Drug Design, Development and Therapy最新文献

{"title":"Comparison of Effect Sevoflurane-Based Anesthesia and Propofol-Based Anesthesia on the Early Postoperative Renal Function of Living Kidney Transplant Donors: A Randomized Controlled Trial.","authors":"Jianyue Cai, Fang Kang, Mingming Han, Xiang Huang, Wenlong Yan, Fuzhen Wan, Juan Li","doi":"10.2147/DDDT.S486393","DOIUrl":"10.2147/DDDT.S486393","url":null,"abstract":"<p><strong>Purpose: </strong>Living kidney transplantation is a common treatment for end-stage renal disease. The impact of anaesthetics on postoperative biomarkers of renal injury in living kidney transplant donors is not well understood.</p><p><strong>Patients and methods: </strong>70 transplant donors who underwent kidney extraction were randomly assigned to following two groups: sevoflurane (S group) and propofol (P group). Urine and blood were collected before induction and 1, 2, 6 days after operation. Kidney injury marker-1 (KIM-1), interleukin-18 (IL-18) and tissue inhibitor of metalloproteinase-2 (TIMP-2) were measured by enzyme-linked immunosorbent assay. Record the cystatin C, glomerular filtration rate, urine output during perioperative period.</p><p><strong>Results: </strong>There were both increases in biomarkers of kidney injury before and 1, 2 and 6 days after the anaesthetic surgery in donors, However, no statistical differences in KIM-1 (P (0.42 pg/mL (95% CI 0.21 to 0.63 pg/mL)) vs S (0.26 pg/mL (95% CI 0.02 to 0.49 pg/mL)), -0.16 pg/mL (95% CI -0.48 to 0.16 pg/mL)), IL-18 (P (178.54 pg/mL (95% CI 110.15 to 24693 pg/mL)) vs S (175.86 pg/mL (95% CI 100.35 to 251.38 pg/mL)), -2.68 pg/mL (95% CI -105.61 to 100.25 pg/mL)), and TIMP-2 (P (12.88 ng/mL (95% CI 8.69 to 17.07 ng/mL)) vs S (14.85 ng/mL (95% CI 10.23 to 19.46 ng/mL)), 1.97 ng/mL (95% CI -4.30 to 8.23 ng/mL)) concentration changes between the two types of anaesthesia.</p><p><strong>Conclusion: </strong>There was no difference between sevoflurane and propofol anaesthesia on postoperative changes in biomarkers of renal injury in living kidney transplant donors.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"491-503"},"PeriodicalIF":4.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051959","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":"Clinical Efficacy Between Intravenous Paracetamol and Intravenous Fentanyl for Propofol Deep Sedation in Colonoscopy: A Randomized Controlled Trial.","authors":"Thanitthi Thiparporn, Wilaiporn Supan, Somchai Amornyotin","doi":"10.2147/DDDT.S479084","DOIUrl":"10.2147/DDDT.S479084","url":null,"abstract":"<p><strong>Introduction: </strong>Sedation practices for colonoscopy indeed vary widely around the globe. Due to a lack of data on intravenous paracetamol, we aimed to investigate the clinical efficacy of intravenous paracetamol compared to intravenous fentanyl under propofol deep sedation for colonoscopy.</p><p><strong>Methods: </strong>A total of 225 patients who underwent colonoscopy at Siriraj Hospital were randomly assigned to two groups. All patients underwent deep sedation with propofol and received intravenous (iv) paracetamol (group P, n = 113) or iv fentanyl (group F, n = 112). All patients received a premedication of 0.02-0.03 mg/kg of midazolam intravenously. Fifteen to thirty minutes before the procedure, patients in group P were administered 1000 mg of iv paracetamol, while those in group F received 0.001 mg/kg of iv fentanyl. All patients were oxygenated with 100% O₂ via a nasal cannula, and deep sedated with titrated intravenous propofol. The primary outcome measure was the success rate of colonoscopy. The colonoscope reaching the ileocecal valve was an important marker for a successful colonoscopy. Secondary outcome measures included endoscopist and patient satisfaction, patient tolerance, ease of the procedure, and sedation-related complications during and immediately after the procedure.</p><p><strong>Results: </strong>All colonoscopies were successfully completed. There were no significant differences in patient characteristics, duration of the procedure, endoscopist and patient satisfaction, patient tolerance, or ease of the procedure between the two groups. However, group F experienced significantly higher rates of upper airway obstruction and oxygen desaturation during the procedure compared to group P. No serious complications were observed in either group.</p><p><strong>Conclusion: </strong>Intravenous paracetamol with propofol deep sedation in adult patients is non-inferior to intravenous fentanyl for successful colonoscopy completion. Sedation-related complications were relatively lower in the propofol deep sedation with iv paracetamol group compared to the propofol deep sedation with iv fentanyl group.</p><p><strong>Registration: </strong>This trial was registered with the Thai Clinical Trial Registry (TCTR 20190321002).</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"471-478"},"PeriodicalIF":4.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051955","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":"Exosomes in Oral Diseases: Mechanisms and Therapeutic Applications.","authors":"Qiandai Miao, Shaoqing Li, Weijia Lyu, Jianxia Zhang, Yan Han","doi":"10.2147/DDDT.S505355","DOIUrl":"10.2147/DDDT.S505355","url":null,"abstract":"<p><p>Exosomes, small extracellular vesicles secreted by various cells, play crucial roles in the pathogenesis and treatment of oral diseases. Recent studies have highlighted their involvement in orthodontics, periodontitis, oral squamous cell carcinoma (OSCC), and hand, foot, and mouth disease (HFMD). Exosomes have a positive effect on the inflammatory environment of the oral cavity, remodeling and regeneration of oral tissues, and offer promising therapeutic options for bone and periodontal tissue restoration. In OSCC tumor-derived exosomes promote cancer progression through cell proliferation, migration, invasion, and angiogenesis, and serve as potential biomarkers for early diagnosis and prognosis. Additionally, engineered exosomes constructed specifically based on exosome properties hold great promise for targeted drug delivery and regenerative therapies such as bone regeneration in orthodontics and periodontal healing. With continued research, exosomes hold great potential for improving diagnosis and treatment in oral diseases, advancing personalized and regenerative therapies.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"457-469"},"PeriodicalIF":4.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045866","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":"Integrated Microbiome and Metabolome Analysis Reveals Correlations Between Gut Microbiota Components and Metabolic Profiles in Mice With Mitoxantrone-Induced Cardiotoxicity.","authors":"Qing Zhang, Deshuai Liang, Chengfang Zhang, Ling Ye, Ping Sun, Hongli Zhu, Yongqin Zhao, Yuewen Li, Yun Guan, Haiguo Zhang","doi":"10.2147/DDDT.S479682","DOIUrl":"10.2147/DDDT.S479682","url":null,"abstract":"<p><strong>Purpose: </strong>Mitoxantrone (MTX) is largely restricted in clinical usage due to its significant cardiotoxicity. Multiple studies have shown that an imbalance in the gut-heart axis plays an important role in the development of cardiovascular disease (CVD). We aim to explore the possible correlations between gut microbiota (GM) compositions and cardiometabolic (CM) disorder in MTX-triggered cardiotoxicity mice.</p><p><strong>Methods: </strong>MTX cumulative dose of 6 mg/kg was administered to healthy Kunming male mice to trigger cardiotoxicity, with 1 mg/kg twice weekly for a duration of 3 weeks. Plasma CK-MB and LDH levels were determined, and the heart tissue histopathology was assessed, followed by utilizing an integrated liquid chromatography-mass spectrometry (LC-MS)-based heart metabolomics study alongside the 16S ribosomal RNA (rRNA) sequencing method to assess MTX impact on GM and CM profiles in mice, establishing associations between GM and CM profiles through the Pearson correlation coefficient calculation.</p><p><strong>Results: </strong>MTX caused CK-MB and LDH level elevations and cardiotoxicity in our mouse model. MTX primarily affected the processes of protein digestion and absorption, mineral absorption, membrane transport, production of aminoacyl-transfer RNA (tRNA), metabolism of nucleotides, lipids, and amino acids, as well as autophagy. Additionally, MTX increased <i>Romboutsia, Enterococcus</i>, and <i>Turicibacter</i> abundances and lowered <i>norank_f__Muribaculaceae, Alistipes, Odoribacter, norank_f__Lachnospiraceae, norank_f__Ruminococcaceae, norank_f__Oscillospiraceae, unclassified_f__Ruminococcaceae, NK4A214_group, Colidextribacter, norank_f__norank_o__Clostridia_vadinBB60_group, Rikenella</i>, and <i>Anaerotruncus</i> abundances. The correlation analyses showcased variations in the abundance of diverse flora, such as <i>Romboutsia, Enterococcus, Turicibacter, and norank</i>_<i>f__Muribaculaceae</i>, which were related to MTX-induced cardiac injury.</p><p><strong>Conclusion: </strong>Our study supports the claim that MTX provokes cardiotoxicity by modifying CM and GM profiles. Our results offer new possibilities for controlling MTX-triggered cardiotoxicity.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"439-455"},"PeriodicalIF":4.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058411","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":"Comprehensive Analysis of Metabolic Changes in Mice Exposed to Corilagin Based on GC-MS Analysis.","authors":"Biao Xu, Changshui Wang, Xiaodong Zhu, Li Zhu, Guangkui Han, Changmeng Cui","doi":"10.2147/DDDT.S482510","DOIUrl":"10.2147/DDDT.S482510","url":null,"abstract":"<p><strong>Background: </strong>Corilagin is widely distributed in various medicinal plants. In recent years, numerous pharmacological activities of Corilagin have been reported, including anti-inflammatory, antiviral, hepatoprotective, anti-tumor, and anti-fibrosis effects. However, there is still a need for systematic metabolomics analysis to further elucidate its mechanisms of action. The aim of this study was to explore the pharmacological mechanism of Corilagin.</p><p><strong>Methods: </strong>This study utilized gas chromatography-mass spectrometry (GC-MS) to analyze central target tissues, comprehensively exploring the pharmacological mechanism of Corilagin in mouse models. We identified the differential metabolites by multivariate analyses, which include principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Using MetaboAnalyst 5.0 and the KEGG database was used to depict the 12 key metabolic pathways.</p><p><strong>Results: </strong>Compared with the control group, the Corilagin induced 20, 9, 11, 7, 16, 19, 14, 15, and 16 differential metabolites in the intestine, lung, kidney, stomach, heart, liver, hippocampus, cerebral cortex, and serum, respectively. And 12 key pathways involving glucose metabolism, lipid metabolism, and amino acid metabolism were identified following Corilagin treatment.</p><p><strong>Conclusion: </strong>This research provides insight into the action mechanism of Corilagin's anti-oxidative, anti-inflammatory, anti-atherosclerotic, hepatoprotective, anti-tumor, and neuroprotective properties.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"389-404"},"PeriodicalIF":4.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045933","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 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}