Drug Design, Development and Therapy最新文献

{"title":"Liu Wei Di Huang Decoction Alleviates Renal Fibrosis by Inhibiting Endothelial Mesenchymal Transitions via Upregulating Sirt1 Expression and Inhibiting the Wnt/β-Catenin Signaling Pathway.","authors":"Hui Wang, Shuang-Shuang Chen, Yong-Xian Zhang, Hai-Bo Gao, Bin Meng, Wei-Yu Wu, Qun Tang","doi":"10.2147/DDDT.S517938","DOIUrl":"10.2147/DDDT.S517938","url":null,"abstract":"<p><strong>Background: </strong>Renal fibrosis (RF) is the final outcome of chronic kidney disease (CKD), which can be triggered by various factors. Liuwei Dihuang Decoction (LWDHD) has been clinically established as an effective treatment for CKD, demonstrating anti-inflammatory, antioxidant, and antifibrotic effects. However, the specific molecular mechanisms underlying the therapeutic effectiveness of LWDHD remain unknown.</p><p><strong>Aim: </strong>Prediction of key active ingredients, targets, and mechanistic pathways of LWDHD in RF treatment.</p><p><strong>Materials and methods: </strong>The bioactive components of LWDHD were identified and quantified using ultra-performance liquid chromatography-tandem quadrupole mass spectrometry (UHPLC-MS/MS). A network pharmacology approach was employed to predict the key targets of these bioactive components. A rat model of renal tubulointerstitial fibrosis was created through unilateral ureteral obstruction (UUO). Rats were divided into six groups: sham operation, UUO, low-dose LWDHD (LW-L), medium-dose LWDHD (LW-M), high-dose LWDHD (LW-H), and enalapril group. Continuous gavage of treatments was administered for 2 weeks. The renal tissues were histopathologically assessed, including HE, Masson's trichrome, and Sirius red staining, immunohistochemistry, co-staining and Western blot analysis to evaluate the effects of LWDHD on renal fibrosis. Transforming growth factor beta-1 (TGF-β1) was employed to stimulate endothelial-mesenchymal transition (EndMT) in EA.hy926 cells. The inhibitory effect of LWDHD on EndMT was validated through cellular morphology observations, Western blotting, and immunofluorescence assays.</p><p><strong>Results: </strong>LWDHD showed promise as a therapeutic agent by alleviating renal pathological injury and lowering collagen fiber accumulation. It enhanced Sirt1 expression while inhibiting the Wnt/β-catenin signaling pathway. Moreover, LWDHD increased the levels of the endothelial marker CD31 and decreased the expression of fibrosis-associated proteins, such as α-smooth muscle actin (α-SMA) and vimentin, thereby mitigating renal fibrosis.</p><p><strong>Conclusion: </strong>LWDHD has the potential to alleviate renal fibrosis, possibly through the upregulation of Sirt1, which inhibits the Wnt/β-catenin signaling pathway and thereby reduces EndMT.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"6587-6603"},"PeriodicalIF":5.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783778","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":"Compare the Effects of 0 mg/kg, 0.1 mg/kg, 0.3 mg/kg and 0.5 mg/kg Esketamine on Emergence Agitation After Tonsillectomy and Adenoidectomy in Children: A Randomized Control Trial.","authors":"Pingping Jiang, Wanxin Liu, Qingmei Peng, Yan Feng, Dan Wang, Kai Luo, San Huang","doi":"10.2147/DDDT.S525687","DOIUrl":"10.2147/DDDT.S525687","url":null,"abstract":"<p><strong>Background: </strong>The probability of children experiencing emergence agitation (EA) in post-anesthesia care unit (PACU) undergoing adenoidectomy and tonsillectomy is up to 80%. This study investigated the effects of pre-anesthesia sedation of esketamine at 0mg/kg (Control group), 0.1mg/kg, 0.3mg/kg and 0.5mg/kg on EA in children.</p><p><strong>Methods: </strong>164 children aged 3-10 years, with American Society of Anesthesiologists (ASA) class I-II were included. Children were randomly divided into groups k₀, k₁, k₃ and k₅, and the intravenous anesthesia doses of esketamine were 0 mg/kg, 0.1 mg/kg, 0.3 mg/kg and 0.5 mg/kg, respectively. EA occurrence was assessed using the Pediatric Anesthesia Emergence Delirium Scale (PAED) and Watcha scale. Anesthesia time, operation time, tracheal catheter removal time, PACU stay time, hospital stay, postoperative face, legs, activity, crying, consolability scale (FLACC), analgesia needs, heart rate (HR), mean arterial pressure (MAP) at different times, and postoperative complications were also recorded in the four groups.</p><p><strong>Results: </strong>There were significant statistical differences in PAED scores [13.00 (7.75), 10.00 (6.00), 9.00 (4.00), 9.00 (2.00), p=0.002], Watcha scores [3.00 (1.00), 3.00 (1.00), 2.00 (1.00), 2.00 (1.00), p<0.001], occurrence of postoperative EA [25 (62.5%), 21 (56.8.8%), 10 (25.6%), 7 (18.9%), p<0.001], and severe postoperative EA [20 (50.0%), 11 (29.7%), 4 (10.3%), 3 (8.1%), p<0.001] among the groups k₀, k₁, k₃ and k₅. There were no significant differences in operation time, duration of anesthesia, postoperative analgesia and antiemetic needs, and residence time in the PACU among the 4 groups (<i>p</i>>0.05). The 0.5 mg/kg group significantly increased the time required for tracheal catheter removal (<i>p</i><0.05). The differences in HR and MAP among the four groups were statistically significant (<i>p</i><0.05).</p><p><strong>Conclusion: </strong>Intravenous administration of esketamine at dose of 0mg/kg, 0.1mg/kg, 0.3mg/kg, and 0.5mg/kg before anesthesia induction leads to differences in the PAED score and incidence of EA of children after adenoidectomy and tonsillectomy. 0.3 mg/kg esketamine appears to offer the optimal balance between efficacy and safety in reducing EA.</p><p><strong>Trial registration number: </strong>ChiCTR2300075038. The trial is publicly available and is registered at www.chictr.org.cn on August 23, 2023.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"6543-6552"},"PeriodicalIF":5.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12318529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774918","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":"Determining the 90% Effective Dose of Remimazolam to Prevent Physical Movement in Surgical Abortions: A Biased-Coin Up-and-Down Sequential Allocation Trial.","authors":"Fuquan Fang, Huiling Li, Lei Li, Bing Yan, Pengfei Yin, Binwei Hu, Shengmei Zhu, Xianhui Kang","doi":"10.2147/DDDT.S492245","DOIUrl":"10.2147/DDDT.S492245","url":null,"abstract":"<p><strong>Background: </strong>Remimazolam is widely employed in surgical abortions. However, its dosing references from clinical studies such as gastrointestinal and bronchoscopic anesthesia have resulted in high incidence of physical movement.</p><p><strong>Purpose: </strong>Determining the optimal dosage (the 90% effective dose [ED90]) for preventing physical movement during surgical abortions.</p><p><strong>Patients and methods: </strong>Fifty-seven individuals aged 18 to 45 undergoing surgical abortion were included. Remimazolam, combined with remifentanil, was utilized for anesthesia induction. Commencing at an initial dose of 0.25 mg/kg of remimazolam, subsequent adjustments relied on the preceding patient's response, employing an up-down sequential allocation utilizing a biased-coin design.</p><p><strong>Results: </strong>Patients received remimazolam doses ranging from 0.25 to 0.65 mg/kg. The estimated ED90, along with its 95% confidence interval (CI), for preventing physical movement was 0.615 mg/kg (0.398-0.629 mg/kg). Patients maintained stable circulation, and no significant adverse events were recorded. Patients reported a satisfaction score of 4.63 ± 0.62 points. Anesthesiologists rated their satisfaction at 4.19 ± 0.61 points, and endoscopists expressed a satisfaction level of 4.53 ± 0.57 points (based on a full score of 5 points, with a minimum of 1 point).</p><p><strong>Conclusion: </strong>The ED90 of remimazolam during surgical abortion to prevent physical movement was determined to be 0.615 mg/kg (95% CI, 0.398-0.629 mg/kg).</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"6379-6389"},"PeriodicalIF":5.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12318863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783775","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":"Histone Lactylation in Diseases: Regulation by Traditional Chinese Medicine and Therapeutic Implications.","authors":"Yuyue Qiu, Xiaoni Shao","doi":"10.2147/DDDT.S524008","DOIUrl":"10.2147/DDDT.S524008","url":null,"abstract":"<p><p>Histone lactylation, as a common post-translational modification (PTM), is crucial in diseases. Aberrant histone lactylation has been linked to disease pathogenesis, thus positioning it as a therapeutic target. This review summarizes the bidirectional relationship between histone lactylation and diseases, emphasizing how Traditional Chinese medicine (TCM) regulates lactate levels to restore histone lactylation homeostasis. Mechanistically, TCM modulates histone lactylation through dual regulation of lactyltransferases and lactate metabolism, thereby influencing disease progression in inflammatory, metabolic, and neoplastic disorders. Notably, TCM is characterized by unique advantages of cost-effectiveness, high efficacy, and minimal adverse effects. For diseases with established drug resistance, TCM offers a promising therapeutic alternative in managing drug-resistant illness by regulating histone lactylation. This review is conducive to understanding the relationship between histone lactylation and disease. TCM effectively treats diseases through the regulation of histone lactylation, thereby highlighting its potential for disease treatment application.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"6435-6459"},"PeriodicalIF":5.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774924","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":"Efficacy and Long-Term Outcomes of Tacrolimus versus Cyclophosphamide and Mycophenolate Mofetil in the Management of Pediatric IgA Vasculitis Nephritis: A Cohort Study in Single-Center.","authors":"Yanxinli Han, Fengjie Yang, Lanqi Zhou, Jing Yang, Yuan Yang, Yi Wang, Liru Qiu, Yu Zhang, Jianhua Zhou","doi":"10.2147/DDDT.S528565","DOIUrl":"10.2147/DDDT.S528565","url":null,"abstract":"<p><strong>Purpose: </strong>IgA vasculitis nephritis (IgAVN) is one of the most common secondary glomerulonephritis in children. Although guidelines have reached a consensus about the effectiveness of cyclophosphamide (CYC) in IgAVN, the recommendations regarding the use of tacrolimus (TAC) and mycophenolate mofetil (MMF) are still inconsistent. Studies have demonstrated that TAC is safe and effective in IgAVN. However, the impact of immunosuppressive agents on the long-term outcome remains ambiguous. Therefore, the objective of this study is to compare the effectiveness and long-term outcome of TAC, CYC, and MMF in combination with glucocorticoid in pediatric IgAVN.</p><p><strong>Patients and methods: </strong>A retrospective analysis was conducted on children with grade II-V IgAVN by renal biopsy at Tongji Hospital from November 2011 to October 2021. The collected clinical, pathological, treatment and follow-up data were analyzed.</p><p><strong>Results: </strong>A total of 422 patients were eligible. Among them, 108 patients received glucocorticoid in combination with oral TAC, 143 with intravenous CYC, and 171 with oral MMF. The complete remission rate (CR) of TAC (25.9%/44.3%) was significantly higher than that of CYC (16.1%/36.4%) at 3 and 6 months. Additionally, mean absolute decrease in urine protein at 1, 3, and 6 months were significantly higher in TAC than that in CYC and MMF groups. Compared to CYC, TAC and MMF groups had significantly lower overall incidence of adverse events (60.2%, 65.7% vs 84.4%). Moreover, TAC and MMF group had a more favorable renal prognosis (grade A and B) and a significantly lower recurrence rate (17.9%, 23.9% vs 41.8%) than CYC.</p><p><strong>Conclusion: </strong>This study reveals that TAC can rapidly and effectively reduce proteinuria and achieve renal complete remission with fewer adverse effects. Moreover, TAC and MMF are more favourable for renal prognosis.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"6413-6422"},"PeriodicalIF":5.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774922","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 Comparative Study of Sugammadex and Neostigmine: A Bibliometric Analysis of the Past 15 Years.","authors":"Dawei Yin, Bin Tang, Xiaoyan Hu, Huan Hu","doi":"10.2147/DDDT.S519235","DOIUrl":"10.2147/DDDT.S519235","url":null,"abstract":"<p><strong>Purpose: </strong>Sugammadex is a novel selective relaxant binding agent for aminosteroid neuromuscular blocking agents (NMBAs). However, existing literature reveals major knowledge gaps regarding its current applications and emerging research trends. Therefore, this study employed bibliometric analysis to map the evolutionary trajectory and research frontiers in sugammadex studies over the past 15 years.</p><p><strong>Methods: </strong>Publications on sugammadex (2009-2024) along with neostigmine studies (1993-2008) were retrieved from the Web of Science Core Collection. Data aggregation was performed using Microsoft Excel, while bibliometric visualizations were generated through the Bibliometrix package in R software. Additional network analyses were conducted using VOSviewer and CiteSpace.</p><p><strong>Results: </strong>The analysis encompassed 765 articles. Sugammadex-related research exhibited a notable upward trend, particularly from 2017 to 2021. The United States of America (USA) emerged as the most productive country in publication output (186 articles) and demonstrated superior quality (h-index: 16). Among institutions, Merck & Co. contributed the highest number of publications (74). Similar to neostigmine, key research areas for sugammadex have included: pharmacokinetics and pharmacodynamics, adverse reactions, clinical applications, and specific patient populations. This focus is evidenced by substantial common references and keywords.</p><p><strong>Conclusion: </strong>Sugammadex surpasses neostigmine in rapidly, effectively, and safely reversing NMB induced by rocuronium/vecuronium across all depths. Its use expands to reversing residual NMB from NMBAs in various patient groups (hepatic/renal impairment, obese, neuromuscular disease, elderly, pediatric) and scenarios like difficult airways. Future research will focus on adverse reactions, effects in special populations, establishing quantitative NMB monitoring standards, and understanding NMBA antagonism failure mechanisms.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"6357-6377"},"PeriodicalIF":5.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12319425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783773","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":"DHLCA Alleviates Diabetic Kidney Disease via TGR5/FXR Activation and Gut Microbiota Remodeling.","authors":"Hua Zhou, Xiaodie Mu, Huiyue Hu, Shuya Zhao, Nan Hu, Min Yang, Jingting Jiang","doi":"10.2147/DDDT.S530823","DOIUrl":"10.2147/DDDT.S530823","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic kidney disease (DKD) is a major contributor to chronic kidney disease worldwide. Bile acids (BAs) are increasingly recognized as key regulators of glucose metabolism and kidney function. This study aimed to investigate the role of BA metabolism in the progression of DKD.</p><p><strong>Methods: </strong>Plasma BA profiles were measured in healthy controls (HC), patients with type 2 diabetes mellitus (T2DM), and patients with DKD using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). After identifying potential BA biomarkers in the clinical cohort, in vivo validation was conducted using dehydrolithocholic acid (DHLCA) intervention in DKD mouse model. Kidney injury markers, as well as the expression of Takeda G protein-coupled receptor 5 (TGR5) and farnesoid X receptor (FXR), were evaluated. In addition, gut microbiota (GM) composition was analyzed via metagenomic sequencing following DHLCA treatment.</p><p><strong>Results: </strong>The plasma DHLCA levels were significantly lower in DKD with macroalbuminuria group compared to T2DM group and DKD with microalbuminuria group (<i>P</i> < 0.01). Partial Spearman correlation analysis adjusted for age and diabetes duration showed that DHLCA levels were negatively correlated with urine albumin (<i>ρ</i> = -0.347; 95% CI, -0.531 to -0.135; q = 0.008) and urine albumin-to-creatinine ratio (UACR) (<i>ρ</i> = -0.332; 95% CI, -0.499 to -0.155; q = 0.010). In vivo, DHLCA administration significantly reduced UACR and fasting blood glucose (FBG) levels (<i>P</i> < 0.01), and improved liver function (ALT, <i>P</i> < 0.05) in DKD mice. DHLCA treatment attenuated renal tubular injury, restored TGR5 and FXR expression in kidney tissue, and decreased levels of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Metagenomic analysis revealed an enrichment of <i>Lachnospiraceae bacterium</i> following DHLCA treatment.</p><p><strong>Conclusion: </strong>DHLCA may represent a promising therapeutic candidate for DKD by targeting the TGR5/FXR signaling pathway and GM remodeling. Its metabolic and kidney benefits, along with an improved hepatic profile and absence of hepatotoxicity, support further translational investigation.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"6469-6485"},"PeriodicalIF":5.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12318845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783776","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":"Determination of the Median Effective Dose (ED50) of Ciprofol for Successful Sedation in Pediatric Patients During General Anesthesia Induction.","authors":"Peihe Nie, Di Wu, Chengjun Du, Xiaoqian Wang, Huan Zhang, Hongyi Xiao","doi":"10.2147/DDDT.S536118","DOIUrl":"10.2147/DDDT.S536118","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the median effective dose (ED50) and 90% effective dose (ED90) of ciprofol for successful sedation during general anesthesia induction in pediatric patients, optimize dosing regimens, and provide reference evidence for clinical practice.</p><p><strong>Patients and methods: </strong>We enrolled pediatric patients aged 3-12 years scheduled for elective surgery under general anesthesia with endotracheal intubation. The first patient received intravenous ciprofol 0.4 mg/kg. Using the modified Dixon's up-and-down sequential method, the ciprofol dose for each subsequent patient was determined based on the previous patient's sedation response. Sedation success was evaluated using two clinical endpoints: loss of eyelash reflex (LER) and acceptance of facemask (AFM). We calculated the ED50, ED90 and their 95% confidence intervals (CI) of ciprofol for successful induction sedation. Secondary outcomes included eyelash reflex disappearance time, vital sign changes during induction, and adverse events.</p><p><strong>Results: </strong>The study achieved 7 transition points (from sedation success to failure) with a total enrollment of 36 pediatric cases. The ED50 and ED90 (with 95% CI) of ciprofol for successful induction sedation in pediatric general anesthesia were 0.618 (0.576~0.666) mg/kg and 0.708 (0.661~0.916) mg/kg, respectively. Eyelash reflex disappearance occurred at 31.04±8.19 seconds post-induction. During anesthesia induction, one case of hypoxemia was observed, while no patients experienced injection pain or hypotension.</p><p><strong>Conclusion: </strong>Ciprofol demonstrates efficacy for anesthesia induction in pediatric patients aged 3-12 years. In the absence of premedication, the median effective dose (ED50) of ciprofol for successful sedation during general anesthesia induction in pediatric patients was 0.618 mg/kg. The recommended dose of ciprofol for induction of general anesthesia in children 3-12 years of age is 0.6-0.7 mg/kg to ensure smooth passage through the mask-assisted respiration phase during induction.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"6391-6397"},"PeriodicalIF":5.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774920","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":"Inhibition of Colorectal Cancer by Perillaldehyde Through Targeting SRD5A1 to Induce Autophagy via the PI3K/AKT Pathway.","authors":"Zhuyun Leng, Yiqian Zhang, Mingming Guo, Yan Chen, Zhiyong Wang","doi":"10.2147/DDDT.S525006","DOIUrl":"10.2147/DDDT.S525006","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is the third most common cancer globally, with treatment challenges persisting. Perillaldehyde (PAH), a major active monomer extracted from Perilla, has shown potential against CRC, though its mechanisms remain unclear. This study aims to assess the therapeutic potential of PAH against CRC and to clarify its mechanisms of action, providing a rationale for PAH as a promising candidate for anti-CRC therapy.</p><p><strong>Methods: </strong>In vitro, we used CCK-8, colony formation, EdU assays, flow cytometry, and Western blotting to assess the effects of PAH on CRC cell proliferation and apoptosis. In vivo, a subcutaneous xenograft mouse model was established to evaluate the anti-CRC efficacy of PAH. Transcriptomic analysis was performed to identify possible mechanisms, particularly related to autophagy, and validated through TEM, immunofluorescence, Western blotting, and inhibitor assays. SRD5A1 was predicted as a potential target using Swiss Target Prediction and confirmed by molecular docking, molecular dynamics simulation, and CETSA. Bioinformatics analysis further assessed the clinical relevance and mechanism of SRD5A1, which was validated using a selective inhibitor.</p><p><strong>Results: </strong>PAH demonstrated inhibitory effects on CRC in both experimental models. RNA-seq and experimental validation suggest that PAH may inhibit CRC by modulating the PI3K/AKT pathway to induce autophagy. Bioinformatics analysis indicates that SRD5A1 could be a potential target of PAH, with PAH treatment reducing SRD5A1 levels and enhancing autophagic activity through PI3K/AKT suppression.</p><p><strong>Conclusion: </strong>PAH appears to inhibit CRC by targeting SRD5A1, thereby promoting autophagy through the PI3K/AKT pathway. This offers new perspectives for both the diagnosis and treatment of CRC.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"6399-6412"},"PeriodicalIF":5.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774925","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 Norepinephrine and Phenylephrine on Tissue Oxygenation During Superficial Temporal Artery-Middle Cerebral Artery Bypass: A Randomized Controlled Trial.","authors":"Jie Cheng, Fang Kang, Mingming Han, Yao Song, Ling Chang, Xiang Huang, Yan Zhang, Juan Li","doi":"10.2147/DDDT.S517391","DOIUrl":"10.2147/DDDT.S517391","url":null,"abstract":"<p><strong>Purpose: </strong>The current study aimed to compare the effects of norepinephrine and phenylephrine on tissue oxygenation and clinical outcomes in Moyamoya disease patients.</p><p><strong>Patients and methods: </strong>Sixty patients scheduled for superficial temporal artery-middle cerebral artery bypass were randomly assigned to either the norepinephrine group or the phenylephrine group. Standard doses of norepinephrine or phenylephrine were infused during surgery to maintain blood pressure fluctuating within ± 10% of baseline values. Cerebral oxygenation, muscle oxygenation, cardiac output, and urine volume were recorded at several timepoints: Before preoxygenation, After intubation, Skin cutting, Superficial temporal artery exposing, Middle cerebral artery exposing, and End of the surgery. Additionally, blood samples were collected from the superior vena cava and radial artery for blood gas analysis, to assess central venous oxygen saturation, blood lactate and calculate oxygen extraction rate. Length of hospital stay, incidence of neurological complications during hospitalization and mortality within 90 days were also recorded.</p><p><strong>Results: </strong>Compared with phenylephrine group, the norepinephrine group exhibited significantly higher cerebral oxygenation, muscle oxygenation and cardiac output at Superficial temporal artery exposing, Middle cerebral artery exposing, and End of the surgery (<i>P</i><0.05). No significant difference was observed between groups at any timepoints regarding urine output, central venous oxygen saturation, blood lactate levels, oxygen extraction rate. Length of hospital stay, incidence of neurological complications during hospitalization and 90-day mortality rate were comparable between groups.</p><p><strong>Conclusion: </strong>The use of norepinephrine, in contrast to phenylephrine, for managing hypotension during superficial temporal artery-middle cerebral artery bypass significantly enhances tissue oxygenation, which may be related to the effective maintenance of cardiac output by norepinephrine.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"6347-6356"},"PeriodicalIF":5.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741582","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}