Drug Design, Development and Therapy最新文献

{"title":"Comparative Analysis of Clinical Efficacy and Safety of Pyrotinib Plus Capecitabine versus Trastuzumab Emtansine (T-DM1) as Second-Line Treatment for HER2-Positive Advanced Breast Cancer: A Retrospective Study.","authors":"Hao Han, Congcong Wang, Fenge Jiang, Ping Sun, Jiannan Liu","doi":"10.2147/DDDT.S516394","DOIUrl":"https://doi.org/10.2147/DDDT.S516394","url":null,"abstract":"<p><strong>Background: </strong>HER2-positive advanced breast cancer poses significant treatment challenges. In China, T-DM1 and pyrotinib are key second-line therapies. A comprehensive evaluation of the comparative efficacy and safety profiles of these therapies is imperative for optimizing therapeutic strategies and enhancing patient outcomes. This study aims to compare the clinical efficacy and safety of T-DM1 against pyrotinib plus capecitabine.</p><p><strong>Methods: </strong>Patients are females with HER2-positive, locally advanced, or metastatic breast cancer who at least 18 years old and have received anti-HER2 therapy in the past. This study included 148 patients who satisfied the inclusion criteria. Of these, 74 patients received intravenous T-DM1 (3.6 mg/kg) every 21 days, while the other 74 patients got oral pyrotinib (400 mg, once daily) plus capecitabine (1000 mg/m², twice daily on days 1-14 of each 21-day cycle). Progression-free survival (PFS) was the main outcome, while overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were the secondary outcomes.</p><p><strong>Results: </strong>The median PFS was 12.2 months for the pyrotinib group vs 9.1 months for the T-DM1 group. The median follow-up was 12.7 months for pyrotinib and 9.3 months for T-DM1. The pyrotinib group had better DCR (56.8% vs 54.1%) and ORR (40.5% vs 29.7%). While adverse events were manageable, the most common severe AE in the pyrotinib group was diarrhea (24.3%), and in the T-DM1 group, it was thrombocytopenia (16.2%). However, by reducing the drug dosage or providing symptomatic treatment, most adverse events could be controlled at grades 1 to 2, indicating that the adverse events were manageable. Neither group recorded any adverse event-related deaths.</p><p><strong>Conclusion: </strong>Pyrotinib plus capecitabine significantly improves median PFS compared to T-DM1 in patients with HER2-positive advanced breast cancer, demonstrating a favorable efficacy profile alongside manageable safety concerns.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2885-2895"},"PeriodicalIF":4.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997108","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":"Single-Cell Transcriptional Analysis Reveals the Mechanism of AZD6738 in HCC Immunotherapy via EZH2 Targeting.","authors":"Ren-Peng Li, Guo-Zhi Wu, Xi-Dong Fang, Wen-Wen Yang, Hui-Yun Zhang, Han-Xun Yue, Ya Zheng, Yu-Ping Wang, Yong-Ning Zhou","doi":"10.2147/DDDT.S508709","DOIUrl":"https://doi.org/10.2147/DDDT.S508709","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to identify specific molecular targets sensitive to AZD6738 through the integration of network pharmacology and transcriptomic methods, and to assess their potential role in the treatment of hepatocellular carcinoma (HCC). Additionally, we explore the specific effects of AZD6738 on the tumor microenvironment and its ability to regulate immune responses.</p><p><strong>Methods: </strong>We employed a combination of network pharmacology and transcriptomic analysis to identify specific molecules associated with HCC, including EZH2, CCNB1, PRKDC, CTSL, PSEN1, SLC6A3, and FKBP1A. Using these molecules and clinical features, we constructed a robust prognostic model for HCC. We further used single-cell transcriptomic technology to screen for core targets and performed spatial transcriptomic analysis to determine their spatial distribution. To validate the efficacy of AZD6738 in vivo, we established a subcutaneous tumor model, with the experimental group receiving oral administration of AZD6738 (75 mg/kg). Finally, we assessed the changes in the immune cell expression profile in tumor tissues post-AZD6738 treatment using flow cytometry.</p><p><strong>Results: </strong>Our study indicates that the high expression of genes such as EZH2, CCNB1, PRKDC, and PSEN1 is associated with poor prognosis in HCC patients. Molecular docking and RT-PCR validation demonstrated that AZD6738 exhibits high affinity for these targets and significantly reduces the mRNA levels of EZH2, PRKDC, and CCNB1 in HCC cell lines, with EZH2 showing the most pronounced decrease. Animal experiments revealed that AZD6738 can enhance the immune microenvironment in liver cancer; specifically, AZD6738 not only promotes the proliferation of CD8+ T cells but also enhances their differentiation into effector memory T cells, indicating that the drug can potentiate anti-tumor immune responses.</p><p><strong>Conclusion: </strong>This study reveals that AZD6738 demonstrates significant therapeutic efficacy by targeting the key molecule EZH2, thereby modulating the tumor microenvironment and enhancing anti-tumor immunity.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2897-2920"},"PeriodicalIF":4.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994821","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":"Effect of Esketamine Compared with Sufentanil Combined with Propofol in Patients Undergoing First Trimester Surgical Abortion: A Randomized, Double-Blinded Clinical Trial.","authors":"Yingchao Guan, Haochen Wang, Xiaojing Cong, Beibei Zhang, Yusong Lin, Xiaodong Wang","doi":"10.2147/DDDT.S515006","DOIUrl":"https://doi.org/10.2147/DDDT.S515006","url":null,"abstract":"<p><strong>Background: </strong>We explored whether esketamine anesthesia during first-trimester surgical abortion can reduce intraoperative hemodynamic fluctuations and improve patients' respiratory function.</p><p><strong>Methods: </strong>A total of 197 patients who underwent a first-trimester surgical abortion were included in the analysis. Patients were randomly assigned to either the esketamine anesthesia group (group E, n=98) or sufentanil anesthesia group (group S, n=99). The primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), heart rate (HR), respiratory rate (RR) and end-tidal carbon dioxide partial pressure (PetCO₂) during the surgery. Secondary outcomes included body movement, apnea, hypoxemia, postoperative nausea and vomiting (PONV), dizziness, anesthesia recovery time, Richmond Agitation and Sedation Scale (RASS) score, and postoperative pain.</p><p><strong>Results: </strong>Patients in Group E had a more stable intraoperative SBP (p=0.001), DBP (p=0.014), MBP (p=0.003), and HR (p=0.001). There was no significant difference in intraoperative RR between the two groups (p=0.108); however, PetCO₂ in group E remained at preoperative levels, whereas it increased in group S during surgery (p<0.001). The risk of apnea and hypoxemia in group E was lower (RR 0.32, 95% CI [0.13, 0.76], p=0.006; RR 0.13, 95% CI [0.03, 0.54], p=0.001). The incidence of intraoperative body movement (50% vs 27%, p=0.003), postoperative dizziness (45% vs 30%, p=0.024), and nausea (7% vs 0%, p=0.007) was higher in group E. There were no differences in anesthesia recovery time, postoperative RASS score, pain, or vomiting.</p><p><strong>Conclusion: </strong>Compared with sufentanil, esketamine anesthesia during the first trimester surgical abortion can maintain stable intraoperative hemodynamics and respiratory function during surgery and reduce apnea and hypoxemia. Esketamine may increase the risk of dizziness and PONV after surgical abortion.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2873-2883"},"PeriodicalIF":4.7,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977595","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":"Research Progress on the Treatment of Related Diseases With <i>Astragalus</i>.","authors":"Xinyu Zhang, Bingying Lin, Xiaoqian Wang, Ninɡji Fanɡ, Lifei Wu, Haitong Wan, Huifen Zhou","doi":"10.2147/DDDT.S494915","DOIUrl":"https://doi.org/10.2147/DDDT.S494915","url":null,"abstract":"<p><p><i>Astragalus mongholicus Bunge [Fabaceae; Astragali radix]</i> is an herb widely used in traditional Chinese medicine. It has diuretic, anti-aging, antihypertensive, immune-boosting, liver-protective, anti-stress and other extensive pharmacological effects. In recent years, <i>Astragalus</i> and its extract have been used to treat lung and stomach qi deficiency as well as general qi deficiency. This paper summarizes the mode of action and mechanisms of <i>Astragalus</i> in treating various diseases, and provides valuable insights for the future application, development, and improvement of <i>Astragalus</i>. In this paper, literature on the use of <i>Astragalus</i> in treating related diseases over the past five years was collected from PubMed and CNKI databases, and the pathogenic mechanisms of <i>Astragalus</i> and its extracts were reviewed. Its mechanism of action is primarily involved in antioxidant protection, anti-inflammatory effects, and anti-apoptotic properties. This provides a new research direction for future studies and clinical treatments using <i>Astragalus</i>.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2845-2862"},"PeriodicalIF":4.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972609","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":"Effect of Different Doses of Esketamine on Postoperative Recovery in Patients Undergoing Gynecologic Laparoscopic Surgery, a Randomized, Double-Blind, Single-Center Clinical Study.","authors":"Tingting Li, Liuhu Han, Zhen Wu, Yanfang Chen, Yiqiao Wang","doi":"10.2147/DDDT.S513571","DOIUrl":"https://doi.org/10.2147/DDDT.S513571","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to explore the effect of preoperative different doses of esketamine on postoperative recovery in patients undergoing gynecologic laparoscopic surgery.</p><p><strong>Methods: </strong>A total of 99 women scheduled for gynecologic laparoscopic surgery under general anesthesia were enrolled and randomized. Three minutes before surgical incision, patients in the three groups were intravenously administered 0.25 mg/kg esketamine, 0.5 mg/kg esketamine, and an equivalent dose of saline, respectively. The primary outcome was the Quality of Recovery-15 (QoR-15) score assessed on 1 day (pod1), 3 days (pod3), and 7 days postoperatively (pod7). Secondary outcomes encompassed the VAS score, MAP, HR, frequency of rescue analgesia and length of hospital stay.</p><p><strong>Results: </strong>Compared with group C, QoR-15 score was significantly improved in group E₁ and E₂ on pod1, while the rest VAS score was significantly decreased at 6h postoperatively (<i>F =</i>19.164, <i>P</i> < 0.001; <i>F</i> = 6.059, <i>P</i> = 0.034). On pod1, the VAS scores at rest and movement in group E₂ were significantly lower than those in group C (<i>P</i> = 0.007, <i>P</i> = 0.038). There was a significant decrease in resting VAS scores in the E₂ group compared with group C on pod3 (<i>P</i> = 0.021). Compared with group C, the QoR-15 score in group E₂ increased on pod7 (<i>P</i> = 0.008), but there was no clinical difference. There was no significant difference in MAP and HR among the three groups at each time point (<i>F</i> = 0.758, <i>P</i> = 0.471; <i>F</i> = 0.232, <i>P</i> = 0.794). There was a significant difference in the number of postoperative rescue analgesia among the three groups (<i>P</i> = 0. 023).</p><p><strong>Conclusion: </strong>Preoperative single small dose of esketamine can improve the quality of recovery 24h after gynecologic laparoscopic surgery patients, decrease the number of rescue analgesia, and may contribute to the rapid recovery of patients. And 0.5 mg/kg esketamine seems to be better.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2833-2843"},"PeriodicalIF":4.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987907","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":"Effects of Fospropofol Disodium and Propofol on the Postoperative Recovery of Elderly Patients Who Underwent Total Hip Arthroplasty: A Retrospective Study.","authors":"Sheng Ding, Zaibao Wang, Chunliu Li, Guizhi Wang, Juan Li, Hongrui Zhu, Keqiang He","doi":"10.2147/DDDT.S501222","DOIUrl":"https://doi.org/10.2147/DDDT.S501222","url":null,"abstract":"<p><strong>Purpose: </strong>Propofol is widely used for general anesthesia in elderly patients. Fospropofol disodium, a precursor of propofol, may reduce the incidence of postoperative nausea and vomiting (PONV). However, the effects of these two drugs on patients' postoperative recovery quality are unclear. The present study aimed to evaluate the effects of the two drugs on postoperative recovery quality in elderly patients who underwent total hip arthroplasty.</p><p><strong>Patients and methods: </strong>We retrospectively analyzed 168 patients from the First Affiliated Hospital of USTC from October 2022 to June 2024. These individuals were assigned to fospropofol disodium group (F) or propofol group (P) according to the patients' anesthesia induction and maintenance medication. The primary outcome was the rate of occurrence of PONV. The secondary outcomes included the time of extubation and the time of stay in post-anesthesia care unit (PACU), hospital length of stay, perioperative hemodynamic data and patients' liver and renal functions.</p><p><strong>Results: </strong>PONV occurred to be lesser in group F than in group P (15.94% vs 33.33%, P < 0.05). Group P spent less in the extubation time (25.71 vs 33.36 min, P < 0.05) and PACU stay length (62.61 vs 65.65 min, P > 0.05), but hospital length of stay is longer (6.24 vs 5.8 days, P > 0.05). Liver and renal functions indexes and hemodynamic data between the 2 groups were similar (P > 0.05). The type of drug was a factor affecting the time of extubation. The type of drug and the patient's gender were influential factors in the incidence of PONV.</p><p><strong>Conclusion: </strong>Fospropofol disodium reduces the incidence of PONV in patients. And the effects of fospropofol disodium on postoperative recovery quality are similar to that of propofol in older patients who underwent total hip arthroplasty.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2767-2777"},"PeriodicalIF":4.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986422","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":"Evaluation of Pharmacokinetics and Safety of the Biosimilar (B01711) and Insulin Degludec/Insulin Aspart (IDegAsp, Ryzodeg) in Healthy Chinese Adults in a Randomized, Open-Label, Single-Dose, Crossover, Phase I Study.","authors":"Hui Liu, Haiyan Cao, Ting Li, Xinlei Chen, Hongling Yu, Jingfang Sun, Yerong Yu","doi":"10.2147/DDDT.S500347","DOIUrl":"https://doi.org/10.2147/DDDT.S500347","url":null,"abstract":"<p><strong>Objective: </strong>B01711 is a biosimilar of insulin degludec/insulin aspart (IDegAsp 70/30). This randomized, open-label, single-dose, crossover, phase I study aimed to evaluate the pharmacokinetics (PK) and safety of B01711 compared to its original product (Ryzodeg) in healthy Chinese volunteers.</p><p><strong>Methods: </strong>The study was conducted between April and August 2022, this study included 32 participants (22 males and 10 females) who received subcutaneous injections of both B01711 and Ryzodeg, with a ≥14-day washout period between treatments. All participants completed the study without any dropouts. Blood samples were collected at pre-defined intervals for PK analysis.</p><p><strong>Results: </strong>The primary PK parameters included the area under the curve (AUC) of insulin degludec (IDeg) from 0 to 24 hours (AUC_{IDeg, 0-24 h}), AUC of insulin aspart (IAsp) from 0 to the time of the last measurable value (AUC_{IAsp, 0-t}), and the peak concentration of IAsp (C_{IAsp, max}). PK equivalence would be established if the 90% confidence intervals (CIs) of least squares (LS) mean ratios of log-transformed values of primary PK endpoints for B01711 compared with Ryzodeg fell within the range of 80.0% to 125.0%. Safety was monitored throughout the study. The LS-mean ratios and corresponding 90% CIs were 106.1% (101.9%, 110.5%) for AUC_{IDeg, 0-24 h}; 103.9% (100.2%, 107.6%) for AUC_{IAsp, 0-t}; and 110.1% (101.0%, 119.9%) for C_{IAsp, max}. Two treatment-emergent adverse events (TEAEs) were reported in two subjects (6.3%) in the B01711 group, and seven TEAEs were reported in seven subjects (21.9%) in the Ryzodeg group. The most common TEAE was a decrease in hemoglobin. The adverse events (AEs) of hypokalemia and hypoglycemia were identified as treatment-related AEs (TRAEs) and all TRAEs were mild.</p><p><strong>Conclusion: </strong>This study demonstrated the PK equivalence of the two drugs and confirmed that both were well-tolerated.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2863-2871"},"PeriodicalIF":4.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982197","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":"Antimicrobial Effects of <i>Kelisha</i> Capsule on <i>Escherichia coli</i> Induced Diarrhea in Mice.","authors":"Guolin Shi, Xiao Lu, Guowei Wang, Kai Qian, Xiaokang Peng, Yangyang Zhu, Jiaxu Wu, Haiyong Ke, Li Chen, Yuanhang Zheng, Tao Yang, Xiaoying Shi, Pintong Huang","doi":"10.2147/DDDT.S511158","DOIUrl":"https://doi.org/10.2147/DDDT.S511158","url":null,"abstract":"<p><strong>Background: </strong><i>Kelisha</i> capsule (<i>KLSC</i>), listed in the Chinese Pharmacopoeia, has been employed for the treatment of infectious diarrhea. Nevertheless, the precise mechanism of <i>KLSC</i> remains to be elucidated.</p><p><strong>Aim of the study: </strong>This work was to investigate the antibacterial mode and therapeutic mechanism of <i>KLSC</i> towards <i>E. coli</i> infected diarrhea.</p><p><strong>Materials and methods: </strong>HPLC identified the primary chemical constituents of <i>KLSC</i>. A model of diarrhea was induced via <i>E. coli</i> injection. The impact of <i>KLSC</i> on <i>E. coli</i>-induced diarrhea was evaluated using a diarrhea score in Babl/c mice. The integrity of the intestinal barrier was assessed through staining and measuring levels of specific proteins. Furthermore, immunofluorescence staining was conducted to identify tight junction proteins in the small intestinal tissue. The full-length 16S rRNA was used to examine gut microbiota. Network pharmacology, molecular docking, and molecular dynamic simulation were used to investigate the impact of <i>KLSC</i> on diarrhea-related inflammation and quantify the expression levels of IL-6 and TNF-<i>α</i> in the blood and small intestine. The in vivo antibacterial activity and mode of action of <i>KLSC</i> were also investigated using IVIS imaging, transmission electron microscopy, scanning electron microscopy, and molecular dynamic simulation.</p><p><strong>Results: </strong><i>KLSC</i> exhibited a positive effect on <i>E. coli</i> infected diarrhea. The content of IL-6 and TNF-<i>α</i> in mice with <i>KLSC</i> was significantly reduced. Additionally, <i>KLSC</i> could restore the intestinal barrier function by reversing small intestine structure and up-regulating the expression of tight junction proteins. The <i>KLSC</i> significantly inhibit pathogenic bacteria and restore the gut microbiota diversity. IVIS Imaging System was visually observed significant antibacterial efficacy of <i>KLSC</i> in vivo. The <i>KLSC</i> disrupted the cell membrane system of <i>E. coli</i> through the interaction between bioactive molecule and bilayer.</p><p><strong>Conclusion: </strong><i>KLSC</i> normalized the gut barrier function, reshaped gut microbiota balance, suppressed the inflammatory pathways, and inhibited the bacterial activity, thereby relieving the diarrhea caused by <i>E. coli</i>.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2779-2794"},"PeriodicalIF":4.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985868","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":"Elucidating the Differential Mechanisms of Jingui Shenqi Pill and Mingmu Dihuang Pill in the Treatment of Diabetic Nephropathy Based on Yin-Yang Theory.","authors":"Shijie Bi, Zhenzhen Xu, Anlei Yuan, Zewen Wang, Yanxia Liu, Bin Yu, Jiaye Tian, Chaoqun Liu, Liansheng Qiao, Zhibin Wang, Yanling Zhang","doi":"10.2147/DDDT.S517143","DOIUrl":"https://doi.org/10.2147/DDDT.S517143","url":null,"abstract":"<p><strong>Background: </strong>The Yin-Yang attributes of MMDH and JGSQ in treating diabetic nephropathy (DN) remain unexplored.</p><p><strong>Methods: </strong>UPLC-MS identified formula components, network pharmacology analyzed common DN targets, and in vitro renal fibrosis models assessed efficacy. Transcriptomics revealed key pathways, and molecular docking simulated component-target interactions.</p><p><strong>Results: </strong>UPLC-MS confirmed the compositional complexity of MMDH and JGSQ. Network pharmacology indicated their involvement in multiple DN-related pathways. In vitro, JGSQ alleviated fibrosis and enhanced adhesion via FN and E-cad, while MMDH reduced interstitial fibrosis via FN and VIM. Transcriptomics showed JGSQ regulates the TGF-β pathway, and MMDH modulates the TNF pathway. Molecular docking confirmed key components binding to TGFB1 and TNFA.</p><p><strong>Conclusion: </strong>MMDH and JGSQ exhibit distinct chemical compositions, targets, and pathways, underscoring their Yin-Yang regulatory roles in kidney function.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2817-2831"},"PeriodicalIF":4.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976630","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":"Metabolism and Excretion of 8-O-Acetylharpagide in Rats and Identification of Its Potential Anti-Breast Cancer Active Metabolites.","authors":"Xinyu Zhao, Sijia Su, Jingna Zhou, Junfeng Gao, Xu Tang, Binyu Wen","doi":"10.2147/DDDT.S487898","DOIUrl":"https://doi.org/10.2147/DDDT.S487898","url":null,"abstract":"<p><strong>Background: </strong><i>Ajuga decumbens</i>, a traditional Chinese medicine, possesses anti-breast cancer effects. Its main component, 8-O-acetylharpagide, exhibits potential anticancer activity; however, the active metabolites and mechanisms underlying its effects remain unclear.</p><p><strong>Methods: </strong>The metabolism and excretion of 8-O-acetylharpagide in rats were investigated using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry analysis of bile, urine, and feces. Active metabolites were identified and evaluated using network pharmacology, molecular docking, and Western blotting assays.</p><p><strong>Results: </strong>A total of 21 metabolites were identified, with demethylation, hydrolysis, and glucuronidation being the primary metabolic pathways. M3 and M5 were identified as key metabolites, showing strong binding affinity to cancer-related targets, such as AKT1, MMP9, and STAT3. M5 displayed strong pharmacokinetic properties, including better lipid solubility and reduced polarity. Network pharmacology analysis indicated that these metabolites exert anticancer effects by modulating the PI3K/AKT signaling pathway. In vivo experiments demonstrated that oral administration of 8-O-acetylharpagide significantly inhibited the proliferation of 4T1 tumor tissues by suppressing the expression of the AKT/NF-κB/MMP9 signaling axis. This may be related to inhibition of the expression of the AKT/NF-κB/MMP9 signaling axis in 4T1 tumor tissues after metabolism of 8-O-acetylharpagide to M5 and M3.</p><p><strong>Conclusion: </strong>As a prodrug, 8-O-acetylharpagide is metabolized to M5, which may subsequently exert an anti-breast cancer effect through downregulation of the AKT/NF-κB/MMP9 signaling axis. This study provides a theoretical basis for the clinical application of <i>Ajuga decumbens</i> in breast cancer therapy.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2795-2815"},"PeriodicalIF":4.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11995923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972606","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}