Drug Design, Development and Therapy最新文献

{"title":"Effect of Neoadjuvant Immunochemotherapy on Postoperative Pulmonary Complications for Locally Advanced Esophageal Cancer: A Propensity Score Matching Cohort Study.","authors":"Wei Du, Xi Qiao, Jifang Yao, Zhijiao Wang, Yuanyuan Shi, Huiqun Jia","doi":"10.2147/DDDT.S537794","DOIUrl":"10.2147/DDDT.S537794","url":null,"abstract":"<p><strong>Purpose: </strong>Neoadjuvant immunochemotherapy (NICT) has shown promise in improving the oncological outcomes of locally advanced esophageal cancer (LAEC). However, concerns remain regarding its potential to induce pulmonary side effects that may increase the risk of perioperative adverse events. This study aimed to compare the incidence of postoperative pulmonary complications (PPCs) in patients receiving NICT and those undergoing non-neoadjuvant therapy.</p><p><strong>Patients and methods: </strong>This retrospective cohort study included 274 patients with LAEC who received either NICT or non-neoadjuvant therapy followed by radical esophagectomy. Propensity score matching was used to balance patient characteristics between the two groups. The primary outcome was the incidence of PPCs within the first seven days postoperatively. Conditional logistic regression models were used to assess the association between NICT and PPCs. Sensitivity analysis using inverse probability of treatment weighting was conducted to validate the robustness of the findings.</p><p><strong>Results: </strong>A total of 182 patients were included in the final analysis, with 91 patients in each group. The incidence of PPCs was significantly higher in the NICT group than in the control group (46.2% vs 26.4%, <i>P</i> = 0.009). Respiratory infections (37.4% vs 22.0%, <i>P</i> = 0.035) and pleural effusions (22.0% vs 9.9%, <i>P</i> = 0.043) were more frequent in the NICT group. New-onset arrhythmia was the most common cardiovascular complication, with tachycardia occurring in 24.2% of patients in the NICT group compared to 9.9% in the control group (<i>P</i> = 0.018). Conditional logistic regression analysis revealed a significant association between NICT and PPCs (OR = 5.648, 95% CI: 1.579-20.204, <i>P</i> = 0.008). Sensitivity analysis using IPTW further confirmed these results (OR = 2.893, 95% CI = 1.537-5.446, <i>P</i> = 0.001).</p><p><strong>Conclusion: </strong>Patients with locally advanced esophageal cancer who received at least two cycles of NICT had a significantly increased risk of developing postoperative pulmonary complications.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7637-7651"},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023072","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":"Generic Intravenous Amisulpride (QLG2069) for the Prevention of Postoperative Nausea and Vomiting in Adults: A Phase III, Multicenter, Randomized, Placebo-Controlled Study.","authors":"Hong Zhang, Saiying Wang, Mengchang Yang, Yanjuan Huang, Kai Wang, Ke Jiang, Foquan Luo, Xianwen Hu, Yi Hong, Furong Huang, Shuan Jin, Feng Qi, Shoushi Wang, Xiaoqing Zhang, Huiyu Luo, Langtao Guo, Longzhen Zhang, Jiangang Li, Yongquan Chen, Zhong Qin, Chun Chen, Jianjun Yang, Wanwei Jiang, Nini Fu, Yunfei Ju, Yuanyuan Li, Juan Wang, Wen Ouyang, Yi Feng","doi":"10.2147/DDDT.S529526","DOIUrl":"10.2147/DDDT.S529526","url":null,"abstract":"<p><strong>Background: </strong>The dopamine D2/D3 antagonist amisulpride has demonstrated its superiority and efficacy in prophylaxis of postoperative nausea and vomiting (PONV). Given the branded intravenous amisulpride (Barhemsys^®) has not been approved in China, there is unmet clinical need for amisulpride. Our primary objective was to ascertain the efficacy and safety of the generic intravenous amisulpride (QLG2069) in the prophylaxis of PONV.</p><p><strong>Methods: </strong>In this phase III, multicenter, randomized, double-blind, placebo-controlled study, 551 adult Chinese patients (with ≥2 Apfel risk factors for PONV) undergoing elective laparoscopic gynecological or abdominal surgery were randomly allocated in a 1:1 ratio to receive either generic intravenous amisulpride or placebo. The primary endpoint was the complete response (CR) rate, defined as the proportion of patients demonstrating neither emetic episodes (vomiting/retching) nor requiring rescue antiemetics throughout the 24-hour postoperative window.</p><p><strong>Results: </strong>Totally, 542 patients (amisulpride group: n=275; placebo group: n=267) were included in the full analysis set. Amisulpride demonstrated significantly higher CR rate compared to placebo (53.82% vs 40.07%; P=0.0011) within 24-h postoperative period. Patients treated with intravenous amisulpride exhibited significantly lower incidence of moderate-to-severe nausea (28.36% vs 37.08%; P=0.0266) and emesis (44.73% vs 57.30%; P=0.0030) compared to the incidence in the placebo group. The proportion of patients without nausea was numerically higher (45.09%) in the amisulpride group compared to that in the placebo group (37.45%), although the difference did not reach statistical significance (P=0.0685). No significant difference in the proportions of patients receiving rescue medication was noticed between the two groups (21.09% vs 28.09%; P=0.0569). The incidence of adverse events were comparable in two groups.</p><p><strong>Conclusion: </strong>The generic intravenous amisulpride was safe and effective in prophylaxis of PONV in Chinese patients with moderate-to-high risk of PONV to were undergoing laparoscopic gynecological or abdominal surgery.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7707-7718"},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023067","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":"Natural Products From Traditional Chinese Medicine: Potential Therapeutic Agents in Cancer Therapy-Induced Cardiotoxicity.","authors":"Ruoyu Jin, Qianhui You, Chenshi Li, Na Zhao, Chengyao Jia, Chinying Koo, Weiwei Zhang, Baonian Liu, Kaijian Huang","doi":"10.2147/DDDT.S545216","DOIUrl":"10.2147/DDDT.S545216","url":null,"abstract":"<p><p>Cancer therapy-induced cardiotoxicity (CTIC) is a serious and increasingly recognized cause of death and disability among cancer survivors. It frequently necessitates the withdrawal or dose reduction of effective anticancer drugs, limiting therapeutic options and affecting patient outcomes. While CTIC poses a major health risk, the precise cellular and molecular mechanisms responsible for this toxicity remain elusive, which complicates the development of preventive and therapeutic strategies. In recent years, natural products derived from Traditional Chinese Medicine (TCM) have gained attention as potentially beneficial agents for CTIC management. These TCM natural products consist of biologically active compounds that often act on multiple therapeutic targets, offering a comprehensive approach to mitigating cardiotoxicity during cancer treatment. This review aims to provide a concise overview of CTIC associated with various anticancer drugs and examine the emerging research on TCM natural products in reducing the cardiotoxic effects related to cancer therapies, highlighting areas where further investigation is needed. In addition, we also provide the challenges and coping strategies faced by basic research and clinical transformation of Chinese medicine monomers.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7653-7680"},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023078","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":"Anticancer, Antioxidant and Antimicrobial Activity of <i>Elaeagnus angustifolia L</i>. Leaf Extract.","authors":"Serap Doğan, Ahmet Meşe, Mehmet Fırat Baran, Ayse Baran, Necmettin Aktepe, Elham Ahmadian, Ali Jimale Mohamed, Aziz Eftekhari, Hüsnü Aktaş","doi":"10.2147/DDDT.S509705","DOIUrl":"10.2147/DDDT.S509705","url":null,"abstract":"<p><strong>Objective: </strong>This study was conducted to determine and compare the antioxidant, cytotoxic, and antimicrobial effects of spindle leaves of <i>Elaeagnus angustifolia</i> L. (<i>E. angustifolia</i>) (oleaster) leaves.</p><p><strong>Methods: </strong>Total phenolic content was measured using the Folin-Ciocalteu method, phenolic compound analysis by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) and antimicrobial effect by the minimum inhibition concentration (MIC) method. The free radical scavenging activity was determined by t<i>he</i> (2,2-Diphenyl-1-picrylhydrazyl) DPPH method, the free radical scavenging activity was determined by the ABTS method, and cytotoxicity assays were performed by the MTT method in human retinal epithelium cells (RPE-1), human osteosarcoma cells (U2OS), and prostate cancer cells (DU-145) cell lines.</p><p><strong>Results: </strong>High amounts of gallic acid, protocatechuic acid, and o-coumaric acid were identified as phenolic compounds. <i>E. angustifolia</i> was found to have a good antioxidant capacity and high free radical scavenging capacity. In this study, for the first time, <i>E. angustifolia</i> leaf extract was used to investigate cytotoxic effects on human retinal epithelium (RPE-1), human osteosarcoma cells (U2OS), and prostate cancer (DU-145) cells and antimicrobial effects on <i>Listeria monocytogenes</i> American Type Culture Collection (ATTC) 7644, Staphylococcus aureus ATCC 29213, <i>Escherichia coli</i> ATCC 25922, <i>Klebsiella pneumonia</i> ATCC 11774, and <i>Candida albicans</i> ATCC 10231 microorganisms. The highest cytotoxic effect was observed in the DU-145 cell line, and the highest antimicrobial effect was observed in <i>Listeria monocytogenes</i> ATTC 7644 and <i>Candida albicans</i> ATCC 10231. The leaf extract of the plant contains some important phenolic compounds and has high free radical scavenging capacity, a good anticancer effect, and effective antimicrobial activity on yeast species such as <i>C. albicans</i>.</p><p><strong>Conclusion: </strong>Our study will contribute greatly to the search for anticancer and antimicrobial agents, especially from a pharmacological perspective, by examining biological activity using three different methods.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7719-7734"},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of EEG Burst Suppression and Hemodynamic Effects Between Remimazolam Tosilate and Etomidate During General Anesthesia Induction: A Retrospective Analysis.","authors":"Ying Cao, Mi Gan, Linling Wan, Jun Lu, Ting Liu, Meiyan Liu, Di Wang, Sen Hong, Lin Zhou, Luying Deng, Zijun Wang, Jingjie Wang, Changyu Sun, Yang Liu, Yanqiu Liu, Meiwu Zhou","doi":"10.2147/DDDT.S528483","DOIUrl":"10.2147/DDDT.S528483","url":null,"abstract":"<p><strong>Background: </strong>Remimazolam tosilate, a novel ultra-short-acting benzodiazepine, demonstrates promising safety profiles in clinical settings. While both remimazolam tosilate and etomidate provide hemodynamic stability during anesthesia induction, limited research has directly compared their effects on electroencephalogram (EEG) burst suppression (periods of transient brain wave silence), a potential predictor of adverse neurological outcomes. This study aims to compare the incidence rate of EEG burst suppression (ESR) with remimazolam tosilate versus etomidate by reviewing the drug regimens used by different anesthesiologists in clinical practice.</p><p><strong>Methods: </strong>This single-center retrospective study analyzed clinical anesthesia induction data from 161 patients from October 2023 to July 2024. Patients received either remimazolam tosilate (0.2 mg/kg, n=86, Group R) or etomidate (0.3 mg/kg, n=75, Group E) for general anesthesia induction. Primary outcomes included ESR and its duration during induction. Second outcomes comprised hemodynamic parameters: systolic blood pressure, diastolic blood pressure mean arterial pressure, and heart rate, measured at baseline (T0), 3 minutes post-induction (T1), immediately after intubation (T2), 5 minutes post-intubation (T3), 10 minutes post-intubation (T4), and adverse events occurrence.</p><p><strong>Results: </strong>Baseline characteristics were comparable except ASA classification (higher ASA III proportion in Group R: 24.4% vs 2.7%, P<0.001). No ESR occurred in Group R versus 29.34% in Group E (P<0.01). Group R had a significantly lower incidence of intubation-related hypertension (10.5% vs 42.7%, P<0.001) and maintained stable blood pressure and HR throughout induction, whereas Group E exhibited marked MAP and HR fluctuations. Other adverse events showed no significant inter-group differences.</p><p><strong>Conclusion: </strong>Remimazolam tosilate demonstrated notable differences compared to etomidate during general anesthesia induction, including the absence of ESR and different hemodynamic response patterns. While these findings suggest potential advantages for certain patient populations, the retrospective design and ASA classification imbalance limit definitive conclusions, warranting prospective validation studies.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7623-7636"},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12415106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029213","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 Epidural Catheter Design on Analgesic Efficacy During Programmed Intermittent Epidural Boluses: A Randomized Double-Blinded Controlled Trial.","authors":"Yibing Yu, Qingsong Zhao, Yu Zang, Zhiqiang Liu, Weijia Du","doi":"10.2147/DDDT.S545076","DOIUrl":"10.2147/DDDT.S545076","url":null,"abstract":"<p><strong>Purpose: </strong>To compare analgesic outcomes between single- and multi-orifice epidural catheters at a 360-mL/h delivery rate during programmed intermittent epidural bolus.</p><p><strong>Patients and methods: </strong>In this prospective randomized double-blinded controlled trial, 102 healthy nulliparous parturients requesting labor analgesia at the Shanghai First Maternity and Infant Hospital were enrolled from July to September 2023. Participants were given either single- or multi-orifice catheters for epidural analgesia (0.1% ropivacaine with 0.3 µg/mL of sufentanil; 10 mL every 45 min at 360 mL/h). The primary outcome was ropivacaine consumption per hour, calculated as the total amount of ropivacaine administered divided by the duration of labor analgesia (mg/h).</p><p><strong>Results: </strong>Median ropivacaine consumption per hour was not significantly different: 12.6 mg/h [11.6-13.2 mg/h] for single-orifice vs 12.8 mg/h [12.3-13.3 mg/h] for multi-orifice catheters (difference 29%; 95% confidence interval [CI], -10.2 to 68.2%; <i>P</i>=0.241). No significant differences were found in patient-controlled epidural analgesia boluses requested and delivered, time to first bolus request, or the number of clinician-administered boluses. However, adequate analgesia at 20 min was higher with single-orifice catheters (84.0% vs 63.5%, difference 22.5%; 95% CI: 9.2% to 35.1%, <i>P</i>=0.019). Median times to adequate analgesia were 8 min [4-16] vs 15 min [9.5-22.5] for single- and multi-orifice catheters (<i>P</i>=0.002). Pain scores differed only at 6 and 18 min. There were no differences in the incidence of motor or unilateral block, side effects, maternal satisfaction, or catheter-related complications between the two groups.</p><p><strong>Conclusion: </strong>Single-orifice catheters did not enhance analgesia quality during labor maintenance under a 360-mL/h programmed intermittent epidural bolus delivery rate but were linked to more rapid analgesic onset than multi-orifice catheters.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7581-7590"},"PeriodicalIF":5.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014164","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":"Norepinephrine or Phenylephrine to Prevent Spinal Anesthesia-Induced Hypotension During Cesarean Section: A Double-Blinded, Randomized, Controlled Study of Fetal Cerebral Perfusion.","authors":"Jinping Liu, Zhimin Sheng, Feihe Guo, Xiao Lin, Li Xu, Lihong Sun, Xiaowei Qian","doi":"10.2147/DDDT.S535671","DOIUrl":"10.2147/DDDT.S535671","url":null,"abstract":"<p><strong>Purpose: </strong>Spinal anesthesia-induced hypotension can cause detrimental effects on both the mother and the fetus, and it remains a significant concern in obstetric anesthesia. The use of vasopressors is considered the most reliable and effective approach. Previous studies have shown that norepinephrine appears to be superior to phenylephrine in maintaining maternal heart rate and cardiac output. Therefore, we hypothesize that norepinephrine is more effective than phenylephrine in maintaining neonatal cerebral perfusion when used to prevent spinal anesthesia-induced hypotension.</p><p><strong>Patients and methods: </strong>This study is a prospective, double-blinded, randomized trial. We enrolled 216 singleton parturients who were scheduled for elective cesarean delivery. The patients received a prophylactic intravenous infusion of either norepinephrine (0.08 μg/kg/min) or phenylephrine (0.5 μg/kg/min). Maternal cardiac output was not routinely monitored during the study period. Fetal ultrasound examinations were performed, with blood velocity measured in the middle cerebral artery and umbilical artery, and the cerebroplacental ratio calculated.</p><p><strong>Results: </strong>Ninety subjects were ultimately analyzed in each group. The changes in blood velocity in the middle cerebral artery and umbilical artery, as well as the calculated cerebroplacental ratio at 3 and 6 minutes after spinal anesthesia, did not differ significantly between the two groups. The estimated difference of ΔCPR in two groups was - 0.01 (95% CI, -0.05-0.02, P = 0.491) at 3 minutes and was 0.02 (95% CI, -0.01-0.07, P = 0.204) at 6 minutes.</p><p><strong>Conclusion: </strong>Prophylactic infusion of norepinephrine or phenylephrine at comparable doses has similar effects on fetal cerebral perfusion.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7571-7580"},"PeriodicalIF":5.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12415114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029295","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":"Anti-Inflammatory Modified Fuzi Decoction Antagonizes Synovial TNF-α/TRAF2/NF-κB Signaling to Remedy Osteoarthritis.","authors":"Yue Wang, Jiadan Ren, Huixin Chen, Xiaotian Chen, Bo Yan, Wenting Xu, Xiujuan Xiao, Qiang Yuan, Letian Shan, Li Zhou","doi":"10.2147/DDDT.S481770","DOIUrl":"10.2147/DDDT.S481770","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the pharmacodynamic effects and therapeutic mechanisms of modified Fuzi decoction (MFZD) in osteoarthritis (OA), particularly OA-related inflammation.</p><p><strong>Methods: </strong>The main components of MFZD were identified using Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS). An OA model was established in Sprague-Dawley rats via intra-articular injection of monoiodoacetate (MIA) to evaluate the anti-OA efficacy of MFZD via gavage. In vivo studies, including pain behavior evaluation, histopathological observation, immunohistochemical analysis, enzyme-linked immunosorbent assay (ELISA), Meso Scale Discovery (MSD), and Western blot (WB), were carried out to demonstrate the anti-inflammatory and anti-degenerative potency of MFZD against OA. Potential targets and pathways of MFZD were identified via network pharmacology analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, respectively. Subsequently, the tumor necrosis factor (TNF) signaling and related targets were validated in vitro by WB. For in vitro validations, primary synovial fibroblasts were isolated from rats and treated with MFZD-containing serum (MFCS) in the presence of TNF-α.</p><p><strong>Results: </strong>UPLC-MS/MS analysis identified key compounds in MFZD, including trans-cinnamaldehyde, atractylenolide I, lobetyolin, paeoniflorin, pachymic acid, carmichaeline, talatisamine, fuziline, benzoylhypacoinine, benzoylmesaconine, benzoylaconine, hypaconitine, deoxyaconitine, mesaconitine, and aconitine. MFZD treatment improved the paw withdrawal threshold (PWT), alleviated histopathological damage, reduced TNF-α and monocyte chemotactic protein-1 (MCP-1) in the serum, and remedied the abnormal anabolism/catabolism of cartilage. TNF signaling was identified through network pharmacology analysis as the anti-inflammatory mechanism of MFZD, and validated by WB results showing that MFCS treatment reduced TNF-α-induced protein expression of p-MKK3/MKK6, p-p38, TRAF2, p-p65, and VCAM1.</p><p><strong>Conclusion: </strong>This study demonstrated that MFZD exerts anti-degenerative and anti-inflammatory potency against OA and revealed the TNF-α/TRAF2/NF-κB signaling related anti-inflammatory mechanism of MFZD for the first time, offering mechanistic insights into its potential in OA therapy.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7603-7621"},"PeriodicalIF":5.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014232","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 Analgesic Efficacy of Liposomal Bupivacaine in Adductor Canal Block Following Knee Arthroplasty: A Single-Center, Prospective, Randomized and Controlled Clinical Trial.","authors":"Min Xu, Sheng Wang, Yan Meng, Chen Gao, Lin Liu, Ji Yuan, Sheng Ding, Xiaoqing Chai, Keqiang He","doi":"10.2147/DDDT.S535901","DOIUrl":"10.2147/DDDT.S535901","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to compare the analgesic efficacy of liposomal bupivacaine with that of traditional ropivacaine in adductor canal blocks for patients undergoing knee arthroplasty.</p><p><strong>Patients and methods: </strong>A total of 119 consenting participants, who were scheduled for elective knee arthroplasty (including total knee replacement and unicompartmental knee replacement) under general anesthesia, were randomly assigned to either receive an ultrasound-guided adductor canal block with ropivacaine or liposomal bupivacaine. The primary endpoint of this study was the pain scores at 2, 24, 48, and 72 hours post-surgery. Secondary outcomes included nausea, vomiting, and pruritis, the ability to engage in physiotherapy on the first day after surgery, postoperative exercise, patient satisfaction with anesthesia, postoperative recovery index, and patient-controlled analgesic presses (12-48 hours) for both groups.</p><p><strong>Results: </strong>The Visual Analog Scale (VAS), assessed from 24 to 72 hours post-follow-up, demonstrated that patients receiving ropivacaine had higher median VAS scores compared to those in the liposomal bupivacaine group, both at rest and during exercise. The weighted AUC numerical rating scale pain scores whether at rest or move in the liposomal bupivacaine group was lower than the standard bupivacaine group with statistical significance. Whether it is 0-24 hours (Rest 58.00 [53.75, 69.00] vs 48.00 [46.50, 58.00]; Move:57.00 [46.00, 59.00] vs 36.00 [35.00, 48.00]) or 0-72 hours (Rest 214.00 [197.75, 237.00] vs 165.00 [143.50, 180.00]; Move:202.00 [190.00, 215.75]vs.156.00 [131.00, 178.00]) From 12 to 48 hours, the ropivacaine group had a significantly higher number of PCIA presses. The liposomal bupivacaine group also achieved greater pain-free bending angles and walking distances compared to the ropivacaine group.</p><p><strong>Conclusion: </strong>Liposomal bupivacaine used in adductor canal block provides extended pain relief in knee arthroplasty patients, aiding early rehabilitation.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7591-7601"},"PeriodicalIF":5.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014221","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":"Ciprofol Alleviates Depressive-Like Behaviors in CUMS Mice Through PPARα-Associated ERK/CREB Signaling Activation.","authors":"Jiaqi Li, Meiqin Chen, Yuan Lin, Qian Wu, Jiahong Shen, Yuxin Wen, Siyue Li, Jie Zhang, Jianliang Sun","doi":"10.2147/DDDT.S532905","DOIUrl":"10.2147/DDDT.S532905","url":null,"abstract":"<p><strong>Background: </strong>Depression is a complex neuropsychiatric disorder involving neuroinflammation, synaptic dysfunction, and neurotransmitter dysregulation. Recent studies have highlighted the therapeutic potential of short-acting anesthetics in the treatment of depression. Ciprofol, a novel intravenous anesthetic with rapid onset and recovery, shows promise, although its antidepressant mechanisms remain underexplored.</p><p><strong>Methods: </strong>We induced a depressive-like phenotype in mice using a 5-week chronic unpredictable mild stress (CUMS) protocol. Following model establishment, the mice received intraperitoneal injections of ciprofol (25 mg/kg) for 7 days. Behavioral assessments included the sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST). To investigate neuroinflammation and microglial activation in the prefrontal cortex (PFC), we employed immunofluorescence staining, three-dimensional reconstruction, and quantitative real-time PCR (qRT-PCR). Synaptic structural changes were assessed using Western blot, three-dimensional reconstruction, and Golgi staining. Furthermore, transcriptome sequencing and Western blot were performed to elucidate the potential mechanisms underlying the antidepressant effects of ciprofol.</p><p><strong>Results: </strong>Ciprofol treatment alleviated CUMS-induced depressive behaviors, as evidenced by reduced immobility time and increased sucrose preference. Ciprofol suppressed PFC microglial activation and downregulated pro-inflammatory cytokines, while preserving synaptic integrity by inhibiting microglia-mediated synaptic phagocytosis. Mechanistic studies suggested that ciprofol's antidepressant effect might be mediated by PPARα activation, which potentially triggers the ERK/CREB pathway, as indicated by transcriptome analysis and Western blot.</p><p><strong>Conclusion: </strong>Ciprofol can alleviate the depressive-like behaviors in CUMS mice by inhibiting the inflammatory response and reducing synaptic loss, and the mechanism may be related to the activation of the PPARα-mediated ERK/CREB pathway.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"7553-7569"},"PeriodicalIF":5.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991440","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}