Current medicinal chemistry最新文献

{"title":"Poria Cocos Polysaccharide Triggers Mitochondrial-mediated Apoptosis in Hepatocellular Carcinoma Cells through P53 and Bioenergetic Collapse.","authors":"Jiaqi Zhao, Xue Yang, Xinze Liu, Xinmin Wu, Zhengwu Liu, Shuang Zu, Anning Li, Lin Feng, Xin Jin, Guangzhe Li, Changbao Chen, Xilin Wan","doi":"10.2174/0109298673421449251221122909","DOIUrl":"https://doi.org/10.2174/0109298673421449251221122909","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to investigate the inhibitory effect of Poria cocos polysaccharide (PCP) on hepatocellular carcinoma cells SMMC-7721 and its potential mechanism.</p><p><strong>Methods: </strong>We performed a series of in vitro experiments to evaluate the effects of PCP on hepatocellular carcinoma cells SMMC-7721. The effects of PCP on SMMC-7721 cell proliferation, apoptosis, migration, invasion, and related protein expression were evaluated by CCK-8 assay, AO/EB and DAPI fluorescent staining, cell scratch healing assay, Transwell assay, and protein immunoblotting assay. in vivo experiments in mice were performed to illustrate the effects of PCP on hepatocellular carcinoma in mice.</p><p><strong>Results: </strong>PCP demonstrated significant efficacy against hepatocellular carcinoma in vitro and in vivo, suppressing SMMC-7721 cells' proliferation, migration, and invasion, and inducing mitochondrial apoptosis via concomitant upregulation of P53, Bax, Caspase-3, Caspase-9, and Cytochrome c, and downregulation of Bcl-2, MMP-2, and MMP-9.</p><p><strong>Discussion: </strong>Hepatocellular carcinoma cells (SMMC-7721) proliferation, migration, and invasion were markedly suppressed, and apoptosis was extensively induced, through modulation of the mitochondrial apoptotic pathway by PCP, thereby conferring significant antitumor activity.</p><p><strong>Conclusion: </strong>This study provides an experimental basis for the application of PCP in the treatment of hepatocellular carcinoma.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834085","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":"Artificial Intelligence in Medication Research and Development: The Pharmaceutical Industry's Future.","authors":"Manaf AlMatar, Emel Eker, Khaoula Balgouthi, Hassan Ali Al-Reasi, Raja Lakhal","doi":"10.2174/0109298673409808251118070544","DOIUrl":"https://doi.org/10.2174/0109298673409808251118070544","url":null,"abstract":"<p><p>It is no wonder that AI is making a major impact in drug development. As AI tools continue to advance and improve, it is easy to understand why pharmaceutical companies are taking a keen interest in AI in drug development and its potential benefits for saving time and money. AI is helping drug development become faster, more accurate, and cost-effective, all while benefiting the bottom line. When machine learning and deep learning come into play in this scenario, the potential for AI and its benefits in drug development is endless. It has already been proven in areas such as predicting drug properties, identifying and validating new targets, developing small molecule drugs, and even speeding up clinical trials through drug repurposing, drug development, and drug outcome predictions. Of course, as in all things in life, there are obstacles and hurdles that need to be addressed and overcome. This includes better data-sharing practices, better standards for algorithms, and even the potential for bringing biology and computer science closer together in order to bring lab work and modeling closer.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765204","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":"IL-1β Blocker and Its Influence on Preserving Lung Tissues Sensitized by Echinococcus granulosus Sac Fluid by Regulating Macrophage Phenotypic Transformation.","authors":"Chun-Sheng Wang, Xilizhati Kulaixi, Jing-Ru Zhou, Xue-Li Pu, Jia-Ling Wang, Xianyidan Abulajiang, Jian-Rong Ye","doi":"10.2174/0109298673425107251229063642","DOIUrl":"https://doi.org/10.2174/0109298673425107251229063642","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to elucidate the molecular mechanisms underlying macrophage involvement in lung injury following sensitization to the cyst fluid induced by Echinococcus granulosus.</p><p><strong>Methods: </strong>Eighteen C57/BL6 mice were randomly divided into three groups, with six mice in each group. After mice were intraperitoneally injected with Echinococcus granulosus, they were raised for 3 months. In the control group (group A, n = 6), normal saline was injected into the abdominal cavity and airway. In the blocker group (group B, n=6), IL-1β blocker was injected through the tail vein, followed by intraperitoneal injection of 0.1 ml/g Echinococcus granulosus cyst fluid and airway injection of 0.05 ml/g Echinococcus granulosus cyst fluid. In the sensitized group (group C, n = 6), 0.1 ml/g Echinococcus granulosus cyst fluid was injected intraperitoneally, and 0.05 ml/g Echinococcus granulosus cyst fluid was injected into the airway. Changes in macrophages in lung tissue were detected by flow cytometry. The pathological sections of lung tissue were prepared, and immunohistochemical analysis was performed. At the same time, the lung tissues of the three groups of mice were analyzed by Western blot and RT-PCR. The protein and mRNA expression of PI3K/AKT/NF-κB and the levels of inflammatory factors IL-6 and TNF-α were detected.</p><p><strong>Results: </strong>After the application of IL-1β blockers, the number of M2-type macrophages in the lungs increased significantly, the mRNA and protein expression levels of PI3K/AKT/ NF-κB and inflammatory factors IL-6 and TNF-α decreased, and the damage was significantly alleviated.</p><p><strong>Discussion: </strong>The findings suggest that IL-1β drives lung injury in E. granulosus sensitization by skewing macrophages toward a pro-inflammatory phenotype and activating the PI3K/AKT/NF-κB pathway. The protective effect of IL-1β blockade highlights its potential as a therapeutic target to modulate macrophage polarization and mitigate inflammation in hydatid disease-related lung injury.</p><p><strong>Conclusion: </strong>IL-1β blockers exert a protective effect on lung injury caused by allergic reactions to the cystic fluid of Echinococcus granulosus by promoting an increase in the M2 phenotype of macrophages.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765181","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":"Metabolites and Polycystic Ovarian Syndrome: A Mendelian Randomization Study.","authors":"Na Aru, Yuntian Chen, Tian Li, Jiaming Liu","doi":"10.2174/0109298673408216260414174125","DOIUrl":"https://doi.org/10.2174/0109298673408216260414174125","url":null,"abstract":"<p><strong>Introduction: </strong>Polycystic ovarian syndrome (PCOS) is a common reproductive disorder that affects a considerable number of women worldwide. Nevertheless, the causal relationship between metabolites and PCOS remains undetermined.</p><p><strong>Methods: </strong>We utilized a comprehensive two-sample Mendelian randomization (MR) analysis, a genetic epidemiological approach that uses genetic variants as instrumental variables to assess causal relationships between exposures and outcomes, to examine the causal link between 1352 metabolites and PCOS. We employed complementary MR methods, such as the inverse-variance weighted (IVW) method, and conducted sensitivity analyses to evaluate the reliability of the outcomes. Reverse MR analysis was performed to evaluate the possibility of reverse causation.</p><p><strong>Results: </strong>Five metabolites were identified to be significantly associated with PCOS risk: Methionine sulfoxide levels (IVW: OR [95%]: 1.549[1.274 to 1.883], p = 1.154E-5), Theophylline levels (IVW: OR [95%]: 0.725[0.589 to 0.890], p = 0.002), 4-hydroxycoumarin levels (IVW: OR [95%]: 0.786[0.658 to 0.940], p = 0.008), Tyramine O-sulfate levels (IVW: OR [95%]: 0.699[0.568 to 0.862], p = 0.0008), and Sulfate of piperine metabolite C16H19NO3 (3) levels (IVW: OR [95%]: 1.296[1.064 to 1.579], p = 0.009). We found PCOS was significantly associated with decreased Tyramine O-sulfate levels using the IVW method (OR [95%]: 0.953[0.917 to 0.991], p = 0.015) in the reverse MR analysis. The results of the sensitivity analyses were consistent with the main findings.</p><p><strong>Discussion: </strong>This study establishes causal relationships between specific metabolites and PCOS, highlighting the significant roles of oxidative stress (methionine sulfoxide), dietary components (theophylline, piperine metabolite), and gut microbiome-derived metabolites. These findings provide novel insights into PCOS pathogenesis and identify potential targets for prevention and treatment. However, the study's limitation to European populations necessitates further validation in diverse ethnic groups.</p><p><strong>Conclusion: </strong>Our MR analysis provides strong evidence supporting a causal association between metabolites and the susceptibility of PCOS.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721859","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":"Determination of the 95% Effective Dose of Remifentanil for Moderate Sedation During Gastroscopy in Obese Patients.","authors":"Rui Ran, Qiyu Chen, Qi Zhu, Zhihui Ma, Jing Zhang, Ying Tian, Shiyu Shu","doi":"10.2174/0109298673450660260406102550","DOIUrl":"https://doi.org/10.2174/0109298673450660260406102550","url":null,"abstract":"<p><strong>Introduction: </strong>Obesity increases the risk of hypoxemia during gastroscopy. The optimal remifentanil dose for effective and safe conscious sedation in this population remained unclear. Applying the biased coin design up-and-down sequential method, we aimed to determine the 95% Effective Dose (ED95) of remifentanil required for gastroscopy in obese patients.</p><p><strong>Materials and methods: </strong>In this prospective interventional dose-finding study, patients aged 18-65 years with a BMI ≥ 30 kg/m2 (ASA class I-III) undergoing elective gastroscopy received remifentanil via target-controlled infusion. Patients with opioid allergy were excluded. A biased coin design-up-and-down method was used to determine the dosage, and the ED95 was estimated using isotonic regression. Ramsay sedation scores, Visual Analog Scale (VAS) pain scores, vital signs, and satisfaction ratings were recorded.</p><p><strong>Results: </strong>Forty-two patients were enrolled. Sedation was successful in 83.3% (35/42) of patients. The estimated ED95 of remifentanil was 0.915 μg/kg (95% CI: 0.790-0.989). The mean procedure time was 5.85 minutes. Hypoxemia occurred in 4.8% (n = 2, lowest SpO2 88%) and sinus bradycardia in 7.1% (n = 3). Patient and endoscopist satisfaction scores were 7.12 ± 1.42 and 6.75 ± 1.62, respectively.</p><p><strong>Discussion: </strong>This study found that remifentanil monotherapy can serve as an effective and safe strategy for conscious sedation in obese patients undergoing gastroscopy. We determined the effective dose ED95 to be 0.915 μg/kg (95% CI, 0.790-0.989), providing a potential evidence-based starting point for clinical practice. The favorable safety profile, characterized by a low incidence of hypoxemia, addressed a critical need for sedation strategies that minimize respiratory depression in this high-risk population. Future research should explore combinations with non-opioid adjuvants to further reduce opioid- related adverse effects and incorporate objective respiratory monitoring, such as capnography, to enhance safety assessment.</p><p><strong>Conclusion: </strong>Remifentanil monotherapy provided effective conscious sedation for gastroscopy in obese patients, showing a high success rate and low incidence of hypoxemia. The ED95 was determined to be 0.915 μg/kg.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722010","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 Clinical and Chemical Research in Occupational Asthma.","authors":"Xi-Ming Yuan","doi":"10.2174/0109298673446940260415101250","DOIUrl":"https://doi.org/10.2174/0109298673446940260415101250","url":null,"abstract":"<p><p>Occupational Asthma (OA) accounts for a significant portion of adult asthma cases and is driven by diverse mechanisms linked to high- and low-molecular-weight workplace exposures. Despite extensive clinical and epidemiological studies, the molecular basis and medicinal chemistry approaches for diagnosing and managing OA remain underexplored. Here, I review the current literature identifying key occupational exposures, emphasizing the paucity of medicinal chemistry research targeting OA-related exposures. I advocate for translational research that integrates innovations in medicinal chemistry with clinical insights, leveraging exposomics to develop personalized exposure assessments and targeted therapeutics. The interdisciplinary approach involving chemical exposomes holds promise for improved OA prevention, diagnosis, and management tailored to specific occupational exposures and patient needs.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721998","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":"An In-Vitro Laboratory Exploration Revealed the Antitumor Effects of Melittin on Osteosarcoma CVCells.","authors":"Yumei Li, Xiaoliang Xie, Haixia Zhu, Deta Chen, Tianyou Fan","doi":"10.2174/0109298673446767260313082429","DOIUrl":"https://doi.org/10.2174/0109298673446767260313082429","url":null,"abstract":"<p><strong>Introduction: </strong>Melittin, a 26-amino acid polypeptide with various pharmacological effects, possesses potential anti-tumor properties. The present study examined the possible mechanisms of action on Osteosarcoma (OS) cells.</p><p><strong>Materials and methods: </strong>A series of in-vitro tests was implemented to investigate the effects of melittin on the survival, apoptosis, migration, and invasion of OS cells (143-B and MG63). An immunoblotting assay was applied to quantify the protein expression of potential mediators. Further, the mechanisms of action of melittin on OS cells were validated through rescue assays.</p><p><strong>Results: </strong>In OS cells 143-B and MG63, melittin treatment evidently reduced the cell viability, migration, and invasion and elevated apoptosis, with downregulated Bcl-2 and upregulated Bax and cleaved caspase-3. Moreover, the phosphorylation of PI3K/AKT/m- TOR was diminished following melittin treatment. In contrast, the rescue assay demonstrated that the anti-OS effects of melittin in vitro were negated by the 740 Y-P (a known PI3K activator). This was evidenced by altered viability, migration, and invasion, reduced apoptosis in OS cells, and the expression of apoptosis-related mediators.</p><p><strong>Discussion: </strong>Utilizing an in-vitro OS cell model, the current study discovered that melittin can suppress the growth, migration, and invasion of OS cells yet promote apoptosis, potentially via targeting PI3K/AKT/mTOR pathway, providing a novel mechanism underlying the effect of melittin on OS cells.</p><p><strong>Conclusion: </strong>The research demonstrated the anti-OS effects of melittin and its possible relationship with the PI3K/AKT/mTOR pathway.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722000","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":"Augmented Anti-leukemic Efficacy of Selenium-Fermented Ferulic Acid Derived from Macrotyloma uniflorum: Insights into in vitro and in vivo Models.","authors":"Amber Rizwan, Husna Shaikh, Humaira Farooqi","doi":"10.2174/0109298673408314251208141045","DOIUrl":"https://doi.org/10.2174/0109298673408314251208141045","url":null,"abstract":"<p><strong>Introduction: </strong>Conventional leukemia therapies often damage healthy cells, creating significant public health challenges. Ferulic acid, extracted from Macrotyloma uniflorum (horse gram), has demonstrated antileukemic properties. Fermentation is known to enhance the bioavailability of active compounds, and selenium offers additional health benefits. This study investigated whether selenium supplementation during fermentation improves the yield and antileukemic potency of ferulic acid compared with non-fermented and selenium-free conditions.</p><p><strong>Materials and methods: </strong>Ferulic acid was extracted under three conditions: non-fermented, fermented, and selenium-supplemented fermentation. Yield quantification was performed for each extract. Antileukemic efficacy was evaluated in HL-60 human leukemia cells. in vivo effects were assessed in female Balb/c mice, including blood cell counts and histopathological changes in the liver, spleen, and bone marrow.</p><p><strong>Results: </strong>Fermentation increased ferulic acid yield by more than 50%, and selenium supplementation further enhanced it by more than 70%. All extracts exhibited antileukemic activity, with the selenium-enriched fermented extract showing the highest efficacy. It induced apoptosis more effectively than vinblastine and significantly reduced HL-60 cell viability. in vivo, the extract selectively decreased leukemic blast cells, red and white blood cells, lymphocytes, neutrophils, and monocytes, while sparing basophils and eosinophils. Histopathological analysis revealed protection of the liver, spleen, and bone marrow from ENU-induced damage.</p><p><strong>Discussion: </strong>Selenium-supplemented fermentation significantly enhanced both the yield and antileukemic activity of ferulic acid. The enriched extract demonstrated selective induction of apoptosis in leukemia cells and protective effects on normal tissues, underscoring its biological relevance and therapeutic potential.</p><p><strong>Conclusion: </strong>Ferulic acid derived from selenium-supplemented fermented Macrotyloma uniflorum exhibited significantly greater antileukemic potency and therapeutic efficacy than ferulic acid from fermented or non-fermented conditions, highlighting its promise as a natural, effective antileukemic agent.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721984","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":"Multi-Omics Analysis Reveals DNASE1L3 in Hepatocellular Carcinoma Prognosis, Immune Microenvironment, and Immunotherapy Response.","authors":"Xilong Tang, Jianjin Xue, Xiao Li, Jie Zhang, Jiajia Zhou","doi":"10.2174/0109298673409582251107054456","DOIUrl":"https://doi.org/10.2174/0109298673409582251107054456","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocellular Carcinoma (HCC) is the most prevalent primary liver cancer, characterized by its poor prognosis. Deoxyribonuclease 1-like 3 (DNASE1L3), a member of the deoxyribonuclease 1 family, has been implicated in various human cancers, but its specific role in HCC remains unclear.</p><p><strong>Methods: </strong>By integrating transcriptomic and proteomic datasets, DNASE1L3 was identified as significantly associated with HCC through WGCNA and Lasso regression analysis. Subsequently, the clinical diagnostic significance of DNASE1L3 was confirmed using data from TCGA. Additionally, we evaluated immune treatment responsiveness by analyzing Tumor Mutation Burden (TMB) values, Tumor Immune Dysfunction and Exclusion (TIDE) scores, and the expression of immune checkpoint genes. Furthermore, DNASE1L3 expression in HCC was examined through single-cell RNA sequencing (scRNA-seq) analysis using the TISCH 2.0 database.</p><p><strong>Results: </strong>DNASE1L3 expression was significantly reduced in HCC and associated with a poor prognosis. The DNASE1L3low group exhibited higher TMB values and expression of immune checkpoint genes, along with a lower TIDE score, suggesting a greater likelihood of successful immunotherapy. Moreover, scRNA-seq analysis revealed that DNASE1L3 was predominantly expressed in HCC endothelial cells, myeloid cells, and innate lymphoid cells.</p><p><strong>Discussion: </strong>Our findings indicate that DNASE1L3 may be a potential biomarker for both predicting prognosis and assessing the effectiveness of immunotherapy, thus providing significant information for forecasting clinical results and responses to immunotherapy in HCC.</p><p><strong>Conclusion: </strong>The findings of this research could facilitate early detection and propose possible therapeutic targets for HCC.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Drug-resistant Cell Subpopulations in Colorectal Cancer Through Single-cell Analysis and Exploration of Potential Therapeutic Strategies.","authors":"Yiquan Chen, Da Wang","doi":"10.2174/0109298673490855260406093651","DOIUrl":"https://doi.org/10.2174/0109298673490855260406093651","url":null,"abstract":"<p><strong>Introduction: </strong>The therapeutic efficacy of Colorectal Cancer (CRC) is often compromised by resistance to the standard chemotherapy agent oxaliplatin.</p><p><strong>Methods: </strong>This study obtained single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database. Differentially Expressed Genes (DEGs) between resistant and sensitive epithelial subpopulations were identified, followed by enrichment analysis. Pseudotemporal trajectory and cell-cell communication were analyzed using Monocle2 and CellChat, respectively. The candidate drug was predicted by Connectivity Map (cMAP) analysis. External validation included assessment of the EpC2 signature in an oxaliplatin-resistant cell line dataset (GSE76092), survival analysis using The Cancer Genome Atlas (TCGA) cohorts, and re-analysis of the GSE179784 dataset to assess the reproducibility of EpC2-like subpopulations and their DNA Damage Repair (DDR) scores.</p><p><strong>Results: </strong>Cell subpopulations were divided into 10 clusters. Among them, epithelial cells comprised 5 subpopulations, with EPC2 identified as a potential oxaliplatin-resistant subset. DEGs were enriched in the TNF and IL-17 pathways. External validation confirmed the enrichment of EpC2 in resistant cell lines and its association with poor survival. Pseudotemporal trajectory revealed that epithelial cells underwent state transitions, forming two distinct branches. The resistant group exhibited enrichment in RNA splicing and NF-κB pathways. Cell-cell communication analysis revealed interactions involving MDK- NCL and PPIA-BSG. Dasatinib was predicted as a candidate drug.</p><p><strong>Discussion: </strong>We identified an oxaliplatin-resistant subpopulation of Epithelial Cells (EpC2) in CRC, elucidated its multi-layered resistance mechanisms, and integrated multi- omics and cMAP database analyses to predict a potential intervention drug.</p><p><strong>Conclusion: </strong>This study provided potential therapeutic possibilities for oxaliplatin resistance, contributing to CRC treatment.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722047","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}