Drug Design, Development and Therapy最新文献

{"title":"Eribulin plus Pyrotinib in Trastuzumab-Resistant, HER2-Positive Advanced Breast Cancer: A Single-Arm, Multicenter Phase II Trial (EPIC Trial).","authors":"Ruoyang Li, Meiqi Wang, Xiangshun Kong, Jie Ma, Xiuheng Qi, Zhenchuan Song","doi":"10.2147/DDDT.S547569","DOIUrl":"10.2147/DDDT.S547569","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to assess the efficacy and safety of combining Eribulin with Pyrotinib in patients diagnosed with advanced HER2-positive breast cancer and exhibiting resistance to trastuzumab. This subgroup of patients typically faces a bleak clinical prognosis with limited guidance available for treatment decisions.</p><p><strong>Patients and methods: </strong>Patients (N=30) with HER2-positive metastatic breast cancer, ECOG 0-1, and prior trastuzumab/taxane therapy received oral Pyrotinib 400 mg daily and intravenous Eribulin 1.4 mg/m² (days 1/8 of 21-day cycles for 6 cycles), followed by Pyrotinib until progression/intolerable toxicity. The primary endpoint was progression-free survival (PFS).</p><p><strong>Results: </strong>Between February 2021 and September 2023, 30 patients were enrolled in the study, with a median age of 57 years. All patients had previously received treatment with trastuzumab and taxanes. As of April 14, 2025, the median follow-up duration was 26 months. 18 patients experienced disease progression or death. The median progression-free survival (PFS) was 13.47 months (95% confidence interval [CI], 8.17-16.27), with a 12-month PFS rate of 61.7% (95% CI, 44.2%-86.0%). 12-month overall survival (OS) rate of 75.3% (95% CI 66.2-84.4). The objective response rate was 56.7% (17/30). The disease control rate (DCR) reached 80.0% (24/30), while the clinical benefit rate (CBR) was 73.3% (22/30). The median overall survival was not reached. Any adverse event (AE) of any grade with an incidence of more than 30% was Neutropenia (73.3%), diarrhea (70%), nausea/vomiting (66.7%), Peripheral neuropathy (63.3%), AST/ALT increased (43.3%), Anorexia (33.3%). There were no treatment-related deaths.</p><p><strong>Conclusion: </strong>The combination of Eribulin and Pyrotinib emerges as a viable treatment option for HER2-positive advanced breast cancer patients who have exhibited resistance to trastuzumab. Despite advancements in anti-HER2 therapies, further research is required to address remaining challenges in this specific clinical scenario.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8463-8474"},"PeriodicalIF":5.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130263","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":"Physiologically Based Pharmacokinetic Modeling and Dose Optimization of Linezolid in Pediatric Patients With Renal Impairment.","authors":"Jia-Qi Lou, Ben-Nian Huo, Ya Yang, Shu-Feng Wang, Lu-Dan Zhang, Yun-Tao Jia, Lin Song","doi":"10.2147/DDDT.S525400","DOIUrl":"10.2147/DDDT.S525400","url":null,"abstract":"<p><strong>Objective: </strong>Linezolid (LZD), a commonly used antimicrobial agent in clinical practice, has not undergone adequate pharmacokinetic (PK) assessment in pediatric populations with renal impairment (RI). Physiologically based pharmacokinetic (PBPK) modeling provides unique benefits for investigating drug pharmacokinetics in specific patient groups. This study aimed to employ the PBPK model to refine and optimize the therapeutic dosing protocol of LZD for RI pediatric patients.</p><p><strong>Methods: </strong>The model was developed and validated for both healthy adults and RI adults, which was subsequently adapted for pediatric applications. Upon verification of the pediatric Based on clinical PK data and real-world study findings, the PBPK model demonstrated precise prediction of LZD exposure in pediatric populations with varying degrees of RI, encompassing weight- and age-associated PK variations.</p><p><strong>Results: </strong>The PBPK modeling simulations exhibited robust agreement with observational data for LZD across both oral and intravenous delivery routes under diverse dosing protocols, as evidenced by the fold error (FE) always between 0.5 and 2 times, geometric mean fold error (GMFE) was less than 2.0 and mean absolute prediction error (MAPE) was within 100%. Pediatric populations with severe or end-stage RI exhibited 1.21-fold and 1.28-fold elevations in plasma concentration-time curve (AUC) values, respectively, relative to healthy pediatric counterparts when administered equivalent 10 mg/kg LZD doses. Pharmacodynamic analysis confirmed that the proposed dosing regimens-8 mg/kg every 8 hours for children with severe or end-stage RI -were effective in achieving the target AUC_0-24/MIC ratio of ≥80 at a susceptible inhibitory concentration of ≤ 2 mg/L.</p><p><strong>Conclusion: </strong>Our model provides a predictive instrument to enhance precision in determining therapeutic LZD dosage regimens for pediatric populations through systematic integration of developmental PK parameters.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8427-8440"},"PeriodicalIF":5.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124656","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":"Population Pharmacokinetic/Pharmacodynamic Modeling of Tacrolimus in Renal Transplant Recipients: Impact of CYP3A5 Genotype and Wuzhi Capsule Co-Medication.","authors":"Qiulin Xiang, Yi Yang, Guoxing Li, Song Chen, Yingying Yang, Ling Liu, Xian Yu","doi":"10.2147/DDDT.S542786","DOIUrl":"10.2147/DDDT.S542786","url":null,"abstract":"<p><strong>Object: </strong>Tacrolimus is a crucial immunosuppressant used to prevent renal transplant rejection. While, long-term application of tacrolimus can lead to several adverse reactions that worsen patient prognosis, such as posttransplantation diabetes mellitus and renal injury. This study developed population pharmacokinetic/pharmacodynamic (PK/PD) models from clinical data to investigate the relationships between tacrolimus dose, exposure, and adverse effects in renal transplant recipients.</p><p><strong>Methods: </strong>Demographics, the CYP3A5 genotype, laboratory results, and co-medications were tested as covariates, and dose simulations were performed based on the final models. The population PK model was described by a one-compartment model with first-order elimination and a fixed absorption rate. The CYP3A5 genotype, Wuzhi (WZ) capsule, and postoperative days were significant covariates of tacrolimus clearance. Fasting plasma glucose (FPG) and estimated glomerular filtration rate (eGFR) were characterized by the trough concentration (C0) of tacrolimus in a PK/linear model and maximal inhibitory effect, respectively. Age significantly influenced the baseline FPG and eGFR. The initial eGFR was strongly affected by hemoglobin.</p><p><strong>Results: </strong>The simulations revealed that patients with CYP3A5*1 treated without WZ capsule, for whom no less than 3 mg q12 h as the initial dose was needed, whereas patients with CYP3A5*3/*3 combined with WZ capsule might experience kidney damage even if the dose is 2 mg q12 h; thus, patients with the CYP3A5*3/*3 genotype combined with WZ capsule are not recommended.</p><p><strong>Conclusion: </strong>The population PK/PD models quantified the relationships between tacrolimus dose, exposure, and adverse effects in renal transplant patients, which could serve as a reference for optimizing the individualized dosage of tacrolimus.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8375-8389"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112030","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":"The Optimal Doses of Dexmedetomidine Combined with Propofol in Patients in Hysteroscopic Surgery: A Randomized Controlled Trial.","authors":"Hongchun Xu, Tong Peng, Dan Xie, Biqian Dong, Tiantian An, Fangjun Wang","doi":"10.2147/DDDT.S544566","DOIUrl":"10.2147/DDDT.S544566","url":null,"abstract":"<p><strong>Background: </strong>Dexmedetomidine has been reported to be utilized in conjunction with propofol during hysteroscopic surgery. However, both dexmedetomidine and propofol have benefits and side-effects, and the optimal doses of dexmedetomidine when utilized in combination with propofol during hysteroscopic surgery remain unestablished.</p><p><strong>Methods: </strong>One hundred and fifty patients undergoing hysteroscopic surgery at the affiliated hospital of North Sichuan Medical College were randomly divided into five groups and administered dexmedetomidine at a dose of 0.4 µg/kg, 0.6 µg/kg, 0.8 µg/kg, or 1.0 µg/kg, or saline, prior to anesthesia induction. Before the surgery, propofol was administered via target-controlled infusion using a pump with the Marsh model. The EC₅₀ of propofol was determined using an up-and-down sequential method with an adjacent concentration gradient of 1.2 to prevent purposeful movements. Hemodynamic parameters and adverse events related to anesthesia were also evaluated. The duration of the procedure and recovery, the amount of propofol required, and the postoperative recovery characteristics were documented.</p><p><strong>Results: </strong>The EC50 of propofol was significantly lower in the Dex 0.6, Dex 0.8, and Dex 1.0 groups compared to the S group (<i>p</i><0.05). As the dose of dexmedetomidine increased, the demand for propofol gradually decreased (<i>p</i><0.01), whereas the incidence of respiratory depression decreased (<i>p</i><0.01). Nevertheless, the incidence of bradycardia slightly increased (<i>p</i>=0.02). No significant differences in the incidence of hypotension were observed among the five groups (<i>p</i>>0.05). The patients in the Dex1.0 groups had higher postoperative comfort scores than those in the S group. At both t1 and t2, Ramsay scores were higher in the Dex0.8 and Dex1.0 groups than in the S group (<i>p</i><0.05). No significant differences were observed in the VAS scores among the five groups.</p><p><strong>Conclusion: </strong>Dexmedetomidine 0.8 µg/kg offers an optimal balance between propofol-sparing effects, sedation quality, and manageable side effects for hysteroscopic surgery.</p><p><strong>Trial registration: </strong>Date of registration: 24/05/2020, registration number: ChiCTR2000033220.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8441-8450"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112122","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":"Comparison of Ciprofol-Based and Propofol-Based Total Intravenous Anesthesia on Postoperative Recovery Quality in Patients Undergoing Hysteroscopic Surgery: A Randomized Non-Inferiority Trial.","authors":"Huan Yang, Yan Yang, Yihao Huang, Tao Liu, Yiheng Wang","doi":"10.2147/DDDT.S543281","DOIUrl":"10.2147/DDDT.S543281","url":null,"abstract":"<p><strong>Purpose: </strong>The 2,6-disubstituted alkylphenol ciprofol is a novel propofol analog for induction and maintenance of anesthesia. We aimed to compare the effects of ciprofol-based and propofol-based total intravenous anesthesia (TIVA) on postoperative recovery quality following hysteroscopic surgery.</p><p><strong>Patients and methods: </strong>In this randomized non-inferiority trial, women scheduled for hysteroscopic surgery at a tertiary hospital were randomly assigned to the ciprofol or propofol groups. The patients were administered intravenous injections of ciprofol (0.4 mg/kg) or propofol (2.0 mg/kg) for anesthesia induction before a maintenance infusion at initial rates of 0.8 or 5.0 mg/kg/h, respectively. The primary outcome was the Quality of Recovery-15 scale (QoR-15) score at 24 h post-surgery, and a non-inferiority margin of -8 was assumed. The secondary outcomes included hemodynamic changes, time to consciousness loss and recovery, incidences of injection pain, body movement, intraoperative respiratory adverse events, and postoperative adverse events.</p><p><strong>Results: </strong>The trial included 120 participants (60 per group). The total QoR-15 score 24 h after surgery in the ciprofol group was comparable to that in the propofol group (median [interquartile range]: 113.5 [111.0, 117.0] vs 112.5 [108.0, 117.0]; median difference [95% confidence interval]: -1.0 [-3.0, 2.0]). There were no significant differences in the five QoR-15 dimensions between the groups. The mean arterial pressure and heart rate during anesthesia induction and surgery were significantly higher in the ciprofol group than in the propofol group, whereas the incidence of injection pain was lower. In addition, there were no significant between-group differences in the time to loss of consciousness or awakening, incidences of intraoperative hypoxemia or laryngospasm, or incidences of postoperative nausea, vomiting, headache, dizziness, and drowsiness.</p><p><strong>Conclusion: </strong>Ciprofol is not inferior to propofol in terms of QoR score. Ciprofol administration is suitable for general anesthesia in female patients during hysteroscopic surgery.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8415-8426"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111458","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":"CYP2C8-Mediated Drug-Drug Interactions and the Factors Influencing the Interaction Magnitude.","authors":"Ling-Ling Zhu, Ling-Yan Yu, Yan-Hong Wang, Quan Zhou","doi":"10.2147/DDDT.S541536","DOIUrl":"10.2147/DDDT.S541536","url":null,"abstract":"<p><strong>Background: </strong>Older adults often have multiple morbidities that may lead to polypharmacy. Cytochrome P450 (CYP) 2C8 has shown significant contributions in the metabolism of various medications; however, its related drug-drug interactions (DDIs) appear to be underrecognized in clinical practice compared to the major CYP enzymes (eg, CYP3A4, CYP2D6). This review summarizes the progress of CYP2C8-mediated DDIs and factors influencing the interaction magnitude.</p><p><strong>Methods: </strong>Using CYP2C8 and drug interactions as the search terms, literature was searched through PubMed, Web of Science, and Embase as of January 2025. Eligible studies were identified following PRISMA guidelines. Screening and inclusion were assessed by two independent reviewers and 57 studies met inclusion/exclusion criteria.</p><p><strong>Results: </strong>Based on authoritative sources (FDA, EMA, DrugBank), and literature, this review identified 5 inducers, 53 strong/moderate inhibitors, and 32 major/intermediate substrates of CYP2C8. Typical examples were illustrated to predict DDIs by in vitro-in vivo extrapolation. The factors influencing DDI magnitude include genetic polymorphisms (CYP2C8, SLCO1B1, UDP-glucuronosyltransferase, and pregnane X receptor), hepatic and renal function, properties of CYP2C8 perpetrators (dose, treatment course, systemic concentrations, time after discontinuation, inhibitory potency, inhibitory abilities of metabolites on CYP2C8), properties of object drugs (whether the active metabolite of object drug is a CYP2C8 substrate, therapeutic index, stereoselectivity), differences in DDI risk for drugs from similar therapeutic classes, and whether multiple interaction mechanisms are involved. Some botanical supplements showed potential to influence CYP2C8 in vitro or in animal experiments.</p><p><strong>Conclusion: </strong>CYP2C8 is an important but underrecognized DME. This article reviewed its main substrates, perpetrators, DDIs, and methods for predicting interactions, and provided the first comprehensive summary of the factors influencing the interaction magnitude. Such knowledge will enhance the awareness of clinical professionals regarding safe medication for older adults. Further advances will emerge if the gaps in current knowledge and priorities for future research are recognized.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8391-8413"},"PeriodicalIF":5.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111460","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":"The Nrf Family and Its Cardioprotective Potential: Mechanisms, Functions, and Therapeutic Perspectives.","authors":"Chao Cui, Hui Song, Yifeng Guo, Jingfei Shi, Biao Geng, Gang Wang","doi":"10.2147/DDDT.S547848","DOIUrl":"10.2147/DDDT.S547848","url":null,"abstract":"<p><p>This review systematically elucidates the molecular mechanisms and therapeutic potential of nuclear factor erythroid 2-related factor (Nrf) family members in the cardiovascular system. As critical components of the CNC-bZIP transcription factor family, the Nrf family (including Nrf-2/NFE2L2, Nrf-1/NFE2L1, and Nrf-3/NFE2L3) orchestrates antioxidant response element (ARE)-dependent gene expression networks, playing pivotal roles in maintaining redox homeostasis, modulating inflammatory responses, improving mitochondrial function, and regulating programmed cell death (apoptosis, autophagy, and pyroptosis). Clinical data have demonstrated that in patients with myocardial infarction, the expression of Nrf-3 gene is significantly upregulated in myocardial cells within the infarcted area. Its high expression is associated with increased in-hospital mortality during the acute phase and accelerated progression of ventricular remodeling. Knockout of the Nrf-3 gene can reduce the acute-phase mortality of myocardial infarction, improve ventricular remodeling, and enhance cardiac function. Additionally, a crossover trial involving 19 participants showed that after 2 months of administration of olive oil by-product pâté tablets, the plasma Nrf-2 level in the subjects increased by 88.9% with concurrent improvement in cardiovascular risk factors. Collectively, these findings confirm the impact of the Nrf family on cardiovascular prognosis and its potential for intervention. Furthermore, we comprehensively analyze the regulatory functions of Nrf members in major cardiovascular pathologies, including myocardial ischemia-reperfusion injury, atherosclerotic plaque formation/stabilization, and heart failure progression. Based on recent advances, we also discuss innovative therapeutic strategies targeting the Nrf pathway, encompassing pharmacological activators, gene/epigenetic therapies, combinatorial approaches, and lifestyle interventions, thereby providing a theoretical framework and novel perspectives for the precision medicine of cardiovascular diseases.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8339-8373"},"PeriodicalIF":5.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112002","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":"Chinese Herbal Medicine in Hypoxic Pulmonary Hypertension Treatment: Mechanisms, Progress, and Future Directions.","authors":"Xunkai Wang, Tang Deng, Houfan Zhu, Jin Peng, Jinxi Liang, Shijie Zhong, Chen Yao, Guiyun Jin","doi":"10.2147/DDDT.S531109","DOIUrl":"10.2147/DDDT.S531109","url":null,"abstract":"<p><p>Hypoxic pulmonary hypertension (HPH) is a severe subtype of pulmonary hypertension(PH) characterized by chronic lung disease or prolonged hypoxia, leading to pulmonary vascular remodeling and right heart failure. Traditional Chinese Medicine (TCM) has garnered significant attention for its potential therapeutic effects on HPH due to its minimal side effects, multiple target actions, affordability, and cultural acceptance. Recent studies have highlighted the potential of TCM in inhibiting pulmonary artery smooth muscle cell proliferation, modulating inflammation, and oxidative stress. This review aims to explore the mechanisms of action of TCM in treating HPH, focusing on its ability to modulate key signaling pathways involved in pulmonary vascular remodeling, such as PI3K/Akt, Nrf2, NF-κB, and RhoA/ROCK. The goal is to provide a comprehensive overview of the current progress and future directions in the application of TCM for HPH treatment. TCM demonstrates significant therapeutic potential in HPH by modulating signaling pathways involved in inflammation, oxidative stress, and pulmonary vascular remodeling. Key compounds such as taxifolin glycoside, resveratrol, and salidroside have shown promising effects in inhibiting abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) and reducing oxidative stress. These mechanisms contribute to the overall efficacy of TCM in preventing and treating HPH. By modulating key signaling pathways and exerting anti-inflammatory and antioxidant effects, TCM offers a promising therapeutic approach for HPH. Further research is needed to validate the clinical efficacy and safety of TCM formulations, and to explore the underlying mechanisms through modern scientific methods. The integration of TCM with modern medicine could provide new strategies for the treatment of HPH.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8265-8294"},"PeriodicalIF":5.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112300","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":"Ginkgolide B Alleviates LPS-Induced Inhibition of Osteogenic Differentiation in Human Periodontal Ligament Stem Cells by Suppressing the p-IκBα/NF-κB Pathway.","authors":"Simeng Du, Daiwei Yang, Qing Liu, Peng Yang, Zhaoyan Wu, Yvxing Zhang, Siyu Chen, Jun Zhang","doi":"10.2147/DDDT.S541290","DOIUrl":"10.2147/DDDT.S541290","url":null,"abstract":"<p><strong>Background: </strong>Ginkgolide B (GB) is a widely utilized natural anti-inflammatory drug in clinical practice. This study investigates GB's effects on human periodontal stem cells (HPDLSCs) osteogenic differentiation under inflammation and its underlying mechanism, while evaluating its protective role against periodontal destruction in a rat periodontitis model.</p><p><strong>Methods: </strong>HPDLSCs were isolated and identified in vitro. Lipopolysaccharide (LPS) was used to establish an inflammatory environment. Proliferation and osteogenic differentiation of HPDLSCs were assessed using the Cell-counting Kit-8 (CCK-8), Alizarin Red Staining (ARS), quantitative calcium assay, alkaline phosphatase (ALP) staining and activity assay, and immunofluorescence assay. In addition, the expression of osteogenesis-related genes and proteins was detected by qRT-PCR and Western blot analysis. To verify the role of the NF-κB (nuclear factor kappa-B) pathway in this mechanism, the expression level of NF-κB pathway-related protein was detected by Western blot analysis after using BAY-11-7082 (a NF-κB signaling pathway inhibitor). The rat periodontitis model was established in vivo experiments. Micro-computed tomography (micro-CT) quantified alveolar bone loss, while immunohistochemical staining (IHC) assessed tissue remodeling. Tests were analyzed using GraphPad Prism 8 software. Differences between more than two groups were analyzed by one-way or two-way analysis of variance (ANOVA) followed by Tukey's test. Values of p < 0.05 were considered statistically significant.</p><p><strong>Results: </strong>LPS treatment triggered inflammation and suppressed osteogenesis in HPDLSCs in vitro, while GB (25, 100 μM) reversed these effects. The results of the Western blot assay showed that both GB and BAY11-7082 exhibited similar inhibitory effects on the NF-κB pathway. In vivo, GB mitigated alveolar bone loss and inflammatory tissue destruction in periodontitis rats.</p><p><strong>Conclusion: </strong>GB can mitigate periodontitis by blocking the NF-κB pathway, offering dual anti-inflammatory and bone-protective effects.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8309-8326"},"PeriodicalIF":5.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111469","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":"Nicorandil Use and Health Status Outcomes in Patients with Angina Pectoris: A Prospective, Multicenter, Cohort Study (GREAT).","authors":"Xiliang Zhao, Guojie Cheng, Liling Sun, Yajuan Liu, Xin Du, Su'e Xu, Litao Wu, Ying Wei, Wei Liu, Lifu Miao, Qihua Zhang, Changsheng Ma, Yong Zeng","doi":"10.2147/DDDT.S506108","DOIUrl":"10.2147/DDDT.S506108","url":null,"abstract":"<p><strong>Purpose: </strong>Coronary artery disease represents a major clinical burden, and angina pectoris is the most frequent manifestation of coronary artery disease. Nicorandil is commonly used for the management of angina pectoris; however, its effects on health status outcomes are unclear.</p><p><strong>Patients and methods: </strong>This multicenter, prospective, cohort study (GREAT) enrolled 1556 adult coronary artery disease patients with angina pectoris from nine hospitals in China. Patients were classified into nicorandil and control groups. The primary outcome was the change in the Seattle Angina Questionnaire summary score (SAQ-SS) from baseline to 12 months. Secondary outcomes included changes in SAQ-SS at 3, 6, and 9 months. Propensity score matching (PSM) was used to reduce bias and control for confounding factors.</p><p><strong>Results: </strong>We analyzed 1528 patients with baseline and 12-month health status data. After PSM, 450 matched pairs of patients were identified. A difference of ≥5 points for SAQ-SS is considered clinically significant. Patients in the nicorandil group reported greater mean improvement in SAQ-SS (17.6 ± 14.0, difference: 2.50, 95% CI: 0.74-4.27; P=0.003) at 12 months compared with the control group (15.1 ± 13.0; <i>P</i>=0.003). Similar trends were noted in SAQ-SS at 3, 6, and 9 months. Additionally, nicorandil users exhibited significantly greater improvements in the SAQ physical limitation (11.7 ± 16.9 vs 8.4 ± 16.9; difference: 3.27, 95% CI, 1.05-5.48; P =0.001) and SAQ-QoL domain (18.9 ± 21.4 vs 16.3 ± 20.4; difference: 2.62, 95% CI, -0.12 to 5.35; P=0.042) at 12 months. Most patients in the entire cohort (78.4%) reported a clinical improvement in SAQ-SS. The nicorandil group had a higher proportion of patients with at least large improvements (≥20 points) in SAQ-SS (42.5% vs 32.9%; difference: 9.7%, 95% CI: 3.3-16.0; P= 0.004).</p><p><strong>Conclusion: </strong>Among patients with angina pectoris, anti-angina treatment improved the majority of patients' health status. Nicorandil-based regimens were associated with a greater health status outcome improvement compared to those not using nicorandil in coronary artery disease patients with angina pectoris. A substantial proportion of patients using nicorandil exhibited noteworthy improvements in health status outcomes at one year.</p><p><strong>Registration: </strong>ClinicalTrials.gov, NCT05050773.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8295-8308"},"PeriodicalIF":5.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111713","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}