Drug Design, Development and Therapy最新文献

{"title":"Effect of Esketamine on Cognitive Recovery After Propofol Sedation for Outpatient Colonoscopy: A Randomized Clinical Trial.","authors":"Deshan Liu, Xiuchai Gao, Yifen Zhuo, Wanjie Cheng, Ying Yang, Xiaoyan Wu, Huobao Yang, Yusheng Yao","doi":"10.2147/DDDT.S503129","DOIUrl":"10.2147/DDDT.S503129","url":null,"abstract":"<p><strong>Purpose: </strong>While esketamine shows promise as an adjunct in procedural sedation, its impact on postoperative cognitive recovery remains incompletely characterized. This study investigated the effects of esketamine on multiple dimensions of recovery, particularly cognition, in patients undergoing colonoscopy with propofol-based sedation.</p><p><strong>Patients and methods: </strong>We conducted this randomized, double-blinded, placebo-controlled trial from January 6, 2023, to May 20, 2024, at two hospitals in China. Patients were randomized in a 1:1 ratio to receive either esketamine 0.2 mg/kg (n = 126) or placebo (n = 126), followed by propofol 1 mg/kg. We administered additional propofol boluses (0.5 mg/kg) to maintain sedation. The study assessed cognitive recovery on postoperative day 3 as the primary outcome, measured by the Postoperative Quality of Recovery Scale (PostopQRS). Secondary outcomes included overall recovery, recovery in other PostopQRS domains, time to discharge, and adverse events.</p><p><strong>Results: </strong>Esketamine significantly enhanced cognitive recovery compared to placebo on postoperative day 3 (95.2% vs 83.3%, relative risk = 1.14; 95% confidence interval: 1.05-1.25, <i>P</i> = 0.002). Discharge times were comparable between groups (odds ratio = 0.70; 95% confidence interval: 0.43-1.16, <i>P</i> = 0.163). The esketamine group demonstrated higher satisfaction (<i>P</i> = 0.003) and significantly reduced incidences of hypotension (14.3% vs 36.5%, <i>P</i> < 0.001), bradycardia (5.6% vs 15.1%, <i>P</i> = 0.013), hypoxemia (2.4% vs 8.7%, <i>P</i> = 0.028), and injection site pain (21.4% vs 48.4%, <i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>Adding esketamine 0.2 mg/kg to propofol for colonoscopy sedation improved postoperative cognitive recovery, enhanced patient satisfaction, and reduced cardiopulmonary adverse events without prolonging discharge time. These findings establish low-dose esketamine as a beneficial adjunct to propofol in procedural sedation for colonoscopy.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"425-437"},"PeriodicalIF":4.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045938","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":"Active Ingredients and Potential Mechanism of Additive Sishen Decoction in Treating Rheumatoid Arthritis with Network Pharmacology and Molecular Dynamics Simulation and Experimental Verification.","authors":"Jinhong Ren, Ze Liu, Xiaoming Qi, Xiangda Meng, Linglin Guo, Yating Yu, Tao Dong, Qingshan Li","doi":"10.2147/DDDT.S489323","DOIUrl":"10.2147/DDDT.S489323","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease in which macrophages produce cytokines that enhance inflammation and contribute to the destruction of cartilage and bone. Additive Sishen decoction (ASSD) is a widely used traditional Chinese medicine for the treatment of RA; however, its active ingredients and the mechanism of its therapeutic effects remain unclear.</p><p><strong>Methods: </strong>To predict the ingredients and key targets of ASSD, we constructed \"drug-ingredient-target-disease\" and protein-protein interaction networks. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to explore the potential mechanism. The activity of the predicted key ingredients was verified in lipopolysaccharide-stimulated macrophages. The binding mode between the key ingredients and key targets was elucidated using molecular docking and molecular dynamics simulation.</p><p><strong>Results: </strong>In all, 75 ASSD active ingredients and 1258 RA targets were analyzed, of which kaempferol, luteolin, and quercetin were considered key components that mainly act through inflammation-related pathways, such as the PI3K-AKT, TNF, and IL-17 signaling pathways, to ameliorate RA. Transcriptome sequencing suggested that kaempferol-, luteolin-, and quercetin-mediated inhibition of glycolysis reduced the lipopolysaccharide-induced production of proinflammatory factors. In vitro experiments indicated that kaempferol, luteolin, and quercetin decreased Glut1 and LDHA expression by diminishing PI3K-AKT signaling to inhibit glycolysis. Molecular dynamic simulation revealed that kaempferol, luteolin, and quercetin stably occupied the hydrophobic pocket of PI3Kδ.</p><p><strong>Conclusion: </strong>Our results show that the PI3Kδ-mediated anti-inflammatory responses elicited by kaempferol, luteolin, and quercetin are crucial for the therapeutic efficacy of ASSD against RA.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"405-424"},"PeriodicalIF":4.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045921","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":"Esketamine at a Clinical Dose Attenuates Cerebral Ischemia/Reperfusion Injury by Inhibiting AKT Signaling Pathway to Facilitate Microglia M2 Polarization and Autophagy.","authors":"Ying Gao, Lu Li, Fang Zhao, Yi Cheng, Mu Jin, Fu-Shan Xue","doi":"10.2147/DDDT.S504179","DOIUrl":"10.2147/DDDT.S504179","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to assess the protective effect of a clinical dose esketamine on cerebral ischemia/reperfusion (I/R) injury and to reveal the potential mechanisms associated with microglial polarization and autophagy.</p><p><strong>Methods: </strong>Experimental cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in adult rats and simulated by oxygen-glucose deprivation (OGD) in BV-2 microglial cells. Neurological and sensorimotor function, cerebral infarct volume, histopathological changes, mitochondrial morphological changes, and apoptosis of ischemic brain tissues were assessed in the presence or absence of esketamine and the autophagy inducer rapamycin. The expression of biomarkers related to microglial M1 and M2 phenotypes in the ischemic brain tissues was determined by immunofluorescence staining and RT-qPCR, and the expression of proteins associated with autophagy and the AKT signaling pathway in the ischemic brain tissues was assayed by Western blotting.</p><p><strong>Results: </strong>Esketamine alone and esketamine combined with rapamycin alleviated neurological impairment, improved sensorimotor function, decreased cerebral infarct volume, and mitigated tissue injury in the MCAO rats. Importantly, esketamine promoted microglial phenotypic transition from M1 to M2 in both the MCAO rats and the OGD-treated BV-2 microglia, induced autophagy, and inactivated AKT signaling. Furthermore, the effects of esketamine were enhanced by addition of autophagy inducer rapamycin.</p><p><strong>Conclusion: </strong>Esketamine at a clinical dose attenuates cerebral I/R injury by inhibiting AKT signaling pathway to facilitate microglial M2 polarization and autophagy. Furthermore, esketamine combined autophagy inducer can provide an improved protection against cerebral I/R injury. Thus, this study provides new insights into the neuroprotective mechanisms of esketamine and the potential therapeutic strategies of cerebral I/R injury.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"369-387"},"PeriodicalIF":4.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Anti-PANoptosis Mechanism of Dachaihu Decoction Against Sepsis-Induced Acute Lung Injury: Network Pharmacology, Bioinformatics, and Experimental Validation.","authors":"Zhen Yang, Xingyu Kao, Lin Zhang, Na Huang, Jingli Chen, Mingfeng He","doi":"10.2147/DDDT.S495225","DOIUrl":"10.2147/DDDT.S495225","url":null,"abstract":"<p><strong>Background: </strong>Dachaihu decoction (DCHD) is a common Chinese medicine formula against sepsis-induced acute lung injury (SALI). PANoptosis is a novel type of programmed cell death. Nevertheless, The mechanisms of DCHD against SALI via anti-PANoptosis remains unknown.</p><p><strong>Methods: </strong>First, we identified the intersecting targets among DCHD, SALI, and PANoptosis using relevant databases and published literature. Then, protein-protein interaction (PPI) network, molecular docking, and functional enrichment analysis were conducted. In vivo, cecal ligation and puncture (CLP) was used to construct a sepsis mouse model, and the therapeutic effects of DCHD on SALI were evaluated using hematoxylin and eosin (H&E) staining, quantitative real-time PCR (qRT-PCR), and ELISA. Finally, qRT-PCR, immunofluorescence staining, and Western blotting were used to verify the effect of DCHD-containing serum (DCHD-DS) on LPS-induced RAW 264.7 macrophages in vitro.</p><p><strong>Results: </strong>82 intersecting targets were identified by mapping the targets of DCHD, SALI, and PANoptosis. Enrichment analysis showed that DCHD against SALI via anti-PANoptosis by modulating tumor necrosis factor (TNF), AGE-RAGE, phosphoinositide 3-kinase (PI3K)-AKT, and Toll-like receptor signaling pathways by targeting Casp3, cellular tumor antigen p53 (TP53), B-cell lymphoma 2 (Bcl2), toll-like receptor-4 (TLR4), STAT3, STAT1, RELA, NF-κB1, myeloid cell leukemia-1 (MCL1), JUN, IL-1β, HSP90AA1, Casp9, Casp8, and Bcl2l1. Molecular docking analysis revealed that the key components of DCHD have a high binding affinity to the core targets. In vivo, DCHD improved lung histopathological injury, reduced inflammatory factor expression, and alleviated oxidative stress injury in lung tissues. In vitro, DCHD-DS alleviated cell morphology changes, the release of pro-inflammatory factors, and p65 nucleus aggregation. Furthermore, we verified that DCHD-DS inhibited PANoptosis by downregulating the PI3K/AKT/NF-κB signalling pathway.</p><p><strong>Conclusion: </strong>DCHD attenuates SALI by inhibiting PANoptosis via control of the PI3K/AKT/NF-κB pathway. Our study provides a solid foundation for investigating the mechanisms of DCHD and its clinical application in the treatment of SALI.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"349-368"},"PeriodicalIF":4.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001949","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":"Huanglian Ejiao Decoction Alleviates Ulcerative Colitis in Mice Through Regulating the Gut Microbiota and Inhibiting the Ratio of Th1 and Th2 Cells.","authors":"Jingyi Tang, Yingnan Hu, Jintao Fang, Weihan Zhu, Wenjun Xu, Dian Yu, Zhipeng Zheng, Qiujing Zhou, Huiying Fu, Wei Zhang","doi":"10.2147/DDDT.S468608","DOIUrl":"10.2147/DDDT.S468608","url":null,"abstract":"<p><strong>Background: </strong>Huanglian-ejiao decoction (HED) is a Chinese traditional medicinal formula evolved from the Shanghan Lun (Treatise on Febrile Diseases). However, HED ultimate mechanism of action remained indistinct. Therefore, this study aimed to investigate whether HED could exert anti-inflammatory effects on 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced colitis (UC) model through the regulation of CD4⁺T subsets and gut microbiota.</p><p><strong>Methods: </strong>Fifty-eight major compounds in HED were identified by UPLC-Q-TOF/MS. The therapeutic efficacy of HED on UC was assessed by evaluating survival rate and so on. Flow cytometry was employed to assay the percentages of CD4⁺T cell. RT-PCR and Western blot took advantage of detecting transcription factors, inflammatory factors, and tight junction proteins. Transcriptome sequencing was performed on colon tissue and 16S rRNA gene sequencing was enforced on intestinal contents.</p><p><strong>Results: </strong>The administration of HED enhanced the survival rate of colitis mice, significantly restored body weight, DAI score, colon weight and index, spleen weight and index. HED effectively reshaped intestinal barrier dysfunction, inhibited the ratio of Th1 to Th2 cells, and preserved Th2/Th1 and Tregs/Th17 balance. Moreover, HED notably decreased the secretion of transcription factors and related cytokines. Interestingly, HED also exerts regulatory effects on gut dysbiosis by cumulative the plenteous of beneficial probiotics like Lactobacillus and Bacteroides, while inhibiting the overgrowth of opportunistic pathogens such as Helicobacter.</p><p><strong>Conclusion: </strong>The regulation of Th2/Th1 and Tregs/Th17 cell balance, as well as the modulation of gut microbiota by HED, provides further experimental evidence for the feasibility of its treatment of UC.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"303-324"},"PeriodicalIF":4.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Cardioprotective Mechanisms of <i>Ligusticum wallichii</i> in Myocardial Infarction Through Network Pharmacology and Experimental Validation.","authors":"Huan Yang, Jun Cao, Lijie Zhou, Jiangchuan Chen, Jiaman Tang, Jiamei Chen, Lengyun Yin, Li Xie, Jianmin Li, Jinwen Luo","doi":"10.2147/DDDT.S481499","DOIUrl":"10.2147/DDDT.S481499","url":null,"abstract":"<p><strong>Background: </strong>Myocardial infarction represents a coronary artery ailment with the highest incidence and fatality rates among cardiovascular conditions. However, effective pharmacological interventions remain elusive. This study seeks to elucidate the molecular mechanisms underlying the effects of <i>Ligusticum wallichii</i> on myocardial infarction through network pharmacology and experimental validation.</p><p><strong>Methods: </strong>Initially, potential targets of <i>Ligusticum wallichii</i>'s active ingredients and myocardial infarction-related targets were retrieved from databases. Subsequently, core targets of <i>Ligusticum wallichii</i> on myocardial infarction were identified via the PPI network analysis and subjected to GO and KEGG pathway enrichment analyses. Molecular docking was employed to validate the binding affinities between the core targets and the bioactive components. The findings from network pharmacology analysis were corroborated through in vitro <i>and</i> in vivo experiments.</p><p><strong>Results: </strong>Seven active ingredients from <i>Ligusticum wallichii</i> were identified, corresponding to 122 targets. Molecular docking revealed robust binding affinities of Myricanone, Senkyunone, and Sitosterol to key target proteins (EGFR, STAT3, and SRC). In vitro, experiments demonstrated that pretreatment with the active components of <i>Ligusticum wallichii</i> protected myocardial cells from OGD exposure and modulated the expression of their key target genes. In vivo, experiments showed that the active components of <i>Ligusticum wallichii</i> significantly improved myocardial infarction via alleviating myocardial fibrosis and oxidative stress and did not elicit toxic effects in mice.</p><p><strong>Conclusion: </strong>The collective findings suggest that <i>Ligusticum wallichii</i> shows promising potential for myocardial infarction treatment by regulating key target proteins (EGFR, STAT3, and SRC), which play roles in oxidative stress and myocardial fibrosis.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"281-302"},"PeriodicalIF":4.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022591","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 Combined With Metabolomics Reveals the Mechanism of Yangxuerongjin Pill Against Type 2 Diabetic Peripheral Neuropathy in Rats.","authors":"Ran Jin, Hailuan Pei, Feng Yue, Xiaodi Zhang, Zhicong Zhang, Yi Xu, Jinsheng Li","doi":"10.2147/DDDT.S473146","DOIUrl":"10.2147/DDDT.S473146","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to explore the mechanism of Yangxuerongjin pill (YXRJP) in the treatment of diabetic peripheral neuropathy (DPN) by network pharmacology and metabolomics technology combined with animal experiments, and to provide scientific basis for the treatment of DPN.</p><p><strong>Methods: </strong>In this study, network pharmacology analysis was applied to identify the active compounds, core targets and signal pathways, which might be responsible for the effect of DPN. The DPN model was established by high-fat diet combined with streptozotocin (STZ) injection, and the rats were given administration for 12 weeks. The body weight, thermal withdrawal latency (TWL), sciatic motor nerve conduction velocity (MNCV), biochemical indexes, pathological sections of sciatic nerve, oxidative stress factors and the expression levels of neuroprotection-related proteins were detected. Metabolomics technology was used to analyze the potential biomarkers and potential metabolic pathways in DPN treated with YXRJP.</p><p><strong>Results: </strong>The results of network pharmacology showed that YXRJP could treat DPN through baicalin, β-sitosterol, 7-methoxy-2-methylisoflavone, aloe-emodin and luteolin on insulin resistance, Toll-like receptor (TLR), tumor necrosis factor (TNF) and other signaling pathways. YXRJP can prolong the TWL, increase the MNCV of the sciatic nerve, alleviate the injury of the sciatic nerve, reduce the levels of triglyceride (TG), improve the expression of Insulin-like growth factor 1 (IGF-1) protein in the sciatic nerve, and reduce the expression of protein kinase B (AKT) protein. Metabolomics results showed that the potential metabolic pathways of YXRJP in the treatment of DPN mainly involved amino acid metabolism such as arginine, alanine, aspartic acid, lipid metabolism and nucleotide metabolism.</p><p><strong>Conclusion: </strong>YXRJP can effectively improve the symptoms of DPN rats and reduce nerve damage. The effects are mainly related to reducing oxidative stress injury, promoting the expression of neuroprotection-related proteins, reducing the expression of inflammation-related proteins, and affecting amino acid metabolism, lipid metabolism, and nucleotide metabolism pathways. Our findings revealed that YXRJP has a good therapeutic potential for DPN, which provides a reference for further studies on YXRJP.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"325-347"},"PeriodicalIF":4.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001964","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":"Impact of Food Physical Properties on Oral Drug Absorption: A Comprehensive Review.","authors":"Ziyang Wang, Wen Xu, Dan Liu, Xiuqi Li, Shupeng Liu, Xiaofei Wu, Hongyun Wang","doi":"10.2147/DDDT.S497515","DOIUrl":"10.2147/DDDT.S497515","url":null,"abstract":"<p><p>Food-Drug Interaction (FDI) refers to the phenomenon where food affects the pharmacokinetic or pharmacodynamic characteristics of a drug, significantly altering the drug's absorption rate or absorption extent. These Interactions are considered as a primary determinant in influencing the bioavailability of orally administered drugs within the gastrointestinal tract. The impact of food on drug absorption is complex and multifaceted, potentially involving alterations in gastrointestinal physiology, increases in splanchnic blood flow rates, and shifts in the gut microbiota's composition. Up to now, extensive research has focused on the interactions between food composition (such as proteins, fats, and vitamins) and drug absorption. In contrast, the impact of food physical properties (such as viscosity, volume, and pH) has received less attention in drug development. This article reviewed the impact of food properties on oral drug absorption based on a comprehensive literature search, focusing on the influence of food volume and food viscosity. From the perspective of pharmacokinetics, we examined interaction trends between food properties and drugs across different classification based on the Biopharmaceutics Classification System (BCS). In addition, we introduced the practical application of physiologically based pharmacokinetic (PBPK) modeling in predicting oral drug absorption under the influence of food Properties.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"267-280"},"PeriodicalIF":4.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001956","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":"Advances in Selenium and Related Compounds Inhibiting Multi-Organ Fibrosis.","authors":"Xixi Xiao, Guoquan Huang, Xinqiao Yu, Yong Tan","doi":"10.2147/DDDT.S488226","DOIUrl":"10.2147/DDDT.S488226","url":null,"abstract":"<p><p>Selenium (Se), a critically essential trace element, plays a crucial role in diverse physiological processes within the human body, such as oxidative stress response, inflammation regulation, apoptosis, and lipid metabolism. Organ fibrosis, a pathological condition caused by various factors, has become a significant global health issue. Numerous studies have demonstrated the substantial impact of Se on fibrotic diseases. This review delves into the latest research advancements in Se and Se-related biological agents for alleviating fibrosis in the heart, liver, lungs, and kidneys, detailing their mechanisms of action within fibrotic pathways. Additionally, the article summa-rizes some of the anti-fibrotic drugs currently in clinical trials for the aforementioned organ fibroses.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"251-265"},"PeriodicalIF":4.7,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001887","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":"Risk Prediction of Liver Injury in Pediatric Tuberculosis Treatment: Development of an Automated Machine Learning Model.","authors":"Ying Zeng, Hong Lu, Sen Li, Qun-Zhi Shi, Lin Liu, Yong-Qing Gong, Pan Yan","doi":"10.2147/DDDT.S495555","DOIUrl":"10.2147/DDDT.S495555","url":null,"abstract":"<p><strong>Purpose: </strong>Drug-induced liver injury (DILI) is one of the most common and serious adverse drug reactions related to first-line anti-tuberculosis drugs in pediatric tuberculosis patients. This study aims to develop an automatic machine learning (AutoML) model for predicting the risk of anti-tuberculosis drug-induced liver injury (ATB-DILI) in children.</p><p><strong>Methods: </strong>A retrospective study was performed on the clinical data and therapeutic drug monitoring (TDM) results of children initially treated for tuberculosis at the affiliated Changsha Central Hospital of University of South China. After the features were screened by univariate risk factor analysis, AutoML technology was used to establish predictive models. The area under the receiver operating characteristic curve (AUC) was used to evaluate model's performance, and then the TreeShap algorithm was employed to interpret the variable contributions.</p><p><strong>Results: </strong>A total of 184 children were enrolled in this study, of whom 19 (10.33%) developed ATB-DILI. Univariate analysis showed that seven variables were risk factors for ATB-DILI, including the plasma peak concentration (C_max) of rifampicin, body mass index (BMI), alanine aminotransferase, total bilirubin, total bile acids, aspartate aminotransferase and creatinine. Among the numerous predictive models constructed by the \"H2O\" AutoML platform, the gradient boost machine (GBM) model exhibited the superior performance with AUCs of 0.838 and 0.784 on the training and testing sets, respectively. The TreeShap algorithm showed that C_max of rifampicin and BMI were important features that affect the AutoML model's performance.</p><p><strong>Conclusion: </strong>The GBM model established by AutoML technology shows high predictive accuracy and interpretability for ATB-DILI in children. The prediction model can assist clinicians to implement timely interventions and mitigation strategies, and formulate personalized medication regimens, thereby minimizing potential harm to high-risk children of ATB-DILI.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"239-250"},"PeriodicalIF":4.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001980","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}