Drug Design, Development and Therapy最新文献

{"title":"Bioequivalence Study of Single-Pill Capsule Formulation of Amlodipine Plus Benazepril in Healthy Chinese Subjects Under Fasting and Fed Conditions.","authors":"Haojing Song, Bo Qiu, Xue Sun, Caihui Guo, Yiting Hu, Zhanjun Dong, Yang Liu, Wanjun Bai","doi":"10.2147/DDDT.S498337","DOIUrl":"10.2147/DDDT.S498337","url":null,"abstract":"<p><strong>Background: </strong>The aim of the study was to evaluate the pharmacokinetic (PK) properties and safety profiles of test and reference amlodipine/benazepril capsules under both fasting and fed states, determine the bioequivalence between the two formulations, and provide sufficient evidence for new drug application.</p><p><strong>Subjects and methods: </strong>The bioequivalence study was conducted utilizing a randomized, open-label design, involving two formulations administered in a single-dose format. Healthy Chinese participants who met the eligibility criteria were administered a single dose of the test or reference amlodipine/benazepril capsule. Blood samples were taken serially for up to 168 hours post-administration during each period, and the plasma levels of amlodipine, benazepril, and benazeprilat were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. For bioequivalence evaluation, geometric mean ratios comparing the pharmacokinetic parameters of the test drug with those of the reference drug were calculated along with their corresponding 90% confidence intervals. Safety assessments were conducted throughout the duration of the study.</p><p><strong>Results: </strong>The PK parameters of the test formulation were found to be comparable to those of the reference formulation under both fasting and fed conditions. The 90% confidence intervals (CIs) for the geometric mean ratios comparing the test and reference formulations for the peak concentration (Cmax), the area under the curve from time zero to the last measurable concentration (AUC_0-t), and the area under the curve from time zero to observed infinity (AUC_0-∞) of amlodipine, benazepril, and benazeprilat fell within the range of 80.00% to 125.00% in both groups. Both formulations were well tolerated by participants, with no serious adverse events reported throughout the trial.</p><p><strong>Conclusion: </strong>The pharmacokinetic bioequivalence between the test and reference formulation in healthy individuals was confirmed under both fasting and fed states, meeting regulatory standards set for the study. Both drug formulations demonstrated safety and tolerability.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1853-1868"},"PeriodicalIF":4.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647644","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":"Response to Professor Hu Jinyu's Letter [Response to Letter].","authors":"Xiaomin Kang, De Jin, Hangyu Ji, Xuedong An, Yuehong Zhang, Liyun Duan, Cunqing Yang, Rongrong Zhou, Yingying Duan, Yuqing Zhang, Yuting Sun, Linlin Jiang, Fengmei Lian, Xiaolin Tong","doi":"10.2147/DDDT.S526865","DOIUrl":"10.2147/DDDT.S526865","url":null,"abstract":"","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1809-1810"},"PeriodicalIF":4.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662837","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":"Network Pharmacology, Molecular Docking and Experimental Validation on Potential Application of Diabetic Wound Healing of <i>Cinnamomum zeylanicum</i> Through Matrix Metalloproteinases-8 And 9 (MMP-8 And MMP-9).","authors":"Sharmin Akter, Shihab Uddin Ahmad, Mohiuddin Ahmed Bhuiyan, Irin Dewan, Rumman Reza, Niaz Morshed, Md Nazmus Samdani, Md Selim Reza, Ajoy Kumer, Isa Naina Mohamed","doi":"10.2147/DDDT.S489113","DOIUrl":"https://doi.org/10.2147/DDDT.S489113","url":null,"abstract":"<p><strong>Background: </strong>Diabetic wounds are a significant clinical challenge due to impaired healing processes often exacerbated by elevated matrix metalloproteinases (MMPs). <i>Cinnamomum zeylanicum</i>, known for its anti-inflammatory and antioxidant properties, has shown potential in promoting wound healing. This study investigates the molecular docking and experimental validation of <i>Cinnamomum zeylanicum</i>'s effects on diabetic wound healing, focusing on its interaction with matrix metalloproteinases-8 (MMP-8) and 9 (MMP-9).</p><p><strong>Methods: </strong>Molecular docking studies were performed to predict the binding affinity of <i>Cinnamomum zeylanicum</i> compounds to MMP-8 and MMP-9. Diabetic wound healing was evaluated using in vivo models where wounds were induced and treated with <i>Cinnamomum zeylanicum</i> extract. Various parameters were measured, including wound contraction, hydroxyproline content, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels. Biochemical analyses included glucose levels, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and histomorphological examination of skin tissues.</p><p><strong>Results: </strong>Molecular docking results indicated a high binding affinity of <i>Cinnamomum zeylanicum's</i> bioactive compounds with MMP-8 and MMP-9, suggesting potential inhibition. Experimental validation showed significant improvement in wound contraction and increased hydroxyproline content, indicating enhanced collagen synthesis. Antioxidant enzyme activities (SOD, GPx, CAT) were significantly elevated, while MDA levels were reduced, reflecting decreased oxidative stress. Biochemical analysis demonstrated improved glucose homeostasis with reduced FBG and enhanced OGTT responses. Histomorphological studies revealed improved tissue architecture and re-epithelialization in treated wounds.</p><p><strong>Conclusion: </strong><i>Cinnamomum zeylanicum</i> exhibits promising potential in diabetic wound healing by modulating MMP-8 and MMP-9 activities, enhancing antioxidant defenses, and improving glucose regulation. These findings support its therapeutic application for diabetic wounds, providing a foundation for further clinical investigations.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1753-1782"},"PeriodicalIF":4.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647677","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":"Analgesic Efficacy of Thoracoscopic Direct-View Versus Ultrasound-Guided Thoracic Paravertebral Block in Multi-Port Video-Assisted Thoracoscopic Lung Surgery: A Randomized Controlled Non-Inferiority Study.","authors":"Yao Tong, Jimin Wu, Xuhui Wu, Yunchang Mo, Faxing Wang","doi":"10.2147/DDDT.S492040","DOIUrl":"10.2147/DDDT.S492040","url":null,"abstract":"<p><strong>Purpose: </strong>This study compares the analgesic effects of the Thoracoscopic Direct-view Thoracic Paravertebral Nerve Block (DTPVB) with those of the Ultrasound-guided Thoracic Paravertebral Nerve Block (UTPVB), providing a clinical reference.</p><p><strong>Patients and methods: </strong>Sixty-eight patients undergoing three-port video-assisted thoracic surgery (VATS) with general anesthesia were randomly assigned to either the DTPVB group (Group D, n = 34) or the UTPVB group (Group U, n = 34). Both groups received a 10 mL injection of 0.75% ropivacaine at the T4 and T7 interspaces. Primary outcomes were cumulative sufentanil equivalents from the start of lung manipulation to 24 hours postoperatively, with group differences assessed against a non-inferiority margin of 5 μg (Δ). Secondary outcomes include postoperative pain scores, analgesic consumption, patient satisfaction, adverse effects, and other related indicators.</p><p><strong>Results: </strong>The cumulative use of sufentanil equivalents from the start of lung manipulation to 24 hours postoperatively was 35.0 ± 6.1 μg in Group D and 33.2 ± 5.6 μg in Group U, with no significant difference (P = 0.217). The difference in cumulative sufentanil equivalents (Group D minus Group U) was 1.8 (95% CI -1.07, 4.65), within the non-inferiority margin of 5 (Δ). Postoperative pain scores, analgesic consumption, adverse effects, and complications were similar were similar between groups. However, DTPVB was associated with lower anxiety and higher satisfaction (P<0.001). At 15 minutes post-block, ropivacaine plasma concentrations were higher in Group D (P=0.024).</p><p><strong>Conclusion: </strong>DTPVB, via transmural pleural puncture, was non-inferior to UTPVB in analgesic efficacy from the beginning of the manipulation of the lungs in operation to 24h postoperatively. DTPVB provides a good alternative, especially for patients who are anxious before surgery, have difficulty cooperating with UTPVB, or in cases where UTPVB puncture fails. However, when using high concentrations of ropivacaine, greater vigilance for toxicity is required.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1825-1838"},"PeriodicalIF":4.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647640","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":"Enhancing Diabetes Treatment: Comparing Pioglitazone/Metformin with Dapagliflozin Versus Basal Insulin/Metformin in Type 2 Diabetes.","authors":"Yi Lin, Jianxia Shi, Xuemei Yu, Jiao Sun, Suo Lixia, Jiaqing Dou, Min Zhang, Xiaohua Li, Zhufang Tian, Hongyan Deng, Bo Feng, Qing Su, Yongde Peng","doi":"10.2147/DDDT.S512872","DOIUrl":"10.2147/DDDT.S512872","url":null,"abstract":"<p><strong>Aim: </strong>The aim of this study was to compare the efficacy and safety of fixed-dose combination (FDC) of pioglitazone and metformin supplemented with dapagliflozin (test group) with those of basal insulin supplemented with metformin (control group) in patients with inadequately controlled type 2 diabetes mellitus (T2DM).</p><p><strong>Methods: </strong>This 16-week, prospective, randomized, open-label study enrolled patients aged 18-75 years with glycated hemoglobin (HbA1c) levels between ≥ 8% and ≤ 11%. The primary endpoint was the proportion of patients who achieved HbA1c < 7% at week 16 without hypoglycemia or weight gain. The secondary endpoints included blood glucose, lipid profile, body weight, body mass index, inflammatory markers, bone Gla-protein, liver enzymes, and patient satisfaction.</p><p><strong>Results: </strong>Among the full analysis set of 147 participants, no significant difference was observed in the primary endpoint between the test group and the control group. However, the test group had a higher percentage of patients who achieved HbA1c <7% at week 16 without hypoglycemia and experienced a weight loss of ≥3% (31.51% vs 13.51%, <i>P</i>=0.009). Patients in the test group whose BMI≥24 kg/m² also achieved a substantial achievement rate (36.73% vs 15.79%, <i>P</i>=0.014). The test group also exhibited a greater reduction in body weight and improvements in 2-hour postprandial glucose level, systolic blood pressure, and lipid profile. Notably, combination therapy did not increase the risk of hypoglycemia or weight gain. Patients in the test group were more satisfied than those in the control group with continuing to accept pioglitazone/metformin FDC combined with dapagliflozin.</p><p><strong>Conclusion: </strong>In the absence of contraindications, pioglitazone/metformin FDC supplemented with dapagliflozin may serve as a safe and effective alternative to basal insulin combined with metformin for rectifying inadequate glucose control, as the former enables metabolic improvements without compromising safety.</p><p><strong>Chinese clinical trial registry number: </strong>CHiCTR2000036076. https://www.chictr.org.cn/showproj.html?proj=58825.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1795-1808"},"PeriodicalIF":4.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647654","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":"A Mechanistic Study of the Feasibility of Ursodeoxycholic Acid in the Treatment of Colon Adenocarcinoma.","authors":"Shuyu Liu, Mengyue Zhou, Xiaoli Huang, Peng Chen, Quanpeng Li, Yuting Wang, Xianxiu Ge, Fei Wang, Jianing Xu, Jiayi Gu, Lin Miao, Xueting Deng","doi":"10.2147/DDDT.S500721","DOIUrl":"https://doi.org/10.2147/DDDT.S500721","url":null,"abstract":"<p><strong>Purpose: </strong>Bile acids promote the progression of colon adenocarcinoma (COAD), and ursodeoxycholic acid (UDCA) is a key drug in promoting bile acid excretion, but its role in COAD unclear. Our study aims to investigate the relationship between COAD and bile acid metabolism and to assess the feasibility of UDCA for the treatment of COAD.</p><p><strong>Methods: </strong>Firstly, biological targets closely related to COAD were identified: Based on the cancer genome atlas (TCGA) database, the core genes of COAD were obtained by differential expression analysis and weighted gene-coexpression network analysis (WGCNA), and subjected to gene ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Secondly, finding a drug by target, after identifying UDCA as a candidate drug, the feasibility of UDCA in treating COAD was verified in reverse: Using databases to collect potential targets for COAD and UDCA, and the intersecting genes were the potential targets for UDCA to exert anti-tumor effects. Then Autodock was used for molecular docking to analyze the interaction between UDCA and core target proteins. Finally, experimental validation was performed: MTT assay, wound healing, transwell migration, and angiogenesis assays were used to detect the effects of UDCA on cell proliferation, migration, invasion, and neovascularization.</p><p><strong>Results: </strong>2064 differential genes were screened from TCGA. WGCNA obtained the module most relevant to CRC, containing 493 genes. KEGG analysis found that overlapping genes were mainly concentrated in bile acid metabolic pathways. A total of 26 UDCA anti-tumor targets were obtained in database, and 5 core targets were selected by STRING database and Cytoscape software: TNF, CYP27B1, MDM2, MMP2, CASP3. Molecular docking results showed that UDCA had good binding activity with the core targets. In vitro experiment showed UDCA effectively inhibited the proliferation, migration, invasion and neovascularization in colon cancer cells.</p><p><strong>Conclusion: </strong>The antitumor activity of ursodeoxycholic acid may be related to cell apoptosis, proliferation, migration and vascular neogenesis.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1839-1852"},"PeriodicalIF":4.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Trends of Tyrosine Kinase Inhibitors in EGFR-Mutated Non-Small Cell Lung Cancer: A Bibliometric Analysis.","authors":"Xiaoyan Chang, Chenghao Wang, Linyou Zhang","doi":"10.2147/DDDT.S510031","DOIUrl":"https://doi.org/10.2147/DDDT.S510031","url":null,"abstract":"<p><strong>Background: </strong>This study seeks to identify research trends and hotspots concerning tyrosine kinase inhibitors (TKIs) for the treatment of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) through a comprehensive bibliometric analysis.</p><p><strong>Methods: </strong>Publications on TKIs and EGFR-mutated NSCLC from 2006 to 2024 were analyzed using VOSviewer, CiteSpace, and R-bibliometrix to visualize collaboration, keyword co-occurrences, and research trends.</p><p><strong>Results: </strong>A total of 962 articles were analyzed, authored by 7,458 researchers from 5,401 institutions across 208 countries. Wu Yi-Long was identified as the most prolific author, contributing 30 publications. AstraZeneca emerged as the industrial leader with 103 articles, while the New England Journal of Medicine was recognized as the primary journal with the highest total link strength. Keyword co-occurrence analysis revealed significant research topics including \"gefitinib\", \"chemotherapy\", \"open label\", and \"erlotinib.\" Moreover, keyword burst analysis indicated notable periods of increased research focus on topics such as \"osimertinib\" and \"liquid biopsy\", suggesting emerging trends and current hotspots in the treatment of EGFR-mutated NSCLC.</p><p><strong>Conclusion: </strong>This analysis highlights research trends on TKIs for EGFR-mutated NSCLC, emphasizing the importance of targeted therapies like gefitinib and osimertinib for future research and clinical practice enhancement.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1703-1719"},"PeriodicalIF":4.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647700","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 Effects of Different Ciprofol Doses on Hemodynamics During Anesthesia Induction in Patients Undergoing Cardiac Surgery: A Randomized, Double-Blind, Controlled Study.","authors":"Yingting Zhou, ZiYou Liu, QianQian Li, PengFei Ni, ZuoHui Li, BeiJia Yu, Min Zhang, Jia Yang, YanHu Xie","doi":"10.2147/DDDT.S505772","DOIUrl":"10.2147/DDDT.S505772","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the effects of different ciprofol doses on hemodynamics in patients undergoing cardiac surgery.</p><p><strong>Methods: </strong>209 patients were randomly divided into four groups: 0.2 mg/kg etomidate group (group E, n = 50), 0.2 mg/kg, 0.3mg/kg, 0.4mg/kg ciprofol group (group A, n = 53, group B, n = 51, group C, n = 54). Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), systemic vascular resistance (SVR), and bispectral index were recorded at the following time points: 5 minutes after entering the operating room (T₀); before anesthesia induction (T₁); immediately after induction (T₂); 1 minute and 2 minutes after induction (T₃~T₄); at intubation (T₅); 1 minute, 3 minutes, 5 minutes and 10 minutes after intubation (T₆~T₉); at skin incision (T₁₀). The incidence of hypotension and bradycardia and the doses of vasoactive drugs were recorded.</p><p><strong>Results: </strong>Compared with T₀, HR, MAP, SV, CO all decreased to varying degrees after administration, and the decrease time in Group B and Group C were earlier than that in other two groups (<i>P</i> < 0.05). SVR increased slowly after T₄ in all groups, but there was no significant differences (<i>P</i> > 0.05). Compared with group E, the norepinephrine dose was significantly lower in groups A and B (both <i>P</i> < 0.05). Group C showed a greater decline in CO and SV than the other three groups from T₇ to T₁₀ (<i>P</i> < 0.05), while there was no significant difference between groups A and E in CO and groups A, B, and E in SV (<i>P</i> > 0.05). No significant differences were observed in MAP, SVR, and the incidences of hypotension and bradycardia among the four groups (<i>P</i> > 0.05).</p><p><strong>Conclusion: </strong>0.2 mg/kg ciprofol has the least impact on hemodynamics in patients undergoing cardiac surgery, and reduced norepinephrine use.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1671-1679"},"PeriodicalIF":4.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647704","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":"Platycodin D Enhances Glioma Sensitivity to Temozolomide by Inhibition of the Wnt/β-Catenin Pathway.","authors":"Haima Li, Jia Ouyang, Xuelian Wang, Chao Qian","doi":"10.2147/DDDT.S503167","DOIUrl":"https://doi.org/10.2147/DDDT.S503167","url":null,"abstract":"<p><strong>Background: </strong>Temozolomide (TMZ) is a first-line chemotherapeutic agent for gliomas. However, its efficacy is limited by drug resistance. Platycodin D (PD) exhibits notable anti-glioma activity The objective of this study was to investigate the potential of PD to augment glioma sensitivity to TMZ and the underlying mechanisms.</p><p><strong>Methods: </strong>Cell viability and proliferation were assessed using CCK-8 and clonogenic assays, respectively, while flow cytometry was used to detect apoptosis. Cell migration and invasion were assessed using Transwell assays. Western blotting and immunohistochemistry analyses were performed to determine protein expression levels. A xenograft glioma model was established to investigate the in vivo effects of PD.</p><p><strong>Results: </strong>PD augmented glioma cell sensitivity to TMZ, as evidenced by heightened inhibition of cell growth, colony formation, migration, and invasion, accompanied by elevated apoptosis. Treatment with PD or a combination of PD and TMZ robustly suppressed the expression of active β-catenin and c-Myc, which was reversed by the β-catenin activator, SKL2001. In vivo experiments demonstrated that PD amplified the anti-glioma efficacy of TMZ, resulting in diminished Ki67 expression and substantially reduced expression of active β-catenin and c-Myc in the tumor tissue.</p><p><strong>Conclusion: </strong>PD augmented glioma cell sensitivity to TMZ by modulating Wnt/β-catenin pathway. Our findings demonstrate the potential of PD as an innovative therapeutic agent to enhance glioma treatment, especially in TMZ-resistant gliomas.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1811-1824"},"PeriodicalIF":4.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647682","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 Preoperative Topical Magnesium Sulfate Spraying and Magnesium Sulfate Gargling for the Prevention of Postoperative Sore Throat after Tracheal Intubation: A Randomized, Double-Blind, Non-Inferiority Trial.","authors":"Linxin Wang, Yuqing Liu, Fangfang Li, Qin Qiu, Xingyu Xiong, Guanglei Wang","doi":"10.2147/DDDT.S502081","DOIUrl":"10.2147/DDDT.S502081","url":null,"abstract":"<p><strong>Background and aim: </strong>Postoperative sore throat is a common complication following endotracheal intubation, which can significantly affect patient comfort and recovery. The purpose of this study is that compares the efficacy of preoperative topical magnesium sulfate spraying with that of magnesium sulfate gargling aimed at preventing postoperative sore throat.</p><p><strong>Patients and methods: </strong>236 Participants were randomly allocated to either the magnesium sulfate spray group (Group A) or the magnesium sulfate gargle group (Group B), with 118 patients in each group. In Group A, during intubation under direct laryngoscopy, 15 mg/kg of magnesium sulfate was sprayed using a single-use otorhinolaryngology anesthesia sprayer onto the pharyngeal mucosa and posterior pharyngeal wall near the glottis. In Group B, gargling with 20 mg/kg of magnesium sulfate for 30 seconds 15 minutes before surgery. The primary outcome measure was the total incidence of postoperative sore throat within 48 hours, with a non-inferiority margin of 0.15.</p><p><strong>Results: </strong>The upper limit of the 95% confidence interval (CI) for the difference in the total incidence of POST between Group A and Group B was below the non-inferiority margin (0.15) (non-inferiority <i>P</i><0.001). The upper limits of the 95% CI for the differences in the incidence rates of POST between Group A and Group B at time points T1- T6 were all below the non-inferiority margin (all non-inferiority <i>P</i><0.001). The total incidence of POST (<i>P</i>=0.046) and the incidence of POST at T2-T4 (all <i>P</i><0.001) in group A were lower than those in group B. The analysis of the individual effects between groups indicated significant differences in POST NRS scores at T1 (<i>P</i>=0.034) and T2-T4 (all <i>P</i><0.001).</p><p><strong>Conclusion: </strong>The local spray of magnesium sulfate on the throat before surgery to prevent postoperative sore throat is not inferior to, and may even be superior to, gargling with magnesium sulfate.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1741-1752"},"PeriodicalIF":4.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647647","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}