Drug Design, Development and Therapy最新文献

{"title":"Fenofibrate as an Adjunct Therapy for Ulcerative Colitis: Targeting Inflammation via SIRT1, NLRP3, and AMPK Pathways: A Randomized Controlled Pilot Study.","authors":"Sumaiah J Alarfaj, Mostafa M Bahaa, Thanaa A Elmasry, Eman I Elberri, Eman El-Khateeb, Amir O Hamouda, Muhammed M Salahuddin, Marwa Kamal, Abdel-Naser Abdel-Atty Gadallah, Nashwa Eltantawy, Mohamed Yasser, Walaa A Negm, Manal A Hamouda, Amsha S Alsegiani, Sarah Alrubia, Mamdouh Eldesoqui, Mahmoud S Abdallah","doi":"10.2147/DDDT.S490772","DOIUrl":"10.2147/DDDT.S490772","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is an idiopathic chronic inflammation of colonic and rectal mucosa. The peroxisome proliferator-activated receptor α (PPARα) has been identified as having protective effects in UC.</p><p><strong>Aim: </strong>The study aimed to investigate the efficacy of fenofibrate, a PPARα agonist, in UC.</p><p><strong>Methods: </strong>A total of 70 patients with mild to moderate UC were allocated randomly and assigned to two groups (n = 35 each) from Gastroenterology Department, Faculty of Medicine, Menoufia University. The mesalamine group received a placebo along with 1 g of mesalamine three times daily, while the fenofibrate group received 1 g of mesalamine three times and fenofibrate 160 mg once daily. The study duration was for six months. A gastroenterologist assessed patients by non-invasive Partial Mayo Score (PMS) and the Inflammatory Bowel Disease Questionnaire (IBDQ) to evaluate clinical response and remission. The serum levels of silent information regulator 1 (SIRT1), NOD-like receptor protein 3 (NLRP3), and adenosine monophosphate activated protein kinase (AMPK), as well as fecal calprotectin levels were examined to determine the biological effect of fenofibrate.</p><p><strong>Results: </strong>After treatment, the fenofibrate group showed statistically significant reductions in PMS (<i>p =</i> 0.044) and improved digestive domain of IBDQ (<i>p =</i> 0.023). Additionally, there were significant decreases in serum NLRP3 (<i>p =</i> 0.041) and fecal calprotectin (<i>p =</i> 0.035), along with significant increases in SIRT1 (<i>p =</i> 0.002) and AMPK (<i>p =</i> 0.0003). The fenofibrate group also had higher response and remission rates compared to the mesalamine group.</p><p><strong>Conclusion: </strong>Fenofibrate may be a promising adjunct for improving clinical outcomes, quality of life, and modulating inflammation in mild to moderate patients with UC.</p><p><strong>Trial registration identifier: </strong>NCT05781698.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"5239-5253"},"PeriodicalIF":4.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686419","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":"Profile of Fruquintinib in the Management of Advanced Refractory Metastatic Colorectal Cancer: Design, Development and Potential Place in Therapy.","authors":"Sebawe Syaj, Anwaar Saeed","doi":"10.2147/DDDT.S388577","DOIUrl":"10.2147/DDDT.S388577","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a prevalent and deadly cancer, with metastatic CRC (mCRC) often leading to poor outcomes despite advancements in screening and chemotherapy. Anti-angiogenic agents targeting vascular endothelial growth factor (VEGF) pathways have become essential in mCRC treatment. Bevacizumab, a VEGF inhibitor, was the first agent used in this context. However, drug resistance prompted the development of more selective inhibitors, such as fruquintinib, a tyrosine kinase inhibitor (TKI) that targets VEGFR-1, -2, and -3. Fruquintinib has shown promise in clinical trials, particularly for third-line mCRC treatment. The Phase III FRESCO trial in China demonstrated its efficacy, significantly improving overall survival (OS) and progression-free survival (PFS) compared to placebo, with manageable safety concerns like hypertension and hand-foot skin reactions. The FRESCO-2 trial extended these findings to European and North American populations, leading to a recent FDA approval for previously treated mCRC patients. The pharmacodynamic profile of fruquintinib includes potent inhibition of VEGFR, angiogenesis, and lymphangiogenesis. It has shown synergistic effects when combined with other treatments like chemotherapy and immune checkpoint inhibitors (ICIs). Current research focuses on exploring fruquintinib's combination with ICIs, such as PD-1 inhibitors, to enhance treatment efficacy, especially in microsatellite stable (MSS) CRC. Ongoing trials are investigating Fruquintinib's potential in combination with other therapies and its use in earlier lines of treatment. While promising, further studies are required to optimize its place in therapy and identify predictive biomarkers for better patient selection.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"5203-5210"},"PeriodicalIF":4.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681101","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":"Catecholamine Vasopressors and the Risk of Atrial Fibrillation After Noncardiac Surgery: A Prospective Observational Study.","authors":"Weichao Li, YuYan Liu, Xunhu Gu","doi":"10.2147/DDDT.S474818","DOIUrl":"10.2147/DDDT.S474818","url":null,"abstract":"<p><strong>Background: </strong>Catecholamine vasopressors are commonly used for intra- or post-operative hypotension for cardiac surgery, which have a side effect of new-onset atrial fibrillation (AF) and myocardial ischemia. However, it is not entirely clear whether catecholamine vasopressors increase the risk of new-onset AF after noncardiac surgery.</p><p><strong>Aim: </strong>The aim of this study was to analyze the association between the use of catecholamine vasopressors and the risk of developing new-onset AF after noncardiac surgery.</p><p><strong>Methods: </strong>In this prospective trial, available data from eligible elderly individuals receiving noncardiac surgery at a single center from November 2022 to January 2024 were gathered. Propensity score matching (PSM) was used to balance patient baseline characteristics and to control for confounders. To determine the association between catecholamine vasopressors and the risk of new-onset AF, univariate and multivariate logistic regression analyses were performed.</p><p><strong>Results: </strong>A total of 6000 subjects were included in this study (mean [SD] age, 70.73 [6.37] years; 910 [50.9%] males). After PSM, the patients were stratified into catecholamine vasopressor (n = 357) and comparator groups (n = 1432). A total of 18/357 patients in the catecholamine vasopressor group developed AF, and 25/1432 patients in the comparator group developed AF (incidence rate, 5.0% vs 1.7%). Compared with the comparator group, the catecholamine vasopressor group had an increased risk of new-onset AF (aOR, 2.77; 95% CI, 1.28-5.89). Some sensitivity analyses also revealed consistent findings of increased new-onset AF risk associated with catecholamine vasopressor treatment.</p><p><strong>Conclusion: </strong>The findings from this study suggest that catecholamine vasopressor treatment is associated with an increased risk of new-onset AF and may help physicians select a modest medication for patients while also assessing the risk of new-onset AF.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"5193-5202"},"PeriodicalIF":4.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681018","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":"Novel Agonists of Adenosine Receptors in Animal Model of Acute Myocardial Infarction.","authors":"Fabricio Beltrame, Bianca Nascimento-Carlos, Jaqueline S da Silva, Rodolfo Couto Maia, Tadeu Lima Montagnoli, Eliezer J Barreiro, Gisele Zapata-Sudo","doi":"10.2147/DDDT.S464712","DOIUrl":"10.2147/DDDT.S464712","url":null,"abstract":"<p><strong>Background and purpose: </strong>Current treatments for acute myocardial infarction (AMI) include pain relief and attempts to improve survival. This study investigated the effects of two new ligands of the adenosine receptor, LASSBio-1027 and LASSBio-1860, on cardiac function in an experimental model of AMI.</p><p><strong>Methods: </strong>AMI was induced in Wistar rats by ligating the anterior descending coronary arteries. Infarcted animals were treated orally with vehicle (DMSO), LASSBio-1027 (30 and 70 μmol/kg), or LASSBio-1860 (70 μmol/kg) for seven days. Hemodynamic parameters were observed using echocardiography, whereas inflammation and fibrosis were detected using histological analysis.</p><p><strong>Results: </strong>MI increased the filling pressure from 23.0 ± 1.6 and 14.0 ± 2.0 to 37.0 ± 3.7 and 33.2 ± 8.0, respectively indicating diastolic dysfunction. However, treatment with LASSBio-1027 (70 μmol/kg) and LASSBio-1860 (70 μmol/kg) reduced this parameter to 23.9 ± 5.4 and 17.1 ± 6.7. An impairment in ejection fraction from 57.1 ± 3.2 to 36.6 ± 2.0% was observed after MI, partially recovered to 47.0 ± 7.4% by LASSBio-1027 and fully restored to 61.8 ± 4.3% after 7 days of treatment with LASSBio-1860. After MI, collagen deposition in LV free wall was increased to 31.4 ± 11.0% and treatment with LASSBio-1027 reduced to 23.4 ± 6.0 and 19.7 ± 8.0% at 30 and 70 μmol/kg, respectively. Similarly, LASSBio-1860 reduced collagen levels to 63.1 ± 2.0%.</p><p><strong>Conclusion: </strong>Fibrosis and inflammatory components of MI reduced following treatment with agonist of adenosine receptor subtype A2A. Cardiac remodeling induced by LASSBio-1027 and LASSBio-1860 may be responsible for the improvement in cardiac function in AMI through the activation of A2A adenosine receptors.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"5211-5223"},"PeriodicalIF":4.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681096","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 Remimazolam and Propofol for Intravenous Anesthesia on Trigeminocardiac Reflex in Percutaneous Balloon Compression for Trigeminal Neuralgia: A Randomized Controlled Trial.","authors":"DongJu Long, Kai Chen, YaXi Li, PeiYao He, XinNing Li, XiuNan Qin, YaPing Wang, YanYing Xiao","doi":"10.2147/DDDT.S473700","DOIUrl":"10.2147/DDDT.S473700","url":null,"abstract":"<p><strong>Background: </strong>Trigeminal neuralgia usually presents as incapacitating facial pain. Percutaneous balloon compression (PBC) is frequently utilized to manage this ailment. Trigeminocardiac reflex (TCR) commonly presents with sudden severe bradycardia or even asystole, alongside a sudden increase in blood pressure during this surgical procedure. Notably, remimazolam has been reported to maintain higher heart rate (HR) levels during anesthesia than propofol. Thus, this study aims to assess the impact of remimazolam anesthesia versus propofol on TCR occurrence during this procedure.</p><p><strong>Methods: </strong>This randomized controlled trial involved patients with trigeminal neuralgia scheduled for elective PBC. Patients were randomly assigned to receive either remimazolam or propofol for anesthesia. The primary outcome was the incidence of TCR, a potential complication during the procedure. Secondary outcomes included the occurrence of severe TCR, usage of atropine, HR at the time of foramen ovale puncture (T4), HR at the time of trigeminal ganglion compression (T5), and any adverse events.</p><p><strong>Results: </strong>A total of 80 patients were included in the study, with 40 patients in each group. The incidence of TCR was significantly lower in the remimazolam group compared to the propofol group (30.0% vs 82.5%; risk difference -52.5%, 95% CI -67.3% to -18.6%; <i>P</i> < 0.001). The remimazolam group also showed a lower incidence of severe TCR (7.5% vs 45.0%) and significantly lower usage of atropine compared to the propofol group (<i>P</i> < 0.001). Furthermore, HR at T4 and T5 were higher in the remimazolam than in the propofol group (<i>P</i> < 0.001). There was no significant difference in the incidence of adverse events between the two groups.</p><p><strong>Conclusion: </strong>In PBC surgery for trigeminal neuralgia, remimazolam-based intravenous anesthesia showed a higher HR and a lower incidence of TCR than propofol without any increased adverse events.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"5225-5237"},"PeriodicalIF":4.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681022","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":"Protective Effect of Modified Suanmei-Tang on Metabolic-Associated Fatty Liver Disease: An Integrated Strategy of Network Pharmacology, Metabolomics, and Transcriptomics.","authors":"Chao Wang, Mei Zhao, Yuanyuan Yue, Chao Hu, Chunqiu Zhou, Zhongyi Zhang, Yunliang He, Yaqi Luo, Tao Shen, Sijie Dang, Yang Yang, Yong Zhang","doi":"10.2147/DDDT.S478072","DOIUrl":"10.2147/DDDT.S478072","url":null,"abstract":"<p><strong>Background: </strong>Modified Suanmei-Tang (MST) comprises four plants common to both traditional Chinese medicine and culinary applications, and it can potentially alleviate metabolic-associated fatty liver disease (MAFLD) triggered by a high-fat diet (HFD).</p><p><strong>Purpose: </strong>This research aims to investigate the impact and underlying mechanisms of MST in ameliorating MAFLD caused by an HFD.</p><p><strong>Methods: </strong>UHPLC-Q-Orbitrap-MS/MS was used to determine the constituents of MST and to evaluate its effects on MAFLD mouse models. Transcriptomics, network pharmacology, and bioinformatics analysis (including Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis) were utilized to further clarify the mechanisms by which MST acts on MAFLD. The experimental methods included ELISA, real time quantitative PCR (RT-qPCR), Western blot, immunohistochemistry, molecular docking, and metabolomics. Transcriptomics was integrated with metabolomics to find correlations between differentially expressed genes and metabolites, and crucial genes were validated through RT-qPCR.</p><p><strong>Results: </strong>A total of 23 components of MST were identified. The formulation was found to alleviate metabolic disorders, obesity, insulin resistance, inflammation, and oxidative stress in mice with MAFLD. The findings indicate that MST promoted autophagy by suppressing phosphorylation in the PI3K/AKT/mTOR pathway and enhancing lipid management in the livers of MAFLD mice.</p><p><strong>Conclusion: </strong>MST could effectively improve lipid metabolism disorders and liver lipid deposition in MAFLD mice, and its mechanism might be related to regulating the PI3K/AKT/mTOR pathway to improve autophagy.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"5161-5182"},"PeriodicalIF":4.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667436","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 Remimazolam- Vs Propofol-Based Intravenous Anesthesia on Surgical Stress Response and Post-Operative Immune Function in Patients with Gastric Radical Surgery.","authors":"Qingqing Xu, Xue Cheng, Hong Sun, Guangyuan Su, Yuanhui Fei, Chunhui Wang, Chao Han","doi":"10.2147/DDDT.S489167","DOIUrl":"10.2147/DDDT.S489167","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to compare the impact of remimazolam-based versus propofol-based intravenous anesthesia on surgical stress and post-operative immune function in patients undergoing gastric radical surgery.</p><p><strong>Patients and methods: </strong>Sixty-eight patients aged 50 to 80 undergoing gastric radical surgery were randomly assigned to the remimazolam group (group R) or the propofol group (group P), receiving remimazolam or propofol-based intravenous anesthesia, respectively. The primary outcome measured was peri-operative serum stress indicators and lymphocyte subtypes. Secondary outcomes included hemodynamic vitals, recovery quality, postoperative pain profiles and potential adverse effects.</p><p><strong>Results: </strong>The demographic and surgical characteristics of the 60 analyzed patients were comparable. The absolute counts of CD3+CD4+ and CD3+CD8+ cell decreased significantly on POD1 compared with baseline. On POD3, the numbers of CD3+CD4+ cells in group R were lower than baseline and Group P, whereas the CD3+CD8+ cell counts in both groups were lower than baseline, with group R higher than group P. The CD3-CD16+CD56+ cell numbers in both groups on POD1 and POD3 decreased significantly compared to baseline with group P lower than group R on POD3. The serum levels of IL-1β, IL-6, TNF-α, ACTH and COR rose sharply 2 hours after the beginning of surgery compared to baseline. Notably, all these parameters in group R were higher than those in group P. Additionally, blood pressure and intra-operative vasoactive drug frequency in group R were higher than that in group P. No significant differences in recovery quality, postoperative pain profiles, and potential adverse effects were observed.</p><p><strong>Conclusion: </strong>Remimazolam-based intravenous anesthesia might favour the recovery of cellular immune function in early postoperative period compared to propofol. On the contrary, remimazolam was inferior to propofol in suppressing surgical stress. Further studies with larger sample sizes are needed to confirm our findings.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"5183-5192"},"PeriodicalIF":4.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, Pharmacological Evaluation of Quinazolin-4(3<i>H</i>)-Ones Bearing Urea Functionality as Potential VEGFR-2 Inhibitors.","authors":"Mohammad M Al-Sanea, Hani M Hafez, Ahmed A B Mohamed, Hamed W El-Shafey, Abdullah A Elgazar, Samar S Tawfik, Wafaa A Ewes, Shaimaa Hussein, Tariq G Alsahli, Abdelrahman Hamdi","doi":"10.2147/DDDT.S490930","DOIUrl":"10.2147/DDDT.S490930","url":null,"abstract":"<p><strong>Background: </strong>In response to the urgent need for continuous discovery of new anti-proliferative agents, a new series of quinazoline compounds <b>5a-r</b> was prepared.</p><p><strong>Methods: </strong>As a reference, four cancer cell lines-HCT116, HePG2, Hela, and MCF-7-and sorafenib (SOR) were used to assess the novel motifs' in vitro anticancer efficacy. The most cytotoxic compounds were tested in a VEGFR-2 suppressive test and flow cytometric test. Docking analysis was done to the three novel motifs.</p><p><strong>Results: </strong>Compound <b>5d</b> showed the best anti-tumor activity of the tested compounds with IC₅₀ 6.09, 2.39, 8.94 and 4.81 μM in succession. In addition, compound <b>5h</b> revealed a potent anticancer effect against HCT116 and HePG2 with IC₅₀ 5.89 and 6.74 μM, respectively. Also, compound <b>5p</b> exhibited very strong activity against HCT116, HePG2 & MCF7 with IC₅₀ 8.32, 9.72 and 7.99, respectively. Compound <b>5p</b> had the highest inhibition against VEGFR-2 with an IC₅₀ of 0.117 μM, in contrast to 0.069 μM for SOR. According to flow cytometric testing, the most effective VEGFR-2 inhibitory agent, <b>5p</b>, was shown to suppress the G1/S cell population in MCF-7 cells. Docking analysis confirmed that the three novel motifs could bind to the VEGFR-2 enzyme's binding region like the co-crystallized ligand SOR did.</p><p><strong>Conclusion: </strong>The enzyme inhibitory test of compound <b>5p</b> showed that it is the most potent hybrid that caused MCF-7 cells to undergo apoptosis and generated a G1/S cell cycle arrest. Confirmation of the obtained results was done with the aid of the docking study, which showed that the three motifs might adhere to the enzyme's major active sites, and the results were in good accordance with the experimental VEGFR-2 inhibitory results. We can conclude that the new quinazoline compounds <b>5a-r</b> could be used as candidates for development of more efficient anticancer inhibitors.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"5109-5127"},"PeriodicalIF":4.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647573","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":"Proteomic Insights into the Effects of Jianweixiaoshi Tablets on Functional Dyspepsia with Spleen Deficiency in Rats.","authors":"Xiaoying Cheng, Jianhua Wan, Denglong Sun, Yang Zhan, Jingting Yu, Yingmeng Li, Yanxia Xiong, Wenjun Liu","doi":"10.2147/DDDT.S477034","DOIUrl":"10.2147/DDDT.S477034","url":null,"abstract":"<p><strong>Background: </strong>Jianweixiaoshi tablets (JWXS) is widely used in traditional Chinese medicine for treating functional dyspepsia with spleen deficiency (SD-FD) in China. However, the molecular mechanisms underlying the therapeutic effects of JWXS remain incompletely understood.</p><p><strong>Methods: </strong>Functional dyspepsia was induced in rats with spleen deficiency by iodoacetamide in combination with the modified multiple platform method. The SD-FD rats were administered JWXS at both low and high doses, as well as domperidone. We conducted a comprehensive evaluation of the treatment effects of JWXS, including body weight, gastrointestinal motility, immune organ index, biochemical analysis, gastrointestinal hormones, and hematological studies. Quantitative proteomic analysis based on data-independent acquisition (DIA) was used to determine the changes in protein profiles of gastric and duodenal tissues in SD-FD rats and JWXS intervention rats.</p><p><strong>Results: </strong>The results showed that JWXS effectively alleviated gastrointestinal motility disorders in SD-FD rats, as indicated by accelerated gastric emptying and intestinal propulsion, increased levels of gastrin, motilin, and ghrelin, and reduced levels of cholecystokinin-octapeptide, vasoactive intestinal peptide, and somatostatin. Additionally, JWXS increased the spleen and thymus index, increased %lymphocyte in blood, reduced white blood cell count and %neutrophil, and improved immune function. Through quantitative proteomic analysis of gastric tissues, we identified 333 differentially expressed proteins in the JWXS treatment group and the model group. Notably, the mechanism by which JWXS accelerated gastric emptying may be related to PLC-γ and SERCA2 in the calcium signaling pathway. Furthermore, JWXS treatment altered the expression of 732 proteins in rat duodenal samples. The differentially expressed proteins were enriched in immune-related functions and pathways, including antigen processing and presentation, as well as the intestinal immune network for IgA production.</p><p><strong>Conclusion: </strong>In conclusion, JWXS exhibits a multi-faceted impact on various pathways, demonstrating its efficacy in treating SD-FD. These findings provide a foundation for the clinical application of JWXS in managing SD-FD.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"5129-5148"},"PeriodicalIF":4.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647635","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-Site Concentration of Remimazolam by Age Groups During Target-Controlled Infusion for Total Intravenous Anesthesia: A Retrospective Comparative Study.","authors":"Jaesik Park, Kwon Hui Seo, Jueun Kwak, Hyebin Baek","doi":"10.2147/DDDT.S480734","DOIUrl":"10.2147/DDDT.S480734","url":null,"abstract":"<p><strong>Purpose: </strong>Pharmacokinetic and pharmacodynamic (PKPD) models exist for remimazolam, but data for target-controlled infusion (TCI) are limited. The Schüttler PKPD model, a three-compartment model including body weight as a covariate, does not account for age as a variable. This study aimed to investigate remimazolam's effect-site concentration (Ce) in different age groups during sedation and general anesthesia with TCI using Schüttler PKPD model.</p><p><strong>Patients and methods: </strong>Records of patients who underwent remimazolam TCI with the Schüttler model were reviewed. During anesthesia induction, the target Ce of remimazolam was gradually increased until loss of responsiveness, and it was titrated to maintain bispectral index of 40-70 during operation. Patients were categorized into young (20-40 years, n=24), middle-aged (41-60 years, n=27), and elderly (61-80 years, n=35) groups. Bispectral index and hemodynamic variables were also assessed.</p><p><strong>Results: </strong>The elderly group had significantly lower remimazolam Ce compared to the young and middle-aged groups at all sedation levels, intubation, and surgery. Mean highest intraoperative Ce was 0.78±0.10, 0.71±0.07, and 0.61±0.10 µg/mL in young, middle-aged, and elderly groups, respectively (<i>P</i><0.001). The recovery of responsiveness during emergence occurred at significantly lower Ce in the elderly group (0.28±0.06 µg/mL) than in the young (0.41±0.07 µg/mL) and middle-aged groups (0.35±0.07 µg/mL, <i>P</i><0.001). Ce during sedation and general anesthesia was comparable between the young and middle-aged groups. The bispectral index was similar across groups but fluctuated more in the elderly group during general anesthesia. Elderly patients also showed the greatest systolic blood pressure suppression (18.4 ± 13.29% before intubation and 34.31 ± 14.91% during surgery).</p><p><strong>Conclusion: </strong>Older patients may require lower target Ce during remimazolam TCI for sedation and anesthesia, with emergence occurring at lower Ce. Blood pressure suppression may be greater in elderly patients under deep sedation or general anesthesia.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"5149-5159"},"PeriodicalIF":4.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647579","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}