in vivo anti-asthmatic potential.</p><p><strong>Methods: </strong>The whole plant was extracted with 80% methanol, fractionated, followed by phytochemical screening, HPLC analysis, and total phenolic and flavonoid quantification. Anti-asthmatic activity was evaluated using an ovalbumin-induced asthma model following oral administration of extracts and fractions. Bronchoalveolar lavage fluid analysis, total and differential leukocyte counts, and lung histopathology were performed. The most active fraction (chloroform) was subjected to column chromatography and GC-MS analysis.</p><p><strong>Results: </strong>Alkaloids, flavonoids, saponins, tannins, and phenolics were detected, with the chloroform fraction exhibiting the highest phenolic and flavonoid contents. HPLC analysis identified quercetin, catechin, and rutin. The chloroform fraction displayed the most potent anti-asthmatic activity, significantly reducing total inflammatory cells by 73.2% (p ˂ 0.001), 63% (p ˂ 0.01) and 57.7% (p < 0.01) at 300, 150 and 75 mg/kg respectively, with marked suppression of eosinophils, neutrophils, lymphocytes and macrophages, and improved histopathology, while the ethyl acetate fraction produced comparable reductions (72.61%, 61.90%, 56.54%) across the same dose range. GC-MS identified caryophyllenyl alcohol and phytol.</p><p><strong>Discussion: </strong>The significant anti-asthmatic activity of Sonchus asper, particularly the chloroform and ethyl acetate fractions, supports existing evidence on flavonoid and phenolic-rich medicinal plants, although the lack of cytokine profiling and molecular mechanistic validation remains a limitation.</p><p><strong>Conclusion: </strong>These findings support the traditional use of Sonchus asper in asthma and identify it as a promising source of anti-inflammatory agents.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833752","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":"Predictive Analyses of Tumor Relapse-free Survival Prognosis Related to Consistency between Different Cancer Tissues and Adjacent Normal Tissues in Drug Repurposing for Solid Tumor via Connectivity Map.","authors":"Mingyue Hao, Dandan Li, Yuanyuan Qiao, Ming Xiong, Jun Li, Wei Ma","doi":"10.2174/0109298673423454251212061448","DOIUrl":"https://doi.org/10.2174/0109298673423454251212061448","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Traditional drug discovery faces challenges, including high costs, time-intensive processes, and inherent risks. The disease-specific signature-based Connectivity Map (CMap) approach is widely utilized. However, the commonly employed method for constructing disease-specific signatures, known as Differentially Expressed Genes (DEGs), suffers from inconsistencies between dysregulated genes and their prognostic implications in tumor tissue, as well as discrepancies in prognosis genes between tumor and normal tissues. In this study, we present predictive analyses of CMap-based drug repurposing for solid tumors that account for discrepancies in gene activity between tumor and adjacent normal tissues.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We propose a predictive approach, Prognosis Consistency Scoring (PCS), designed to address these inconsistencies by analyzing six types of solid tumors: BRCA, HNSC, LIHC, LUAD, LUSC, and THCA. PCS measures the consistency of gene prognosis between tumor and normal tissues by integrating the Recurrence- Free Survival (RFS) prognostic power of genes in both contexts. Disease-specific signatures are then constructed based on PCS, and drug repurposing is performed using the CMap and Lincs Unified Environment (CLUE). The predicted drugs were validated using data from DrugBank, ClinicalTrials, CancerDrugs_DB, Re- DO_Trials_DB, GDSC2, CTRPv2, and PRISM. Biological enrichment analysis was conducted via the Metascape platform.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Our findings reveal that these inconsistencies are pervasive. Compared to signatures based on DEGs, PCS-based signatures exhibit superior performance, identifying more drugs with higher prediction accuracy, as confirmed by DrugBank annotations. Notably, a significant proportion of predicted drugs without corresponding indications were subsequently validated in the ClinicalTrials database. For instance, three trials support the efficacy of gemcitabine in LIHC, and two trials support the use of dasatinib for the treatment of LUAD and LUSC. The prediction accuracy of PCS is higher than that of DEGs (20/31 vs. 1/31, Fisher's exact test, p-value &lt; 0.001). In the CancerDrugs_DB and ReDO_Trials_DB databases, the performance of PCS was also influenced by DEGs. In the three in vitro tumor cell line drug response databases, including GDSC2, CTRPv2, and PRISM, PCS outperformed DEGs. Comparative analysis between PCS and Tumor Prognosis Score (TPS) indicates that, although TPS is a component of PCS, the performance of PCS is still influenced by TPS. Additionally, PCS-based signatures demonstrated elevated disease specificity and association with Drug-Related Genes (DRGs).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;New drug discovery is time-consuming and risky. To address this, we proposed PCS, a method that improves drug repurposing accuracy by considering consistency between gene dysregulation and prognosis in tumor and normal tissues. PCS outperformed DEG-based a","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834074","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":"Uncovering Cancer-Associated Adipocytes: An Emerging Force Reshaping the Immunotherapy Landscape for Breast Cancer.","authors":"Ke Qian, Shujun Xu, Ke Zhang, Hongyan Zhang","doi":"10.2174/0109298673424411251204102903","DOIUrl":"https://doi.org/10.2174/0109298673424411251204102903","url":null,"abstract":"<p><p>The progression of breast cancer is intricately linked to the dynamic crosstalk between tumor cells and stromal cells. Within this complex interplay, Cancer-Associated Adipocytes (CAAs) have emerged as pivotal stromal components driving breast cancer malignancy by establishing a unique \"adipose-immune\" interface-one that integrates adipose-derived metabolic cues with immune cell dynamics to create a niche that accelerates tumor invasion, angiogenesis, and treatment resistance. This review systematically analyzes the roles of CAAs in breast cancer pathogenesis, focusing on how CAAs regulate the Tumor Immune Microenvironment (TIME) and the Adipose Tissue Microenvironment (ATME) individually and how they influence therapeutic responses through their interplay. A particular emphasis is placed on the functional heterogeneity of CAAs across different breast cancer subtypes and metabolic contexts, and its implications for shaping immunosuppressive niches and immunotherapy resistance. Specific mechanisms include: reshaping adipokine and inflammatory cytokine profiles to foster a pro-tumorigenic secretory landscape; inducing metabolic reprogramming in tumor cells to sustain aggressive growth; mediating intercellular signaling via exosomes to propagate malignant traits; altering immune cell functional states to shift toward an immunosuppressive phenotype; and promoting the establishment of immune escape pathways. Based on these mechanisms, the review synthesizes CAA-targeted therapeutic strategies for breast cancer, including: disrupting key adipokine-mediated signaling cascades to interrupt tumor-stroma communication, modulating CAA-secreted factors to reorient immune cell activities toward anti-tumor functions, and rewiring lipid metabolic pathways in the TIME to enhance therapeutic sensitivity. In-depth dissection of CAA functional networks is crucial for elucidating their pathogenic significance in breast cancer and fueling precision immunotherapy innovation, as such insights may open avenues for rebalancing TIME immune interactions and boosting immunotherapeutic efficacy.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834671","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}