Drug Design, Development and Therapy最新文献

{"title":"Deciphering the Role of Oroxylin A in Liver Fibrosis.","authors":"Siqing Wang, Jing Wu, Jian Sun, Wei Chen, Zhaochun Tian, Shuhong Huang, Meng Wang","doi":"10.2147/DDDT.S530387","DOIUrl":"10.2147/DDDT.S530387","url":null,"abstract":"<p><p>Liver fibrosis is a dynamic and complex process characterized by the excessive accumulation of extracellular matrix (ECM) components, driven by a heterogeneous population of hepatic myofibroblasts (MFs). Current treatments for liver fibrosis primarily include pharmacological interventions such as antiviral and anti-fibrotic therapies, alongside lifestyle modifications, including dietary changes and alcohol abstinence. However, the therapeutic outcomes remain suboptimal. Existing anti-fibrotic medications are unable to fully reverse liver fibrosis, particularly in its advanced stages, and some drugs may even induce adverse effects. Recently, the challenge of combating liver fibrosis has attracted increasing attention from both the academic community and the general public, leading to extensive research efforts and several significant discoveries. Hepatocyte senescence, an irreversible and inevitable process, plays a crucial role in the onset and progression of various liver diseases. It serves as a key regulatory factor in the development of liver fibrosis, exerting a considerable impact on its progression. Senescent hepatocytes secrete the senescence-associated secretory phenotype (SASP), which interacts with hepatic stellate cells (HSCs), promoting their transformation into MFs. Additionally, SASP fosters a cellular microenvironment conducive to the advancement of hepatic fibrosis, thereby accelerating its progression. This review comprehensively examines the natural flavonoid compound Oroxylin A (OA), which regulates hepatocyte senescence in the context of liver fibrosis. The paper also discusses the current research landscape, trends, and critical challenges related to hepatocyte senescence in liver fibrosis, along with the mechanisms through which OA influences hepatocyte senescence, either promoting or delaying its onset.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8891-8902"},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231835","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":"Geniposide Stabilized Atherosclerosis Plaque by Induced M2 Polarization via PPARγ Signaling Pathway.","authors":"Zheng Jin, Qingmin Chu, Zhiyi Du, Junlong Li, Wei Wu, Xiaoxiong Zhou, Huanyi Zhao","doi":"10.2147/DDDT.S499890","DOIUrl":"10.2147/DDDT.S499890","url":null,"abstract":"<p><strong>Objective: </strong>The instability of atherosclerotic (AS) plaque constitutes a critical trigger for acute intravascular thrombosis and cardiovascular disease. Prior studies have found that <i>Geniposide</i> (Gen) is capable of regulating macrophage polarization and stabilizing AS plaque. However, its potential mechanism is not clear. Given the role of peroxisome proliferator-activated receptor γ (PPARγ) in mediating macrophage polarization, this study aims to investigate the relationship between Gen, PPARγ and macrophage polarization.</p><p><strong>Methods: </strong>In vitro, RAW264.7 was used to investigate the effects of Gen on polarization phenotype, anti-inflammatory activity, and its correlation with PPARγ. In vivo, ApoE^-/- mice were fed with a high-fat diet to induce AS and were used to evaluate the pharmacological effects of Gen. Additionally, the relationship between Gen, PPARγ and M2 polarization in AS was verified.</p><p><strong>Results: </strong>In vitro, Gen upregulated the expressions of M2 macrophage markers (CD163, IL-10, Arg-1). Moreover, Gen increased the expressions of PPARγ target genes (CD36, ABCG1) and activated PPARγ activity, which could be inhibited by PPARγ antagonist GW9662. In vivo, the intervention of Gen on AS model of ApoE^-/- mice played a role in reducing the blood lipid, stabilizing AS plaques and down-regulating the level of inflammatory factors. Consistent with the results in vitro, Gen was able to regulate the expression of macrophage polarization and increase the expression of PPARγ, while GW9662 treatment inhibited the expression of M2 phenotypic markers.</p><p><strong>Conclusion: </strong>Gen regulates macrophage polarization to M2 phenotype and plays a role in inhibiting inflammation and stabilizing plaque by mediating PPARγ activation, which suggests that Gen may be a promising agent for AS.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8805-8821"},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231672","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":"Emodin Alleviates Monocrotaline-Induced Pulmonary Arterial Hypertension by Directly Targeting TAK1.","authors":"Yaolei Zhang, Mingmei Zhang, Ting Li, Yunchuan Liu, Zihan Li, Longfu Zhou, Yonghe Hu","doi":"10.2147/DDDT.S540915","DOIUrl":"10.2147/DDDT.S540915","url":null,"abstract":"<p><strong>Purpose: </strong>Pulmonary arterial hypertension (PAH) is a group of diseases characterized by elevated pulmonary arterial pressure. The malignant proliferation of pulmonary artery smooth muscle cells is a major pathological hallmark of PAH. Emodin, a natural compound with known antiviral, anti-inflammatory, and anti-proliferative properties, has shown potential in alleviating PAH. Our aim is to elucidate the core pathways and molecular targets through which emodin exerts its therapeutic effects in alleviating PAH.</p><p><strong>Methods: </strong>Firstly, potential targets of emodin in alleviating PAH were predicted using network pharmacology. Molecular docking was used to predict the binding affinity between emodin and its targets, and the interactions between emodin and these targets were verified using the Cellular Thermal Shift Assay, Co-immunoprecipitation, and Immunofluorescence. Ultrasound and pathological analyses were employed to evaluate the effects of emodin on monocrotaline-induced PAH. Finally, the results obtained from network pharmacology were validated using hematoxylin and eosin staining, ultrasound imaging, Western blotting, and polymerase chain reaction.</p><p><strong>Results: </strong>Emodin relieves PAH by inhibiting PASMC proliferation, reducing right ventricular hypertrophy, and decreasing lung inflammation. It targets eight proteins in 15 pathways, including IL-17 signaling. Molecular docking shows emodin binds to key IL-17 pathway molecules, reducing IL-17A, IL-17RA, and Phospho-TAK1 expression. Emodin binds competitively to TAK1, preventing its interaction with MKK3, inhibiting TAK1 phosphorylation and downstream pathway activation, thus suppressing inflammation. The indispensable role of TAK1 in mediating emodin's effects was corroborated through pharmacological blockade with Takinib, a highly potent and selective TAK1 inhibitor.</p><p><strong>Conclusion: </strong>The experiment has demonstrated for the first time that emodin directly targets TAK1, downregulates the expression of IL-17A, IL-17RA, and Phospho-TAK1, blocks the activation of the IL-17 signaling pathway, inhibits PASMCs proliferation, and alleviates PAH. This study provides a theoretical basis for the clinical application of emodin.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8843-8864"},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231844","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":"Combined Esketamine and Dexmedetomidine Decreases the Risk of Postoperative Delirium in Neurosurgical Pediatrics: A Randomized Controlled Trial.","authors":"Chen-Yu Wen, Ju Bao, Yin Zhou, Dong-Liang Mu, Ting Ding","doi":"10.2147/DDDT.S550647","DOIUrl":"10.2147/DDDT.S550647","url":null,"abstract":"<p><strong>Purpose: </strong>Present study was designed to investigate whether combined esketamine and dexmedetomidine could decrease the risk of postoperative delirium in neurosurgical pediatric.</p><p><strong>Patients and methods: </strong>In this prospective randomized controlled study, pediatrics (aged 2-16 years) who were scheduled for selective neurosurgery were enrolled. Patients were randomized to receive combined esketamine (0.5 mg/kg) and dexmedetomidine (0.5 μg/kg) or normal saline as placebo at anesthesia induction. Primary outcome was the incidence of delirium within postoperative the first five days which was assessed twice daily using the Cornell Assessment of Pediatric Delirium (CAPD). CAPD≥ 10 at any assessment point was considered as delirium. Secondary outcomes included the incidence of emergence delirium, non-delirium complications within postoperative 30 days, postoperative length of in-hospital stay, and medical cost during hospitalization. The change of systematic inflammation was reflected by Neutrophil-to-Lymphocyte Ratio.</p><p><strong>Results: </strong>From July 2021 to March 2023, 270 patients were screened, and 190 patients were randomized. Median age of enrolled patients was similar between two groups (63.0 [43.3, 111.3] vs 70.0 [46.3, 114.8] months, P = 0.883). Patients in esketamine-dex group suffered lower incidence of postoperative delirium than control group (intention-to-treat analysis: 22.8% [21/92] vs 38.0% [35/92], RR = 0.600, 95% CI 0.380-0.948, P = 0.025; per-protocol analysis: 22.0% [20/91] vs 38.2% [34/89], RR = 0.575, 95% CI 0.360-0.919, P = 0.018). The incidence of emergence delirium was lower in esketamine-dex group than control group (20.7% [19/92] vs 50.0% [46/92], RR = 0.413, 95% CI 0.263-0.648, P < 0.001). Patients in esketamine-dex group had lower medical cost (P < 0.001), and there was no statistical significance in the incidence of non-delirium complications within postoperative 30 days and postoperative length of in-hospital stay. The neutrophil-to-lymphocyte ratios at postoperative first and third day were comparable between two groups. Safety outcomes such as bradycardia and hypotension were comparable between groups.</p><p><strong>Conclusion: </strong>Combined esketamine and dexmedetomidine could decrease the risk postoperative delirium and emergence delirium in pediatrics after neurosurgery.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8865-8877"},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231862","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 Novel Letrozole Stair-Step Duration Regimen for Ovulation Induction in Women with Polycystic Ovary Syndrome and Letrozole Resistance.","authors":"Xiuxian Zhu, Jingwen Lang, Yunqing Zhi, Qiaoling Wang, Yonglun Fu","doi":"10.2147/DDDT.S538102","DOIUrl":"10.2147/DDDT.S538102","url":null,"abstract":"<p><strong>Background: </strong>Letrozole is the first-line treatment for ovulation induction in women with polycystic ovary syndrome (PCOS). However, a subset of patients remains anovulatory despite standard treatment, a condition termed \"letrozole resistance\". This retrospective cohort study aimed to evaluate the effectiveness and time efficiency of a novel \"letrozole stair-step duration regimen\", which skips progestin-induced withdrawal bleeding and proceeds directly to an extended letrozole course after anovulatory cycles, compared with a previously established \"2-step extended letrozole regimen\".</p><p><strong>Methods: </strong>We analyzed 158 women with PCOS and letrozole resistance who underwent ovulation induction at two university-affiliated reproductive centers between March 2018 and September 2024. Participants received either the stair-step duration regimen (n = 62) or the 2-step extended regimen (n = 96). Outcomes compared included follicular development, hormone profiles, ovulation, and pregnancy outcomes. The primary outcome was the ovulation rate.</p><p><strong>Results: </strong>Ovulation rates were comparable between groups [95.16% vs 94.79%]. Clinical pregnancy rates [23.73% (14/59) vs 20.88% (19/91), P = 0.681] and live birth rates [16.95% (11/59) vs 18.68% (17/91), P = 0.824] also showed no significant differences. However, the stair-step group achieved ovulation in a significantly shorter time, with a median of 36 days (interquartile range [IQR] 32-54) versus 47 days (IQR 45-51) in the extended regimen group (P < 0.001).</p><p><strong>Conclusion: </strong>The letrozole stair-step duration regimen is a time-saving and effective ovulation induction protocol for women with PCOS and letrozole resistance, yielding comparable reproductive outcomes in a shorter treatment duration.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8793-8803"},"PeriodicalIF":5.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231852","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":"Huangqi Baihe Granules Attenuate Hypobaric Hypoxia-Induced Brain Injury via HIF-1a/p53/Caspase-3 Pathway.","authors":"Xinjue Zhang, Wangjie Cao, Mingyue Pan, Jiawei Huo, Nengxian Zhang, Jiawang Guo, Yong Huang, Yongqi Liu, Hongxia Gong, Yun Su","doi":"10.2147/DDDT.S525602","DOIUrl":"10.2147/DDDT.S525602","url":null,"abstract":"<p><strong>Background: </strong>High altitude cerebral edema (HACE), a severe central nervous system dysfunction caused by acute plateau hypoxia, involves oxidative stress and apoptosis. Huangqi Baihe granules (HQBHG) show efficacy against these processes, but their mechanism remains unclear.</p><p><strong>Purpose: </strong>This study evaluated Huangqi Baihe granules (HQBHG)'s efficacy in treating High altitude cerebral edema (HACE) and elucidated its mechanism.</p><p><strong>Methods: </strong>UPLC-MS/MS characterized Huangqi Baihe granules (HQBHG)'s chemical composition. Seventy-two SD rats were divided into six groups: No-treatment Control (NC), Hypobaric Hypoxia Model (HHM), positive drug Dexamethasone (Dex, 5 mg/kg), and HQBHG low/medium/high-dose groups (1.105 g/kg d, 2.21 g/kg d, 4.42 g/kg d). Except NC, all underwent 72-hour 6000 m hypobaric hypoxia to establish High altitude cerebral edema (HACE). Brain barrier permeability (wet-dry ratio, Evans Blue staining), oxidative stress markers (Reactive oxygen species, Superoxide dismutase), and histopathology (HE/Nissl staining) were assessed. Network pharmacology (TCMSP, GenGards, OMIM, Drugbank) and transcriptomics identified Huangqi Baihe granules (HQBHG) targets and pathways. Apoptosis signaling (HIF-1α/p53/Caspase-3) was validated via immunofluorescence, TUNEL, Transmission Electron Microscope, Western Blotting, and qRT-PCR.</p><p><strong>Results: </strong>Hypobaric hypoxia caused brain injury and blood-brain barrier disruption. Network and transcriptome analyses linked Huangqi Baihe granules (HQBHG)'s effects to HIF-1α/p53/Caspase-3 pathway, involving key genes. Huangqi Baihe granules (HQBHG) intervention attenuated brain injury, oxidative stress, and apoptosis, suppressing HIF-1α/p53/Caspase-3 pathway activation.</p><p><strong>Conclusion: </strong>We demonstrated for the first time that Huangqi Baihe granules (HQBHG) may reduce brain tissue injury by regulating the HIF-1α/p53/Caspase-3 signaling pathway, ameliorating blood-brain barrier disruption induced by low-pressure hypoxia, imbalance of oxidative stress in the brain tissues, and inhibiting apoptosis in the brain cells.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8823-8841"},"PeriodicalIF":5.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12493868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231710","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":"Synergistic Innovative Therapies in Dermatology: Integrating Platelet Derivatives, Biomaterials, and Exogenous Bioactive Substances for Enhancing Skin Repair and Regeneration.","authors":"Eduardo Anitua, Roberto Tierno, Gorka Orive, Mohammad Hamdan Alkhraisat","doi":"10.2147/DDDT.S546097","DOIUrl":"10.2147/DDDT.S546097","url":null,"abstract":"<p><strong>Background: </strong>The treatment of dermatological diseases has evolved significantly with the advent of advanced therapeutic strategies involving platelet-rich products. These products are rich in morphogens, growth factors, and proteins that play a crucial role in tissue regeneration and wound healing. Their combination with different biomaterials has been engineered to enhance the biomaterials' safety and performance in the context of tissue healing.</p><p><strong>Objective: </strong>This narrative review aims to explore the current evidence on the biological mechanisms, efficacy, and clinical applications of these combined therapies. Furthermore, we examine the potential advantages of synergistic effects and the challenges associated with optimizing treatment protocols.</p><p><strong>Methods: </strong>Relevant literature was retrieved through a structured search strategy implemented across PubMed, Scopus, and Google Scholar databases. Studies included investigated co-administration of platelet-rich products with other agents in topical, injectable, or composite formulations for dermatological conditions with no restriction regarding publication date.</p><p><strong>Results: </strong>The review summarizes in vitro and in vivo biological effects of various biopolymers and active substances combined with platelet-rich products, highlighting diverse application strategies and their effectiveness across dermatological contexts.</p><p><strong>Conclusion: </strong>Adding platelet-rich products has shown promising results in enhancing therapeutic outcomes for various dermatological conditions, including chronic wounds, burns, scars, and skin aging. Although promising results have been reported, the need for critical thinking regarding the selection of the biomaterial and the platelet-rich products, standardized methodologies, large-scale randomized controlled trials, and long-term follow-up studies is emphasized to fully establish the clinical benefits of these combined treatments in dermatology.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8755-8782"},"PeriodicalIF":5.1,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231715","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":"Pharmacokinetics, Relative Bioavailability, and Safety of the SHR0302 Oral Solution and Tablets: A Single-Center, Randomized, Open-Label, Crossover (Two-Formulation, Two-Period) Phase I Trial in Healthy Chinese Volunteers.","authors":"Xin Gao, Kai Shen, Dan Tang, Wenjing Bai, Juan Wang, Tingting Wang, Xin Wang","doi":"10.2147/DDDT.S513537","DOIUrl":"10.2147/DDDT.S513537","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates the pharmacokinetic characteristics and relative bioavailability of SHR0302 oral solution and tablets in healthy Chinese male volunteers.</p><p><strong>Patients and methods: </strong>This single-center, randomized, open-label, crossover (two-formulation, two-period) phase I study enrolled 16 healthy male volunteers. Participants were randomized 1:1 to receive single dose 8mg of either the SHR0302 oral solution or the SHR0302 tablet. Blood samples were collected according to the protocol requirements, and SHR0302 plasma concentrations were analyzed using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Pharmacokinetic parameters were calculated using a non-compartmental analysis in Phoenix WinNonlin (version 8.3). Data processing and analysis of pharmacokinetic characteristics and relative bioavailability were conducted using SAS software (version 9.4). Safety was assessed through treatment-emergent adverse events (TEAEs), vital signs, physical examinations, 12-lead electrocardiograms, and laboratory tests.</p><p><strong>Results: </strong>All 16 enrolled subjects completed the study. The geometric mean ratio (90% confidence interval) for C_max of SHR0302 oral solution versus tablets was 1.04 (0.998, 1.09), and the geometric mean ratios (90% confidence intervals) for AUC₀-_t and AUC₀-_inf were both 1.04 (1.02, 1.06). These results fell entirely within the bioequivalence range of 80% to 125%. Among the 16 subjects, 5 (31.3%) experienced a total of 6 TEAEs, all of which were mild in severity. No serious adverse events were reported.</p><p><strong>Conclusion: </strong>In healthy Chinese male volunteers, the bioavailability of the SHR0302 oral solution was comparable to that of the SHR0302 tablet. The drug was safe and well tolerated following a single dose.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8783-8792"},"PeriodicalIF":5.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205916","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":"Investigating the Mechanism of Jiawei Weijin Decoction in Treating Non-Small Cell Lung Cancer Using Network Pharmacology, Bioinformatics Analysis and Experimental Validation.","authors":"Bo Xu, Yihan Yu, Jixian Zhang, Bo Jiang, Le Yan, Saili Chen, Linling Hu, Qing Miao, Yu Qi","doi":"10.2147/DDDT.S516745","DOIUrl":"10.2147/DDDT.S516745","url":null,"abstract":"<p><strong>Purpose: </strong>Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide. While Qianjin Weijin Decoction is widely used in China for lung cancer treatment, Jiawei Qianjin Weijin Decoction (JWWJD), a modified version, has shown enhanced anti-metastatic effects. However, its active components and underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>The effect of JWWJD against NSCLC was evaluated in vitro and in vivo, and the mechanisms were identified in combination with transcriptomics. Network pharmacology and bioinformatics were used to construct an anti-NSCLC prognostic model with JWWJD. The correlation between the expression of the prognostic gene and clinicopathological features was evaluated. The main active components of JWWJD were identified by LC-MS/MS and its anticancer effect and mechanism were investigated in vitro and in vivo.</p><p><strong>Results: </strong>JWWJD-containing serum significantly suppressed cell proliferation and migration, and induced apoptosis in NCI-A549 and NCI-H23 cells. Among different concentrations tested, 20% drug-containing serum showed the most potent inhibitory effect on NSCLC progression (all <i>P</i>-values < 0.05). In a BALB/c-nu mouse xenograft model, oral administration of high-dose JWWJD reduced tumor volume by 27.76% compared to control (<i>P</i> < 0.001). Transcriptomic analysis revealed that JWWJD treatment led to significant downregulation of SPP1 (Fold Change = 0.687, FDR < 0.05), a gene highly associated with poor prognosis in NSCLC patients. Using LC-MS/MS, curcumol was identified as the key active component in JWWJD. Molecular studies demonstrated that curcumol directly binds to SPP1 with strong affinity (KD = 4.55×10^-6 M), downregulates its expression, and inhibits NSCLC cell migration and invasion. In vivo experiments showed that curcumol reduced tumor volume by 24.88% (<i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>Our study, integrating transcriptomics, bioinformatics, LC-MS/MS, and experimental validation, revealed that JWWJD alleviates NSCLC metastasis by directly targeting SPP1. JWWJD and its active compound curcumol show promise as alternative therapies for NSCLC patients.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8711-8743"},"PeriodicalIF":5.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198586","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":"Labor Analgesia Initiation with Dural Puncture Epidural versus Standard Epidural Techniques: A Prospective Randomized Dose Allocation Study of Ropivacaine.","authors":"Fei Xiao, Dan M Drzymalski, Yu-Fang Dong, Jia-Yue Huang, Yan Gao, Hai-Ya Yan, Hui-Jing Hu","doi":"10.2147/DDDT.S547879","DOIUrl":"10.2147/DDDT.S547879","url":null,"abstract":"<p><strong>Background: </strong>When compared to the standard epidural technique, the dural puncture epidural (DPE) technique is reported to provide quicker onset of labor analgesia and improved quality of analgesia. Recently, the DPE technique was found to lower the effective dose for 90% (ED90) of patients receiving bupivacaine for labor analgesia by 35%. However, key pharmacological differences between bupivacaine and ropivacaine and the effect of a DPE technique on ropivacaine doses have not been studied. Therefore, we aimed to determine the effective dose for 50% (ED50) and ED90 of ropivacaine for labor analgesia in parturients when initiated with the DPE and standard epidural techniques.</p><p><strong>Methods: </strong>Study participants were randomized to receive one of the five doses of ropivacaine (12, 15, 18, 21, and 24 mg) undergoing one of the two epidural techniques (either a DPE or standard epidural technique). A total volume of 20 mL of local anesthetic was administered epidurally. Effective analgesia was defined as the patient reporting an NRS pain score < 3 at 20 minutes following drug administration. The ED50 and ED90 values of epidural ropivacaine for labor analgesia were determined using probit analysis, and comparisons were made using the relative median potency ratio.</p><p><strong>Results: </strong>The ED50 of ropivacaine for initiating labor analgesia using the DPE vs standard epidural techniques was 18.6 mg (95% CI, 16.4 to 21.1 mg) vs 19.2 mg (95% CI, 17.0 to 21.8 mg), respectively. The ED90 values were 30.5 mg (95% CI, 26.6 to 38.3 mg) vs 31.1 mg (95% CI, 27.1 to 39.2 mg), respectively. The relative median potency ratio for ropivacaine with DPE vs standard epidural technique was -0.6 (95% CI, -4.0 to 2.6).</p><p><strong>Conclusion: </strong>Our findings suggest that there is no dose-sparing effect of ropivacaine when using the DPE technique vs a standard epidural technique for labor analgesia.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"8745-8753"},"PeriodicalIF":5.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205893","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}