Drug Design, Development and Therapy最新文献

{"title":"<i>Anemarrhena asphodeloides</i> Bunge-<i>Fritillaria Cirrhosae</i> Bulbus Herb Pair Alleviates Ovalbumin-Induced Asthma by Regulating Arachidonic Acid Pathway.","authors":"Xi Tian, Qingfei Cui, Jinhuan Wei, Qian Zhang, Huiyi Zhang, Mengxin Yang, Yiqi Xing, Yukun Niu, Wenyu Li, Nan Wang, Yiran Jin, Yingfeng Du","doi":"10.2147/DDDT.S514891","DOIUrl":"10.2147/DDDT.S514891","url":null,"abstract":"<p><strong>Background: </strong>In traditional Chinese Medicine (TCM), Zhimu (<i>Anemarrhena asphodeloides</i> Bunge, ZM) - Chuanbeimu (<i>Fritillaria Cirrhosae</i> Bulbus, CBM) (ZC) is one of the most classical herb pairs used in the treatment of lung diseases such as asthma. This study aimed to investigate how ZC affects asthma and its mechanism.</p><p><strong>Methods: </strong>Asthma model rats were sensitized by ovalbumin. The anti-asthma efficacy of ZM, CBM and ZC were evaluated through analysis of lung function, pathological sections and biochemical indices. Metabolomics based on UHPLC-QTOF-MS was conducted to determine the synergistic anti-asthma effect of combination therapy. Asthma targets and mechanism prediction were performed using network pharmacology. Then, the potential anti-asthma mechanism of ZC was explored using RT-qPCR.</p><p><strong>Results: </strong>According to the lung function test, Hematoxylin-Eosin Staining experiment, ZC herb pair had an obvious anti-asthma effect over either ZM or CBM alone. It has also been demonstrated that positive effect of ZC against Th1/Th2 immune imbalance. Both metabolomics and network pharmacology were highly enriched in the arachidonic acid metabolism pathway. The mRNA expression levels of ALOX5, PLA2G4A and CYP1A2, critical targets in arachidonic acid metabolism, were significantly down-regulated by RT-qPCR.</p><p><strong>Conclusion: </strong>By reducing the expression of cytokines and chemokines mediated by the arachidonic acid metabolism pathway, ZC could alleviate OVA-induced asthma in vivo. It was the first to demonstrate the complex mechanism of ZC for the treatment of asthma. Meanwhile, a new paradigm was established for evaluating the pharmacological effects of TCM drugs for asthma based on multiple mechanisms.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4407-4427"},"PeriodicalIF":4.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198468","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 and Synthesis of Novel 5,6,7,8-Tetrahydropyrido[2,3-<i>D</i>]pyrimidine Derivatives as VCP/p97 Inhibitors for the Treatment of Acute Myeloid Leukemia (AML).","authors":"Xueyuan Wang, Zebo Long, Tiantian Wen, Hang Miao, Xinran Ye, Meng Lei, Yongqiang Zhu","doi":"10.2147/DDDT.S509036","DOIUrl":"10.2147/DDDT.S509036","url":null,"abstract":"<p><strong>Background: </strong>VCP/p97 plays an important role in endoplasmic reticulum related degradation pathways, and inhibition of p97 was shown to induce ER stress and subsequently cell death in a variety of solid tumors and hematoma. For acute myeloid leukemia (AML) cells, inhibition of p97 activity leads to the accumulation of ubiquitylated proteins, activation of unfolded protein response (UPR) and apoptosis.</p><p><strong>Methods: </strong>We have designed and synthesized a series of novel 5,6,7,8-tetrahydropyridine[2,3-d]pyrimidine derivatives. After synthesizing all the target compounds, the optimal lead compound was identified through screening for enzyme inhibitory activity and anti-tumor cell proliferation activity. Subsequently, the liver microsomal stability and pharmacokinetics of the lead compound was investigated. Finally, the in vivo antitumor efficacy of the lead compound was evaluated to assess its potential for the treatment of acute myeloid leukemia (AML).</p><p><strong>Results: </strong>Compound <b>V12</b> and metabolite <b>V13</b>, which was screened by enzyme inhibition activity, showed strong inhibitory activities against a variety of cell lines with IC₅₀ values less than 1 μM. In pharmacokinetic studies, after intragastric administration of <b>V12</b> (10 mg/kg) in SD rats, <b>V12</b> was rapidly metabolized to<b>V13</b>. The oral half-life of <b>V13</b> in plasma was 3.5 h, and the C_max and AUC_0-inf values of <b>V13</b> reached 1070 ng/mL and 1412 ng•h/mL, respectively, showing good pharmacokinetic properties. In addition, compound <b>V12</b> showed a strong anti-tumor therapeutic effect in vivo and lower toxic side effects in the human AML (Molm-13) mouse xenograft model.</p><p><strong>Conclusion: </strong>These results indicate that compound V12 is a potent p97 inhibitor with excellent in vitro and in vivo antitumor efficacy, which might provide a new therapeutic strategy for the treatment of AML.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4457-4479"},"PeriodicalIF":4.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198522","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 the Dural Puncture Epidural and Conventional Epidural Analgesia Maintained Using Programmed Epidural Boluses for Labor Analgesia.","authors":"Xiaofei Mo, Jie Yu, Zhimin Qin, Junyi Ma, Yueyue Chen, Xi Chen","doi":"10.2147/DDDT.S521681","DOIUrl":"10.2147/DDDT.S521681","url":null,"abstract":"<p><strong>Purpose: </strong>Research indicates that the dural puncture epidural (DPE) technique offers quicker analgesia onset compared to the conventional epidural (EP) technique. Programmed intermittent epidural bolus (PIEB) is superior to continuous epidural infusion (CEI) for maintaining labor analgesia, providing better pain relief and less motor block. Few studies have explored if combining DPE with the PIEB offers additional benefits in analgesia onset, maintenance, local anesthetic consumption, and side effects compared to DPE with EP. We hypothesized that DPE, when combined with PIEB, not only speeds up analgesia onset but also improves neuraxial analgesia maintenance over EP.</p><p><strong>Patients and methods: </strong>A total of 126 term nulliparous women with singleton pregnancies with a VAS pain score >50 mm and cervical dilation <5 cm were randomized to receive EP+PIEB or DPE+PIEB for labor analgesia, initiated with 15 mL of 0.0625% ropivacaine with 0.4 µg/mL of sufentanil using the EP or DPE technique (using 25-gauge Whitacre needle) technique and both maintained with the same solution for PIEB (fixed volume 10 mL, intervals 45 minutes, lockout interval 15 minutes) with labor analgesia. The primary outcome was time to achieving adequate analgesia, defined as a VAS pain score ≤30 mm. Secondary outcomes included pain scores, motor blockade, obstetric and neonatal outcomes, and satisfaction with analgesia.</p><p><strong>Results: </strong>Adequate analgesia was achieved faster in the DPE+PIEB group than in the EP+PIEB group (hazard ratio 2.409; 95% CI 1.670 to 3.474, <i>P</i><0.001). The median time (interquartile range) to VAS pain score ≤30 mm was 10 (7 to 13) minutes for the DPE+PIEB group and 15 (11 to 19) minutes for the EP+PIEB group (<i>P</i><0.001). No differences in any of the secondary outcomes between the two groups were observed.</p><p><strong>Conclusion: </strong>DPE with PIEB accelerated onset time but did not improve maintenance of neuraxial labor analgesia over DPE with EP.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4373-4382"},"PeriodicalIF":4.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198521","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":"Simultaneous Determination of Unbound Plasma Concentration of Methotrexate and 7-Hydroxymethotrexate in Children Patients Receiving High-Dose Methotrexate Therapy.","authors":"Wei-Chong Dong, Shuai-Shuai Gao, Bo Shi, Hao-Ran Li, Ye Jiang, Jia-Liang Guo, Zhi-Qing Zhang, Ying-Ze Zhang","doi":"10.2147/DDDT.S516431","DOIUrl":"10.2147/DDDT.S516431","url":null,"abstract":"<p><strong>Background: </strong>High-dose methotrexate (HD-MTX) is seen as an effective therapy for acute lymphoblastic leukemia (ALL); however, it is extremely toxic. Monitoring the plasma concentrations of methotrexate (MTX) and its important metabolite, 7-hydroxy-methotrexate (7-OH-MTX), on a routine basis aids in dose modification of rescue medications and in avoiding toxicity. The pharmacologically active and toxic effects of drugs are due to the unbound portion, as most drugs are bound to plasma proteins to some degree. However, the simultaneous measurement of unbound plasma concentrations of MTX and 7-OH-MTX has not been reported.</p><p><strong>Methods: </strong>We developed and validated a hollow fiber centrifugal ultrafiltration (HFCF-UF) technology to simultaneously analyze unbound MTX and 7-OH-MTX concentrations in human plasma. In total, 234 plasma samples from 58 children diagnosed with ALL who were administered HD-MTX were used in our study. We investigated the connection between unbound and total plasma concentrations of MTX and 7-OH-MTX, as well as how these concentrations relate to liver and renal function.</p><p><strong>Results: </strong>The method that was developed is both simple and accurate. A weak linear relationship was observed between the concentrations of unbound and total 7-OH-MTX (<i>r</i> ² = 0.732). The concentration of total MTX and unbound 7-OH-MTX were both positively correlated with creatinine (Cr) levels and negatively correlated with Creatinine clearance (CCr). There was a wide variation in the concentration ratios of 7-OH-MTX to MTX, both total and unbound, and these ratios were significantly lower in individuals with impaired liver function.</p><p><strong>Conclusion: </strong>The total concentration of 7-OH-MTX is an unreliable predictor of unbound concentration, necessitating the monitoring of unbound levels. The concentration ratios of 7-OH-MTX to MTX (both total and unbound) could be more accurate and sensitive biomarkers for predicting hepatotoxicity.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4383-4396"},"PeriodicalIF":4.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12124301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198525","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 of Tranexamic Acid in Chinese Population Undergoing Cardiac Surgery with Cardiopulmonary Bypass.","authors":"Yue Liu, Chenghui Zhou, Hong Lv, Lei Tian, Juanjuan Jiang, Jia Shi","doi":"10.2147/DDDT.S493485","DOIUrl":"10.2147/DDDT.S493485","url":null,"abstract":"<p><strong>Background: </strong>Population pharmacokinetics (PK) models could provide specific references for the formulation of personal drug delivery protocols, however, there is no population PK study of tranexamic acid (TXA) have been conducted in the Chinese population. The aim of this study was to establish a population PK model based on the data of perioperative plasma concentrations in Chinese participants, and to provide a reference for individualized administration of TXA.</p><p><strong>Methods: </strong>Participants undergoing cardiac surgery were randomly assigned to high-dose of TXA group (a 30-mg/kg bolus, a 16-mg/kg/h maintenance dose, and a 2-mg/kg prime, n = 7) and low-dose group of TXA (a 10-mg/kg bolus, a 2-mg/kg/h maintenance dose, and a 1-mg/kg prime, n = 9). Blood samples were collected at 14 time points and the concentration of TXA was determined by liquid chromatography-tandem mass spectrometry. Modelling was performed using Phoenix NLME 8.3 software.</p><p><strong>Results: </strong>The primary covariate identified was body weight, while no significant influence of cardiopulmonary bypass (CPB) on the PK was detected. The population estimates for clearance (CL₁), volume of the central compartment (V₁), diffusional clearance (CL₂), and volume of peripheral compartment (V₂) were 4.7 L/h, 4.9 L, 17.0 L/h, and 11.1 L, respectively, assuming a bodyweight of 70 kg.</p><p><strong>Conclusion: </strong>This study provides the first population PK model of TXA in the Chinese population undergoing cardiac surgery with CPB. The model could serve as a reference for the future development of individualized TXA administration strategies, with target-controlled infusion (TCI) emerging as a viable option.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4343-4353"},"PeriodicalIF":4.7,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198523","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":"Mechanism of Action and Efficacy of Wu-Hua-Yan-Xiao in the Treatment of Pediatric Acute Pharyngitis Based on Network Pharmacology and Experimental Validation.","authors":"Xinyun Zhang, Zengyu Zhang, Yingzi Xu, Jiawei Luo, Zihao Shen, Hao Liang, Yidi Zeng, Wanghua Liu, Caixing Zheng, Jinxia Li","doi":"10.2147/DDDT.S513073","DOIUrl":"10.2147/DDDT.S513073","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Wu-Hua-Yan-Xiao (WHYX) is an innovative volatile oil formulation derived from the traditional Yinqiao-Mabo decoction, developed for the treatment of pediatric acute pharyngitis.</p><p><strong>Materials and methods: </strong>Network pharmacology was utilized to identify active components and potential therapeutic targets of WHYX in acute pharyngitis. Compounds in WHYX were characterized using UHPLC-QE-MS. A pediatric acute pharyngitis rat model was established by administering 25% ammonia to the pharyngeal mucosa of young rats. WHYX was delivered via aerosol inhalation at gradient concentrations. Histopathological changes in pharyngeal tissues were evaluated by H&E staining. Serum levels of IL-6, IL-1β, TNF-α, and PGE2 were quantified by ELISA. Expression levels of TNF-α, TP53, IL17A, IL6, and Bcl-2 were assessed by qRT-PCR and Western blotting. Apoptosis was analyzed through immunofluorescence staining for Caspase-3 and TUNEL.</p><p><strong>Results: </strong>Network pharmacology identified 130 active compounds and 600 gene targets, with 194 overlapping drug-disease targets. TP53 signaling emerged as a central regulatory pathway. Compared with the model group, the high-dose WHYX volatile oil group showed marked improvements in pharyngeal pathology, significant reductions in inflammatory cytokines, downregulation of TNF-α, TP53, IL17A, IL6, and Bcl-2 expression, and suppressed apoptosis <i>(P</i> < 0.05). Therapeutic effects were comparable to or exceeded those observed in the positive control group. (<i>P < 0.05</i>).</p><p><strong>Conclusion: </strong>The WHYX formula alleviates inflammation, reduces apoptosis, and protects pharyngeal tissue in young rats with acute pharyngitis. Aerosol inhalation of WHYX presents a direct, effective, and non-invasive strategy for pediatric acute pharyngitis management.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4321-4342"},"PeriodicalIF":4.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12120256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180560","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":"Dasatinib Dose Optimization Based on Therapeutic Drug Monitoring in Patients with Chronic-Phase Chronic Myeloid Leukemia.","authors":"Fang Cheng, Zheng Cui, Qiang Li, Liu Wang, Yu Zhang, Weiming Li","doi":"10.2147/DDDT.S521260","DOIUrl":"10.2147/DDDT.S521260","url":null,"abstract":"<p><strong>Background: </strong>Although a dosage decrease regimen for chronic phase chronic myeloid leukemia (CML-CP) has been suggested, there is a marked lack of guidance on individualizing medication dosages for patients.</p><p><strong>Methods: </strong>Our aim was to explore the application of therapeutic drug monitoring (TDM) as a strategy for optimizing dasatinib dosage in patients with CML-CP.</p><p><strong>Results: </strong>It was observed that patients administered a dosage of 100 mg exhibited significantly higher concentrations than those given 50 mg, with no marked difference in concentration between branded and generic drugs. Further analysis unveiled a robust correlation between peak concentration (C_max) and clinical response (major molecular response (MMR): 103.8 ± 54.0 ng/mL versus 48.6 ± 13.9 ng/mL, P < 0.001; deep molecular response (DMR): 112.7 ± 57.6 ng/mL versus 66.2 ± 36.1 ng/mL, P = 0.001). Patients with a C_max >51.85ng/mL were more likely to achieve MMR, while those with a C_max surpassing 112.5 ng/mL had a higher probability of attaining DMR. We successfully implemented dasatinib dose reduction based on concentrations without loss of DMR in 22 patients undergoing first-line therapy. Moreover, trough concentrations (C_min) >2.48 ng/mL were closely associated with the onset of pleural effusion. Older patients demonstrated higher C_min and C_max, irrespective of whether they were on a 50 mg or 100 mg dosage regimen.</p><p><strong>Conclusion: </strong>TDM-based dose optimization could lead to beneficial clinical outcomes for patients with CML-CP. Furthermore, in terms of blood drug concentration, our findings supply additional evidence supporting the first-line treatment regimen of 50 mg daily.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4311-4320"},"PeriodicalIF":4.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157451","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":"Semaglutide Alleviates Ovarian Oxidative Stress and Autophagy via the PI3K/AKT/mTOR Pathway in Mice with Polycystic Ovary Syndrome.","authors":"Sili Guo, Xiaohan Li, Mei Liu, Meiqi Feng, Xi Wang, Haibo Xue, Lei Zhang","doi":"10.2147/DDDT.S522730","DOIUrl":"10.2147/DDDT.S522730","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a typical reproductive endocrine system disease with high incidence rate among childbearing age women. Several clinical data show that glucagon-like peptide-1 receptor agonists (GLP-1RAs) might have therapeutic effects on PCOS, but the mechanisms are still unclear. Here, we aim to assess the effects of semaglutide (a weekly preparation of GLP-1RAs) on PCOS in vivo.</p><p><strong>Methods: </strong>C57BL/6J female mice aged 3 weeks were subcutaneously injected with dehydroepiandrosterone and fed high-fat diet for 3 weeks to establish PCOS model. Then, we randomly divided the modeled mice into PCOS group (n=6), S-Low group (n=6), and S-High group (n=6). Additionally, six normal mice served as controls. Mice in S-Low and S-High group were intraperitoneally injected with corresponding dose of semaglutide every week for 4 weeks. The estrus cycle was observed daily. At the end of the experiment, body weight, blood glucose, and serum hormone levels were measured. Ovarian morphology was also observed. Then, the oxidative stress markers, autophagy-related proteins and CYP19A1, StAR, and CYP17A1 expression in ovarian tissue were measured. Finally, we used Western blot to detect the expression of PI3K/AKT/mTOR and downstream proteins.</p><p><strong>Results: </strong>After treatment with semaglutide, the estrous rhythm of PCOS mice was restored, the number of ovarian vesicles decreased, serum hormone imbalance corrected, and glucose tolerance improved. The relative expression of CYP17A1, StAR, Beclin-1, and LC3B, as well as MDA, were significantly reduced, while CYP19A1, p62, GSH, and SOD were significantly increased. Finally, semaglutide alleviates ovarian oxidative stress and autophagy via the PI3K/AKT/mTOR pathway.</p><p><strong>Conclusion: </strong>Semaglutide alleviates autophagy and ovarian oxidative stress via the PI3K/AKT/mTOR pathway in mice with PCOS.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4297-4310"},"PeriodicalIF":4.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157460","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":"Dexmedetomidine Cannot Attenuate Liver Injury and Improve Outcomes Following Laparoscopic Living Donor Hepatectomy: A Randomised Controlled Trial.","authors":"Ling-Li Cui, Liang Zhang, Shen Liu, Qian Zhu, Fu-Shan Xue","doi":"10.2147/DDDT.S524343","DOIUrl":"10.2147/DDDT.S524343","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the effects of intraoperative dexmedetomidine (DEX) administration on postoperative ischaemia/reperfusion injury (HIRI) and clinical outcomes of patients undergoing the laparoscopic living donor hepatectomy (LLDH).</p><p><strong>Patients and methods: </strong>Fifty-five patients who underwent the LLDH were randomly assigned to the DEX or control group. The DEX group received an intravenous infusion of DEX with an bolus dose of 1 µg/kg for 15 min before anaesthesia induction, followed by a continuous infusion at a rate of 0.4 µg/kg/h until the portal branch was disconnected. The control group was given an intravenous infusion of 0.9% saline at same volume and rate. The primary outcome was peak serum aspartate aminotransferase (AST) level during the first 72 h postoperatively. The secondary outcomes included other variables of postoperative liver and kidney function, intraoperative hemodynamic changes, postoperative recovery outcomes and the occurrence of complications.</p><p><strong>Results: </strong>The peak serum AST level during the first 72 h postoperatively was not significantly different between groups (DEX vs control: 288 [194-466] vs 324 [194-437] IU/L; difference, -1.2 IU/L; 95% CI, -86.9 to 88.0; <i>P</i>=0.973). The intraoperative mean artery pressure was not significantly different, but intraoperative heart rate was significantly decreased in the DEX group. There were no significant differences between groups in other secondary outcomes.</p><p><strong>Conclusion: </strong>This study demonstrates that intraoperative DEX administration at the studied dosage regimens cannot attenuate postoperative HIRI and does not improve clinical outcomes in patients undergoing the LLDH.</p><p><strong>Clinical trial registration: </strong>www.chictr.org.cn, ChiCTR2000040629.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4263-4274"},"PeriodicalIF":4.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149720","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":"Olive Oil Solution of Volatile Oil from <i>Citri Reticulatae Pericarpium Viride</i> Alleviates Slow-Transit Constipation via Regulating SCF/c-Kit Signaling Pathway and Intestinal Flora.","authors":"Shuting Zou, Bin Xie, Zhentao An, Fang Li, Li Cui, Zhenhai Zhang, Weiquan Bu, Dandan He","doi":"10.2147/DDDT.S517114","DOIUrl":"10.2147/DDDT.S517114","url":null,"abstract":"<p><strong>Objective: </strong>The aroma of the aromatic class of traditional Chinese medicines can promote gastrointestinal peristalsis. This study aimed to explore the mechanisms by which volatile oil from <i>Citri Reticulatae Pericarpium Viride</i> (VOCRPV) alleviates slow-transit constipation (STC).</p><p><strong>Methods: </strong>The main active ingredients in VOCRPV were determined by High-Performance Liquid Chromatography (HPLC). Due to poor stability, an olive oil solution was prepared to enhance the volatile oil's stability. A mouse model of STC was induced using loperamide hydrochloride. The mice's body weight was monitored weekly. The number of fecal pellets, fecal water content, and small intestinal propulsion rate were detected. The colon tissues were analyzed using HE staining. The serum content of gastrointestinal hormones was measured using the corresponding ELISA kit. The protein expressions of stem cell factor (SCF) and c-Kit in colon tissues were detected by Western blot and immunohistochemistry methods. The 16S rRNA gene sequencing was used to detect the intestinal flora.</p><p><strong>Results: </strong>The contents of p-isopropyl toluene, γ-Terpinene, and d-Limonene were determined by HPLC. VOCRPV and its olive oil solution significantly enhanced body weight, increased the number of fecal pellets, improved fecal water content, and boosted small intestinal propulsion rate in mice with loperamide-induced STC, while also repairing colon mucosa damage. They also increased gastrin (Gas) and motilin (MTL) levels in treated mice, upregulated the expression of SCF and c-Kit proteins, and restored intestinal flora balance in STC mice.</p><p><strong>Conclusion: </strong>VOCRPV could effectively alleviate STC, and olive oil enhances its therapeutic effect. VOCRPV alleviates STC by elevating Gas and MTL levels, activating the SCF/c-Kit signaling pathway, and modulating intestinal flora.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"4275-4295"},"PeriodicalIF":4.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157455","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}