International Journal of Medical Sciences最新文献

{"title":"miR-548aj-3p and miR-3127-3p suppress RANKL-facilitated inflammatory cytokines and catabolic factor in osteoarthritis and rheumatoid arthritis.","authors":"Yu-Han Wang, Chin-Horng Su, Li-Chai Chen, Ju-Fang Liu, Chun-Hao Tsai, Yi-Chin Fong, Chih-Yuan Ko, Hsien-Te Chen, Lun-Chien Lo, Chih-Hsin Tang","doi":"10.7150/ijms.110812","DOIUrl":"10.7150/ijms.110812","url":null,"abstract":"<p><p>Osteoarthritis (OA) and rheumatoid arthritis (RA) are highly prevalent joint diseases globally. The common pathological features include synovial inflammation, swelling, joint destruction, and bone remodeling. Arthritis development is associated with joint inflammation, particularly in inflamed synovial cells. Synovial inflammation contributes to joint destruction. The receptor activator of nuclear factor kappa-B ligand (RANKL) is a vital factor that is linked to the activity of osteoclasts and the erosion of bone. Increased levels of RANKL play a role in the course of arthritis. Adverse effects and individual differences in therapeutic efficacy are limits of arthritis medications. More effective treatment and drug options are needed to improve disease progression. miRNAs directly modulate gene transcription as a potential option for arthritis therapeutics. The GEO dataset from the synovium of normal, OA, and RA patients indicated that the expression levels of RANKL were upregulated and related to arthritis features. We found that RANKL stimulation in OA and RA synovial fibroblasts decreased miR-548aj-3p and miR-3127-3p expression and enhanced interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and matrix metalloproteinase-13 (MMP-13) production by using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). miRNA sequencing analysis and target prediction tools identified that miR-548aj-3p and miR-3127-3p regulate IL-1β, IL-6, and MMP-13 expression and are inhibited by RANKL stimulation. Administration of miR-548aj-3p and miR-3127-3p mimics significantly inhibited RANKL-induced expression of IL-1β, IL-6, and MMP-13 at both the mRNA and protein levels. We propose a potentially efficacious miRNA therapeutic approach for the treatment of arthritis, with a specific focus on OA and RA.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 14","pages":"3650-3663"},"PeriodicalIF":3.2,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12434817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming the Delivery Challenges in CRISPR/Cas9 Gene Editing for Effective Cancer Treatment: A Review of Delivery Systems.","authors":"Shuting Tang, Xiaoyi Chen, Xiangmin Tong, Lifen Zhu","doi":"10.7150/ijms.112724","DOIUrl":"10.7150/ijms.112724","url":null,"abstract":"<p><p>Therapeutic strategies based on gene editing provide the ability to modify faulty genes contributing to the development of diseases such as cancer by directly altering the cellular machinery. The clustered regularly interspaced short palindromic repeats associated nuclease 9 (CRISPR/Cas9) system is currently the primary tool used for gene editing. Several effective Cas9 variants have already been established to address the complex genetic modifications that arise during diseases. Although gene-editing systems have made significant advancements, a primary obstacle that requires attention is the transportation of CRISPR/Cas to diverse target cells, both <i>in vivo</i> and <i>in vitro</i>, to render them suitable for clinical implementation. Various strategies can be utilized to facilitate the transportation of the CRISPR/Cas systems into mammalian cells. Herein, we reviewed contemporary research about delivery systems for gene-editing systems that interact effectively in biological systems. This review explores the benefits and drawbacks of using extracellular vesicles and viral vectors as vehicles for delivering the CRISPR/Cas system in the context of cancer treatment.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 14","pages":"3625-3649"},"PeriodicalIF":3.2,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12434829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-Term Effects of Platelet-Rich Plasma on the Clinical Outcomes of Dental Autotransplantation in Teeth with Complete and Incomplete Root Development: A Randomized Cohort Study.","authors":"Aysenur Genc, Betul Gedik, Mehmet Ali Erdem, Abdulkadir Burak Cankaya","doi":"10.7150/ijms.113282","DOIUrl":"10.7150/ijms.113282","url":null,"abstract":"<p><p><b>Background:</b> Dental autotransplantation, the surgical relocation of a tooth within the same individual, offers a valuable alternative to implants for preserving alveolar bone integrity and achieving functional restoration. This study aimed to assess the short-term impact of platelet-rich plasma (PRP) on clinical outcomes in autotransplanted teeth with fully and partially developed roots. <b>Methods:</b> A total of 20 patients, aged 18-25, were randomly assigned to either a PRP or non-PRP group, with subgroups based on root development stage. Key outcomes-including tooth vitality, periodontal probing depth, mobility, pain, and root resorption-were evaluated at 1 week, 1, 3, 6, and 12 months post-transplant. <b>Results:</b> Findings indicated no statistically significant differences between PRP-treated and control groups across all outcomes, suggesting limited PRP efficacy in enhancing short-term outcomes in mature teeth with developed roots. <b>Conclusions:</b> These results underscore the importance of root maturity and atraumatic surgical technique in autotransplantation success, while highlighting that PRP may not significantly affect outcomes in teeth with completed root development.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 14","pages":"3617-3624"},"PeriodicalIF":3.2,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12434814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NDUFS1 upregulates ENaCα by NAD+ to promote alveolar fluid clearance in acute lung injury.","authors":"Mengmeng Wang, Mengting Chen, Jianping Zhu, Yu Zhang, Jian Lu, Zhiying Yue, Zhengfeng Yang, Ruilan Wang","doi":"10.7150/ijms.112248","DOIUrl":"https://doi.org/10.7150/ijms.112248","url":null,"abstract":"<p><p>Alveolar edema and following respiratory distress results in the aggravation of epithelial damage and the progression of acute lung injury (ALI), however, with unclear molecular mechanism remained to be elucidated. Through proteomic screening and scRNA-seq mining analysis, we detected the decline expression of NDUFS1 in epithelial cells in lungs from paraquat/LPS-induced ALI models. NDUFS1 deficiency in alveolar epithelial cells reduced ENaCα expression, which impaired alveolar fluid clearance (AFC) and led to alveolar edema. Mechanistically, NDUSF1 deficiency in alveolar epithelial cells leads to mitochondrial dysfunction such as reduced complex I activity, impaired NAD+ production and increased ROS, these contributed to the decline of ENaCα. Supplementing NAD+ via Olaparib treatment alleviated the reduction of ENaCα abundance raised by NDUFS1 deficiency, improved AFC, and suppressed the progression of ALI. In summary, our study suggests that NDUFS1 promotes AFC by regulating ENaCα via NAD+ in pulmonary epithelial cells during ALI.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 13","pages":"3477-3489"},"PeriodicalIF":3.2,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal Effects of Lipid Oversupply on Energy Metabolism and Mitochondrial Homeostasis in Hepatocytes.","authors":"Cheng-Chieh Chuang, Ying-Hao Chen, Fang-Yeh Chu, Ching-Ping Yang, Hsiang-Ling Ho, Fu-Pang Chang, Yu-Li Lo, Chun-Jung Chen, Yih-Hsin Chang","doi":"10.7150/ijms.104128","DOIUrl":"10.7150/ijms.104128","url":null,"abstract":"<p><p>Obesity is closely associated with multiple metabolic disorders such as non-alcoholic fatty liver disease (NAFLD). Patients with NAFLD are susceptible to develop irreversible life-threatening diseases, however, the evolution concerning mitochondrial and metabolic alterations during NAFLD development and progression remain elusive. This study focused on uncovering the sequential events of energy metabolism and mitochondrial homeostasis of hepatocytes under the environment of lipid oversupply by <i>in vitro</i> and <i>in vivo</i> strategies. Long-chain fatty acid (FA) synthesis and lipid storage were first induced by providing hepatocytes with sufficient energy source, followed by suppressed glucose metabolic efficiency and decreased mitochondrial mass. Intriguingly, distinctive features of hepatic cancer cells in response to FA oversupply were characterized. Insulin signaling and glucose uptake were rapidly deterred while lipid β-oxidation was significantly boosted. Enhanced mitochondrial biogenesis was identified as compensatory feedback for mitochondrial dysfunction. FA-induced mitophagy, cell morphological transition and higher N-cadherin expression potentiates epithelial-mesenchymal transition (EMT) which confers the cells with higher plasticity and accelerates NAFLD progression to irreversible hepatic diseases. This study provides evidence elucidating the temporal events caused by FA oversupply, moreover, delineates the facilitative role of excess nutrients in shaping the environment for lipid-laden hepatocytes to acquire malignant traits. Given the rapidly increasing global prevalence of metabolic disorders and the heterogeneous manifestations exhibited by NAFLD during disease progression, better understanding of the sequential events caused by FA overload aids in identifying promising targets and developing tailor-made treatment protocol according to individual disease status and conditions.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 14","pages":"3664-3681"},"PeriodicalIF":3.2,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12434833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Matrix Stiffness Enhancement Promotes Docetaxel Resistance in Prostate Cancer via Inhibition of Apoptosis Mediated by Upregulation of PRRX1.","authors":"Jiahao Chen, Mengting Chen, Zhiwen Xie, Luheng Shen, Juntao Jiang, Shujie Xia","doi":"10.7150/ijms.111171","DOIUrl":"https://doi.org/10.7150/ijms.111171","url":null,"abstract":"<p><p><b>Background:</b> Prostate cancer (PCa) poses a significant health burden for men, with docetaxel constituting the primary therapeutic option for patients with metastatic PCa. However, the mechanisms governing docetaxel resistance remain incompletely understood. Several studies have implicated the role of the extracellular matrix (ECM) stiffness in cancer drug resistance, yet the precise role of ECM stiffness in docetaxel resistance in PCa remains elusive. The aim of this study was to explore the influence of ECM stiffness on docetaxel resistance in PCa and elucidate the underlying molecular mechanisms, thereby providing novel insights into PCa treatment. <b>Methods:</b> Polyacrylamide gels of varying stiffness were utilized to mimic different ECM stiffness conditions. The sensitivity of PCa cells to docetaxel was evaluated using CCK-8, TUNEL staining, flow cytometry, and western blotting. RNA-seq was employed to analyze the transcriptomic effects of different ECM stiffness on PC-3 cells. Western blotting, qPCR, and siRNA were utilized to validate the regulatory role of the key gene in the sensitivity of PCa cells to docetaxel under varying stiffness conditions. <b>Results:</b> Our findings indicate that high ECM stiffness enhances docetaxel resistance in PCa cells by inhibiting docetaxel-induced apoptosis. This process is mediated through the integrin-related mechanotransduction pathway. Specifically, high ECM stiffness upregulates the expression of PRRX1, thereby promoting docetaxel resistance in PCa cells. <b>Conclusions:</b> High ECM stiffness promotes docetaxel resistance in PCa, with PRRX1 identified as a pivotal gene in this process. These findings contribute to a deeper understanding of the mechanisms underlying docetaxel resistance in PCa and may inform the development of novel therapeutic strategies.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 13","pages":"3454-3463"},"PeriodicalIF":3.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total Bile Acids: A Game-Changer in Predicting Short-Term Outcomes in AIS Patients Undergoing Thrombolysis.","authors":"Zhuohang Liu, Min Chu, Zengyu Zhang, Jing Zhao","doi":"10.7150/ijms.108310","DOIUrl":"https://doi.org/10.7150/ijms.108310","url":null,"abstract":"<p><p><b>Introduction:</b> Total bile acids (TBAs) are emerging as potential prognostic biomarkers in acute ischemic stroke (AIS). This study aimed to evaluate the association between TBA levels and long-term outcomes in AIS patients receiving intravenous thrombolysis (IVT). <b>Methods:</b> A total of 231 AIS patients treated with IVT were prospectively enrolled. TBA levels were measured on admission. The primary outcome was the 3-month modified Rankin Scale (mRS) score. Logistic regression, restricted cubic splines (RCS), and decision curve analysis (DCA) were used to assess associations. Machine learning (ML) models were employed to validate predictive performance. <b>Results:</b> High TBA (> 5 μmol/L) patients showed significantly better functional outcomes (91.2% vs 60.2%, P < 0.001). Multivariate analysis confirmed higher TBA independently predicted favorable outcomes (adjusted OR = 0.74, 95%CI:0.59-0.93), with TBA-integrated models showing superior discrimination (AUC = 0.970 vs ≤ 0.64 for NIHSS/TOAST). Restricted cubic spline analysis revealed a J-shaped non-linear relationship between TBA levels and outcome probability. Critically, a predictive model combining TBA with clinical factors demonstrated superior discriminative ability (AUC = 0.970), significantly outperforming traditional scores (NIHSS AUC = 0.64; TOAST AUC = 0.55). Decision curve analysis confirmed the model's clinical utility. Machine learning validation, particularly using Random Forest (accuracy: 93.8%, AUC: 93.14%, Brier score: 0.072), further substantiated TBA's predictive value. Feature importance analysis identified TBA (25.85) and hemoglobin (24.34) as the primary predictors, substantially exceeding others (e.g., NT-proBNP:3.60; admission NIHSS: 3.41; eGFR-EPI: 3.28). <b>Conclusion:</b> TBA is independently associated with functional outcomes after IVT and may serve as a novel prognostic biomarker in AIS.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 13","pages":"3464-3476"},"PeriodicalIF":3.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 Pituitary-Target Gland Axis on RAAS in the Context of COVID-19.","authors":"Baofeng Wu, Ru Li, Qinhao Liu, Shuqing Jin, Hongxia Wei, Ming Xu, Yi Zhang, Yunfeng Liu","doi":"10.7150/ijms.114924","DOIUrl":"10.7150/ijms.114924","url":null,"abstract":"<p><p>The pituitary gland is a very important endocrine gland in the human body. It secretes and releases many hormones crucial for controlling physiological processes, such as energy metabolism, human growth and development, and reproduction. The renin-angiotensin-aldosterone system regulates water and salt homeostasis, controlling blood pressure. Since the discovery of the renin-angiotensin-aldosterone system, exploring and studying its role in pathophysiology has never stopped, and patients have benefited from drug-based and clinical studies. This review focuses on the effects of the pituitary-target gland axis (pituitary-thyroid axis, pituitary-adrenal axis, pituitary-growth hormone axis, pituitary-gonadal axis) and some hormones secreted and stored by the pituitary gland on the RAAS. While considering that SARS-CoV-2 reinfection still occurs, we aim to provide new insights into water-electrolyte balance and blood pressure regulation.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 13","pages":"3439-3453"},"PeriodicalIF":3.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144953178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-bisabolol protects against neonatal asthma by suppressing airway inflammatory signaling.","authors":"Rekha Thiruvengadam, Mydhili Govindarasu, Jamal Mohammed Ali Khaled, Seungho Lee, Jin Hee Kim","doi":"10.7150/ijms.96371","DOIUrl":"10.7150/ijms.96371","url":null,"abstract":"<p><p><b>Objective:</b> This study aimed to evaluate the anti-inflammatory effects of alpha-bisabolol (AB) in allergic airway inflammation-induced rat pups. <b>Methods:</b> We evaluated the anti-adverse effects of AB against allergic airway inflammation-induced male Wistar rat pups, with four categorized groups including vehicle-controls (group 1), controls treated with 25 mg/kg of AB (group 2), allergic airway inflammation-induced cases (group 3), and cases treated with 25 mg/kg of AB before allergic airway inflammation induction (group 4). Lung histopathology, bronchoalveolar lavage fluid eosinophils, and several inflammatory markers were also examined in each group. <b>Results:</b> AB significantly decreased mucous gland hypertrophy, eosinophil infiltration, and oxidative stress marker levels in the allergic airway inflammation-induced AB-pretreated rats. Moreover, AB pretreatment significantly reduced the levels of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8, IL-17, monocyte chemoattractant protein-1, C-X-C chemokine receptor type 4 (CXCR4), and thymic stromal lymphopoietin, which were increased in allergic airway inflammation-induced cases. Furthermore, transcription of <i>cyclooxygenase-2</i>, <i>tumor necrosis factor-α</i>, <i>CXCR4</i>, <i>toll-like receptor 4</i>, <i>Eotaxin-1</i>, and <i>regulated upon activation normal T cell expressed and secreted</i> were significantly suppressed in allergic airway inflammation-induced AB-pretreated rats. <b>Conclusions:</b> These results indicate that AB can protect against neonatal asthma by inhibiting acute or chronic inflammation induced during disease onset.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 13","pages":"3429-3438"},"PeriodicalIF":3.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Atractylodes macrocephala</i> Koidzumi modulates human colonic motility via ICCs pacemaker suppression and cAMP/ATP-sensitive K⁺ channel pathways.","authors":"Tae Sik Sung, Seok Jae Ko, Woo-Gyun Choi, Jae-Woo Park, Byung Joo Kim","doi":"10.7150/ijms.116169","DOIUrl":"10.7150/ijms.116169","url":null,"abstract":"<p><p><i>Atractylodes macrocephala</i> Koidzumi (AMK) is a traditional herbal medicine used for digestive disorders, yet its effects on colonic motility remain poorly understood. This study aimed to investigate the impact of AMK on human colonic contractility and pacemaker activity of interstitial cells of Cajal (ICCs), as well as its <i>in vivo</i> effect on intestinal transit. Human colonic tissues were obtained during non-obstructive colon surgery and used to assess spontaneous smooth muscle contractions and migrating motor complexes (MMCs). Electrophysiological recordings of pacemaker potentials were performed in murine colonic ICCs using whole-cell patch clamp. Pharmacological studies examined the involvement of ATP-sensitive K⁺ channels and cAMP signaling. The intestinal transit rate (ITR) was evaluated in a neostigmine-induced hypermotility mouse model. AMK treatment significantly reduced spontaneous contractions and MMCs in human colonic segments in a dose-dependent manner. In muine colonic ICCs, AMK suppressed pacemaker potentials, with an IC₅₀ of 37.89 µg/mL. This inhibitory effect was reversed by glibenclamide and 8-bromo-cAMP, suggesting involvement of ATP-sensitive K⁺ channels and cAMP-dependent pathways. <i>In vivo</i>, AMK attenuated neostigmine-induced increases in ITR. These findings highlight AMK's potential as a modulator of gastrointestinal motility.</p>","PeriodicalId":14031,"journal":{"name":"International Journal of Medical Sciences","volume":"22 13","pages":"3412-3421"},"PeriodicalIF":3.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}