Drug Design, Development and Therapy最新文献

{"title":"Dose-Response Analysis of Nalbuphine for Alleviating Catheter-Related Bladder Discomfort After Ureteroscopic Lithotripsy in Men: A Retrospective Study.","authors":"Jiayi Tang, Huadong Ni, Ming Yao","doi":"10.2147/DDDT.S511613","DOIUrl":"10.2147/DDDT.S511613","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to determine the median effective dose (ED50) and effective dose 95% (ED95) of nalbuphine for alleviating moderate-severe catheter-related bladder discomfort (CRBD) after ureteroscopic lithotripsy (URL) in male patients using probit regression analysis.</p><p><strong>Patients and methods: </strong>This retrospective study analyzed anesthesia records of all male patients who underwent URL and received nalbuphine under general anesthesia at Jiaxing University Affiliated Hospital between August 2023 and August 2024. Patients were categorized into four groups based on nalbuphine dosage: 0.025, 0.05, 0.075, and 0.10 mg/kg. Data on patient demographics, CRBD scores, agitation scores, the Ramsay sedation scale, and urinary catheter-related pain (UCRP) scores were collected 5 min after laryngeal mask removal. Hemodynamic parameters, including mean blood pressure, heart rate (HR), and oxygen saturation (SPO₂), were collected at various time points: post-operation (T0), and at immediately (T1), 5 (T2), 10 (T3), 20 (T4), and 30 min (T5) after laryngeal mask removal. The incidence of adverse events was documented. Probit regression analysis was employed to calculate the ED50 and ED95 of nalbuphine for alleviating moderate-severe CRBD.</p><p><strong>Results: </strong>Data from 76 anesthesia records were retrieved. CRBD, agitation, and UCRP scores decreased with increasing nalbuphine doses, while the Ramsay sedation scores increased. No significant differences were observed in hemodynamic parameters across dose groups at any time point (P > 0.05). Similarly, the incidence of adverse effects did not differ significantly among the groups (P > 0.05). Probit regression analysis revealed that the ED50 of nalbuphine for alleviating moderate-severe CRBD following URL in male patients was 0.03 mg/kg (95% confidence interval [CI]: 0.013-0.046), while the ED95 was 0.108 mg/kg (95% CI: 0.085-0.188).</p><p><strong>Conclusion: </strong>Nalbuphine is a safe and effective agent for mitigating CRBD, with an ED50 of 0.03 mg/kg and ED95 of 0.108 mg/kg.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5283-5292"},"PeriodicalIF":4.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474250","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":"Opioid-Free Anesthesia Improved the Quality of Recovery After Thyroidectomy Through Pre-Emptive and Preventive Analgesia: A Randomized Controlled Trial.","authors":"Ye Zhang, Xiaotong Xian, Furui Wang, Bochong Zhou, Yuwen Wang, Penglei Wang, Yun Li, Yun Wu","doi":"10.2147/DDDT.S520856","DOIUrl":"10.2147/DDDT.S520856","url":null,"abstract":"<p><strong>Background: </strong>Opioid-free anesthesia (OFA) is increasingly being adopted to provide effective analgesia and reduce opioid-related adverse events. However, existing literature on OFA remains contentious, and its impact on postoperative recovery following thyroidectomy has not been evaluated. Therefore, we examined the hypothesis that OFA enhances the early quality of recovery in patients undergoing thyroid surgery.</p><p><strong>Methods: </strong>In this randomized controlled trial, 204 adult patients undergoing thyroidectomy were randomly assigned to receive either OFA (esketamine, dexmedetomidine, and bilateral superficial cervical plexus blocks) or opioid-based anesthesia (OBA, sufentanil and remifentanil). The primary outcome was the quality of recovery on the first postoperative day, assessed using the quality of recovery-15 scale. Secondary outcomes included sleep quality score, area under the curve of pain intensity. Anesthesia-related complications were also recorded.</p><p><strong>Results: </strong>On the first postoperative day, the OFA group had a significantly higher quality of recovery-15 score versus the OBA group (137.6 [5.6] vs 128.2 [10.5], mean difference = 9.4, 95% CI, 7.0-11.7, <i>P</i> < 0.001). Patients in the OFA group also had better sleep quality (mean difference = 7.8, <i>P</i> < 0.001), lower area under the curve of pain intensity versus those in the OBA group. The incidence of postoperative nausea and vomiting was lower (1.0% vs 18.6%, <i>P</i> < 0.001) in the OFA group versus the OBA group. Patients receiving OFA had a delayed extubation and prolonged postanesthesia care unit stay.</p><p><strong>Conclusion: </strong>We showed that with a pre-emptive and preventive analgesia effect, OFA improved quality of recovery, sleep quality, pain, and postoperative nausea and vomiting after thyroidectomy. However, a prolonged emergence recovery was observed when patients receiving OFA strategy, warranting further investigation to optimize agent design and monitoring method to balance the intraoperative anesthesia depth.</p><p><strong>Name of trial registry: </strong>Chinese Clinical Trial Registry.</p><p><strong>Registration number: </strong>ChiCTR2300070794; URL: https://www.chictr.org.cn/showproj.html?proj=196152.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5243-5254"},"PeriodicalIF":4.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474252","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, Pharmacodynamic, Safety and Tolerability of Fazamorexant, a Novel Dual Orexin Receptor Antagonist: Report of the First-in-Human Study.","authors":"Jun Ni, Lu Jin, Dong Zhao, Wen Zhang, Baoshun Li, Xingxing Huang, Xiaohua Hao","doi":"10.2147/DDDT.S501111","DOIUrl":"10.2147/DDDT.S501111","url":null,"abstract":"<p><strong>Purpose: </strong>This is the first-in-human study to investigate the pharmacokinetic and pharmacodynamic profiles, safety, and tolerability of Fazamorexant (a novel dual orexin receptor antagonist) in healthy subjects.</p><p><strong>Methods: </strong>Here, we summarize pharmacokinetic, pharmacodynamic, and safety data from the randomized, double-blind placebo-controlled studies in healthy adults: single ascending doses (2-80 mg; N = 64), multiple ascending doses (10-60 mg; N = 40).</p><p><strong>Results: </strong>Following single and multiple dosing, the pharmacokinetic profile was characterized by quick absorption and elimination, with median t_max of 0.625-1.25 h and arithmetic mean t_1/2 of 1.91-3.68 h. C_max and AUC_0-t were positively correlated with doses and no apparent Fazamorexant plasma accumulation was detected on Day 7. The hypnotic effects were observed after administration and the effects of high dose groups were slightly higher than that of low dose groups, the results of pharmacodynamics showed a dose-dependent effect and the change in SSS from baseline was greatest in the 80 mg group (2.5). There were no clinically relevant effects of gender on Fazamorexant pharmacokinetics. No serious dose-dependent adverse events (AEs) or deaths were observed during the study.</p><p><strong>Conclusion: </strong>Fazamorexant at a single dose of 2-80 mg or 10-60 mg at multiple doses presented satisfactory safety and tolerability in healthy subjects. The findings in this comprehensive first-in-humans study support the continued investigation of Fazamorexant as a therapeutic option for insomnia therapy.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5271-5282"},"PeriodicalIF":4.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474178","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":"Design, Synthesis, and Evaluation of Nitroxide Radical Derivatives Based on Rhein as Potential Anti-Aging Agents Targeting the Keap1-Nrf2 Pathway.","authors":"Jie Wang, Xuejing Peng, Xinyue Zhang, Jia Lin, Qili Zhang, Jiaojiao Li, Longchen Cui, Lei Zhao","doi":"10.2147/DDDT.S516209","DOIUrl":"10.2147/DDDT.S516209","url":null,"abstract":"<p><strong>Purpose: </strong>Targeting the crucial Keap1-Nrf2-ARE antioxidant pathway, we selected Rhein - a natural anthraquinone from traditional Chinese medicine with established Keap1-Nrf2 inhibitory activity as our lead compound. Through rational structural modification by incorporating nitroxide radicals at the 3-carboxyl position, we aimed to develop enhanced Keap1-Nrf2 modulators with anti-aging potential.</p><p><strong>Patients and methods: </strong>A series of rhein nitroxide derivatives were synthesized, and their free radical scavenging activity was assessed in vitro using DPPH and ABTS methods. Compound <b>4b</b>, demonstrating significant activity, was selected for further evaluation. Its effects on the survival of L02 hepatocytes under oxidative stress and the lifespan and stress tolerance of <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) were investigated. Additionally, the impacts of <b>4b</b> on antioxidant enzyme activity, malondialdehyde (MDA) levels, and reactive oxygen species (ROS) accumulation under oxidative stress were assessed. Molecular docking was conducted to analyze interactions between <b>4b</b> and the Kelch domain of Keap1.</p><p><strong>Results: </strong>Compound <b>4b</b> exhibited potent free radical scavenging activity, with IC₅₀ values of 0.51 ± 0.09 mM against DPPH radicals and 0.12 ± 0.03 mM against ABTS radicals. It significantly improved the survival rate of L02 hepatocytes under oxidative stress, maintaining 95.42% viability (<i>p</i> < 0.01). In the <i>C. elegans</i> model, <b>4b</b> extended the average lifespan and enhanced stress resistance, increasing GSH activity, reducing MDA content, and decreasing ROS accumulation. Molecular docking showed that <b>4b</b> penetrates deeply into the Kelch domain of Keap1, forming stable interactions with key residues.</p><p><strong>Conclusion: </strong>Compound <b>4b</b> demonstrates superior antioxidant and anti-aging effects compared to the parent compound rhein, representing a highly promising anti-aging candidate and Keap1-Nrf2 signaling pathway modulator with potential as a novel therapeutic agent for age-related diseases.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5153-5167"},"PeriodicalIF":4.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474249","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":"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":"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":"Cumulative Live Birth Rates in Women Undergoing Progestin-Primed Ovarian Stimulation Using Medroxyprogesterone Acetate, Dydrogesterone, and Progesterone: A Retrospective Analysis.","authors":"Fenglu Wu, Jing Lin, Jing Zhang, Xinggang Wang, Jialyu Huang, Jiaying Lin","doi":"10.2147/DDDT.S523076","DOIUrl":"10.2147/DDDT.S523076","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate possible differences in cumulative live birth rates (CLBRs) among three progestins medroxyprogesterone acetate (MPA), dydrogesterone (DYG), and Progesterone within the progestin-primed ovarian stimulation (PPOS) protocol.</p><p><strong>Patients and methods: </strong>This retrospective study included 21,159 women undergoing one of three ovarian stimulation protocols, hMG + MPA, hMG + DYG, or hMG + Progesterone, between September 2013 and January 2024 in our centre. Patients received oral progestins once daily as per their assigned protocol with human menopausal gonadotropin initiated on menstrual cycle day 3. The primary outcome was the CLBR. Secondary outcomes comprised ovarian stimulation parameters, pregnancy outcomes per embryo transfer, and cumulative outcomes per individual.</p><p><strong>Results: </strong>The CLBR demonstrated no statistically significant differences across the three progestin regimens: MPA (6409/14,930, 42.9%), DYG (1430/3205, 44.6%), and Progesterone (1297/3024, 42.9%; p = 0.203). Kaplan-Meier analysis revealed progressive CLBR accumulation through 5 frozen-thawed embryo transfer (FET) cycles, reaching 87.6%, 95.6%, and 93.7% for MPA, DYG, and Progesterone groups, respectively, with all groups achieving 50% CLBR by the second cycle. Cox regression adjusted for confounders confirmed comparable CLBR trajectories (p > 0.05), while multivariable logistic regression showed no association between progestin type and per-cycle live birth rate (p > 0.05). Notably, the Progesterone group exhibited elevated serum progesterone levels (trigger day: p < 0.05), whereas both DYG and Progesterone groups demonstrated higher LH levels than MPA (p < 0.05).</p><p><strong>Conclusion: </strong>Our findings establish clinical equivalence in cumulative live birth outcomes among MPA, DYG, and Progesterone when implemented within the PPOS framework. This evidence supports protocol flexibility in progestin selection, enabling personalized decisions based on pharmacological characteristics, cost considerations, and patient tolerance.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"5193-5207"},"PeriodicalIF":4.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474248","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":"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":"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":"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":"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}