Biomedicines最新文献

{"title":"Clinical and dGEMRIC Evaluation of Microfragmented Adipose Tissue Versus Hyaluronic Acid in Inflammatory Phenotype of Knee Osteoarthritis: A Randomized Controlled Trial.","authors":"Vilim Molnar, Željko Jeleč, Eduard Rod, Damir Hudetz, Petar Brlek, Igor Borić, Vid Matišić, Jana Mešić, Eduard Stjepan Pavelić, Dinko Vidović, Dejan Blažević, Fabijan Čukelj, Srećko Sabalić, Josip Štivičić, Tomislav Dujmović, Mario Starešinić, Martin Čemerin, David Glavaš Weinberger, Iva Molnar, Martina Smolić, Dragan Primorac","doi":"10.3390/biomedicines13092301","DOIUrl":"10.3390/biomedicines13092301","url":null,"abstract":"<p><p><b>Background</b>: Knee osteoarthritis (OA) is a leading cause of disability, with limited therapies that modify both symptoms and structural degeneration. Autologous microfragmented adipose tissue (MFAT) has emerged as a promising regenerative option, especially in phenotypically distinct OA subgroups. This randomized controlled trial evaluated the clinical and structural efficacy of intra-articular MFAT versus hyaluronic acid (HA) in patients with early to moderate inflammatory phenotype knee OA. <b>Methods</b>: Fifty-three patients were randomized in a 2:1 ratio to receive either MFAT (n = 35) or HA (n = 18). Patients were followed-up for six months post-injection and evaluated using patient-reported outcome measures (KOOS, WOMAC, VAS) and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). A responder analysis defined structural response as ≥10% increase in dGEMRIC in ≥3 of 7 predefined cartilage regions. <b>Results</b>: Both MFAT and HA led to statistically significant improvements in clinical scores and cartilage glycosaminoglycan content. MFAT showed greater mean improvements across most clinical and dGEMRIC measures, although without reaching statistical significance, except for KOOS Symptoms (MFAT: +25.0 vs. HA: +12.7, <i>p</i> = 0.008). Responder-level analysis revealed that all patients who demonstrated structural response also experienced clinically meaningful pain improvement (KOOS Pain ≥ 10), while no patient showed structural benefit without parallel symptomatic relief. <b>Conclusions</b>: MFAT led to greater improvement in symptoms related to joint stiffness, swelling, and crepitus compared to HA, reflecting its potential benefit in targeting the inflammatory features of knee OA. Importantly, HA also led to significant clinical and structural improvements, supporting its continued role as a standard-of-care comparator in knee OA management. Furthermore, the correlation between dGEMRIC and clinical response suggests its utility as a predictive biomarker of treatment success.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alveolar Epithelial Cell Dysfunction in Acute Respiratory Distress Syndrome: Mechanistic Insights and Targeted Interventions.","authors":"Jing Wang, Jie Chao","doi":"10.3390/biomedicines13092299","DOIUrl":"10.3390/biomedicines13092299","url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS) is a life-threatening condition with high mortality. A central driver in its pathogenesis is alveolar epithelial cell (AEC) dysfunction, which leads to disruption of the epithelial barrier, impaired fluid clearance, and dysregulated inflammatory responses. This review summarizes the key mechanisms underlying AEC injury, including programmed cell death (apoptosis, pyroptosis, necroptosis, ferroptosis), oxidative stress, mitochondrial dysfunction, epigenetic reprogramming (DNA methylation, histone modifications), metabolic rewiring (succinate accumulation), and spatiotemporal heterogeneity revealed by single-cell sequencing and spatial transcriptomics. Multicellular crosstalk involving epithelial-immune-endothelial networks and the gut-lung axis further shapes disease progression. Building on these mechanistic foundations, we evaluate emerging AEC-targeted interventions such as pharmacologic agents (antioxidants, anti-inflammatories), biologics (mesenchymal stem cells and engineered exosomes), and gene-based approaches (adeno-associated virus and CRISPR-Cas9 systems delivered via smart nanocarriers). Complementary strategies include microbiome modulation through probiotics, short-chain fatty acids, or fecal microbiota transplantation, and biomarker-guided precision medicine (e.g., sRAGE, exosomal miRNAs) to enable promise individualized regimens. We also discuss translational hurdles, including nanotoxicity, mesenchymal stem cell (MSC) heterogeneity, and gene-editing safety, and highlight future opportunities involving AI-driven multi-omics, lung-on-chip platforms, and epithelium-centered regenerative therapies. By integrating mechanistic insights with innovative therapeutic strategies, this review aims to outline a roadmap toward epithelium-targeted, precision-guided therapies for ARDS.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TAFRO Syndrome-A Decade Later, Still Racing Against Time.","authors":"Yasufumi Masaki","doi":"10.3390/biomedicines13092303","DOIUrl":"10.3390/biomedicines13092303","url":null,"abstract":"<p><p>Since its first description in Japan in 2010 [...].</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial for the Special Issue: Recent Advances in Adipokines-2nd Edition.","authors":"Christa Buechler","doi":"10.3390/biomedicines13092293","DOIUrl":"10.3390/biomedicines13092293","url":null,"abstract":"<p><p>Adipokines are a steadily growing group of bioactive proteins that have mostly been studied in relation to obesity and obesity-associated metabolic diseases [...].</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tolerability and Shared Decision-Making in the Hormonal Management of Endometriosis-Associated Pain.","authors":"Diogo Pinto da Costa Viana, Leonardo Jacobsen, Igor Padovesi, Ana Comin, Eline Lobo de Souza Correia, Daniela Da Maia Fernandes, Ana Carolina Pires Dias","doi":"10.3390/biomedicines13092294","DOIUrl":"10.3390/biomedicines13092294","url":null,"abstract":"<p><p><b>Background</b>: The management of endometriosis-associated pain has traditionally focused on analgesic efficacy. However, with high-level evidence demonstrating therapeutic equivalence among principal hormonal classes, the paradigm has shifted towards a patient-centred approach prioritising long-term tolerability and shared decision-making. Objectives: This review critically synthesises the evidence for the three main hormonal therapies-gonadotropin-releasing hormone (GnRH) analogues, dienogest, and gestrinone-focusing on their distinct tolerability and safety profiles to inform this modern clinical framework. <b>Methods</b>: This narrative review followed the SANRA (Scale for the Assessment of Narrative Review Articles) guidelines. The literature search was performed in PubMed, Embase, and Web of Science in June 2025. <b>Results</b>: Our comparative analysis, based on a structured literature search adhering to SANRA guidelines, shows that while all three classes are effective, they present distinct benefit-risk profiles: GnRH analogues offer potent pain relief but induce a hypoestrogenic state requiring add-back therapy to mitigate bone loss and vasomotor symptoms; dienogest preserves bone mineral density but is associated with challenging bleeding patterns and potential mood disturbances; gestrinone provides robust efficacy with a favourable cardiovascular and skeletal safety profile, although its androgenic effects can significantly impact patient adherence. <b>Conclusions</b>: In the absence of a clear hierarchy of efficacy, the optimal therapeutic choice is not determined by potency, but by a collaborative process in which patient values and tolerance for specific adverse effects guide selection. This review provides a framework to facilitate this shared decision-making (SDM) in clinical practice.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in MASLD After Age 50: Presentation, Diagnosis, and Clinical Implications.","authors":"Ilaria Milani, Maria Eugenia Parrotta, Luca Colangeli, Marianna Chinucci, Simonetta Palleschi, Barbara Rossi, Paolo Sbraccia, Alessandro Mantovani, Frida Leonetti, Valeria Guglielmi, Danila Capoccia","doi":"10.3390/biomedicines13092292","DOIUrl":"10.3390/biomedicines13092292","url":null,"abstract":"<p><p><b>Background</b>: Age over 50, menopause, obesity and type 2 diabetes (T2D) are key risk factors for Metabolic dysfunction-associated steatotic liver disease (MASLD). This observational study aimed to assess sex differences in anthropometric and clinical profile, including non-invasive liver steatosis indices, in subjects with MASLD, obesity and/or T2D, aged ≥ 50 years. <b>Methods</b>: Anthropometric and clinical parameters, non-invasive indices for steatosis and fibrosis and FibroScan^® data were collected. <b>Results</b>: Among 213 patients (65.7% women, median age 63.0 years and mean Body Mass Index (BMI 34.9 kg/m²), men had higher body weight and waist circumference (WC), whereas women showed higher BMI and waist-to-height ratio (WHtR), and were more likely to exceed WC sex-specific and WHtR risk cut-offs. While transaminases values were higher in men, sex-specific cut-offs revealed that women more frequently exceeded these thresholds. No sex-differences were found for Fatty Liver Index (FLI), Fibrosis-4 (FIB-4) or FibroScan^®, although higher rate of mild fibrosis in women. The diagnostic accuracy of FLI for detecting steatosis was significantly higher in men and unsatisfactory in women (Area Under the ROC Curve, AUC 0.863 vs. 0.655). <b>Conclusions</b>: While MASLD is more common in men, these results suggest that postmenopausal women with visceral obesity showed similar or worse liver and cardiometabolic profiles than men, despite appearing healthier based on standard clinical parameters. Notably, common markers like transaminases and the FLI were less accurate in detecting steatosis in women, underscoring the need for sex-specific diagnostic criteria and greater clinical attention to older women, particularly those with central obesity, to ensure early identification and management of MASLD.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rebuilding Mitochondrial Homeostasis and Inhibiting Ferroptosis: Therapeutic Mechanisms and Prospects for Spinal Cord Injury.","authors":"Qin Wang, Qingqing Qin, Wenqiang Liang, Haoran Guo, Yang Diao, Shengsheng Tian, Xin Wang","doi":"10.3390/biomedicines13092290","DOIUrl":"10.3390/biomedicines13092290","url":null,"abstract":"&lt;p&gt;&lt;p&gt;During the pathological process of spinal cord injury (SCI), ferroptosis is closely related to mitochondrial homeostasis. Following the occurrence of SCI, the interruption of local blood supply leads to mitochondrial damage within cells and a reduction in Adenosine triphosphate (ATP) production. This results in the loss of transmembrane ion gradients, causing an influx of Ca&lt;sup&gt;2+&lt;/sup&gt; into the cells, which in turn generates a significant amount of Reactive oxygen species (ROS) and reactive nitrogen species. This leads to severe mitochondrial dysfunction and an imbalance in mitochondrial homeostasis. Ferroptosis is a form of programmed cell death that differs from other types of apoptosis, as it is dependent on the accumulation of iron and lipid peroxides, along with their byproducts. The double bond structures in intracellular polyunsaturated fatty acids (PUFA) are particularly susceptible to attack by ROS, leading to the formation of lipid alkyl free radicals. This accumulation of lipid peroxides within the cells triggers ferroptosis. After SCI, the triggering of ferroptosis is closely associated with the \"death triangle\"-a core network that catalyzes cell death through the interaction of three factors: local iron overload, collapse of antioxidant defenses, and dysregulation of PUFA metabolism (where PUFA are susceptible to attack by reactive ROS leading to lipid peroxidation). These three elements interact to form a central network driving cell death. In the pathological cascade of SCI, mitochondria serve as both a major source of ROS and a primary target of their attack, playing a crucial role in the initiation and execution of cellular ferroptosis. Mitochondrial homeostasis imbalance is not only a key inducer of the \"death triangle\" (such as the intensification of lipid peroxidation by mitochondrial ROS), but is also reverse-regulated by the \"death triangle\" (such as the destruction of mitochondrial structure by lipid peroxidation products). Through the cascade reaction of this triangular network, mitochondrial homeostasis imbalance and the \"death triangle\" jointly drive the progression of secondary damage. This study aims to synthesize the mechanisms by which various therapeutic approaches mitigate SCI through targeted regulation of mitochondrial homeostasis and inhibition of ferroptosis. Unlike previous research, we integrate the bidirectional regulatory relationship between \"mitochondrial homeostasis disruption\" and \"ferroptosis\" in SCI, and emphasize their importance as a synergistic therapeutic target. We not only elaborate in detail how mitochondrial homeostasis-including biogenesis, dynamics, and mitophagy-modulates the initiation and execution of ferroptosis, but also summarize recent strategies that simultaneously target both processes to achieve neuroprotection and functional recovery. Furthermore, this review highlights the translational potential of various treatments in blocking the pathological cascade driven by oxidati","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Significance of Venous-to-Arterial CO₂ Difference in Critically Ill Patients After Major Abdominal Surgery.","authors":"Gyeo Ra Lee, Eun Young Kim","doi":"10.3390/biomedicines13092295","DOIUrl":"10.3390/biomedicines13092295","url":null,"abstract":"<p><p><b>Purpose:</b> The venous-to-arterial carbon dioxide partial pressure difference [P(v-a)CO₂] reflects the adequacy of tissue perfusion, with elevated values suggesting impaired clearance of CO₂. While its prognostic role has been investigated in septic shock and high-risk surgery, evidence in postoperative critically ill patients remains limited. This study aimed to evaluate the prognostic value of ΔP(v-a)CO₂ after major abdominal surgery and its relationship with microcirculatory markers. <b>Methods</b>: We retrospectively analyzed 86 patients admitted to the intensive care unit (ICU) after major abdominal surgery between September 2020 and October 2023. Arterial and central venous blood gas analyses were performed immediately postoperatively and at 24 h. Patients were stratified into groups according to ΔP(v-a)CO₂ (≤ 0 vs. >0). Postoperative outcomes and correlations with central venous oxygen saturation (ScvO₂) were assessed. <b>Results</b>: In the subgroup analysis of patients with an initial P(v-a)CO₂ > 6 mmHg, those in the ΔP(v-a)CO₂ > 0 group required mechanical ventilation (54.5% vs. 22.2%, <i>p = 0.033</i>) and continuous renal replacement therapy (36.4% vs. 8.9%, <i>p = 0.020</i>) more frequently, with longer durations of both interventions (<i>p = 0.011</i> and <i>p = 0.016</i>, respectively). ICU length of stay and the incidence of acute kidney injury were significantly lower in the ΔP(v-a)CO₂ ≤ 0 group. In addition, a modest negative correlation was observed between ScvO₂ measured at 24 h postoperatively and ΔP(v-a)CO₂. <b>Conclusions</b>: ΔP(v-a)CO₂ may serve as a useful marker for postoperative risk stratification in critically ill patients undergoing major abdominal surgery. However, given the retrospective design, small sample size, and single-center setting, these findings should be considered hypothesis-generating and require confirmation in larger, prospective multicenter studies.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-Dimensional Cartilage Tissue Engineering Using Placenta-Derived Extra-Embryonic Mesenchymal Stem Cells: From Isolation to Differentiation.","authors":"Cem Mujde, Atil Bisgin","doi":"10.3390/biomedicines13092291","DOIUrl":"10.3390/biomedicines13092291","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Mesenchymal stem cells (MSCs) offer promising prospects for novel treatment modalities in cellular therapies and artificial organ production. Despite a surge in artificial tissue research, there is a dearth of comprehensive studies detailing the entire process from stem cells to tissue production, coupled with a scarcity. This study, however, presents the utility of extra-embryonic MSCs derived from placental tissue, traditionally considered as medical waste. <b>Methods</b>: Within a 3-dimensional cell culture system, histological assessments, and comprehensive optimization studies, the entire process required for artificial tissue production is addressed. <b>Results</b>: The results obtained are encouraging regarding the advancement of cellular therapies and artificial tissue engineering. However, challenges such as biopolymer degradation highlight the necessity for multistep approaches. Each analysis within this study delves into the discussion and optimization of key steps in artificial tissue production. <b>Conclusions:</b> Consequently, this study not only represents one of the first of its kind but also lays the groundwork for future investigations into relevant clinical applications.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Valemetostat-SAHA-Driven Acetylation of p53 via SET/TAF-Iβ Displacement and p300 Activation Modulates Cell Cycle Regulators in Pancreatic Cancer Cells.","authors":"Michele Di Crosta, Francesca Chiara Ragone, Rossella Benedetti, Gabriella D'Orazi, Roberta Santarelli, Maria Saveria Gilardini Montani, Mara Cirone","doi":"10.3390/biomedicines13092279","DOIUrl":"10.3390/biomedicines13092279","url":null,"abstract":"<p><p><b>Background/Objective:</b> Aberrant acetylation and methylation of histone and non-histone proteins contribute to carcinogenesis. Among non-histone proteins, wild-type (wt) p53 is particularly notable for the critical role that acetylation and methylation play in regulating its stability and function. Although with opposite outcomes, these post-translational modifications (PTMs) can also affect mutant forms of p53 (mutp53), which are frequently detected in cancers. These proteins may acquire oncogenic properties, activating signaling pathways that promote carcinogenesis. Acetylation activates wtp53, while this PTM has been shown to destabilize mutp53, reducing cancer aggressiveness and improving the efficacy of anticancer therapies. In this study, we investigated the possibility of targeting mutp53 in pancreatic cancer cells by using a combination of EZH2 and HDAC inhibitors. <b>Methods:</b> Western blotting, qRT-PCR, and ChIP experiments were performed to address this question. <b>Results:</b> We found that the EZH2 inhibitor Valemetostat (DS) in combination with the histone deacetylase inhibitor SAHA displaced the SET/TAF-Iβ oncoprotein from mutp53 and increased its interaction with the acetyltransferase p300, which was responsible for p53 acetylation. Moreover, mutp53 was downregulated, p21 was upregulated, and CHK1 was reduced, increasing DNA damage and leading to a stronger impairment of pancreatic cancer cell survival compared with single-agent treatments. <b>Conclusions:</b> Our results reveal that combining epigenetic drugs such as Valemetostat and SAHA could be exploited to target mutp53 and improve the outcome of treatments for aggressive tumors harboring it, such as in pancreatic cancer.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 9","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}