Drug Design, Development and Therapy最新文献

{"title":"Jingfang Granules for Diabetic Wound Healing: Insights from Network Pharmacology and Experimental Validation.","authors":"Rongrong Wang, Qian Wang, Mingfei Liu, He Xiao, Guimin Zhang, Jingchun Yao, Ming Liu","doi":"10.2147/DDDT.S516298","DOIUrl":"10.2147/DDDT.S516298","url":null,"abstract":"<p><strong>Background: </strong>Diabetic wounds are one of the most common complications of diabetes mellitus. Jingfang Granules (JFG), a combination of 11 herbs, has been clinically used for treating colds and the flu and for preventing various skin diseases.</p><p><strong>Purpose: </strong>The present study was designed to evaluate the therapeutic effect of JFG on diabetic wounds and to elucidate the associated mechanisms.</p><p><strong>Methods: </strong>JFG serum was prepared using Sprague-Dawley rats and the phytochemicals of JFG in the serum were identified using UHPLC-ESI-QE-Orbitrap-MS. A cell viability assay and cellular angiogenesis methods were performed to evaluate wound healing in vitro. Diabetic wounds were developed using streptozotocin-induced diabetic rats to investigate the efficacy of JFG on diabetic wounds in vivo. Network pharmacology analysis, molecular docking, and Western blot were performed to elucidate the potential mechanisms of JFG in diabetic wound healing.</p><p><strong>Results: </strong>JFG serum attenuated H₂O₂-induced and high glucose-induced oxidative damage, significantly reduced lipopolysaccharide-induced upregulation of inflammatory cytokines, and promoted angiogenesis in vitro. In diabetic rats, JFG effectively promoted wound healing, reduced blood glucose and lipid levels, and alleviated oxidative stress and inflammation. A total of 56 phytochemicals were identified in the JFG serum. Six core targets (AKT1, EGFR, MAPK3, MAPK1, IL6, and TNF) and the PI3K-AKT and MAPK signaling pathways were identified by network pharmacology analysis, which were further validated by subsequent experimental methods.</p><p><strong>Conclusion: </strong>JFG could accelerate diabetic wound healing by alleviating oxidative damage, suppressing inflammation, promoting angiogenesis, and regulating metabolic abnormalities, with involvement of the PI3K-AKT and MAPK signaling pathways.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4835-4860"},"PeriodicalIF":4.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246902","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 Pharmacokinetics and Pharmacodynamics with Enterohepatic Recirculation of Co-Medication of Rosuvastatin and Ezetimibe.","authors":"Hyungmi An, Dongseong Shin","doi":"10.2147/DDDT.S522863","DOIUrl":"10.2147/DDDT.S522863","url":null,"abstract":"<p><strong>Objective: </strong>Combination therapy with rosuvastatin and ezetimibe is generally administered to patients with high cardiovascular risk. The objective of this study was to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of the interaction between rosuvastatin and ezetimibe that incorporates enterohepatic recirculation (EHC).</p><p><strong>Methods: </strong>Concentration-time data were obtained from a two-part, open-label, multiple-dose crossover, drug interaction study. In total, 50 healthy male subjects received both monotherapy and co-therapy (Part A: rosuvastatin and co-therapy; Part B: ezetimibe and co-therapy). Rosuvastatin (20 mg) or ezetimibe (10 mg) were administered once daily for 7 days as monotherapy or co-therapy. Plasma concentrations were measured for PK analysis until 72 h post-dose at steady state. The changes in low-density lipoprotein cholesterol (LDL-C) levels from baseline to steady state at 24 h after the last administration were measured. A population PK/PD model incorporating EHC was developed using Monolix 2024R1. Covariate effects were explored, and the final model was evaluated through goodness-of-fit diagnostics and visual predictive checks. Model-based simulations were conducted to compare the LDL-C lowering effects of monotherapy and co-therapy.</p><p><strong>Results: </strong>A population PK/PD model was established using a two-compartment model for rosuvastatin and a four-compartment model for ezetimibe incorporating EHC via intermittent gallbladder emptying. No significant PK interaction was observed. An indirect response PD model reflected the independent LDL-C lowering effects of both drugs. Simulations showed LDL-C reductions of -51.0% (rosuvastatin), -25.3% (ezetimibe), and -60.7% (co-therapy), supporting the additive efficacy of co-therapy. EHC increased the exposure of total ezetimibe with limited LDL-C lowering effects.</p><p><strong>Conclusion: </strong>The overall PK interaction between rosuvastatin and total ezetimibe was not significant. The developed PK/PD model incorporating EHC successfully described the independent LDL-C lowering effects. These findings support the additive benefit of co-therapy of rosuvastatin and ezetimibe and may guide future research toward personalized lipid-lowering strategies.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4777-4787"},"PeriodicalIF":4.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257608","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":"Comparing Liposomal Bupivacaine and Ropivacaine in Serratus Anterior Plane Block for Thoracoscopic Lobectomy: A Randomized Controlled Trial.","authors":"Yang Zhang, Wei Li, Aiping Wei, Shibiao Chen, Xiuhong Wang","doi":"10.2147/DDDT.S513287","DOIUrl":"10.2147/DDDT.S513287","url":null,"abstract":"<p><strong>Background: </strong>The optimal analgesic regimen after video-assisted thoracoscopic surgery (VATS) is unclear. We aimed to examine whether ultrasound-guided serratus anterior plane block (SAPB) with liposomal bupivacaine could provide continuous and effective analgesic effects for lung cancer patients undergoing VATS.</p><p><strong>Methods: </strong>A total of 64 patients were randomly allocated to receive either the liposomal bupivacaine (LB group) or the ropivacaine (RO group). The primary outcome was pain score at rest and on movement in the first three days after surgery. The secondary outcomes included intraoperative remifentanil consumption, perioperative consumption of sufentanil and flurbiprofen axetil, time to extubation, time to first bowel movement, time to first flatus, incidence of postoperative nausea and vomiting (PONV), length of intensive care unit (ICU) stay, length of hospital stay, hospitalization costs, and early recovery quality as assessed by QoR-15 score.</p><p><strong>Results: </strong>The LB group had significantly lower pain scores at rest and on movement at 12h, 24h, 36h, 48h, and 72h after surgery, and lower pain scores on movement at 8h after surgery, when compared with the RO group. Perioperative sufentanil consumption and postoperative flurbiprofen axetil consumption were significantly reduced in the LB group than in the RO group. In addition, compared with the RO group, the LB group had earlier first flatus, mobilization, and urinary catheter removal, shorter ICU stay, lower incidence of PONV, and lower hospitalization costs. The QoR-15 scores in the first three days after surgery were significantly higher in the LB group than in the RO group. There were no statistically significant differences between the two groups regarding time to extubation, intraoperative remifentanil consumption, and length of hospital stay.</p><p><strong>Conclusion: </strong>Ultrasound-guided SAPB with liposomal bupivacaine was effective in relieving postoperative pain for three days after surgery in patients undergoing VATS.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4717-4726"},"PeriodicalIF":4.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257606","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":"Lobetyolin Suppressed Osteoclastogenesis and Alleviated Bone Loss in Ovariectomy-Induced Osteoporosis via Hindering p50/p65 Nuclear Translocation and Downstream NFATc1/c-Fos Expression.","authors":"Chunmei Xiu, Hua Luo, Weixing Huang, Shaohua Fan, Chiting Yuan, Jiangjie Chen, Chenghao Xu, Can Yao, Dun Hong, Liwei Zhang","doi":"10.2147/DDDT.S515930","DOIUrl":"10.2147/DDDT.S515930","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the therapeutic potential of lobetyolin (LBT), a bioactive compound derived from <i>Codonopsis pilosula</i>, against bone loss in postmenopausal osteoporosis (PMOP).</p><p><strong>Methods: </strong>To investigate the therapeutic potential of LBT in osteoporosis, a multifaceted approach involving network pharmacology and molecular docking was employed to identify relevant targets and elucidate mechanisms of action. In vitro experiments evaluated LBT's impact on osteoclastogenesis, bone resorption, and osteoblast differentiation using bone marrow macrophages (BMMs) and bone marrow mesenchymal stromal cells (BMSCs). The inhibition of RANKL-activated NF-κB signaling and downstream NFATc1/c-Fos pathways was analyzed via Western blot and immunofluorescence. Additionally, an in vivo ovariectomy (OVX)-induced osteoporosis mouse model was utilized to examine the effects of LBT on bone architecture, assessed through micro-CT imaging and histological analyses.</p><p><strong>Results: </strong>LBT effectively suppressed RANKL-driven osteoclast differentiation in vitro without cytotoxic effects, reducing osteoclast numbers, size, and resorptive function. It also downregulated osteoclast-specific genes expressions, inhibited ROS production, and disrupted the NF-κB signaling cascade by blocking p50/p65 nuclear translocation. Moreover, LBT mitigated LPS-induced osteogenic impairment, enhancing osteoblast differentiation and mineralization. In the OVX mouse model, LBT treatment improved bone microstructure. Histological analyses further corroborated LBT's role in reducing osteoclast activity and promoting bone formation.</p><p><strong>Conclusion: </strong>LBT exerts a dual effect on bone remodeling, simultaneously inhibiting osteoclast-mediated bone resorption and promoting osteoblast-driven bone formation. By targeting key pathways such as NF-κB/NFATc1/c-Fos and reducing inflammatory responses, LBT emerges as a potential therapeutic agent for managing PMOP and other conditions associated with excessive bone loss, offering a safer alternative to current treatments.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4689-4715"},"PeriodicalIF":4.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246913","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":"<i>Sheng-Jiang Powder</i> Alleviates Th17/Treg Immune Imbalance of Experimental Autoimmune Encephalomyelitis by Regulating the Fatty Acids Metabolism.","authors":"Lulu Wu, Haoyou Xu, Hui Xia, Lilin Peng, Lulu Qin, Qian Gong, Min Zhao, Zhibing Wu, Yuanqi Zhao, Zequan Zheng","doi":"10.2147/DDDT.S510620","DOIUrl":"10.2147/DDDT.S510620","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is one of the leading causes of disability among young people, and the immune imbalance between T helper cell 17 (Th17) and regulatory T cells (Tregs) plays a crucial role in its pathogenesis. Currently, MS treatment relies significantly on immunosuppressive drugs or glucocorticoids, which often have side effects and limitations in efficacy. Sheng-Jiang powder (SJP), a traditional Chinese medicine formula, has demonstrated anti-inflammatory effects and may offer a novel therapeutic option for MS.</p><p><strong>Aim: </strong>This study aimed to investigate the therapeutic efficacy and underlying mechanism of SJP in myelin oligodendrocyte glycoprotein 35-55 (MOG35-55)-induced experimental autoimmune encephalomyelitis (EAE) mice.</p><p><strong>Methods: </strong>The efficacy of SJP was assessed using the MOG35-55-induced EAE model. Disease severity was monitored based on the clinical symptoms, body weight, and pathological damage. Furthermore, Th17/Treg balance in the peripheral and central immune systems was assessed. Metabolomic analysis was performed to detect differential metabolites in serum, and the effects of fatty acids on the lipoxygenase (LOX) metabolic pathway were investigated.</p><p><strong>Results: </strong>SJP alleviated MOG35-55-induced EAE symptoms and histological damage, restored the peripheral Th17/Treg immune balance, decreased pro-inflammatory cytokine levels, and increased anti-inflammatory cytokine levels. SJP intervention also influenced omega-3 polyunsaturated fatty acid (PUFA) metabolism and absorption in EAE mice, promoting an anti-inflammatory process associated with 12/15-lipoxygenase(12/15-LOX) upregulation and 5-lipoxygenase(5-LOX) downregulation.</p><p><strong>Conclusion: </strong>This study suggests that SJP is a viable treatment option for MS, and traditional Chinese medicine therapies for autoimmune diseases will continue to be developed.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4755-4776"},"PeriodicalIF":4.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246900","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":"Integration of Network Pharmacology, Transcriptomics, and Metabolomics Strategies to Uncover the Mechanism of Chaihuang Qingfu Pill in Treating Sepsis-Induced Liver Injury.","authors":"Chenbin Zhang, Fang Chen, Yu Jiang, Jun Deng, Xiao Yan, Xin Yin, Bowu Su, Wen Liu","doi":"10.2147/DDDT.S521626","DOIUrl":"10.2147/DDDT.S521626","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Sepsis is a critical condition triggered by infection and characterized by systemic inflammation and subsequent multiorgan failure. Chaihuang Qingfu Pill (CHQF), an in-hospital formulation developed by Hunan Provincial People's Hospital, is derived from the traditional Chinese medicine compound Qingyi Decoction through optimized herbal compatibility. It possesses pharmacological activities including heat-clearing and purgation, choleretic and anti-jaundice effects, as well as Qi-regulation and mass-resolving properties. Clinically, CHQF is primarily used in the treatment of cholecystitis, pancreatitis, and hepatitis, and has shown potential therapeutic effects in alleviating sepsis-associated liver injury. However, the precise molecular mechanisms and omics-based investigations of CHQF in the context of sepsis remain poorly understood. The NF-κB signaling pathway serves as a central regulatory hub of the inflammatory response. Its activation leads to the excessive expression of pro-inflammatory mediators and cytokines, thereby exacerbating tissue damage and promoting the progression of inflammatory diseases. Consequently, targeting the NF-κB pathway may represent an effective therapeutic strategy for the treatment of sepsis. This study aims to systematically investigate the molecular basis of CHQF in the mitigation of sepsis-associated liver damage.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;To explore the mechanism of CHQF for the treatment of sepsis-induced liver injury.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A sepsis mouse model was established via cecal ligation and puncture (CLP). The pharmacological mechanisms of CHQF were explored using network pharmacology, transcriptomics, and metabolomics, which enabled the identification of potential therapeutic targets and pathways, as further validated by in vivo and in vitro experiments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;CHQF administration significantly improved the survival rates, reduced systemic inflammation, and restored liver function in CLP-induced sepsis mice, while also mitigating liver tissue injury. Network pharmacological analysis revealed paeoniflorin, quercetin, hyperforin, and wogonin as the core bioactive compounds of CHQF. Transcriptomic profiling identified key targets, including CD14, CXCL2, CCL2, BIRC5, and CXCL8, and demonstrated a significant downregulation of inflammatory cytokines such as TNF-α, IL-6, IL-1β, IL-17, CCL2, CCL3, CCL4, CXCL2, CXCL3, and CXCL5, alongside NF-κB signaling pathway inhibition. Metabolomic analysis indicated that CHQF treatment reduced the levels of sepsis-related metabolites, including lysophosphatidylcholine (22:6), lysophosphatidylcholine (18:1), 1-LGPC, and C17-sphinganine.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Collectively, these findings suggest that CHQF alleviates sepsis-induced liver injury by modulating the inflammatory response via NF-κB signaling pathway inhibition. This study provides novel insights into the complex molecular mec","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4665-4688"},"PeriodicalIF":4.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246901","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 Efficacy of Sodium Bicarbonate Ringer's Solution and Lactate Ringer's Solution in Patients Undergoing Long-Term Abdominal Open Surgery: A Multicenter Prospective Randomized Controlled Study.","authors":"Susu Zhou, Kai Zhao, Chunmei Liu, Hong Luo, Jun Shi, Chunhong Liu, Xiaoming Li, Fang Gao, Xiangnan Wu, Qin Shen, Wenhua Yuan, Xiaoqing Chai, Xin Wei","doi":"10.2147/DDDT.S514725","DOIUrl":"10.2147/DDDT.S514725","url":null,"abstract":"<p><strong>Purpose: </strong>Sodium bicarbonate Ringer's solution (BRS) is an intravenous fluid that does not rely on hepatic or renal metabolism. It contains bicarbonate ions (HCO₃ ^-) and lacks lactate ions. This study hypothesizes that BRS is more effective in maintaining acid-base balance during prolonged open abdominal surgeries. The aim is to investigate the effects of sodium bicarbonate Ringer's solution on lactate metabolism, acid-base balance, and clinical outcomes in patients undergoing extended-duration open abdominal surgery, with the objective of refining fluid replacement strategies for this patient population.</p><p><strong>Patients and methods: </strong>A multicenter randomized controlled trial was conducted involving 112 patients undergoing open abdominal surgery. Participants were randomly assigned to either the BRS group (n=55) or the lactated Ringer's solution (LRS) group (n=57). The primary outcome was the incidence of postoperative hyperlactacidemia, while secondary outcomes included serum lactate (Lac), pH, base excess (BE), buffered base (BB), bicarbonate (HCO₃ ^-), blood glucose (Glu), electrolytes, postoperative liver and kidney function, and postoperative complications. Linear regression analysis was performed to identify factors influencing lactate concentration.</p><p><strong>Results: </strong>The incidence of hyperlactic acidemia was lower in Group A compared to Group B (9.1% vs 19.3%, <i>P</i> = 0.177), although the difference did not reach statistical significance. No significant differences were observed in lactate (Lac), pH, base excess (BE), bicarbonate (BB), HCO₃⁻, glucose (Glu), or electrolytes between the two groups at any time point (<i>P</i> _time < 0.001, <i>P</i> _group > 0.05, <i>P</i> _{time * group} > 0.05). Linear regression analysis revealed that diabetes, hypotension and blood loss were significant factors influencing blood lactate concentration <i>(R²</i> = 0.349, <i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>Sodium bicarbonate Ringer's solution and lactate Ringer's solution are both safe options for fluid replacement during long-term open abdominal surgeries. There is no significant difference observed in perioperative lactate levels, acid-base balance, or clinical postoperative outcomes between the two solutions.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4617-4628"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246914","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 Influence of Age on the Effective Dosage of Intravenous Remimazolam for the Relief of Preoperative Anxiety in Pediatric Patients at Median and 95% Effective Doses: A Prospective Study.","authors":"Yueyue Chen, Wenhua Zhang, Junyi Ma, Wenxing Liu, Xingrong Song, Xi Chen","doi":"10.2147/DDDT.S515924","DOIUrl":"10.2147/DDDT.S515924","url":null,"abstract":"<p><strong>Purpose: </strong>Preoperative anxiety is an urgent problem in pediatric patients. This trial evaluated intravenous remimazolam for preoperative sedation in pediatric patients, assessing efficacy, safety, and age-dependent dose effects.</p><p><strong>Patients and methods: </strong>In this two-part study, Aged 1~6 years old, 293 ASA I-II children [Parental Separation Anxiety Score (PSAS) ≥3 after nonpharmacological interventions] were enrolled. Part I: children were divided into 5 groups according to their age, and the trial was conducted by the Dixon-Massey sequential method. The first child in each group received a dose of 0.3 mg/kg of remimazolam, with a drug dose gradient of 0.05 mg/kg. Part II: 150 children were randomly selected and assigned to receive remimazolam 0.2-0.3 mg/kg. The main observations of this study were sedation effect and safety.</p><p><strong>Results: </strong>The ED₅₀ and 95% confidence interval (CI) for children aged 1-2 years was 0.14 (0.11-0.16) mg/kg, for children aged 2-3 years was 0.14 (0.11-0.17) mg/kg, for children aged 3-4 years was 0.16 (0.12-0.19) mg/kg, and for children aged 4-5 years was 0.14 (0.11-0.16) mg/kg, 5-6 years 0.13 (0.10-0.16) mg/kg, with no significant difference between age groups (P=0.525). The ED₉₅ for preoperative sedation in children aged 1-6 years was 0.29 mg/kg (95% CI: 0.27-0.40). The difference in MOAA/S scores between the different dose groups in Part II was statistically significant (p<0.001) at 2 minutes after dosing. None of the adverse events that occurred after the use of remimazolam in this trial required the use of medication for intervention.</p><p><strong>Conclusion: </strong>Remimazolam can be effectively used for preoperative sedation in children aged 1-6 years with low circulatory and respiratory effects, and there was no difference in the effective dose of the drug by age.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4605-4615"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246915","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 Intraoperative Intravenous Infusion of Esketamine Combined with Dexmedetomidine on Postoperative Sleep Disturbance in Patients Undergoing Radical Mastectomy.","authors":"Xingyu Geng, Yutian Pu, Ziwei Hu, Heling Zhang, Maosan Wang, Can Fang, Gaochao Lv, Wanting Li, Xinyue Zhang, Xiaoxuan Fan, Su Liu, Xiuxia Chen, Jingru Wu","doi":"10.2147/DDDT.S510222","DOIUrl":"10.2147/DDDT.S510222","url":null,"abstract":"<p><strong>Objective: </strong>Postoperative sleep disturbance(POSD) is a problem in breast cancer patients after surgery. Little is known about the differences in the treatment of POSD with esketamine combined with dexmedetomidine under the same circumstances. We investigated the effects of intraoperative esketamine combined with intravenous dexmedetomidine on the incidence of POSD and postoperative sleep architecture.</p><p><strong>Methods: </strong>A single-center, randomized, double-blind controlled trial was conducted. A total of 100 participants were randomly assigned to four groups: the esketamine group (Group E), the dexmedetomidine group (Group D), the esketamine combined with dexmedetomidine group (Group ED), and the control group (Group S) (n=25 each). The intervention drugs were continuously infused until the placement of the drainage tube. The primary outcome measure was the incidence of POSD, defined as an Athens Insomnia Scale (AIS) score >6 on at least one of the first three postoperative days. The secondary outcome measure was the duration of sleep structure, which was collected using the Fitbit Charge 2^® smartwatch (Fitbit, Inc. San Francisco, California, USA).</p><p><strong>Results: </strong>In the first three postoperative days, the incidence of POSD was similar across the four groups (<i>P</i>=0.947). However, on postoperative day 3 (POD3), there was a significant interaction between esketamine and dexmedetomidine (<i>P</i>=0.004). Further simple effect analysis revealed that, in the absence of esketamine, dexmedetomidine had a significant effect on POSD on POD3 (OR=0.196, [0.056-0.691]; <i>P</i>=0.019). In the absence of dexmedetomidine, esketamine had a significant effect on POSD on POD3 (OR=0.248, [0.074-0.833]; <i>P</i>=0.042). Dexmedetomidine reduced rapid eye movement (REM) sleep on postoperative day 1 (<i>P</i>=0.042). Esketamine reduced nighttime awakening time on POD1 (<i>P</i>=0.036) and POD3 (<i>P</i>=0.020).</p><p><strong>Conclusion: </strong>Intraoperative infusion of esketamine combined with dexmedetomidine had no significant effect on POSD, but dexmedetomidine reduced REM sleep, and esketamine reduced the nocturnal awakening time.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4629-4640"},"PeriodicalIF":4.7,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224719","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":"Rhein Alleviates Cisplatin-Induced Acute Kidney Injury via Downregulation of NOX4-COX2/PGFS Signaling Pathway.","authors":"Xi Yuan, Luosha Long, Minghui Wang, Wenhao Chen, Baien Liang, Long Xu, Weidong Wang, Chunling Li","doi":"10.2147/DDDT.S515409","DOIUrl":"10.2147/DDDT.S515409","url":null,"abstract":"<p><strong>Purpose: </strong>Cisplatin (cis-diamminedichloroplatinum II, CDDP), a widely used chemotherapeutic agent, is clinically limited by nephrotoxicity. Rhein, an anthraquinone from <i>Radix Rhein Et Rhizome</i>, shows nephroprotective potential. This study investigated Rhein's protective effects and mechanisms in CDDP-induced acute kidney injury (AKI).</p><p><strong>Methods: </strong>Network pharmacology identified active components and target genes of <i>Radix Rhein Et Rhizome</i>. Bioinformatics analysis screened differentially expressed genes and conducted functional enrichment (GO/HALLMARK). Molecular docking and molecular dynamic (MD) simulations confirmed Rhein's binding to target proteins. CDDP-induced AKI mouse models and human proximal tubular epithelial cells (HK2) injury models were established to reveal Rhein's nephroprotective mechanisms. Lewis lung carcinoma (LLC) tumor-bearing mice and human A549 lung cancer cells further validated Rhein's compatibility with CDDP antitumor efficacy.</p><p><strong>Results: </strong>Network pharmacology revealed 12 bioactive components and 420 potential targets of <i>Radix Rhein Et Rhizome</i>, with Rhein as the core component interacting with 50 cross-validated targets. Protein-protein interaction (PPI) network analysis prioritized 16 hub genes functionally enriched in oxidative stress (GO) and inflammatory/apoptotic pathways (HALLMARK). Molecular docking and MD simulations demonstrated Rhein's robust binding stability with NOX4, COX2, and PGFS, indicating multi-target modulation. In vivo, Rhein attenuated CDDP-induced AKI by reducing plasma creatinine, renal KIM-1/NGAL expression, and suppressing tubular apoptosis and inflammation. In vitro, Rhein mitigated CDDP-triggered HK2 cell injury through reducing ROS levels and inhibiting the NOX4-NFκB-COX2/PGFS axis. Notably, Rhein preserved CDDP's tumor-suppressive effects in both LLC-bearing mice and A549 cells.</p><p><strong>Conclusion: </strong>Rhein protects against CDDP-induced AKI by inhibiting oxidative stress and inflammation through targeting the NOX4-NFκB-COX2/PGFS pathway, without compromising CDDP's antitumor activity. These findings highlight Rhein as a promising adjunctive therapy for CDDP-associated nephrotoxicity.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4641-4664"},"PeriodicalIF":4.7,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224721","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}