European journal of pharmacology最新文献

{"title":"Tetrandrine and adriamycin reverse multidrug resistance by regulating NLRP3/Caspase-1/GSDMD signaling in human breast cancer cells","authors":"Guosong Xin ,&nbsp;Yanxiu Hou ,&nbsp;Yuhan Liu ,&nbsp;Hairu Li","doi":"10.1016/j.ejphar.2025.177635","DOIUrl":"10.1016/j.ejphar.2025.177635","url":null,"abstract":"<div><h3>Purpose</h3><div>This study examined the effects and underlying mechanisms of tetrandrine (TET) combined with adriamycin (ADR) in reversing multidrug resistance (MDR) in breast cancer cells.</div></div><div><h3>Methods</h3><div>Cell viability, proliferation, and drug resistance were assessed via the MTT assay. Small interfering RNA (siRNA) transfection was used to knock down GSDMD expression in MCF-7/ADR cells. Pyroptosis induction by the combined TET and ADR treatment was evaluated through morphological observations, cytotoxicity assays, and flow cytometry. The expression levels of mRNA and proteins were analyzed using qRT-PCR and western blotting, respectively.</div></div><div><h3>Results</h3><div>At non-cytotoxic concentrations, the combined treatment of TET and ADR significantly inhibited the growth of MCF-7/ADR cells, demonstrating a synergistic effect in reversing MDR. This combination effectively reduced MDR protein expression in MCF-7/ADR cells via GSDMD modulation, which diminished efflux activity and promoted ADR accumulation. The increased accumulation of ADR subsequently activated the NLRP3/Caspase-1/GSDMD signaling pathway, leading to elevated LDH release and enhanced pyroptosis rates.</div></div><div><h3>Conclusion</h3><div>The combined use of TET and ADR not only suppresses MCF-7/ADR cell growth but also reverses MDR by targeting the NLRP3/Caspase-1/GSDMD pyroptosis pathway. These findings propose a promising therapeutic strategy for combatting MDR in breast cancer and highlight the potential for further clinical application of this combination therapy.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177635"},"PeriodicalIF":4.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851706","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":"Cannabinoid agonist WIN55,212-2 prevents scopolamine-induced impairment of spatial memory in rats","authors":"Marta Moreno-Rodríguez ,&nbsp;Iker Bengoetxea de Tena ,&nbsp;Jonatan Martínez-Gardeazabal ,&nbsp;Gorka Pereira-Castelo ,&nbsp;Alberto Llorente-Ovejero ,&nbsp;Iván Manuel ,&nbsp;Rafael Rodríguez-Puertas","doi":"10.1016/j.ejphar.2025.177612","DOIUrl":"10.1016/j.ejphar.2025.177612","url":null,"abstract":"<div><div>The endocannabinoid system is involved in diverse processes, like learning and memory, governed by cholinergic neurotransmission. Recent research demonstrates that in a rat model of dementia derived from basal forebrain cholinergic degeneration, WIN55,212-2, a potent cannabinoid receptor agonist, improves cognition through increased cortical choline levels. However, the effect of cannabinoids on cholinergic deficits is still under investigation. In this work, we studied the effect of this treatment in a pharmacological rat model of transient cholinergic hypofunction by the acute administration of the muscarinic antagonist, scopolamine (2 mg/kg), in spatial, recognition and aversive memory tests. Scopolamine induced memory impairment was observed in the three tests and, importantly, the cannabinoid subchronic treatment with low doses of WIN55,212-2 (0.5 mg/kg) prevented this deleterious effect in spatial memory when evaluated in Barnes maze test. Autoradiographic studies indicate that, following the WIN55,212-2 treatment, cannabinoid receptor density increased in the motor and somatosensory cortices. In layers I-V of the motor cortex, the activity of cannabinoid and muscarinic receptors also increased. These results suggest that WIN55,212-2, through the activation of cannabinoid receptors, indirectly elevates the muscarinic tone in key cortical areas for learning and memory, preventing the memory deficits induced by scopolamine specifically in spatial memory. This highlights the importance of the crosstalk between the endocannabinoid and the cholinergic system for learning and memory processes and suggest that cannabinoid agonists might be an alternative for the treatment of cognitive deficits associated with cholinergic dysfunction.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177612"},"PeriodicalIF":4.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863940","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":"Discovery of cinnamoyl–flavonoid hybrid derivatives as inhibitors of SARS-CoV-2 Mpro and anti-inflammatory agents: Experimental and in silico insights into their efficacy against lipopolysaccharide-induced lung injury","authors":"Kraikrit Utama ,&nbsp;Nopawit Khamto ,&nbsp;Atchara Janthong ,&nbsp;Chanidapha Thiraphatchotiphum ,&nbsp;Sittiruk Roytrakul ,&nbsp;Jiraporn Kantapan ,&nbsp;Puttinan Meepowpan ,&nbsp;Padchanee Sangthong","doi":"10.1016/j.ejphar.2025.177636","DOIUrl":"10.1016/j.ejphar.2025.177636","url":null,"abstract":"<div><div>The chemical structures of the parental compounds of flavonoids from <em>Boesenbergia rotunda</em> were modified by conjugation with cinnamic acid to form cinnamoyl–flavonoid hybrid derivatives with enhanced anti-inflammatory and SARS-CoV-2 M^pro-inhibitory properties. Cinnamoyl–flavonoid hybrid derivatives <strong>6</strong> and <strong>10</strong> showed the potential to inhibit SARS-CoV-2 M^pro with IC₅₀ values of 52.49 and 22.62 μM. Compounds <strong>6</strong> and <strong>10</strong> showed lower cytotoxicity in the human lung cell lines MRC-5 and A549 at concentrations greater than 50 μM. The effects of compounds <strong>6</strong> and <strong>10</strong> on cell viability were studied in a 3D co-culture model of A549 and MRC-5 treated with lipopolysaccharide (LPS) and observed through confocal microscopy. Compounds <strong>6</strong> and <strong>10</strong> downregulated <em>p6</em>5 mRNA expression, resulting in a reduction of pro-inflammatory cytokines, including Interleukin 8 (IL-8) and Monocyte Chemoattractant Protein-1 (MCP-1/CCL2), leading to an anti-inflammatory response through Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling pathways. Compound <strong>6</strong> showed potential anti-inflammatory activity, downregulating <em>Bcl-2 Associated X</em> gene (<em>BAX)</em>, which resulted in inhibition of apoptotic cell death when compared to compound <strong>10</strong>. <em>In silico</em> molecular dynamic simulation shed light on how these cinnamoyl–flavonoid hybrid derivatives interact with myeloid differentiation factor 2 (MD-2), which is involved in the inflammatory response. Our findings suggest that cinnamoyl–flavonoid hybrid derivatives show potential as anti-inflammatory drugs and anti-SARS-CoV-2 drugs.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177636"},"PeriodicalIF":4.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881596","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":"Synergistic effects of BET inhibitors and ferroptosis inducers via targeted inhibition of the BRD4/c-Myc/NRF2 pathway in AML","authors":"Mengjun Zhong ,&nbsp;Shuxin Zhong ,&nbsp;Kangjie Qiu ,&nbsp;Xueting Peng ,&nbsp;Xin Liu ,&nbsp;Songnan Sui ,&nbsp;Zhangshuai Dai ,&nbsp;Xianfeng Wang ,&nbsp;Dingrui Nie ,&nbsp;Zhi Yu ,&nbsp;Quan Yu ,&nbsp;Cunte Chen ,&nbsp;Yangqiu Li ,&nbsp;Chengwu Zeng","doi":"10.1016/j.ejphar.2025.177652","DOIUrl":"10.1016/j.ejphar.2025.177652","url":null,"abstract":"<div><div>In acute myeloid leukemia (AML), high expression of BRD4 is associated with poor prognosis. BET inhibitors that mainly inhibit BRD4 can induce AML cell death, but some AML cells are insensitive to BET inhibitors. We found that BET inhibitors could promote the up-regulation of the ferroptosis signaling pathway in AML. In this study, we intend to investigate the synergistic effects of BET inhibitors with ferroptosis inducers in AML cells. The combination of BET inhibitors with ferroptosis inducers (RSL3, FIN56, and Erastin) markedly reduced AML cell viability and increased cell death, as demonstrated by CCK-8 assays and flow cytometry analysis across multiple AML cell lines and primary AML patient samples. Moreover, BET inhibitors combined with ferroptosis inducers elevated the lipid reactive oxygen species (ROS) levels, indicating heightened lipid peroxidation, a hallmark of ferroptosis. Mechanistically, BET inhibitor and ferroptosis inducer co-targeted the BRD4/c-Myc/NRF2 axis, leading to downregulation of NRF2, key regulators of AML cell survival and oxidative stress resistance. NRF2 knockdown amplified the anti-AML effect of this combined treatment, whereas NRF2 overexpression negated this synergy, highlighting its critical role in mediating ferroptosis resistance. Finally, survival analyses of AML patients from the TCGA and GSE71014 datasets revealed that elevated expression of BRD4, NRF2, and its downstream target GPX4, an essential ferroptosis regulator, correlated with poor overall survival, highlighting the clinical relevance of our findings. In all, combining BET inhibition with ferroptosis induction could enhance anti-leukemia effect and represent a novel therapeutic strategy for targeting AML cells.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177652"},"PeriodicalIF":4.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859101","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 interplay between gut microbiome, epigenetics, and substance use disorders: from molecular to clinical perspectives","authors":"Keivan Sahebi ,&nbsp;Mona Arianejad ,&nbsp;Soha Azadi ,&nbsp;Fatemeh Hosseinpour-Soleimani ,&nbsp;Radmehr Kazemi ,&nbsp;Amir Tajbakhsh ,&nbsp;Manica Negahdaripour","doi":"10.1016/j.ejphar.2025.177630","DOIUrl":"10.1016/j.ejphar.2025.177630","url":null,"abstract":"<div><div>Substance use disorders (SUDs) involve a complex series of central and peripheral pathologies, leading to impairments in cognitive, behavioral, and physiological processes. Emerging evidence indicates a more significant role for the microbiome-gut-brain axis (MGBA) in SUDs than previously recognized. The MGBA is interconnected with various body systems by producing numerous metabolites, most importantly short-chain fatty acids (SCFAs), cytokines, and neurotransmitters. These mediators influence the human body's epigenome and transcriptome. While numerous epigenetic alterations in different brain regions have been reported in SUD models, the intricate relationship between SUDs and the MGBA suggests that the gut microbiome may partially contribute to the underlying mechanisms of SUDs. Promising results have been observed with gut microbiome-directed interventions in patients with SUDs, including prebiotics, probiotics, antibiotics, and fecal microbiota transplantation. Nonetheless, the long-term epigenetic effects of these interventions remain unexplored. Moreover, various confounding factors and study limitations have hindered the identification of molecular mechanisms and clinical applications of gut microbiome interventions in SUDs. In the present review, we will (i) provide a comprehensive discussion on how the gut microbiome influences SUDs, with an emphasis on epigenetic alterations; (ii) discuss the current evidence on the bidirectional relationship of gut microbiome and SUDs, highlighting potential targets for intervention; and (iii) review recent advances in gut microbiome-directed therapies, along with their limitations and future directions.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177630"},"PeriodicalIF":4.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863657","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":"TRPM4 channels contribute to Adriamycin chemoresistance in breast cancer cells","authors":"Juan Guo ,&nbsp;Fang Liu ,&nbsp;Xinyue Yang ,&nbsp;Mengyuan Wang ,&nbsp;Shangze Yang ,&nbsp;Kun Lan ,&nbsp;Li Yan ,&nbsp;Ruiyuan Cao ,&nbsp;Xingjuan Chen ,&nbsp;Wu Zhong","doi":"10.1016/j.ejphar.2025.177637","DOIUrl":"10.1016/j.ejphar.2025.177637","url":null,"abstract":"<div><div>Chemoresistance presents a critical challenge in breast cancer treatment. Here, we report that transient receptor potential melastatin 4 (TRPM4) plays a role in modulating doxorubicin (ADR) resistance in breast cancer cells. TRPM4 expression was significantly upregulated at both the mRNA and protein levels in MCF-7/ADR cells, a human breast cancer cell line resistant to the chemotherapy drug ADR. Pharmacological inhibition or knockdown of TRPM4 restored ADR sensitivity, while its overexpression in non-resistant MCF-7 cells diminished drug response, confirming the regulatory role of TRPM4 in resistance mechanisms. Western blot analyses confirmed that elevated TRPM4 expression drives P-glycoprotein (P-gp) upregulation in both MCF-7/ADR and KBv200 cells (KB vinblastine 200 resistant cell line), as well as in Huh7 (human hepatocellular carcinoma cell line) and HCT116 (human colorectal cancer cell line). In addition, we demonstrate that TRPM4 inhibition suppresses the level of NF-κB, a pivotal transcription factor regulating P-gp expression. Furthermore, we found that TRPM4-mediated cellular swelling, rather than membrane depolarization, is the primary driver of P-gp overexpression. Drug-resistant MCF-7/ADR cells exhibited significantly larger cell sizes compared to non-resistant MCF-7 cells, and this effect was reversed following TRPM4 inhibition. The swelling was induced by hypotonic stress rather than changes in membrane potential, further confirming the role of TRPM4 in P-gp regulation through volume changes. Analysis of the TCGA (The Cancer Genome Atlas) database revealed that elevated TRPM4 expression correlates with reduced patient survival, suggesting that TRPM4 plays a role in both drug resistance and tumor progression. Our findings provide new insights into the role of TRPM4 in resistance mechanisms and propose that targeting TRPM4 could represent an innovative therapeutic strategy to overcome chemoresistance and enhance drug efficacy in breast cancer.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177637"},"PeriodicalIF":4.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851707","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":"Presence of dysfunctional soluble guanylate cyclase in mesenteric resistance arteries from rats with mild ligature-induced periodontitis","authors":"Flavia Neto de Jesus ,&nbsp;Simone Aparecida Teixeira ,&nbsp;Leonardo André da Costa Marques ,&nbsp;Marinella Holzhausen ,&nbsp;Camila Ferreira Wenceslau ,&nbsp;Edlaine Linares ,&nbsp;Soraia Kátia Pereira Costa ,&nbsp;Luciana Venturini Rossoni ,&nbsp;Ohara Augusto ,&nbsp;Marcelo Nicolás Muscará","doi":"10.1016/j.ejphar.2025.177632","DOIUrl":"10.1016/j.ejphar.2025.177632","url":null,"abstract":"<div><div>Periodontitis is notable for its high prevalence in the oral cavity and its association with systemic diseases. Functional alterations in vasomotor activity occur in the arteries of rats with mild periodontitis, primarily due to decreased soluble guanylate cyclase (sGC) enzyme activity. This study aims to investigate the functional response of mesenteric resistance arteries (MRA) obtained from rats with mild periodontitis. Vascular reactivity of MRAs from rats in the ligature (L) or sham (S) groups was assessed using a wire myograph. Additionally, antioxidant enzyme activity, the presence of nitrated proteins, cyclic guanosine monophosphate (cGMP) levels, and electron paramagnetic resonance (EPR) spectroscopy were analyzed. The MRAs from the L group showed lower pD2 values in response to sodium nitroprusside or sildenafil and decreased Emax to the sGC stimulator Bay 41–2271 compared to the S group. However, no differences were observed between the groups with respect to the sGC activator Bay 60–2770. The L group exhibited increased nitrotyrosine protein expression, enhanced catalase activity, and reduced superoxide dismutase activity, along with decreased cGMP content after SNP stimulation. The EPR spectrum of the L group showed a weak peak at g 6.00, compared to the S group, confirming the oxidation of sGC heme-iron (Fe⁺²) to heme-Fe⁺³. In the early phase of bilateral ligature-induced periodontitis in rats, functional changes in the nitric oxide (NO)-cGMP pathway occur in the MRA due to reduced sGC activity and excessive production of iNOS-derived NO, superoxide anion, or a combination of both.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"998 ","pages":"Article 177632"},"PeriodicalIF":4.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881595","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":"Ozone protects from myocardial ischemia-reperfusion injury via inhibition of the NLRP3 inflammasome","authors":"Guohao Xu ,&nbsp;Xiaotong Sun ,&nbsp;Jianxiong An ,&nbsp;Fan Sun ,&nbsp;Chengming Zhang ,&nbsp;John P. Williams","doi":"10.1016/j.ejphar.2025.177631","DOIUrl":"10.1016/j.ejphar.2025.177631","url":null,"abstract":"<div><div>Ischemic heart disease (IHD) is a leading cause of morbidity and mortality worldwide. Myocardial ischemia/reperfusion injury (MIRI) is the primary cause of myocardial injury triggered by post-myocardial infarction reperfusion therapy. Its pathogenesis involves Ca²⁺ overload, the production of large amounts of oxygen-free radicals, inflammation, and cell necrosis. Growing evidence suggests that the NLRP3 inflammasome significantly contributes to the sterile inflammatory response and pyroptosis in MIRI, linking damage sensing to the initiation and amplification of the inflammatory response. Reportedly, ozone exerts anti-inflammatory and anti-infection effects by activating the antioxidant system. Additional evidence suggests that ozone inhibits NLRP3 inflammasome expression to relieve ischemic injury. In this study, we aimed to explore whether pretreating the myocardium with ozone protects it from MIRI by inhibiting the NLRP3 inflammasome. Rats were subjected to rectal infusion of ozone for 5 consecutive days, followed by ligation of the left anterior descending coronary artery for 30 min and reperfusion for 120 min to induce MIRI. Experimental results were obtained using echocardiography, triphenyltetrazolium chloride and hematoxylin and eosin staining, western blotting, and enzyme-linked immunosorbent assay. The results showed that ozone significantly improved the diastolic function of the heart, reduced the area of myocardial infarction, and decreased the expression levels of NLRP3, pro-caspase-1, ASC, and the secretion of caspase-1, interleukin (IL)-1β, and IL-18. In summary, these findings reveal that ozone pretreatment can alleviate the damage that occurs during MIRI by inhibiting the NLRP3 Inflammasome.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177631"},"PeriodicalIF":4.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850155","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":"Advancing therapeutic approaches and shaping future perspectives in the management of autosomal dominant polycystic kidney disease (ADPKD): Insights from clinical trials","authors":"Murali Krishna Moka ,&nbsp;Deepalaxmi Rathakrishnan ,&nbsp;Sriram D.K. ,&nbsp;Melvin George","doi":"10.1016/j.ejphar.2025.177634","DOIUrl":"10.1016/j.ejphar.2025.177634","url":null,"abstract":"<div><h3>Background</h3><div>Autosomal dominant polycystic kidney disease (ADPKD) is a genetically inherited disorder characterized by progressive renal cyst formation, leading to end-stage renal disease (ESRD). The disease causes a continuous decline in renal function, resulting in significantly enlarged kidneys that adversely affect the patient's quality of life (QOL). Despite the identification of causative gene mutations, no approved therapeutic intervention halts cystogenesis or prevents renal failure.</div></div><div><h3>Objectives</h3><div>This review aims to evaluate the potential of emerging pharmacological interventions and investigational treatments to decelerate cyst growth and disease progression in ADPKD, with a focus on clinical trial outcomes and regulatory advancements.</div></div><div><h3>Methods</h3><div>Data from clinical trials (phases I-IV) were systematically reviewed to assess the effectiveness and safety of various therapeutic strategies for ADPKD. Mechanism-agnostic approaches, biomarker integration, and regulatory developments were also analyzed to understand their role in improving clinical management.</div></div><div><h3>Results</h3><div>Clinical studies indicate that pharmacological interventions and investigational therapies show promise in slowing cyst growth and disease progression. The U.S. FDA's adoption of mechanism-agnostic strategies and biomarker-based approaches has enhanced the framework for managing ADPKD. However, genetic heterogeneity and disease complexity remain significant barriers.</div></div><div><h3>Conclusion</h3><div>While a definitive cure for ADPKD remains elusive, recent therapeutic advancements provide hope for improving disease management and patient outcomes. Continued innovation and research are essential to overcome challenges in cystogenesis prevention and develop curative strategies.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177634"},"PeriodicalIF":4.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851673","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":"Harnessing histone deacetylase inhibitors for enhanced cancer immunotherapy","authors":"Fatemeh Hedayat ,&nbsp;Elnaz Faghfuri","doi":"10.1016/j.ejphar.2025.177620","DOIUrl":"10.1016/j.ejphar.2025.177620","url":null,"abstract":"<div><div>Many cancers are capable of hindering the immune response against tumor cells, promoting their growth and spread; this has inspired research aimed at reversing these processes to reactivate the immune system, resulting in significant therapeutic advantages. One of the strategies being explored involves histone deacetylase (HDAC) inhibitors (HDACis), which represent a new category of targeted therapies that alter the immune system's reaction to cancer via epigenetic changes. Recently, six HDACis have been authorized for clinical applications.</div><div>This review aims to provide a concise overview of how different classes of HDACis affect the immune system, based on both in vitro, in vivo, and clinical studies, and explore the latest advancements in combining new immunotherapies with these drugs.</div><div>HDACis have been found to influence how various cancer treatments work by, for instance, enhancing access to exposed DNA through the relaxation of chromatin, disrupting DNA repair mechanisms, and boosting the expression of immune checkpoint receptors. Combining HDACis with immunotherapy could enhance antitumor effects and reduce drug resistance.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"997 ","pages":"Article 177620"},"PeriodicalIF":4.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834286","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}