European journal of pharmacology最新文献

{"title":"Investigating the role of 1,8-Cineole in mitigating ferroptosis in a HFSD/STZ diabetes mellitus type 2-induced model: A GEO data analysis approach.","authors":"Hong Yang, Yongxin Chen, Guoping Wu, Pengyan Ren, Tingting Chen, Jia Liu, Bao Zhang, Xiao Ma, Feng Jiang, Yue Li, Ling Tao, Xiangchun Shen","doi":"10.1016/j.ejphar.2025.177846","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.177846","url":null,"abstract":"<p><p>Fructus Alpiniae Zerumbet (FAZ), a folk medicinal herb used by the Miao people in Guizhou, China, is rich in 1,8-Cineole - a bioactive monoterpene oxide with antioxidant and neuroprotective properties. However, its therapeutic potential against pancreatic β cells dysfunction, a hallmark of type 2 diabetes mellitus (T2DM), remains unexplored. This study investigated the molecular mechanism by which 1,8-Cineole mitigates hyperglycemia induced β cells ferroptosis. Using high-fat and high-sugar diet / streptozotocin (HFSD/STZ) diabetes mellitus type 2-induced model (DM) and high glucose (HG)-treated β cells model. We demonstrated that 1,8-Cineole ameliorated pancreatic islet structural disorganization and pathological glycogen deposition in diabetic mice. Mechanistically, 1,8-Cineole suppressed lipid peroxidation and iron overload while restoring the expression of ferroptosis markers (GPX4 and COX2). It concurrently resolved autophagy deficiency, evidenced by upregulated LC3II/I ratio, enhanced Beclin-1 expression, and stabilized p62. Bioinformatic analysis of diabetic pancreatic transcriptomes (GEO dataset GSE25724) linked ferroptosis and PI3K/AKT/mTOR signaling to β cells dysfunction. Cellular thermal shift assay (CETSA) and molecular docking confirmed direct binding of 1,8-Cineole to PI3K with favorable binding energy at the catalytic site. Pharmacological validation using 740-YP (YP, a PI3K agonist) and LY294002 (LY, a PI3K inhibitor) revealed that 1,8-Cineole exerted its anti-ferroptotic effects via PI3K/AKT/mTOR pathway activation. Co-treatment with 740-YP synergistically enhanced β cells protection, whereas LY294002 abrogated 1,8-Cineole's efficacy. Collectively, these findings unveil 1,8-Cineole as a novel PI3K/AKT/mTOR activator that rescues β cells function via coordinated regulation of autophagy and ferroptosis, thereby providing a mechanistic foundation for its therapeutic application in DM.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177846"},"PeriodicalIF":4.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ROS confer resistance to 3 TC in p53 mutant colorectal cancer by promoting autophagy and ER stress.","authors":"Yiting Lu, Ying Jiang, Xinyu Liao, Junqi Xiang, Xiaohui Xu, Yidan Han, Lin Cui, Jian Zhang, Yue Li, Xia Zhang, Yunlong Lei, Longhao Li","doi":"10.1016/j.ejphar.2025.177837","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.177837","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is among the most frequently diagnosed cancers globally. Lamivudine (3 TC), a nucleoside reverse transcriptase inhibitor (NRTI) commonly used for treating Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV), has recently demonstrated anticancer activity against p53-mutant CRC in Phase 2 clinical trials. However, the underlying mechanisms remain elusive. Our study revealed that 3 TC promotes the accumulation of reactive oxygen species (ROS), which potentially counters its anticancer efficacy in p53-mutant CRC cells. Furthermore, we observed that ROS induced by 3 TC stimulates autophagy independently of the protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway and also activates the activating transcription factor 4 (ATF4)-mediated endoplasmic reticulum (ER) stress pathway. By inhibiting autophagy and ER stress, the anticancer effect of 3 TC was enhanced. In summary, our findings demonstrate that ROS accumulation attenuates the anticancer efficacy of 3 TC by promoting autophagy and ER stress, providing novel insights into the molecular mechanisms underlying 3 TC's therapeutic role in p53-mutant CRC.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177837"},"PeriodicalIF":4.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LSI312A modulates myeloid-derived suppressor cell-mediated immunosuppression via NLRP3 inflammasome inhibition","authors":"Chaelin Lee,&nbsp;Inmoo Rhee","doi":"10.1016/j.ejphar.2025.177836","DOIUrl":"10.1016/j.ejphar.2025.177836","url":null,"abstract":"<div><div>Myeloid-derived suppressor cells (MDSCs) are immune suppressive cells that inhibit neighboring immune cells activity and promote tumor growth by producing anti-inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS), and cytokines. They also induce pro-inflammatory cytokines like IL-1β, further enhancing immunosuppression and resistance to therapy. The NLRP3 inflammasome plays a crucial role in host defense against infections but also contributes to autoimmune diseases and cancer when dysregulated. Due to its role in inflammation and cancer, the NLRP3 inflammasome is a potential therapeutic target. Here, we demonstrate that LSI312A, a biosynthetic compound of Homoisoflavanoids, inhibits NLRP3-mediated inflammasome activation in MDSCs. LSI312A downregulated pro-caspase-1, and pro-IL-1β in the Toll-like receptor 4 (TLR4)-induced NLRP3 inflammasome pathway. It also reduced NO production and IL-1β secretion. In an acute bacterial infection mouse model, LSI312A depleted MDSCs by inhibiting NLRP3 inflammasome activation, while sparing other immune cells. These findings suggest that LSI312A modulates MDSC-mediated immunosuppression and highlights its potential as an adjuvant therapy for cancer treatment.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1002 ","pages":"Article 177836"},"PeriodicalIF":4.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Gut Microbiota in Tirzepatide-Mediated Alleviation of High-Fat Diet-Induced Obesity.","authors":"Ruonan Wang, Zijing Lin, Mingjie He, Yi Liao, Yunfei Xu, Chengzhi Chen, Xinhao Duan, XueJun Jiang, Jingfu Qiu","doi":"10.1016/j.ejphar.2025.177827","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.177827","url":null,"abstract":"<p><strong>Purpose: </strong>In this study, we aim to explore the effects of tirzepatide on the gut microbiota in mice with obesity induced by a high-fat diet.</p><p><strong>Methods: </strong>Forty male C57BL/6J mice, aged six weeks, were randomly assigned to one of four experimental groups: normal control diet, normal control diet with tirzepatide treatment (NCD+TZP), high-fat diet and high-fat diet with tirzepatide treatment (HFD+TZP). Mice in the HFD group were fed a high-fat diet for ten weeks to establish an obesity model. Subsequently, the NCD+TZP and HFD+TZP groups received subcutaneous tirzepatide injections for 14 days, while the NCD and HFD groups were administered an equivalent volume of saline solution.</p><p><strong>Results: </strong>The results showed that tirzepatide significantly suppressed weight gain, reduced the area under the curve in glucose tolerance tests, improved insulin resistance, and decreased adipose tissue mass in mice. Moreover, tirzepatide effectively attenuated lipid deposition and fat droplet formation in the livers of obese mice while modulating the expression of genes implicated in abnormal glucose metabolism. Regarding gut microbiota, tirzepatide alleviated high-fat diet-induced dysbiosis by altering microbial composition and diversity. Following high-fat diet exposure, the abundance of certain bacterial genera-including Akkermansia, Bacteroides, Mucispirillum, Enterococcus, and Alistipes-significantly declines, whereas Faecalibaculum, Allobaculum, and Ileibacterium exhibit notable increases. Tirzepatide intervention facilitated the restoration of gut microbiota homeostasis after high-fat diet exposure. Additionally, correlation analyses revealed that Akkermansia, Bacteroides, and Enterococcus levels negatively correlate with weight gain, blood glucose levels, and various obesity-related indicators, whereas Ileibacterium and Allobaculum abundance positively associates with obesity-related traits.</p><p><strong>Conclusion: </strong>In summary, our findings indicate that tirzepatide has the potential to alleviate high-fat diet-induced gut microbiota dysbiosis in mice. Furthermore, changes in the abundance of specific microbial communities linked to obesity-related outcomes may play a role in the anti-obesity effects of tirzepatide.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177827"},"PeriodicalIF":4.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oleocanthalic acid improves MASH features via a NOX1-dependent mechanism","authors":"Yahima Frion-Herrera ,&nbsp;Ilaria Zanotto ,&nbsp;Martina Colognesi ,&nbsp;Anna Signor ,&nbsp;Doretta Cuffaro ,&nbsp;Adriana Chilin ,&nbsp;Marco Macchia ,&nbsp;Giovanni Marzaro ,&nbsp;Maria Digiacomo ,&nbsp;Daniela Gabbia ,&nbsp;Sara De Martin","doi":"10.1016/j.ejphar.2025.177847","DOIUrl":"10.1016/j.ejphar.2025.177847","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disease with increasing incidence. This study aimed at assessing the beneficial effects of oleocanthalic acid (OcA), extracted from extra virgin olive oil, in cellular models of MASH. OcA effects on lipid accumulation, oxidative stress, inflammation, and fibrosis were evaluated on 2D HepG2 cells treated with a palmitic and oleic acid mixture (1:2 0.1 mM) to induce steatosis, HepG2 co-cultured with THP-1-derived M1-like macrophages, multicellular spheroids (MCS) composed of HepG2 and TGFβ1-activated LX-2 cells co-cultured with macrophages, and spheroids of 3T3-L1-derived adipocytes. OcA effect was assessed by evaluating lipid droplets after Bodipy stain, reactive oxygen species (ROS), and mRNA expression by qPCR. The expression of the fibrogenic marker <em>α</em>-smooth muscle actin (Acta2) was assessed by ICC. OcA interaction with the pro-oxidant NADPH oxidases NOX1 and NOX4 was investigated <em>via</em> molecular docking simulations. OcA reduced the size and number of lipid droplets and ROS in HepG2 cells. In the MCS model, besides reducing lipid accumulation, OcA promoted a switch in macrophages towards an anti-inflammatory phenotype. OcA decreased Acta2 expression in activated LX-2 cells and prevented the LX-2 cell activation induced by the secretome of 3T3-L1-derived adipocyte spheroids. Molecular docking simulations suggested that OcA could act as a selective NOX1 inhibitor, binding to NOX1 in close contact with the FAD molecule. In conclusion, OcA demonstrated promising anti-steatotic, anti-inflammatory, and anti-fibrotic effects in different <em>in vitro</em> models of MASH, thus representing a potential therapeutic option for preventing lipid accumulation and fibrogenesis in MASH, with a NOX1-dependend mechanism of action.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1002 ","pages":"Article 177847"},"PeriodicalIF":4.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telmisartan and/or vitamin D3 ameliorate skeletal muscle injury in a rat model of metabolic syndrome: A new insight into PPAR-γ/AT₁ receptor/GLUT4 axis.","authors":"Nehal S Wahba, Naglaa Z Eleiwa, Nada M Eisa, Salah A Ghareib","doi":"10.1016/j.ejphar.2025.177845","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.177845","url":null,"abstract":"<p><strong>Aims: </strong>The current study investigated the potential molecular mechanisms of telmisartan and vitamin D3 against the progression of skeletal muscle injury in a metabolic syndrome (MetS) rat model and the capacity of vitamin D3 to potentiate telmisartan effects.</p><p><strong>Main methods: </strong>This 12-week study comprised a 6-week induction phase to establish MetS, followed by a 6-week treatment phase. MetS was induced by supplementing drinking water with 10% fructose and providing a diet enriched with 24% fat and 3% NaCl. Following the induction phase and along with fructose/fat/NaCl feeding, MetS rats exhibiting weight gain, dysglycemia, atherogenic dyslipidemia, hyperuricemia, hypertension, and soleus muscle dysfunction were treated orally with telmisartan (5 mg/kg), vitamin D3 (10 μg/kg) or both daily for an additional 6 weeks before sacrifice.</p><p><strong>Key findings: </strong>MetS rats exhibited increased soleus muscle oxidative stress, inflammation, and insulin resistance, accompanied by functional decline and structural damages (interstitial edema, leukocytic infiltration, degenerative myopathy, and fibrosis). Telmisartan and vitamin D3 significantly mitigated these detrimental effects. While telmisartan demonstrated broad protective effects, it failed to combat the MetS-induced muscular fibrosis. Conversely, vitamin D3 played a prominent anti-fibrotic role, which significantly contributed to the observed functional and structural recovery of MetS-induced skeletal muscle damage.</p><p><strong>Significance: </strong>Our data provide a molecular basis for treating MetS-induced skeletal muscle injury through the co-administration of vitamin D3 and telmisartan, a unique angiotensin II type 1 receptor (AT₁ receptor) blocker and partial peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist. A new insight has been introduced into PPAR-γ/AT₁ receptor/glucose transporter type 4 (GLUT4) axis.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177845"},"PeriodicalIF":4.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carnosine improves colonic hyperpermeability through the brain histamine H1 receptor, basal forebrain cholinergic neurons, adenosine A2B receptors and vagus nerve in rats","authors":"Masatomo Ishioh ,&nbsp;Tsukasa Nozu ,&nbsp;Saori Miyagishi ,&nbsp;Takuya Funayama ,&nbsp;Nobuhiro Ueno ,&nbsp;Kaoru Takakusaki ,&nbsp;Toshikatsu Okumura","doi":"10.1016/j.ejphar.2025.177844","DOIUrl":"10.1016/j.ejphar.2025.177844","url":null,"abstract":"<div><div>Leaky gut is implicated in disorders such as irritable bowel syndrome (IBS) and Alzheimer's disease (AD). Our previous study demonstrated that brain histamine H1 receptor signaling—mediated via basal forebrain cholinergic neurons (BFCNs), adenosine A2B receptors, and the vagus nerve—regulates intestinal barrier function. In this study, we investigated the role of carnosine, a dipeptide composed of beta-alanine and L-histidine, in modulating intestinal barrier integrity. In an LPS-induced leaky gut rat model, intracisternal administration of carnosine improved colonic permeability as determined by the Evans blue dye method. This effect was abolished by brain H1 receptor antagonism, vagotomy, and inhibition of either BFCNs or adenosine A2B signaling, suggesting that carnosine acts via these central pathways. Similarly, high-dose intraperitoneal carnosine alleviated colonic hyperpermeability, with its effect also blocked by the same interventions. Additionally, exercise reduced LPS-induced hyperpermeability—an effect eliminated by brain histamine H1 receptor blockade. These findings indicate that peripheral carnosine, including muscle-derived carnosine, contributes to the central regulation of the intestinal barrier. Enhanced barrier integrity, which reduces visceral hypersensitivity, suggests that carnosine may be an effective therapeutic for IBS. Moreover, the decline in muscle carnosine observed in sarcopenia, coupled with an increased dementia risk, supports its therapeutic potential for AD. Collectively, the present study underscores the promise of carnosine and muscle-derived strategies in managing leaky gut-related disorders.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1002 ","pages":"Article 177844"},"PeriodicalIF":4.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mendelian randomization analysis with the GEO database: Exploring the molecular mechanism underlying insulin therapy for perioperative neurocognitive disorders","authors":"Chenxin Jian ,&nbsp;Ji Xia ,&nbsp;Nisha Wang ,&nbsp;Yajuan Li ,&nbsp;Lei Shi ,&nbsp;Qiyang Ding ,&nbsp;Yixiao Yan ,&nbsp;Jiansheng He ,&nbsp;Hao Tian ,&nbsp;Wei Gao","doi":"10.1016/j.ejphar.2025.177843","DOIUrl":"10.1016/j.ejphar.2025.177843","url":null,"abstract":"<div><div>Central insulin resistance is a significant factor in perioperative neurocognitive disorders (PND), yet the therapeutic effects and underlying molecular mechanisms of insulin remain unclear. We conducted a bidirectional Mendelian randomization (MR) study to investigate the causal relationships between insulin use and PND. The forward MR analysis revealed that insulin use considerably reduced the risk of delirium (odds ratio [OR] = 0.01, 95 % confidence interval [CI]: 0.0007–0.22, P = 0.003) and enhanced cognitive performance (OR = 8.03, 95 % CI: 2.83–22.78, P = 0.001). Importantly, the reverse MR analysis indicated that cognitive impairment or delirium did not causally affect insulin use (OR ≈ 1.0, P &gt; 0.5). Utilizing GEO datasets, we identified 63 differentially expressed genes (DEGs) common to both postoperative delirium and insulin treatment. Subsequent analyses, including the construction of a protein-protein interaction network and Gene Ontology (GO) and KEGG pathway analyses, identified EPN2, DNAJC6, ARFGAP1, and HIP1R as key hub genes that could serve as potential therapeutic targets for PND. Further research showed that these hub genes are part of a multi-pathway interactive network, which may significantly contribute to the onset and progression of PND, with insulin also affecting their regulation. Our results establish a unidirectional genetic causality for the therapeutic effects of insulin in PND and reveal new molecular targets, thereby improving our understanding of the mechanisms behind insulin treatment for PND.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1002 ","pages":"Article 177843"},"PeriodicalIF":4.2,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α-Cyperone safeguards against cerebral ischaemia‒reperfusion injury through the activation of the Nrf2 signalling pathway.","authors":"Hailong Yu, Ying Chen, Tianlan Qu, Jing Hang, Xiaoyun Huang, Aipeng Hu, Tianwei Wang, Yahao Gao, Jun Shao, Yuping Li, Yingzhu Chen","doi":"10.1016/j.ejphar.2025.177842","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.177842","url":null,"abstract":"<p><p>Neuroinflammation is a significant factor that exacerbates secondary damage following cerebral ischaemia/reperfusion (CI/R) injury. α-Cyperone (CYP), the principal active constituent of the traditional Chinese medicine Cyperus rotundus L., decreases inflammation. Nonetheless, its impact on CI/R injury remains unknown. Here, we examined the potential involvement of CYP in regulating CI/R injury-induced oxidative stress and apoptosis. Middle cerebral artery occlusion was used to establish a model of CI/R injury in male C57BL/6J mice. CYP (5 or 10 mg/kg) was administered by intraperitoneal injection 30 minutes, 24 hours, and 48 hours after model establishment. CYP markedly diminished the lesion volume, enhanced neuronal function and reduced apoptosis and oxidative stress. Moreover, CYP increased Nrf2, HO-1, NQO1, and SOD-1 expression in vivo, protecting neurons against hemin stimulation by facilitating Nrf2 nuclear translocation. ML385 (an Nrf2 inhibitor) fully abolished the protective effects of CYP in vivo following CI/R injury. Our data indicate that CYP mitigates CI/R injury-induced apoptosis and oxidative stress through Nrf2 signalling pathway activation, suggesting the possible therapeutic effect of CYP on CI/R injury.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177842"},"PeriodicalIF":4.2,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current biological, chemical and physical gene delivery approaches for producing induced pluripotent stem cells (iPSCs).","authors":"Elahe Izadi, Seyedeh Shima Mohammad, Mazdak Ganjalikhani Hakemi, Shirin Eshghi, Leila Saremi, Zohreh Saltanatpour, Amir Ali Hamidieh","doi":"10.1016/j.ejphar.2025.177786","DOIUrl":"https://doi.org/10.1016/j.ejphar.2025.177786","url":null,"abstract":"<p><p>The discovery of induced pluripotent stem cells (iPSCs) has revolutionized the research platform for disease modeling, drug discovery, cell therapy and regenerative medicine. Due to the importance of iPSCs over the past decade, various studies have focused on finding a safe and efficient gene delivery system to introduce reprogramming factors (RFs) into somatic cells, particularly for clinical applications. However, generated iPSCs from any source must undergo genomic, epigenomic, and functional characterizations to ensure they are free of somatic memories and safe for clinical application. In this review, almost all the employed cargos for delivering RFs into somatic cells were investigated, focusing on biological, chemical, and physical approaches to promote reprogramming efficiency and reduce exogenous factors. Moreover, the advantages and disadvantages of each approach were highlighted and cutting-edge technologies in iPSCs technology were also discussed. This review aims to provide a comprehensive overview discussing how to improve the efficiency and quality of iPSCs production.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177786"},"PeriodicalIF":4.2,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}