Drug Design, Development and Therapy最新文献

{"title":"Traditional Chinese Medicines as Anticancer Agents for Non-Small Cell Lung Cancer with EGFR Mutations: A Review.","authors":"Zhiying Wang, Zhixian Zhong, Wenxiao Yang, Yun Li, Ke Zhang, Yabin Gong, Lijing Jiao, Ling Xu","doi":"10.2147/DDDT.S522445","DOIUrl":"https://doi.org/10.2147/DDDT.S522445","url":null,"abstract":"<p><p>Non‑small cell lung cancer (NSCLC) accounts for 85% of all cases of lung cancer cases. Epidermal growth factor receptor (EGFR) with L858R/T790M mutations are commonly found in clinical practice and usually results in resistance to first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Osimertinib is currently the first-line treatment choice for patients with EGFR L858R/T790M mutations, however, as to other EGFR-TKIs, resistance inevitably occurs. There is substantial evidence supporting the efficacy of traditional Chinese medicine (TCM) in the prevention and treatment of non-small cell lung cancer (NSCLC). The mechanisms underlying these effects involve the modulation of key cellular processes, including proliferation, apoptosis, cell cycle regulation, migration, invasion, autophagy, and epithelial-mesenchymal transition. TCM achieves these effects by regulating multiple signaling pathways and mechanisms, while also exhibiting synergistic interactions with EGFR tyrosine kinase inhibitors (TKIs). This review highlights the mechanisms through which TCM influences NSCLC patients harboring EGFR mutations, offering a promising therapeutic strategy for those with EGFR-TKI resistance.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5169-5191"},"PeriodicalIF":4.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Ciprofol Alone versus Ciprofol with Fentanyl for Upper Gastrointestinal Endoscopy: A Randomized, Double-Blind, Controlled Trial.","authors":"Lu Liu, Feng Li, Yanxia Wei, Li Luo, Li Shen, Jie Li, Ninglin Sun, Bin Qian, Dawei Sun","doi":"10.2147/DDDT.S516064","DOIUrl":"https://doi.org/10.2147/DDDT.S516064","url":null,"abstract":"<p><strong>Background: </strong>Ciprofol is increasingly used in surgical procedures, and anesthesiologists have observed that it provides deeper sedation compared to propofol. However, it remains unclear whether the use of ciprofol alone, without combining opioids, is sufficient for upper gastrointestinal endoscopy. This study aims to address this question.</p><p><strong>Objective: </strong>To determine whether ciprofol alone is non-inferior to ciprofol combined with fentanyl regarding sedation success and safety.</p><p><strong>Methods: </strong>In this randomized, double-blind trial, 344 adult patients (ASA I-II, aged 18-70 years) undergoing elective upper gastrointestinal endoscopy were randomized to receive either ciprofol with saline (CS group) or ciprofol with fentanyl (CF group). Participants in both groups received an initial ciprofol dose of (0.4 mg/kg). The CF group received (1 µg/kg) intravenously before ciprofol administration, while the CS group received an equivalent volume of saline. Additional ciprofol doses (0.15-0.30 mg/kg) were administered as needed. The primary outcome was sedation success, defined as procedure completion with no more than two additional ciprofol doses within any 5-minute interval. Secondary outcomes included the incidence of hypotension and hypoxemia, as well as adverse events.</p><p><strong>Results: </strong>Sedation success rates were 99.4% for CS and 100% for CF, demonstrating non-inferiority (difference: -0.6%, 95% CI: -0.02, 0.01). The CS group had lower respiratory depression rates and better hemodynamic stability but higher intraoperative coughing (18.1% vs 2.9%, P=0.01). Induction and recovery times were slightly longer in the CS group, and postoperative dizziness was more common (15.2% vs 7%, P=0.03).</p><p><strong>Conclusion: </strong>Ciprofol alone is non-inferior to ciprofol with fentanyl for sedation in upper gastrointestinal endoscopy and offers advantages in respiratory and hemodynamic stability. However, it is associated with increased coughing, minor delays in induction and recovery, and more postoperative dizziness.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5231-5241"},"PeriodicalIF":4.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Target Mechanism of Compound Qingdai Capsule for Treatment of Psoriasis: Multi-Omics Analysis and Experimental Verification.","authors":"Yuanyuan Qiao, Canzhe Li, Chupeng Chen, Peilin Wu, Yibing Yang, Mingxiang Xie, Na Liu, Jiangyong Gu","doi":"10.2147/DDDT.S523836","DOIUrl":"https://doi.org/10.2147/DDDT.S523836","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a chronic skin disease affected by genetic and autoimmunity. The traditional Chinese medicine, Compound Qingdai Capsule (CQC), has shown potential benefits in treating psoriasis in clinical settings. Despite its efficacy, the molecular mechanisms underpinning its therapeutic action remain unclear.</p><p><strong>Purpose: </strong>This study aimed to unravel the molecular mechanism of Compound Qingdai Capsule for psoriasis based on the psoriasis pathogenic pathway network, integrating multi-omics analysis, systems pharmacology, machine learning modeling, and animal experimentation.</p><p><strong>Methods: </strong>Psoriasis pathogenic pathway network was constructed through employing bioinformatics analysis and psoriasis-related multi-omics data mining. The ingredients of CQC were detected by UPLC-MS/MS, and target prediction was performed by systems pharmacology. Machine learning, including Lasso regression, Random Forest, and Support Vector Machine (SVM), were utilized to screen core targets of psoriasis. Molecular docking was employed to evaluate the binding affinity between ingredients and core targets. The expression levels of core targets were determined using qRT-PCR and ELISA.</p><p><strong>Results: </strong>Psoriasis-related datasets GSE201827 and GSE174763 were comprehensively analyzed to obtain 635 psoriasis-related genes. These genes were further enriched to elucidate signaling pathways involved, leading to the construction of psoriasis pathogenic pathway network. Utilizing UPLC-MS/MS, 29 main ingredients of CQC were characterized. CQC ingredients-targets network was constructed using these ingredients and their targets. Screening of CQC anti-psoriasis core targets using machine learning algorithm. Molecular docking confirmed good binding affinity between these targets and ingredients. Imiquimod (IMQ) induced psoriasis-like rat validated the anti-psoriasis effect of CQC by alleviating symptoms, reducing spleen and thymus index, and modulating the expressions of core targets at mRNA and protein levels.</p><p><strong>Conclusion: </strong>CQC effectively modulates the expression levels of AURKB, CCNB1, CCNB2, CCNE1, CDK1, and JAK3 through various ingredients, such as astilbin, salvianolic acid A, and engeletin, via multiple pathways, thereby alleviating psoriasis-like symptoms.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5209-5230"},"PeriodicalIF":4.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycolytic Dysfunction in Granulosa Cells and Its Contribution to Metabolic Dysfunction in Polycystic Ovary Syndrome.","authors":"Zhenzhen Cao, Qin Zhou, Jie An, Xiaojing Guo, XiaoFang Jia, Yuena Qiu","doi":"10.2147/DDDT.S525651","DOIUrl":"https://doi.org/10.2147/DDDT.S525651","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder in women of reproductive age, marked by hyperandrogenism, ovulatory dysfunction, and insulin resistance, accompanied by significant metabolic disturbances, including glycolytic dysfunction, mitochondrial impairment, and increased oxidative stress. In granulosa cells (GCs), disrupted glycolysis impairs follicular development and compromises oocyte quality, exacerbating reproductive and metabolic abnormalities. At the molecular level, dysregulated energy-sensing pathways, such as AMPK and mTOR, reduce glucose uptake, lower ATP generation, and enhance oxidative stress, fueling disease progression. Epigenetic changes and non-coding RNAs further modulate glycolytic enzyme expression, destabilizing metabolic homeostasis within ovarian follicles. Therapeutically, restoring glycolytic balance using agents like metformin, resveratrol, mogroside V, and nicotinamide mononucleotide (NMN) has shown promise in improving glycolysis, insulin sensitivity, and ovarian function in various models. This review synthesizes current evidence on glycolysis's critical role in PCOS pathophysiology, its influence on follicular energetics and oocyte quality, and highlights metabolic targets for future therapies, offering a foundation for novel mechanism-driven interventions in PCOS management.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5255-5270"},"PeriodicalIF":4.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Therapeutic Potential of FSGTC for Osteoarthritis: A Comprehensive Study Combining Nested Case Analysis, Network Pharmacology, and Experimental Validation.","authors":"Mingyu He, Jian Liu, Wu Gao, Yanqiu Sun, Xiaolu Chen, Yanyan Fang","doi":"10.2147/DDDT.S517935","DOIUrl":"https://doi.org/10.2147/DDDT.S517935","url":null,"abstract":"<p><strong>Objective: </strong>This research aims to clarify the clinical efficacy and potential mechanisms of Fengshi Gutong capsule (FSGTC) in improving inflammatory response and hypercoagulability in osteoarthritis (OA) patients, and to evaluate the safety of FSGTC.</p><p><strong>Methods: </strong>A nested case-control study and association rule analysis were used to evaluate the effects of FSGTC on inflammation, coagulation, and liver and kidney function in OA patients. Screening key pathways for FSGTC treatment of OA through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Subsequently, Hematoxylin-eosin staining (HE), Safranine O-Fast Green staining (S&O), and Immunohistochemistry (IHC) were used to evaluate the effects of FSGTC on cartilage injury, inflammatory cell infiltration, and protein expression in OA rats induced by monosodium iodoacetate (MIA). ELISA detects the expression of pro-inflammatory and procoagulant factors. Organ index and HE staining of organs to evaluate the safety of FSGTC treatment. Subsequently, further validate the above results in IL-1β - stimulated chondrocytes.</p><p><strong>Results: </strong>The clinical data analysis showed that FSGTC can significantly improve inflammation and coagulation indicators in OA patients. The KEGG pathway enrichment analysis results showed that PI3K/AKT is a key signaling pathway for FSGTC intervention in OA. Animal experiments have shown that FSGTC can alleviate cartilage damage and reduce inflammatory cell infiltration in OA rats, while having no effect on organs such as liver, heart, spleen, and kidney. The cell experiment results further confirmed that FSGTC increases chondrocyte viability and reduces the expression levels of COX2, PGE2 and PAI-1 by inhibiting the activation of the PI3K/AKT signaling pathway.</p><p><strong>Conclusion: </strong>FSGTC can alleviate inflammation and hypercoagulability in OA, and this therapeutic effect is attributed to its inhibition of PI3K/AKT pathway activation, thereby reducing the release of pro-inflammatory and procoagulant factors in OA patients, and the above drugs do not affect the liver and kidney function of patients.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5123-5141"},"PeriodicalIF":4.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comparative Evaluation of the Safety and Efficacy of Oliceridine and Sufentanil in Gastrointestinal Endoscopy: A Single-Center, Randomized Controlled Trial.","authors":"Baoyu Ma, Ying Li, Cuibo Leng, Aozhang Ji, Ning Zhang, Xinyi Tao, Qianqian Cao, Shoushi Wang","doi":"10.2147/DDDT.S512529","DOIUrl":"https://doi.org/10.2147/DDDT.S512529","url":null,"abstract":"<p><strong>Purpose: </strong>Gastrointestinal (GI) endoscopic sedation employs a range of medication regimens; however, safer and more effective sedation protocols must be identified. Oliceridine, a novel biased µ-opioid receptor agonist, can reduce opioid-related adverse events. However, compared to traditional opioids, data on its use in GI endoscopic sedation remain limited.</p><p><strong>Patients and methods: </strong>This single-center, randomized controlled clinical trial was conducted between April and July 2024. In total, 628 patients scheduled for GI endoscopy were randomly assigned to receive either remimazolam-etomidate-oliceridine or remimazolam-etomidate-sufentanil for sedation. The primary outcome was the incidence of respiratory depression, and the secondary outcomes included the incidence of hypoxemia, need for airway intervention, procedure- and sedation-related metrics, sedation success rate, and adverse events.</p><p><strong>Results: </strong>Among the 628 patients, 305 and 307 were randomized in the oliceridine and sufentanil groups, respectively, and completed the trial. Respiratory depression occurred in 43 patients (14.1%) in the oliceridine group compared to 67 patients (21.8%) in the sufentanil group (odds ratio, 0.59; 95% CI, 0.39-0.90; <i>p</i>=0.013). No significant differences were observed in the incidence of hypoxemia between the groups; however, the need for airway intervention was significantly higher in the sufentanil group (<i>p</i><0.001). The sedation success rates were 99.7% and 100% in the oliceridine and sufentanil groups, respectively. Additionally, the oliceridine group demonstrated lower incidence of hypotension (11.8% vs 18.2%, <i>p</i>=0.026), postoperative nausea and vomiting (4.6% vs 10.1%, <i>p</i>=0.009), and higher patient satisfaction scores (9 [9,9] vs 9 [8,9], <i>p</i>=0.003).</p><p><strong>Conclusion: </strong>The sedation success rate for GI endoscopy using remimazolam and etomidate in combination with either oliceridine or sufentanil approaches 100%, with oliceridine demonstrating superior safety and enhanced patient satisfaction.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5111-5121"},"PeriodicalIF":4.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Model-Informed Precision Dosing of Remimazolam in General Anesthesia Patients.","authors":"Yueting Chen, Zuo-Jing Zhang, Xiao-Feng Zhang, Yuan Peng, Zheng Jiao, Jing-Xiang Wu","doi":"10.2147/DDDT.S495604","DOIUrl":"https://doi.org/10.2147/DDDT.S495604","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to characterize the pharmacokinetics/pharmacodynamics (PK/PD) of remimazolam in patients under general anesthesia using a population analysis and to develop a web-based dashboard tool that directly displays the optimal dosing regimen for general anesthesia.</p><p><strong>Patients and methods: </strong>A total of 20 patients received remimazolam for general anesthesia, during which intensive arterial blood samples and bispectral index (BIS) values were collected. A population PK/PD model was established, and goodness-of-fit and visual predictive check plots were utilized to evaluate the model's accuracy. Additionally, RxODE and Shiny in R were used to design a web-based dashboard tool to recommend optimal dosing regimens.</p><p><strong>Results: </strong>The three-compartment model with first elimination best described the PK profiles of remimazolam. PK parameters were weight-adjusted via allometric scaling. The correlation between drug exposure and the BIS was optimally characterized through an effect compartment model employing an inhibitory sigmoid Emax model. In addition, a web-based dashboard tool was created to offer initial personalized dosing strategies for general anesthesia procedures, enhanced by graphical representations of the PK/PD profiles associated with the recommended dosing regimens.</p><p><strong>Conclusion: </strong>The developed population PK/PD model effectively captured the dose-exposure-response relationship for remimazolam, allowing for the optimization of personalized dosing strategies.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5099-5109"},"PeriodicalIF":4.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of Novel Anti-Acetylcholinesterase Peptides Using a Machine Learning and Molecular Docking Approach.","authors":"Wei Xiao, Liu-Zhen Chen, Jun Chang, Yi-Wen Xiao","doi":"10.2147/DDDT.S523769","DOIUrl":"10.2147/DDDT.S523769","url":null,"abstract":"<p><strong>Objective: </strong>Alzheimer's disease poses a significant threat to human health. Currenttherapeutic medicines, while alleviate symptoms, fail to reverse the disease progression or reduce its harmful effects, and exhibit toxicity and side effects such as gastrointestinal discomfort and cardiovascular disorders. The major challenge in developing machine learning models for anti-acetylcholinesterase peptides discovery is the limited availability of active peptide data in public databases. This study primarily aims to address this challenge and secondarily to discover novel, safer, and less toxic anti-acetylcholinesterase peptides for better Alzheimer's disease treatment.</p><p><strong>Methods: </strong>A Random Forest Classifier model was constructed from a hybrid dataset of non-peptide small molecules and peptides. It was applied to screen a custom peptide library. The binding affinities of the predicted peptides to acetylcholinesterase were assessed via molecular docking, and top ranked peptides were selected for experimental assay.</p><p><strong>Results: </strong>The top six peptides (IFLSMC, WCWIYN, WIGCWD, LHTMELL, WHLCVLF, and VWIIGFEHM) were selected for experimental validation. Their inhibitiory effects on acetylcholinesterase were determined to be 0.007, 3.4, 1.9, 10.6, 1.5, and 3.9 μmol/L, respectively.</p><p><strong>Discussion: </strong>Predicting anti-acetylcholinesterase peptides is challenging due to the absence of a comprehensive, publicly accessible peptide database. Traditional approaches using only non-peptide small molecules for model construction often have poor performance on predicting active peptides. Here, we developed a machine-learning model from a hybrid dataset of non-peptide small molecules and peptides, which find six potent peptides. This model was as/superior accuracy compared to small-molecule-only models reported before, but has a significant higher capability of discriminating active peptides. Our work shows that hybrid datasets can boost machine-learning model prediction in peptide drug discovery.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5085-5098"},"PeriodicalIF":4.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Letermovir for Cytomegalovirus Prophylaxis Following Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients.","authors":"Yongbing Zhu, Li Wang, Yu Xiang, Yaqin Wang, Ai Zhang, Yao Wang, Mengmeng Yin, Jianxin Dun, Yuting Xu, Qun Hu, Wen Yu, Aiguo Liu","doi":"10.2147/DDDT.S513383","DOIUrl":"10.2147/DDDT.S513383","url":null,"abstract":"<p><strong>Purpose: </strong>Cytomegalovirus (CMV) infection represents a severe complication following hematopoietic cell transplantation (HCT), resulting in high mortality. The prevention of CMV reactivation is crucial for enhancing patient prognosis post-HCT. Letermovir prophylaxis has effectively reduced the incidence of clinically significant CMV infection (csCMVi) in adult HCT recipients. However, clinical data in pediatric patients remain limited.</p><p><strong>Patients and methods: </strong>We included 106 children who underwent HCT at our hospital between March 2019 and July 2024. The patients were grouped based on whether or not they received letermovir prophylaxis. By analyzing their general characteristics and laboratory findings, exploring the risk factors of csCMVi, and assessing the efficacy and safety of letermovir in pediatric patients.</p><p><strong>Results: </strong>Among the 106 patients, all patients were at high risk for CMV reactivation. Forty-four received letermovir prophylaxis, while 62 did not. CsCMVi occurred in 45 patients, with a significantly lower incidence in the letermovir group compared to the control group (5 [11.3%] vs 40 [64.5%], p < 0.001). Umbilical cord blood (UCB) was used in 7 patients (15.9%) in the letermovir group and in 1 patient in the control group (<i>p</i> < 0.05). There was no statistically significant difference in all-cause mortality between the two groups. Grade II-IV GvHD and the use of letermovir were associated with csCMVi, with letermovir identified as the only independent preventive factor for csCMVi during the first 100 days post-HCT, especially in patients with 4-5 risk factors of csCMVi. In patients with aplastic anemia, the incidence of csCMVi was notably lower in those who received letermovir prophylaxis. No patients in the study withdrew from treatment due to adverse reactions.</p><p><strong>Conclusion: </strong>Letermovir is both effective and safe for CMV prophylaxis in pediatric patients following HCT, especially in patients with more risk factors of csCMVi. Grade II-IV GvHD increases the risk of csCMVi, while letermovir prophylaxis reduces the risk.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5059-5069"},"PeriodicalIF":4.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Edaravone in Digestive Diseases - A Narrative Review.","authors":"Haiyun Lei, Mingchun Wang, Ma Huang, Xiaoyun Fu","doi":"10.2147/DDDT.S522011","DOIUrl":"10.2147/DDDT.S522011","url":null,"abstract":"<p><p>Digestive diseases represent a diverse and complex group of systemic disorders, often marked by intricate pathogenic mechanisms and substantial rates of morbidity, disability, and mortality. While effective therapies exist for certain conditions, such as peptic ulcers, gastrointestinal hemorrhage, and viral hepatitis, many others remain difficult to manage due to their limited treatment options, poor response to current therapies, and multifactorial etiologies. As a result, there is a pressing need to develop novel therapeutic agents that offer greater specificity and improved clinical outcomes. Edaravone, a free radical scavenger widely used in the management of neurological disorders, has demonstrated a favorable safety profile and minimal adverse effects. Recent research has expanded our understanding of Edaravone's pharmacological actions, revealing its broad therapeutic potential beyond the nervous system. Its capacity to neutralize reactive oxygen species, reduce oxidative stress, suppress inflammation, inhibit apoptosis, modulate immune function, and enhance tissue repair positions it as a promising candidate for treating digestive disorders. This review highlights current advances in the application of Edaravone in digestive disease models and clinical settings, to offer new perspectives for future prevention, therapeutic strategies, and scientific investigation in this field.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5071-5084"},"PeriodicalIF":4.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}